Differentiating pathway-specific from nonspecific effects in high-throughput toxicity data: A foundation for prioritizing adverse outcome pathway development

EPA Science Inventory

The U.S. Environmental Protection Agency’s ToxCast program has screened thousands of chemicals for biological activity, primarily using high-throughput in vitro bioassays. Adverse outcome pathways (AOPs) offer a means to link pathway-specific biological activities with potential ...

Biological oxygen demand in soils and hydrogel compositions for plant protection of the rhizosphere

NASA Astrophysics Data System (ADS)

Valentinovich Smagin, Andrey

2018-02-01

Potential biological activity of mineral and organogenic samples from light-textured sod-podzolic soils as well as of hydrogel compositions for protecting the root layer from pathogenic microflora and unfavorable edaphic factors were studied in laboratory conditions by oxygen consumption under the optimal hydrothermic conditions with portable gas analyzers. We have conducted ecological standardization of biological activity and organic matter destruction estimated by biological oxygen demand (BOD) in the widespread sandy soils. The primary outcome was the scale of gradations of biological oxygen uptake in soils with a range of quantities of potential biological activity from “very low” (<2 g·m-3·hour-1) to “extremely high” (>140 g·m-3·hour-1), obtained on the basis of statistical processing of data array 1308 measurements. Acrylic polymer hydrogels had BOD = 0.2-2 g·m-3·hour-1, which corresponded to the periods of their half-lives from 0.2±0.1 to 6.8± 4.5 years, or relatively low resistance to biodestruction. In contrast to the pure gels, hydrogel compositions for rhizosphere based on ionic and colloidal silver showed low biological activity (BOD=0.01-0.2 g·m-3· hour-1) and, accordingly, significant resistance to biodegradation with half-lives from 5 to 70 years and above.

Isolation, Separation, and Preconcentration of Biologically Active Compounds from Plant Matrices by Extraction Techniques.

PubMed

Raks, Victoria; Al-Suod, Hossam; Buszewski, Bogusław

2018-01-01

Development of efficient methods for isolation and separation of biologically active compounds remains an important challenge for researchers. Designing systems such as organomineral composite materials that allow extraction of a wide range of biologically active compounds, acting as broad-utility solid-phase extraction agents, remains an important and necessary task. Selective sorbents can be easily used for highly selective and reliable extraction of specific components present in complex matrices. Herein, state-of-the-art approaches for selective isolation, preconcentration, and separation of biologically active compounds from a range of matrices are discussed. Primary focus is given to novel extraction methods for some biologically active compounds including cyclic polyols, flavonoids, and oligosaccharides from plants. In addition, application of silica-, carbon-, and polymer-based solid-phase extraction adsorbents and membrane extraction for selective separation of these compounds is discussed. Potential separation process interactions are recommended; their understanding is of utmost importance for the creation of optimal conditions to extract biologically active compounds including those with estrogenic properties.

More insights into the pharmacological effects of artemisinin.

PubMed

Zyad, Abdelmajid; Tilaoui, Mounir; Jaafari, Abdeslam; Oukerrou, Moulay Ali; Mouse, Hassan Ait

2018-02-01

Artemisinin is one of the most widely prescribed drugs against malaria and has recently received increased attention because of its other potential biological effects. The aim of this review is to summarize recent discoveries of the pharmaceutical effects of artemisinin in basic science along with its mechanistic action, as well as the intriguing results of recent clinical studies, with a focus on its antitumor activity. Scientific evidence indicates that artemisinin exerts its biological activity by generating reactive oxygen species that damage the DNA, mitochondrial depolarization, and cell death. In the present article review, scientific evidence suggests that artemisinin is a potential therapeutic agent for various diseases. Thus, this review is expected to encourage interested scientists to conduct further preclinical and clinical studies to evaluate these biological activities. Copyright © 2017 John Wiley & Sons, Ltd.

Lysine acetyltransferase inhibitors: structure-activity relationships and potential therapeutic implications.

PubMed

Fiorentino, Francesco; Mai, Antonello; Rotili, Dante

2018-05-01

Lysine acetylation is a post-translational modification of both histone and nonhistone proteins that is catalyzed by lysine acetyltransferases and plays a key role in numerous biological contexts. The dysregulation of this enzyme activity is implicated in many human pathologies such as cancer, neurological and inflammatory disorders. Many lysine acetyltransferase inhibitors (KATi) have been developed so far, but there is still the need for new, more potent, metabolically stable and selective KATi as chemical tools for studying KAT biology and/or as potential therapeutic agents. This review will examine the features of KAT enzymes and related diseases, with particular emphasis on KATi (bisubstrate analogs, natural compounds and synthetic derivatives), analyzing their mechanism of action, structure-activity relationships, pharmacokinetic/pharmacodynamic properties and potential future applications.

Generation and Biological Activities of Oxidized Phospholipids

PubMed Central

Oskolkova, Olga V.; Birukov, Konstantin G.; Levonen, Anna-Liisa; Binder, Christoph J.; Stöckl, Johannes

2010-01-01

Abstract Glycerophospholipids represent a common class of lipids critically important for integrity of cellular membranes. Oxidation of esterified unsaturated fatty acids dramatically changes biological activities of phospholipids. Apart from impairment of their structural function, oxidation makes oxidized phospholipids (OxPLs) markers of “modified-self” type that are recognized by soluble and cell-associated receptors of innate immunity, including scavenger receptors, natural (germ line-encoded) antibodies, and C-reactive protein, thus directing removal of senescent and apoptotic cells or oxidized lipoproteins. In addition, OxPLs acquire novel biological activities not characteristic of their unoxidized precursors, including the ability to regulate innate and adaptive immune responses. Effects of OxPLs described in vitro and in vivo suggest their potential relevance in different pathologies, including atherosclerosis, acute inflammation, lung injury, and many other conditions. This review summarizes current knowledge on the mechanisms of formation, structures, and biological activities of OxPLs. Furthermore, potential applications of OxPLs as disease biomarkers, as well as experimental therapies targeting OxPLs, are described, providing a broad overview of an emerging class of lipid mediators. Antioxid. Redox Signal. 12, 1009–1059. PMID:19686040

Biologically active chitosan systems for tissue engineering and regenerative medicine.

PubMed

Jiang, Tao; Kumbar, Sangamesh G; Nair, Lakshmi S; Laurencin, Cato T

2008-01-01

Biodegradable polymeric scaffolds are widely used as a temporary extracellular matrix in tissue engineering and regenerative medicine. By physical adsorption of biomolecules on scaffold surface, physical entrapment of biomolecules in polymer microspheres or hydrogels, and chemical immobilization of oligopeptides or proteins on biomaterials, biologically active biomaterials and scaffolds can be derived. These bioactive systems show great potential in tissue engineering in rendering bioactivity and/or specificity to scaffolds. This review highlights some of the biologically active chitosan systems for tissue engineering application and the associated strategies to develop such bioactive chitosan systems.

Structure-Based Virtual Screening of Protein Tyrosine Phosphatase Inhibitors: Significance, Challenges, and Solutions.

PubMed

Reddy, Rallabandi Harikrishna; Kim, Hackyoung; Cha, Seungbin; Lee, Bongsoo; Kim, Young Jun

2017-05-28

Phosphorylation, a critical mechanism in biological systems, is estimated to be indispensable for about 30% of key biological activities, such as cell cycle progression, migration, and division. It is synergistically balanced by kinases and phosphatases, and any deviation from this balance leads to disease conditions. Pathway or biological activity-based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome, and cause diverse diseases ranging from diabetes, rheumatoid arthritis, and numerous cancers. Protein tyrosine phosphatases (PTPs) are of prime importance in the process of dephosphorylation and catalyze several biological functions. Abnormal PTP activities are reported to result in several human diseases. Consequently, there is an increased demand for potential PTP inhibitory small molecules. Several strategies in structure-based drug designing techniques for potential inhibitory small molecules of PTPs have been explored along with traditional drug designing methods in order to overcome the hurdles in PTP inhibitor discovery. In this review, we discuss druggable PTPs and structure-based virtual screening efforts for successful PTP inhibitor design.

The Relative Importance of Spatial Versus Temporal Structure in the Perception of Biological Motion: An Event-Related Potential Study

ERIC Educational Resources Information Center

Hirai, Masahiro; Hiraki, Kazuo

2006-01-01

We investigated how the spatiotemporal structure of animations of biological motion (BM) affects brain activity. We measured event-related potentials (ERPs) during the perception of BM under four conditions: normal spatial and temporal structure; scrambled spatial and normal temporal structure; normal spatial and scrambled temporal structure; and…

Ficus carica L. (Moraceae): Phytochemistry, Traditional Uses and Biological Activities.

PubMed

Mawa, Shukranul; Husain, Khairana; Jantan, Ibrahim

2013-01-01

This paper describes the botanical features of Ficus carica L. (Moraceae), its wide variety of chemical constituents, its use in traditional medicine as remedies for many health problems, and its biological activities. The plant has been used traditionally to treat various ailments such as gastric problems, inflammation, and cancer. Phytochemical studies on the leaves and fruits of the plant have shown that they are rich in phenolics, organic acids, and volatile compounds. However, there is little information on the phytochemicals present in the stem and root. Reports on the biological activities of the plant are mainly on its crude extracts which have been proven to possess many biological activities. Some of the most interesting therapeutic effects include anticancer, hepatoprotective, hypoglycemic, hypolipidemic, and antimicrobial activities. Thus, studies related to identification of the bioactive compounds and correlating them to their biological activities are very useful for further research to explore the potential of F. carica as a source of therapeutic agents.

Short-Term Effect of Vermicompost Application on Biological Properties of an Alkaline Soil with High Lime Content from Mediterranean Region of Turkey

PubMed Central

Uz, Ilker; Tavali, Ismail Emrah

2014-01-01

This study was conducted to investigate direct short-term impact of vermicompost on some soil biological properties by monitoring changes after addition of vermicompost as compared to farmyard manure in an alkaline soil with high lime content from semiarid Mediterranean region of Turkey. For this purpose, mixtures of soil and organic fertilizers in different doses were incubated under greenhouse condition. Soil samples collected in regular intervals were analyzed for biological parameters including dehydrogenase, β-glucosidase, urease, alkaline phosphatase activities, and total number of aerobic mesophilic bacteria. Even though soil dehydrogenase activity appeared to be dose-independent based on overall evaluation, organic amendments were found to elevate dehydrogenase activity when sampling periods are evaluated individually. β-glucosidase, urease, alkaline phosphatase activity, and aerobic mesophilic bacterial numbers in vermicompost treatments fluctuated but remained significantly above the control. A slight but statistically significant difference was detected between organic amendments in terms of urease activity. Vermicompost appeared to more significantly increase bacterial number in soil. Clearly, vermicompost has a potential to be used as an alternative to farmyard manure to improve and maintain soil biological activity in alkaline calcareous soils from the Mediterranean region of Turkey. Further studies are needed to assess its full potential for these soils. PMID:25254238

Diversity of Secondary Metabolites from Marine Bacillus Species: Chemistry and Biological Activity

PubMed Central

Mondol, Muhammad Abdul Mojid; Shin, Hee Jae; Islam, Mohammad Tofazzal

2013-01-01

Marine Bacillus species produce versatile secondary metabolites including lipopeptides, polypeptides, macrolactones, fatty acids, polyketides, and isocoumarins. These structurally diverse compounds exhibit a wide range of biological activities, such as antimicrobial, anticancer, and antialgal activities. Some marine Bacillus strains can detoxify heavy metals through reduction processes and have the ability to produce carotenoids. The present article reviews the chemistry and biological activities of secondary metabolites from marine isolates. Side by side, the potential for application of these novel natural products from marine Bacillus strains as drugs, pesticides, carotenoids, and tools for the bioremediation of heavy metal toxicity are also discussed. PMID:23941823

Mannich bases in medicinal chemistry and drug design.

PubMed

Roman, Gheorghe

2015-01-07

The biological activity of Mannich bases, a structurally heterogeneous class of chemical compounds that are generated from various substrates through the introduction of an aminomethyl function by means of the Mannich reaction, is surveyed, with emphasis on the relationship between structure and biological activity. The review covers extensively the literature reports that have disclosed Mannich bases as anticancer and cytotoxic agents, or compounds with potential antibacterial and antifungal activity in the last decade. The most relevant studies on the activity of Mannich bases as antimycobacterial agents, antimalarials, or antiviral candidates have been included as well. The review contains also a thorough coverage of anticonvulsant, anti-inflammatory, analgesic and antioxidant activities of Mannich bases. In addition, several minor biological activities of Mannich bases, such as their ability to regulate blood pressure or inhibit platelet aggregation, their antiparasitic and anti-ulcer effects, as well as their use as agents for the treatment of mental disorders have been presented. The review gives in the end a brief overview of the potential of Mannich bases as inhibitors of various enzymes or ligands for several receptors. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical Characteristics, Synthetic Methods, and Biological Potential of Quinazoline and Quinazolinone Derivatives

PubMed Central

2014-01-01

The heterocyclic fused rings quinazoline and quinazolinone have drawn a huge consideration owing to their expanded applications in the field of pharmaceutical chemistry. Quinazoline and quinazolinone are reported for their diversified biological activities and compounds with different substitutions bring together to knowledge of a target with understanding of the molecule types that might interact with the target receptors. Quinazolines and quinazolinones are considered as an important chemical for the synthesis of various physiological significance and pharmacological utilized molecules. Quinazolines and quinazolinone are a large class of biologically active compounds that exhibited broad spectrum of biological activities such as anti-HIV, anticancer, antifungal, antibacterial, antimutagenic, anticoccidial, anticonvulsant, anti-inflammatory, antidepressant, antimalarial, antioxidant, antileukemic, and antileishmanial activities and other activities. Being considered as advantaged scaffold, the alteration is made with different substituent. PMID:25692041

Prioritization of pharmaceuticals for potential environmental hazard through leveraging a large scale mammalian pharmacological dataset

EPA Science Inventory

To proceed in the investigation of potential effects of thousands of active pharmaceutical ingredients (API) which may enter the aquatic environment, a cohesive research strategy, specifically a prioritization is paramount. API are biologically active, with specific physiologica...

In Vitro Biologic Activities of the Antimicrobials Triclocarban, Its Analogs, and Triclosan in Bioassay Screens: Receptor-Based Bioassay Screens

PubMed Central

Ahn, Ki Chang; Zhao, Bin; Chen, Jiangang; Cherednichenko, Gennady; Sanmarti, Enio; Denison, Michael S.; Lasley, Bill; Pessah, Isaac N.; Kültz, Dietmar; Chang, Daniel P.Y.; Gee, Shirley J.; Hammock, Bruce D.

2008-01-01

Background Concerns have been raised about the biological and toxicologic effects of the antimicrobials triclocarban (TCC) and triclosan (TCS) in personal care products. Few studies have evaluated their biological activities in mammalian cells to assess their potential for adverse effects. Objectives In this study, we assessed the activity of TCC, its analogs, and TCS in in vitro nuclear-receptor–responsive and calcium signaling bioassays. Materials and methods We determined the biological activities of the compounds in in vitro, cell-based, and nuclear-receptor–responsive bioassays for receptors for aryl hydrocarbon (AhR), estrogen (ER), androgen (AR), and ryanodine (RyR1). Results Some carbanilide compounds, including TCC (1–10 μM), enhanced estradiol (E2)-dependent or testosterone-dependent activation of ER- and AR-responsive gene expression up to 2.5-fold but exhibited little or no agonistic activity alone. Some carbanilides and TCS exhibited weak agonistic and/or antagonistic activity in the AhR-responsive bioassay. TCS exhibited antagonistic activity in both ER- and AR-responsive bioassays. TCS (0.1–10 μM) significantly enhanced the binding of [3H]ryanodine to RyR1 and caused elevation of resting cytosolic [Ca2+] in primary skeletal myotubes, but carbanilides had no effect. Conclusions Carbanilides, including TCC, enhanced hormone-dependent induction of ER- and AR-dependent gene expression but had little agonist activity, suggesting a new mechanism of action of endocrine-disrupting compounds. TCS, structurally similar to noncoplanar ortho-substituted poly-chlorinated biphenyls, exhibited weak AhR activity but interacted with RyR1 and stimulated Ca2+ mobilization. These observations have potential implications for human and animal health. Further investigations are needed into the biological and toxicologic effects of TCC, its analogs, and TCS. PMID:18795164

NANOSILVER MOVEMENT THROUGH BIOLOGICAL BARRIERS RELATES TO PHYSICOCHEMICAL PROPERTIES

EPA Science Inventory

Linking the physicochemical (PC) properties of engineered nanomaterials (NM) to their biological activity is critical for identifying their (toxic) mode of action, and developing appropriate and effective risk assessment guidelines. Particle surface charge (zeta potential), surfa...

Ellagic Acid: A Logical Lead for Drug Development?

PubMed

Shakeri, Abolfazl; Zirak, Mohammad Reza; Sahebkar, Amirhossein

2018-01-01

Naturally occurring polyphenols are the subject of increasing attention due to their potent antioxidant activity and their marked effects on the prevention of various oxidative stress-associated diseases such as cancer. Ellagic acid (EA) is an herbal polyphenol that is structurally a condensed dimer of gallic acid. This review aims to provide a comprehensive and updated overview on the biological activities of EA and potential therapeutic applications. EA is found in fruits and nuts, either in the combined form with hexahydroxydiphenic acid or in the bound form (ellagitannins). EA exhibits many biological properties such as antioxidant, anti-diabetic, anticancer and apoptosis-inducing activities. These biological and pharmacological properties are relevant to the treatment of several human diseases. Owing to its multiple mechanisms of action, EA represents a potential therapeutic agent against human diseases particularly cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Biologically active protein fragments containing specific binding regions of serum albumin or related proteins

NASA Technical Reports Server (NTRS)

Carter, Daniel C. (Inventor)

1998-01-01

In accordance with the present invention, biologically active protein fragments can be constructed which contain only those specific portions of the serum albumin family of proteins such as regions known as subdomains IIA and IIIA which are primarily responsible for the binding properties of the serum albumins. The artificial serums that can be prepared from these biologically active protein fragments are advantageous in that they can be produced much more easily than serums containing the whole albumin, yet still retain all or most of the original binding potential of the full albumin proteins. In addition, since the protein fragment serums of the present invention can be made from non-natural sources using conventional recombinant DNA techniques, they are far safer than serums containing natural albumin because they do not carry the potentially harmful viruses and other contaminants that will be found in the natural substances.

Composition and biological activities of hydrolyzable tannins of fruits of Phyllanthus emblica.

PubMed

Yang, Baoru; Liu, Pengzhan

2014-01-22

Fruits of emblic leafflower have been used as food and traditional medicine in Asia. A wide range of biological activities have been shown in modern research suggesting potential of the fruits as healthy food and raw material for bioactive ingredients of food. Hydrolyzable tannins are among the major bioactive components of the fruits. Mucic acid gallate, mucic acid lactone gallate, monogalloylglucose, gallic acid, digalloylglucose, putranjivain A, galloyl-HHDP-glucose, elaeocarpusin, and chebulagic acid are the most abundant hydrolyzable tannins. The compositional profiles of tannins in the fruits vary depending on the cultivars as well as ripening stages. Fruits and tannin-rich extracts of fruits have shown antidiabetic, antimicrobial, anti-inflammatory, and immune-regulating activities in vitro and in animal studies. The fruits and fruit extracts have manifested protective effects on organs/tissues from damages induced by chemicals, stresses, and aging in animal models. The fruits and fruit extracts have potential in inhibiting the growth of cancer cells and reducing DNA damage induced by chemicals and radiation. Antioxidative activities are likely among the mechanisms of the biological activities and physiological effects. Human intervention/clinical studies are needed to investigate the bioavailability and metabolism of the tannins and to substantiate the health benefits in humans. Emblic leafflower may be a potential raw material for natural food preservatives.

Synthesis and biological evaluation of arctigenin ester and ether derivatives as activators of AMPK.

PubMed

Shen, Sida; Zhuang, Jingjing; Chen, Yijia; Lei, Min; Chen, Jing; Shen, Xu; Hu, Lihong

2013-07-01

A series of new arctigenin and 9-deoxy-arctigenin derivatives bearing different ester and ether side chains at the phenolic hydroxyl positions are designed, synthesized, and evaluated for activating AMPK potency in L6 myoblasts. Initial biological evaluation indicates that some alkyl ester and phenethyl ether arctigenin derivatives display potential activities in AMPK phosphorylation improvement. Further structure-activity relationship analysis shows that arctigenin ester derivatives 3a, 3h and 9-deoxy-arctigenin phenethyl ether derivatives 6a, 6c, 6d activate AMPK more potently than arctigenin. Moreover, the 2-(3,4-dimethoxyphenyl)ethyl ether moiety of 6c has been demonstrated as a potential functional group to improve the effect of AMPK phosphorylation. The structural optimization of arctigenin leads to the identification of 6c as a promising lead compound that exhibits excellent activity in AMPK activation. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies.

PubMed

Simic, Milena; Paunovic, Nikola; Boric, Ivan; Randjelovic, Jelena; Vojnovic, Sandra; Nikodinovic-Runic, Jasmina; Pekmezovic, Marina; Savic, Vladimir

2016-01-01

A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to those of clinically used voriconazole. Selected compounds were also screened against voriconazole resistant Candida krusei 6258 and a clinical isolate Candida parapsilosis CA-27. Although the activity against these targets needs to be improved further, the results emphasise additional potential of this new class of antifungal compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

Summary Report: Pilot Study of an Innovative Biological Treatment Process for the Removal of Ammonia from a Small Drinking Water System

EPA Science Inventory

The use of biologically active filtration to oxidize ammonia as a full-scale drinking water treatment process has not been thoroughly considered in the United States. A number of concerns with biological water treatment exist including the potential release of excessive numbers o...

A Review on Phytoconstituents and Biological activities of Cuscuta species.

PubMed

Ahmad, Ateeque; Tandon, Sudeep; Xuan, Tran Dang; Nooreen, Zulfa

2017-08-01

The genus Cuscuta belonging to the Cuscutaceae family comprises of about 100-170 species spread around the world. Although several species have been studied for their phytochemical characterization and biological activities but still many species are yet unexplored till date. Cuscuta are parasitic plants generally of yellow, orange, red or rarely green color. The Cuscuta species were reported rich in flavonoid and glycosidic constituents along with alkaloids, fatty acids, fixed oil, minerals, essential oil and others phytomolecules also etc. Flavonoids and other molecules of Cuscuta species were reported for different types of biological activities such as antiproliferative activity, antioxidant activity, anti-inflammatory, hepatoprotective, antimicrobial and anxiolytic activity, while some other flavonoids have exhibited potential antiviral and anticancer especially in ovarian and breast cancer activities. This review is an attempt to compile all the available data for the 24 different of Cuscuta species on the basis of different types of phytochemical constituents and biological studies as above. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Analysis of synthetic and biological microparticles on several flow cytometric platforms***

EPA Science Inventory

Biological microparticles (MPs) are potentially important biomarkers for thrombosis, cancer, glomerulonephritis and other disease states. These MPs are generally accepted to be membrane vesicles extruded following cellular activation. While human blood cells range from 10-15 micr...

For support of USAMRMC Biological Weapons Convention, treaty and statement implementation activities. Final report, 1 March 1996-28 February 1997

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fox, J.

Program of work to provide support to the Biological Arms Control Treaty Office (BACTO) of the U.S. Army Medical Research and Material Command (USAMRMC), in the development of Army and U.S. Government negotiation, implementation and compliance policies and preparations regarding potential verification and confidence measures for the 1975 Biological Weapons Convention (BWC) and related biological weapons agreements. Support services provided included the preparation of Army installations and commands for implementation of visits pursuant to the U.S./UK/Russian Trilateral Statement on BW. Support included site assistance visit, development of required facility documentation and briefings, identification of additional facilities potentially subject to access,more » and support to DOD development of guidelines, procedures, documentation, and other materials for the conduct of visits. Specific tasks under this contract included: identification and delineation of `Military Biological Facilities` and related activities at Army installations; development of visit implementation documentation for the Army; assessment of potentially at-risk equities and sensitivities at relevant facilities; facility staff training and preparation; and review and modification of facility inputs to annual BWC Confidence Building Measure Declarations. Also supported the provision of timely and critical technical support to the Joint Staff and OSD in the development of DoD negotiation biological arms control positions.« less

Late-stage diversification of biologically active pyridazinones via a direct C-H functionalization strategy.

PubMed

Li, Wei; Fan, Zhoulong; Geng, Kaijun; Xu, Youjun; Zhang, Ao

2015-01-14

Divergent C-H functionalization reactions (arylation, carboxylation, olefination, thiolation, acetoxylation, halogenation, naphthylation) using a pyridazinone moiety as an internal directing group were successfully established. This approach offers a late-stage, ortho-selective diversification of a biologically active pyridazinone scaffold. Seven series of novel pyridazinone analogues were synthesized conveniently as the synthetic precursors of potential sortase A (SrtA) inhibitors.

Comparison of Biological Activity of Human Anti-Apical Membrane Antigen-1 Antibodies Induced by Natural Infection and Vaccination

PubMed Central

Miura, Kazutoyo; Zhou, Hong; Moretz, Samuel E.; Diouf, Ababacar; Thera, Mahamadou A; Dolo, Amagana; Doumbo, Ogobara; Malkin, Elissa; Diemert, David; Miller, Louis H.; Mullen, Gregory E.D.; Long, Carole A.

2009-01-01

Vaccines represent a significant potential means of decreasing global morbidity and mortality due to malaria. Clinical trials in the U.S. with Plasmodium falciparum Apical Membrane Antigen 1 (AMA1) showed that the vaccine induced biologically active antibodies judged by an in vitro parasite Growth Inhibition Assay (GIA). However, the same vaccine in Malian adults did not increase biological activity although it elevated ELISA titers. As GIA has been used to evaluate the biological activity of antibodies induced by blood-stage malarial vaccine candidates, we explored this discrepancy in this study. We affinity purified AMA1-specific antibodies from both US vaccinees and from non-vaccinated individuals living in a malaria-endemic area of Mali, and performed ELISA and GIA. Both AMA1-specifc antibodies induced by vaccination (US) and by natural infection (Mali) have comparable biological activity in GIA when the ELISA titer is normalized. However, a fraction of Malians’ IgG which did not bind to AMA1 protein (Mali-non-AMA1 IgG) reduced the biological activity of the AMA1 antibodies from US vaccinees; in contrast, US-non-AMA1 IgGs did not show a reduction of the biological activity. Further investigation revealed that the reduction was due to malaria-specific IgGs in the Mali-non-AMA1 IgGs. The fact that both US- and Mali-AMA1-specific antibodies showed comparable biological activity supports further development of AMA1-based vaccines. However, the reduction of biological activity of AMA1-specific antibody by other malaria-specific IgGs likely explains the limited effect on growth-inhibitory activity of antibodies induced by AMA1 vaccination in Malian adults and may complicate efforts to develop a blood-stage malaria vaccine. PMID:19050299

Microbial mats as a biological treatment approach for saline wastewaters: the case of produced water from hydraulic fracturing.

PubMed

Akyon, Benay; Stachler, Elyse; Wei, Na; Bibby, Kyle

2015-05-19

Treatment of produced water, i.e. wastewater from hydraulic fracturing, for reuse or final disposal is challenged by both high salinity and the presence of organic compounds. Organic compounds in produced water may foul physical-chemical treatment processes or support microbial corrosion, fouling, and sulfide release. Biological approaches have potential applications in produced water treatment, including reducing fouling of physical-chemical treatment processes and decreasing biological activity during produced water holding; however, conventional activated sludge treatments are intolerant of high salinity. In this study, a biofilm treatment approach using constructed microbial mats was evaluated for biodegradation performance, microbial community structure, and metabolic potential in both simulated and real produced water. Results demonstrated that engineered microbial mats are active at total dissolved solids (TDS) concentrations up to at least 100,000 mg/L, and experiments in real produced water showed a biodegradation capacity of 1.45 mg COD/gramwet-day at a TDS concentration of 91,351 mg/L. Additionally, microbial community and metagenomic analyses revealed an adaptive microbial community that shifted based upon the sample being treated and has the metabolic potential to degrade a wide array of contaminants, suggesting the potential of this approach to treat produced waters with varying composition.

Physical activity and telomere biology: exploring the link with aging-related disease prevention.

PubMed

Ludlow, Andrew T; Roth, Stephen M

2011-02-21

Physical activity is associated with reduced risk of several age-related diseases as well as with increased longevity in both rodents and humans. Though these associations are well established, evidence of the molecular and cellular factors associated with reduced disease risk and increased longevity resulting from physical activity is sparse. A long-standing hypothesis of aging is the telomere hypothesis: as a cell divides, telomeres shorten resulting eventually in replicative senescence and an aged phenotype. Several reports have recently associated telomeres and telomere-related proteins to diseases associated with physical inactivity and aging including cardiovascular disease, insulin resistance, and hypertension. Interestingly several reports have also shown that longer telomeres are associated with higher physical activity levels, indicating a potential mechanistic link between physical activity, reduced age-related disease risk, and longevity. The primary purpose of this review is to discuss the potential importance of physical activity in telomere biology in the context of inactivity- and age-related diseases. A secondary purpose is to explore potential mechanisms and important avenues for future research in the field of telomeres and diseases associated with physical inactivity and aging.

Analyzing cell fate control by cytokines through continuous single cell biochemistry.

PubMed

Rieger, Michael A; Schroeder, Timm

2009-10-01

Cytokines are important regulators of cell fates with high clinical and commercial relevance. However, despite decades of intense academic and industrial research, it proved surprisingly difficult to describe the biological functions of cytokines in a precise and comprehensive manner. The exact analysis of cytokine biology is complicated by the fact that individual cytokines control many different cell fates and activate a multitude of intracellular signaling pathways. Moreover, although activating different molecular programs, different cytokines can be redundant in their biological effects. In addition, cytokines with different biological effects can activate overlapping signaling pathways. This prospect article will outline the necessity of continuous single cell biochemistry to unravel the biological functions of molecular cytokine signaling. It focuses on potentials and limitations of recent technical developments in fluorescent time-lapse imaging and single cell tracking allowing constant long-term observation of molecules and behavior of single cells. (c) 2009 Wiley-Liss, Inc.

Synthesis, biological evaluation, and molecular modeling of cinnamic acyl sulfonamide derivatives as novel antitubulin agents.

PubMed

Luo, Yin; Qiu, Ke-Ming; Lu, Xiang; Liu, Kai; Fu, Jie; Zhu, Hai-Liang

2011-08-15

A series of novel cinnamic acyl sulfonamide derivatives (9a-16e) have been designed and synthesized and their biological activities were also evaluated as potential tubulin polymerization inhibitors. Among all the compounds, 10c showed the most potent growth inhibitory activity against B16-F10 cancer cell line in vitro, with an IC(50) value of 0.8μg/mL. Docking simulation was performed to insert compound 10c into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. Based on the preliminary results, compound 10c with potent inhibitory activity in tumor growth may be a potential anticancer agent. Copyright © 2011 Elsevier Ltd. All rights reserved.

Medicinal Properties of the Genus Clitocybe and of Lectins from the Clouded Funnel Cap Mushroom, C. nebularis (Agaricomycetes): A Review.

PubMed

Pohleven, Jure; Kos, Janko; Sabotic, Jerica

2016-01-01

Current knowledge of the medicinal properties of Basidiomycetes mushroom species of the genus Clitocybe and of the biological activity of C. nebularis fruiting bodies is reviewed. The main focus is the therapeutic potential of lectins from C. nebularis. Species of the genus Clitocybe, including C. nebularis, have not been traditionally considered as medicinal mushrooms; however, recent studies have demonstrated their antitumor, immunomodulatory, and antioxidative properties, their antimicrobial (antiviral, antibacterial, and antifungal) activities against various bacteria and fungi, as well as their potential use in therapy for alcoholism and as psychotropic agents. These activities have been shown to be due to various compounds, either isolated or in extracts, mainly polysaccharides but also phenols, ribonucleosides, and proteins. These include laccase, protease inhibitors, and lectins. C. nebularis has been shown to be rich in a variety of lectins and isolectins with distinct carbohydrate-binding specificities, showing versatile biological activities. They exhibit immunostimulatory and adhesion-/phagocytosis-promoting properties, as well as toxicity in various invertebrates. Mushroom species of the genus Clitocybe, including C. nebularis, thus constitute a valuable source of compounds showing diverse biological activities with a broad potential for applications in biomedicine or biotechnology. On the basis of such evidence reviewed here, we propose that C. nebularis and other Clitocybe species can be considered to be medicinal mushrooms.

Synthetic biology: An emerging research field in China

PubMed Central

Pei, Lei; Schmidt, Markus; Wei, Wei

2011-01-01

Synthetic biology is considered as an emerging research field that will bring new opportunities to biotechnology. There is an expectation that synthetic biology will not only enhance knowledge in basic science, but will also have great potential for practical applications. Synthetic biology is still in an early developmental stage in China. We provide here a review of current Chinese research activities in synthetic biology and its different subfields, such as research on genetic circuits, minimal genomes, chemical synthetic biology, protocells and DNA synthesis, using literature reviews and personal communications with Chinese researchers. To meet the increasing demand for a sustainable development, research on genetic circuits to harness biomass is the most pursed research within Chinese researchers. The environmental concerns are driven force of research on the genetic circuits for bioremediation. The research on minimal genomes is carried on identifying the smallest number of genomes needed for engineering minimal cell factories and research on chemical synthetic biology is focused on artificial proteins and expanded genetic code. The research on protocells is more in combination with the research on molecular-scale motors. The research on DNA synthesis and its commercialisation are also reviewed. As for the perspective on potential future Chinese R&D activities, it will be discussed based on the research capacity and governmental policy. PMID:21729747

Biological Activity of Ionic Liquids and Their Application in Pharmaceutics and Medicine.

PubMed

Egorova, Ksenia S; Gordeev, Evgeniy G; Ananikov, Valentine P

2017-05-24

Ionic liquids are remarkable chemical compounds, which find applications in many areas of modern science. Because of their highly tunable nature and exceptional properties, ionic liquids have become essential players in the fields of synthesis and catalysis, extraction, electrochemistry, analytics, biotechnology, etc. Apart from physical and chemical features of ionic liquids, their high biological activity has been attracting significant attention from biochemists, ecologists, and medical scientists. This Review is dedicated to biological activities of ionic liquids, with a special emphasis on their potential employment in pharmaceutics and medicine. The accumulated data on the biological activity of ionic liquids, including their antimicrobial and cytotoxic properties, are discussed in view of possible applications in drug synthesis and drug delivery systems. Dedicated attention is given to a novel active pharmaceutical ingredient-ionic liquid (API-IL) concept, which suggests using traditional drugs in the form of ionic liquid species. The main aim of this Review is to attract a broad audience of chemical, biological, and medical scientists to study advantages of ionic liquid pharmaceutics. Overall, the discussed data highlight the importance of the research direction defined as "Ioliomics", studies of ions in liquids in modern chemistry, biology, and medicine.

Molecularly stabilised ultrasmall gold nanoparticles: synthesis, characterization and bioactivity

NASA Astrophysics Data System (ADS)

Leifert, Annika; Pan-Bartnek, Yu; Simon, Ulrich; Jahnen-Dechent, Willi

2013-06-01

Gold nanoparticles (AuNPs) are widely used as contrast agents in electron microscopy as well as for diagnostic tests. Due to their unique optical and electrical properties and their small size, there is also a growing field of potential applications in medical fields of imaging and therapy, for example as drug carriers or as active compounds in thermotherapy. Besides their intrinsic optical properties, facile surface decoration with (bio)functional ligands renders AuNPs ideally suited for many industrial and medical applications. However, novel AuNPs may have toxicological profiles differing from bulk and therefore a thorough analysis of the quantitative structure-activity relationship (QSAR) is required. Several mechanisms are proposed that cause adverse effects of nanoparticles in biological systems. Catalytic generation of reactive species due to the large and chemically active surface area of nanomaterials is well established. Because nanoparticles approach the size of biological molecules and subcellular structures, they may overcome natural barriers by active or passive uptake. Ultrasmall AuNPs with sizes of 2 nm or less may even behave as molecular ligands. These types of potential interactions would imply a size and ligand-dependent behaviour of any nanomaterial towards biological systems. Thus, to fully understand their QSAR, AuNPs bioactivity should be analysed in biological systems of increasing complexity ranging from cell culture to whole animal studies.

Unlocking the chemotherapeutic potential of beta-aminovinyl ketones and related compounds.

PubMed

Gaber, Hatem M; Bagley, Mark C

2009-07-01

The role of beta-aminovinyl ketones as synthetic intermediates has been well categorised, but recent developments have shown an interesting array of applications and new chemotherapeutic potential, both in the preparation of biologically active heterocycles and as pharmacophores in their own right.Medicinal chemists are accustomed to using the products of Knoevenagel-type condensations as auxiliaries for the synthesis of N-containing heteroaromatic compounds. One such example of these chemical building blocks are beta-aminovinyl ketones-valuable synthetic intermediates that have been used in the preparation of pyridines, pyrimidines, pyrazoles, and many other heterocyclic motifs. This review highlights their recent use in the synthesis of biologically active targets as part of drug discovery programmes and in natural product synthesis. However, it is becoming increasingly evident that the enaminone motif may serve as a therapeutic pharmacophore in its own right. This review highlights the range of biological responses that beta-aminovinyl ketones elicit, including as antitumour, antibacterial, and anticonvulsant agents. Thus, with a broad spectrum of biological properties and as versatile chemical intermediates, it is clear that beta-aminovinyl ketones offer great potential in the search for new chemotherapeutic agents.

Overview on Biological Activities and Molecular Characteristics of Sulfated Polysaccharides from Marine Green Algae in Recent Years

PubMed Central

Wang, Lingchong; Wang, Xiangyu; Wu, Hao; Liu, Rui

2014-01-01

Among the three main divisions of marine macroalgae (Chlorophyta, Phaeophyta and Rhodophyta), marine green algae are valuable sources of structurally diverse bioactive compounds and remain largely unexploited in nutraceutical and pharmaceutical areas. Recently, a great deal of interest has been developed to isolate novel sulfated polysaccharides (SPs) from marine green algae because of their numerous health beneficial effects. Green seaweeds are known to synthesize large quantities of SPs and are well established sources of these particularly interesting molecules such as ulvans from Ulva and Enteromorpha, sulfated rhamnans from Monostroma, sulfated arabinogalactans from Codium, sulfated galacotans from Caulerpa, and some special sulfated mannans from different species. These SPs exhibit many beneficial biological activities such as anticoagulant, antiviral, antioxidative, antitumor, immunomodulating, antihyperlipidemic and antihepatotoxic activities. Therefore, marine algae derived SPs have great potential for further development as healthy food and medical products. The present review focuses on SPs derived from marine green algae and presents an overview of the recent progress of determinations of their structural types and biological activities, especially their potential health benefits. PMID:25257786

Biological activities of Agave by-products and their possible applications in food and pharmaceuticals.

PubMed

López-Romero, Julio Cesar; Ayala-Zavala, Jesús Fernando; González-Aguilar, Gustavo Adolfo; Peña-Ramos, Etna Aida; González-Ríos, Humberto

2018-05-01

Agave leaves are considered a by-product of alcoholic beverage production (tequila, mezcal and bacanora) because they are discarded during the production process, despite accounting for approximately 50% of the total plant weight. These by-products constitute a potential source of Agave extracts rich in bioactive compounds, such as saponins, phenolic compounds and terpenes, and possess different biological effects, as demonstrated by in vitro and in vivo tests (e.g. antimicrobial, antifungal, antioxidant, anti-inflammatory, antihypertensive, immunomodulatory, antiparasitic and anticancer activity). Despite their positive results in biological assays, Agave extracts have not been widely evaluated in food systems and pharmaceutical areas, and these fields represent a potential route to improve the usage of Agave plants as food additives and agents for treating medical diseases. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Potential for enhancement of aerobic biological removal of recalcitrant organic matter in bleached pulp mill effluents.

PubMed

Mounteer, A H; Souza, L C; Silva, C M

2007-02-01

Increasingly stringent effluent quality limits for bleached kraft pulp mills pose a great challenge to mill wastewater system managers since these limits can require levels of chemical oxygen demand (COD) removal efficiency rarely reported for biological treatment of these types of effluents. The present study was therefore undertaken to better understand the nature of recalcitrant COD in bleached kraft pulp effluents that persists through the biological treatment system. Bleaching effluents from a Brazilian eucalypt bleached kraft pulp mill were collected and treated in a bench-scale sequencing batch reactor. Organic matter in raw and treated effluents was characterized before and after separation into low and high molecular mass fractions. Biological treatment removed 71% of the COD, with 83% removal of the low molecular mass COD but only 36% removal of the high molecular mass COD. Microorganisms capable of degrading the recalcitrant COD were isolated from enrichment cultures of the original activated sludge fed on fractions of the bleaching effluent that presented low biodegradabilities. Use of a microbial consortium composed of ten of these isolates to treat the biologically treated effluent removed a further 12% of the effluent COD, all from the high molecular mass fraction. Results of this research indicate that microorganisms with potential for degrading recalcitrant COD are present in activated sludge, but that these are not metabolically active during normal activated sludge treatment of mill effluents. The use of biological selectors in the treatment system to promote growth of such microorganisms may enhance removal of recalcitrant organic matter.

Active Learning Not Associated with Student Learning in a Random Sample of College Biology Courses

PubMed Central

Andrews, T. M.; Leonard, M. J.; Colgrove, C. A.; Kalinowski, S. T.

2011-01-01

Previous research has suggested that adding active learning to traditional college science lectures substantially improves student learning. However, this research predominantly studied courses taught by science education researchers, who are likely to have exceptional teaching expertise. The present study investigated introductory biology courses randomly selected from a list of prominent colleges and universities to include instructors representing a broader population. We examined the relationship between active learning and student learning in the subject area of natural selection. We found no association between student learning gains and the use of active-learning instruction. Although active learning has the potential to substantially improve student learning, this research suggests that active learning, as used by typical college biology instructors, is not associated with greater learning gains. We contend that most instructors lack the rich and nuanced understanding of teaching and learning that science education researchers have developed. Therefore, active learning as designed and implemented by typical college biology instructors may superficially resemble active learning used by education researchers, but lacks the constructivist elements necessary for improving learning. PMID:22135373

Moonlighting proteins in cancer.

PubMed

Min, Kyung-Won; Lee, Seong-Ho; Baek, Seung Joon

2016-01-01

Since the 1980s, growing evidence suggested that the cellular localization of proteins determined their activity and biological functions. In a classical view, a protein is characterized by the single cellular compartment where it primarily resides and functions. It is now believed that when proteins appear in different subcellular locations, the cells surpass the expected activity of proteins given the same genomic information to fulfill complex biological behavior. Many proteins are recognized for having the potential to exist in multiple locations in cells. Dysregulation of translocation may cause cancer or contribute to poorer cancer prognosis. Thus, quantitative and comprehensive assessment of dynamic proteins and associated protein movements could be a promising indicator in determining cancer prognosis and efficiency of cancer treatment and therapy. This review will summarize these so-called moonlighting proteins, in terms of a coupled intracellular cancer signaling pathway. Determination of the detailed biological intracellular and extracellular transit and regulatory activity of moonlighting proteins permits a better understanding of cancer and identification of potential means of molecular intervention. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Assessment of biological effects of environmental pollution in Mersin Bay (Turkey, northeastern Mediterranean Sea) using Mullus barbatus and Liza ramada as target organisms.

PubMed

Yılmaz, Doruk; Kalay, Mustafa; Dönmez, Erdem; Yılmaz, Nejat

2016-01-01

The increasing emphasis on the assessment and monitoring of marine ecosystems has revealed the need to use appropriate biological indicators for these areas. Enzyme activities and histopathology are increasingly being used as indicators of environmental stress since they provide a definite biological end-point of pollutant exposure. As part of an ecotoxicological assessment of Mersin Bay, EROD enzyme activity and histopathological response in selected organs and tissues of two species of fish, Mullus barbatus (red mullet) and Liza ramada (thinlip grey mullet), captured from area were examined. Pollutant (Organochlorines (OC), alkylphenols (APs) and BPA) levels and biomarker responses in tissue samples were evaluated together for their potential to alter the metabolism and cellular aspects in liver and gonad. Elevated induction of EROD activity and histopathological alterations in contaminated samples from Mersin Bay was observed compared to reference site indicating the exposure to potential pollutants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Endophytic Actinobacteria from the Brazilian Medicinal Plant Lychnophora ericoides Mart. and the Biological Potential of Their Secondary Metabolites.

PubMed

Conti, Raphael; Chagas, Fernanda Oliveira; Caraballo-Rodriguez, Andrés Mauricio; Melo, Weilan Gomes da Paixão; do Nascimento, Andréa Mendes; Cavalcanti, Bruno Coêlho; de Moraes, Manoel Odorico; Pessoa, Cláudia; Costa-Lotufo, Letícia Veras; Krogh, Renata; Andricopulo, Adriano Defini; Lopes, Norberto Peporine; Pupo, Mônica Tallarico

2016-06-01

Endophytic actinobacteria from the Brazilian medicinal plant Lychnophora ericoides were isolated for the first time, and the biological potential of their secondary metabolites was evaluated. A phylogenic analysis of isolated actinobacteria was accomplished with 16S rRNA gene sequencing, and the predominance of the genus Streptomyces was observed. All strains were cultured on solid rice medium, and ethanol extracts were evaluated with antimicrobial and cytotoxic assays against cancer cell lines. As a result, 92% of the extracts showed a high or moderate activity against at least one pathogenic microbial strain or cancer cell line. Based on the biological and chemical analyses of crude extracts, three endophytic strains were selected for further investigation of their chemical profiles. Sixteen compounds were isolated, and 3-hydroxy-4-methoxybenzamide (9) and 2,3-dihydro-2,2-dimethyl-4(1H)-quinazolinone (15) are reported as natural products for the first time in this study. The biological activity of the pure compounds was also assessed. Compound 15 displayed potent cytotoxic activity against all four tested cancer cell lines. Nocardamine (2) was only moderately active against two cancer cell lines but showed strong activity against Trypanosoma cruzi. Our results show that endophytic actinobacteria from L. ericoides are a promising source of bioactive compounds. © 2016 Verlag Helvetica Chimica Acta AG, Zürich.

Active ingredients of ginger as potential candidates in the prevention and treatment of diseases via modulation of biological activities

PubMed Central

Rahmani, Arshad H; shabrmi, Fahad M Al; Aly, Salah M

2014-01-01

The current mode of treatment based on synthetic drugs is expensive and also causes genetic and metabolic alterations. However, safe and sound mode of treatment is needed to control the diseases development and progression. In this regards, medicinal plant and its constituents play an important role in diseases management via modulation of biological activities. Ginger, the rhizome of the Zingiber officinale, has shown therapeutic role in the health management since ancient time and considered as potential chemopreventive agent. Numerous studies based on clinical trials and animal model has shown that ginger and its constituents shows significant role in the prevention of diseases via modulation of genetic and metabolic activities. In this review, we focused on the therapeutics effects of ginger and its constituents in the diseases management, and its impact on genetic and metabolic activities. PMID:25057339

PVP and PEG doped CuO nanoparticles are more biologically active: Antibacterial, antioxidant, antidiabetic and cytotoxic perspective.

PubMed

Javed, Rabia; Ahmed, Madiha; Haq, Ihsan Ul; Nisa, Sobia; Zia, Muhammad

2017-10-01

Search for biologically active nanoparticles is prerequisite for biomedical applications. CuO nanoparticles synthesized by co-precipitation method are capped by polyethylene-glycol (PEG) and polyvinyl-pyrrolidone (PVP) on the surface by simple adsorption. Physical and chemical properties carried out by SEM, XRD and FTIR confirm nanometer in size and efficient capping of PVP and PEG on CuO NPs. Biological assays reveal higher activities of CuO-PEG and CuO-PVP as compared to the uncapped CuO nanoparticles. CuO-PEG shows better antitumor activity against Streptomyces as compared with CuO-PVP and CuO NPs. Both the capped NPs are significantly active for α-amylase inhibition assay. CuO-PVP demonstrates significantly better activity against bacterial strains followed by CuO-PEG and uncapped CuO. PVP coated CuO NPs also shows strong DPPH based free radical scavenging activity, total reducing power potential, total antioxidative potential and also carries flavonoid and phenolics properties determines to querecetin and gallic acid equivalence, respectively. It can be concluded that PVP and PEG capped CuO NPs are more capable to be used in biomedical applications as drug and diagnostic carrier molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

The development of synthetic biology: a patent analysis.

PubMed

van Doren, Davy; Koenigstein, Stefan; Reiss, Thomas

2013-12-01

In the past decades, synthetic biology has gained interest regarding research and development efforts within the biotechnology domain. However, it is unclear to what extent synthetic biology has matured already into being commercially exploitable. By means of a patent analysis, this study shows that there is an increasing trend regarding synthetic biology related patent applications. The majority of retrieved patents relates to innovations facilitating the realisation of synthetic biology through improved understanding of biological systems. In addition, there is increased activity concerning the development of synthetic biology based applications. When looking at potential application areas, the majority of synthetic biology patents seems most relevant for the medical, energy and industrial sector. Furthermore, the analysis shows that most activity has been carried out by the USA, with Japan and a number of European countries considerably trailing behind. In addition, both universities and companies are major patent applicant actor types. The results presented here form a starting point for follow-up studies concerning the identification of drivers explaining the observed patent application trends in synthetic biology.

Traditional Uses, Chemical Constituents, and Biological Activities of Bixa orellana L.: A Review

PubMed Central

Vilar, Daniela de Araújo; Vilar, Marina Suênia de Araujo; Moura, Túlio Flávio Accioly de Lima e; Raffin, Fernanda Nervo; de Oliveira, Márcia Rosa; Franco, Camilo Flamarion de Oliveira; de Athayde-Filho, Petrônio Filgueiras; Diniz, Margareth de Fátima Formiga Melo; Barbosa-Filho, José Maria

2014-01-01

Bixa orellana L., popularly known as “urucum,” has been used by indigenous communities in Brazil and other tropical countries for several biological applications, which indicates its potential use as an active ingredient in pharmaceutical products. The aim of this work was to report the main evidence found in the literature, concerning the ethnopharmacology, the biological activity, and the phytochemistry studies related to Bixa orellana L. Therefore, this work comprises a systematic review about the use of Bixa orellana in the American continent and analysis of the data collected. This study shows the well-characterized pharmacological actions that may be considered relevant for the future development of an innovative therapeutic agent. PMID:25050404

Chemical and Biological Contract Manufacturing Services: Potential Proliferation Concerns and Impacts on Strategic Trade Controls

DOE PAGES

Carrera, Julie A.; Castiglioni, Andrew J.; Heine, Peter M.

2017-04-01

The use of contract manufacturing services in the chemical, pharmaceutical, and biotechnology industries has grown significantly in recent years, but the potential for such service providers to be exploited for chemical or biological weapons proliferation has garnered relatively little attention, despite the role of contract manufacturers in the A.Q. Khan nuclear proliferation network. Here, we examine the dual-use potential and global spread of chemical and biological contract manufacturing and their ramifications for related strategic trade controls (STCs). Hundreds of providers of dual-use contract services were found worldwide, but they were primarily located in jurisdictions with comprehensive STC regulations. This thenmore » provides some degree of protection against their misuse. However, the results outlined below also suggest that chemical and biological contract manufacturers are a critical community to target for STC outreach activities and efforts to increase industry compliance. Targeted outreach would help prevent contract manufacturing service providers from unwittingly contributing to the production and proliferation of chemical and biological weapons.« less

Chemical and Biological Contract Manufacturing Services: Potential Proliferation Concerns and Impacts on Strategic Trade Controls

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carrera, Julie A.; Castiglioni, Andrew J.; Heine, Peter M.

The use of contract manufacturing services in the chemical, pharmaceutical, and biotechnology industries has grown significantly in recent years, but the potential for such service providers to be exploited for chemical or biological weapons proliferation has garnered relatively little attention, despite the role of contract manufacturers in the A.Q. Khan nuclear proliferation network. Here, we examine the dual-use potential and global spread of chemical and biological contract manufacturing and their ramifications for related strategic trade controls (STCs). Hundreds of providers of dual-use contract services were found worldwide, but they were primarily located in jurisdictions with comprehensive STC regulations. This thenmore » provides some degree of protection against their misuse. However, the results outlined below also suggest that chemical and biological contract manufacturers are a critical community to target for STC outreach activities and efforts to increase industry compliance. Targeted outreach would help prevent contract manufacturing service providers from unwittingly contributing to the production and proliferation of chemical and biological weapons.« less

Mast cells: potential positive and negative roles in tumor biology.

PubMed

Marichal, Thomas; Tsai, Mindy; Galli, Stephen J

2013-11-01

Mast cells are immune cells that reside in virtually all vascularized tissues. Upon activation by diverse mechanisms, mast cells can secrete a broad array of biologically active products that either are stored in the cytoplasmic granules of the cells (e.g., histamine, heparin, various proteases) or are produced de novo upon cell stimulation (e.g., prostaglandins, leukotrienes, cytokines, chemokines, and growth factors). Mast cells are best known for their effector functions during anaphylaxis and acute IgE-associated allergic reactions, but they also have been implicated in a wide variety of processes that maintain health or contribute to disease. There has been particular interest in the possible roles of mast cells in tumor biology. In vitro studies have shown that mast cells have the potential to influence many aspects of tumor biology, including tumor development, tumor-induced angiogenesis, and tissue remodeling, and the shaping of adaptive immune responses to tumors. Yet, the actual contributions of mast cells to tumor biology in vivo remain controversial. Here, we review some basic features of mast cell biology with a special emphasis on those relevant to their potential roles in tumors. We discuss how using in vivo tumor models in combination with models in which mast cell function can be modulated has implicated mast cells in the regulation of host responses to tumors. Finally, we summarize data from studies of human tumors that suggest either beneficial or detrimental roles for mast cells in tumors. ©2013 AACR.

DOE Office of Scientific and Technical Information (OSTI.GOV)

JOHNSON, A.R.

Biological control is any activity taken to prevent, limit, clean up, or remediate potential environmental, health and safety, or workplace quality impacts from plants, animals, or microorganisms. At Hanford the principal emphasis of biological control is to prevent the transport of radioactive contamination by biological vectors (plants, animals, or microorganisms), and where necessary, control and clean up resulting contamination. Other aspects of biological control at Hanford include industrial weed control (e.g.; tumbleweeds), noxious weed control (invasive, non-native plant species), and pest control (undesirable animals such as rodents and stinging insects; and microorganisms such as molds that adversely affect the qualitymore » of the workplace environment). Biological control activities may be either preventive (apriori) or in response to existing contamination spread (aposteriori). Surveillance activities, including ground, vegetation, flying insect, and other surveys, and apriori control actions, such as herbicide spraying and placing biological barriers, are important in preventing radioactive contamination spread. If surveillance discovers that biological vectors have spread radioactive contamination, aposteriori control measures, such as fixing contamination, followed by cleanup and removal of the contamination to an approved disposal location are typical response functions. In some cases remediation following the contamination cleanup and removal is necessary. Biological control activities for industrial weeds, noxious weeds and pests have similar modes of prevention and response.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

JOHNSON, A.R.

Biological control is any activity taken to prevent, limit, clean up, or remediate potential environmental, health and safety, or workplace quality impacts from plants, animals, or microorganisms. At Hanford the principal emphasis of biological control is to prevent the transport of radioactive contamination by biological vectors (plants, animals, or microorganisms), and where necessary, control and clean up resulting contamination. Other aspects of biological control at Hanford include industrial weed control (e.g.; tumbleweeds), noxious weed control (invasive, non-native plant species), and pest control (undesirable animals such as rodents and stinging insects, and microorganisms such as molds that adversely affect the qualitymore » of the workplace environment). Biological control activities may be either preventive (a priori) or in response to existing contamination spread (a posteriori). Surveillance activities, including ground, vegetation, flying insect, and other surveys, and a priori control actions, such as herbicide spraying and placing biological barriers, are important in preventing radioactive contamination spread. If surveillance discovers that biological vectors have spread radioactive contamination, a posteriori control measures, such as fixing contamination, followed by cleanup and removal of the contamination to an approved disposal location are typical response functions. In some cases remediation following the contamination cleanup and removal is necessary. Biological control activities for industrial weeds, noxious weeds and pests have similar modes of prevention and response.« less

Biological potential of oxo-vanadium salicylediene amino-acid complexes as cytotoxic, antimicrobial, antioxidant and DNA interaction.

PubMed

Adam, Mohamed Shaker S; Elsawy, Hany

2018-05-04

New series of oxo-vanadium N-salicyledieneamino acid Schiff base complexes are synthesized and characterized. They are synthesized from the reaction of sodium salicylaldehyde-5-sulfonate, some amino acids, alanine (VOHL1), leucine (VOHL2) or glycine (VOHL3) in an aqueous media, and leucine (VOHLpy1) or tryptophan (VOHLpy2) in pyridine with vanadyl acetylacetonate. The complexes are characterized by EA, TGA, IR, UV-Visible and mass spectra, conductivity and magnetic measurements. The biological activity of the VO-complexes shows that VOHL1, VOHL2 and VOHL3 exhibit anti-proliferative effect and may be used as anticancer drugs. VO-complexes manifest high toxicity, except VOHL2 is less toxic, and could be applied for the human being. VOHL1, VOHL2 and VOHL3 display remarkable SOD like potential and act as high inhibiting reagents. VOHLpy1 and VOHLpy2 show low inhibiting potentials. VO-complexes have good anti-oxidant effect, in which VOHL3 affords the best antioxidant activity. The interaction between VO-complexes and DNA is studied spectrophotometrically and by gel electrophoresis. Binding constants and spectrophotometric parameters indicate a strong interaction between VO-complexes and DNA. VO-complexes have respectable anti-bacterial and antifungal activities, where VOHL3 shows the maximum potential. DFT calculations of VOHL1 and VOHL3 were discussed in the light of their biological activity, which are convenient with the obtained results. Copyright © 2018 Elsevier B.V. All rights reserved.

Generation of structurally novel short carotenoids and study of their biological activity

PubMed Central

Kim, Se H.; Kim, Moon S.; Lee, Bun Y.; Lee, Pyung C.

2016-01-01

Recent research interest in phytochemicals has consistently driven the efforts in the metabolic engineering field toward microbial production of various carotenoids. In spite of systematic studies, the possibility of using C30 carotenoids as biologically functional compounds has not been explored thus far. Here, we generated 13 novel structures of C30 carotenoids and one C35 carotenoid, including acyclic, monocyclic, and bicyclic structures, through directed evolution and combinatorial biosynthesis, in Escherichia coli. Measurement of radical scavenging activity of various C30 carotenoid structures revealed that acyclic C30 carotenoids showed higher radical scavenging activity than did DL-α-tocopherol. We could assume high potential biological activity of the novel structures of C30 carotenoids as well, based on the neuronal differentiation activity observed for the monocyclic C30 carotenoid 4,4′-diapotorulene on rat bone marrow mesenchymal stem cells. Our results demonstrate that a series of structurally novel carotenoids possessing biologically beneficial properties can be synthesized in E. coli. PMID:26902326

Generation of structurally novel short carotenoids and study of their biological activity.

PubMed

Kim, Se H; Kim, Moon S; Lee, Bun Y; Lee, Pyung C

2016-02-23

Recent research interest in phytochemicals has consistently driven the efforts in the metabolic engineering field toward microbial production of various carotenoids. In spite of systematic studies, the possibility of using C30 carotenoids as biologically functional compounds has not been explored thus far. Here, we generated 13 novel structures of C30 carotenoids and one C35 carotenoid, including acyclic, monocyclic, and bicyclic structures, through directed evolution and combinatorial biosynthesis, in Escherichia coli. Measurement of radical scavenging activity of various C30 carotenoid structures revealed that acyclic C30 carotenoids showed higher radical scavenging activity than did DL-α-tocopherol. We could assume high potential biological activity of the novel structures of C30 carotenoids as well, based on the neuronal differentiation activity observed for the monocyclic C30 carotenoid 4,4'-diapotorulene on rat bone marrow mesenchymal stem cells. Our results demonstrate that a series of structurally novel carotenoids possessing biologically beneficial properties can be synthesized in E. coli.

Understanding the sorption and biotransformation of organic micropollutants in innovative biological wastewater treatment technologies.

PubMed

Alvarino, T; Suarez, S; Lema, J; Omil, F

2018-02-15

New technologies for wastewater treatment have been developed in the last years based on the combination of biological reactors operating under different redox conditions. Their efficiency in the removal of organic micropollutants (OMPs) has not been clearly assessed yet. This review paper is focussed on understanding the sorption and biotransformation of a selected group of 17 OMPs, including pharmaceuticals, hormones and personal care products, during biological wastewater treatment processes. Apart from considering the role of "classical" operational parameters, new factors such as biomass conformation and particle size, upward velocity applied or the addition of adsorbents have been considered. It has been found that the OMP removal by sorption not only depends on their physico-chemical characteristics and other parameters, such as the biomass conformation and particle size, or some operational conditions also relevant. Membrane biological reactors (MBR), have shown to enhance sorption and biotransformation of some OMPs. The same applies to technologies bases on direct addition of activated carbon in bioreactors. The OMP biotransformation degree and pathway is mainly driven by the redox potential and the primary substrate activity. The combination of different redox potentials in hybrid reactor systems can significantly enhance the overall OMP removal efficiency. Sorption and biotransformation can be synergistically promoted in biological reactors by the addition of activated carbon. The deeper knowledge of the main parameters influencing OMP removal provided by this review will allow optimizing the biological processes in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

Phylogenetic Diversity and Biological Activity of Actinobacteria Isolated from the Chukchi Shelf Marine Sediments in the Arctic Ocean

PubMed Central

Yuan, Meng; Yu, Yong; Li, Hui-Rong; Dong, Ning; Zhang, Xiao-Hua

2014-01-01

Marine environments are a rich source of Actinobacteria and have the potential to produce a wide variety of biologically active secondary metabolites. In this study, we used four selective isolation media to culture Actinobacteria from the sediments collected from the Chukchi Shelf in the Arctic Ocean. A total of 73 actinobacterial strains were isolated. Based on repetitive DNA fingerprinting analysis, we selected 30 representatives for partial characterization according to their phylogenetic diversity, antimicrobial activities and secondary-metabolite biosynthesis genes. Results from the 16S rRNA gene sequence analysis indicated that the 30 strains could be sorted into 18 phylotypes belonging to 14 different genera: Agrococcus, Arsenicicoccus, Arthrobacter, Brevibacterium, Citricoccus, Janibacter, Kocuria, Microbacterium, Microlunatus, Nocardioides, Nocardiopsis, Saccharopolyspora, Salinibacterium and Streptomyces. To our knowledge, this paper is the first report on the isolation of Microlunatus genus members from marine habitats. Of the 30 isolates, 11 strains exhibited antibacterial and/or antifungal activity, seven of which have activities against Bacillus subtilis and Candida albicans. All 30 strains have at least two biosynthetic genes, one-third of which possess more than four biosynthetic genes. This study demonstrates the significant diversity of Actinobacteria in the Chukchi Shelf sediment and their potential for producing biologically active compounds and novel material for genetic manipulation or combinatorial biosynthesis. PMID:24663116

Colloidal transport through trap arrays controlled by active microswimmers

NASA Astrophysics Data System (ADS)

Yang, Wen; Misko, Vyacheslav R.; Marchesoni, Fabio; Nori, Franco

2018-07-01

We investigate the dynamics of a binary mixture consisting of active and passive colloidal particles diffusing in a 2D array of truncated harmonic wells, or traps. We explore the possibility of using a small fraction of active particles to manipulate a much larger fraction of passive particles, for instance, to confine them in or extract them from the traps. The results of our study have potential application in biology and medical sciences, for example, to remove dead cells or undesired contaminants from biological systems by means of self-propelled nano-robots.

Chemical composition, antimicrobial, insecticidal, phytotoxic and antioxidant activities of Mediterranean Pinus brutia and Pinus pinea resin essential oils.

PubMed

Ulukanli, Zeynep; Karabörklü, Salih; Bozok, Fuat; Ates, Burhan; Erdogan, Selim; Cenet, Menderes; Karaaslan, Merve Göksin

2014-12-01

Essential oils of the resins of Pinus brutia and Pinus pinea were evaluated for their biological potential. Essential oils were characterized using GC-MS and GC/FID. in vitro antimicrobial, phytotoxic, antioxidant, and insecticidal activities were carried out using the direct contact and the fumigant assays, respectively. The chemical profile of the essential oils of the resins of P. pinea and P. brutia included mainly α-pinene (21.39% and 25.40%), β-pinene (9.68% and 9.69%), and caryophyllene (9.12% and 4.81%). The essential oils of P. pinea and P. brutia exerted notable antimicrobial activities on Micrococcus luteus and Bacillus subtilis, insecticidal activities on Ephestia kuehniella eggs, phytotoxic activities on Lactuca sativa, Lepidium sativum, and Portulaca oleracea, as well as antioxidant potential. Indications of the biological activities of the essential oils suggest their use in the formulation of ecofriendly and biocompatible pharmaceuticals. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Biodegradation of phytosanitary products in biological wastewater treatment.

PubMed

Massot, A; Estève, K; Noilet, P; Méoule, C; Poupot, C; Mietton-Peuchot, M

2012-04-15

Agricultural activity generates two types of waste: firstly, biodegradable organic effluents generally treated by biological processes and, secondly, phytosanitary effluents which contain residues of plant protection products. The latter are collected and treated. Current technological solutions are essentially based on concentration or physical-chemical processes. However, recent improvements in the biodegradability of pesticides open the way to the consideration of alternative, biological, treatment using mixed liquor from wastewater plant activated sludge. The feasibility of the biological treatment of viticultural effluents has been evaluated by the application of pesticides to activated sludge. The necessity for selection of a pesticide-resistant biomass has been highlighted. The elimination of the phytosanitary products shows the potential of a resistant biomass in the treatment of pesticides. The aerated biological storage ponds at three wineries, followed by a sand or reed-bed filter, were used for the treatment of the total annual volume of the viticulture effluents and validate the laboratory experiments. The results show that the biological purification of pesticides by activated sludge is possible by allowing approximately 8 days for biomass adaptation. Stability of purification occurs between 20 and 30 days. Copyright © 2012 Elsevier Ltd. All rights reserved.

Helleborus purpurascens-Amino Acid and Peptide Analysis Linked to the Chemical and Antiproliferative Properties of the Extracted Compounds.

PubMed

Segneanu, Adina-Elena; Grozescu, Ioan; Cziple, Florentina; Berki, Daniel; Damian, Daniel; Niculite, Cristina Mariana; Florea, Alexandru; Leabu, Mircea

2015-12-11

There is a strong drive worldwide to discover and exploit the therapeutic potential of a large variety of plants. In this work, an alcoholic extract of Helleborus purpurascens (family Ranunculaceae) was investigated for the identification of amino acids and peptides with putative antiproliferative effects. In our work, a separation strategy was developed using solvents of different polarity in order to obtain active compounds. Biochemical components were characterized through spectroscopic (mass spectroscopy) and chromatographic techniques (RP-HPLC and GC-MS). The biological activity of the obtained fractions was investigated in terms of their antiproliferative effects on HeLa cells. Through this study, we report an efficient separation of bioactive compounds (amino acids and peptides) from a plant extract dependent on solvent polarity, affording fractions with unaffected antiproliferative activities. Moreover, the two biologically tested fractions exerted a major antiproliferative effect, thereby suggesting potential anticancer therapeutic activity.

Biological Evaluation of Endophytic Fungus Chaetomium sp. NF15 of Justicia adhatoda L.: A Potential Candidate for Drug Discovery

PubMed Central

Fatima, Nighat; Mukhtar, Usman; Ihsan-Ul-Haq; Ahmed Qazi, Muneer; Jadoon, Muniba; Ahmed, Safia

2016-01-01

Background The endophytes of medicinal plants, such as Justicia adhatoda L., represent a promising and largely underexplored domain that is considered as a repository of biologically active compounds. Objectives The aim of present study was isolation, identification, and biological evaluation of endophytic fungi associated with the J. adhatoda L. plant for the production of antimicrobial, antioxidant, and cytotoxic compounds Materials and Methods Endophytic fungi associated with the J. adhatoda L. plant were isolated from healthy plant parts and taxonomically characterized through morphological, microscopic, and 18S rDNA sequencing methods. The screening for bioactive metabolite production was achieved using ethyl acetate extracts, followed by the optimization of different parameters for maximum production of bioactive metabolites. Crude and partially purified extracts were used to determine the antimicrobial, antioxidant, and cytotoxic potential Results Out of six endophytic fungal isolates, Chaetomium sp. NF15 showed the most promising biological activity and was selected for detailed study. The crude ethyl acetate extract of NF15 isolate after cultivation under optimized culture conditions showed promising antimicrobial activity, with significant inhibition of the clinical isolates of Staphylococcus aureus (87%, n=42), Pseudomonas aeruginosa (> 85%, n = 41), and Candida albicans (62%, n = 24). Conclusions The present study confirms the notion of selecting endophytic fungi of medicinal plant Justicia for the bioassay-guided isolation of its bioactive compounds, and demonstrates that endophytic fungus Chaetomium sp. NF15 could be a potential source of bioactive metabolites PMID:27635208

Antibacterial, Antiradical Potential and Phenolic Compounds of Thirty-One Polish Mushrooms

PubMed Central

Los, Renata; Malm, Anna

2015-01-01

Background Among many sources of natural bioactive substances, mushrooms constitute a huge and almost unexplored group. Fungal compounds have been repeatedly reported to exert biological effects which have prompted their use in pharmaceutical and cosmetic industry. Therefore, the aim of this study was analysis of chemical composition and biological activity of 31 wild growing mushroom species (including saprophytic and parasitic) from Poland. Methods Qualitative and quantitative LC-ESI-MS/MS analysis of fourteen phenolic acids in the mushrooms analysed was performed. Moreover, total phenolic content was determined by the modified Folin-Ciocalteau method. Antioxidative activity of ethanolic extracts towards DPPH• free radical was examined. Antibacterial activity against Gram-positive (S. epidermidis, S. aureus, B. subtilis, M. luteus) and Gram-negative (E. coli, K. pneumoniae, P. aeruginosa, P. mirabilis) microbial strains was analyzed. Results As a result, the first such broad report on polyphenolic composition, antiradical and antimicrobial potential of wild growing Polish mushrooms was developed. Mushroom extracts were found to contain both benzoic (protocatechuic, 4-OH-benzoic, vanillic, syringic) and cinnamic acid derivatives (caffeic, p-coumaric, ferulic). Total phenolic content in mushrooms ranged between 2.79 and 53.13 mg gallic acid equivalent /g of dried extract in Trichaptum fuscoviolaceum and Fomes fomentarius, respectively. Fungi showed much differentiated antiradical activity, from highly active F. fomentarius to poorly effective Russula fragilis (IC50 1.39 to 120.54 mg per mg DPPH•, respectively). A quite considerable relationship between phenolic content and antiradical activity has been demonstrated. Mushrooms varied widely in antimicrobial potential (MIC from 0.156 to 5 mg/ml). Generally, a slightly higher activity against Gram-positive than Gram-negative strains was observed. This is the first study concerning the chemical composition and biological activity of the majority of investigated species. PMID:26468946

Potential amoebicidal activity of hydrazone derivatives: synthesis, characterization, electrochemical behavior, theoretical study and evaluation of the biological activity.

PubMed

Toledano-Magaña, Yanis; García-Ramos, Juan Carlos; Navarro-Olivarria, Marisol; Flores-Alamo, Marcos; Manzanera-Estrada, Mayra; Ortiz-Frade, Luis; Galindo-Murillo, Rodrigo; Ruiz-Azuara, Lena; Meléndrez-Luevano, Ruth Ma; Cabrera-Vivas, Blanca M

2015-05-29

Four new hydrazones were synthesized by the condensation of the selected hydrazine and the appropriate nitrobenzaldehyde. A complete characterization was done employing 1H- and 13C-NMR, electrochemical techniques and theoretical studies. After the characterization and electrochemical analysis of each compound, amoebicidal activity was tested in vitro against the HM1:IMSS strain of Entamoeba histolytica. The results showed the influence of the nitrobenzene group and the hydrazone linkage on the amoebicidal activity. meta-Nitro substituted compound 2 presents a promising amoebicidal activity with an IC50 = 0.84 μM, which represents a 7-fold increase in cell growth inhibition potency with respect to metronidazole (IC50 = 6.3 μM). Compounds 1, 3, and 4 show decreased amoebicidal activity, with IC50 values of 7, 75 and 23 µM, respectively, as a function of the nitro group position on the aromatic ring. The observed differences in the biological activity could be explained not only by the redox potential of the molecules, but also by their capacity to participate in the formation of intra- and intermolecular hydrogen bonds. Redox potentials as well as the amoebicidal activity can be described with parameters obtained from the DFT analysis.

Development of novel therapeutic drugs in humans from plant antimicrobial peptides.

PubMed

da Rocha Pitta, Maira Galdino; da Rocha Pitta, Marina Galdino; Galdino, Suely Lins

2010-05-01

All living organisms, ranging from microorganisms to plants and mammals, have evolved mechanisms to actively defend themselves against pathogen attack. A wide range of biological activities have been attributed to plant antimicrobial peptides (AMPs) including growth inhibitory effects on a broad range of fungi, Gram-positive and Gram-negative bacteria, viruses, neoplasic cells and parasitic protozoa. Classes of AMPs, their mechanisms of action, biological activity, and cytotoxicity towards host cells are discussed. A particular focus regards AMP candidates with potential for use in defense against biological warfare agents. This field is young, but provides additional stimulus to consideration of these molecules as a new class of therapeutic agents and promises to revolutionize treatment of many infectious diseases.

Biological activity of green-synthesized silver nanoparticles depends on the applied natural extracts: a comprehensive study.

PubMed

Rónavári, Andrea; Kovács, Dávid; Igaz, Nóra; Vágvölgyi, Csaba; Boros, Imre Miklós; Kónya, Zoltán; Pfeiffer, Ilona; Kiricsi, Mónika

2017-01-01

Due to obvious disadvantages of the classical chemical methods, green synthesis of metallic nanoparticles has attracted tremendous attention in recent years. Numerous environmentally benign synthesis methods have been developed yielding nanoparticles via low-cost, eco-friendly, and simple approaches. In this study, our aim was to determine the suitability of coffee and green tea extracts in green synthesis of silver nanoparticles as well as to compare the performance of the obtained materials in different biological systems. We successfully produced silver nanoparticles (C-AgNP and GT-AgNP) using coffee and green tea extracts; moreover, based on our comprehensive screening, we delineated major differences in the biological activity of C-AgNPs and GT-AgNPs. Our results indicate that although GT-AgNPs exhibited excellent antimicrobial activity against all the examined microbial pathogens, these particles were also highly toxic to mammalian cells, which limits their potential applications. On the contrary, C-AgNPs manifested substantial inhibitory action on the tested microbes but were nontoxic to human and mouse cells, indicating an outstanding capacity to discriminate between potential pathogens and mammalian cells. These results clearly show that the various green materials used for stabilization and for reduction of metal ions have a defining role in determining and fine-tuning the biological activity of the obtained nanoparticles.

Biological activity of green-synthesized silver nanoparticles depends on the applied natural extracts: a comprehensive study

PubMed Central

Rónavári, Andrea; Kovács, Dávid; Igaz, Nóra; Vágvölgyi, Csaba; Boros, Imre Miklós; Kónya, Zoltán; Pfeiffer, Ilona; Kiricsi, Mónika

2017-01-01

Due to obvious disadvantages of the classical chemical methods, green synthesis of metallic nanoparticles has attracted tremendous attention in recent years. Numerous environmentally benign synthesis methods have been developed yielding nanoparticles via low-cost, eco-friendly, and simple approaches. In this study, our aim was to determine the suitability of coffee and green tea extracts in green synthesis of silver nanoparticles as well as to compare the performance of the obtained materials in different biological systems. We successfully produced silver nanoparticles (C-AgNP and GT-AgNP) using coffee and green tea extracts; moreover, based on our comprehensive screening, we delineated major differences in the biological activity of C-AgNPs and GT-AgNPs. Our results indicate that although GT-AgNPs exhibited excellent antimicrobial activity against all the examined microbial pathogens, these particles were also highly toxic to mammalian cells, which limits their potential applications. On the contrary, C-AgNPs manifested substantial inhibitory action on the tested microbes but were nontoxic to human and mouse cells, indicating an outstanding capacity to discriminate between potential pathogens and mammalian cells. These results clearly show that the various green materials used for stabilization and for reduction of metal ions have a defining role in determining and fine-tuning the biological activity of the obtained nanoparticles. PMID:28184158

Effect of capping agents: Structural, optical and biological properties of ZnO nanoparticles

NASA Astrophysics Data System (ADS)

Javed, Rabia; Usman, Muhammad; Tabassum, Saira; Zia, Muhammad

2016-11-01

Different biological activities of capped and uncapped ZnO nanoparticles were investigated, and the effects of potential capping agents on these biological activities were studied. ZnO nanoparticles were synthesized and capped by polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) using a simple chemical method of co-precipitation. Characterization by X-ray diffraction (XRD), Fourier transform Infrared spectroscopy (FTIR) and UV-vis spectroscopy confirmed the crystallinity, size, functional group, and band gap of synthesized nanoparticles. Reduction in size occurred from 34 nm to 26 nm due to surfactant. Results of all biological activities indicated significantly higher values in capped as compared to uncapped nanoparticles. Antibacterial activity against Staphylococcus aureus (ATCC 6538), Bacillus subtilis (ATCC 6633), Escherichia coli (ATCC15224), and Acetobacter was obtained. This activity was more prominent against Gram-positive bacteria, and ZnO-PVP nanoparticles elucidated highest antibacterial activity (zone of inhibition 17 mm) against Gram-positive, Bacillus subtilis species. Antioxidant activities including total flavonoid content, total phenolic content, total antioxidant capacity, total reducing power and %age inhibition of DPPH, and antidiabetic activity against α-amylase enzyme found to be exhibited highest by ZnO-PEG nanoparticles.

Protein Hydrolysates and Biopeptides: Production, Biological Activities, and Applications in Foods and Health Benefits. A Review.

PubMed

Nasri, M

In recent years, a great deal of interest has been expressed regarding the production, characterization, and applications of protein hydrolysates and food-derived biopeptides due to their numerous beneficial health effects. In this regard, research is mainly focused on investigating the therapeutic potential of these natural compounds. Based on their amino acids composition, sequences, hydrophobicity, and length, peptides released from food proteins, beyond their nutritional properties, can exhibit various biological activities including antihypertensive, antioxidative, antithrombotic, hypoglycemic, hypocholesterolemic, and antibacterial activities among others. Protein hydrolysates are essentially produced by enzymatic hydrolysis of whole protein sources by appropriate proteolytic enzymes under controlled conditions, followed by posthydrolysis processing to isolate desired and potent bioactive peptides from a complex mixture of active and inactive peptides. Therefore, because of their human health potential and safety profiles, protein hydrolysates and biopeptides may be used as ingredients in functional foods and pharmaceuticals to improve human health and prevent diseases. In this review, we have focused on the major variables influencing the enzymatic process of protein hydrolysates production. The biological properties of protein hydrolysates will be described as well as their applications in foods and health benefits. © 2017 Elsevier Inc. All rights reserved.

Student anxiety in introductory biology classrooms: Perceptions about active learning and persistence in the major.

PubMed

England, Benjamin J; Brigati, Jennifer R; Schussler, Elisabeth E

2017-01-01

Many researchers have called for implementation of active learning practices in undergraduate science classrooms as one method to increase retention and persistence in STEM, yet there has been little research on the potential increases in student anxiety that may accompany these practices. This is of concern because excessive anxiety can decrease student performance. Levels and sources of student anxiety in three introductory biology lecture classes were investigated via an online survey and student interviews. The survey (n = 327) data revealed that 16% of students had moderately high classroom anxiety, which differed among the three classes. All five active learning classroom practices that were investigated caused student anxiety, with students voluntarily answering a question or being called on to answer a question causing higher anxiety than working in groups, completing worksheets, or answering clicker questions. Interviews revealed that student anxiety seemed to align with communication apprehension, social anxiety, and test anxiety. Additionally, students with higher general anxiety were more likely to self-report lower course grade and the intention to leave the major. These data suggest that a subset of students in introductory biology experience anxiety in response to active learning, and its potential impacts should be investigated.

Fabrication, characterization and bioevaluation of silibinin loaded chitosan nanoparticles.

PubMed

Pooja, Deep; Babu Bikkina, Dileep J; Kulhari, Hitesh; Nikhila, Nalla; Chinde, Srinivas; Raghavendra, Y M; Sreedhar, B; Tiwari, Ashok K

2014-08-01

Silibinin is reported to possess multiple biological activities. However, its hydrophobic nature limits its bioavailability compromising in vivo biological activities. Nanoparticles-based delivery of such molecules has emerged as new technique to resolve these issues. Bio-degradable, compatible and adhesive nature of chitosan has recently attracted its suitability as a carrier for biologically active molecules. This study presents fabrication and characterization of chitosan-tripolyphosphate based encapsulation of silibinin. Various preparations of silibinin encapsulated chitosan-tripolyphosphate nanoparticles were studied for particle size, morphology, zeta-potential, and encapsulation efficiencies. Preparations were also evaluated for cytotoxic activities in vitro. The optimized silibinin loaded chitosan nanoparticles were of 263.7±4.1nm in particle size with zeta potential 37.4±1.57mV. Nanoparticles showed high silibinin encapsulation efficiencies (82.94±1.82%). No chemical interactions between silibinin and chitosan were observed in FTIR analysis. Powder X-ray diffraction analysis revealed transformed physical state of silibinin after encapsulation. Surface morphology and thermal behaviour were determined using TEM and DSC analysis. Encapsulated silibinin displayed increased dissolution and better cytotoxicity against human prostate cancer cells (DU145) than silibinin alone. Copyright © 2014 Elsevier B.V. All rights reserved.

Student anxiety in introductory biology classrooms: Perceptions about active learning and persistence in the major

PubMed Central

2017-01-01

Many researchers have called for implementation of active learning practices in undergraduate science classrooms as one method to increase retention and persistence in STEM, yet there has been little research on the potential increases in student anxiety that may accompany these practices. This is of concern because excessive anxiety can decrease student performance. Levels and sources of student anxiety in three introductory biology lecture classes were investigated via an online survey and student interviews. The survey (n = 327) data revealed that 16% of students had moderately high classroom anxiety, which differed among the three classes. All five active learning classroom practices that were investigated caused student anxiety, with students voluntarily answering a question or being called on to answer a question causing higher anxiety than working in groups, completing worksheets, or answering clicker questions. Interviews revealed that student anxiety seemed to align with communication apprehension, social anxiety, and test anxiety. Additionally, students with higher general anxiety were more likely to self-report lower course grade and the intention to leave the major. These data suggest that a subset of students in introductory biology experience anxiety in response to active learning, and its potential impacts should be investigated. PMID:28771564

Epigenetic potential of resveratrol and analogs in preclinical models of prostate cancer

USDA-ARS?s Scientific Manuscript database

Prostate cancer is affected by lifestyle, particularly diet. Dietary polyphenols such as resveratrol possess anticancer properties and, therefore, chemopreventive and therapeutic potentials. Resveratrol has pleiotropic effect exerting its biological activity through multiple pathways and targets ass...

Yucca Mountain Biological Resources Monitoring Program. Progress report, January 1994--December 1994

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-07-01

The US Department of Energy (DOE) is required by the Nuclear Waste Policy Act of 1982 (as amended in 1987) to study and characterize the suitability of Yucca Mountain as a potential geological repository for high-level nuclear waste. During site characterization, the DOE will conduct a variety of geotechnical, geochemical, geological, and hydrological studies to determine the suitability of Yucca Mountain as a potential repository. To ensure that site characterization activities do not adversely affect the environment at Yucca Mountain, a program has been implemented to monitor and mitigate potential impacts and ensure activities comply with applicable environmental regulations. Thismore » report describes the activities and accomplishments of EG and G Energy Measurements, Inc. (EG and G/EM) from January 1994 through December 1994 for six program areas within the Terrestrial Ecosystem component of the environmental program for the Yucca Mountain Site Characterization Project (YMP): Site Characterization Effects, Desert Tortoises (Gopherus agassizii), Habitat Reclamation, Monitoring and Mitigation, Radiological Monitoring, and Biological Support.« less

Yucca Mountain biological resources monitoring program; Annual report FY92

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1993-02-01

The US Department of Energy (DOE) is required by the Nuclear Waste Policy Act of 1982 (as amended in 1987) to study and characterize Yucca Mountain as a potential site for a geologic repository for high-level nuclear waste. During site characterization, the DOE will conduct a variety of geotechnical, geochemical, geological, and hydrological studies to determine the suitability of Yucca Mountain as a potential repository. To ensure that site characterization activities (SCA) do not adversely affect the environment at Yucca Mountain, an environmental program has been implemented to monitor and mitigate potential impacts and ensure activities comply with applicable environmentalmore » regulations. This report describes the activities and accomplishments of EG&G Energy Measurements, Inc. (EG&G/EM) during fiscal year 1992 (FY92) for six program areas within the Terrestrial Ecosystem component of the YMP environmental program. The six program areas are Site Characterization Effects, Desert Tortoises, Habitat Reclamation, Monitoring and Mitigation, Radiological Monitoring, and Biological Support.« less

Short-term C mineralization (aka the flush of CO2) as an indicator of soil biological health

USDA-ARS?s Scientific Manuscript database

Soil biological activity is a key component of soil health assessments, as it (a) indicates soil nutrient cycling capacity from various organic matter sources to inorganic availability, (b) relates to soil structural conditions, (c) informs about the potential to harbor biodiversity in soil, and (d)...

Novel Natural Products from Extremophilic Fungi.

PubMed

Zhang, Xuan; Li, Shou-Jie; Li, Jin-Jie; Liang, Zi-Zhen; Zhao, Chang-Qi

2018-06-04

Extremophilic fungi have been found to develop unique defences to survive extremes of pressure, temperature, salinity, desiccation, and pH, leading to the biosynthesis of novel natural products with diverse biological activities. The present review focuses on new extremophilic fungal natural products published from 2005 to 2017, highlighting the chemical structures and their biological potential.

Coriander (Coriandrum sativum L.) and its bioactive constituents.

PubMed

Laribi, Bochra; Kouki, Karima; M'Hamdi, Mahmoud; Bettaieb, Taoufik

2015-06-01

Coriander (Coriandrum sativum L.), a member of the Apiaceae family, is among most widely used medicinal plant, possessing nutritional as well as medicinal properties. Thus, the aim of this updated review is to highlight the importance of coriander as a potential source of bioactive constituents and to summarize their biological activities as well as their different applications from data obtained in recent literature, with critical analysis on the gaps and potential for future investigations. A literature review was carried out by searching on the electronic databases including PubMed, Scopus, ScienceDirect, and Google Scholar for studies focusing on the biological and pharmacological activities of coriander seed and herb bioactive constituents. All recent English-language articles published between 2000 and 2014 were searched using the terms 'C. sativum', 'medicinal plant', 'bioactive constituents', and 'biological activities'. Subsequently, coriander seed and herb essential oils have been actively investigated for their chemical composition and biological activities including antimicrobial, antioxidant, hypoglycemic, hypolipidemic, anxiolytic, analgesic, anti-inflammatory, anti-convulsant and anti-cancer activities, among others. Although coriander has been reported to possess a wide range of traditional medicinal uses, no report is available in its effectiveness use in reactive airway diseases such as asthma and bronchiolitis. In brief, the information presented herein will be helpful to create more interest towards this medicinal species by defining novel pharmacological and clinical applications and hence, may be useful in developing new drug formulations in the future or by employing coriander bioactive constituents in combination with conventional drugs to enhance the treatment of diseases such as Alzheimer and cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

The biological activities and chemical composition of Pereskia species (Cactaceae)--a review.

PubMed

Pinto, Nícolas de Castro Campos; Scio, Elita

2014-09-01

The exploration of nature as a source of sustainable, novel bioactive substances continues to grow as natural products play a significant role in the search for new therapeutic and agricultural agents. In this context, plants of the genus Pereskia (Cactaceae) have been studied for their biological activities, and are evolving as an interesting subject in the search for new, bioactive compounds. These species are commonly used as human foodstuffs and in traditional medicine to treat a variety of diseases. This review focuses on the bioactivity and chemical composition of the genus Pereskia, and aims to stimulate further studies on the chemistry and biological potential of the genus.

Accessing Nature’s diversity through metabolic engineering and synthetic biology

PubMed Central

King, Jason R.; Edgar, Steven; Qiao, Kangjian; Stephanopoulos, Gregory

2016-01-01

In this perspective, we highlight recent examples and trends in metabolic engineering and synthetic biology that demonstrate the synthetic potential of enzyme and pathway engineering for natural product discovery. In doing so, we introduce natural paradigms of secondary metabolism whereby simple carbon substrates are combined into complex molecules through “scaffold diversification”, and subsequent “derivatization” of these scaffolds is used to synthesize distinct complex natural products. We provide examples in which modern pathway engineering efforts including combinatorial biosynthesis and biological retrosynthesis can be coupled to directed enzyme evolution and rational enzyme engineering to allow access to the “privileged” chemical space of natural products in industry-proven microbes. Finally, we forecast the potential to produce natural product-like discovery platforms in biological systems that are amenable to single-step discovery, validation, and synthesis for streamlined discovery and production of biologically active agents. PMID:27081481

Phytochemical Profile and Evaluation of the Biological Activities of Essential Oils Derived from the Greek Aromatic Plant Species Ocimum basilicum, Mentha spicata, Pimpinella anisum and Fortunella margarita.

PubMed

Fitsiou, Eleni; Mitropoulou, Gregoria; Spyridopoulou, Katerina; Tiptiri-Kourpeti, Angeliki; Vamvakias, Manolis; Bardouki, Haido; Panayiotidis, Mihalis Ι; Galanis, Alex; Kourkoutas, Yiannis; Chlichlia, Katerina; Pappa, Aglaia

2016-08-16

Natural products, known for their medicinal properties since antiquity, are continuously being studied for their biological properties. In the present study, we analyzed the composition of the volatile preparations of essential oils of the Greek plants Ocimum basilicum (sweet basil), Mentha spicata (spearmint), Pimpinella anisum (anise) and Fortunella margarita (kumquat). GC/MS analyses revealed that the major components in the essential oil fractions, were carvone (85.4%) in spearmint, methyl chavicol (74.9%) in sweet basil, trans-anethole (88.1%) in anise, and limonene (93.8%) in kumquat. We further explored their biological potential by studying their antimicrobial, antioxidant and antiproliferative activities. Only the essential oils from spearmint and sweet basil demonstrated cytotoxicity against common foodborne bacteria, while all preparations were active against the fungi Saccharomyces cerevisiae and Aspergillus niger. Antioxidant evaluation by DPPH and ABTS radical scavenging activity assays revealed a variable degree of antioxidant potency. Finally, their antiproliferative potential was tested against a panel of human cancer cell lines and evaluated by using the sulforhodamine B (SRB) assay. All essential oil preparations exhibited a variable degree of antiproliferative activity, depending on the cancer model used, with the most potent one being sweet basil against an in vitro model of human colon carcinoma.

Synthesis, crystal structure, cytotoxic, antileishmanial activities and docking studies on N,N‧-(ethane-1,2-diyl)bis(3-methylbenzamide)

NASA Astrophysics Data System (ADS)

Aziz, Hamid; Saeed, Aamer; Jabeen, Farukh; Simpson, Jim; Munawar, Amna; Qasim, Muhammad

2018-03-01

Amide derivatives have gained considerable attention because of their extensive range of biological activities and pharmaceutical applications. The current paper presents the synthesis of N, N‧-(ethane-1,2-diyl) bis (3-methylbenzamide), (I), its molecular and crystal structure and an evaluation of its likely biological activity, including cytotoxicity (LD50 = 37.21 μg/ml) and antileishmanial activity (IC50 = 5.77 μg/ml). Moreover, a docking simulation was used to determine the possible interaction sites of the compound (I) with TryR, an enzyme involved in the redox metabolism of the leishmania parasite. Docking computations demonstrate that the compound established prominent binding interactions with the key residues of the TryR and possess the potential to effectively inhibit the catalytic activities of the enzyme. Thus the results suggest that this compound can serve as a potential scaffold for the treatment of leishmaniasis and deserves further development.

First identification of boronic species as novel potential inhibitors of the Staphylococcus aureus NorA efflux pump.

PubMed

Fontaine, Fanny; Hequet, Arnaud; Voisin-Chiret, Anne-Sophie; Bouillon, Alexandre; Lesnard, Aurélien; Cresteil, Thierry; Jolivalt, Claude; Rault, Sylvain

2014-03-27

Overexpression of efflux pumps is an important mechanism of bacterial resistance that results in the extrusion of antimicrobial agents outside the bacterial cell. Inhibition of such pumps appears to be a promising strategy that could restore the potency of existing antibiotics. The NorA efflux pump of Staphylococcus aureus confers resistance to a wide range of unrelated substrates, such as hydrophilic fluoroquinolones, leading to a multidrug-resistance phenotype. In this work, approximately 150 heterocyclic boronic species were evaluated for their activity against susceptible and resistant strains of S. aureus. Twenty-four hit compounds, although inactive when tested alone, were found to potentiate ciprofloxacin activity by a 4-fold increase at concentrations ranging from 0.5 to 8 μg/mL against S. aureus 1199B, which overexpresses NorA. Boron-free analogues showed no biological activity, thus revealing that the boron atom is crucial for biological activity. This work describes the first reported efflux pump inhibitory activity of boronic acid derivatives.

Top 10 research questions related to growth and maturation of relevance to physical activity, performance, and fitness.

PubMed

Malina, Robert M

2014-06-01

Growth, maturation, and development dominate the daily lives of children and adolescents for approximately the first 2 decades of life. Growth and maturation are biological processes, while development is largely a behavioral process. The 3 processes occur simultaneously and interact. They can be influenced by physical activity and also can influence activity, performance, and fitness. Allowing for these potential interactions, 10 questions on growth and maturation that have relevance to physical activity, performance, and fitness are presented. The questions are not mutually exclusive and address several broadly defined topical areas: exercise and growth, body weight status (body mass index, adiposity rebound, "unhealthy weight gain"), movement proficiency (hypothesized barrier, role in obesity), individual differences, tracking, maturity-associated variation in performance, and corresponding variation in physical activity. Central to the discussion of each is the need for a biocultural approach recognizing the interactions of biology and behavior as potential influences on the variables of interest.

Biological Potential in Serpentinizing Systems

NASA Technical Reports Server (NTRS)

Hoehler, Tori M.

2016-01-01

Generation of the microbial substrate hydrogen during serpentinization, the aqueous alteration of ultramafic rocks, has focused interest on the potential of serpentinizing systems to support biological communities or even the origin of life. However the process also generates considerable alkalinity, a challenge to life, and both pH and hydrogen concentrations vary widely across natural systems as a result of different host rock and fluid composition and differing physical and hydrogeologic conditions. Biological potential is expected to vary in concert. We examined the impact of such variability on the bioenergetics of an example metabolism, methanogenesis, using a cell-scale reactive transport model to compare rates of metabolic energy generation as a function of physicochemical environment. Potential rates vary over more than 5 orders of magnitude, including bioenergetically non-viable conditions, across the range of naturally occurring conditions. In parallel, we assayed rates of hydrogen metabolism in wells associated with the actively serpentinizing Coast Range Ophiolite, which includes conditions more alkaline and considerably less reducing than is typical of serpentinizing systems. Hydrogen metabolism is observed at pH approaching 12 but, consistent with the model predictions, biological methanogenesis is not observed.

Curcumin conjugated with PLGA potentiates sustainability, anti-proliferative activity and apoptosis in human colon carcinoma cells.

PubMed

Waghela, Bhargav N; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M; Pathak, Chandramani

2015-01-01

Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy.

Potential Pharmacological Resources: Natural Bioactive Compounds from Marine-Derived Fungi

PubMed Central

Jin, Liming; Quan, Chunshan; Hou, Xiyan; Fan, Shengdi

2016-01-01

In recent years, a considerable number of structurally unique metabolites with biological and pharmacological activities have been isolated from the marine-derived fungi, such as polyketides, alkaloids, peptides, lactones, terpenoids and steroids. Some of these compounds have anticancer, antibacterial, antifungal, antiviral, anti-inflammatory, antioxidant, antibiotic and cytotoxic properties. This review partially summarizes the new bioactive compounds from marine-derived fungi with classification according to the sources of fungi and their biological activities. Those fungi found from 2014 to the present are discussed. PMID:27110799

Natural Product Potential of the Genus Nocardiopsis

PubMed Central

Ibrahim, Alyaa Hatem; Desoukey, Samar Yehia; Fouad, Mostafa A.; Kamel, Mohamed Salah; Gulder, Tobias A. M.; Abdelmohsen, Usama Ramadan

2018-01-01

Actinomycetes are a relevant source of novel bioactive compounds. One of the pharmaceutically and biotechnologically important genera that attract natural products research is the genus Nocardiopsis, mainly for its ability to produce a wide variety of secondary metabolites accounting for its wide range of biological activities. This review covers the literature from January 2015 until February 2018 making a complete survey of all the compounds that were isolated from the genus Nocardiopsis, their biological activities, and natural sources, whenever applicable. PMID:29710816

Overexpression of miR-9 in mast cells is associated with invasive behavior and spontaneous metastasis

PubMed Central

2014-01-01

Background While microRNA (miRNA) expression is known to be altered in a variety of human malignancies contributing to cancer development and progression, the potential role of miRNA dysregulation in malignant mast cell disease has not been previously explored. The purpose of this study was to investigate the potential contribution of miRNA dysregulation to the biology of canine mast cell tumors (MCTs), a well-established spontaneous model of malignant mast cell disease. Methods We evaluated the miRNA expression profiles from biologically low-grade and biologically high-grade primary canine MCTs using real-time PCR-based TaqMan Low Density miRNA Arrays and performed real-time PCR to evaluate miR-9 expression in primary canine MCTs, malignant mast cell lines, and normal bone marrow-derived mast cells (BMMCs). Mouse mast cell lines and BMMCs were transduced with empty or pre-miR-9 expressing lentiviral constructs and cell proliferation, caspase 3/7 activity, and invasion were assessed. Transcriptional profiling of cells overexpressing miR-9 was performed using Affymetrix GeneChip Mouse Gene 2.0 ST arrays and real-time PCR was performed to validate changes in mRNA expression. Results Our data demonstrate that unique miRNA expression profiles correlate with the biological behavior of primary canine MCTs and that miR-9 expression is increased in biologically high grade canine MCTs and malignant cell lines compared to biologically low grade tumors and normal canine BMMCs. In transformed mouse malignant mast cell lines expressing either wild-type (C57) or activating (P815) KIT mutations and mouse BMMCs, miR-9 overexpression significantly enhanced invasion but had no effect on cell proliferation or apoptosis. Transcriptional profiling of normal mouse BMMCs and P815 cells possessing enforced miR-9 expression demonstrated dysregulation of several genes, including upregulation of CMA1, a protease involved in activation of matrix metalloproteases and extracellular matrix remodeling. Conclusions Our findings demonstrate that unique miRNA expression profiles correlate with the biological behavior of canine MCTs. Furthermore, dysregulation of miR-9 is associated with MCT metastasis potentially through the induction of an invasive phenotype, identifying a potentially novel pathway for therapeutic intervention. PMID:24517413

USE OF AN INTEGRATED APPROACH TO EVALUATE YOUNG CHILDREN'S ACTIVITIES

EPA Science Inventory

Linking a young child's activity pattern data with the environmental, biological, and personal samples that are collected during an exposure assessment is important in evaluating potential exposures and dose associated with environmental contaminants. A number of different appro...

Exploring the biological activities of Echeveria leucotricha.

PubMed

Martínez Ruiz, María G; Gómez-Velasco, Anaximandro; Juárez, Zaida N; Hernández, Luis R; Bach, Horacio

2013-01-01

Echeveria leucotricha J. A. Purpus (Crassulaceae) was evaluated for its potential antibacterial, antifungal, antiparasitic, cytotoxic and anti-inflammatory bioactivities. Aerial parts were extracted with hexane, methanol and chloroform, and fractionated accordingly. Biological activity was assessed in vitro against five Gram-positive and four Gram-negative bacteria, four human pathogenic fungi and the protozoan Leishmania donovani. Extracts and fractions showing bioactivities were further investigated for their cytotoxic activities on macrophages. Results show that several extracts and fractions exhibited significant antibacterial, antifungal, and antiparasitic activities, but no anti-inflammatory activity was recorded. Here, we report for the first time, and to the best of our knowledge, these bioactivities, which suggest that this plant can be used in the traditional Mexican medicine.

From Extremophiles to Star Trek, The Use of Synthetic Biology in Astrobiology

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.; Fujishima, Kosuke; Lima, Ivan Paulino; Gentry, Diana; Phan, Samson; Navarette, Jesica; Palmer, Jesse; Burnier, Andre

2012-01-01

Synthetic biology – the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes – has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving biotic functions using only the most thermodynamically stable amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids. In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as bio-mining, human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

Data-mining of potential antitubercular activities from molecular ingredients of traditional Chinese medicines.

PubMed

Jamal, Salma; Scaria, Vinod

2014-01-01

Background. Traditional Chinese medicine encompasses a well established alternate system of medicine based on a broad range of herbal formulations and is practiced extensively in the region for the treatment of a wide variety of diseases. In recent years, several reports describe in depth studies of the molecular ingredients of traditional Chinese medicines on the biological activities including anti-bacterial activities. The availability of a well-curated dataset of molecular ingredients of traditional Chinese medicines and accurate in-silico cheminformatics models for data mining for antitubercular agents and computational filters to prioritize molecules has prompted us to search for potential hits from these datasets. Results. We used a consensus approach to predict molecules with potential antitubercular activities from a large dataset of molecular ingredients of traditional Chinese medicines available in the public domain. We further prioritized 160 molecules based on five computational filters (SMARTSfilter) so as to avoid potentially undesirable molecules. We further examined the molecules for permeability across Mycobacterial cell wall and for potential activities against non-replicating and drug tolerant Mycobacteria. Additional in-depth literature surveys for the reported antitubercular activities of the molecular ingredients and their sources were considered for drawing support to prioritization. Conclusions. Our analysis suggests that datasets of molecular ingredients of traditional Chinese medicines offer a new opportunity to mine for potential biological activities. In this report, we suggest a proof-of-concept methodology to prioritize molecules for further experimental assays using a variety of computational tools. We also additionally suggest that a subset of prioritized molecules could be used for evaluation for tuberculosis due to their additional effect against non-replicating tuberculosis as well as the additional hepato-protection offered by the source of these ingredients.

Data-mining of potential antitubercular activities from molecular ingredients of traditional Chinese medicines

PubMed Central

Jamal, Salma

2014-01-01

Background. Traditional Chinese medicine encompasses a well established alternate system of medicine based on a broad range of herbal formulations and is practiced extensively in the region for the treatment of a wide variety of diseases. In recent years, several reports describe in depth studies of the molecular ingredients of traditional Chinese medicines on the biological activities including anti-bacterial activities. The availability of a well-curated dataset of molecular ingredients of traditional Chinese medicines and accurate in-silico cheminformatics models for data mining for antitubercular agents and computational filters to prioritize molecules has prompted us to search for potential hits from these datasets. Results. We used a consensus approach to predict molecules with potential antitubercular activities from a large dataset of molecular ingredients of traditional Chinese medicines available in the public domain. We further prioritized 160 molecules based on five computational filters (SMARTSfilter) so as to avoid potentially undesirable molecules. We further examined the molecules for permeability across Mycobacterial cell wall and for potential activities against non-replicating and drug tolerant Mycobacteria. Additional in-depth literature surveys for the reported antitubercular activities of the molecular ingredients and their sources were considered for drawing support to prioritization. Conclusions. Our analysis suggests that datasets of molecular ingredients of traditional Chinese medicines offer a new opportunity to mine for potential biological activities. In this report, we suggest a proof-of-concept methodology to prioritize molecules for further experimental assays using a variety of computational tools. We also additionally suggest that a subset of prioritized molecules could be used for evaluation for tuberculosis due to their additional effect against non-replicating tuberculosis as well as the additional hepato-protection offered by the source of these ingredients. PMID:25081126

Solid-Phase and Microwave-Assisted Syntheses of 2,5-Diketopiperazines: Small Molecules with Great Potential

PubMed Central

O'Neill, J.C.; Blackwell, H. E.

2008-01-01

Diketopiperazines (DKPs) are a well-known class of heterocycles that have recently emerged as a promising biologically active scaffold. Solid-phase organic synthesis has become an important tool in the combinatorial exploration of these privileged structures, expediting the synthesis and, therefore, the discovery of active compounds. To date, certain DKPs have shown potent activities against a range of diseases and biological phenomena, including bacterial infections, various cancers, asthma, infertility, premature labor, and HIV. Recent applications of solid-phase DKP synthesis, with a particular focus on cyclative cleavage and microwave-assisted reactions, are highlighted herein. PMID:18288948

Chemistry and biological activity of platinum amidine complexes.

PubMed

Michelin, Rino A; Sgarbossa, Paolo; Sbovata, Silvia Mazzega; Gandin, Valentina; Marzano, Cristina; Bertani, Roberta

2011-07-04

Platinum amidine complexes represent a new class of potential antitumor drugs that contain the imino moiety HN=C(sp(2)) bonded to the platinum center. They can be related to the iminoether derivatives, which were recently shown to be the first Pt(II) compounds with a trans configuration endowed with anticancer activity. The chemical and biological properties of platinum amidine complexes, and more generally of platinum imino derivatives, can be rationally modified through suitable synthetic procedures with the aim of improving their cytotoxicity and antitumor activity. The addition of protic nucleophiles to nitriles coordinated to platinum in various oxidation states can offer a wide variety of complexes with chemical, structural, and physical properties specifically tuned for a more efficacious biological response. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Precursor-Directed Combinatorial Biosynthesis of Cinnamoyl, Dihydrocinnamoyl, and Benzoyl Anthranilates in Saccharomyces cerevisiae

DOE PAGES

Eudes, Aymerick; Teixeira Benites, Veronica; Wang, George; ...

2015-10-02

Biological synthesis of pharmaceuticals and biochemicals offers an environmentally friendly alternative to conventional chemical synthesis. These alternative methods require the design of metabolic pathways and the identification of enzymes exhibiting adequate activities. Cinnamoyl, dihydrocinnamoyl, and benzoyl anthranilates are natural metabolites which possess beneficial activities for human health, and the search is expanding for novel derivatives that might have enhanced biological activity. For example, biosynthesis in Dianthus caryophyllus is catalyzed by hydroxycinnamoyl/benzoyl-CoA:anthranilate N-hydroxycinnamoyl/ benzoyltransferase (HCBT), which couples hydroxycinnamoyl-CoAs and benzoyl-CoAs to anthranilate. We recently demonstrated the potential of using yeast (Saccharomyces cerevisiae) for the biological production of a few cinnamoyl anthranilatesmore » by heterologous co-expression of 4-coumaroyl:CoA ligase from Arabidopsis thaliana (4CL5) and HCBT. Here we report that, by exploiting the substrate flexibility of both 4CL5 and HCBT, we achieved rapid biosynthesis of more than 160 cinnamoyl, dihydrocinnamoyl, and benzoyl anthranilates in yeast upon feeding with both natural and non-natural cinnamates, dihydrocinnamates, benzoates, and anthranilates. Our results demonstrate the use of enzyme promiscuity in biological synthesis to achieve high chemical diversity within a defined class of molecules. Finally, this work also points to the potential for the combinatorial biosynthesis of diverse and valuable cinnamoylated, dihydrocinnamoylated, and benzoylated products by using the versatile biological enzyme 4CL5 along with characterized cinnamoyl-CoA- and benzoyl-CoA-utilizing transferases.« less

Glycosylation Is a Major Regulator of Phenylpropanoid Availability and Biological Activity in Plants

PubMed Central

Le Roy, Julien; Huss, Brigitte; Creach, Anne; Hawkins, Simon; Neutelings, Godfrey

2016-01-01

The phenylpropanoid pathway in plants is responsible for the biosynthesis of a huge amount of secondary metabolites derived from phenylalanine and tyrosine. Both flavonoids and lignins are synthesized at the end of this very diverse metabolic pathway, as well as many intermediate molecules whose precise biological functions remain largely unknown. The diversity of these molecules can be further increased under the action of UDP-glycosyltransferases (UGTs) leading to the production of glycosylated hydroxycinnamates and related aldehydes, alcohols and esters. Glycosylation can change phenylpropanoid solubility, stability and toxic potential, as well as influencing compartmentalization and biological activity. (De)-glycosylation therefore represents an extremely important regulation point in phenylpropanoid homeostasis. In this article we review recent knowledge on the enzymes involved in regulating phenylpropanoid glycosylation status and availability in different subcellular compartments. We also examine the potential link between monolignol glycosylation and lignification by exploring co-expression of lignin biosynthesis genes and phenolic (de)glycosylation genes. Of the different biological roles linked with their particular chemical properties, phenylpropanoids are often correlated with the plant's stress management strategies that are also regulated by glycosylation. UGTs can for instance influence the resistance of plants during infection by microorganisms and be involved in the mechanisms related to environmental changes. The impact of flavonoid glycosylation on the color of flowers, leaves, seeds and fruits will also be discussed. Altogether this paper underlies the fact that glycosylation and deglycosylation are powerful mechanisms allowing plants to regulate phenylpropanoid localisation, availability and biological activity. PMID:27303427

Biomaterials and biologics in craniofacial reconstruction.

PubMed

Engstrand, Thomas

2012-01-01

Complications related to surgery, including infection, wound dehiscence, and implant protrusion, are costly and may cause severe morbidity to patients. The choice of implants materials is critical for a successful outcome, particularly in craniofacial reconstructions. This review discusses the potential benefits and drawbacks of biologically active materials used for craniofacial bone repair as alternatives to inert implant prostheses.

Synthesis and biological activity of imidazopyridine anticoccidial agents: part I.

PubMed

Scribner, Andrew; Dennis, Richard; Hong, Jean; Lee, Shuliang; McIntyre, Donald; Perrey, David; Feng, Dennis; Fisher, Michael; Wyvratt, Matthew; Leavitt, Penny; Liberator, Paul; Gurnett, Anne; Brown, Chris; Mathew, John; Thompson, Donald; Schmatz, Dennis; Biftu, Tesfaye

2007-01-01

Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we present the synthesis and biological activity of imidazo[1,2-a]pyridine anticoccidial agents. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

Design, synthesis and biological evaluation of novel 6H-benzo[c]chromen-6-one, and 7,8,9,10-tetrahydro-benzo[c]chromen-6-one derivatives as potential cholinesterase inhibitors.

PubMed

Gulcan, Hayrettin Ozan; Unlu, Serdar; Esiringu, Ilker; Ercetin, Tugba; Sahin, Yasemin; Oz, Demet; Sahin, Mustafa Fethi

2014-10-01

Hydroxylated 6H-benzo[c]chromen-6-one derivatives (i.e., urolithins) are the main bioavailable metabolites, and biomarkers of ellagitannins present in various nutrition. Although these dietaries, the sources of urolithins, are employed in folk medicine as cognitive enhancer in the treatment of Alzheimer's Disease, urolithins have negligible potential to inhibit acetylcholinesterase and butyrylcholinesterase enzymes, the validated targets of Alzheimer's Disease. Therefore, within this research, a series of 6H-benzo[c]chromen-6-one, and 7,8,9,10-tetrahydro-benzo[c]chromen-6-one derivatives has been designed, synthesized, and their biological activities were evaluated as potential acetylcholinesterase and butyrylcholinesterase inhibitors. The compounds synthesized exerted comparable activity in comparison to rivastigmine, galantamine, and donepezil both in in vitro and in vivo studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Studies on novel 2-imidazolidinones and tetrahydropyrimidin-2(1H)-ones as potential TACE inhibitors: design, synthesis, molecular modeling, and preliminary biological evaluation.

PubMed

DasGupta, Shirshendu; Murumkar, Prashant R; Giridhar, Rajani; Yadav, Mange Ram

2009-05-15

Compounds belonging to the class of 2-imidazolidinones and tetrahydropyrimidin-2(1H)-ones were synthesized and evaluated for their TACE inhibitory activity. Most of the compounds showed very good TACE inhibitory activity. Docking study clearly indicates importance of the P1' group of the inhibitor for the TACE inhibitory activity. This work proves that these two classes of molecules could be used as potential leads for the development of TACE inhibitors.

Strategies to enhance biologically active-secondary metabolites in cell cultures of Artemisia - current trends.

PubMed

Ali, Mohammad; Abbasi, Bilal Haider; Ahmad, Nisar; Khan, Haji; Ali, Gul Shad

2017-11-01

The genus Artemisia has been utilized worldwide due to its immense potential for protection against various diseases, especially malaria. Artemisia absinthium, previously renowned for its utilization in the popular beverage absinthe, is gaining resurgence due to its extensive pharmacological activities. Like A. annua, this species exhibits strong biological activities like antimalarial, anticancer and antioxidant. Although artemisinin was found to be the major metabolite for its antimalarial effects, several flavonoids and terpenoids are considered to possess biological activities when used alone and also to synergistically boost the bioavailability of artemisinin. However, due to the limited quantities of these metabolites in wild plants, in vitro cultures were established and strategies have been adopted to enhance medicinally important secondary metabolites in these cultures. This review elaborates on the traditional medicinal uses of Artemisia species and explains current trends to establish cell cultures of A. annua and A. absinthium for enhanced production of medicinally important secondary metabolites.

Biological properties of 6-gingerol: a brief review.

PubMed

Wang, Shaopeng; Zhang, Caihua; Yang, Guang; Yang, Yanzong

2014-07-01

Numerous studies have revealed that regular consumption of certain fruits and vegetables can reduce the risk of many diseases. The rhizome of Zingiber officinale (ginger) is consumed worldwide as a spice and herbal medicine. It contains pungent phenolic substances collectively known as gingerols. 6-Gingerol is the major pharmacologically-active component of ginger. It is known to exhibit a variety of biological activities including anticancer, anti-inflammation, and anti-oxidation. 6-Gingerol has been found to possess anticancer activities via its effect on a variety of biological pathways involved in apoptosis, cell cycle regulation, cytotoxic activity, and inhibition of angiogenesis. Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, 6-gingerol has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various diseases. Taken together, this review summarizes the various in vitro and in vivo pharmacological aspects of 6-gingerol and the underlying mechanisms.

Soil Biological Activity Contributing to Phosphorus Availability in Vertisols under Long-Term Organic and Conventional Agricultural Management

PubMed Central

Bhat, Nisar A.; Riar, Amritbir; Ramesh, Aketi; Iqbal, Sanjeeda; Sharma, Mahaveer P.; Sharma, Sanjay K.; Bhullar, Gurbir S.

2017-01-01

Mobilization of unavailable phosphorus (P) to plant available P is a prerequisite to sustain crop productivity. Although most of the agricultural soils have sufficient amounts of phosphorus, low availability of native soil P remains a key limiting factor to increasing crop productivity. Solubilization and mineralization of applied and native P to plant available form is mediated through a number of biological and biochemical processes that are strongly influenced by soil carbon/organic matter, besides other biotic and abiotic factors. Soils rich in organic matter are expected to have higher P availability potentially due to higher biological activity. In conventional agricultural systems mineral fertilizers are used to supply P for plant growth, whereas organic systems largely rely on inputs of organic origin. The soils under organic management are supposed to be biologically more active and thus possess a higher capability to mobilize native or applied P. In this study we compared biological activity in soil of a long-term farming systems comparison field trial in vertisols under a subtropical (semi-arid) environment. Soil samples were collected from plots under 7 years of organic and conventional management at five different time points in soybean (Glycine max) -wheat (Triticum aestivum) crop sequence including the crop growth stages of reproductive significance. Upon analysis of various soil biological properties such as dehydrogenase, β-glucosidase, acid and alkaline phosphatase activities, microbial respiration, substrate induced respiration, soil microbial biomass carbon, organically managed soils were found to be biologically more active particularly at R2 stage in soybean and panicle initiation stage in wheat. We also determined the synergies between these biological parameters by using the methodology of principle component analysis. At all sampling points, P availability in organic and conventional systems was comparable. Our findings clearly indicate that owing to higher biological activity, organic systems possess equal capabilities of supplying P for crop growth as are conventional systems with inputs of mineral P fertilizers. PMID:28928758

[The hygienic evaluation of the mutagenic potential of industrial wastes].

PubMed

Zhurkov, V S; Rusakov, N V; Tonkopiĭ, N I; Sycheva, L P; Akhal'tseva, L V; Neiaskina, E V; Pirtakhiia, N V; Malysheva, A G; Rastiannikov, E G

1998-01-01

A combination of two approaches to assessing the carcinogenic and mutagenic potentials of industrial waste is proposed. One approach includes determination of the carcinogenic and mutagenic properties of individual chemicals of waste, the other involves biological indication of the cumulative mutagenic activity of waste samples. The mutagenic potential of some waste samples of aircraft industry was determined.

Ice nucleation by cellulose and its potential impact on clouds and climate

NASA Astrophysics Data System (ADS)

Hiranuma, Naruki; Möhler, Ottmar; Yamashita, Katsuya; Tajiri, Takuya; Saito, Atsushi; Kiselev, Alexei; Hoose, Corinna; Murakami, Masataka

2014-05-01

Biological aerosol particles have recently been accentuated by their efficient ice nucleating activity as well as potential impact on clouds and global climate. Despite their potential importance, little is known about the abundance of biological particles in the atmosphere and their role compared to non-biological material and, consequently, their potential role in the cloud-hydrology and climate system is also poorly constrained. However, field observations show that the concentration of airborne cellulose, which is one of the most important derivatives of glucose and atmospherically relevant biopolymers, is consistently prevalent (>10 ng per cubic meter) throughout the whole year even at remote- and elevated locations. Here we use a novel cloud simulation chamber in Tsukuba, Japan to demonstrate that airborne cellulose of biological origin can act as efficient ice nucleating particles in super-cooled clouds of the lower and middle troposphere. In specific, we measured the surface-based ice nucleation activity of microcrystalline cellulose particles immersed in cloud droplets, which may add crucial importance to further quantify the role of biological particles as ice nuclei in the troposphere. Our results suggest that the concentration of ice nucleating cellulose to become significant (>0.1 per liter) below about -17 °C and nearly comparable to other known ice nucleating clay mineral particles (e.g., illite rich clay mineral - INUIT comparisons are also presented). An important and unique characteristic of microcrystalline cellulose compared to other particles of biological origin is its high molecular packing density, enhancing resistance to hydrolysis degradation. More in-depth microphysical understandings as well as quantitative observations of ice nucleating cellulose particles in the atmosphere are necessary to allow better estimates of their effects on clouds and the global climate. Acknowledgement: We acknowledge support by German Research Society (DfG) and Ice Nucleation research UnIT (FOR 1525 INUIT).

Passive Antibody Administration (Immediate Immunity) as a Specific Defense Against Biological Weapons

PubMed Central

2002-01-01

The potential threat of biological warfare with a specific agent is proportional to the susceptibility of the population to that agent. Preventing disease after exposure to a biological agent is partially a function of the immunity of the exposed individual. The only available countermeasure that can provide immediate immunity against a biological agent is passive antibody. Unlike vaccines, which require time to induce protective immunity and depend on the host’s ability to mount an immune response, passive antibody can theoretically confer protection regardless of the immune status of the host. Passive antibody therapy has substantial advantages over antimicrobial agents and other measures for postexposure prophylaxis, including low toxicity and high specific activity. Specific antibodies are active against the major agents of bioterrorism, including anthrax, smallpox, botulinum toxin, tularemia, and plague. This article proposes a biological defense initiative based on developing, producing, and stockpiling specific antibody reagents that can be used to protect the population against biological warfare threats. PMID:12141970

Marine natural product peptides with therapeutic potential: Chemistry, biosynthesis, and pharmacology.

PubMed

Gogineni, Vedanjali; Hamann, Mark T

2018-01-01

The oceans are a uniquely rich source of bioactive metabolites, of which sponges have been shown to be among the most prolific producers of diverse bioactive secondary metabolites with valuable therapeutic potential. Much attention has been focused on marine bioactive peptides due to their novel chemistry and diverse biological properties. As summarized in this review, marine peptides are known to exhibit various biological activities such as antiviral, anti-proliferative, antioxidant, anti-coagulant, anti-hypertensive, anti-cancer, antidiabetic, antiobesity, and calcium-binding activities. This review focuses on the chemistry and biology of peptides isolated from sponges, bacteria, cyanobacteria, fungi, ascidians, and other marine sources. The role of marine invertebrate microbiomes in natural products biosynthesis is discussed in this review along with the biosynthesis of modified peptides from different marine sources. The status of peptides in various phases of clinical trials is presented, as well as the development of modified peptides including optimization of PK and bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

Denosumab for bone diseases: translating bone biology into targeted therapy.

PubMed

Tsourdi, Elena; Rachner, Tilman D; Rauner, Martina; Hamann, Christine; Hofbauer, Lorenz C

2011-12-01

Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.

Plant oligosaccharides - outsiders among elicitors?

PubMed

Larskaya, I A; Gorshkova, T A

2015-07-01

This review substantiates the need to study the plant oligoglycome. The available information on oligosaccharins - physiologically active fragments of plant cell wall polysaccharides - is summarized. The diversity of such compounds in chemical composition, origin, and proved biological activity is highlighted. At the same time, plant oligosaccharides can be considered as outsiders among elicitors of various natures in research intensity of recent decades. This review discusses the reasons for such attitude towards these regulators, which are largely connected with difficulties in isolation and identification. Together with that, approaches are suggested whose potentials can be used to study oligosaccharins. The topics of oligosaccharide metabolism in plants, including the ways of formation, transport, and inactivation are presented, together with data on biological activity and interaction with plant hormones. The current viewpoints on the mode of oligosaccharin action - perception, signal transduction, and possible "targets" - are considered. The potential uses of such compounds in medicine, food industry, agriculture, and biotechnology are discussed.

Diversity and activity of nitrogen fixing archaea and bacteria associated with micro-environments of wetland rice

NASA Astrophysics Data System (ADS)

Schmidt, Hannes; Woebken, Dagmar

2017-04-01

Wetland rice is one of the world's most important crop plants. The cultivation on waterlogged paddy soils is strongly limited by nitrogen (N), which is typically supplied by industrial fertilizers that are not only costly but also exhibit hazardous effects on the environment. It has been reported that "Biological Nitrogen Fixation" through N2-fixing bacteria and archaea (diazotrophs) can alleviate the N-shortage in rice cultivation, thus carrying out an important ecosystem function. However, our understanding of the diversity and in situ N2 fixation activity of diazotrophs in flooded rice fields is still rudimentary. Moreover, knowledge on the impact of biochemical gradients established by root activity (i.e. exudation, radial oxygen loss) on the functioning of N-fixing microorganisms in paddy soil ecosystems is limited. We aimed at studying underlying processes on biologically relevant scales. Greenhouse studies were performed to identify key factors that control rice-diazotroph association and related N2 fixation activities. Paddy soils of different geographical origin were cultivated with two commercially used genotypes of wetland rice. Samples were separated into bulk soil, rhizosphere soil, rhizoplane, and roots at flowering stage of rice plant development. These samples were subjected to functional assays and various molecular biological techniques in order to analyze the associated diazotroph communities. Based on Illumina amplicon sequencing of nifH genes and transcripts, we show that the diversity and potential activity of diazotroph communities varies according to micro-environments. We will comparatively discuss the influence of (a) the soil microbial "seed bank" and (b) plant genotype in shaping the respective microbiomes and selecting for potentially active diazotrophs. Actual N2 fixation activities of soil-genotype combinations and micro-environments will be shown on the basis of incubation assays using 15N2-containing atmospheres. Areas of potential N-transfer between diazotrophs and rice roots will be presented via the detection and visualization of spatial colonization patterns of selected diazotrophic groups on rice rhizoplanes. Our approach will help to increase the understanding of the contribution of Biological Nitrogen Fixation to rice cultivation in paddy soil ecosystems.

Removal of novel antiandrogens identified in biological effluents of domestic wastewater by activated carbon.

PubMed

Ma, Dehua; Chen, Lujun; Liu, Rui

2017-10-01

Environmental antiandrogenic (AA) contaminants in effluents from wastewater treatment plants have the potential for negative impacts on wildlife and human health. The aim of our study was to identify chemical contaminants with likely AA activity in the biological effluents and evaluate the removal of these antiandrogens (AAs) during advanced treatment comprising adsorption onto granular activated carbon (GAC). In this study, profiling of AA contaminants in biological effluents and tertiary effluents was conducted using effect-directed analysis (EDA) including high performance liquid chromatography (HPLC) fractionation, a recombinant yeast screen containing androgen receptor (YAS), in combination with mass spectrometry analyses. Analysis of a wastewater secondary effluent from a membrane bioreactor revealed complex profiles of AA activity comprising 14 HPLC fractions and simpler profiles of GAC effluents with only 2 to 4 moderately polar HPLC fractions depending on GAC treatment conditions. Gas chromatography-mass spectrometry and ultra-high performance liquid chromatography-nanospray mass spectrometry analyses of AA fractions in the secondary effluent resulted in detection of over 10 chemical contaminants, which showed inhibition of YAS activity and were potential AAs. The putative AAs included biocides, food additives, flame retardants, pharmaceuticals and industrial contaminants. To our knowledge, it is the first time that the AA properties of N-ethyl-2-isopropyl-5-methylcyclohexanecarboxamide (WS3), cetirizine, and oxcarbazepine are reported. The EDA used in this study was proven to be a powerful tool to identify novel chemical structures with AA activity in the complex aquatic environment. The adsorption process to GAC of all the identified antiandrogens, except WS3 and triclosan, fit well with the pseudo-second order kinetics models. Adsorption to GAC could further remove most of the AAs identified in the biological effluents with high efficiencies. Copyright © 2017 Elsevier B.V. All rights reserved.

Antimicrobial activity and physical characterization of silver nanoparticles green synthesized using nitrate reductase from Fusarium oxysporum.

PubMed

Gholami-Shabani, Mohammadhassan; Akbarzadeh, Azim; Norouzian, Dariush; Amini, Abdolhossein; Gholami-Shabani, Zeynab; Imani, Afshin; Chiani, Mohsen; Riazi, Gholamhossein; Shams-Ghahfarokhi, Masoomeh; Razzaghi-Abyaneh, Mehdi

2014-04-01

Nanostructures from natural sources have received major attention due to wide array of biological activities and less toxicity for humans, animals, and the environment. In the present study, silver nanoparticles were successfully synthesized using a fungal nitrate reductase, and their biological activity was assessed against human pathogenic fungi and bacteria. The enzyme was isolated from Fusarium oxysporum IRAN 31C after culturing on malt extract-glucose-yeast extract-peptone (MGYP) medium. The enzyme was purified by a combination of ultrafiltration and ion exchange chromatography on DEAE Sephadex and its molecular weight was estimated by gel filtration on Sephacryl S-300. The purified enzyme had a maximum yield of 50.84 % with a final purification of 70 folds. With a molecular weight of 214 KDa, it is composed of three subunits of 125, 60, and 25 KDa. The purified enzyme was successfully used for synthesis of silver nanoparticles in a way dependent upon NADPH using gelatin as a capping agent. The synthesized silver nanoparticles were characterized by X-ray diffraction, dynamic light scattering spectroscopy, and transmission and scanning electron microscopy. These stable nonaggregating nanoparticles were spherical in shape with an average size of 50 nm and a zeta potential of -34.3. Evaluation of the antimicrobial effects of synthesized nanoparticles by disk diffusion method showed strong growth inhibitory activity against all tested human pathogenic fungi and bacteria as evident from inhibition zones that ranged from 14 to 25 mm. Successful green synthesis of biologically active silver nanoparticles by a nitrate reductase from F. oxysporum in the present work not only reduces laborious downstream steps such as purification of nanoparticle from interfering cellular components, but also provides a constant source of safe biologically-active nanomaterials with potential application in agriculture and medicine.

Biological and pharmacological evaluation of dimethoxycurcumin: A metabolically stable curcumin analogue with a promising therapeutic potential.

PubMed

Teymouri, Manouchehr; Barati, Nastaran; Pirro, Matteo; Sahebkar, Amirhosein

2018-01-01

Dimethoxycurcumin (DiMC) is a synthetic analog of curcumin with superior inter-related pro-oxidant and anti-cancer activity, and metabolic stability. Numerous studies have shown that DiMC reserves the biologically beneficial features, including anti-inflammatory, anti-carcinogenic, and cytoprotective properties, almost to the same extent as curcumin exhibits. DiMC lacks the phenolic-OH groups as opposed to curcumin, dimethoxycurcumin, and bis-demethoxycurcumin that all vary in the number of methoxy groups per molecule, and has drawn the attentions of researchers who attempted to discover the structure-activity relationship (SAR) of curcumin. In this regard, tetrahydrocurcumin (THC), the reduced and biologically inert metabolite of curcumin, denotes the significance of the conjugated α,β diketone moiety for the curcumin activity. DiMC exerts unique molecular activities compared to curcumin, including induction of androgen receptor (AR) degradation and suppression of the transcription factor activator protein-1 (AP-1). The enhanced AR degradation on DiMC treatment suggests it as a novel anticancer agent against resistant tumors with androgenic etiology. Further, DiMC might be a potential treatment for acne vulgaris. DiMC induces epigenetic alteration more effectively than curcumin, although both showed no direct DNA hypomethylating activity. Given the metabolic stability, nanoparticulation of DiMC is more promising for in vivo effectiveness. However, studies in this regard are still in its infancy. In the current review, we portray the various molecular and biological functions of DiMC reported so far. Whenever possible, the efficiency is compared with curcumin and the reasons for DiMC being more metabolically stable are elaborated. We also provide future perspective investigations with respect to varying DiMC-nanoparticles. © 2016 Wiley Periodicals, Inc.

Cytotoxic effect of silver nanoparticles synthesized from Padina tetrastromatica on breast cancer cell line

NASA Astrophysics Data System (ADS)

Gnana Selvi, B. Clara; Madhavan, J.; Santhanam, Amutha

2016-09-01

In recent years researchers were attracted towards marine sources due to the presence of active components in it. Seaweeds were widely used in pharmaceutical research for their known biological activities. The biological synthesis method of silver nanoparticles (AgNPs) using Padina tetrastromatica seaweed extract and their cytotoxicity against breast cancer MCF-7 cells was reported in this study. The synthesized AgNPs using seaweed extract were subjected to x-ray diffraction, UV-visible spectroscopy, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, transmission electron microscope, energy dispersive x-ray, zeta potential to elucidate the structural, morphology, size as well as surface potential parameters. An absorption peak at 430 nm in UV-visible spectrum reveals the excitation and surface plasmon resonance of AgNPs. FE-SEM micrographs exhibits the biosynthesized AgNPs, which are pre-dominantly round shaped and the size ranges between 40-50 nm. The zeta potential value of -27.6 mV confirms the stable nature of biosynthesized silver nanoparticles. Furthermore, the biological synthesized Ag NPs exhibited a dose-dependent cytotoxicity against human breast cancer cell (MCF-7) and the inhibitory concentration (IC50) was found for AgNPs against MCF-7 at 24 h incubation. Biological method of synthesizing silver nanoparticles shows a environmental friendly property which helps in effective electrifying usage in many fields.

Tramesan, a novel polysaccharide from Trametes versicolor. Structural characterization and biological effects

PubMed Central

Sveronis, Aris; Cescutti, Paola; Rizzo, Roberto

2017-01-01

Mushrooms represent a formidable source of bioactive compounds. Some of these may be considered as biological response modifiers; these include compounds with a specific biological function: antibiotics (e.g. plectasin), immune system stimulator (e,g, lentinan), antitumor agents (e.g. krestin, PSK) and hypolipidemic agents (e.g. lovastatin) inter alia. In this study, we focused on the Chinese medicinal mushroom “yun zhi”, Trametes versicolor, traditionally used for (cit.) “replenish essence and qi (vital energy)”. Previous studies indicated the potential activity of extracts from culture filtrate of asexual mycelia of T. versicolor in controlling the growth and secondary metabolism (e.g. mycotoxins) of plant pathogenic fungi. The quest of active principles produced by T. versicolor, allowed us characterising an exo-polysaccharide released in its culture filtrate and naming it Tramesan. Herein we evaluate the biological activity of Tramesan in different organisms: plants, mammals and plant pathogenic fungi. We suggest that the bioactivity of Tramesan relies mostly on its ability to act as pro antioxidant molecule regardless the biological system on which it was applied. PMID:28829786

Tramesan, a novel polysaccharide from Trametes versicolor. Structural characterization and biological effects.

PubMed

Scarpari, Marzia; Reverberi, Massimo; Parroni, Alessia; Scala, Valeria; Fanelli, Corrado; Pietricola, Chiara; Zjalic, Slaven; Maresca, Vittoria; Tafuri, Agostino; Ricciardi, Maria R; Licchetta, Roberto; Mirabilii, Simone; Sveronis, Aris; Cescutti, Paola; Rizzo, Roberto

2017-01-01

Mushrooms represent a formidable source of bioactive compounds. Some of these may be considered as biological response modifiers; these include compounds with a specific biological function: antibiotics (e.g. plectasin), immune system stimulator (e,g, lentinan), antitumor agents (e.g. krestin, PSK) and hypolipidemic agents (e.g. lovastatin) inter alia. In this study, we focused on the Chinese medicinal mushroom "yun zhi", Trametes versicolor, traditionally used for (cit.) "replenish essence and qi (vital energy)". Previous studies indicated the potential activity of extracts from culture filtrate of asexual mycelia of T. versicolor in controlling the growth and secondary metabolism (e.g. mycotoxins) of plant pathogenic fungi. The quest of active principles produced by T. versicolor, allowed us characterising an exo-polysaccharide released in its culture filtrate and naming it Tramesan. Herein we evaluate the biological activity of Tramesan in different organisms: plants, mammals and plant pathogenic fungi. We suggest that the bioactivity of Tramesan relies mostly on its ability to act as pro antioxidant molecule regardless the biological system on which it was applied.

How does curcumin work with poor bioavailability? Clues from experimental and theoretical studies

NASA Astrophysics Data System (ADS)

Shen, Liang; Liu, Cui-Cui; An, Chun-Yan; Ji, Hong-Fang

2016-02-01

Curcumin is a natural product with multiple biological activities and numerous potential therapeutic applications. However, its poor systemic bioavailability fails to explain the potent pharmacological effects and hinders its clinical application. Using experimental and theoretical approaches, we compared curcumin and its degradation products for its biological activities against Alzheimer’s disease (AD), including the superoxide anion radical (O2.-)-scavenging activity, Aβ fibrils (fAβ) formation-inhibiting activity, and enzymatic inhibition activity. We showed that compared to the parent compound curcumin, the degradation products mixture possessed higher O2.--scavenging activity and stronger inhibition against fAβ formation. The docking simulations revealed that the bioactive degradation products should make important contribution to the experimentally observed enzymatic inhibition activities of curcumin. Given that curcumin is readily degraded under physiological condition, our findings strongly suggested that the degradation products should make important contribution to the diverse biological activities of curcumin. Our novel findings not only provide novel insights into the complex pharmacology of curcumin due to its poor bioavailability, but also open new avenues for developing therapeutic applications of this natural product.

Gynura procumbens: An Overview of the Biological Activities

PubMed Central

Tan, Hui-Li; Chan, Kok-Gan; Pusparajah, Priyia; Lee, Learn-Han; Goh, Bey-Hing

2016-01-01

Gynura procumbens (Lour.) Merr. (Family Asteraceae) is a medicinal plant commonly found in tropical Asia countries such as China, Thailand, Indonesia, Malaysia, and Vietnam. Traditionally, it is widely used in many different countries for the treatment of a wide variety of health ailments such as kidney discomfort, rheumatism, diabetes mellitus, constipation, and hypertension. Based on the traditional uses of G. procumbens, it seems to possess high therapeutic potential for treatment of various diseases making it a target for pharmacological studies aiming to validate and provide scientific evidence for the traditional claims of its efficacy. Although there has been considerable progress in the research on G. procumbens, to date there is no review paper gathering the reported biological activities of G. procumbens. Hence, this review aims to provide an overview of the biological activities of G. procumbens based on reported in vitro and in vivo studies. In brief, G. procumbens has been reported to exhibit antihypertensive, cardioprotective, antihyperglycemic, fertility enhancement, anticancer, antimicrobial, antioxidant, organ protective, and antiinflammatory activity. The commercial applications of G. procumbens have also been summarized in this paper based on existing patents. The data compiled illustrate that G. procumbens is a potential natural source of compounds with various pharmacological actions which can be utilized for the development of novel therapeutic agents. PMID:27014066

Nutritional, biochemical, and pharmaceutical potential of proteins and peptides from jatropha: review.

PubMed

Devappa, Rakshit K; Makkar, Harinder P S; Becker, Klaus

2010-06-09

Increased bioenergy consciousness and high demand for animal products have propelled the search for alternative resources that could meet the dual demands. Jatropha seeds have potential to fit these roles in view of their multipurpose uses, broad climatic adaptability features, and high oil and protein contents. During the past five years many large-scale cultivation projects have been undertaken to produce jatropha seed oil as a feedstock for the biodiesel industry. The present review aims at providing biological significance of jatropha proteins and peptides along with their nutritional and therapeutic applications. The nutritional qualities of the kernel meal and protein concentrates or isolates prepared from seed cake are presented, enabling their efficient use in animal nutrition. In addition, (a) biologically active proteins involved in plant protection, for example, aquaporin and betaine aldehyde dehydrogenase, which have roles in drought resistance, and beta-glucanase, which has antifungal activity, as well as those having pharmaceutical properties, and (b) cyclic peptides with various biological activities such as antiproliferative, immunomodulatory, antifungal, and antimalarial activity are discussed. It is expected that the information collated will open avenues for new applications of proteins present in jatropha plant, thereby contributing to enhance the financial viability and sustainability of a jatropha-based biodiesel industry.

Biological capacitance studies of anodes in microbial fuel cells using electrochemical impedance spectroscopy.

PubMed

Lu, Zhihao; Girguis, Peter; Liang, Peng; Shi, Haifeng; Huang, Guangtuan; Cai, Lankun; Zhang, Lehua

2015-07-01

It is known that cell potential increases while anode resistance decreases during the start-up of microbial fuel cells (MFCs). Biological capacitance, defined as the apparent capacitance attributed to biological activity including biofilm production, plays a role in this phenomenon. In this research, electrochemical impedance spectroscopy was employed to study anode capacitance and resistance during the start-up period of MFCs so that the role of biological capacitance was revealed in electricity generation by MFCs. It was observed that the anode capacitance ranged from 3.29 to 120 mF which increased by 16.8% to 18-20 times over 10-12 days. Notably, lowering the temperature and arresting biological activity via fixation by 4% para formaldehyde resulted in the decrease of biological capacitance by 16.9 and 62.6%, indicating a negative correlation between anode capacitance and anode resistance of MFCs. Thus, biological capacitance of anode should play an important role in power generation by MFCs. We suggest that MFCs are not only biological reactors and/or electrochemical cells, but also biological capacitors, extending the vision on mechanism exploration of electron transfer, reactor structure design and electrode materials development of MFCs.

Comparative assessment of ceramic media for drinking water biofiltration.

PubMed

Sharma, Dikshant; Taylor-Edmonds, Liz; Andrews, Robert C

2018-01-01

Media type is a critical design consideration when implementing biofiltration for drinking water treatment. Granular activated carbon (GAC) has been shown to provide superior performance when compared to a wide range of media types, largely due to its higher surface area. Engineered ceramic media is an attractive alternative to GAC as it has a similar surface area but at a lower cost. This pilot-scale biofiltration study compared the performance of GAC, anthracite and two different effective sizes of ceramic (CER) media (1.0 mm and 1.2 mm), in terms of dissolved organic carbon (DOC), head loss, turbidity, and disinfection by-product formation potential (DBPFP). Biological acclimation was monitored using adenosine tri-phosphate (ATP) measurements; biomass was further examined using laccase and esterase enzyme activity assays. When compared to other media types examined, biological GAC had higher (p > 0.05) removals of DOC (9.8 ± 3.8%), trihalomethane formation potential (THMFP, 26.3 ± 10.2%), and haloacetic acid formation potential (HAAFP, 27.2 ± 14.0%). CER media required 6-7 months to biologically acclimate, while filters containing GAC and anthracite were biologically active (>100 ng of ATP/g media) following 30-45 days of operation. Once acclimated, ATP values of 243 and 208 ng/g attained for CER 1.0 and 1.2, respectively, were statistically comparable to GAC (244 ng/g) and higher than anthracite (110 ng/g), however this did not translate into greater organics removal. Esterase and laccase enzyme kinetics were highest for GAC, while CER was shown to have greater biodegradation potential than anthracite. The four media types attained similar turbidity reduction (p > 0.05), however ceramic media filters were observed to have run times which were 1.5-2.3 times longer when compared to anthracite, which could represent potential cost savings in terms of energy for pumping and backwash requirements. Overall, ceramic media was shown to be a potential alternative to anthracite when considering biofiltration, especially during cold water conditions (T < 10 °C). Copyright © 2017 Elsevier Ltd. All rights reserved.

Moringa Genus: A Review of Phytochemistry and Pharmacology

PubMed Central

Abd Rani, Nur Zahirah; Husain, Khairana; Kumolosasi, Endang

2018-01-01

Moringa is a genus of medicinal plants that has been used traditionally to cure wounds and various diseases such as colds and diabetes. In addition, the genus is also consumed as a source of nutrients and widely used for purifying water. The genus consists of 13 species that have been widely cultivated throughout Asia and Africa for their multiple uses. The purpose of this review is to provide updated and categorized information on the traditional uses, phytochemistry, biological activities, and toxicological research of Moringa species in order to explore their therapeutic potential and evaluate future research opportunities. The literature reviewed for this paper was obtained from PubMed, ScienceDirect, and Google Scholar journal papers published from 1983 to March 2017. Moringa species are well-known for their antioxidant, anti-inflammatory, anticancer, and antihyperglycemic activities. Most of their biological activity is caused by their high content of flavonoids, glucosides, and glucosinolates. By documenting the traditional uses and biological activities of Moringa species, we hope to support new research on these plants, especially on those species whose biological properties have not been studied to date. PMID:29503616

Just-in-Time Teaching in Biology: Creating an Active Learner Classroom Using the Internet

ERIC Educational Resources Information Center

Marrs, Kathleen A.; Novak, Gregor

2004-01-01

Just-in-Time Teaching (ITT) is a teaching and learning approach that combines the best features of traditional in-class instruction with the communication and resource potential available via the Web. We describe here how ITT can be used to teach biology to undergraduate and graduate level students, both science majors as well as non science…

Students' Knowledge Construction in Small Groups in the Seventh Grade Biology Laboratory: Verbal Communication and Physical Engagement.

ERIC Educational Resources Information Center

She, Hsiao-Ching

1999-01-01

Reports on a study of seventh-grade students' interactions in small groups during a biology laboratory activity. Finds that girls have the potential to perform equally as well as do boys in the science laboratory and that both individual and gender differences contribute to students' differential verbal communication and laboratory engagement.…

Phoretic Self-Propulsion

NASA Astrophysics Data System (ADS)

Moran, Jeffrey L.; Posner, Jonathan D.

2017-01-01

It is well-known that micro- and nanoparticles can move by phoretic effects in response to externally imposed gradients of scalar quantities such as chemical concentration or electric potential. A class of active colloids can propel themselves through aqueous media by generating local gradients of concentration and electrical potential via surface reactions. Phoretic active colloids can be controlled using external stimuli and can mimic collective behaviors exhibited by many biological swimmers. Low-Reynolds number physicochemical hydrodynamics imposes unique challenges and constraints that must be understood for the practical potential of active colloids to be realized. Here, we review the rich physics underlying the operation of phoretic active colloids, describe their interactions and collective behaviors, and discuss promising directions for future research.

Serotonin (5-HT) released by activated white blood cells in a biological fuel cell provide a potential energy source for electricity generation.

PubMed

Justin, Gusphyl A; Sun, Mingui; Zhang, Yingze; Cui, X Tracy; Sclabassi, Robert

2006-01-01

Previous studies by our group have demonstrated the ability of white blood cells to generate small electrical currents, on the order of 1-3 microA/cm(2), when placed at the anode compartment of a proton exchange membrane (PEM) biological fuel cell. In this research study, an electrochemical technique is used to further investigate the electron transfer ability of activated white blood cells at interfacing electrodes in an attempt to elucidate the mechanism of electron transfer in the original biological fuel cell experiments. Cyclic voltammograms were obtained for human white blood cells using a three-electrode system. The working and counter electrodes were made from carbon felt and platinum, respectively, while the reference was a saturated calomel electrode (SCE). Oxidation peaks were observed at an average potential of 363 mV vs. SCE for the PMA/ionomycin activated white blood cells in glucose solution. However a corresponding reduction peak was not observed, suggesting irreversibility of the redox reaction. The cyclic voltammograms recorded for the white blood cells bear very close similarities to those of the neurotransmitter serotonin (5-HT). Serotonin released by white blood cells into the extracellular environment may be irreversibly oxidized at the working electrode in the cyclic voltammetry experiments and at the PEM biological fuel cell anode in our earlier electrochemical cell studies.

Synthesis of novel Schiff's bases of highly potential biological activities and their structure investigation.

PubMed

Zayed, Ehab M; Zayed, M A

2015-05-15

Novel bisaldehyde-hydrazide Schiff's bases AS1 (2,2'-(ethane-1,2-diylbis(oxy))dibenzaldehyde terephthalohydrazide) and AS2 (N',N'″-(((ethane-1,2-diylbis(oxy))bis(2,1-phenylene))bis(methanylylidene))di(benzohydrazide)) were prepared as new macrocyclic compounds via condensation reactions. AS1 had been prepared by condensation between (2,2'-(ethane-1,2-diylbis(oxy))dibenzaldehyde) bisaldehyde and terephthalohydrazide in a ratio1:1. AS2 had been obtained by condensation between (2,2'-(ethane-1,2-diylbis(oxy))dibenzaldehyde) bisaldehyde and benzohydrazide in ratio 1:2. The structures of AS1 and AS2 were characterized by elemental analysis (EA), mass (MS), FT-IR and (1)H-NMR spectra, and thermal analyses (TG, DTG). The activation thermodynamic parameters such as ΔE(∗), ΔH(∗), ΔS(∗) and ΔG(∗) were calculated from the TG curves using Coats-Redfern method. It is important to investigate their molecular structures to know the active groups and weak bonds responsible for their biological activities. Consequently in the present work, the obtained thermal (TA) and mass (MS) practical results are confirmed by semi-empirical MO-calculations (MOCS) using PM3 procedure. Their biological activities had been tested in vitro against Escherichia coli, Proteus vulgaris, Bacillus subtilis and Staphylococcus aurous bacteria in order to assess their anti-microbial potential. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis of novel Schiff's bases of highly potential biological activities and their structure investigation

NASA Astrophysics Data System (ADS)

Zayed, Ehab M.; Zayed, M. A.

2015-05-01

Novel bisaldehyde-hydrazide Schiff's bases AS1 (2,2‧-(ethane-1,2-diylbis(oxy))dibenzaldehyde terephthalohydrazide) and AS2 (N‧,N‧″-(((ethane-1,2-diylbis(oxy))bis(2,1-phenylene))bis(methanylylidene))di(benzohydrazide)) were prepared as new macrocyclic compounds via condensation reactions. AS1 had been prepared by condensation between (2,2‧-(ethane-1,2-diylbis(oxy))dibenzaldehyde) bisaldehyde and terephthalohydrazide in a ratio1:1. AS2 had been obtained by condensation between (2,2‧-(ethane-1,2-diylbis(oxy))dibenzaldehyde) bisaldehyde and benzohydrazide in ratio 1:2. The structures of AS1 and AS2 were characterized by elemental analysis (EA), mass (MS), FT-IR and 1H-NMR spectra, and thermal analyses (TG, DTG). The activation thermodynamic parameters such as ΔE∗, ΔH∗, ΔS∗ and ΔG∗ were calculated from the TG curves using Coats-Redfern method. It is important to investigate their molecular structures to know the active groups and weak bonds responsible for their biological activities. Consequently in the present work, the obtained thermal (TA) and mass (MS) practical results are confirmed by semi-empirical MO-calculations (MOCS) using PM3 procedure. Their biological activities had been tested in vitro against Escherichia coli, Proteus vulgaris, Bacillus subtilis and Staphylococcus aurous bacteria in order to assess their anti-microbial potential.

HPLC profiling of antimicrobial and antioxidant phyco sugars isolated from the South West coast of India.

PubMed

Kailas, Abhilash Parameswaran; Nair, Sukumaran Muraleedharan

2016-10-20

Phyco sugars isolated from the South West coast of India are commercially and therapeutically interesting due to their various biological activities. These sugars were isolated from six (three red and three green) seaweed species using water at 100°C followed by precipitation using ethanol. The physical, chemical and biological characteristics were explored with specific highlights onto the specific rotation, HPLC-RI sugar speciation, antioxidant and antimicrobial activities. The biological properties were evaluated based on multiple methods and standards, such that the actual nature of the sugar is understood. G. corticata var. cylindrica (31.66%) had the highest sugar content. All the sugars had levo rotatory specific rotation and interesting chemical characteristics. Sugars isolated had competitive biological activities and had the presence of seven monosaccharides and one disaccharide. The results highlighted the socio-economic importance of seaweeds which could be developed as a potential source of bioactive compounds in the upcoming future. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthetic Astrobiology

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2015-01-01

Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

Structural and biological evaluation of a novel series of benzimidazole inhibitors of Francisella tularensis enoyl-ACP reductase (FabI)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehboob, Shahila; Song, Jinhua; Hevener, Kirk E.

Francisella tularensis, the causative agent of tularemia, presents a significant biological threat and is a Category A priority pathogen due to its potential for weaponization. In the bacterial FASII pathway we found it a viable target for the development of novel antibacterial agents treating Gram-negative infections. Here, we report the advancement of a promising series of benzimidazole FabI (enoyl-ACP reductase) inhibitors to a second-generation using a systematic, structure-guided lead optimization strategy, and the determination of several co-crystal structures that confirm the binding mode of designed inhibitors. Furthermore, these compounds display an improved low nanomolar enzymatic activity as well as promisingmore » low microgram/mL antibacterial activity against both F. tularensis and Staphylococcus aureus and its methicillin-resistant strain (MRSA). Finally, the improvements in activity accompanying structural modifications lead to a better understanding of the relationship between the chemical structure and biological activity that encompasses both enzymatic and whole-cell activity.« less

Structural and biological evaluation of a novel series of benzimidazole inhibitors of Francisella tularensis enoyl-ACP reductase (FabI)

DOE PAGES

Mehboob, Shahila; Song, Jinhua; Hevener, Kirk E.; ...

2015-01-29

Francisella tularensis, the causative agent of tularemia, presents a significant biological threat and is a Category A priority pathogen due to its potential for weaponization. In the bacterial FASII pathway we found it a viable target for the development of novel antibacterial agents treating Gram-negative infections. Here, we report the advancement of a promising series of benzimidazole FabI (enoyl-ACP reductase) inhibitors to a second-generation using a systematic, structure-guided lead optimization strategy, and the determination of several co-crystal structures that confirm the binding mode of designed inhibitors. Furthermore, these compounds display an improved low nanomolar enzymatic activity as well as promisingmore » low microgram/mL antibacterial activity against both F. tularensis and Staphylococcus aureus and its methicillin-resistant strain (MRSA). Finally, the improvements in activity accompanying structural modifications lead to a better understanding of the relationship between the chemical structure and biological activity that encompasses both enzymatic and whole-cell activity.« less

Catalytic Asymmetric Synthesis of Butenolides and Butyrolactones

PubMed Central

2017-01-01

γ-Butenolides, γ-butyrolactones, and derivatives, especially in enantiomerically pure form, constitute the structural core of numerous natural products which display an impressive range of biological activities which are important for the development of novel physiological and therapeutic agents. Furthermore, optically active γ-butenolides and γ-butyrolactones serve also as a prominent class of chiral building blocks for the synthesis of diverse biological active compounds and complex molecules. Taking into account the varying biological activity profiles and wide-ranging structural diversity of the optically active γ-butenolide or γ-butyrolactone structure, the development of asymmetric synthetic strategies for assembling such challenging scaffolds has attracted major attention from synthetic chemists in the past decade. This review offers an overview of the different enantioselective synthesis of γ-butenolides and γ-butyrolactones which employ catalytic amounts of metal complexes or organocatalysts, with emphasis focused on the mechanistic issues that account for the observed stereocontrol of the representative reactions, as well as practical applications and synthetic potentials. PMID:28640622

From Synthesis to Biological Impact of Pd (II) Complexes: Synthesis, Characterization, and Antimicrobial and Scavenging Activity

PubMed Central

Sharma, Nitin Kumar; Ameta, Rakesh Kumar; Singh, Man

2016-01-01

The Pd (II) complexes with a series of halosubstituted benzylamine ligands (BLs) have been synthesized and characterized with different spectroscopic technique such as FTIR, UV/Vis, LCMS, 1H, and 13C NMR. Their molecular sustainability in different solvents such as DMSO, DMSO : H2O, and DMSO : PBS at physiological condition (pH 7.2) was determined by UV/Vis spectrophotometer. The in vitro antibacterial and antifungal activities of the complexes were investigated against Gram-positive and Gram-negative microbes and two different fungi indicated their significant biological potential. Additionally, their antioxidant activity has been analyzed with DPPH• free radical through spectrophotometric method and the result inferred them as an antioxidant. The stronger antibacterial and antioxidant activities of the synthesized complexes suggested them as a stronger antimicrobial agent. Our study advances the biological importance of palladium (II) amine complexes in the field of antimicrobial and antioxidant activities. PMID:27119023

Some biologically active oxovanadium(IV) complexes of triazole derived Schiff bases: their synthesis, characterization and biological properties.

PubMed

Chohan, Zahid H; Sumrra, Sajjad H

2010-10-01

A series of biologically active oxovanadium(IV) complexes of triazole derived Schiff bases L(1)-L(5) have been synthesized and characterized by their physical, analytical, and spectral data. The synthesized ligands potentially act as bidentate, in which the oxygen of furfural and nitrogen of azomethine coordinate with the oxovanadium atom to give a stoichiometry of vanadyl complexes 1:2 (M:L) in a square-pyramidal geometry. In vitro antibacterial and antifungal activities on different species of pathogenic bacteria (E. coli, S. flexneri, P. aeruginosa, S. typhi, S. aureus, and B. subtilis) and fungi (T. longifusus, C. albicans, A. flavus, M. canis, F. solani, and C. glabrata) have been studied. All compounds showed moderate to significant antibacterial activity against one or more bacterial strains and good antifungal activity against most of the fungal strains. The brine shrimp bioassay was also carried out to check the cytotoxicity of coordinated and uncoordinated synthesized compounds.

Recent developments in therapeutic applications of Cyanobacteria.

PubMed

Raja, Rathinam; Hemaiswarya, Shanmugam; Ganesan, Venkatesan; Carvalho, Isabel S

2016-05-01

The cyanobacteria (blue-green algae) are photosynthetic prokaryotes having applications in human health with numerous biological activities and as a dietary supplement. It is used as a food supplement because of its richness in nutrients and digestibility. Many cyanobacteria (Microcystis sp, Anabaena sp, Nostoc sp, Oscillatoria sp., etc.) produce a great variety of secondary metabolites with potent biological activities. Cyanobacteria produce biologically active and chemically diverse compounds belonging to cyclic peptides, lipopeptides, fatty acid amides, alkaloids and saccharides. More than 50% of the marine cyanobacteria are potentially exploitable for extracting bioactive substances which are effective in killing cancer cells by inducing apoptotic death. Their role as anti-viral, anti-tumor, antimicrobial, anti-HIV and a food additive have also been well established. However, such products are at different stages of clinical trials and only a few compounds have reached to the market.

Canine Adipose-Derived Stem Cells: Purinergic Characterization and Neurogenic Potential for Therapeutic Applications.

PubMed

Roszek, Katarzyna; Makowska, Noemi; Czarnecka, Joanna; Porowińska, Dorota; Dąbrowski, Marcin; Danielewska, Justyna; Nowak, Wiesław

2017-01-01

The presented results evidence that canine adipose-derived stem cells (ADSCs) represent the premature population of stem cells with great biological potential and properties. ADCS are easy to obtain and culture, able to differentiate into the neurogenic lineage as well as it is easy to control their proliferation rate with nucleotides and nucleosides or analogues. We report that in vitro cultured canine ADSCs response to adenosine- and ATP-mediated stimulation. Differences in canine ADSCs and human mesenchymal stem cells in ecto-nucleotidase activity have been observed. The ecto-nucleotidase activity changes during ADSCs in vitro transdifferentiation into neurogenic lineage are fast and simple to analyze. Therefore, the simple analysis of ecto-enzymes activity allows for verification of the stem cells quality: their stemness or initiation of the differentiation process. The biological potential of the cells isolated from canine fat, as well as the good quality control of this cell culture, make them a promising tool for both experimental and therapeutic usage. J. Cell. Biochem. 118: 58-65, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Antioxidant Cerium Oxide Nanoparticles in Biology and Medicine

PubMed Central

Nelson, Bryant C.; Johnson, Monique E.; Walker, Marlon L.; Riley, Kathryn R.; Sims, Christopher M.

2016-01-01

Previously, catalytic cerium oxide nanoparticles (CNPs, nanoceria, CeO2-x NPs) have been widely utilized for chemical mechanical planarization in the semiconductor industry and for reducing harmful emissions and improving fuel combustion efficiency in the automobile industry. Researchers are now harnessing the catalytic repertoire of CNPs to develop potential new treatment modalities for both oxidative- and nitrosative-stress induced disorders and diseases. In order to reach the point where our experimental understanding of the antioxidant activity of CNPs can be translated into useful therapeutics in the clinic, it is necessary to evaluate the most current evidence that supports CNP antioxidant activity in biological systems. Accordingly, the aims of this review are three-fold: (1) To describe the putative reaction mechanisms and physicochemical surface properties that enable CNPs to both scavenge reactive oxygen species (ROS) and to act as antioxidant enzyme-like mimetics in solution; (2) To provide an overview, with commentary, regarding the most robust design and synthesis pathways for preparing CNPs with catalytic antioxidant activity; (3) To provide the reader with the most up-to-date in vitro and in vivo experimental evidence supporting the ROS-scavenging potential of CNPs in biology and medicine. PMID:27196936

THE FUTURE OF TOXICOLOGY-PREDICTIVE TOXICOLOGY ...

EPA Pesticide Factsheets

A chemistry approach to predictive toxicology relies on structure−activity relationship (SAR) modeling to predict biological activity from chemical structure. Such approaches have proven capabilities when applied to well-defined toxicity end points or regions of chemical space. These approaches are less well-suited, however, to the challenges of global toxicity prediction, i.e., to predicting the potential toxicity of structurally diverse chemicals across a wide range of end points of regulatory and pharmaceutical concern. New approaches that have the potential to significantly improve capabilities in predictive toxicology are elaborating the “activity” portion of the SAR paradigm. Recent advances in two areas of endeavor are particularly promising. Toxicity data informatics relies on standardized data schema, developed for particular areas of toxicological study, to facilitate data integration and enable relational exploration and mining of data across both historical and new areas of toxicological investigation. Bioassay profiling refers to large-scale high-throughput screening approaches that use chemicals as probes to broadly characterize biological response space, extending the concept of chemical “properties” to the biological activity domain. The effective capture and representation of legacy and new toxicity data into mineable form and the large-scale generation of new bioassay data in relation to chemical toxicity, both employing chemical stru

Where Synthetic Biology Meets ET

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2016-01-01

Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. And what about the limits for life? Can we create organisms that expand the envelope for life? In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

Glycolipids from seaweeds and their potential biotechnological applications.

PubMed

Plouguerné, Erwan; da Gama, Bernardo A P; Pereira, Renato C; Barreto-Bergter, Eliana

2014-01-01

Marine macroalgae, or seaweeds, are a formidable source of natural compounds with diverse biological activities. In the last five decades it has been estimated that more than 3000 natural compounds were discovered from these organisms. The great majority of the published works have focused on terpenoids. In comparison, glycolipids are a neglected class of macroalgal secondary metabolites therefore remaining as a largely unknown reservoir of molecular diversity. Nevertheless, the interest regarding these compounds has been growing fast in the last decades as activities of ecological or pharmaceutical interest have been highlighted. This paper will review recent work regarding isolation and structural characterization of glycolipids from seaweeds and their prospective biological activities.

Cubanes: Super explosives and potential pharmaceutical intermediates

NASA Technical Reports Server (NTRS)

Bashir-Hashemi, A.

1994-01-01

The cubane molecule, in which eight carbon atoms are locked in a cubic framework, shows great potential for both military and pharmaceutical applications. Octanitrocubane, with a predicted density of 2.1 g/cc and strain energy of more than 165 kcal/mol, is considered to be the 'super-explosive', while cubane derivatives submitted to the National Institutes of Health for preliminary biological activity screening have displayed promising anti-cancer and anti-HIV activity.

Fatty acids and related Kv2 channel blockers: electrophysiology and toxicity on mosquitoes

USDA-ARS?s Scientific Manuscript database

Ligand-gated ion channels form an important superfamily of proteins involved in many biological processes. Among them, the potassium channels constitute a very diverse group involved in neural signaling, neuronal activity and action potential. Among the different types of channel activation, voltage...

Measuring potential denitrification enzyme activity rates using the membrane inlet mass spectrometer

EPA Science Inventory

The denitrification enzyme activity (DEA) assay, provides a quantitative assessment of the multi enzyme, biological process of reactive nitrogen removal via the reduction of N03 to N2. Measured in soil, usually under non limiting carbon and nitrate concentrations, this short ter...

Biological Activity of Peanut (Arachis hypogaea) Phytoalexins and Selected Natural and Synthetic Stilbenoids

PubMed Central

SOBOLEV, VICTOR S.; KHAN, SHABANA I.; TABANCA, NURHAYAT; WEDGE, DAVID E.; MANLY, SUSAN P.; CUTLER, STEPHEN J.; COY, MONIQUE R.; BECNEL, JAMES J.; NEFF, SCOTT A.; GLOER, JAMES B.

2011-01-01

The peanut plant (Arachis hypogaea L.), when infected by a microbial pathogen, is capable of producing stilbene-derived compounds that are considered antifungal phytoalexins. In addition, the potential health benefits of other stilbenoids from peanuts, including resveratrol and pterostilbene, have been acknowledged by several investigators. Despite considerable progress in peanut research, relatively little is known about the biological activity of the stilbenoid phytoalexins. This study investigated the activities of some of these compounds in a broad spectrum of biological assays. Since peanut stilbenoids appear to play roles in plant defense mechanisms, they were evaluated for their effects on economically important plant pathogenic fungi of the genera Colletotrichum, Botrytis, Fusarium, and Phomopsis. We further investigated these peanut phytoalexins, together with some related natural and synthetic stilbenoids (a total of 24 compounds) in a panel of bioassays to determine their anti-inflammatory, cytotoxic, and antioxidant activities in mammalian cells. Several of these compounds were also evaluated as mammalian opioid receptor competitive antagonists. Assays for adult mosquito and larvae toxicity were also performed. The results of these studies reveal that peanut stilbenoids, as well as related natural and synthetic stilbene derivatives, display a diverse range of biological activities. PMID:21314127

Curcumin Conjugated with PLGA Potentiates Sustainability, Anti-Proliferative Activity and Apoptosis in Human Colon Carcinoma Cells

PubMed Central

Waghela, Bhargav N.; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M.; Pathak, Chandramani

2015-01-01

Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy. PMID:25692854

Research and Teaching: "It's Not You, It's the Room"--Are the High-Tech, Active Learning Classrooms Worth It?

ERIC Educational Resources Information Center

Cotner, Sehoya; Loper, Jessica; Walker, J. D.; Brooks, D. Christopher

2013-01-01

Several institutions have redesigned traditional learning spaces to better realize the potential of active, experiential learning. We compare student performance in traditional and active learning classrooms in a large, introductory biology course using the same syllabus, course goals, exams, and instructor. Using ACT scores as predictive, we…

The rise of biosimilars: potential benefits and drawbacks in rheumatoid arthritis.

PubMed

Yoo, Dae Hyun

2014-08-01

Although biologic agents are effective in the treatment of rheumatoid arthritis, the high price of drugs and restricted health care budgets have restricted easy access to biologics. Eventually, the use of biologic disease-modifying antirheumatic drugs might be inversely associated with disease activity in countries with low gross domestic product. The EMA approved an infliximab biosimilar for the first time in September 2013. The first approval of a biosimilar monoclonal antibody by a major regulatory authority provided a global standard for subsequent biosimilars and for biopharmaceutical companies developing biosimilars. Biosimilars with a highly similar quality and efficacy profile at an acceptable lower cost would significantly increase affordability of biologic disease-modifying antirheumatic drugs in the treatment of rheumatoid arthritis. Here, we will review the current status of first biosimilar antibody agent and the potential discussion points raised against biosimilars. In addition, the importance of awareness on biosimilars for stakeholders is discussed.

Antioxidant, antibacterial, cytotoxic, and apoptotic activity of stem bark extracts of Cephalotaxus griffithii Hook. f.

PubMed

Moirangthem, Dinesh Singh; Talukdar, Narayan Chandra; Kasoju, Naresh; Bora, Utpal

2012-04-03

Cephalotaxus spp. are known to possess various therapeutic potentials. Cephalotaxus griffithii, however, has not been evaluated for its biological potential. The reason may be the remoteness and inaccessibility of the habitat where it is distributed. The main aim of this study was to: (1) evaluate multiple biological potentials of stem bark of C. griffithii, and (2) identify solvent extract of stem bark of C. griffithii to find the one with the highest specific biological activity. Dried powder of stem bark of C. griffithii was exhaustively extracted serially by soaking in petroleum ether, acetone and methanol to fractionate the chemical constituents into individual fractions or extracts. The extracts were tested for total phenolic and flavonoid content, antioxidant (DPPH radical scavenging, superoxide radical scavenging, and reducing power models), antibacterial (disc diffusion assay on six bacterial strains), cytotoxic (MTT assay on HeLa cells), and apoptotic activity (fluorescence microscopy, DNA fragmentation assay, and flow cytometry on HeLa cells). Among the three extracts of stem bark of C. griffithii, the acetone extract contained the highest amount of total phenolics and flavonoids and showed maximum antioxidant, antibacterial, cytotoxic (IC50 of 35.5 ± 0.6 μg/ml; P < 0.05), and apoptotic (46.3 ± 3.6% sub-G0/G1 population; P < 0.05) activity, followed by the methanol and petroleum ether extracts. However, there was no significant difference observed in IC50 values (DPPH scavenging assay) of the acetone and methanol extracts and the positive control (ascorbic acid). In contrast, superoxide radical scavenging assay-based antioxidant activity (IC50) of the acetone and methanol extracts was significantly lower than the positive control (P < 0.05). Correlation analysis suggested that phenolic and flavonoid content present in stem bark of C. griffithii extracts was responsible for the high antioxidant, cytotoxic, and apoptotic activity (P < 0.05). Stem bark of C. griffithii has multiple biological effects. These results call for further chemical characterization of acetone extract of stem bark of C. griffithii for specific bioactivity.

Bioactive Natural Products Prioritization Using Massive Multi-informational Molecular Networks.

PubMed

Olivon, Florent; Allard, Pierre-Marie; Koval, Alexey; Righi, Davide; Genta-Jouve, Gregory; Neyts, Johan; Apel, Cécile; Pannecouque, Christophe; Nothias, Louis-Félix; Cachet, Xavier; Marcourt, Laurence; Roussi, Fanny; Katanaev, Vladimir L; Touboul, David; Wolfender, Jean-Luc; Litaudon, Marc

2017-10-20

Natural products represent an inexhaustible source of novel therapeutic agents. Their complex and constrained three-dimensional structures endow these molecules with exceptional biological properties, thereby giving them a major role in drug discovery programs. However, the search for new bioactive metabolites is hampered by the chemical complexity of the biological matrices in which they are found. The purification of single constituents from such matrices requires such a significant amount of work that it should be ideally performed only on molecules of high potential value (i.e., chemical novelty and biological activity). Recent bioinformatics approaches based on mass spectrometry metabolite profiling methods are beginning to address the complex task of compound identification within complex mixtures. However, in parallel to these developments, methods providing information on the bioactivity potential of natural products prior to their isolation are still lacking and are of key interest to target the isolation of valuable natural products only. In the present investigation, we propose an integrated analysis strategy for bioactive natural products prioritization. Our approach uses massive molecular networks embedding various informational layers (bioactivity and taxonomical data) to highlight potentially bioactive scaffolds within the chemical diversity of crude extracts collections. We exemplify this workflow by targeting the isolation of predicted active and nonactive metabolites from two botanical sources (Bocquillonia nervosa and Neoguillauminia cleopatra) against two biological targets (Wnt signaling pathway and chikungunya virus replication). Eventually, the detection and isolation processes of a daphnane diterpene orthoester and four 12-deoxyphorbols inhibiting the Wnt signaling pathway and exhibiting potent antiviral activities against the CHIKV virus are detailed. Combined with efficient metabolite annotation tools, this bioactive natural products prioritization pipeline proves to be efficient. Implementation of this approach in drug discovery programs based on natural extract screening should speed up and rationalize the isolation of bioactive natural products.

Reductions of dissolved organic matter and disinfection by-product precursors in full-scale wastewater treatment plants in winter.

PubMed

Xue, Shuang; Jin, Wujisiguleng; Zhang, Zhaohong; Liu, Hong

2017-07-01

The reductions of dissolved organic matter (DOM) and disinfection byproduct precursors in four full-scale wastewater treatment plants (WWTPs) (Liaoning Province, China) where different biological treatment processes were employed in winter were investigated. The total removal efficiencies of dissolved organic carbon (DOC), ultraviolet light at 254 nm (UV-254), trihalomethane formation potential (THMFP), and haloacetic acid formation potential (HAAFP) were in the range of 70.3-76.0%, 49.6-57.3%, 54.4-65.0%, and 53.7-63.8% in the four WWTPs, respectively. The biological treatment was the predominant process responsible for the removal of DOC, THMFP, and HAAFP in WWTPs. Differences in the reduction of UV-254 were not significant (p > 0.05) among biochemical reaction pool, secondary sedimentation tank, and disinfection tank. Biological aerated filter and suspended carrier activated sludge processes achieved higher DOM removal than the conventional active sludge and anaerobic-anoxic-oxic processes. Hydrophobic neutral and hydrophilic fraction were removed to a higher degree through biological treatment than the other three DOM fractions. HAAFP removal was more efficient than THMFP reduction during biological treatment. During primary treatment, fluorescent materials in secondary sedimentation tanks were preferentially removed, as compared to the bulk DOM. Humic-like fluorescent compounds were not readily eliminated during biological treatment. The fluorescent materials were more susceptible to chlorine than nonfluorescent compounds. Copyright © 2017. Published by Elsevier Ltd.

Synthetic biology in the UK - An outline of plans and progress.

PubMed

Clarke, L J; Kitney, R I

2016-12-01

Synthetic biology is capable of delivering new solutions to key challenges spanning the bioeconomy, both nationally and internationally. Recognising this significant potential and the associated need to facilitate its translation and commercialisation the UK government commissioned the production of a national Synthetic Biology Roadmap in 2011, and subsequently provided crucial support to assist its implementation. Critical infrastructural investments have been made, and important strides made towards the development of an effectively connected community of practitioners and interest groups. A number of Synthetic Biology Research Centres, DNA Synthesis Foundries, a Centre for Doctoral Training, and an Innovation Knowledge Centre have been established, creating a nationally distributed and integrated network of complementary facilities and expertise. The UK Synthetic Biology Leadership Council published a UK Synthetic Biology Strategic Plan in 2016, increasing focus on the processes of translation and commercialisation. Over 50 start-ups, SMEs and larger companies are actively engaged in synthetic biology in the UK, and inward investments are starting to flow. Together these initiatives provide an important foundation for stimulating innovation, actively contributing to international research and development partnerships, and helping deliver useful benefits from synthetic biology in response to local and global needs and challenges.

Attempts to develop a new nuclear measurement technique of β-glucuronidase levels in biological samples

NASA Astrophysics Data System (ADS)

Ünak, T.; Avcibasi, U.; Yildirim, Y.; Çetinkaya, B.

2003-01-01

β-Glucuronidase is one of the most important hydrolytic enzymes in living systems and plays an essential role in the detoxification pathway of toxic materials incorporated into the metabolism. Some organs, especially liver and some tumour tissues, have high level of β-glucuronidase activity. As a result the enzymatic activity of some kind of tumour cells, the radiolabelled glucuronide conjugates of cytotoxic, as well as radiotoxic compounds have potentially very valuable diagnostic and therapeutic applications in cancer research. For this reason, a sensitive measurement of β-glucuronidase levels in normal and tumour tissues is a very important step for these kinds of applications. According to the classical measurement method of β-glucuronidase activity, in general, the quantity of phenolphthalein liberated from its glucuronide conjugate, i.e. phenolphthalein-glucuronide, by β-glucuronidase has been measured by use of the spectrophotometric technique. The lower detection limit of phenolphthalein by the spectrophotometric technique is about 1-3 μg. This means that the β-glucuronidase levels could not be detected in biological samples having lower levels of β-glucuronidase activity and therefore the applications of the spectrophotometric technique in cancer research are very seriously limited. Starting from this consideration, we recently attempted to develop a new nuclear technique to measure much lower concentrations of β-glucuronidase in biological samples. To improve the detection limit, phenolphthalein-glucuronide and also phenyl-N-glucuronide were radioiodinated with 131I and their radioactivity was measured by use of the counting technique. Therefore, the quantity of phenolphthalein or aniline radioiodinated with 131I and liberated by the deglucuronidation reactivity of β-glucuronidase was used in an attempt to measure levels lower than the spectrophotometric measurement technique. The results obtained clearly verified that 0.01 pg level of phenolphthalein or aniline could easily be detected at least 106 times more sensitively. The preliminary results obtained on some biological samples have shown that β-glucuronidase levels could reasonably be measured by use of the nuclear technique. In addition, our results also indicate the potential application of the radiolabelling technique to measure very low β-glucuronidase levels in different biological samples in cancer research and other related fields. The objective of our study is to demonstrate the potential application of the nuclear measurement technique in different biological samples.

Biologically Inspired Micro-Flight Research

NASA Technical Reports Server (NTRS)

Raney, David L.; Waszak, Martin R.

2003-01-01

Natural fliers demonstrate a diverse array of flight capabilities, many of which are poorly understood. NASA has established a research project to explore and exploit flight technologies inspired by biological systems. One part of this project focuses on dynamic modeling and control of micro aerial vehicles that incorporate flexible wing structures inspired by natural fliers such as insects, hummingbirds and bats. With a vast number of potential civil and military applications, micro aerial vehicles represent an emerging sector of the aerospace market. This paper describes an ongoing research activity in which mechanization and control concepts for biologically inspired micro aerial vehicles are being explored. Research activities focusing on a flexible fixed- wing micro aerial vehicle design and a flapping-based micro aerial vehicle concept are presented.

Time-dependent effects of ultraviolet and nonthermal atmospheric pressure plasma on the biological activity of titanium

NASA Astrophysics Data System (ADS)

Choi, Sung-Hwan; Jeong, Won-Seok; Cha, Jung-Yul; Lee, Jae-Hoon; Yu, Hyung-Seog; Choi, Eun-Ha; Kim, Kwang-Mahn; Hwang, Chung-Ju

2016-09-01

Here, we evaluated time-dependent changes in the effects of ultraviolet (UV) and nonthermal atmospheric pressure plasma (NTAPPJ) on the biological activity of titanium compared with that of untreated titanium. Grade IV machined surface titanium discs (12-mm diameter) were used immediately and stored up to 28 days after 15-min UV or 10-min NTAPPJ treatment. Changes of surface characteristics over time were evaluated using scanning electron microscopy, surface profiling, contact angle analysis, X-ray photoelectron spectroscopy, and surface zeta-potential. Changes in biological activity over time were as determined by analysing bovine serum albumin adsorption, MC3T3-E1 early adhesion and morphometry, and alkaline phosphatase (ALP) activity between groups. We found no differences in the effects of treatment on titanium between UV or NTAPPJ over time; both treatments resulted in changes from negatively charged hydrophobic (bioinert) to positively charged hydrophilic (bioactive) surfaces, allowing enhancement of albumin adsorption, osteoblastic cell attachment, and cytoskeleton development. Although this effect may not be prolonged for promotion of cell adhesion until 4 weeks, the effects were sufficient to maintain ALP activity after 7 days of incubation. This positive effect of UV and NTAPPJ treatment can enhance the biological activity of titanium over time.

Yellow-Cedar, Callitropsis (Chamaecyparis) nootkatensis, Secondary Metabolites, Biological Activities, and Chemical Ecology.

PubMed

Karchesy, Joseph J; Kelsey, Rick G; González-Hernández, M P

2018-05-01

Yellow-cedar, Callitropsis nootkatensis, is prevalent in coastal forests of southeast Alaska, western Canada, and inland forests along the Cascades to northern California, USA. These trees have few microbial or animal pests, attributable in part to the distinct groups of biologically active secondary metabolites their tissues store for chemical defense. Here we summarize the new yellow-cedar compounds identified and their biological activities, plus new or expanded activities for tissues, extracts, essential oils and previously known compounds since the last review more than 40 years ago. Monoterpene hydrocarbons are the most abundant compounds in foliage, while heartwood contains substantial quantities of oxygenated monoterpenes and oxygenated sesquiterpenes, with one or more tropolones. Diterpenes occur in foliage and bark, whereas condensed tannins have been isolated from inner bark. Biological activities expressed by one or more compounds in these groups include fungicide, bactericide, sporicide, acaricide, insecticide, general cytotoxicity, antioxidant and human anticancer. The diversity of organisms impacted by whole tissues, essential oils, extracts, or individual compounds now encompasses ticks, fleas, termites, ants, mosquitoes, bacteria, a water mold, fungi and browsing animals. Nootkatone, is a heartwood component with sufficient activity against arthropods to warrant research focused toward potential development as a commercial repellent and biopesticide for ticks, mosquitoes and possibly other arthropods that vector human and animal pathogens.

Synthesis, Biological Evaluation and Molecular Docking of New Benzenesulfonylhydrazone as Potential anti-Trypanosoma cruzi Agents.

PubMed

Elizondo-Jimenez, Silvia; Moreno-Herrera, Antonio; Reyes-Olivares, Rogelio; Dorantes-Gonzalez, Edith; Nogueda-Torres, Benjamín; Oliveira, Eduardo A Gamosa de; Romeiro, Nelilma C; Lima, Lidia M; Palos, Isidro; Rivera, Gildardo

2017-01-01

Chagas disease is a public health problem caused by Trypanosoma cruzi. Cruzain is a pharmacological target for designing a new drug against this parasite. Hydrazone and Nacylhydrazone derivatives have been traditionally associated as potential Cruzain inhibitors. Additionally, benzenesulfonyl derivatives show trypanocidal activity. Therefore, in this study, the combination of both structures has been taken into account for drug design. Seven benzenesulfonylhydrazone (BS-H) and seven N-propionyl benzenesulfonylhydrazone (BS-NAH) derivatives were synthetized and elucidated by infrared spectroscopy, nuclear magnetic resonance, and elemental analysis. All compounds were evaluated biologically in vitro against two strains of Trypanosoma cruzi (NINOA and INC-5), which are endemic in Mexico, and compared with the reference drugs nifurtimox and benznidazole. In order to gain insight into the putative molecular origin of the trypanocidal properties of these derivatives, docking studies were carried out with Cruzain. Compounds 4 and 6 (BS-H) and 10, 12-14 (BS-NAH) showed the best biological activity against NINOA and INC-5 strains, respectively. Compound 13 was the most potent trypanocidal compound showing a LC50 of 0.06 µM against INC-5 strain. However, compound 4 showed the best activity against both strains (LC50 <30 µM). Theoretical binding modes obtained suggested covalent binding that could explain their biological activity. Benzenesulfonyl and N-propionyl benzenesulfonyl hydrazone derivatives are good options for developing new trypanocidal agents. Particularly, compound 4 could be considered a lead compound. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Characteristics of highly cross-linked polyethylene wear debris in vivo

PubMed Central

Baxter, Ryan M.; MacDonald, Daniel W.; Kurtz, Steven M.; Steinbeck, Marla J.

2014-01-01

Despite the widespread implementation of highly cross-linked polyethylene (HXLPE) liners to reduce the clinical incidence of osteolysis, it is not known if the improved wear resistance will outweigh the inflammatory potential of HXLPE wear debris generated in vivo. Thus, we asked: What are the differences in size, shape, number, and biological activity of polyethylene wear particles obtained from primary total hip arthroplasty revision surgery of conventional polyethylene (CPE) versus remelted or annealed HXLPE liners? Pseudocapsular tissue samples were collected from revision surgery of CPE and HXLPE (annealed and remelted) liners, and digested using nitric acid. The isolated polyethylene wear particles were evaluated using scanning electron microscopy. Tissues from both HXLPE cohorts contained an increased percentage of submicron particles compared to the CPE cohort. However, the total number of particles was lower for both HXLPE cohorts, as a result there was no significant difference in the volume fraction distribution and specific biological activity (SBA; the relative biological activity per unit volume) between cohorts. In contrast, based on the decreased size and number of HXLPE wear debris there was a significant decrease in total particle volume (mm3/g of tissue). Accordingly, when the SBA was normalized by total particle volume (mm3/gm tissue) or by component wear volume rate (mm3/year), functional biological activity of the HXLPE wear debris was significantly decreased compared to the CPE cohort. Indications for this study are that the osteolytic potential of wear debris generated by HXLPE liners in vivo is significantly reduced by improvements in polyethylene wear resistance. PMID:23436587

Do-it-yourself biology: challenges and promises for an open science and technology movement.

PubMed

Landrain, Thomas; Meyer, Morgan; Perez, Ariel Martin; Sussan, Remi

2013-09-01

The do-it-yourself biology (DIYbio) community is emerging as a movement that fosters open access to resources permitting modern molecular biology, and synthetic biology among others. It promises in particular to be a source of cheaper and simpler solutions for environmental monitoring, personal diagnostic and the use of biomaterials. The successful growth of a global community of DIYbio practitioners will depend largely on enabling safe access to state-of-the-art molecular biology tools and resources. In this paper we analyze the rise of DIYbio, its community, its material resources and its applications. We look at the current projects developed for the international genetically engineered machine competition in order to get a sense of what amateur biologists can potentially create in their community laboratories over the coming years. We also show why and how the DIYbio community, in the context of a global governance development, is putting in place a safety/ethical framework for guarantying the pursuit of its activity. And finally we argue that the global spread of DIY biology potentially reconfigures and opens up access to biological information and laboratory equipment and that, therefore, it can foster new practices and transversal collaborations between professional scientists and amateurs.

Astaxanthin: Sources, Extraction, Stability, Biological Activities and Its Commercial Applications—A Review

PubMed Central

Ambati, Ranga Rao; Siew Moi, Phang; Ravi, Sarada; Aswathanarayana, Ravishankar Gokare

2014-01-01

There is currently much interest in biological active compounds derived from natural resources, especially compounds that can efficiently act on molecular targets, which are involved in various diseases. Astaxanthin (3,3′-dihydroxy-β, β′-carotene-4,4′-dione) is a xanthophyll carotenoid, contained in Haematococcus pluvialis, Chlorella zofingiensis, Chlorococcum, and Phaffia rhodozyma. It accumulates up to 3.8% on the dry weight basis in H. pluvialis. Our recent published data on astaxanthin extraction, analysis, stability studies, and its biological activities results were added to this review paper. Based on our results and current literature, astaxanthin showed potential biological activity in in vitro and in vivo models. These studies emphasize the influence of astaxanthin and its beneficial effects on the metabolism in animals and humans. Bioavailability of astaxanthin in animals was enhanced after feeding Haematococcus biomass as a source of astaxanthin. Astaxanthin, used as a nutritional supplement, antioxidant and anticancer agent, prevents diabetes, cardiovascular diseases, and neurodegenerative disorders, and also stimulates immunization. Astaxanthin products are used for commercial applications in the dosage forms as tablets, capsules, syrups, oils, soft gels, creams, biomass and granulated powders. Astaxanthin patent applications are available in food, feed and nutraceutical applications. The current review provides up-to-date information on astaxanthin sources, extraction, analysis, stability, biological activities, health benefits and special attention paid to its commercial applications. PMID:24402174

Active matter at the interface between materials science and cell biology

NASA Astrophysics Data System (ADS)

Needleman, Daniel; Dogic, Zvonimir

2017-09-01

The remarkable processes that characterize living organisms, such as motility, self-healing and reproduction, are fuelled by a continuous injection of energy at the microscale. The field of active matter focuses on understanding how the collective behaviours of internally driven components can give rise to these biological phenomena, while also striving to produce synthetic materials composed of active energy-consuming components. The synergistic approach of studying active matter in both living cells and reconstituted systems assembled from biochemical building blocks has the potential to transform our understanding of both cell biology and materials science. This methodology can provide insight into the fundamental principles that govern the dynamical behaviours of self-organizing subcellular structures, and can lead to the design of artificial materials and machines that operate away from equilibrium and can thus attain life-like properties. In this Review, we focus on active materials made of cytoskeletal components, highlighting the role of active stresses and how they drive self-organization of both cellular structures and macroscale materials, which are machines powered by nanomachines.

Single molecule thermodynamics in biological motors.

PubMed

Taniguchi, Yuichi; Karagiannis, Peter; Nishiyama, Masayoshi; Ishii, Yoshiharu; Yanagida, Toshio

2007-04-01

Biological molecular machines use thermal activation energy to carry out various functions. The process of thermal activation has the stochastic nature of output events that can be described according to the laws of thermodynamics. Recently developed single molecule detection techniques have allowed each distinct enzymatic event of single biological machines to be characterized providing clues to the underlying thermodynamics. In this study, the thermodynamic properties in the stepping movement of a biological molecular motor have been examined. A single molecule detection technique was used to measure the stepping movements at various loads and temperatures and a range of thermodynamic parameters associated with the production of each forward and backward step including free energy, enthalpy, entropy and characteristic distance were obtained. The results show that an asymmetry in entropy is a primary factor that controls the direction in which the motor will step. The investigation on single molecule thermodynamics has the potential to reveal dynamic properties underlying the mechanisms of how biological molecular machines work.

Biological Effects of Space Radiation and Development of Effective Countermeasures

PubMed Central

Kennedy, Ann R.

2014-01-01

As part of a program to assess the adverse biological effects expected from astronaut exposure to space radiation, numerous different biological effects relating to astronaut health have been evaluated. There has been major focus recently on the assessment of risks related to exposure to solar particle event (SPE) radiation. The effects related to various types of space radiation exposure that have been evaluated are: gene expression changes (primarily associated with programmed cell death and extracellular matrix (ECM) remodeling), oxidative stress, gastrointestinal tract bacterial translocation and immune system activation, peripheral hematopoietic cell counts, emesis, blood coagulation, skin, behavior/fatigue (including social exploration, submaximal exercise treadmill and spontaneous locomotor activity), heart functions, alterations in biological endpoints related to astronaut vision problems (lumbar puncture/intracranial pressure, ocular ultrasound and histopathology studies), and survival, as well as long-term effects such as cancer and cataract development. A number of different countermeasures have been identified that can potentially mitigate or prevent the adverse biological effects resulting from exposure to space radiation. PMID:25258703

Biological effects of space radiation and development of effective countermeasures

NASA Astrophysics Data System (ADS)

Kennedy, Ann R.

2014-04-01

As part of a program to assess the adverse biological effects expected from astronauts' exposure to space radiation, numerous different biological effects relating to astronauts' health have been evaluated. There has been major focus recently on the assessment of risks related to exposure to solar particle event (SPE) radiation. The effects related to various types of space radiation exposure that have been evaluated are: gene expression changes (primarily associated with programmed cell death and extracellular matrix (ECM) remodeling), oxidative stress, gastrointestinal tract bacterial translocation and immune system activation, peripheral hematopoietic cell counts, emesis, blood coagulation, skin, behavior/fatigue (including social exploration, submaximal exercise treadmill and spontaneous locomotor activity), heart functions, alterations in biological endpoints related to astronauts' vision problems (lumbar puncture/intracranial pressure, ocular ultrasound and histopathology studies), and survival, as well as long-term effects such as cancer and cataract development. A number of different countermeasures have been identified that can potentially mitigate or prevent the adverse biological effects resulting from exposure to space radiation.

Multiple, novel biologically active endophytic actinomycetes isolated from upper Amazonian rainforests.

PubMed

Bascom-Slack, Carol A; Ma, Cong; Moore, Emily; Babbs, Beatrice; Fenn, Kathleen; Greene, Joshua S; Hann, Bradley D; Keehner, Jocelyn; Kelley-Swift, Elizabeth G; Kembaiyan, Vivek; Lee, Sun Jin; Li, Puyao; Light, David Y; Lin, Emily H; Schorn, Michelle A; Vekhter, Daniel; Boulanger, Lori-Ann; Hess, W M; Vargas, Percy Núñez; Strobel, Gary A; Strobel, Scott A

2009-08-01

Microbial biodiversity provides an increasingly important source of medically and industrially useful compounds. We have isolated 14 actinomycete species from a collection of approximately 300 plant stem samples from the upper Amazonian rainforest in Peru. All of the cultured isolates produce substances with inhibitory activity directed at a range of potential fungal and bacterial pathogens. For some organisms, this activity is very broad in spectrum while other organisms show specific activity against a limited number of organisms. Two of these organisms preferentially inhibit bacterial test organisms over eukaryotic organisms. rDNA sequence analysis indicates that these organisms are not equivalent to any other cultured deposits in GenBank. Our results provide evidence of the untapped biodiversity in the form of biologically active microbes present within the tissues of higher plants.

Respirometric screening of several types of manure and mixtures intended for composting.

PubMed

Barrena, Raquel; Turet, Josep; Busquets, Anna; Farrés, Moisès; Font, Xavier; Sánchez, Antoni

2011-01-01

The viability of mixtures from manure and agricultural wastes as composting sources were systematically studied using a physicochemical and biological characterization. The combination of different parameters such as C:N ratio, free air space (FAS) and moisture content can help in the formulation of the mixtures. Nevertheless, the composting process may be challenging, particularly at industrial scales. The results of this study suggest that if the respirometric potential is known, it is possible to predict the behaviour of a full scale composting process. Respiration indices can be used as a tool for determining the suitability of composting as applied to manure and complementary wastes. Accordingly, manure and agricultural wastes with a high potential for composting and some proposed mixtures have been characterized in terms of respiration activity. Specifically, the potential of samples to be composted has been determined by means of the oxygen uptake rate (OUR) and the dynamic respirometric index (DRI). During this study, four of these mixtures were composted at full scale in a system consisting of a confined pile with forced aeration. The biological activity was monitored by means of the oxygen uptake rate inside the material (OURinsitu). This new parameter represents the real activity of the process. The comparison between the potential respirometric activities at laboratory scale with the in situ respirometric activity observed at full scale may be a useful tool in the design and optimization of composting systems for manure and other organic agricultural wastes. Copyright © 2010 Elsevier Ltd. All rights reserved.

[Detection of Physiological Activity of Pharmaceuticals in Wastewater and River Water].

PubMed

Ihara, Masaru; Zhang, Han; Hanamoto, Seiya; Tanaka, Hiroaki

2018-01-01

　Pharmaceuticals are widely found in aquatic environments worldwide. Concern about their potential risks to aquatic species has been raised because they are designed to be biologically active. To address this concern, we must know whether biological activity of pharmaceuticals can be detected in waters. Nearly half of all marketed pharmaceuticals act by binding to the G protein-coupled receptor (GPCR). In this study, we measured the physiological activity of GPCR-acting pharmaceuticals in effluent from a wastewater treatment plant (WWTP) and upstream and downstream of its outfall in Japan during 2 years. We used the in vitro transforming growth factor-α (TGFα) shedding assay, which accurately and sensitively detects GPCR activation, to investigate the antagonistic activities of water extracts against receptors for dopamine (D2) and histamine (H1). Activities detected in waters were quantified as antagonist equivalent quantities (EQs). In WWTP effluent extracts, antagonistic activity was detected at several hundred ng/L of sulpiride-EQ (D2) and several μg/L of diphenhydramine (DIP)-EQ (H1). In downstream river water extracts, antagonistic activity against H1 was around several hundred ng/L of DIP-EQ, higher than that upstream owing to the WWTP effluent. This review discusses the research needed to resolve the concern about potential risks of pharmaceuticals in waters to aquatic species.

BIOPEP database and other programs for processing bioactive peptide sequences.

PubMed

Minkiewicz, Piotr; Dziuba, Jerzy; Iwaniak, Anna; Dziuba, Marta; Darewicz, Małgorzata

2008-01-01

This review presents the potential for application of computational tools in peptide science based on a sample BIOPEP database and program as well as other programs and databases available via the World Wide Web. The BIOPEP application contains a database of biologically active peptide sequences and a program enabling construction of profiles of the potential biological activity of protein fragments, calculation of quantitative descriptors as measures of the value of proteins as potential precursors of bioactive peptides, and prediction of bonds susceptible to hydrolysis by endopeptidases in a protein chain. Other bioactive and allergenic peptide sequence databases are also presented. Programs enabling the construction of binary and multiple alignments between peptide sequences, the construction of sequence motifs attributed to a given type of bioactivity, searching for potential precursors of bioactive peptides, and the prediction of sites susceptible to proteolytic cleavage in protein chains are available via the Internet as are other approaches concerning secondary structure prediction and calculation of physicochemical features based on amino acid sequence. Programs for prediction of allergenic and toxic properties have also been developed. This review explores the possibilities of cooperation between various programs.

The effect of stereochemistry on the biological activity of natural phytotoxins, fungicides, insecticides and herbicides.

PubMed

Evidente, Antonio; Cimmino, Alessio; Andolfi, Anna

2013-02-01

Phytotoxins are secondary microbial metabolites that play an essential role in the development of disease symptoms induced by fungi on host plants. Although phytotoxins can cause extensive-and in some cases devastating-damage to agricultural crops, they can also represent an important tool to develop natural herbicides when produced by fungi and plants to inhibit the growth and spread of weeds. An alternative strategy to biologically control parasitic plants is based on the use of plant and fungal metabolites, which stimulate seed germination in the absence of the host plant. Nontoxigenic fungi also produce bioactive metabolites with potential fungicide and insecticide activity, and could be applied for crop protection. All these metabolites represent important tools to develop eco-friendly pesticides. This review deals with the relationships between the biological activity of some phytotoxins, seed germination stimulants, fungicides and insecticides, and their stereochemistry. Copyright © 2012 Wiley Periodicals, Inc.

Metagenomic approaches to exploit the biotechnological potential of the microbial consortia of marine sponges.

PubMed

Kennedy, Jonathan; Marchesi, Julian R; Dobson, Alan D W

2007-05-01

Natural products isolated from sponges are an important source of new biologically active compounds. However, the development of these compounds into drugs has been held back by the difficulties in achieving a sustainable supply of these often-complex molecules for pre-clinical and clinical development. Increasing evidence implicates microbial symbionts as the source of many of these biologically active compounds, but the vast majority of the sponge microbial community remain uncultured. Metagenomics offers a biotechnological solution to this supply problem. Metagenomes of sponge microbial communities have been shown to contain genes and gene clusters typical for the biosynthesis of biologically active natural products. Heterologous expression approaches have also led to the isolation of secondary metabolism gene clusters from uncultured microbial symbionts of marine invertebrates and from soil metagenomic libraries. Combining a metagenomic approach with heterologous expression holds much promise for the sustainable exploitation of the chemical diversity present in the sponge microbial community.

Synthesis and biological evaluation of platensimycin analogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Hong C.; Ding, Fa-Xiang; Singh, Sheo B.

2009-07-23

Platensimycin (1) displays antibacterial activity due to its inhibition of the elongation condensing enzyme (FabF), a novel mode of action that could potentially lead to a breakthrough in developing a new generation of antibiotics. The medicinal chemistry efforts were focused on the modification of the enone moiety of platensimycin and several analogs showed significant activity against FabF and possess antibacterial activity.

Antimicrobial, Antioxidant, Anti-Inflammatory, and Cytotoxic Activities of Propolis from the Stingless Bee Tetragonisca fiebrigi (Jataí).

PubMed

Campos, Jaqueline Ferreira; Dos Santos, Uilson Pereira; da Rocha, Paola Dos Santos; Damião, Marcio José; Balestieri, José Benedito Perrella; Cardoso, Claudia Andrea Lima; Paredes-Gamero, Edgar Julian; Estevinho, Leticia Miranda; de Picoli Souza, Kely; Dos Santos, Edson Lucas

2015-01-01

Propolis from stingless bees Tetragonisca fiebrigi found in Brazil is used in folk medicine by their nutritional and therapeutic properties. However, there are no scientific records evidencing such properties. The present study was designed to investigate the chemical composition and the biological properties of propolis from T. fiebrigi. For this, the chemical composition of the ethanol extract of propolis (EEP) was determined by GC-MS and presented phenolic compounds, alcohol, and terpenes as its major class compounds. The antimicrobial activity was accessed in gram-positive and gram-negative bacteria and in fungi, isolated from different biological fluids and reference strains. The EEP was active against all microorganisms and showed antioxidant activity by scavenging free radicals, inhibiting hemolysis and lipid peroxidation in human erythrocytes incubated with an oxidizing agent. The anti-inflammatory potential of the EEP was confirmed by inhibition of the hyaluronidase enzyme. The cytotoxic activity was concentration-dependent against K562 cells, with a predominance of death by necrosis. Taken together, these results show that propolis from T. fiebrigi has important therapeutic activities, which suggest its potential application in the pharmaceutical industry, as well as in health foods, beverages, and nutritional supplements.

Design and synthesis of some new 2,3'-bipyridine-5-carbonitriles as potential anti-inflammatory/antimicrobial agents.

PubMed

Elzahhar, Perihan A; Elkazaz, Salwa; Soliman, Raafat; El-Tombary, Alaa A; Shaltout, Hossam A; El-Ashmawy, Ibrahim M; Abdel Wahab, Abeer E; El-Hawash, Soad A

2017-08-01

Inflammation may cause accumulation of fluid in the injured area, which may promote bacterial growth. Other reports disclosed that non-steroidal anti-inflammatory drugs may enhance progression of bacterial infection. This work describes synthesis of new series of 2,3'-bipyridine-5-carbonitriles as structural analogs of etoricoxib, linked at position-6 to variously substituted thio or oxo moieties. Biological screening results revealed that compounds 2b, 4b, 7e and 8 showed significant acute and chronic AI activities and broad spectrum of antimicrobial activity. In addition, similarity ensemble approach was applied to predict potential biological targets of the tested compounds. Then, pharmacophore modeling study was employed to determine the most important structural parameters controlling bioactivity. Moreover, title compounds showed physicochemical properties within those considered adequate for drug candidates. This study explored the potential of such series of compounds as structural leads for further modification to develop a new class of dual AI-antimicrobial agents.

Effect of fortification with parsley (Petroselinum crispum Mill.) leaves on the nutraceutical and nutritional quality of wheat pasta.

PubMed

Sęczyk, Łukasz; Świeca, Michał; Gawlik-Dziki, Urszula; Luty, Marcin; Czyż, Jarosław

2016-01-01

This study examines the nutraceutical (phenolics content, antioxidant activity, biological activity) and nutritional potential (starch and protein digestibility) of wheat pasta supplemented with 1-4% of powdered parsley leaves. Compared to the control, the potentially bioaccessible fraction of pasta fortified with 4% parsley leaves was characterized by 67% increased phenolics content, a 146% higher antiradical ability and 220% additional reducing power. Elevation of these parameters in fortified pasta was accompanied by an augmentation of its antiproliferative effect on carcinoma cells, which confirms their biological relevance. Supplementation of pasta had no significant effect on starch digestibility, while negatively affecting protein digestibility (a reduction by about 20% for pasta with a 4% supplement). Electrophoretic and chromatographic analyses indicated the presence of phenolic interactions with proteins and/or digestive enzymes. Fortification improved the nutraceutical and nutritional potential of the studied pasta; however, the final effect is made by many factors, including phenolics-food matrix interactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

The growing role of biologics and biosimilars in the United States: Perspectives from the APhA Biologics and Biosimilars Stakeholder Conference.

PubMed

Crespi-Lofton, Judy; Skelton, Jann B

The American Pharmacists Association (APhA) convened the Biologics and Biosimilars Stakeholder Conference on November 30, 2016, in Washington DC. The objectives of the Conference were to determine the key issues and challenges within the marketplace for biologics, follow-on biologics (FOBs), and biosimilars, identify potential roles and responsibilities of pharmacists regarding biologic and biosimilar medications, and identify actions or activities that pharmacists may take to optimize the safe and cost-effective use of biologics and biosimilars. National thought leaders and stakeholder representatives, including individuals from the Food and Drug Administration, Centers for Medicare and Medicaid Services, a private third-party payer, manufacturers, and several national organizations of health care professionals, participated in the conference. Information shared by this group was supplemented with relevant legal and regulatory information and published literature. Biologics play a valuable role in the treatment of numerous health conditions, but their associated costs, which tend to be greater than those of small-molecule drugs, place a burden on the health care system. Biosimilars (both noninterchangeable and interchangeable) are highly similar copies of the originator biologic and offer the potential to reduce costs and improve patient access to biological products by increasing treatment options and creating a more competitive market. Despite the potential benefits of biosimilars, certain factors may limit their uptake. The conference participants explored issues that different stakeholders think influence the use of biologics, including biosimilars, in the United States. Barriers included technology, prescriber-pharmacist communication, legislation and regulations, limited patient and health care practitioner knowledge of biological products, patient and health care practitioner perceptions of biosimilars, and evolving science or lack of long-term data. After participants identified issues, they discussed strategies to address these concerns, including the need to enhance the education of pharmacists, prescribers, and patients regarding biologic products, including biosimilars and FOBs; the passage of state laws and regulations that do not impede the use of biosimilars, including interchangeable biosimilars; the use of product-specific tracking information in electronic health records and surveillance systems; bidirectional communication among pharmacists, prescribers, and other members of the care team to support pharmacovigilance and the maintenance of accurate patient records; and the development of evidence-based third-party payer policies. Patient access to safe and cost-effective treatments is an important goal for the health care system. As the availability and use of biosimilars, including those determined to be interchangeable, increases, their potential to lower costs and improve patient access to treatment grows. However, the extent of such growth is, in part, dependent on various stakeholders' decisions to provide, pay for, or use these products in a safe and thoughtful manner. Ongoing stakeholder collaboration, educational activities, and review of current government or payer policies are required to optimize the uptake of biological products, including biosimilars. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Processing and characterization of silk sericin from Bombyx mori and its application in biomaterials and biomedicines.

PubMed

Cao, Ting-Ting; Zhang, Yu-Qing

2016-04-01

Bombyx mori silk is composed of 60-80% fibroin, 15-35% sericin and 1-5% non-sericin component including wax, pigments, sugars and other impurities. For two decades, the protein-based silk fibroin was extensively used in the research and development of medical biomaterials and biomedicines. Sericin is frequently ignored and abandoned as a byproduct or waste in the processing of traditional silk fabrics, silk floss or modern silk biomaterials. However, similar to fibroin, sericin is not only a highly useful biological material, but also a lot of biological activity. Moreover, the non-sericin component present with sericin in the cocoon shell also has a strong biological activity. In this review, the extraction and recovery methods of sericin and the non-sericin component from the cocoon layer are reported, and their composition, properties and biological activity are described to produce a comprehensive report on biomedical materials and biological drugs. In addition, related problems or concerns present in the research and development of sericin are discussed, and a potential application of sericin in sustainable development is also presented. Copyright © 2015 Elsevier B.V. All rights reserved.

In vitro and in vivo biological activities of anthocyanins from Nitraria tangutorun Bobr. fruits.

PubMed

Ma, Tao; Hu, Na; Ding, Chenxi; Zhang, Qiulong; Li, Wencong; Suo, Yourui; Wang, Honglun; Bai, Bo; Ding, Chenxu

2016-03-01

Anthocyanins are the main compounds in Nitraria tangutorun Bobr. The enrichment and purification of anthocyanins on macroporous resins were investigated. Regarding anthocyanin purification, static adsorption and desorption were studied. The optimal experimental conditions were the following: resin type: X-5; static adsorption time: 6h; desorption solution: ethanol-water-HCl (80:19:1, V/V/V; pH 1); desorption time: 40min. Furthermore, the in vitro and in vivo biological activities of the anthocyanins were evaluated. The anthocyanins showed ideal scavenging effects on free radicals in vitro, especially on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl free radical (OH). In the animal experiment, blood lipid metabolism of hyperlipidemia rats was regulated by anthocyanin contents. The superoxide dismutase (SOD) activity and the total antioxidant capacity (TAC) of hyperlipidemia rats were also improved by anthocyanins. These results showed that anthocyanins from N. tangutorun Bobr. fruits had potential biological activities in vivo as well as in vitro. Copyright © 2015. Published by Elsevier Ltd.

Defining the Synthetic Biology Supply Chain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frazar, Sarah L.; Hund, Gretchen E.; Bonheyo, George T.

In this article, a team of experts in synthetic biology, data analytics, and national security describe the overall supply chain surrounding synthetic biology. The team analyzes selected interactions within that network to better understand the risks raised by synthetic biology and identifies opportunities for risk mitigation. To introduce the concept, the article will briefly describe how an understanding of supply chains has been important in promoting nuclear nonproliferation objectives. The article concludes by assessing the structure and networks identified in the supply chains to reveal potential opportunities for future biodefense research and development; options for additional information exchange; and meansmore » to interdict, detect, or deter suspicious activity.« less

Ecdysteroid 7,9(11)-dien-6-ones as potential photoaffinity labels for ecdysteroid binding proteins

PubMed Central

Bourne, Pauline C.; Whiting, Pensri; Dhadialla, Tarlochan S.; Hormann, Robert E.; Girault, Jean-Pierre; Harmatha, Juraj; Lafont, René; Dinan, Laurence

2002-01-01

Three ecdysteroid 7,9(11)-dien-7-ones (dacryhainansterone, 25-hydroxydacryhainansterone and kaladasterone) were prepared by dehydration of the corresponding 11a-hydroxy ecdysteroids (ajugasterone C, turkesterone and muristerone A, respectively). The biological activities of the dienones in the Drosophila melanogaster BII cell bioassay, which reflect the affinity for the ecdysteroid receptor complex, showed that the dienones retain high biological activity. Irradiation at 350 nm of the ecdysteroid dienones (100 nM) with bacterially-expressed dipteran and lepidopteran ecdysteroid receptor proteins (DmEcR/DmUSP or CfEcR/CfUSP), followed by loading with [3H]ponasterone A revealed that irradiation of dacryhainansterone or kaladasterone resulted in blocking of >70% of the specific binding sites. Thus, ecdysteroid dienones show considerable potential as photoaffinity analogues for ecdysteroid binding proteins. PMID:15455045

Ras Dimer Formation as a New Signaling Mechanism and Potential Cancer Therapeutic Target

PubMed Central

Chen, Mo; Peters, Alec; Huang, Tao; Nan, Xiaolin

2016-01-01

The K-, N-, and HRas small GTPases are key regulators of cell physiology and are frequently mutated in human cancers. Despite intensive research, previous efforts to target hyperactive Ras based on known mechanisms of Ras signaling have been met with little success. Several studies have provided compelling evidence for the existence and biological relevance of Ras dimers, establishing a new mechanism for regulating Ras activity in cells additionally to GTP-loading and membrane localization. Existing data also start to reveal how Ras proteins dimerize on the membrane. We propose a dimer model to describe Ras-mediated effector activation, which contrasts existing models of Ras signaling as a monomer or as a 5-8 membered multimer. We also discuss potential implications of this model in both basic and translational Ras biology. PMID:26423697

Microbial growth under a high-pressure CO2 environment

NASA Astrophysics Data System (ADS)

Thompson, J. R.; Hernandez, H. H.

2009-12-01

Carbon capture and storage (CCS) of CO2 has the potential to significantly reduce the emission of greenhouse gasses associated with fossil fuel combustion. The largest potential for storing captured CO2 in the United Sates is in deep geologic saline formations. Currently, little is known about the effects of CO2 storage on biologically active microbial communities found in the deep earth biosphere. Therefore, to investigate how deep earth microbial communities will be affected by the storage of CO2, we have built a high-pressure microbial growth system in which microbial samples are subjected to a supercritical CO2 (scCO2) environment. Recently we have isolated a microbial consortium that is capable of growth and extracellular matrix production in nutrient media under a supercritical CO2 headspace. This consortium was cultivated from hydrocarbon residues associated with saline formation waters and includes members of the gram-positive Bacillus genus. The cultivation of actively growing cells in an environment containing scCO2 is unexpected based on previous experimental evidence of microbial sterilization attributed to the acidic, desiccating, and solvent-like properties of scCO2. Such microbial consortia have potential for development as (i) biofilm barriers for geological carbon-dioxide sequestration, and as (ii) agents of biocatalysis in environmentally-friendly supercritical (sc) CO2 solvent systems. The discovery that microbes can remain biologically active, and grow, in these environments opens new frontiers for the use of self-regenerating biological systems in engineering applications.

Detoxification of sewage sludge by natural attenuation and implications for its use as a fertilizer on agricultural soils.

PubMed

Mazzeo, Dânia Elisa Christofoletti; Casado, Marta; Piña, Benjamin; Marin-Morales, Maria Aparecida

2016-12-01

Sewage Sludges (SS) from wastewater treatment systems constitute a potential alternative to agricultural fertilizers. However, their use is limited by the presence of toxic substances that may represent significant hazards for the environment and for human health. To test the potential of natural processes to attenuate their putative toxic activities, actual SS samples from domestic sewage were buried in holes in a pollution-free environment for different periods of time, up to one year. Aqueous and organic extracts were obtained after each period of natural attenuation, and their respective toxicity was tested for estrogenic and dioxin-like activity by yeast-based bioassays (ER-RYA and AhR-RYA, respectively) and for general toxicity and teratogenicity in zebrafish embryos. Dioxin-like activity was also tested in zebrafish embryos by monitoring the induction of the marker gene cyp1a. Whereas the results showed essentially no estrogenic activity, both dioxin-like activity and embryotoxicity were observed in the initial samples, decreasing significantly after six months of attenuation. Chemical analysis of toxic SS samples showed the presence of low levels of dioxins and furans, and relatively high levels of m- and p-cresol, at concentrations that only partially justify the observed biological effects. Our data indicates the presence of largely uncharacterized hydrophilic compounds with high biological activity in SS, constituting a potential risk of groundwater pollution upon their disposal into the environment. It also shows that this potential impact may be significantly mitigated by attenuation protocols, as the one presented here. Copyright © 2016 Elsevier B.V. All rights reserved.

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses

PubMed Central

2017-01-01

Introduction Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. Aim The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. Methods A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. Results The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Conclusion Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk factors. PMID:29077727

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses.

PubMed

Sultana, Janet; Calabró, Marco; Garcia-Serna, Ricard; Ferrajolo, Carmen; Crisafulli, Concetta; Mestres, Jordi; Trifirò', Gianluca

2017-01-01

Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk factors.

Activity-based proteome profiling of potential cellular targets of Orlistat--an FDA-approved drug with anti-tumor activities.

PubMed

Yang, Peng-Yu; Liu, Kai; Ngai, Mun Hong; Lear, Martin J; Wenk, Markus R; Yao, Shao Q

2010-01-20

Orlistat, or tetrahydrolipstatin (THL), is an FDA-approved antiobesity drug with potential antitumor activities. Cellular off-targets and potential side effects of Orlistat in cancer therapies, however, have not been extensively explored thus far. In this study, we report the total of synthesis of THL-like protein-reactive probes, in which extremely conservative modifications (i.e., an alkyne handle) were introduced in the parental THL structure to maintain the native biological properties of Orlistat, while providing the necessary functionality for target identification via the bio-orthogonal click chemistry. With these natural productlike, cell-permeable probes, we were able to demonstrate, for the first time, this chemical proteomic approach is suitable for the identification of previously unknown cellular targets of Orlistat. In addition to the expected fatty acid synthase (FAS), we identified a total of eight new targets, some of which were further validated by experiments including Western blotting, recombinant protein expression, and site-directed mutagenesis. Our findings have important implications in the consideration of Orlistat as a potential anticancer drug at its early stages of development for cancer therapy. Our strategy should be broadly useful for off-target identification against quite a number of existing drugs and/or candidates, which are also covalent modifiers of their biological targets.

DNA Adducts from Anticancer Drugs as Candidate Predictive Markers for Precision Medicine

PubMed Central

2016-01-01

Biomarker-driven drug selection plays a central role in cancer drug discovery and development, and in diagnostic strategies to improve the use of traditional chemotherapeutic drugs. DNA-modifying anticancer drugs are still used as first line medication, but drawbacks such as resistance and side effects remain an issue. Monitoring the formation and level of DNA modifications induced by anticancer drugs is a potential strategy for stratifying patients and predicting drug efficacy. In this perspective, preclinical and clinical data concerning the relationship between drug-induced DNA adducts and biological response for platinum drugs and combination therapies, nitrogen mustards and half-mustards, hypoxia-activated drugs, reductase-activated drugs, and minor groove binding agents are presented and discussed. Aspects including measurement strategies, identification of adducts, and biological factors that influence the predictive relationship between DNA modification and biological response are addressed. A positive correlation between DNA adduct levels and response was observed for the majority of the studies, demonstrating the high potential of using DNA adducts from anticancer drugs as mechanism-based biomarkers of susceptibility, especially as bioanalysis approaches with higher sensitivity and throughput emerge. PMID:27936622

Synthetic Astrobiology

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2016-01-01

Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. And what about the limits for life? Can we create organisms that expand the envelope for life? In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

A new class of potential chloroquine-resistance reversal agents for Plasmodia: syntheses and biological evaluation of 1-(3'-diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines.

PubMed

Batra, S; Srivastava, P; Roy, K; Pandey, V C; Bhaduri, A P

2000-09-07

1-(3'-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines were synthesized and evaluated for CQ-resistant reversal activity. In general the compounds of the series elicit better biological response than their phenylmethyl analogues. The most active compound 4b has been evaluated in vivo in detail, and the results are presented. The possible mode of action of the compounds of this series is by inhibition of the enzyme heme oxygenase, thereby increasing the levels of heme and hemozoin, which are lethal to the parasite.

Novel antiprotozoal products: imidazole and benzimidazole N-oxide derivatives and related compounds.

PubMed

Aguirre, Gabriela; Boiani, Mariana; Cerecetto, Hugo; Gerpe, Alejandra; González, Mercedes; Sainz, Yolanda Fernández; Denicola, Ana; De Ocáriz, Carmen Ochoa; Nogal, Juan José; Montero, David; Escario, José Antonio

2004-05-01

The syntheses and biological evaluation of the first anti-protozoa imidazole N-oxide and benzimidazole N-oxide and their derivatives are reported. They were tested in vitro against two different protozoa, Trypanosoma cruzi and Trichomonas vaginalis. Derivative 7c, ethyl-1-(i-butyloxycarbonyloxy)-6-nitrobenzimid-azole-2-carboxylate, displayed activity on both protozoa. Lipophilicity and redox potential were experimentally determined in order to study the relationship with activity of the compounds. These properties are well related with the observed bioactivity. Imidazole and benzimidazole N-oxide derivatives are becoming leaders for further chemical modifications and advanced biological studies.

Biological Activities of Polyphenols from Grapes

PubMed Central

Xia, En-Qin; Deng, Gui-Fang; Guo, Ya-Jun; Li, Hua-Bin

2010-01-01

The dietary consumption of grape and its products is associated with a lower incidence of degenerative diseases such as cardiovascular disease and certain types of cancers. Most recent interest has focused on the bioactive phenolic compounds in grape. Anthocyanins, flavanols, flavonols and resveratrol are the most important grape polyphenols because they possess many biological activities, such as antioxidant, cardioprotective, anticancer, anti-inflammation, antiaging and antimicrobial properties. This review summarizes current knowledge on the bioactivities of grape phenolics. The extraction, isolation and identification methods of polyphenols from grape as well as their bioavailability and potential toxicity also are included. PMID:20386657

Design, synthesis and preliminary biological evaluation of indoline-2,3-dione derivatives as novel HDAC inhibitors.

PubMed

Jin, Kang; Li, Shanshan; Li, Xiaoguang; Zhang, Jian; Xu, Wenfang; Li, Xuechen

2015-08-01

Histone deacetylases (HDACs) are zinc-dependent or NAD(+) dependent enzymes and play a critical role in the process of tumor development. Herein a series of indoline-2,3-dione derivatives have been designed and synthesized as potential HDACs inhibitors. The preliminary biological evaluation showed that most compounds synthesized have exhibited moderate Hela cell nuclear extract inhibitory activities, among which compound 25a (IC50=10.13 nM) has shown the best efficacy. The anti-proliferative activities of some of these compounds were also discussed. Copyright © 2015. Published by Elsevier Ltd.

Influence of operating parameters on the biodegradation of steroid estrogens and nonylphenolic compounds during biological wastewater treatment processes.

PubMed

Koh, Yoong K K; Chiu, Tze Y; Boobis, Alan R; Scrimshaw, Mark D; Bagnall, John P; Soares, Ana; Pollard, Simon; Cartmell, Elise; Lester, John N

2009-09-01

This study investigated operational factors influencing the removal of steroid estrogens and nonylphenolic compounds in two sewage treatment works, one a nitrifying/denitrifying activated sludge plant and the other a nitrifying/denitrifying activated sludge plant with phosphorus removal. Removal efficiencies of >90% for steroid estrogens and for longer chain nonylphenol ethoxylates (NP4-12EO) were observed at both works, which had equal sludge ages of 13 days. However, the biological activity in terms of milligrams of estrogen removed per day per tonne of biomass was found to be 50-60% more efficient in the nitrifying/denitrifying activated sludge works compared to the works which additionallyincorporated phosphorusremoval. A temperature reduction of 6 degrees C had no impact on the removal of free estrogens, but removal of the conjugated estrone-3-sulfate was reduced by 20%. The apparent biomass sorption (LogKp) values were greater in the nitrifying/denitrifying works than those in the nitrifying/denitrifying works with phosphorus removal for both steroid estrogens and honylphenolic compounds possibly indicating a different cell surface structure and therefore microbial population. The difference in biological activity (mg tonne(-1) d(-1)) identified in this study, of up to seven times, suggests thatthere is the potential for enhancing the removal of estrogens and nonylphenols if more detailed knowledge of the factors responsible for these differences can be identified and maximized, thus potentially improving the quality of receiving waters.

Inhibitors of peptidases: how they influence the biological activities of substance P, neurokinins, kinins and angiotensins in isolated vessels.

PubMed

Rouissi, N; Nantel, F; Drapeau, G; Rhaleb, N E; Dion, S; Regoli, D

1990-01-01

Myotropic effects of various peptides were measured in three isolated vessels, the dog carotid artery, the rabbit pulmonary artery and the rat portal vein in the absence and in presence of several peptidase inhibitors, in order to evaluate the interference by metabolism with the peptides' biological activities. After adequate controls, captopril (4.6 x 10(-6) mol/l), thiorphan (1.0 x 10(-6) mol/l), phosphoramidon (4.6 x 10(-6) mol/l), chymostatin (1 mg/l), bestatin (8.1 x 10(-6) mol/l) or bacitracin (1.4 x 10(-5) mol/l) were left in contact with the tissues for 20-40 min to inhibit tissue peptidases before measuring again the biological effects of the various peptides. In some experiments, mergetpa (5.4 x 10(-6) mol/l) was used. All peptidase inhibitors were inactive on their own and only captopril potentiated the effects of substance P, neurokinins, bradykinin and inhibited angiotensin I in two preparations, the dog carotid artery, the rat portal vein, and, excluding bradykinin, also in the rabbit pulmonary artery. Captopril and thiorphan significantly potentiated the maximal response of the rat portal vein to substance P and mergetpa inhibited completely the effect of bradykinin on the rabbit pulmonary artery. The present findings suggest that the most active proteolytic enzyme interfering with the biological effects of vasoactive peptides on three isolated vessels is the angiotensin-converting enzyme (kininase II).

Sechium edule (Jacq.) Swartz, a New Cultivar with Antiproliferative Potential in a Human Cervical Cancer HeLa Cell Line.

PubMed

Salazar-Aguilar, Sandra; Ruiz-Posadas, Lucero Del Mar; Cadena-Iñiguez, Jorge; Soto-Hernández, Marcos; Santiago-Osorio, Edelmiro; Aguiñiga-Sánchez, Itzen; Rivera-Martínez, Ana Rocío; Aguirre-Medina, Juan Francisco

2017-07-25

The Sechium edule Perla Negra cultivar is a recently-obtained biological material whose progenitors are S. edule var. nigrum minor and S. edule var. amarus silvestrys, the latter of which has been reported to have antiproliferative activity against the HeLa P-388 and L-929 cancer cell lines. The present study aimed to determine if the methanolic extract of the fruit of the Perla Negra cultivar had the same biological activity. The methanolic extract was phytochemically characterized by thin layer chromatography (TLC) and column chromatography (CC), identifying the terpenes and flavonoids. The compounds identified via high performance liquid chromatography (HPLC) were Cucurbitacins B, D, E, and I for the terpene fractions, and Rutin, Phlorizidin, Myricetin, Quercetin, Naringenin, Phloretin, Apigenin, and Galangin for the flavonoid fractions). Biological activity was evaluated with different concentrations of the methanolic extract in the HeLa cell line and normal lymphocytes. The methanolic extract inhibited the proliferation of HeLa cells (IC 50 1.85 µg·mL -1 ), but the lymphocytes were affected by the extract (IC 50 30.04 µg·mL -1 ). Some fractions, and the pool of all of them, showed inhibition higher than 80% at a concentration of 2.11 µg·mL -1 . Therefore, the biological effect shown by the methanolic extract of the Perla Negra has some specificity in inhibiting tumor cells and not normal cells; an unusual feature among molecules investigated as potential biomedical agents.

Sechium edule (Jacq.) Swartz, a New Cultivar with Antiproliferative Potential in a Human Cervical Cancer HeLa Cell Line

PubMed Central

Salazar-Aguilar, Sandra; Ruiz-Posadas, Lucero del Mar; Cadena-Iñiguez, Jorge; Santiago-Osorio, Edelmiro; Aguiñiga-Sánchez, Itzen; Rivera-Martínez, Ana Rocío; Aguirre-Medina, Juan Francisco

2017-01-01

The Sechium edule Perla Negra cultivar is a recently-obtained biological material whose progenitors are S. edule var. nigrum minor and S. edule var. amarus silvestrys, the latter of which has been reported to have antiproliferative activity against the HeLa P-388 and L-929 cancer cell lines. The present study aimed to determine if the methanolic extract of the fruit of the Perla Negra cultivar had the same biological activity. The methanolic extract was phytochemically characterized by thin layer chromatography (TLC) and column chromatography (CC), identifying the terpenes and flavonoids. The compounds identified via high performance liquid chromatography (HPLC) were Cucurbitacins B, D, E, and I for the terpene fractions, and Rutin, Phlorizidin, Myricetin, Quercetin, Naringenin, Phloretin, Apigenin, and Galangin for the flavonoid fractions). Biological activity was evaluated with different concentrations of the methanolic extract in the HeLa cell line and normal lymphocytes. The methanolic extract inhibited the proliferation of HeLa cells (IC50 1.85 µg·mL−1), but the lymphocytes were affected by the extract (IC50 30.04 µg·mL−1). Some fractions, and the pool of all of them, showed inhibition higher than 80% at a concentration of 2.11 µg·mL−1. Therefore, the biological effect shown by the methanolic extract of the Perla Negra has some specificity in inhibiting tumor cells and not normal cells; an unusual feature among molecules investigated as potential biomedical agents. PMID:28757593

Synthesis and biological evaluation of enantiomerically pure cyclopropyl analogues of combretastatin A4.

PubMed

Ty, Nancy; Pontikis, Renée; Chabot, Guy G; Devillers, Emmanuelle; Quentin, Lionel; Bourg, Stéphane; Florent, Jean-Claude

2013-03-01

To evaluate the influence of stereochemistry on biological activities of cis-cyclopropyl combretastatin A4 (CA4) analogues, we have prepared several cyclopropyl compounds in their pure enantiomeric forms. The key reactions in our synthesis are the cyclopropanation of a (Z)-alkenylboron compound bearing a chiral auxiliary, and the cross-coupling of both enantiomeric cyclopropyl trifluoroborate salts with aryl and olefinic halides. Three pairs of cis-cyclopropyl CA4 analogues were evaluated for their potential antivascular activities. The diarylcyclopropyl compounds with SR-configuration (-)-1b, (-)-2b and the cyclopropylvinyl enantiomer (+)-3a with RR-configuration were the most potent tubulin polymerization inhibitors. A correlation was noted between anti-tubulin activity and rounding up activity of endothelial cells. The cytotoxic activity on B16 melanoma cells was in the submicromolar range for most compounds, but unlike the anti-tubulin activity, there was no difference in cytotoxic activity between racemic and enantiomerically pure forms for the three series of compounds. Molecular docking studies within the colchicine binding site of tubulin were in good agreement with the tubulin polymerization inhibitory data and confirmed the importance of the configuration of the synthesized cis-cyclopropyl CA4 analogues for potential antivascular activities. Copyright © 2013. Published by Elsevier Ltd.

C-terminal Lysine-Linked Magainin 2 with Increased Activity Against Multidrug-Resistant Bacteria.

PubMed

Lorenzón, Esteban N; Santos-Filho, Norival A; Ramos, Matheus A S; Bauab, Tais M; Camargo, Ilana L B C; Cilli, Eduardo M

2016-01-01

Due to the growing problem of antibiotic-resistant microorganisms, the development of novel antimicrobial agents is a very important challenge. Dimerization of cationic antimicrobial peptides (cAMPs) is a potential strategy for enhancing antimicrobial activity. Here, we studied the effects of magainin 2 (MG2) dimerization on its structure and biological activity. Lysine and glutamic acid were used to synthesize the C- and N-terminal dimers of MG2, respectively, in order to evaluate the impact of linker position used to obtain the dimers. Both MG2 and its dimeric versions showed a random coil structure in aqueous solution. However, in the presence of a structure-inducing solvent or a membrane mimetic, all peptides acquired helical structure. N-terminal dimerization did not affect the biological activity of the peptide. On the other hand, the C-terminal dimer, (MG2)2K, showed antimicrobial activity 8-16 times higher than that of MG2, and the time required to kill Escherichia coli was lower. The enhanced antimicrobial activity was related to membrane permeabilization. (MG2)2K was also more active against multidrug-resistant bacteria of clinical origin. Overall, the results presented here demonstrate that C-terminal lysine-linked dimerization improve the activity of MG2, and (MG2)2K can be considered as a potential antimicrobial agent.

Critical tests for determination of microbiological quality and biological activity in commercial vermicompost samples of different origins.

PubMed

Grantina-Ievina, Lelde; Andersone, Una; Berkolde-Pīre, Dace; Nikolajeva, Vizma; Ievinsh, Gederts

2013-12-01

The aim of the present paper was to show that differences in biological activity among commercially produced vermicompost samples can be found by using a relatively simple test system consisting of microorganism tests on six microbiological media and soilless seedling growth tests with four vegetable crop species. Significant differences in biological properties among analyzed samples were evident both at the level of microbial load as well as plant growth-affecting activity. These differences were mostly manufacturer- and feedstock-associated, but also resulted from storage conditions of vermicompost samples. A mature vermicompost sample that was produced from sewage sludge still contained considerable number of Escherichia coli. Samples from all producers contained several potentially pathogenic fungal species such as Aspergillus fumigatus, Pseudallescheria boidii, Pseudallescheria fimeti, Pseudallescheria minutispora, Scedosporium apiospermum, Scedosporium prolificans, Scopulariopsis brevicaulis, Stachybotrys chartarum, Geotrichum spp., Aphanoascus terreus, and Doratomyces columnaris. In addition, samples from all producers contained plant growth-promoting fungi from the genera Trichoderma and Mortierella. The described system can be useful both for functional studies aiming at understanding of factors affecting quality characteristics of vermicompost preparations and for routine testing of microbiological quality and biological activity of organic waste-derived composts and vermicomposts.

Anti-inflammatory, Analgesic and Antiulcer properties of Porphyra vietnamensis.

PubMed

Bhatia, Saurabh; Sharma, Kiran; Sharma, Ajay; Nagpal, Kalpana; Bera, Tanmoy

2015-01-01

Aim of the present work was to investigate the anti-inflammatory, analgesic and antiulcer effects of red seaweed Porphyra vietnamensis (P. vietnamenis). Aqueous (POR) and alcoholic (PE) fractions were successfully isolated from P. vietnamenis. Further biological investigations were performed using a classic test of paw edema induced by carrageenan, writhing induced by acetic acid, hot plate method and naproxen induced gastro-duodenal ulcer. Among the fractions POR showed better activity. POR and PE significantly (p < 0.05) reduced carrageenan induced paw edema in a dose dependent manner. In the writhing test POR significantly (p < 0.05) reduced abdominal writhes than PE. In hot plate method POR showed better analgesic activity than PE. POR showed comparable ulcers reducing potential (p<0.01) to that of omeprazole, and has more ulcer reducing potential then PE. The results of this study demonstrated that P. vietnamenis aqueous fraction possesses biological activity that is close to the standards taken for the treatment of peripheral painful or/and inflammatory and ulcer conditions.

Design, synthesis and biological evaluation of hybrids of β-carboline and salicylic acid as potential anticancer and apoptosis inducing agents

PubMed Central

Xu, Qi-Bing; Chen, Xiang-Fan; Feng, Jiao; Miao, Jie-Fei; Liu, Ji; Liu, Feng-Tao; Niu, Bi-Xi; Cai, Jin-Yang; Huang, Chao; Zhang, Yanan; Ling, Yong

2016-01-01

A novel series of hybrids (7a-l, 8a-l) from β-carboline and salicylic acid (SA) were designed and synthesized, and their in vitro biological activities were evaluated. Most of the hybrids displayed potent antiproliferative activity against five cancer cell lines in vitro, showing potencies superior to 5-FU and harmine. In particular, compound 8h selectively inhibited proliferation of liver cancer SMMC-7721 cells but not normal liver LO2 cells, and displayed greater inhibitory selectivity than intermediate 5h and SA. 8h also induced cancer cell apoptosis in an Annexin V-FITC/propidium iodide flow cytometry assay, and triggered the mitochondrial/caspase apoptosis by decreasing mitochondrial membrane potential which was associated with up-regulation of Bax, down-regulation of Bcl-2 and activation levels of the caspase cascade in a concentration-dependent manner. Our findings suggest that the β-carboline/SA hybrids may hold greater promise as therapeutic agents for the intervention of human cancers. PMID:27824091

Anti-inflammatory, Analgesic and Antiulcer properties of Porphyra vietnamensis

PubMed Central

Bhatia, Saurabh; Sharma, Kiran; Sharma, Ajay; Nagpal, Kalpana; Bera, Tanmoy

2015-01-01

Objectives: Aim of the present work was to investigate the anti-inflammatory, analgesic and antiulcer effects of red seaweed Porphyra vietnamensis (P. vietnamenis). Materials and Methods: Aqueous (POR) and alcoholic (PE) fractions were successfully isolated from P. vietnamenis. Further biological investigations were performed using a classic test of paw edema induced by carrageenan, writhing induced by acetic acid, hot plate method and naproxen induced gastro-duodenal ulcer. Results: Among the fractions POR showed better activity. POR and PE significantly (p < 0.05) reduced carrageenan induced paw edema in a dose dependent manner. In the writhing test POR significantly (p < 0.05) reduced abdominal writhes than PE. In hot plate method POR showed better analgesic activity than PE. POR showed comparable ulcers reducing potential (p<0.01) to that of omeprazole, and has more ulcer reducing potential then PE. Conclusions: The results of this study demonstrated that P. vietnamenis aqueous fraction possesses biological activity that is close to the standards taken for the treatment of peripheral painful or/and inflammatory and ulcer conditions. PMID:25767759

Identification of lipid fraction constituents from grasshopper (Chorthippus spp.) abdominal secretion with potential activity in wound healing with the use of GC-MS/MS technique.

PubMed

Buszewska-Forajta, Magdalena; Siluk, Danuta; Struck-Lewicka, Wiktoria; Raczak-Gutknecht, Joanna; Markuszewski, Michał J; Kaliszan, Roman

2014-02-01

In recent years biologically active compounds isolated from insects call special interest of drug researchers. According to some Polish etnopharmacological observations, secretion from the grasshopper's abdomen (Orthoptera family) is believed to speed up the process of wound healing. In the present work we focused on determination of main components of the lipid fraction of material from grasshopper abdomen using GC-MS/MS. Samples were qualitatively analyzed using gas chromatography coupled with mass spectrometry. Both liquid-liquid extraction and solid-phase extraction pretreatment methods were used to concentrate and fractionate the compounds from the insect. In the derivatized fractions ca. 350 compounds were identified, including substances of known biological activity. The potential agents affecting wound healing have been indicated. A set of compounds characteristic for all the studied Chorthippus spp., have been identified. Data analysis revealed different lipidomic profiles of grasshoppers depending on the insects origin and collection area. Copyright © 2013 Elsevier B.V. All rights reserved.

Advances in Development of Antimicrobial Peptidomimetics as Potential Drugs.

PubMed

Molchanova, Natalia; Hansen, Paul R; Franzyk, Henrik

2017-08-29

The rapid emergence of multidrug-resistant pathogens has evolved into a global health problem as current treatment options are failing for infections caused by pan-resistant bacteria. Hence, novel antibiotics are in high demand, and for this reason antimicrobial peptides (AMPs) have attracted considerable interest, since they often show broad-spectrum activity, fast killing and high cell selectivity. However, the therapeutic potential of natural AMPs is limited by their short plasma half-life. Antimicrobial peptidomimetics mimic the structure and biological activity of AMPs, but display extended stability in the presence of biological matrices. In the present review, focus is on the developments reported in the last decade with respect to their design, synthesis, antimicrobial activity, cytotoxic side effects as well as their potential applications as anti-infective agents. Specifically, only peptidomimetics with a modular structure of residues connected via amide linkages will be discussed. These comprise the classes of α-peptoids ( N -alkylated glycine oligomers), β-peptoids ( N -alkylated β-alanine oligomers), β³-peptides, α/β³-peptides, α-peptide/β-peptoid hybrids, α/γ N -acylated N -aminoethylpeptides (AApeptides), and oligoacyllysines (OAKs). Such peptidomimetics are of particular interest due to their potent antimicrobial activity, versatile design, and convenient optimization via assembly by standard solid-phase procedures.

Catalytically-active inclusion bodies-Carrier-free protein immobilizates for application in biotechnology and biomedicine.

PubMed

Krauss, Ulrich; Jäger, Vera D; Diener, Martin; Pohl, Martina; Jaeger, Karl-Erich

2017-09-20

Bacterial inclusion bodies (IBs) consist of unfolded protein aggregates and represent inactive waste products often accumulating during heterologous overexpression of recombinant genes in Escherichia coli. This general misconception has been challenged in recent years by the discovery that IBs, apart from misfolded polypeptides, can also contain substantial amounts of active and thus correctly or native-like folded protein. The corresponding catalytically-active inclusion bodies (CatIBs) can be regarded as a biologically-active sub-micrometer sized biomaterial or naturally-produced carrier-free protein immobilizate. Fusion of polypeptide (protein) tags can induce CatIB formation paving the way towards the wider application of CatIBs in synthetic chemistry, biocatalysis and biomedicine. In the present review we summarize the history of CatIBs, present the molecular-biological tools that are available to induce CatIB formation, and highlight potential lines of application. In the second part findings regarding the formation, architecture, and structure of (Cat)IBs are summarized. Finally, an overview is presented about the available bioinformatic tools that potentially allow for the prediction of aggregation and thus (Cat)IB formation. This review aims at demonstrating the potential of CatIBs for biotechnology and hopefully contributes to a wider acceptance of this promising, yet not widely utilized, protein preparation. Copyright © 2017 Elsevier B.V. All rights reserved.

Preliminary nutritional and biological potential of Artocarpus heterophyllus L. shell powder.

PubMed

Sharma, Anubhuti; Gupta, Priti; Verma, A K

2015-03-01

Artocarpus heterophyllus shell powder was investigated in terms of its nutritional and biological potential. A thorough examination of shell powder demonstrated its potential as a source of minerals, β carotene and dietary fiber, which were assessed gravimetrically & spectrophotometrically. This showed 3.05 ± 0.19 g 100 g(-1) DW of alkaloids followed by saponins and tannins. Three different extracts; acetone, methanol, & mix solvent were used to evaluate phenolic & flavonoid content, antioxidant & antimicrobial activity, GC/MS screening and quantitative analysis of polyphenols. Among all, the methanol extract showed highest antioxidant activity evaluated by DPPH, FRAP & ABTS assays and was significantly correlated with phenolic and flavonoid contents. Phenolic & flavonoid content was found to be 158 ± 0.34 mg (GAE) and 10.0 ± 0.64 mg (CE) respectively. The results of antimicrobial activity showed that L. monocytogenes was more susceptible to all extracts followed by other microorganisms. Catechin, ascorbic & chlorogenic acids were identified as major polyphenols analyzed by LC-MS/MS. GC/MS analysis showed that it contains a variety of compounds with different therapeutic activities. The study revealed that A. heterophyllus shell is a good source of natural antioxidants & other bioactive compounds and can be used in cosmetics, medicines and functional food application.

Potential effects of curcumin on peroxisome proliferator-activated receptor-gamma in vitro and in vivo

USDA-ARS?s Scientific Manuscript database

Natural peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists are found in food and may be important for health through their anti-inflammatory properties. Curcumin (Cur) is a bright yellow spice, derived from the rhizome of Curcuma longa Linn. It has been shown to have many biologi...

Synthesis and biological activity of imidazopyridine anticoccidial agents: Part II.

PubMed

Scribner, Andrew; Dennis, Richard; Lee, Shuliang; Ouvry, Gilles; Perrey, David; Fisher, Michael; Wyvratt, Matthew; Leavitt, Penny; Liberator, Paul; Gurnett, Anne; Brown, Chris; Mathew, John; Thompson, Donald; Schmatz, Dennis; Biftu, Tesfaye

2008-06-01

Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Recently, we reported the synthesis and biological activity of potent imidazo[1,2-a]pyridine anticoccidial agents. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we report the synthesis and anticoccidial activity of a second set of such compounds, focusing on derivatization of the amine side chain at the imidazopyridine 7-position. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

Antifungal potential of marine natural products.

PubMed

El-Hossary, Ebaa M; Cheng, Cheng; Hamed, Mostafa M; El-Sayed Hamed, Ashraf Nageeb; Ohlsen, Knut; Hentschel, Ute; Abdelmohsen, Usama Ramadan

2017-01-27

Fungal diseases represent an increasing threat to human health worldwide which in some cases might be associated with substantial morbidity and mortality. However, only few antifungal drugs are currently available for the treatment of life-threatening fungal infections. Furthermore, plant diseases caused by fungal pathogens represent a worldwide economic problem for the agriculture industry. The marine environment continues to provide structurally diverse and biologically active secondary metabolites, several of which have inspired the development of new classes of therapeutic agents. Among these secondary metabolites, several compounds with noteworthy antifungal activities have been isolated from marine microorganisms, invertebrates, and algae. During the last fifteen years, around 65% of marine natural products possessing antifungal activities have been isolated from sponges and bacteria. This review gives an overview of natural products from diverse marine organisms that have shown in vitro and/or in vivo potential as antifungal agents, with their mechanism of action whenever applicable. The natural products literature is covered from January 2000 until June 2015, and we are reporting the chemical structures together with their biological activities, as well as the isolation source. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Manipulation of long-term dynamics in a colloidal active matter system using speckle light fields

NASA Astrophysics Data System (ADS)

Pince, Ercag; Velu, Sabareesh K. P.; Callegari, Agnese; Elahi, Parviz; Gigan, Sylvain; Volpe, Giovanni; Volpe, Giorgio

Particles undergoing a stochastic motion within a disordered medium is a ubiquitous physical and biological phenomena. Examples can be given from organelles performing tasks in the cytoplasm to large animals moving in patchy environment. Here, we use speckle light fields to study the anomalous diffusion in an active matter system consisting of micron-sized silica particles(diameter 5 μm) and motile bacterial cells (E. coli). The speckle light fields are generated by mode mixing inside a multimode optical fiber where a small amount of incident laser power is needed to obtain an effective disordered optical landscape for the purpose of optical manipulation. We experimentally show how complex potentials contribute to the long-term dynamics of the active matter system and observed an enhanced diffusion of particles interacting with the active bacterial bath in the speckle light fields. We showed that this effect can be tuned and controlled by varying the intensity and the statistical properties of the speckle pattern. Potentially, these results could be of interest for many technological applications, such as the manipulation of microparticles inside optically disordered media of biological interest.

Citridones, new potentiators of antifungal miconazole activity, produced by Penicillium sp. FKI-1938. I. Taxonomy, fermentation, isolation and biological properties.

PubMed

Fukuda, Takashi; Yamaguchi, Yuichi; Masuma, Rokuro; Tomoda, Hiroshi; Omura, Satoshi

2005-05-01

New phenylfuropyridinones and related compounds, designated citridones A, B, B' and C, were isolated along with known CJ-16,173, from the culture broth of Penicillium sp. FKI-1938 by solvent extraction, silica gel column chromatography and HPLC. Citridones (75 microM) potentiate the miconazole activity against Candida albicans, decreasing the IC50 value of miconazole from 14.5 nM to 3.5 to approximately 6.3 nM.

Polyphenols, their metabolites and derivatives as drug leads.

PubMed

Almeida, Filipa A; Dos Santos, Cláudia Nunes; Ventura, Maria Rita

2018-05-15

In this non-comprehensive review, the potential of natural polyphenols as lead compounds for the design and synthesis of new molecules with potential application in several diseases was highlighted. Organic synthesis has been essential for the development of new analogues of naturally found polyphenols, providing a wide range of structural modifications for structure-activity relationship studies and improving or modulating the biological activity of the promising compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Soluble Epidermal Growth Factor Receptors (sEGFRs) in Cancer: Biological Aspects and Clinical Relevance.

PubMed

Maramotti, Sally; Paci, Massimiliano; Manzotti, Gloria; Rapicetta, Cristian; Gugnoni, Mila; Galeone, Carla; Cesario, Alfredo; Lococo, Filippo

2016-04-19

The identification of molecules that can reliably detect the presence of a tumor or predict its behavior is one of the biggest challenges of research in cancer biology. Biological fluids are intriguing mediums, containing many molecules that express the individual health status and, accordingly, may be useful in establishing the potential risk of cancer, defining differential diagnosis and prognosis, predicting the response to treatment, and monitoring the disease progression. The existence of circulating soluble growth factor receptors (sGFRs) deriving from their membrane counterparts has stimulated the interest of researchers to investigate the use of such molecules as potential cancer biomarkers. But what are the origins of circulating sGFRs? Are they naturally occurring molecules or tumor-derived products? Among these, the epidermal growth factor receptor (EGFR) is a cell-surface molecule significantly involved in cancer development and progression; it can be processed into biological active soluble isoforms (sEGFR). We have carried out an extensive review of the currently available literature on the sEGFRs and their mechanisms of regulation and biological function, with the intent to clarify the role of these molecules in cancer (and other pathological conditions) and, on the basis of the retrieved evidences, speculate about their potential use in the clinical setting.

The search for life on Europa: limiting environmental factors, potential habitats, and Earth analogues.

PubMed

Marion, Giles M; Fritsen, Christian H; Eicken, Hajo; Payne, Meredith C

2003-01-01

The putative ocean of Europa has focused considerable attention on the potential habitats for life on Europa. By generally clement Earth standards, these Europan habitats are likely to be extreme environments. The objectives of this paper were to examine: (1) the limits for biological activity on Earth with respect to temperature, salinity, acidity, desiccation, radiation, pressure, and time; (2) potential habitats for life on Europa; and (3) Earth analogues and their limitations for Europa. Based on empirical evidence, the limits for biological activity on Earth are: (1) the temperature range is from 253 to 394 K; (2) the salinity range is a(H2O) = 0.6-1.0; (3) the desiccation range is from 60% to 100% relative humidity; (4) the acidity range is from pH 0 to 13; (5) microbes such as Deinococcus are roughly 4,000 times more resistant to ionizing radiation than humans; (6) the range for hydrostatic pressure is from 0 to 1,100 bars; and (7) the maximum time for organisms to survive in the dormant state may be as long as 250 million years. The potential habitats for life on Europa are the ice layer, the brine ocean, and the seafloor environment. The dual stresses of lethal radiation and low temperatures on or near the icy surface of Europa preclude the possibility of biological activity anywhere near the surface. Only at the base of the ice layer could one expect to find the suitable temperatures and liquid water that are necessary for life. An ice layer turnover time of 10 million years is probably rapid enough for preserving in the surface ice layers dormant life forms originating from the ocean. Model simulations demonstrate that hypothetical oceans could exist on Europa that are too cold for biological activity (T < 253 K). These simulations also demonstrate that salinities are high, which would restrict life to extreme halophiles. An acidic ocean (if present) could also potentially limit life. Pressure, per se, is unlikely to directly limit life on Europa. But indirectly, pressure plays an important role in controlling the chemical environments for life. Deep ocean basins such as the Mariana Trench are good analogues for the cold, high-pressure ocean of Europa. Many of the best terrestrial analogues for potential Europan habitats are in the Arctic and Antarctica. The six factors likely to be most important in defining the environments for life on Europa and the focus for future work are liquid water, energy, nutrients, low temperatures, salinity, and high pressures.

PGDP Trichloroethene Biodegradation Investigation Summary Report: Regional Gravel Aquifer & Northwest Plume

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hampson, Steve

The evaluation of biological degradation processes addressed by this report are part of a broad trichloroethene (TCE) Fate and Transport Investigation that includes four (4) topics of phased investigation (Table ES1) relative to degradation and/or attenuation of TCE in the Regional Gravel Aquifer (RGA) underlying the United States Department of Energy Paducah Gaseous Diffusion Plant (PGDP). In order of implementation the project phases are: (1) derivation of a TCE first-order rate constant by normalization of TCE values against technetium-99 ( 99Tc) and chloride. 2) identification of the presence of microbes capable of aerobic co-metabolic TCE biodegradation using enzyme activity probesmore » (this report); 3) Compound-specific isotope analysis (CSIA) to support prevalence of biotic and/or abiotic degradation processes; and 4) evaluation of potential abiotic RGA-TCE attenuation mechanisms including sorption. This report summarizes the Phase II activities related to the identification and evaluation of biological degradation processes that may be actively influencing TCE fate and transport in the RGA contaminant plumes at the United States Department of Energy (DOE) PGDP and its environs (Figure ES1). The goals of these activities were to identify active biological degradation mechanisms in the RGA through multiple lines of evidence and to provide DOE with recommendations for future TCE biological degradation investigations.« less

Review on Abyssomicins: Inhibitors of the Chorismate Pathway and Folate Biosynthesis.

PubMed

Sadaka, Carmen; Ellsworth, Edmund; Hansen, Paul Robert; Ewin, Richard; Damborg, Peter; Watts, Jeffrey L

2018-06-06

Antifolates targeting folate biosynthesis within the shikimate-chorismate-folate metabolic pathway are ideal and selective antimicrobials, since higher eukaryotes lack this pathway and rely on an exogenous source of folate. Resistance to the available antifolates, inhibiting the folate pathway, underlines the need for novel antibiotic scaffolds and molecular targets. While para-aminobenzoic acid synthesis within the chorismate pathway constitutes a novel molecular target for antifolates, abyssomicins are its first known natural inhibitors. This review describes the abyssomicin family, a novel spirotetronate polyketide Class I antimicrobial. It summarizes synthetic and biological studies, structural, biosynthetic, and biological properties of the abyssomicin family members. This paper aims to explain their molecular target, mechanism of action, structure⁻activity relationship, and to explore their biological and pharmacological potential. Thirty-two natural abyssomicins and numerous synthetic analogues have been reported. The biological activity of abyssomicins includes their antimicrobial activity against Gram-positive bacteria and mycobacteria, antitumor properties, latent human immunodeficiency virus (HIV) reactivator, anti-HIV and HIV replication inducer properties. Their antimalarial properties have not been explored yet. Future analoging programs using the structure⁻activity relationship data and synthetic approaches may provide a novel abyssomicin structure that is active and devoid of cytotoxicity. Abyssomicin J and atrop- o -benzyl-desmethylabyssomicin C constitute promising candidates for such programs.

Mangiferin: A xanthonoid with multipotent anti-inflammatory potential.

PubMed

Saha, Sukanya; Sadhukhan, Pritam; Sil, Parames C

2016-09-10

Over the last era, small molecules sourced from different plants have gained attention for their varied and long-term medicinal benefits. Their advantageous therapeutic effects in diverse pathological complications lead researchers to give an ever-increasing emphasis on them and discover their novel therapeutic potentials. Among these, the heat stable, xanthonoid group of organic molecules has gained special importance with distinctive regards to the bioactive molecule mangiferin due to its solubility in water. Mangiferin, a yellow polyphenol having C-glycosyl xanthone structure, is widely present in different edible sources like mango, and possesses numerous biological activities. Extensive research with this molecule shows its antioxidant, anti-inflammatory, antidiabetic, anticancer, antimicrobial, analgesic, and immunomodulatory properties. Thus, it provides protection against a wide range of physiological disorders. The C-glucosyl linkage and polyhydroxy groups in mangiferin's structure contribute essentially to its free radical-scavenging activity. Moreover, its ability in regulating various transcription factors like NF-κB, Nrf-2, etc. and modulating the expression of different proinflammatory signaling intermediates like tumor necrosis factor-α, COX-2, etc. contribute to its anti-inflammatory, anticancer, and antidiabetic potentials. In this comprehensive article, information has been provided about the sources, chemical structure, metabolism, and different biological activities of mangiferin with special emphasis on the underlying cellular signal transduction pathways. Insights into an in-depth assessment of mangiferin's anti-inflammatory therapeutic potential have also been discussed in detail. On an overall perspective, this review aims to stage mangiferin's diversified therapeutic applications and its emerging possibility as a promising drug in future based on its anti-inflammatory property. © 2016 BioFactors, 42(5):459-474, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

A review: Potential and challenges of biologically activated carbon to remove natural organic matter in drinking water purification process.

PubMed

Korotta-Gamage, Shashika Madushi; Sathasivan, Arumugam

2017-01-01

The use of biologically activated carbon (BAC) in drinking water purification is reviewed. In the past BAC is seen mostly as a polishing treatment. However, BAC has the potential to provide solution to recent challenges faced by water utilities arising from change in natural organic matter (NOM) composition in drinking water sources - increased NOM concentration with a larger fraction of hydrophilic compounds and ever increasing trace level organic pollutants. Hydrophilic NOM is not removed by traditional coagulation process and causes bacterial regrowth and increases disinfection by-products (DBPs) formation during disinfection. BAC can offer many advantages by removing hydrophilic fraction and many toxic and endocrine compounds which are not otherwise removed. BAC can also aid the other downstream processes if used as a pre-treatment. Major drawback of BAC was longer empty bed contact time (EBCT) required for an effective NOM removal. This critical review analyses the strategies that have been adopted to enhance the biological activity of the carbon by operational means and summarises the surface modification methods. To maximize the benefit of the BAC, a rethink of current treatment plant configuration is proposed. If the process can be expedited and adopted appropriately, BAC can solve many of the current problems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Persistent organic pollutants and related biological responses measured in coastal fish using chemical and biological screening methods.

PubMed

Tairova, Zhanna; Strand, Jakob; Bossi, Rossana; Larsen, Martin M; Förlin, Lars; Bignert, Anders; Hedman, Jenny; Gercken, Jens; Lang, Thomas; Fricke, Nicolai F; Asmund, Gert; Long, Manhai; Bonefeld-Jørgensen, Eva C

2017-01-01

The aim of this study was to investigate the spatial distribution, levels of dioxin-like compounds (DLC), and biological responses in two fish species. The viviparous eelpout (Zoarces viviparus) was collected from various locations in the Baltic Sea and in fjords of Kattegat and Skagerrak, while shorthorn sculpin (Myoxocephalus scorpius) was obtained at the polychlorinated biphenyl (PCB) polluted site in North West Greenland. Significant differences were detected both in contaminant levels and relative contributions from either polychlorinated dibenzodioxins (PCDD) or polychlorinated dibenzofurans (PCDF or furans) and mono-ortho- and non-ortho (coplanar) polychlorinated biphenyls (dl-PCB). Fish from the eastern Baltic Sea generally displayed higher contributions from PCDD/F compared to dl-PCB, whereas dl-PCB were generally predominated in fish from Danish, Swedish, and German sites. Levels of dl-PCB in muscle tissues were above OSPAR environmental assessment criteria (EAC) for PCB118, indicating a potential risk of adverse biological effects in the ecosystem, whereas levels of the total WHO-TEQs were below threshold for sea food suggesting limited risks for humans. No significant relationships between levels of DLC (expressed as WHO-TEQ), and biological responses such as the induction of CYP1A enzymatic activity and fry reproductive disorders were observed in eelpout. No marked relationship between WHO-TEQ and combined biological aryl hydrocarbon receptor-mediated transactivity (expressed as AhR-TEQ) was noted. However, there was a positive correlation between polycyclic aromatic hydrocarbon (PAH) metabolites and induction of CYP1A activity, suggesting that PAH exhibited greater potential than DLC to produce biological effects in eelpout from the Baltic Sea.

Novel thrombopoietin mimetic peptides bind c-Mpl receptor: Synthesis, biological evaluation and molecular modeling.

PubMed

Liu, Yaquan; Tian, Fang; Zhi, Dejuan; Wang, Haiqing; Zhao, Chunyan; Li, Hongyu

2017-02-01

Thrombopoietin (TPO) acts in promoting the proliferation of hematopoietic stem cells and by initiating specific maturation events in megakaryocytes. Now, TPO-mimetic peptides with amino acid sequences unrelated to TPO are of considerable pharmaceutical interest. In the present paper, four new TPO mimetic peptides that bind and activate c-Mpl receptor have been identified, synthesized and tested by Dual-Luciferase reporter gene assay for biological activities. The molecular modeling research was also approached to understand key molecular mechanisms and structural features responsible for peptide binding with c-Mpl receptor. The results presented that three of four mimetic peptides showed significant activities. In addition, the molecular modeling approaches proved hydrophobic interactions were the driven positive forces for binding behavior between peptides and c-Mpl receptor. TPO peptide residues in P7, P13 and P7' positions were identified by the analysis of hydrogen bonds and energy decompositions as the key ones for benefiting better biological activities. Our data suggested the synthesized peptides have considerable potential for the future development of stable and highly active TPO mimetic peptides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ion-driven photoluminescence modulation of quasi-two-dimensional MoS2 nanoflakes for applications in biological systems.

PubMed

Ou, Jian Zhen; Chrimes, Adam F; Wang, Yichao; Tang, Shi-yang; Strano, Michael S; Kalantar-zadeh, Kourosh

2014-02-12

Quasi-two-dimensional (quasi-2D) molybdenum disulfide (MoS2) is a photoluminescence (PL) material with unique properties. The recent demonstration of its PL, controlled by the intercalation of positive ions, can lead to many opportunities for employing this quasi-2D material in ion-related biological applications. Here, we present two representative models of biological systems that incorporate the ion-controlled PL of quasi-2D MoS2 nanoflakes. The ion exchange behaviors of these two models are investigated to reveal enzymatic activities and cell viabilities. While the ion intercalation of MoS2 in enzymatic activities is enabled via an external applied voltage, the intercalation of ions in cell viability investigations occurs in the presence of the intrinsic cell membrane potential.

National Wind Technology Center sitewide, Golden, CO: Environmental assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1996-11-01

The National Renewable Energy Laboratory (NREL), the nation`s primary solar and renewable energy research laboratory, proposes to expand its wind technology research and development program activities at its National Wind Technology Center (NWTC) near Golden, Colorado. NWTC is an existing wind energy research facility operated by NREL for the US Department of Energy (DOE). Proposed activities include the construction and reuse of buildings and facilities, installation of up to 20 wind turbine test sites, improvements in infrastructure, and subsequent research activities, technology testing, and site operations. In addition to wind turbine test activities, NWTC may be used to support othermore » NREL program activities and small-scale demonstration projects. This document assesses potential consequences to resources within the physical, biological, and human environment, including potential impacts to: air quality, geology and soils, water resources, biological resources, cultural and historic resources, socioeconomic resources, land use, visual resources, noise environment, hazardous materials and waste management, and health and safety conditions. Comment letters were received from several agencies in response to the scoping and predecisional draft reviews. The comments have been incorporated as appropriate into the document with full text of the letters contained in the Appendices. Additionally, information from the Rocky Flats Environmental Technology Site on going sitewide assessment of potential environmental impacts has been reviewed and discussed by representatives of both parties and incorporated into the document as appropriate.« less

Potential nitrogen fixation activity of different aged biological soil crusts from rehabilitated grasslands of the hilly Loess Plateau, China

USGS Publications Warehouse

Zhao, Y.; Xu, M.; Belnap, J.

2010-01-01

Biological soil crusts (biocrusts) cover up to 60–70% of the soil surface in grasslands rehabilitated during the "Grain for Green" project implemented in the hilly Loess Plateau region in 1999. As biocrusts fix nitrogen (N), they are an important part of restoring soil fertility. We measured nitrogenase activity (NA) in biocrusts from sites rehabilitated at six different time periods to estimate 1) the effects of moisture content and temperature on NA in biocrusts of different ages and 2) the potential N contribution from biocrusts to soils and plants in this region. Results show that NA in the biocrusts was mostly controlled by the species composition, as the activity of biocrusts dominated by free-living soil cyanobacteria was significantly higher than that of moss-dominated biocrusts. Nitrogenase activity was also influenced by soil moisture content and ambient temperature, with a significant decline in activity when moisture levels were decreased to 20% field water-holding capacity. The optimal temperature for NA was 35–40 °C and 30–40 °C for cyanobacteria- and moss-dominated biocrusts, respectively. Biocrust fixed N is likely an important source of N in this ecosystem, as we estimated annual potential N inputs per hectare in these grasslands to be up to 13 kg N ha-1 and 4 kg N ha-1 for cyanobacteria- and moss-dominated biocrusts, respectively.

Enhancing biological control of basal stem rot disease (Ganoderma boninense) in oil palm plantations.

PubMed

Susanto, A; Sudharto, P S; Purba, R Y

2005-01-01

Basal Stem Rot (BSR) disease caused by Ganoderma boninense is the most destructive disease in oil palm, especially in Indonesia and Malaysia. The available control measures for BSR disease such as cultural practices and mechanical and chemical treatment have not proved satisfactory due to the fact that Ganoderma has various resting stages such as melanised mycelium, basidiospores and pseudosclerotia. Alternative control measures to overcome the Ganoderma problem are focused on the use of biological control agents and planting resistant material. Present studies conducted at Indonesian Oil Palm Research Institute (IOPRI) are focused on enhancing the use of biological control agents for Ganoderma. These activities include screening biological agents from the oil palm rhizosphere in order to evaluate their effectiveness as biological agents in glasshouse and field trials, testing their antagonistic activities in large scale experiments and eradicating potential disease inoculum with biological agents. Several promising biological agents have been isolated, mainly Trichoderma harzianum, T. viride, Gliocladium viride, Pseudomonas fluorescens, and Bacillus sp. A glasshouse and field trial for Ganoderma control indicated that treatment with T. harzianum and G. viride was superior to Bacillus sp. A large scale trial showed that the disease incidence was lower in a field treated with biological agents than in untreated fields. In a short term programme, research activities at IOPRI are currently focusing on selecting fungi that can completely degrade plant material in order to eradicate inoculum. Digging holes around the palm bole and adding empty fruit bunches have been investigated as ways to stimulate biological agents.

Raman spectroscopy of volcanic lavas and inclusions of relevance to astrobiological exploration.

PubMed

Jorge-Villar, Susana E; Edwards, Howell G M

2010-07-13

Volcanic eruptions and lava flows comprise one of the most highly stressed terrestrial environments for the survival of biological organisms; the destruction of botanical and biological colonies by molten lava, pyroclastic flows, lahars, poisonous gas emissions and the deposition of highly toxic materials from fumaroles is the normal expectation from such events. However, the role of lichens and cyanobacteria in the earlier colonization of volcanic lava outcrops has now been recognized. In this paper, we build upon earlier Raman spectroscopic studies on extremophilic colonies in old lava flows to assess the potential of finding evidence of biological colonization in more recent lava deposits that would inform, first, the new colonization of these rocks and also provide evidence for the relict presence of biological colonies that existed before the volcanism occurred and were engulfed by the lava. In this research, samples were collected from a recent expedition to the active volcano at Kilauea, Hawaii, which comprises very recent lava flows, active fumaroles and volcanic rocks that had broken through to the ocean and had engulfed a coral reef. The Raman spectra indicated that biological and geobiological signatures could be identified in the presence of geological matrices, which is encouraging for the planned exploration of Mars, where it is believed that there is evidence of an active volcanism that perhaps could have preserved traces of biological activity that once existed on the planet's surface, especially in sites near the old Martian oceans.

Reading about the actions of others: biological motion imagery and action congruency influence brain activity.

PubMed

Deen, Ben; McCarthy, Gregory

2010-05-01

Prior neuroimaging research has implicated regions within and near the posterior superior temporal sulcus (pSTS) in the visual processing of biological motion and of the intentions implied by specific movements. However, it is unknown whether this region is engaged during the processing of human motion at a conceptual level, such as during story comprehension. Here, we obtained functional magnetic resonance images from subjects reading brief stories that described a human character's background and then concluded with an action or decision made by the character. Half of the stories contained incidental descriptions of biological motion (such as the character's walking or grasping) while the remaining half did not. As a second factor, the final action of the story was either congruent or incongruent with the character's background and implied goals and intentions. Stories that contained biological motion strongly activated the pSTS bilaterally, along with ventral temporal areas, premotor cortex, left motor cortex, and the precuneus. Active regions of pSTS in individual subjects closely overlapped with regions identified with a separate biological motion localizer (point-light display) task. Reading incongruent versus congruent stories activated dorsal anterior cingulate cortex and bilateral anterior insula. These results support the hypothesis that reading can engage higher visual cortex in a content-specific manner, and suggest that the presence of biological motion should be controlled as a potential confound in fMRI studies using story comprehension tasks. 2010. Published by Elsevier Ltd.

Predicting the biological condition of streams: Use of geospatial indicators of natural and anthropogenic characteristics of watersheds

USGS Publications Warehouse

Carlisle, D.M.; Falcone, J.; Meador, M.R.

2009-01-01

We developed and evaluated empirical models to predict biological condition of wadeable streams in a large portion of the eastern USA, with the ultimate goal of prediction for unsampled basins. Previous work had classified (i.e., altered vs. unaltered) the biological condition of 920 streams based on a biological assessment of macroinvertebrate assemblages. Predictor variables were limited to widely available geospatial data, which included land cover, topography, climate, soils, societal infrastructure, and potential hydrologic modification. We compared the accuracy of predictions of biological condition class based on models with continuous and binary responses. We also evaluated the relative importance of specific groups and individual predictor variables, as well as the relationships between the most important predictors and biological condition. Prediction accuracy and the relative importance of predictor variables were different for two subregions for which models were created. Predictive accuracy in the highlands region improved by including predictors that represented both natural and human activities. Riparian land cover and road-stream intersections were the most important predictors. In contrast, predictive accuracy in the lowlands region was best for models limited to predictors representing natural factors, including basin topography and soil properties. Partial dependence plots revealed complex and nonlinear relationships between specific predictors and the probability of biological alteration. We demonstrate a potential application of the model by predicting biological condition in 552 unsampled basins across an ecoregion in southeastern Wisconsin (USA). Estimates of the likelihood of biological condition of unsampled streams could be a valuable tool for screening large numbers of basins to focus targeted monitoring of potentially unaltered or altered stream segments. ?? Springer Science+Business Media B.V. 2008.

Size-dependent tuning of horseradish peroxidase bioreactivity by gold nanoparticles

NASA Astrophysics Data System (ADS)

Wu, Haohao; Liu, Yi; Li, Meng; Chong, Yu; Zeng, Mingyong; Lo, Y. Martin; Yin, Jun-Jie

2015-02-01

Molecules with diverse biological functions, such as heme peroxidases, can be useful tools for identifying potential biological effects of gold nanoparticles (AuNPs) at the molecular level. Here, using UV-Vis, circular dichroism, dynamic light scattering, and electron spin resonance spectroscopy, we report tuning of horseradish peroxidase (HRP) bioactivity by reactant-free AuNPs with diameters of 5, 10, 15, 30 and 60 nm (Au-5 nm, Au-10 nm, Au-15 nm, Au-30 nm and Au-60 nm). HRP conjugation to AuNPs was observed with only Au-5 nm and Au-10 nm prominently increasing the α-helicity of the enzyme to extents inversely related to their size. Au-5 nm inhibited both HRP peroxidase activity toward 3,3',5,5'-tetramethylbenzidine and HRP compound I/II reactivity toward 5,5-dimethyl-1-pyrroline N-oxide. Au-5 nm enhanced the HRP peroxidase activity toward ascorbic acid and the HRP compound I/II reactivity toward redox-active residues in the HRP protein moiety. Further, Au-5 nm also decreased the catalase- and oxidase-like activities of HRP. Au-10 nm showed similar, but weaker effects, while Au-15 nm, Au-30 nm and Au-60 nm had no effect. Results suggest that AuNPs can size-dependently enhance or inhibit HRP bioreactivity toward substrates with different redox potentials via a mechanism involving extension of the HRP substrate access channel and decline in the redox potentials of HRP catalytic intermediates.Molecules with diverse biological functions, such as heme peroxidases, can be useful tools for identifying potential biological effects of gold nanoparticles (AuNPs) at the molecular level. Here, using UV-Vis, circular dichroism, dynamic light scattering, and electron spin resonance spectroscopy, we report tuning of horseradish peroxidase (HRP) bioactivity by reactant-free AuNPs with diameters of 5, 10, 15, 30 and 60 nm (Au-5 nm, Au-10 nm, Au-15 nm, Au-30 nm and Au-60 nm). HRP conjugation to AuNPs was observed with only Au-5 nm and Au-10 nm prominently increasing the α-helicity of the enzyme to extents inversely related to their size. Au-5 nm inhibited both HRP peroxidase activity toward 3,3',5,5'-tetramethylbenzidine and HRP compound I/II reactivity toward 5,5-dimethyl-1-pyrroline N-oxide. Au-5 nm enhanced the HRP peroxidase activity toward ascorbic acid and the HRP compound I/II reactivity toward redox-active residues in the HRP protein moiety. Further, Au-5 nm also decreased the catalase- and oxidase-like activities of HRP. Au-10 nm showed similar, but weaker effects, while Au-15 nm, Au-30 nm and Au-60 nm had no effect. Results suggest that AuNPs can size-dependently enhance or inhibit HRP bioreactivity toward substrates with different redox potentials via a mechanism involving extension of the HRP substrate access channel and decline in the redox potentials of HRP catalytic intermediates. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07056a

Marine-Derived Bioactive Peptides for Biomedical Sectors: A Review.

PubMed

Ruiz-Ruiz, Federico; Mancera-Andrade, Elena I; Iqbal, Hafiz M N

2017-01-01

Marine-based resources such as algae and other marine by-products have been recognized as rich sources of structurally diverse bioactive peptides. Evidently, their structural characteristics including unique amino acid residues are responsible for their biological activity. Several of the above-mentioned marine-origin species show multi-functional bioactivities that are useful for a new discovery and/or reinvention of biologically active ingredients, nutraceuticals and/or pharmaceuticals. Therefore, in recent years, marine-derived bioactive peptides have gained a considerable attention with high-value biomedical and/or pharmaceutical potentials. Furthermore, a wider spectrum of bioactive peptides can be produced through proteolytic-assisted hydrolysis of various marine resources under controlled physicochemical (pH and temperature of the reaction media) environment. Owing to their numerous health-related beneficial effects and therapeutic potential in the treatment and/or prevention of many diseases, such marine-derived bioactive peptides exhibit a wider spectrum of biological activities such as anti-cancerous, anti-proliferative, anti-coagulant, antibacterial, antifungal, and anti-tumor activities among many others. Based on emerging evidence of marine-derived peptide mining, the above-mentioned marine resources contain noteworthy levels of high-value protein. The present review article mainly summarizes the marine-derived bioactive peptides and emphasizing their potential applications in biomedical and/or pharmaceutical sectors of the modern world. In conclusion, recent literature has provided evidence that marine-derived bioactive peptides play a critical role in human health along with many possibilities of designing new functional nutraceuticals and/or pharmaceuticals to clarify potent mechanisms of action for a wider spectrum of diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Biological Activity Assessment in Mexican Tropical Soils with Different Hydrocarbon Contamination Histories.

PubMed

Riveroll-Larios, Jessica; Escalante-Espinosa, Erika; Fócil-Monterrubio, Reyna L; Díaz-Ramírez, Ildefonso J

The use of soil health indicators linked to microbial activities, such as key enzymes and respirometric profiles, helps assess the natural attenuation potential of soils contaminated with hydrocarbons. In this study, the intrinsic physicochemical characteristics, biological activity and biodegradation potential were recorded for two soils with different contamination histories (>5 years and <1 months). The enzymatic activity (lipase and dehydrogenase) as well as microbiological and mineralisation profiles were measured in contaminated soil samples. Soil suspensions were tested as microbial inocula in biodegradation potential assays using contaminated perlite as an inert support. The basal respiratory rate of the recently contaminated soil was 15-38 mg C-CO 2  kg -1 h -1 , while the weathered soil presented a greater basal mineralisation capacity of 55-70 mg C-CO 2 kg -1 h -1 . The basal levels of lipase and dehydrogenase were significantly greater than those recorded in non-contaminated soils (551 ± 21 μg pNP g -1 ). Regarding the biodegradation potential assessment, the lipase (1000-3000 μg pNP g -1 of perlite) and dehydrogenase (~3000 μg INF g -1 of perlite) activities in the inoculum of the recently contaminated soil were greater than those recorded in the inoculum of the weathered soil. This was correlated with a high mineralisation rate (~30 mg C-CO 2 kg -1 h -1 ) in the recently contaminated soil and a reduction in hydrocarbon concentration (~30 %). The combination of an inert support and enzymatic and respirometric analyses made it possible to detect the different biodegradation capacities of the studied inocula and the natural attenuation potential of a recently contaminated soil at high hydrocarbon concentrations.

Hydrocarbon-stapled lipopeptides exhibit selective antimicrobial activity.

PubMed

Jenner, Zachary B; Crittenden, Christopher M; Gonzalez, Martín; Brodbelt, Jennifer S; Bruns, Kerry A

2017-05-01

Antimicrobial peptides (AMPs) occur widely in nature and have been studied for their therapeutic potential. AMPs are of interest due to the large number of possible chemical structural combinations using natural and unnatural amino acids, with varying effects on their biological activities. Using physicochemical properties from known naturally occurring amphipathic cationic AMPs, several hydrocarbon-stapled lipopeptides (HSLPs) were designed, synthesized, and tested for antimicrobial properties. Peptides were chemically modified by N-terminal acylation, C-terminal amidation, and some were hydrocarbon stapled by intramolecular olefin metathesis. The effects of peptide length, amphipathic character, and stapling on antimicrobial activity were tested against Escherichia coli, three species of Gram-positive bacteria (Staphylococcus aureus, Bacillus megaterium, and Enterococcus faecalis), and two strains of Candida albicans. Peptides were shown to disrupt liposomes of different phospholipid composition, as measured by leakage of a fluorescent compound from vesicles. Peptides with (S)-2-(4'-pentenyl)-alanine substituted for l-alanine in a reference peptide showed a marked increase in antimicrobial activity, hemolysis, and membrane disruption. Stapled peptides exhibited slightly higher antimicrobial potency; those with greatest hydrophobic character showed the greatest hemolysis and liposome leakage, but lower antimicrobial activity. The results support a model of HSLPs as membrane-disruptive AMPs with potent antimicrobial activity and relatively low hemolytic potential at biologically active peptide concentrations. © 2017 Wiley Periodicals, Inc.

Isolation and analysis of bacteria with antimicrobial activities from the marine sponge Haliclona simulans collected from Irish waters.

PubMed

Kennedy, Jonathan; Baker, Paul; Piper, Clare; Cotter, Paul D; Walsh, Marcella; Mooij, Marlies J; Bourke, Marie B; Rea, Mary C; O'Connor, Paula M; Ross, R Paul; Hill, Colin; O'Gara, Fergal; Marchesi, Julian R; Dobson, Alan D W

2009-01-01

Samples of the marine sponge Haliclona simulans were collected from Irish coastal waters, and bacteria were isolated from these samples. Phylogenetic analyses of the cultured isolates showed that four different bacterial phyla were represented; Bacteriodetes, Actinobacteria, Proteobacteria, and Firmicutes. The sponge bacterial isolates were assayed for the production of antimicrobial substances, and biological activities against Gram-positive and Gram-negative bacteria and fungi were demonstrated, with 50% of isolates showing antimicrobial activity against at least one of the test strains. Further testing showed that the antimicrobial activities extended to the important pathogens Pseudomonas aeruginosa, Clostridium difficile, multi-drug-resistant Staphylococcus aureus, and pathogenic yeast strains. The Actinomycetes were numerically the most abundant producers of antimicrobial activities, although activities were also noted from Bacilli and Pseudovibrio isolates. Surveys for the presence of potential antibiotic encoding polyketide synthase and nonribosomal peptide synthetase genes also revealed that genes for the biosynthesis of these secondary metabolites were present in most bacterial phyla but were particularly prevalent among the Actinobacteria and Proteobacteria. This study demonstrates that the culturable fraction of bacteria from the sponge H. simulans is diverse and appears to possess much potential as a source for the discovery of new medically relevant biological active agents.

GRIND2-based 3D-QSAR and prediction of activity spectra for symmetrical bis-pyridinium salts with promastigote antileishmanial activity.

PubMed

Diniz, Evelyn Mirella Lopes Pina; Tomich de Paula da Silva, Carlos Henrique; Gómez-Perez, Verónica; Federico, Leonardo Bruno; Campos Rosa, Joaquín María

2017-08-01

Leishmaniasis is a major group of neglected tropical diseases caused by the protozoan parasite Leishmania. About 12 million people are affected in 98 countries and 350 million people worldwide are at risk of infection. Current leishmaniasis treatments rely on a relatively small arsenal of drugs, including amphotericin B, pentamidine and others, which in general have some type of inconvenience. Recently, we have synthesized antileishmanial bis-pyridinium derivatives and symmetrical bis-pyridinium cyclophanes. These compounds are considered structural analogues of pentamidine, where the amidino moiety, protonated at physiological pH, is replaced by a positively charged nitrogen atom as a pyridinium ring. In this work, a statistically significant GRIND2-based 3D-QSAR model was built and biological activity predictions were in silico carried out allowing rationalization of the different activities recently obtained against Leishmania donovani (in L. donovani promastigotes) for a data set of 19 bis-pyridinium compounds. We will emphasize the most important structural requirements to improve the biological activity and probable interactions with the biological receptor as a guide for lead and prototype optimization. In addition, since no information about the actual biological target for this series of active compounds is provided, we have used Prediction of Activity Spectra for Biologically Active Substances to propose our compounds as potential nicotinic α6β3β4α5 receptor antagonists. This proposal is reinforced by the high structural similarity observed between our compounds and several anthelmintic drugs in current clinical use, which have the same drug action mechanism here predicted. Such new findings would be confirmed with further and additional experimental assays.

Exploring 'new' bioactivities of polymers at the nano-bio interface.

PubMed

Wang, Chunming; Dong, Lei

2015-01-01

A biological system is essentially an elegant assembly of polymeric nanostructures. The polymers in the body, biomacromolecules, are both building blocks and versatile messengers. We propose that non-biologically derived polymers can be potential therapeutic candidates with unique advantages. Emerging findings about polycations, polysaccharides, immobilised multivalent ligands, and biomolecular coronas provide evidence that polymers are activated at the nano-bio interface, while emphasising the current theoretical and practical challenges. Our increasing understanding of the nano-bio interface and evolving approaches to establish the therapeutic potential of polymers enable the development of polymer drugs with high specificities for broad applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

Glycation of antibodies: Modification, methods and potential effects on biological functions.

PubMed

Wei, Bingchuan; Berning, Kelsey; Quan, Cynthia; Zhang, Yonghua Taylor

Glycation is an important protein modification that could potentially affect bioactivity and molecular stability, and glycation of therapeutic proteins such as monoclonal antibodies should be well characterized. Glycated protein could undergo further degradation into advance glycation end (AGE) products. Here, we review the root cause of glycation during the manufacturing, storage and in vivo circulation of therapeutic antibodies, and the current analytical methods used to detect and characterize glycation and AGEs, including boronate affinity chromatography, charge-based methods, liquid chromatography-mass spectrometry and colorimetric assay. The biological effects of therapeutic protein glycation and AGEs, which ranged from no affect to loss of activity, are also discussed.

The State, Potential Distribution, and Biological Implications of Methane in the Martian Crust

NASA Technical Reports Server (NTRS)

Max, Michael D.; Clifford, Stephen M.

2000-01-01

The search for life on Mars has recently focused on its potential survival in deep (>2 km) subpermafrost aquifers where anaerobic bacteria, similar to those found in deep subsurface ecosystems on Earth, may have survived in an environment that has remained stable for billions of years. An anticipated by-product of this biological activity is methane. The detection of large deposits of methane gas and hydrate in the Martian cryosphere, or as emissions from deep fracture zones, would provide persuasive evidence of indigenous life and confirm the presence of a valuable in situ resource for use by future human explorers.

Electrically active bioceramics: a review of interfacial responses.

PubMed

Baxter, F R; Bowen, C R; Turner, I G; Dent, A C E

2010-06-01

Electrical potentials in mechanically loaded bone have been implicated as signals in the bone remodeling cycle. Recently, interest has grown in exploiting this phenomenon to develop electrically active ceramics for implantation in hard tissue which may induce improved biological responses. Both polarized hydroxyapatite (HA), whose surface charge is not dependent on loading, and piezoelectric ceramics, which produce electrical potentials under stress, have been studied in order to determine the possible benefits of using electrically active bioceramics as implant materials. The polarization of HA has a positive influence on interfacial responses to the ceramic. In vivo studies of polarized HA have shown polarized samples to induce improvements in bone ingrowth. The majority of piezoelectric ceramics proposed for implant use contain barium titanate (BaTiO(3)). In vivo and in vitro investigations have indicated that such ceramics are biocompatible and, under appropriate mechanical loading, induce improved bone formation around implants. The mechanism by which electrical activity influences biological responses is yet to be clearly defined, but is likely to result from preferential adsorption of proteins and ions onto the polarized surface. Further investigation is warranted into the use of electrically active ceramics as the indications are that they have benefits over existing implant materials.

Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the Malaria Box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues.

PubMed

Vallone, Alessandra; D'Alessandro, Sarah; Brogi, Simone; Brindisi, Margherita; Chemi, Giulia; Alfano, Gloria; Lamponi, Stefania; Lee, Soon Goo; Jez, Joseph M; Koolen, Karin J M; Dechering, Koen J; Saponara, Simona; Fusi, Fabio; Gorelli, Beatrice; Taramelli, Donatella; Parapini, Silvia; Caldelari, Reto; Campiani, Giuseppe; Gemma, Sandra; Butini, Stefania

2018-04-25

Therapies addressing multiple stages of Plasmodium falciparum life cycle are highly desirable for implementing malaria elimination strategies. MMV019918 (1, 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine) was selected from the MMV Malaria Box for its dual activity against both asexual stages and gametocytes. In-depth structure-activity relationship studies and cytotoxicity evaluation led to the selection of 25 for further biological investigation. The potential transmission blocking activity of 25 versus P. falciparum was confirmed through the standard membrane-feeding assay. Both 1 and 25 significantly prolonged atrioventricular conduction time in Langendorff-isolated rat hearts, and showed inhibitory activity of Ba 2+ current through Ca v 1.2 channels. An in silico target-fishing study suggested the enzyme phosphoethanolamine methyltransferase (PfPMT) as a potential target. However, compound activity against PfPMT did not track with the antiplasmodial activity, suggesting the latter activity relies on a different molecular target. Nevertheless, 25 showed interesting activity against PfPMT, which could be an important starting point for the identification of more potent inhibitors active against both sexual and asexual stages of the parasite. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical Composition and Biological Activity of Extracts Obtained by Supercritical Extraction and Ethanolic Extraction of Brown, Green and Red Propolis Derived from Different Geographic Regions in Brazil

PubMed Central

Machado, Bruna Aparecida Souza; Silva, Rejane Pina Dantas; Barreto, Gabriele de Abreu; Costa, Samantha Serra; da Silva, Danielle Figuerêdo; Brandão, Hugo Neves; da Rocha, José Luiz Carneiro; Dellagostin, Odir Antônio; Henriques, João Antônio Pegas; Umsza-Guez, Marcelo Andres; Padilha, Francine Ferreira

2016-01-01

The variations in the chemical composition, and consequently, on the biological activity of the propolis, are associated with its type and geographic origin. Considering this fact, this study evaluated propolis extracts obtained by supercritical extraction (SCO2) and ethanolic extraction (EtOH), in eight samples of different types of propolis (red, green and brown), collected from different regions in Brazil. The content of phenolic compounds, flavonoids, in vitro antioxidant activity (DPPH and ABTS), Artepillin C, p-coumaric acid and antimicrobial activity against two bacteria were determined for all extracts. For the EtOH extracts, the anti-proliferative activity regarding the cell lines of B16F10, were also evaluated. Amongst the samples evaluated, the red propolis from the Brazilian Northeast (states of Sergipe and Alagoas) showed the higher biological potential, as well as the larger content of antioxidant compounds. The best results were shown for the extracts obtained through the conventional extraction method (EtOH). However, the highest concentrations of Artepillin C and p-coumaric acid were identified in the extracts from SCO2, indicating a higher selectivity for the extraction of these compounds. It was verified that the composition and biological activity of the Brazilian propolis vary significantly, depending on the type of sample and geographical area of collection. PMID:26745799

Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives.

PubMed

Šegan, Sandra; Trifković, Jelena; Verbić, Tatjana; Opsenica, Dejan; Zlatović, Mario; Burnett, James; Šolaja, Bogdan; Milojković-Opsenica, Dušanka

2013-01-01

The physicochemical properties, retention parameters (R(M)(0)), partition coefficients (logP(OW)), and pK(a) values for a series of thirteen 1,7-bis(aminoalkyl) diazachrysene (1,7-DAAC) derivatives were determined in order to reveal the characteristics responsible for their biological behavior. The investigated compounds inhibit three unrelated pathogens (the Botulinum neurotoxin serotype A light chain (BoNT/A LC), Plasmodium falciparum malaria, and Ebola filovirus) via three different mechanisms of action. To determine the most influential factors governing the retention and activities of the investigated diazachrysenes, R(M)(0), logP(OW), and biological activity values were correlated with 2D and 3D molecular descriptors, using a partial least squares regression. The resulting quantitative structure-retention (property) relationships indicate the importance of descriptors related to the hydrophobicity of the molecules (e.g., predicted partition coefficients and hydrophobic surface area). Quantitative structure-activity relationship models for describing biological activity against the BoNT/A LC and malarial strains also include overall compound polarity, electron density distribution, and proton donor/acceptor potential. Furthermore, models for Ebola filovirus inhibition are presented qualitatively to provide insights into parameters that may contribute to the compounds' antiviral activities. Overall, the models form the basis for selecting structural features that significantly affect the compound's absorption, distribution, metabolism, excretion, and toxicity profiles. Copyright © 2012 Elsevier B.V. All rights reserved.

Biologic Potential of Calcium Phosphate Biopowders Produced via Decomposition Combustion Synthesis

PubMed Central

Vollmer, N.; King, K.B.; Ayers, R.

2015-01-01

The aim of this research was to evaluate the biologic potential of calcium phosphate (CaP) biopowders produced with a novel reaction synthesis system. Decomposition combustion synthesis (DCS) is a modified combustion synthesis method capable of producing CaP powders for use in bone tissue engineering applications. During DCS, the stoichiometric ratio of reactant salt to fuel was adjusted to alter product chemistry and morphology. In vitro testing methods were utilized to determine the effects of controlling product composition on cytotoxicity, proliferation, biocompatibility and biomineralization. In vitro, human fetal osteoblasts (ATCC, CRL-11372) cultured with CaP powder displayed a flattened morphology, and uniformly encompassed the CaP particulates. Matrix vesicles containing calcium and phosphorous budded from the osteoblast cells. CaP powders produced via DCS are a source of biologically active, synthetic, bone graft substitute materials PMID:26034341

Synthesis, structural characterization and biological activity of two diastereomeric JA-Ile macrolactones.

PubMed

Jimenez-Aleman, Guillermo H; Machado, Ricardo A R; Görls, Helmar; Baldwin, Ian T; Boland, Wilhelm

2015-06-07

Jasmonates are phytohormones involved in a wide range of plant processes, including growth, development, senescence, and defense. Jasmonoyl-L-isoleucine (JA-Ile, 2), an amino acid conjugate of jasmonic acid (JA, 1), has been identified as a bioactive endogenous jasmonate. However, JA-Ile (2) analogues trigger different responses in the plant. ω-Hydroxylation of the pentenyl side chain leads to the inactive 12-OH-JA-Ile (3) acting as a “stop” signal. On the other hand, a lactone derivative of 12-OH-JA (5) (jasmine ketolactone, JKL) occurs in nature, although with no known biological function. Inspired by the chemical structure of JKL (6) and in order to further explore the potential biological activities of 12-modified JA-Ile derivatives, we synthesized two macrolactones (JA-Ile-lactones (4a) and (4b)) derived from 12-OH-JA-Ile (3). The biological activity of (4a) and (4b) was tested for their ability to elicit nicotine production, a well-known jasmonate dependent secondary metabolite. Both macrolactones showed strong biological activity, inducing nicotine accumulation to a similar extent as methyl jasmonate does in Nicotiana attenuata leaves. Surprisingly, the highest nicotine contents were found in plants treated with the JA-Ile-lactone (4b), which has (3S,7S) configuration at the cyclopentanone not known from natural jasmonates. Macrolactone (4a) is a valuable standard to explore for its occurrence in nature.

Use of biological characteristics of common carp (Cyprinus carpio) to indicate exposure to hormonally active agents in selected Minnesota streams, 1999

USGS Publications Warehouse

Lee, Kathy E.; Blazer, Vicki; Denslow, Nancy D.; Goldstein, Robert M.; Talmage, Philip J.

2000-01-01

The presence of HAAs in selected Minnesota streams was indicated by biological characteristics in common carp. Biological characteristics used in this study identified WWTP effluent as a potential source of HAAs. Additionally, fish located at sites upstream of WWTP effluent primarily draining agricultural land show indications of HAAs, which may be the result of agricultural runoff or other sources of HAAs. There was variability among all sites and among sites within each site group. Differences among sites may be due to differences in water chemistry or fish exposure time. Natural variation in the biological characteristics may account for some of the differences observed in this study. This study and others indicate the presence of HAAs in surface water and the potential signs of endocrine disruption in resident fish populations. Detailed controlled studies could confirm the effects of particular chemicals such as pesticides or components of WWTPs on fish reproduction and population structure.

The medicinal chemistry of botulinum, ricin and anthrax toxins.

PubMed

Hicks, Rickey P; Hartell, Mark G; Nichols, Daniel A; Bhattacharjee, Apurba K; van Hamont, John E; Skillman, Donald R

2005-01-01

The potential use of weapons of mass destruction (nuclear, biological or chemical) by terrorist organizations represents a major threat to world peace and safety. Only a limited number of vaccines are available to protect the general population from the medical consequences of these weapons. In addition there are major health concerns associated with a pre-exposure mass vaccination of the general population. To reduce or eliminate the impact of these terrible threats, new drugs must be developed to safely treat individuals exposed to these agents. A review of all therapeutic agents under development for the treatment of the illnesses and injuries that result from exposure to nuclear, biological or chemical warfare agents is beyond the scope of any single article. The intent here is to provide a focused review for medicinal and organic chemists of three widely discussed and easily deployed biological warfare agents, botulinum neurotoxin and ricin toxins and the bacteria Bacillus anthracis. Anthrax will be addressed because of its similarity in both structure and mechanism of catalytic activity with botulinum toxin. The common feature of these three agents is that they exhibit their biological activity via toxin enzymatic hydrolysis of a specific bond in their respective substrate molecules. A brief introduction to the history of each of the biological warfare agents is presented followed by a discussion on the mechanisms of action of each at the molecular level, and a review of current potential inhibitors under investigation.

Fungal phytotoxins with potential herbicidal activity: chemical and biological characterization.

PubMed

Cimmino, Alessio; Masi, Marco; Evidente, Marco; Superchi, Stefano; Evidente, Antonio

2015-12-19

Covering: 2007 to 2015 Fungal phytotoxins are secondary metabolites playing an important role in the induction of disease symptoms interfering with host plant physiological processes. Although fungal pathogens represent a heavy constraint for agrarian production and for forest and environmental heritage, they can also represent an ecofriendly alternative to manage weeds. Indeed, the phytotoxins produced by weed pathogenic fungi are an efficient tool to design natural, safe bioherbicides. Their use could avoid that of synthetic pesticides causing resistance in the host plants and the long term impact of residues in agricultural products with a risk to human and animal health. The isolation and structural and biological characterization of phytotoxins produced by pathogenic fungi for weeds, including parasitic plants, are described. Structure activity relationships and mode of action studies for some phytotoxins are also reported to elucidate the herbicide potential of these promising fungal metabolites.

Allosteric cross-talk in chromatin can mediate drug-drug synergy

NASA Astrophysics Data System (ADS)

Adhireksan, Zenita; Palermo, Giulia; Riedel, Tina; Ma, Zhujun; Muhammad, Reyhan; Rothlisberger, Ursula; Dyson, Paul J.; Davey, Curt A.

2017-03-01

Exploitation of drug-drug synergism and allostery could yield superior therapies by capitalizing on the immensely diverse, but highly specific, potential associated with the biological macromolecular landscape. Here we describe a drug-drug synergy mediated by allosteric cross-talk in chromatin, whereby the binding of one drug alters the activity of the second. We found two unrelated drugs, RAPTA-T and auranofin, that yield a synergistic activity in killing cancer cells, which coincides with a substantially greater number of chromatin adducts formed by one of the compounds when adducts from the other agent are also present. We show that this occurs through an allosteric mechanism within the nucleosome, whereby defined histone adducts of one drug promote reaction of the other drug at a distant, specific histone site. This opens up possibilities for epigenetic targeting and suggests that allosteric modulation in nucleosomes may have biological relevance and potential for therapeutic interventions.

Syntheses of some α-cyclic tripeptides as potential inhibitors for HMG-CoA Reductase.

PubMed

Chakraborty, Subrata; Lin, Shih-Hung; Shiuan, David; Tai, Dar-Fu

2015-08-01

α-Cyclic tripeptides (CtPs) are the most rigid members of the cyclic peptide family. However, due to their synthetic difficulty, biological activity has remained undisclosed. The incorporation of side-chain-protected natural amino acids into functional CtPs was performed to explore the potential biological functions. Several novel CtPs that consist of protected serine (S(Bn)) and/or glutamate (E(OBn)) were prepared from corresponding linear tripeptides by chemical synthesis. There is a strong possibility for CtPs that contain 3 phenyl groups to correlate with atorvastatin structure. The binding effects in human HMG-CoA reductase (hHMGR) activities were first evaluated by molecular docking. High docking scores were received with these CtPs for enzyme. Therefore, enzymatic assays were carried out and the compound cyclo(S(Bn))3 was indeed able to moderately inhibit hHMGR (IC50 = 110 μM).

Synergistic potentiation of D-fraction with vitamin C as possible alternative approach for cancer therapy.

PubMed

Konno, Sensuke

2009-07-30

Maitake D-fraction or PDF is the bioactive extract of maitake mushroom (Grifola frondosa) and its active constituent is the protein-bound polysaccharide (proteoglucan), or more specifically known as beta-glucan. PDF has been extensively studied and a number of its medicinal potentials/properties have been unveiled and demonstrated. Those include various physiological benefits ranging from immunomodulatory and antitumor activities to treatment for hypertension, diabetes, hypercholesterolemia, viral infections (hepatitis B and human immunodeficiency virus), and obesity. Particularly, two major biological activities of PDF, immunomodulatory and antitumor activities, have been the main target for scientific and clinical research. To demonstrate and confirm such biological activities, numerous studies have been performed in vitro and in vivo or in clinical settings. These studies showed that PDF was indeed capable of modulating immunologic and hematologic parameters, inhibiting or regressing the cancer cell growth, and even improving quality of life of cancer patients. Synergistic potentiation of PDF with vitamin C demonstrated in vitro is rather interesting and may have clinical implication, because such combination therapy appears to help improve the efficacy of currently ongoing cancer therapies. Recently, intravenous administration of vitamin C has been often used to increase its physiological concentration and this useful procedure may further make this combination therapy feasible. Therefore, PDF may have great potential, either being used solely or combined with other agents, for cancer therapy. Such relevant and detailed studies will be described and discussed herein with a special focus on the combination of PDF and vitamin C as a viable therapeutic option.

A Comparative Study of Instructor and Student-Led Learning in a Large Nonmajors Biology Course: Student Performance and Perceptions

ERIC Educational Resources Information Center

Bernot, Melody J.; Metzler, Jennifer

2014-01-01

Traditional lectures have come under increasing criticism as research indicates lectures may be less effective in achieving learning outcomes than other teaching methods. Student engagement and success can potentially be improved by changing traditional lectures to instructional methods using active learning techniques. Active learning refers to…

Tomato powder inhibits hepatic steatosis and inflammation potentially through restoring SIRT1 activity and adiponectin function independent of carotenoid cleavage enzymes in mice

USDA-ARS?s Scientific Manuscript database

Scope: Beta-carotene-15,15'-oxygenase (BCO1) and beta-carotene-9',10'-oxygenase (BCO2) metabolize lycopene to biologically active metabolites, which can ameliorate nonalcoholic fatty liver disease (NAFLD). We investigated the effects of tomato powder (TP), a whole food containing substantial lycopen...

Aloe vera: Potential candidate in health management via modulation of biological activities

PubMed Central

Rahmani, Arshad H.; Aldebasi, Yousef H.; Srikar, Sauda; Khan, Amjad A.; Aly, Salah M.

2015-01-01

Treatment based on natural products is rapidly increasing worldwide due to the affordability and fewer side effects of such treatment. Various plants and the products derived from them are commonly used in primary health treatment, and they play a pivotal role in the treatment of diseases via modulation of biochemical and molecular pathways. Aloe vera, a succulent species, produces gel and latex, plays a therapeutic role in health management through antioxidant, antitumor, and anti-inflammatory activities, and also offers a suitable alternative approach for the treatment of various types of diseases. In this review, we summarize the possible mechanism of action and the therapeutic implications of Aloe vera in health maintenance based on its modulation of various biological activities. PMID:26392709

Synthesis and biological evaluation of sulfur-containing cinnamate and salicylate derivatives.

PubMed

Chiang, Chih-Chia; Chang, Tsu-Chung; Tsai, Hou-Jen; Hsu, Ling-Yih

2008-03-01

UV irradiation induced formation of reactive oxygen radical species and matrix metalloproteinases (MMPs) are thought to be involved in photo-damage to the skin. MMP-1 is the major collagenolytic enzyme responsible for collagen destruction in skin tissue. To develop new anti-photoaging agents, a series of 2,2'-dithiocinnamate derivatives and 2,2'-dithio or 2-thiobenzoate derivatives were designed and synthesized. The biological activities of the synthesized compounds were assayed for ABTS [2,2'-azinobis-(3-ethyl-benzo-thiazoline-6-sulfonic acid)] radical scavenging activity, MMP-1 inhibitory activity, and cytotoxicity to human dermal fibroblast cells. Compounds with potential of resistance to UV irradiation were identified. These compounds are expected to be useful for preventing photo-damage to the skin.

Benzoin Schiff Bases: Design, Synthesis, and Biological Evaluation as Potential Antitumor Agents.

PubMed

Sabbah, Dima A; Al-Tarawneh, Fatima; Talib, Wamidh H; Sweidan, Kamal; Bardaweel, Sanaa K; Al-Shalabi, Eveen; Zhong, Haizhen A; Abu Sheikha, Ghassan; Abu Khalaf, Reema; Mubarak, Mohammad S

2018-04-12

Phosphoinositide 3-kinase α (PI3Kα) is an attractive target for anticancer drug design. Target compounds were designed to probe the significance of alcohol and imine moieties tailored on a benzoin scaffold to better understand the structure activity relation (SAR) and improve their biological activity as anticancer compounds. Chemical synthesis of the targeted compounds, biological evaluation tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, as well as Glide docking studies were employed in this investigation. A new series of 1,2-diphenylimino ethanol was successfully synthesized and characterized by means of FT-IR, HRMS, NMR, and by elemental analysis. Biological screening revealed that the newly synthesized compounds inhibit PI3Kα activity in human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines. Results additionally showed that these compounds exhibit selective antiproliferative activity, induce apoptosis, and suppress the VEGF production. Compounds 2b, 2d, and 2g displayed promising inhibitory activity in HCT-116 suggesting that hydrophobic and/or hydrogen bond-acceptor mediate(s) ligand-receptor interaction on o- and m-positions. Furthermore, compounds 2g, 2i, 2j, and 2h, bearing hydrophobic moiety on m- and p-position, exerted high antiproliferative activity in T47D and MCF-7 cells, whereas compound 2e showed selectivity against T47D and MCF-7. Molecular docking studies against PI3Kα and caspase-3 demonstrated a strong correlation between the predicted binding affinity (ΔGobsd) and IC50 values of prepared compounds for the caspase-3 model, implying that the cellulous inhibitory activity was caspase-3-dependent. Moreover, Glide docking against PI3Kα identified Ser774, Lys802, E849, V851, and Asp933 as key binding residues. The series exerted a potential PI3Kα inhibitory activity in human carcinoma cell lines expressing PI3Kα. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Design, Synthesis and Biological Activities of Novel Gemini 20S-Hydroxyvitamin D3 Analogs

PubMed Central

LIN, ZONGTAO; MAREPALLY, SRINIVASA R.; KIM, TAE-KANG; JANJETOVIC, ZORICA; OAK, ALLEN SW.; POSTLETHWAITE, ARNOLD E.; MYERS, LINDA K.; TUCKEY, ROBERT C.; SLOMINSKI, ANDRZEJ T.; MILLER, DUANE D.; LI, WEI

2017-01-01

Vitamin D3 (D3) can be metabolized by cytochrome P450scc (CYP11A1) into 20S-hydroxyvitamin D3 (20D3) as a major metabolite. This bioactive metabolite has shown strong antiproliferative, antifibrotic, pro-differentiation and anti-inflammatory effects while being non-toxic (non-calcemic) at high concentrations. Since D3 analogs with two symmetric side chains (Gemini analogs) result in potent activation of the vitamin D receptor (VDR), we hypothesized that the chain length and composition of these types of analogs also containing a 20-hydroxyl group would affect their biological activities. In this study, we designed and synthesized a series of Gemini 20D3 analogs. Biological tests showed that some of these analogs are partial VDR activators and can significantly stimulate the expression of mRNA for VDR and VDR-regulated genes including CYP24A1 and transient receptor potential cation channel V6 (TRPV6). These analogs inhibited the proliferation of melanoma cells with potency comparable to that of 1α,25-dihydroxyvitamin D3. Moreover, these analogs reduced the level of interferon γ and up-regulated the expression of leukocyte associated immunoglobulin-like receptor 1 in splenocytes, indicating that they have potent anti-inflammatory activities. There are no clear correlations between the Gemini chain length and their VDR activation or biological activities, consistent with the high flexibility of the ligand-binding pocket of the VDR. PMID:26976974

Super-resolution binding activated localization microscopy through reversible change of DNA conformation.

PubMed

Szczurek, Aleksander; Birk, Udo; Knecht, Hans; Dobrucki, Jurek; Mai, Sabine; Cremer, Christoph

2018-01-01

Methods of super-resolving light microscopy (SRM) have found an exponentially growing range of applications in cell biology, including nuclear structure analyses. Recent developments have proven that Single Molecule Localization Microscopy (SMLM), a type of SRM, is particularly useful for enhanced spatial analysis of the cell nucleus due to its highest resolving capability combined with very specific fluorescent labeling. In this commentary we offer a brief review of the latest methodological development in the field of SMLM of chromatin designated DNA Structure Fluctuation Assisted Binding Activated Localization Microscopy (abbreviated as fBALM) as well as its potential future applications in biology and medicine.

Properties and applications of antimicrobial peptides in biodefense against biological warfare threat agents.

PubMed

Dawson, Raymond Murray; Liu, Chun-Qiang

2008-01-01

Recent advances in knowledge of the properties of antimicrobial peptides (AMPs) are reviewed. AMPs are typically small, positively charged, amphipathic peptides that interact electrostatically and non-stereospecifically with the bacterial cell membrane, resulting in its permeabilization and cell death. Classes of AMPs, their mechanisms of action, hemolytic activity, and cytotoxicity towards host cells are discussed. A particular focus is AMPs with potential for use in defense against biological warfare agents. Some AMPs cytotoxic to Bacillus anthracis have been described. Synthesis of these peptides in multivalent form leads to a synergistic increase in antibacterial activity. Strategies to enhance the potency, stability, and selectivity of AMPs are discussed.

Bioactive Natural Products of Marine Sponges from the Genus Hyrtios.

PubMed

Shady, Nourhan Hisham; El-Hossary, Ebaa M; Fouad, Mostafa A; Gulder, Tobias A M; Kamel, Mohamed Salah; Abdelmohsen, Usama Ramadan

2017-05-11

Marine sponges are known as a rich source for novel bioactive compounds with valuable pharmacological potential. One of the most predominant sponge genera is Hyrtios , reported to have various species such as Hyrtios erectus , Hyrtios reticulatus , Hyrtios gumminae , Hyrtios communis , and Hyrtios tubulatus and a number of undescribed species. Members of the genus Hyrtios are a rich source of natural products with diverse and valuable biological activities, represented by different chemical classes including alkaloids, sesterterpenes and sesquiterpenes. This review covers the literature until June 2016, providing a complete survey of all compounds isolated from the genus Hyrtios with their corresponding biological activities whenever applicable.

Fungal Phytotoxins with Potential Herbicidal Activity to Control Chenopodium album.

PubMed

Cimmino, Alessio; Masi, Marco; Evidente, Marco; Evidente, Antonio

2015-06-01

This review deals with the isolation and chemical and biological characterization of phytotoxins produced by Ascochyta caulina and Phoma chenopodiicola proposed as mycoherbicides for the biological control of Chenopodium album, a worldwide spread weed which causes serious problems to some agrarian crops, including sugar beet and maize. Studies on the structure activity relationships and on the modes of actions of toxins isolated are also described, as well as the optimization of analytical methods focused on selection of the best fungal toxin producers. The attempts to scale up production of these phytotoxins aimed to obtain sufficient amounts for their application in greenhouse and field trials are also reported.

Super-resolution binding activated localization microscopy through reversible change of DNA conformation

PubMed Central

Knecht, Hans; Dobrucki, Jurek; Mai, Sabine

2018-01-01

ABSTRACT Methods of super-resolving light microscopy (SRM) have found an exponentially growing range of applications in cell biology, including nuclear structure analyses. Recent developments have proven that Single Molecule Localization Microscopy (SMLM), a type of SRM, is particularly useful for enhanced spatial analysis of the cell nucleus due to its highest resolving capability combined with very specific fluorescent labeling. In this commentary we offer a brief review of the latest methodological development in the field of SMLM of chromatin designated DNA Structure Fluctuation Assisted Binding Activated Localization Microscopy (abbreviated as fBALM) as well as its potential future applications in biology and medicine. PMID:29297245

Human skin gene expression: Natural (trans) resveratrol versus five resveratrol analogs for dermal applications.

PubMed

Lephart, Edwin D; Andrus, Merritt B

2017-09-01

Resveratrol (RV) is a polyphenolic compound naturally produced by plants. Polyphenolic compounds incorporated into medicinal products are beneficial but, RV is rapidly metabolized with an associated decline in biological activity. This study tested RV as the standard and compared five structurally modified RV analogs: butyrate, isobutyrate, palmitoate, acetate, and diacetate (to improve functionality) at 1% concentration(s) for 24 h in epiderm full thickness cultures by gene array/qPCR mRNA analysis. When silent mating type information regulation 2 homolog 1, extracellular elements (collagen1A1, 3A1, 4A1; elastin, tissue inhibitor of matrix metalloproteinase 1, fibrillin 1 laminin beta1 and matrix metalloproteinase 9), anti-aging and aging genes, inflammatory biomarkers (interleukin-1A [IL1A], IL1R2, IL-6 and IL-8), nerve growth factor, and the antioxidants (proliferating cell nuclear antigen, catalase, superoxide dismutase and metallothionein 1H/2H) were evaluated, ranking each from highest-to-lowest for gene expression: butyrate > isobutyrate > diacetate > acetate > palmitoate. This study showed that the butyrate and isobutyrate analogs are more biologically active compared to resveratrol and have potential use in topical applications to improve dermal and other health applications. Impact statement Resveratrol has been reported to have a wide variety of health benefits but its rapid metabolism especially after oral ingestion results in very low bioavailability. Notably, the first human skin gene expression study of resveratrol was not published until 2014. The purpose of this study was to determine if increased stability and biological activity could be obtained by modifying the chemical structure of natural (trans) resveratrol and quantifying human gene expression by qPCR of skin biomarkers that enhance dermal health. Five resveratrol analogs were synthesized that increased their lipophilic index to enhance tissue penetration and augment biological activities on the measured parameters that expand the current knowledge of structure/function relationships. The butyrate and isobutyrate modifications displayed gene expression values significantly above resveratrol and suggest that oral application of these and potentially other resveratrol analogs may yield similar results to improve stability and biological activity to benefit/address various disorders/diseases.

Marine Antifreeze Proteins: Structure, Function, and Application to Cryopreservation as a Potential Cryoprotectant

PubMed Central

Kim, Hak Jun; Lee, Jun Hyuck; Hur, Young Baek; Lee, Chang Woo; Park, Sun-Ha; Koo, Bon-Won

2017-01-01

Antifreeze proteins (AFPs) are biological antifreezes with unique properties, including thermal hysteresis (TH), ice recrystallization inhibition (IRI), and interaction with membranes and/or membrane proteins. These properties have been utilized in the preservation of biological samples at low temperatures. Here, we review the structure and function of marine-derived AFPs, including moderately active fish AFPs and hyperactive polar AFPs. We also survey previous and current reports of cryopreservation using AFPs. Cryopreserved biological samples are relatively diverse ranging from diatoms and reproductive cells to embryos and organs. Cryopreserved biological samples mainly originate from mammals. Most cryopreservation trials using marine-derived AFPs have demonstrated that addition of AFPs can improve post-thaw viability regardless of freezing method (slow-freezing or vitrification), storage temperature, and types of biological sample type. PMID:28134801

Chicken cathelicidin-2-derived peptides with enhanced immunomodulatory and antibacterial activities against biological warfare agents.

PubMed

Molhoek, E Margo; van Dijk, Albert; Veldhuizen, Edwin J A; Dijk-Knijnenburg, Helma; Mars-Groenendijk, Roos H; Boele, Linda C L; Kaman-van Zanten, Wendy E; Haagsman, Henk P; Bikker, Floris J

2010-09-01

Host defence peptides (HDPs) are considered to be excellent candidates for the development of novel therapeutic agents. Recently, it was demonstrated that the peptide C1-15, an N-terminal segment of chicken HDP cathelicidin-2, exhibits potent antibacterial activity while lacking cytotoxicity towards eukaryotic cells. In the present study, we report that C1-15 is active against bacteria such as Bacillus anthracis and Yersinia pestis that may potentially be used by bioterrorists. Substitution of single and multiple phenylalanine (Phe) residues to tryptophan (Trp) in C1-15 resulted in variants with improved antibacterial activity against B. anthracis and Y. pestis as well as decreased salt sensitivity. In addition, these peptides exhibited enhanced neutralisation of lipopolysaccharide (LPS)-induced release of pro-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs). The antibacterial and LPS-neutralising activities of these C1-15-derived peptides are exerted at concentrations far below the concentrations that are toxic to human PBMCs. Taken together, we show that Phe-->Trp substitutions in C1-15 variants enhances the antibacterial and LPS-neutralising activities against pathogenic bacteria, including those that may potentially be used as biological warfare agents. Copyright (c) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Flavonoid Composition and Biological Activities of Ethanol Extracts of Caryocar coriaceum Wittm., a Native Plant from Caatinga Biome.

PubMed

Alves, Daniela Ribeiro; Maia de Morais, Selene; Tomiotto-Pellissier, Fernanda; Miranda-Sapla, Milena Menegazzo; Vasconcelos, Fábio Roger; da Silva, Isaac Neto Goes; Araujo de Sousa, Halisson; Assolini, João Paulo; Conchon-Costa, Ivete; Pavanelli, Wander Rogério; Freire, Francisco das Chagas Oliveira

2017-01-01

Caryocar coriaceum fruits, found in Brazilian Cerrado and Caatinga, are commonly used as food and in folk medicine, as anti-inflammatory, bactericide, fungicide, leishmanicide, and nematicide. Due to the biological potential of this plant, this study focuses on the evaluation of antifungal and antileishmanial activities, including anticholinesterase and antioxidant tests, correlating with total phenols and flavonoids content. Peel extracts contain higher yield of phenols and flavonoids as analyzed by spectrophotometric methods. HPLC analysis of flavonoids revealed that isoquercitrin is the main flavonoid in both parts of the fruit, and peel extract showed the best antioxidant activity. In the inhibition of the acetylcholinesterase assay, both extracts demonstrate action comparable to physostigmine. The antimicrobial activity of extracts was evaluated against strains of Malassezia sp. and Microsporum canis , using the broth microdilution technique, in which the extracts showed similar MIC and MFC. The extracts present antileishmanial activity and low toxicity on murine macrophages and erythrocytes. Therefore, these results suggest a potential for the application of C. coriaceum fruit's ethanol extracts in the treatment against dermatophyte fungi and leishmaniasis, probably due to the presence of active flavonoids. Further in vivo studies are recommended aiming at the development of possible new pharmaceutical compounds.

Flavonoid Composition and Biological Activities of Ethanol Extracts of Caryocar coriaceum Wittm., a Native Plant from Caatinga Biome

PubMed Central

Alves, Daniela Ribeiro; Tomiotto-Pellissier, Fernanda; da Silva, Isaac Neto Goes; Araujo de Sousa, Halisson; Assolini, João Paulo; Freire, Francisco das Chagas Oliveira

2017-01-01

Caryocar coriaceum fruits, found in Brazilian Cerrado and Caatinga, are commonly used as food and in folk medicine, as anti-inflammatory, bactericide, fungicide, leishmanicide, and nematicide. Due to the biological potential of this plant, this study focuses on the evaluation of antifungal and antileishmanial activities, including anticholinesterase and antioxidant tests, correlating with total phenols and flavonoids content. Peel extracts contain higher yield of phenols and flavonoids as analyzed by spectrophotometric methods. HPLC analysis of flavonoids revealed that isoquercitrin is the main flavonoid in both parts of the fruit, and peel extract showed the best antioxidant activity. In the inhibition of the acetylcholinesterase assay, both extracts demonstrate action comparable to physostigmine. The antimicrobial activity of extracts was evaluated against strains of Malassezia sp. and Microsporum canis, using the broth microdilution technique, in which the extracts showed similar MIC and MFC. The extracts present antileishmanial activity and low toxicity on murine macrophages and erythrocytes. Therefore, these results suggest a potential for the application of C. coriaceum fruit's ethanol extracts in the treatment against dermatophyte fungi and leishmaniasis, probably due to the presence of active flavonoids. Further in vivo studies are recommended aiming at the development of possible new pharmaceutical compounds. PMID:29081821

Chemical biology tools to study pantetheinases of the vanin family.

PubMed

Schalkwijk, Joost; Jansen, Patrick

2014-08-01

VNNs (vanins) are pantetheinases that hydrolyse pantetheine to pantothenic acid and cysteamine. Studies with Vnn1-knockout mice have indicated a role of VNN-1 in inflammation and stress responses. VNN-1 is highly expressed in liver and is under transcriptional control of PPAR (peroxisome-proliferator-activated receptor)-α and nutritional status, suggesting a role in energy metabolism. Recently, the specific substrates and inhibitors of VNNs were obtained as tools to study VNN biology and to investigate whether VNNs are potential drug targets. Oral administration of RR6, a pantothenone with nanomolar anti-VNN potency, completely inhibited plasma VNN activity in rats and showed favourable pharmacokinetics. Prolonged RR6 administration caused alterations of hepatic and plasma lipid concentrations upon fasting. VNN inhibitors were found to protect pantothenamides (pantetheine analogues with antibiotic activity) against breakdown by plasma VNN, thereby preserving their antibiotic activity. Combination of pantothenamides with a VNN inhibitor showed a strong activity against Staphylococcus aureus and Staphylococcus pneumoniae when assayed in the presence of 10% serum. Recent studies have reported plasma stable pantothenamides that were active against the malaria parasite Plasmodium falciparum. We conclude that VNN inhibitors and pantothenate derivatives that target enzymes in the CoA (coenzyme A) biosynthetic pathway may have potential use as novel drugs in infection, inflammation and metabolism.

Neuroprotective effects of phloretin and its glycosylated derivative on rotenone-induced toxicity in human SH-SY5Y neuronal-like cells.

PubMed

Barreca, Davide; Currò, Monica; Bellocco, Ersilia; Ficarra, Silvana; Laganà, Giuseppina; Tellone, Ester; Laura Giunta, Maria; Visalli, Giuseppa; Caccamo, Daniela; Galtieri, Antonio; Ientile, Riccardo

2017-07-08

Phloretin and phlorizin are the two strong natural antioxidants whose biological and pharmacological applications are rapidly growing in different human pathological conditions. The neuroprotective activity of the two flavonoids has been analyzed on cell culture of neuroblastoma cells. The neuroprotective activity of the two flavonoids has been analyzed on cell culture of neuroblastoma cells and evaluated by testing cell vitality, mitochondrial transmembrane potential and ROS production, antioxidant enzymes detection, activation of caspase 3, DNA damage, protein carbonylation, lipid peroxidation, and superoxide anion scavenging activity. Incubation of cells with rotenone caused cell death and significant increase in intracellular reactive oxygen species, activation of caspase 3, and variation in mitochondrial transmembrane potential. Although, rotenone exposure caused a significant increase of antioxidant enzymes, high levels of lipid peroxidation were also observed. Phloretin or phlorizin, at micromolar concentration, reduced rotenone-induced cell death by scavenging ability against superoxide anion radical, one of the main effectors of rotenone toxicity at level of mitochondrial respiratory chain complex I. Under our experimental conditions, a reduction of the intracellular ROS levels with consequent normalization of the aforementioned antioxidant enzymes occurred. Concomitantly, we observed the inhibition of caspase 3 activity and DNA damage. This study shows the promising neuroprotective ability of the two dihydrochalcones able to protect human differentiated neuroblastoma cells (commonly used as model of Parkinson's disease) from injury induced by rotenone, actively scavenging ROS, normalizing mitochondrial transmembrane potential and consequently avoiding energy depletion. © 2017 BioFactors, 43(4):549-557, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Photoaffinity-labeled Cytokinins

PubMed Central

Theiler, Jane B.; Leonard, Nelson J.; Schmitz, Ruth Y.; Skoog, Folke

1976-01-01

Two new azidopurine derivatives, 2-azido-N6-(Δ2-isopentenyl)adenine and 2-azido-N6-benzyladenine, have been synthesized as potential photoaffinity labels for probing cytokinin-binding sites. The preparation and the biological activity of these compounds are described. PMID:16659772

A practical guide about biosimilar data for health care providers treating inflammatory diseases.

PubMed

Markenson, Joseph; Alvarez, Daniel F; Jacobs, Ira; Kirchhoff, Carol

2017-01-01

To make informed decisions about the safety, efficacy, and clinical utility of a biosimilar, health care providers should understand the types and be able to analyze data generated from a biosimilar development program. This article reviews the biosimilar guidelines, the biosimilar development process to provide education and context about biosimilarity, and uses examples from infliximab biosimilars to review the terminology and potential types of analyses that may be used to compare potential biosimilars to the originator biologic. A biosimilar is a biologic product that is highly similar to an approved (originator) biologic, notwithstanding minor differences in clinically inactive components, and with no clinically meaningful differences in terms of the safety, purity, and potency of the product. Due to their complex nature and production in living systems, it is not possible to exactly duplicate the approved originator biologic. To ensure biosimilars provide consistent, safe, and effective treatment comparable to the originator biologic, extensive analyses of the potential biosimilar are conducted, including side-by-side analytical, nonclinical, and clinical comparisons. A key goal is to determine whether there are sufficient relevant similarities in chemical composition, biologic activity, and pharmacokinetic aspects between the potential biosimilar and the originator. Regulatory approvals and marketing authorizations for biosimilars are made on a case-by-case and agency-by-agency basis after evaluating the totality of the evidence generated from the entire development program. Understanding how regulatory agencies review data for approval can help health care providers make appropriate decisions when biosimilars become available for use in the treatment of inflammatory diseases, and therefore they should review the literature to gain further information about specific biosimilars.

The anti-tumor effect and biological activities of the extract JMM6 from the stem-barks of the Chinese Juglans mandshurica Maxim on human hepatoma cell line BEL-7402.

PubMed

Zhang, Yongli; Cui, Yuqiang; Zhu, Jiayong; Li, Hongzhi; Mao, Jianwen; Jin, Xiaobao; Wang, Xiangsheng; Du, Yifan; Lu, Jiazheng

2013-01-01

Juglans mandshurica Maxim is a traditional herbal medicines in China, and its anti-tumor bioactivities are of research interest. Bioassay-guided fractionation method was employed to isolate anti-tumor compounds from the stem barks of the Juglans mandshurica Maxim. The anti-tumor effect and biological activities of the extracted compound JMM6 were studied in BEL-7402 cells by MTT, Cell cycle analysis, Hoechst 33342 staining, Annexin V-FITC/PI assay and Detection of mitochondrial membrane potential (ΔΨm). After treatment with the JMM6, the growth of BEL-7402 cells was inhibited and cells displayed typical morphological apoptotic characteristics. Further investigations revealed that treatment with JMM6 mainly caused G2/M cell cycle arrest and induced apoptosis in BEL-7402 cells. To evaluate the alteration of mitochondria in JMM6 induced apoptosis. The data showed that JMM6 decreased significantly the ΔΨm, causing the depolarization of the mitochondrial membrane. Our results show that the JMM6 will have a potential advantage of anti-tumor, less harmful to normal cells. This paper not only summarized the JMM6 pick-up technology from Juglans mandshurica Maxim and biological characteristic, but also may provide further evidence to exploit the potential medicine compounds from the stem-barks of the Chinese Juglans mandshurica Maxim.

Investigation of Marine-Derived Fungal Diversity and Their Exploitable Biological Activities

PubMed Central

Hong, Joo-Hyun; Jang, Seokyoon; Heo, Young Mok; Min, Mihee; Lee, Hwanhwi; Lee, Young Min; Lee, Hanbyul; Kim, Jae-Jin

2015-01-01

Marine fungi are potential producers of bioactive compounds that may have pharmacological and medicinal applications. Fungi were cultured from marine brown algae and identified using multiple target genes to confirm phylogenetic placement. These target genes included the internal transcribed spacer (ITS), the nuclear large subunit (LSU), and the β-tubulin region. Various biological activities of marine-derived fungi were evaluated, including their antifungal, antioxidant and cellulolytic enzyme activities. As a result, a total of 50 fungi was isolated from the brown algae Sargassum sp. Among the 50 isolated fungi, Corollospora angusta was the dominant species in this study. The genus Arthrinium showed a relatively strong antifungal activity to all of the target plant pathogenic fungi. In particular, Arthrinium saccharicola KUC21221 showed high radical scavenging activity and the highest activities in terms of filter paper units (0.39 U/mL), endoglucanase activity (0.38 U/mL), and β-glucosidase activity (1.04 U/mL). PMID:26133554

Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia

NASA Astrophysics Data System (ADS)

Li, Hongyu; Valkenier, Hennie; Judd, Luke W.; Brotherhood, Peter R.; Hussain, Sabir; Cooper, James A.; Jurček, Ondřej; Sparkes, Hazel A.; Sheppard, David N.; Davis, Anthony P.

2016-01-01

Transmembrane anion transporters (anionophores) have potential for new modes of biological activity, including therapeutic applications. In particular they might replace the activity of defective anion channels in conditions such as cystic fibrosis. However, data on the biological effects of anionophores are scarce, and it remains uncertain whether such molecules are fundamentally toxic. Here, we report a biological study of an extensive series of powerful anion carriers. Fifteen anionophores were assayed in single cells by monitoring anion transport in real time through fluorescence emission from halide-sensitive yellow fluorescent protein. A bis-(p-nitrophenyl)ureidodecalin shows especially promising activity, including deliverability, potency and persistence. Electrophysiological tests show strong effects in epithelia, close to those of natural anion channels. Toxicity assays yield negative results in three cell lines, suggesting that promotion of anion transport may not be deleterious to cells. We therefore conclude that synthetic anion carriers are realistic candidates for further investigation as treatments for cystic fibrosis.

The Effect of Hypoxia on Mesenchymal Stem Cell Biology

PubMed Central

Ejtehadifar, Mostafa; Shamsasenjan, Karim; Movassaghpour, Aliakbar; Akbarzadehlaleh, Parvin; Dehdilani, Nima; Abbasi, Parvaneh; Molaeipour, Zahra; Saleh, Mahshid

2015-01-01

Although physiological and pathological role of hypoxia have been appreciated in mammalians for decades however the cellular biology of hypoxia more clarified in the past 20 years. Discovery of the transcription factor hypoxia-inducible factor (HIF)-1, in the 1990s opened a new window to investigate the mechanisms behind hypoxia. In different cellular contexts HIF-1 activation show variable results by impacting various aspects of cell biology such as cell cycle, apoptosis, differentiation and etc. Mesenchymal stem cells (MSC) are unique cells which take important role in tissue regeneration. They are characterized by self-renewal capacity, multilineage potential, and immunosuppressive property. Like so many kind of cells, hypoxia induces different responses in MSCs by HIF- 1 activation. The activation of this molecule changes the growth, multiplication, differentiation and gene expression profile of MSCs in their niche by a complex of signals. This article briefly discusses the most important effects of hypoxia in growth kinetics, signalling pathways, cytokine secretion profile and expression of chemokine receptors in different conditions. PMID:26236651

DOE Office of Scientific and Technical Information (OSTI.GOV)

Medyantseva, E.P.; Budnikov, G.K.; Balakaeva, T.A.

The interest in the analytical chemistry of ruthenium and its compounds has recently been increasing. Ruthenium compounds can be used an antitumor agents and in the treatment of tuberculosis and fungal infections. It has been suggested that there is a specific relationship between the reduction potentials of the compounds and their biological activity. Of greatest interest among the biologically active compounds are the compounds with nitrogen-containing heterocycles. In order to obtain information on the degree of oxidation of the central atom in the complexes and to select the optimum conditions for the determination of the mono- and bi-nuclear complexes ofmore » ruthenium compounds with biologically active ligands such as imidazole (Im), histidine (His), benzimidazole (BIm) and its methyl derivative [1,2(CH{sub 3}){sub 2} - BIm], benzohyroxamic acid (Bha), and 1-phenyl-2-methylamino-1-propanol or ephedrine (Eph) in the present work, the authors studied their electrochemical behavior at dropping mercury (dme) and a platinum electrodes. 6 refs., 1 fig., 2 tabs.« less

[Piezoelectric property of novel biological piezoelectric ceramic HALNK and its effect on the functional expression of rat osteoblast cells].

PubMed

Wang, Peng; Zhang, Jin-Chao; Zhang, Xiao-Zhou; Liu, Zhi-Qin; Chen, Que-Ting; Sun, Jing; Chen, Zhi-Qing

2009-09-01

To test the Piezoelectric property of novel biological piezoelectric ceramic HALNK and its effect on the proliferation and differentiation of rat osteoblast cells. The biological piezoelectric ceramic HALNK1/9 and HALNK5/5 were prepared by mixing Hydroxyapatite (HA) with lithium sodium potassium niobate (LNK) piezoelectric ceramic at a ratio of 1/9 and 5/5 (wt/wt), respectively. After poling treatment, the piezoelectric constants were measured. The osteoblast cells were then seeded on the surfaces of HALNK. The proliferation and differentiation activities of the osteoblast cells were evaluated by MTT assays, ALP activities and scanning electron microscopy examinations. Cells grown on the surfaces of HALNK showed normal morphology, and had better proliferation and differentiation activities than the control. The growth of osteoblastic cells on the surface of HALNK1/9 was significantly better than others. The surface of HALNK 1/9 possesses better piezoelectric property and osteogenesis potential than HALNK5/5.

Dietary flavonoid aglycones and their glycosides: Which show better biological significance?

PubMed

Xiao, Jianbo

2017-06-13

The dietary flavonoids, especially their glycosides, are the most vital phytochemicals in diets and are of great general interest due to their diverse bioactivity. The natural flavonoids almost all exist as their O-glycoside or C-glycoside forms in plants. In this review, we summarized the existing knowledge on the different biological benefits and pharmacokinetic behaviors between flavonoid aglycones and their glycosides. Due to various conclusions from different flavonoid types and health/disease conditions, it is very difficult to draw general or universally applicable comments regarding the impact of glycosylation on the biological benefits of flavonoids. It seems as though O-glycosylation generally reduces the bioactivity of these compounds - this has been observed for diverse properties including antioxidant activity, antidiabetes activity, anti-inflammation activity, antibacterial, antifungal activity, antitumor activity, anticoagulant activity, antiplatelet activity, antidegranulating activity, antitrypanosomal activity, influenza virus neuraminidase inhibition, aldehyde oxidase inhibition, immunomodulatory, and antitubercular activity. However, O-glycosylation can enhance certain types of biological benefits including anti-HIV activity, tyrosinase inhibition, antirotavirus activity, antistress activity, antiobesity activity, anticholinesterase potential, antiadipogenic activity, and antiallergic activity. However, there is a lack of data for most flavonoids, and their structures vary widely. There is also a profound lack of data on the impact of C-glycosylation on flavonoid biological benefits, although it has been demonstrated that in at least some cases C-glycosylation has positive effects on properties that may be useful in human healthcare such as antioxidant and antidiabetes activity. Furthermore, there is a lack of in vivo data that would make it possible to make broad generalizations concerning the influence of glycosylation on the benefits of flavonoids for human health. It is possible that the effects of glycosylation on flavonoid bioactivity in vitro may differ from that seen in vivo. With in vivo (oral) treatment, flavonoid glycosides showed similar or even higher antidiabetes, anti-inflammatory, antidegranulating, antistress, and antiallergic activity than their flavonoid aglycones. Flavonoid glycosides keep higher plasma levels and have a longer mean residence time than those of aglycones. We should pay more attention to in vivo benefits of flavonoid glycosides, especially C-glycosides.

Evaluation of Biologically Active Compounds from Calendula officinalis Flowers using Spectrophotometry

PubMed Central

2012-01-01

Background This study aimed to quantify the active biological compounds in C. officinalis flowers. Based on the active principles and biological properties of marigolds flowers reported in the literature, we sought to obtain and characterize the molecular composition of extracts prepared using different solvents. The antioxidant capacities of extracts were assessed by using spectrophotometry to measure both absorbance of the colorimetric free radical scavenger 2,2-diphenyl-1-picrylhydrazyl (DPPH) as well as the total antioxidant potential, using the ferric reducing power (FRAP) assay. Results Spectrophotometric assays in the ultraviolet-visible (UV-VIS) region enabled identification and characterization of the full range of phenolic and flavonoids acids, and high-performance liquid chromatography (HPLC) was used to identify and quantify phenolic compounds (depending on the method of extraction). Methanol ensured more efficient extraction of flavonoids than the other solvents tested. Antioxidant activity in methanolic extracts was correlated with the polyphenol content. Conclusions The UV-VIS spectra of assimilator pigments (e.g. chlorophylls), polyphenols and flavonoids extracted from the C. officinalis flowers consisted in quantitative evaluation of compounds which absorb to wavelengths broader than 360 nm. PMID:22540963

Impact of biological activated carbon pre-treatment on the hydrophilic fraction of effluent organic matter for mitigating fouling in microfiltration.

PubMed

Pramanik, Biplob Kumar; Roddick, Felicity A; Fan, Linhua

2017-07-24

The hydrophilic (HPI) fraction of effluent organic matter, which has protein and carbohydrate contents, has a high propensity to foul low-pressure membranes. Biological activated carbon (BAC) filtration was examined as a pre-treatment for reducing the fouling of a microfiltration (MF) membrane (0.1 µm PVDF) by the HPI organic fraction extracted from a biologically treated secondary effluent (BTSE). Although the BAC removed less dissolved organic carbon, carbohydrate and protein from the HPI fraction than the granular activated carbon treatment which was used for comparison, it led to better improvement in permeate flux. This was shown to be due to the removal/breakdown of the HPI fraction resulting in less deposition of these organics on the membrane, many components of which are high molecular weight biopolymers (such as protein and carbohydrate molecules) through biodegradation and adsorption of those molecules on the biofilm and activated carbon. This study established the potential of BAC pre-treatment for reducing the HPI fouling of the membrane and thus improving the performance for the MF of BTSE for water reclamation.

Lipo-chitin oligosaccharides, plant symbiosis signalling molecules that modulate mammalian angiogenesis in vitro.

PubMed

Djordjevic, Michael A; Bezos, Anna; Susanti; Marmuse, Laurence; Driguez, Hugues; Samain, Eric; Vauzeilles, Boris; Beau, Jean-Marie; Kordbacheh, Farzaneh; Rolfe, Barry G; Schwörer, Ralf; Daines, Alison M; Gresshoff, Peter M; Parish, Christopher R

2014-01-01

Lipochitin oligosaccharides (LCOs) are signaling molecules required by ecologically and agronomically important bacteria and fungi to establish symbioses with diverse land plants. In plants, oligo-chitins and LCOs can differentially interact with different lysin motif (LysM) receptors and affect innate immunity responses or symbiosis-related pathways. In animals, oligo-chitins also induce innate immunity and other physiological responses but LCO recognition has not been demonstrated. Here LCO and LCO-like compounds are shown to be biologically active in mammals in a structure dependent way through the modulation of angiogenesis, a tightly-regulated process involving the induction and growth of new blood vessels from existing vessels. The testing of 24 LCO, LCO-like or oligo-chitin compounds resulted in structure-dependent effects on angiogenesis in vitro leading to promotion, or inhibition or nil effects. Like plants, the mammalian LCO biological activity depended upon the presence and type of terminal substitutions. Un-substituted oligo-chitins of similar chain lengths were unable to modulate angiogenesis indicating that mammalian cells, like plant cells, can distinguish between LCOs and un-substituted oligo-chitins. The cellular mode-of-action of the biologically active LCOs in mammals was determined. The stimulation or inhibition of endothelial cell adhesion to vitronectin or fibronectin correlated with their pro- or anti-angiogenic activity. Importantly, novel and more easily synthesised LCO-like disaccharide molecules were also biologically active and de-acetylated chitobiose was shown to be the primary structural basis of recognition. Given this, simpler chitin disaccharides derivatives based on the structure of biologically active LCOs were synthesised and purified and these showed biological activity in mammalian cells. Since important chronic disease states are linked to either insufficient or excessive angiogenesis, LCO and LCO-like molecules may have the potential to be a new, carbohydrate-based class of therapeutics for modulating angiogenesis.

Multidirectional Efficacy of Biologically Active Nitro Compounds Included in Medicines.

PubMed

Olender, Dorota; Żwawiak, Justyna; Zaprutko, Lucjusz

2018-05-29

The current concept in searching for new bioactive products, including mainly original active substances with potential application in pharmacy and medicine, is based on compounds with a previously determined structure, well-known properties, and biological activity profile. Nowadays, many commonly used drugs originated from natural sources. Moreover, some natural materials have become the source of leading structures for processing further chemical modifications. Many organic compounds with great therapeutic significance have the nitro group in their structure. Very often, nitro compounds are active substances in many well-known preparations belonging to different groups of medicines that are classified according to their pharmacological potencies. Moreover, the nitro group is part of the chemical structure of veterinary drugs. In this review, we describe many bioactive substances with the nitro group, divided into ten categories, including substances with exciting activity and that are currently undergoing clinical trials.

Design, synthesis, molecular modeling and biological evaluation of novel 2,3-dihydrophthalazine-1,4-dione derivatives as potential anticonvulsant agents

NASA Astrophysics Data System (ADS)

El-Helby, Abdel Ghany A.; Ayyad, Rezk R.; Sakr, Helmy M.; Abdelrahim, Adel S.; El-Adl, K.; Sherbiny, Farag S.; Eissa, Ibrahim H.; Khalifa, Mohamed M.

2017-02-01

In view of their expected anticonvulsant activity, some novel derivatives of 2,3-dihydrophthalazine-1,4-dione 4-22 were designed, synthesized and evaluated using pentylenetetrazole (PTZ) and picrotoxin as convulsion-inducing models. Moreover, the most active compounds were tested against electrical induced convulsion using maximal electroshock (MES) models of seizures. Most of the tested compounds showed considerable anticonvulsant activity in at least one of the anticonvulsant tests. Compounds 13 and 14g were proved to be the most potent compounds of this series with relatively low toxicity in the median lethal dose test when compared with the reference drug. Molecular modeling studies were done to verify the biological activity. The obtained results showed that the most potent compounds could be useful as a template for future design, optimization, and investigation to produce more active analogues.

Dapson in heterocyclic chemistry, part VIII: synthesis, molecular docking and anticancer activity of some novel sulfonylbiscompounds carrying biologically active 1,3-dihydropyridine, chromene and chromenopyridine moieties.

PubMed

Al-Said, Mansour S; Ghorab, Mostafa M; Nissan, Yassin M

2012-07-02

Several new sulfonebiscompounds having a biologically active 1,2-dihydropyridine-2-one 3-19, acrylamide 20, chromene 21, 22 and chromenopyridine 23, 24 moieties were synthesized and evaluated as potential anticancer agents. The structures of the products were confirmed via elemental analyses and spectral data. The screening tests showed that many of the biscompounds obtained exhibited good anticancer activity against human breast cell line (MCF7) comparable to doxorubicin which was used as reference drug. Compounds 11, 17 and 24 showed IC50 values 35.40 μM, 29.86 μM and 30.99 μM, respectively. In order to elucidate the mechanism of action of the synthesized compounds as anticancer agents, docking on the active site of farnesyltransferase and arginine methyltransferase was also performed and good results were obtained.

The relation between growth of four microbes on six different plasterboards and biological activity of spores.

PubMed

Murtoniemi, T; Hirvonen, M-R; Nevalainen, A; Suutari, M

2003-03-01

Microbial growth on water-damaged building materials is commonly associated with adverse health effects in the occupants. We examined the growth of Stachybotrys chartarum, Aspergillus versicolor, Penicillium spinulosum, and Streptomyces californicus, isolated from water-damaged buildings, on six different brands of plasterboards. The microbial growth was compared with the biological activity of the spores, that is the potential to induce cytotoxicity and proinflammatory mediators in RAW264.7 macrophages. These results showed that the microbial growth on plasterboard depended on both the microbial strain and the brand of plasterboard used. The biological activity of spores appeared to be regulated by different growth conditions on plasterboards so that good microbial growth was associated with a low bioactivity of the spores, whereas the spores collected from plasterboard supporting only weak growth usually were biologically active. Cytotoxicity of either S. chartarum or A. versicolor did not correlate with any particular growth conditions or induced inflammatory responses. Instead, there were positive correlations between cytotoxicity and levels of induced proinflammatory cytokines for P. spinulosum and S. californicus. These data suggest that both the microbial growth on plasterboard and the resulting bioactivity of spores vary and might be affected by changing the growth conditions provided by the plasterboards.

Biologically active ligands for yersinia outer protein H (YopH): feature based pharmacophore screening, docking and molecular dynamics studies.

PubMed

Tamilvanan, Thangaraju; Hopper, Waheeta

2014-01-01

Yersinia pestis, a Gram negative bacillus, spreads via lymphatic to lymph nodes and to all organs through the bloodstream, causing plague. Yersinia outer protein H (YopH) is one of the important effector proteins, which paralyzes lymphocytes and macrophages by dephosphorylating critical tyrosine kinases and signal transduction molecules. The purpose of the study is to generate a three-dimensional (3D) pharmacophore model by using diverse sets of YopH inhibitors, which would be useful for designing of potential antitoxin. In this study, we have selected 60 biologically active inhibitors of YopH to perform Ligand based pharmacophore study to elucidate the important structural features responsible for biological activity. Pharmacophore model demonstrated the importance of two acceptors, one hydrophobic and two aromatic features toward the biological activity. Based on these features, different databases were screened to identify novel compounds and these ligands were subjected for docking, ADME properties and Binding energy prediction. Post docking validation was performed using molecular dynamics simulation for selected ligands to calculate the Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF). The ligands, ASN03270114, Mol_252138, Mol_31073 and ZINC04237078 may act as inhibitors against YopH of Y. pestis.

Structure-Based Design: Synthesis, X-ray Crystallography, and Biological Evaluation of N-Substituted-4-Hydroxy-2-Quinolone-3-Carboxamides as Potential Cytotoxic Agents.

PubMed

Sabbah, Dima A; Hishmah, Bayan; Sweidan, Kamal; Bardaweel, Sanaa; AlDamen, Murad; Zhong, Haizhen A; Abu Khalaf, Reema; Hasan Ibrahim, Ameerah; Al-Qirim, Tariq; Abu Sheikha, Ghassan; Mubarak, Mohammad S

2018-01-01

Oncogenic potential of phosphatidylinositol 3-kinase (PI3Kα) has been highlighted as a therapeutic target for anticancer drug design. Target compounds were designed to address the effect of different substitution patterns at the N atom of the carboxamide moiety on the bioactivity of this series. Synthesis of the targeted compounds, crystallography, biological evaluation tests against human colon carcinoma (HCT-116), and Glide docking studies. A new series of N-substituted- 4-hydroxy-2-quinolone-3-carboxamides was prepared and characterized by means of FT-IR, 1H and 13C NMR, and elemental analysis. In addition, the identity of the core nucleus 5 was successfully characterized with the aid of X-ray crystallography. Biological activity of prepared compounds was investigated in vitro against human colon carcinoma (HCT-116) cell line. Results revealed that these compounds inhibit cell proliferation and induce apoptosis through an increase in caspase-3 activity and a decrease in DNA cellular content. Compounds 7, 14, and 17 which have H-bond acceptor moiety on p-position displayed promising PI3Kα inhibitory activity. On the other hand, derivatives tailored with bulky and hydrophobic motifs (16 and 18) on o- and m-positions exhibited moderate activity. Molecular docking studies against PI3Kα and caspase-3 showed an agreement between the predicted binding affinity (ΔGobsd) and IC50 values of the derivatives for the caspase-3 model. Furthermore, Glide docking studies against PI3Kα demonstrated that the newly synthesized compounds accommodate PI3Kα kinase catalytic domain and form H-bonding with key binding residues. The series exhibited a potential PI3Kα inhibitory activity in HCT-116 cell line. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Characterization of the In Vitro Kinetic Interaction of Chlorpyrifos-Oxon with Rat Salivary Cholinesterase: A Potential Biomonitoring Matrix

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kousba, Ahmed A.; Poet, Torka S.; Timchalk, Charles

2003-02-12

Chlorpyrifos (CPF) is a commonly used organophosphate insecticide (OP). The primary mechanism of action for CPF involves the inhibition of acetylcholinesterase (AChE) by the active metabolite, CPF-oxon, with subsequent accumulation of acetylcholine (ACh) resulting in a wide range of neutotoxicity. CPF-oxon, can likewise inhibit other non-target cholinesterases (ChE) such as butyrylcholinesterase (BuChE), which represents a detoxification mechanism and a potential biomarker of exposure/response. Biological monitoring for OPs has focused on measuring parent chemical or metabolite in blood and urine or blood ChE inhibition. Salivary biomonitoring has recently been explored as a practical method for examination of chemical exposure; however, theremore » are a limited number of studies exploring its use for OPs. To evaluate the use of salivary ChE as a biological monitor for OP exposure, the current study characterized salivary ChE activity in Sprague-Dawley rats through its comparison with brain and plasma ChE using BW284C51 and iso-OMPA as selective inhibitors of AChE and BuChE, respectively. The study also estimated the kinetic constants describing BuChE interaction with CPF-oxon. A modified Ellman assay in conjunction with pharmacodynamic (PD) modeling was used to characterize the in vitro titration of diluted rat salivary ChE enzyme with CPF-oxon. The results indicated that, more than 95% of rat salivary ChE activity was associated with BuChE activity, total BuChE active site concentration was 0.0012 0.00013 nmol/ml saliva, reactivation rate constant (Kr) was 0.068 0.008 h-1 and inhibitory (Ki) rate constant of 8.825 and 9.80 nM-1h-1 determined experimentally and using model optimization respectively. These study results would be helpful for further evaluating the potential utility of salivary ChE as a practical tool for biological monitor of OP exposures.« less

Chemistry, Pharmacology and Health Benefits of Anthocyanins.

PubMed

Smeriglio, Antonella; Barreca, Davide; Bellocco, Ersilia; Trombetta, Domenico

2016-08-01

Anthocyanins are naturally occurring molecules belonging to the flavonoid class characterized by the presence of chromophores. Apart from their well-known antioxidant activity, they show a wide variety of health-promoting properties for human health, ranging from cytoprotective, antimicrobial and antitumour activities to neuroprotective, anti-obesity and lipidomic potential, properties for which anthocyanins have been prescribed as medicines in several countries for thousands of years. Despite this, these phytochemicals have received less attention than other flavonoids, and there is still a gap in the literature, particularly regarding pharmacological and toxicological aspects. Moreover, epidemiological evidence suggests a direct correlation between anthocyanin intake and a lower incidence of chronic and degenerative diseases. In light of this, the aim of this review is to cover the current literature on anthocyanins, their biological in vitro and in vivo effects and their potential therapeutic applications, as well as their bioavailability and pharmacokinetics, all of which are essential to gain a better understanding of their biological effectiveness and potential toxicity. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

An investigation into studying of the activated sludge foaming potential by using physicochemical parameters.

PubMed

Hladikova, K; Ruzickova, I; Klucova, P; Wanner, J

2002-01-01

This paper examines how the physicochemical characteristics of the solids are related to foam formation and describes how the foaming potential of full-scale plants can be assessed. The relations among activated sludge and biological foam hydrophobicity, scum index, aeration tank cover and filamentous population are evaluated. Individual parameter comparison reveals the scumming intensity can be estimated only on the assumption that foams is already established. None of the above mentioned characteristics can be reliably used to predict the foaming episodes at wastewater treatment plants.

Synthesis and biological evaluation of 2-thioxopyrimidin-4(1H)-one derivatives as potential non-nucleoside HIV-1 reverse transcriptase inhibitors.

PubMed

Khalifa, Nagy M; Al-Omar, Mohamed A

2014-11-12

A series of new 5-allyl-6-benzylpyrimidin-4(3H)-ones bearing different substituents at the C-2 position of the pyrimidine core have been synthesized and evaluated for their in vitro activities against human immunodeficiency virus type 1 (HIV-1) in the human T-lymphotropic type (MT-4 cell cultures). The majority of the title compounds showed moderate to good activities against HIV-1. Amongst them, 5-allyl-6-benzyl-2-(3-hydroxypropylthio)pyrimidin-4(3H)-one analogue 11c exhibited the most potent anti-HIV-1 activity (IC50 0.32 µM). The biological testing results clearly indicated that the substitution at C-2 position of the pyrimidine ring could increase the anti-HIV-1 reverse transcriptase (RT) activity.

Synthesis and Biological Evaluation of 2-Thioxopyrimidin-4(1H)-one Derivatives as Potential Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors

PubMed Central

Khalifa, Nagy M.; Al-Omar, Mohamed A.

2014-01-01

A series of new 5-allyl-6-benzylpyrimidin-4(3H)-ones bearing different substituents at the C-2 position of the pyrimidine core have been synthesized and evaluated for their in vitro activities against human immunodeficiency virus type 1 (HIV-1) in the human T-lymphotropic type (MT-4 cell cultures). The majority of the title compounds showed moderate to good activities against HIV-1. Amongst them, 5-allyl-6-benzyl-2-(3-hydroxypropylthio)pyrimidin-4(3H)-one analogue 11c exhibited the most potent anti-HIV-1 activity (IC50 0.32 µM). The biological testing results clearly indicated that the substitution at C-2 position of the pyrimidine ring could increase the anti-HIV-1 reverse transcriptase (RT) activity. PMID:25397597

The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study.

PubMed

Millward, M J; House, C; Bowtell, D; Webster, L; Olver, I N; Gore, M; Copeman, M; Lynch, K; Yap, A; Wang, Y; Cohen, P S; Zalcberg, J

2006-10-09

Midostaurin (PKC412A), N-benzoyl-staurosporine, potently inhibits protein kinase C alpha (PKCalpha), VEGFR2, KIT, PDGFR and FLT3 tyrosine kinases. In mice, midostaurin slows growth and delays lung metastasis of melanoma cell lines. We aimed to test midostaurin's safety, efficacy and biologic activity in a Phase IIA clinical trial in patients with metastatic melanoma. Seventeen patients with advanced metastatic melanoma received midostaurin 75 mg p.o. t.i.d., unless toxicity or disease progression supervened. Patient safety was assessed weekly, and tumour response was assessed clinically or by CT. Tumour biopsies and plasma samples obtained at entry and after 4 weeks were analysed for midostaurin concentration, PKC activity and multidrug resistance. No tumour responses were seen. Two (12%) patients had stable disease for 50 and 85 days, with minor response in one. The median overall survival was 43 days. Seven (41%) discontinued treatment with potential toxicity, including nausea, vomiting, diarrhoea and/or fatigue. One patient had >50% reduction in PKC activity. Tumour biopsies showed two PKC isoforms relatively insensitive to midostaurin, out of three patients tested. No modulation of multidrug resistance was demonstrated. At this dose schedule, midostaurin did not show clinical or biologic activity against metastatic melanoma. This negative trial reinforces the importance of correlating biologic and clinical responses in early clinical trials of targeted therapies.

Endophytic actinobacteria: Diversity, secondary metabolism and mechanisms to unsilence biosynthetic gene clusters.

PubMed

Dinesh, Raghavan; Srinivasan, Veeraraghavan; T E, Sheeja; Anandaraj, Muthuswamy; Srambikkal, Hamza

2017-09-01

Endophytic actinobacteria, which reside in the inner tissues of host plants, are gaining serious attention due to their capacity to produce a plethora of secondary metabolites (e.g. antibiotics) possessing a wide variety of biological activity with diverse functions. This review encompasses the recent reports on endophytic actinobacterial species diversity, in planta habitats and mechanisms underlying their mode of entry into plants. Besides, their metabolic potential, novel bioactive compounds they produce and mechanisms to unravel their hidden metabolic repertoire by activation of cryptic or silent biosynthetic gene clusters (BGCs) for eliciting novel secondary metabolite production are discussed. The study also reviews the classical conservative techniques (chemical/biological/physical elicitation, co-culturing) as well as modern microbiology tools (e.g. next generation sequencing) that are being gainfully employed to uncover the vast hidden scaffolds for novel secondary metabolites produced by these endophytes, which would subsequently herald a revolution in drug engineering. The potential role of these endophytes in the agro-environment as promising biological candidates for inhibition of phytopathogens and the way forward to thoroughly exploit this unique microbial community by inducing expression of cryptic BGCs for encoding unseen products with novel therapeutic properties are also discussed.

The Synthesis and Biological Characterization of Acetal-Free Mimics of the Tumor-Associated Carbohydrate Antigens.

PubMed

Sadraei, Seyed I; Reynolds, Michael R; Trant, John F

2017-01-01

Carcinomas express unique carbohydrates, known as tumor-associated carbohydrate antigens (TACAs), on their surface. These are potential targets for anticancer vaccines; however, to date, no such vaccine has reached the clinic. One factor that may complicate the success of this effort is the lability of the glycosidic bond. Acetal-free carbohydrates are analogues that lack the glycosidic linkage by replacing either the endo or exo oxygen with a methylene. This chapter summarizes the seminal syntheses of the mucin TACAs, provides an overview of common techniques for the synthesis of carbasugars and C-glycosides, reviews the syntheses published to date of acetal-free TACA analogues, and provides an overview of their observed biological activity. We conclude by offering a summation of the challenges remaining to the field biologically and the potential that acetal-free TACAs have of answering several basic questions in carbohydrate immunology. © 2017 Elsevier Inc. All rights reserved.

Chronic ozone exposure alters the secondary metabolite profile, antioxidant potential, anti-inflammatory property, and quality of red pepper fruit from Capsicum baccatum.

PubMed

Bortolin, Rafael Calixto; Caregnato, Fernanda Freitas; Divan Junior, Armando Molina; Zanotto-Filho, Alfeu; Moresco, Karla Suzana; Rios, Alessandro de Oliveira; Salvi, Aguisson de Oliveira; Ortmann, Caroline Flach; de Carvalho, Pâmela; Reginatto, Flávio Henrique; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

2016-07-01

Tropospheric ozone (O3) background concentrations have increased since pre-industrial times, reaching phytotoxic concentrations in many regions globally. However, the effect of high O3 concentrations on quality of fruit and vegetables remains unknown. Here, we evaluated whether O3 pollution alters the quality of Capsicum baccatum peppers by changing the secondary compound profiles and biological activity of the fruit. C. baccatum pepper plants were exposed to ozone for 62 days in an open-top chamber at a mean O3 concentration of 171.6µg/m(3). Capsaicin levels decreased by 50% in the pericarp, but remained unchanged in the seeds. In contrast, the total carotenoid content increased by 52.8% in the pericarp. The content of total phenolic compounds increased by 17% in the pericarp. The total antioxidant potential decreased by 87% in seeds of O3-treated plants. The seeds contributed more than the pericarp to the total radical-trapping antioxidant potential and total antioxidant reactivity. O3 treatment impaired the ferric-reducing antioxidant power of the seeds and reduced NO(•)-scavenging activity in the pericarp. However, O3 treatment increased ferrous ion-chelating activity and hydroxyl radical-scavenging activity in the pericarp. Our results confirm that O3 alters the secondary metabolite profile of C. baccatum pepper fruits and, consequently, their biological activity profile. Copyright © 2016 Elsevier Inc. All rights reserved.

Rtt109-dependent histone H3 K56 acetylation and gene activity are essential for the biological control potential of Beauveria bassiana.

PubMed

Cai, Qing; Wang, Juan-Juan; Shao, Wei; Ying, Sheng-Hua; Feng, Ming-Guang

2018-04-27

Rtt109 is a histone acetyltransferase that catalyzes histone H3K56 acetylation required for genomic stability, DNA damage repair and virulence-related gene activity in yeast-like human pathogens but remains functionally unknown in fungal insect pathogens. This study seeks to elucidate catalytic activity of Rtt109 orthologue and its possible role in sustaining biological control potential of Beauveria bassiana, a fungal entomopathogen. Deletion of rtt109 in B. bassiana abolished histone H3K56 acetylation and triggered histone H2A-S129 phosphorylation. Consequently, the deletion mutant showed increased sensitivities to the stresses of DNA damage, oxidation, cell wall perturbation, high osmolarity and heat shock during colony growth, severe conidiation defects under normal culture conditions, reduced conidial hydrophobicity, decreased conidial UV-B resistance, and attenuated virulence through normal cuticle infection. These phenotypic changes correlated well with reduced transcript levels of many genes, which encode the families of H2A-S129 dephosphorylation-related protein phosphotases, DNA damage-repairing factors, antioxidant enzymes, heat-shock proteins, key developmental activators, hydrophobins and cuticle-degrading Pr1 proteases respectively. Rtt109 can acetylate H3K56 and dephosphorylate H2A-S129 in direct and indirect manners respectively, and hence plays an essential role in sustaining genomic stability and global gene activity required for conidiation capacity, environmental fitness and pest-control potential in B. bassiana. This article is protected by copyright. All rights reserved.

Evaluation of hyaluronic acid-protein conjugates for polymer masked-unmasked protein therapy.

PubMed

Ferguson, Elaine L; Alshame, Alshame M J; Thomas, David W

2010-12-15

Bioresponsive polymers may effectively be utilized to enhance the circulation time and stability of biologically active proteins and peptides, while reducing their immunogenicity and toxicity. Recently, dextrin-epidermal growth factor (EGF) conjugates, which make use of the Polymer-masked UnMasked Protein Therapy (PUMPT) concept, have been developed and shown potential as modulators of impaired wound healing. This study investigated the potential of PUMPT using hyaluronic acid (HA) conjugates to mask activity and enhance protein stability, while allowing restoration of biological activity following triggered degradation. HA fragments (Mw ∼90,000g/mol), obtained by acid hydrolysis of Rooster comb HA, were conjugated to trypsin as a model enzyme or to EGF as a model growth factor. Conjugates contained 2.45 and 0.98% (w/w) trypsin or EGF, respectively, and contained <5% free protein. HA conjugation did not significantly alter trypsin's activity. However, incubation of the conjugate with physiological concentrations of HAase increased its activity to ∼145% (p<0.001) that of the free enzyme. In contrast, when HA-EGF conjugates were tested in vitro, no effect on cell proliferation was seen, even in the presence of HAase. HA conjugates did not display typical masking/unmasking behavior, HA-trypsin conjugates exhibited ∼52% greater stability in the presence of elastase, compared to free trypsin, demonstrating the potential of HA conjugates for further development as modulators of tissue repair. Copyright © 2010 Elsevier B.V. All rights reserved.

Biological activity of neosergeolide and isobrucein B (and two semi-synthetic derivatives) isolated from the Amazonian medicinal plant Picrolemma sprucei (Simaroubaceae).

PubMed

Silva, Ellen C C; Cavalcanti, Bruno C; Amorim, Rodrigo C N; Lucena, Jorcilene F; Quadros, Dulcimar S; Tadei, Wanderli P; Montenegro, Raquel C; Costa-Lotufo, Letícia V; Pessoa, Cláudia; Moraes, Manoel O; Nunomura, Rita C S; Nunomura, Sergio M; Melo, Marcia R S; Andrade-Neto, Valter F de; Silva, Luiz Francisco R; Vieira, Pedro Paulo R; Pohlit, Adrian M

2009-02-01

In the present study, in vitro techniques were used to investigate a range of biological activities of known natural quassinoids isobrucein B (1) and neosergeolide (2), known semi-synthetic derivative 1,12-diacetylisobrucein B (3), and a new semi-synthetic derivative, 12-acetylneosergeolide (4). These compounds were evaluated for general toxicity toward the brine shrimp species Artemia franciscana, cytotoxicity toward human tumour cells, larvicidal activity toward the dengue fever mosquito vector Aedes aegypti, haemolytic activity in mouse erythrocytes and antimalarial activity against the human malaria parasite Plasmodium falciparum. Compounds 1 and 2 exhibited the greatest cytotoxicity against all the tumor cells tested (IC50 = 5-27 microg/L) and against multidrug-resistant P. falciparum K1 strain (IC50 = 1.0-4.0 g/L) and 3 was only cytotoxic toward the leukaemia HL-60 strain (IC50 = 11.8 microg/L). Quassinoids 1 and 2 (LC50 = 3.2-4.4 mg/L) displayed greater lethality than derivative 4 (LC50 = 75.0 mg/L) toward A. aegypti larvae, while derivative 3 was inactive. These results suggest a novel application for these natural quassinoids as larvicides. The toxicity toward A. franciscana could be correlated with the activity in several biological models, a finding that is in agreement with the literature. Importantly, none of the studied compounds exhibited in vitro haemolytic activity, suggesting specificity of the observed cytotoxic effects. This study reveals the biological potential of quassinoids 1 and 2 and to a lesser extent their semi-synthetic derivatives for their in vitro antimalarial and cytotoxic activities.

Comparative Study of the Biological Activity of Allantoin and Aqueous Extract of the Comfrey Root.

PubMed

Savić, Vesna Lj; Nikolić, Vesna D; Arsić, Ivana A; Stanojević, Ljiljana P; Najman, Stevo J; Stojanović, Sanja; Mladenović-Ranisavljević, Ivana I

2015-08-01

This study investigates the biological activity of pure allantoin (PA) and aqueous extract of the comfrey (Symphytum officinale L.) root (AECR) standardized to the allantoin content. Cell viability and proliferation of epithelial (MDCK) and fibroblastic (L929) cell line were studied by using MTT test. Anti-irritant potential was determined by measuring electrical capacitance, erythema index (EI) and transepidermal water loss of artificially irritated skin of young healthy volunteers, 3 and 7 days after application of creams and gels with PA or AECR. Pure allantoin showed mild inhibitory effect on proliferation of both cell lines at concentrations 40 and 100 µg/ml, but more pronounced on MDCK cells. Aqueous extract of the comfrey root effect on cell proliferation in concentrations higher than 40 µg/ml was significantly stimulatory for L929 but inhibitory for MDCK cells. Pharmaceutical preparations that contained AECR showed better anti-irritant potential compared with PA. Creams showed better effect on hydration and EI compared with the gels that contained the same components. Our results indicate that the biological activity of the comfrey root extract cannot be attributed only to allantoin but is also likely the result of the interaction of different compounds present in AECR. Topical preparations that contain comfrey extract may have a great application in the treatment of skin irritation. Copyright © 2015 John Wiley & Sons, Ltd.

Synthesizing a Berberine Derivative and Evaluating Antimicrobial Activity to Reinforce with Students the Potential Significance of Small Chemical Structure Changes for Biological Systems

ERIC Educational Resources Information Center

Rodrigues, Catarina A. B.; Neto, Iris; Rijo, Patricia; Afonso, Carlos A. M.

2018-01-01

The convenient synthesis of dihydroberberine by the reduction of berberine is described as an experiment for an upper-division undergraduate organic chemistry laboratory course. Students obtained up to 74% yield of the desired pure product without the use of chromatographic techniques. The antimicrobial activities of both compounds against…

Counter-Chemical, Biological, Radiological, and Nuclear Operations

DTIC Science & Technology

2007-01-26

environment. (Page 10) Consequence management activities serve to reduce the effects of a CBRN attack or event, and assist in the restoration of...can be used quite effectively as attack agents. Toxic Industrial Chemicals (TICs), Toxic Industrial Materials (TIMs), and other potentially...CBRN pillars. Consequence Management Consequence management (CM) activities serve to reduce the effects of a CBRN attack or event, and assist in

Angiotensin-Converting Enzyme 2 Metabolizes and Partially Inactivates Pyr-Apelin-13 and Apelin-17: Physiological Effects in the Cardiovascular System.

PubMed

Wang, Wang; McKinnie, Shaun M K; Farhan, Maikel; Paul, Manish; McDonald, Tyler; McLean, Brent; Llorens-Cortes, Catherine; Hazra, Saugata; Murray, Allan G; Vederas, John C; Oudit, Gavin Y

2016-08-01

Apelin peptides mediate beneficial effects on the cardiovascular system and are being targeted as potential new drugs. However, apelin peptides have extremely short biological half-lives, and improved understanding of apelin peptide metabolism may lead to the discovery of biologically stable analogues with therapeutic potential. We examined the ability of angiotensin-converting enzyme 2 (ACE2) to cleave and inactivate pyr-apelin 13 and apelin 17, the dominant apelin peptides. Computer-assisted modeling shows a conserved binding of pyr-apelin 13 and apelin 17 to the ACE2 catalytic site. In ACE2 knockout mice, hypotensive action of pyr-apelin 13 and apelin 17 was potentiated, with a corresponding greater elevation in plasma apelin levels. Similarly, pharmacological inhibition of ACE2 potentiated the vasodepressor action of apelin peptides. Biochemical analysis confirmed that recombinant human ACE2 can cleave pyr-apelin 13 and apelin 17 efficiently, and apelin peptides are degraded slower in ACE2-deficient plasma. The biological relevance of ACE2-mediated proteolytic processing of apelin peptides was further supported by the reduced potency of pyr-apelin 12 and apelin 16 on the activation of signaling pathways and nitric oxide production from endothelial cells. Importantly, although pyr-apelin 13 and apelin 17 rescued contractile function in a myocardial ischemia-reperfusion model, ACE2 cleavage products, pyr-apelin 12 and 16, were devoid of these cardioprotective effects. We designed and synthesized active apelin analogues that were resistant to ACE2-mediated degradation, thereby confirming that stable apelin analogues can be designed as potential drugs. We conclude that ACE2 represents a major negative regulator of apelin action in the vasculature and heart. © 2016 American Heart Association, Inc.

New insights into the enhancement of biochemical degradation potential from waste activated sludge with low organic content by Potassium Monopersulfate treatment.

PubMed

Jin, Baodan; Niu, Jintao; Dai, Jingwen; Li, Nuonan; Zhou, Ping; Niu, Jiahui; Zhang, Ju; Tao, Hongfan; Ma, Zhigang; Zhang, Zhongfang

2018-05-18

Waste activated sludge with low organic content (WAS-LOC) always led to the failure of anaerobic fermentation. A potentially practical technology based on SO 4 - , i.e. Potassium Monopersulfate (PMS) was used into WAS-LOC anaerobic fermentation system and had been presented to greatly improve both the intracellular and extracellular constituents, which improved the biological enzyme activity and produced a mass of short-chain fatty acids (SCFAs). Results showed that the maximal SCFAs production was 716.72 mg chemical oxygen demand (COD)/L (0.08 mg PMS/mg SS), which increased to 43.70 times comparing to that of 0.00 mg PMS/mg SS level (16.40 mgCOD/L). The activities of biological enzymes increased 1.42 times for protease, 4.38 times for α-glucosidase, 2.1 times for alkaline phosphatase, 1.70 times for acidic phosphatase and 1.37 times for dehydrogenase respectively comparing to natural fermentation system, but the coenzyme 420 was restrained prominently. PMS positively enriched the abundance of microbial community responsible for WAS-LOC hydrolysis and SCFAs production. Copyright © 2018 Elsevier Ltd. All rights reserved.

Functional evaluation of synthetic flavonoids and chalcones for potential antiviral and anticancer properties.

PubMed

Mateeva, Nelly; Eyunni, Suresh V K; Redda, Kinfe K; Ononuju, Ucheze; Hansberry, Tony D; Aikens, Cecilia; Nag, Anita

2017-06-01

Flavonoids, stilbenes, and chalcones are plant secondary metabolites that often possess diverse biological activities including anti-inflammatory, anti-cancer, and anti-viral activities. The wide range of bioactivities poses a challenge to identify their targets. Here, we studied a set of synthetically generated flavonoids and chalcones to evaluate for their biological activity, and compared similarly substituted flavonoids and chalcones. Substituted chalcones, but not flavonoids, showed inhibition of viral translation without significantly affecting viral replication in cells infected with hepatitis C virus (HCV). We suggest that the chalcones used in this study inhibit mammalian target of rapamycin (mTOR) pathway by ablating phosphorylation of ribosomal protein 6 (rps6), and also the kinase necessary for phosphorylating rps6 in Huh7.5 cells (pS6K1). In addition, selected chalcones showed inhibition of growth in Ishikawa, MCF7, and MDA-MB-231 cells resulting an IC 50 of 1-6µg/mL. When similarly substituted flavonoids were used against the same set of cancer cells, we did not observe any inhibitory effect. Together, we report that chalcones show potential for anti-viral and anti-cancer activities compared to similarly substituted flavonoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Medicinal chemistry and pharmacology focused on cannabidiol, a major component of the fiber-type cannabis].

PubMed

Takeda, Shuso

2013-01-01

Considerable attention has focused on cannabidiol (CBD), a major non-psychotropic constituent of fiber-type cannabis plant, and it has been reported to possess diverse biological activities. Although CBD is obtained from non-enzymatic decarboxylation of its parent molecule, cannabidiolic acid (CBDA), several studies have investigated whether CBDA itself is biologically active. In the present report, the author summarizes findings indicating that; 1) CBDA is a selective cyclooxygenase-2 (COX-2) inhibitor, and ii) CBDA possesses an anti-migrative potential for highly invasive cancer cells, apparently through a mechanism involving inhibition of cAMP-dependent protein kinase A, coupled with an activation of the small GTPase, RhoA. Further, the author introduces recent findings on the medicinal chemistry and pharmacology of the CBD derivative, CBD-2',6'-dimethyl ether (CBDD), that exhibits inhibitory activity toward 15-lipoxygenase (15-LOX), an enzyme responsible for the production of oxidized low-density lipoprotein (LDL). These studies establish CBD as both an important experimental tool and as a lead compound for pharmaceutical development. In this review, the author further discusses the potential uses of CBD and its derivatives in future medicines.

Characterization and structure elucidation of antibacterial compound of Streptomyces sp. ECR77 isolated from east coast of India.

PubMed

Thirumurugan, D; Vijayakumar, R

2015-05-01

Forty marine actinobacteria were isolated from the sediments of east coast (Bay of Bengal) region of Tamilnadu, India. Morphologically distinct colonies were primarily tested against fish pathogenic bacteria such as Vibrio cholerae, V. parahaemolyticus, V. alginolyticus, Pseudomonas fluorescens and Aeromonas hydrophila by cross-streak plate method. The secondary metabolites produced by the highly potential strain cultured on starch casein broth were extracted separately with various solvents such as alcohol, ethyl acetate, methanol, petroleum ether and chloroform. The antibacterial assay of the bioactive compounds was tested against the fish pathogenic bacteria by well diffusion method. Of the various solvents used, the ethyl acetate extract of the isolate had good antibacterial activity. The potential strain was identified as Streptomyces labedae by phenotypic, 16S rRNA gene sequence and phylogenetic analysis. Purification of the biologically active compounds by column chromatography led to isolation of 27 fractions. The biologically active fraction was re-chromatographed on a silica gel column to obtain a single active compound, namely N-isopentyltridecanamide. The structure of the compounds was elucidated on the basis of ultra violet, Fourier transform infrared and nuclear magnetic resonance spectra.

Enhanced Removal of Lead by Chemically and Biologically Treated Carbonaceous Materials

PubMed Central

Mahmoud, Mohamed E.; Osman, Maher M.; Ahmed, Somia B.; Abdel-Fattah, Tarek M.

2012-01-01

Hybrid sorbents and biosorbents were synthesized via chemical and biological treatment of active carbon by simple and direct redox reaction followed by surface loading of baker's yeast. Surface functionality and morphology of chemically and biologically modified sorbents and biosorbents were studied by Fourier Transform Infrared analysis and scanning electron microscope imaging. Hybrid carbonaceous sorbents and biosorbents were characterized by excellent efficiency and superiority toward lead(II) sorption compared to blank active carbon providing a maximum sorption capacity of lead(II) ion as 500 μmol g−1. Sorption processes of lead(II) by these hybrid materials were investigated under the influence of several controlling parameters such as pH, contact time, mass of sorbent and biosorbent, lead(II) concentration, and foreign ions. Lead(II) sorption mechanisms were found to obey the Langmuir and BET isotherm models. The potential applications of chemically and biologically modified-active carbonaceous materials for removal and extraction of lead from real water matrices were also studied via a double-stage microcolumn technique. The results of this study were found to denote to superior recovery values of lead (95.0–99.0 ± 3.0–5.0%) by various carbonaceous-modified-bakers yeast biosorbents. PMID:22629157

Natural Proline-Rich Cyclopolypeptides from Marine Organisms: Chemistry, Synthetic Methodologies and Biological Status.

PubMed

Fang, Wan-Yin; Dahiya, Rajiv; Qin, Hua-Li; Mourya, Rita; Maharaj, Sandeep

2016-10-26

Peptides have gained increased interest as therapeutics during recent years. More than 60 peptide drugs have reached the market for the benefit of patients and several hundreds of novel therapeutic peptides are in preclinical and clinical development. The key contributor to this success is the potent and specific, yet safe, mode of action of peptides. Among the wide range of biologically-active peptides, naturally-occurring marine-derived cyclopolypeptides exhibit a broad range of unusual and potent pharmacological activities. Because of their size and complexity, proline-rich cyclic peptides (PRCPs) occupy a crucial chemical space in drug discovery that may provide useful scaffolds for modulating more challenging biological targets, such as protein-protein interactions and allosteric binding sites. Diverse pharmacological activities of natural cyclic peptides from marine sponges, tunicates and cyanobacteria have encouraged efforts to develop cyclic peptides with well-known synthetic methods, including solid-phase and solution-phase techniques of peptide synthesis. The present review highlights the natural resources, unique structural features and the most relevant biological properties of proline-rich peptides of marine-origin, focusing on the potential therapeutic role that the PRCPs may play as a promising source of new peptide-based novel drugs.

Second generation benzofuranone ring substituted noscapine analogs: Synthesis and biological evaluation

PubMed Central

Mishra, Ram Chandra; Karna, Prasanthi; Gundala, Sushma Reddy; Pannu, Vaishali; Stanton, Richard A.; Gupta, Kamlesh Kumar; Robinson, Mary; Lopus, Manu; Wilson, Leslie; Henary, Maged; Aneja, Ritu

2011-01-01

Microtubules, composed of α/β tubulin heterodimers, represent a validated target for cancer chemotherapy. Thus, tubulin- and microtubule-binding antimitotic drugs such as taxanes and vincas are widely employed for the chemotherapeutic management of various malignancies. Although quite successful in the clinic, these drugs are associated with severe toxicity and drug resistance problems. Noscapinoids represent an emerging class of microtubule-modulating anticancer agents based upon the parent molecule noscapine, a naturally-occurring non-toxic cough-suppressant opium alkaloid. Here we report in silico molecular modeling, chemical synthesis and biological evaluation of novel analogs derived by modification at position-7 of the benzofuranone ring system of noscapine. The synthesized analogs were evaluated for their tubulin polymerization activity and their biological activity was examined by their antiproliferative potential using representative cancer cell lines from varying tissue-origin [A549 (lung), CEM (lymphoma), MIA PaCa-2 (pancreatic), MCF-7 (breast) and PC-3 (prostate)]. Cell-cycle studies were performed to explore their ability to halt the cell-cycle and induce subsequent apoptosis. The varying biological activity of these analogs that differ in the nature and bulk of substituent at position-7 was rationalized utilizing predictive in silico molecular modeling. PMID:21501599

Natural Proline-Rich Cyclopolypeptides from Marine Organisms: Chemistry, Synthetic Methodologies and Biological Status

PubMed Central

Fang, Wan-Yin; Dahiya, Rajiv; Qin, Hua-Li; Mourya, Rita; Maharaj, Sandeep

2016-01-01

Peptides have gained increased interest as therapeutics during recent years. More than 60 peptide drugs have reached the market for the benefit of patients and several hundreds of novel therapeutic peptides are in preclinical and clinical development. The key contributor to this success is the potent and specific, yet safe, mode of action of peptides. Among the wide range of biologically-active peptides, naturally-occurring marine-derived cyclopolypeptides exhibit a broad range of unusual and potent pharmacological activities. Because of their size and complexity, proline-rich cyclic peptides (PRCPs) occupy a crucial chemical space in drug discovery that may provide useful scaffolds for modulating more challenging biological targets, such as protein-protein interactions and allosteric binding sites. Diverse pharmacological activities of natural cyclic peptides from marine sponges, tunicates and cyanobacteria have encouraged efforts to develop cyclic peptides with well-known synthetic methods, including solid-phase and solution-phase techniques of peptide synthesis. The present review highlights the natural resources, unique structural features and the most relevant biological properties of proline-rich peptides of marine-origin, focusing on the potential therapeutic role that the PRCPs may play as a promising source of new peptide-based novel drugs. PMID:27792168

Effects of humic acids from landfill leachate on plants: An integrated approach using chemical, biochemical and cytogenetic analysis.

PubMed

Morozesk, Mariana; Bonomo, Marina Marques; Souza, Iara da Costa; Rocha, Lívia Dorsch; Duarte, Ian Drumond; Martins, Ian Oliveira; Dobbss, Leonardo Barros; Carneiro, Maria Tereza Weitzel Dias; Fernandes, Marisa Narciso; Matsumoto, Silvia Tamie

2017-10-01

Biological process treatment of landfill leachate produces a significant amount of sludge, characterized by high levels of organic matter from which humic acids are known to activate several enzymes of energy metabolism, stimulating plant growth. This study aimed to characterize humic acids extracted from landfill sludge and assess the effects on plants exposed to different concentrations (0.5, 1, 2 and 4 mM C L -1 ) by chemical and biological analysis, to elucidate the influence of such organic material and minimize potential risks of using sludge in natura. Landfill humic acids showed high carbon and nitrogen levels, which may represent an important source of nutrients for plants. Biochemical analysis demonstrated an increase of enzyme activity, especially H + -ATPase in 2 mM C L -1 landfill humic acid. Additionally, cytogenetic alterations were observed in meristematic and F 1 cells, through nuclear abnormalities and micronuclei. Multivariate statistical analysis provided integration of physical, chemical and biological data. Despite all the nutritional benefits of humic acids and their activation of plant antioxidant systems, the observed biological effects showed concerning levels of mutagenicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

ToxCast: Using high throughput screening to identify profiles of biological activity

EPA Science Inventory

ToxCast, the United States Environmental Protection Agency’s chemical prioritization research program, is developing methods for utilizing computational chemistry and bioactivity profiling to predict potential for toxicity and prioritize limited testing resources (www.epa.gov/toc...

Applications of high throughput screening to identify profiles of biological activity

EPA Science Inventory

ToxCast, the United States Environmental Protection Agency’s chemical prioritization research program, is developing methods for utilizing computational chemistry and bioactivity profiling to predict potential for toxicity and prioritize limited testing resources (www.epa.gov/toc...

Emerging mechanistic targets in lung injury induced by combustion-generated particles.

EPA Science Inventory

ABSTRACT The mechanism for biological effect following pulmonary exposure to combustion-generated particles is incompletely defined. Transient receptor potential (TRP) cation channels were identified as “particle sensors” in that their activation was coupled with the initiation ...

Structure investigation of three hydrazones Schiff's bases by spectroscopic, thermal and molecular orbital calculations and their biological activities

NASA Astrophysics Data System (ADS)

Belal, Arafa A. M.; Zayed, M. A.; El-Desawy, M.; Rakha, Sh. M. A. H.

2015-03-01

Three Schiff's bases AI (2(1-hydrazonoethyl)phenol), AII (2, 4-dibromo 6-(hydrazonomethyl)phenol) and AIII (2(hydrazonomethyl)phenol) were prepared as new hydrazone compounds via condensation reactions with molar ratio (1:1) of reactants. Firstly by reaction of 2-hydroxy acetophenone solution and hydrazine hydrate; it gives AI. Secondly condensation between 3,5-dibromo-salicylaldehyde and hydrazine hydrate gives AII. Thirdly condensation between salicylaldehyde and hydrazine hydrate gives AIII. The structures of AI-AIII were characterized by elemental analysis (EA), mass (MS), FT-IR and 1H NMR spectra, and thermal analyses (TG, DTG, and DTA). The activation thermodynamic parameters, such as, ΔE∗, ΔH∗, ΔS∗ and ΔG∗ were calculated from the TG curves using Coats-Redfern method. It is important to investigate their molecular structures to know the active groups and weak bond responsible for their biological activities. Consequently in the present work, the obtained thermal (TA) and mass (MS) practical results are confirmed by semi-empirical MO-calculations (MOCS) using PM3 procedure. Their biological activities have been tested in vitro against Escherichia coli, Proteus vulgaris, Bacillissubtilies and Staphylococcus aurous bacteria in order to assess their anti-microbial potential.

Evaluation of Antioxidant, Anticholinesterase, and Antidiabetic Potential of Dry Leaves and Stems in Tamarix aphylla Growing Wild in Tunisia.

PubMed

Mahfoudhi, Adel; Grosso, Clara; Gonçalves, Rui F; Khelifi, Eltaief; Hammami, Saoussen; Achour, Sami; Trabelsi-Ayadi, Malika; Valentão, Patrícia; Andrade, Paula B; Mighri, Zine

2016-12-01

Tamarix aphylla (L.) Karst. has a wide geographic distribution and was employed in traditional medicine as astringent, anti-rheumatic and to treat fever. T. aphylla leaves and stems extracts were studied from both chemical and biological points of view to assess the antidiabetic, anticholinesterase and antioxidant potential of this species. The HPLC/Diode Array Detector (DAD) analysis showed the presence of 14 phenolic compounds (gallic, caffeic, p-coumaric, ferulic and ellagic acids, kaempferol, quercetin, quercetin 3-O-galactoside and six flavonol derivatives). This is the first study reporting a comparative study of the biological activities of different extracts from T. aphylla. High activities were obtained against DPPH radical, superoxide anion radical (O2∙-) and nitric oxide radical ( • NO) in a concentration-dependent manner, the most active extracts being the polar ones. T. aphylla also showed moderate protective effects against acetylcholinesterase, but no effects were observed against butyrylcholinesterase. Against α-glucosidase the MeOH extracts displayed IC 50 values from 8.41 to 24.81 μg/ml. © 2016 Wiley-VHCA AG, Zurich, Switzerland.

Proteomic characterisation of toxins isolated from nematocysts of the South Atlantic jellyfish Olindias sambaquiensis.

PubMed

Weston, Andrew J; Chung, Ray; Dunlap, Walter C; Morandini, André C; Marques, Antonio C; Moura-da-Silva, Ana M; Ward, Malcolm; Padilla, Gabriel; da Silva, Luiziana Ferreira; Andreakis, Nikos; Long, Paul F

2013-09-01

Surprisingly little is known of the toxic arsenal of cnidarian nematocysts compared to other venomous animals. Here we investigate the toxins of nematocysts isolated from the jellyfish Olindias sambaquiensis. A total of 29 unique ms/ms events were annotated as potential toxins homologous to the toxic proteins from diverse animal phyla, including cone-snails, snakes, spiders, scorpions, wasp, bee, parasitic worm and other Cnidaria. Biological activities of these potential toxins include cytolysins, neurotoxins, phospholipases and toxic peptidases. The presence of several toxic enzymes is intriguing, such as sphingomyelin phosphodiesterase B (SMase B) that has only been described in certain spider venoms, and a prepro-haystatin P-IIId snake venom metalloproteinase (SVMP) that activates coagulation factor X, which is very rare even in snake venoms. Our annotation reveals sequence orthologs to many representatives of the most important superfamilies of peptide venoms suggesting that their origins in higher organisms arise from deep eumetazoan innovations. Accordingly, cnidarian venoms may possess unique biological properties that might generate new leads in the discovery of novel pharmacologically active drugs. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Antibacterial activity of extracts from five medicinal plants and their formula against bacteria that cause chronic wound infection.

PubMed

Temrangsee, Pornthep; Kondo, Sumalee; Itharat, Arunporn

2011-12-01

Chronic wound is caused by various factors such as chemotherapy, gene damage, treatment with steroids, diabetes mellitus, renal failure, blood pressure, infection and nutritional factors. One of the most common causes is bacterial infection. Antibacterial activity of several herbal plants has been reported. Thai medicinal plants which possess biological activities are potential to develop an alternative treatment of bacterial infection. To study efficiency of extracts from medicinal plants and their formula against bacteria that cause chronic wound infection. Extraction of Thai medicinal plants including Curcuma longa Linn, Rhinacanthus nasutus Linn, Garcinia mangostana Linn, Caesalpinia sappan Linn and Centellia asiatica Linn was performed by maceration with 95% ethanol and decoction followed by freeze dry. Formulation was conducted by varying the ratio of each components. Antibacterial activity were determined disk diffusion and broth dilution against Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter baumanii, Escherichia coli and Klebsiella pneumoniae. Ethanolic extracts exhibited better antibacterial activity against tested strains than water extracts. Antibacterial activity of Caesalpinia sappan Linn. against S. aureus and MRSA showed the most effective with MIC value of 0.625 mg/ml. One of the five different formulas which contained two times proportion of C. sappan revealed that this formula was able to inhibit all tested strains with the MIC ranging between 0.156 mg/ml and 10 mg/ml. C. sappan is the most effective herbal plant. The formula with two times proportion of C. sappan is potentially best formula for development of medicinal product of chronic wound infection. The potential active compound of C. sappan is suggested for further investigation of antimicrobial activity and other biological properties.

Synthesis, characterization and deepening in the comprehension of the biological action mechanisms of a new nickel complex with antiproliferative activity.

PubMed

Buschini, Annamaria; Pinelli, Silvana; Pellacani, Claudia; Giordani, Federica; Ferrari, Marisa Belicchi; Bisceglie, Franco; Giannetto, Marco; Pelosi, Giorgio; Tarasconi, Pieralberto

2009-05-01

Thiosemicarbazones are versatile organic compounds that present considerable pharmaceutical interest because of a wide range of properties. In our laboratory we synthesised some new metal-complexes with thiosemicarbazones derived from natural aldehydes which showed peculiar biological activities. In particular, a nickel complex [Ni(S-tcitr)(2)] (S-tcitr=S-citronellalthiosemicarbazonate) was observed to induce an antiproliferative effect on U937, a human histiocytic lymphoma cell line, at low concentrations (IC(50)=14.4microM). Therefore, we decided to study the interactions of this molecule with various cellular components and to characterise the induced apoptotic pathway. Results showed that [Ni(S-tcitr)(2)] causes programmed cell death via down-regulation of Bcl-2, alteration of mitochondrial membrane potential and caspase-3 activity, regardless of p53 function. The metal complex is not active on G(0) cells (i.e. fresh leukocytes) but is able to induce perturbation of the cell cycle on stimulated lymphocytes and U937 cells, in which a G(2)/M block was detected. It reaches the nucleus where it induces, at low concentrations (2.5-5.0microM), DNA damage, which could be partially ascribed to oxidative stress. [Ni(S-tcitr)(2)] is moreover able to strongly reduce the telomerase activity. Although the biological target of this metal complex is still unknown, the reported data suggest that [Ni(S-tcitr)(2)] could be a good model for the synthesis of new metal thiosemicarbazones with specific biological activity.

Mitochondrial pharmacology: electron transport chain bypass as strategies to treat mitochondrial dysfunction.

PubMed

Atamna, Hani; Mackey, Jeanette; Dhahbi, Joseph M

2012-01-01

Mitochondrial dysfunction (primary or secondary) is detrimental to intermediary metabolism. Therapeutic strategies to treat/prevent mitochondrial dysfunction could be valuable for managing metabolic and age-related disorders. Here, we review strategies proposed to treat mitochondrial impairment. We then concentrate on redox-active agents, with mild-redox potential, who shuttle electrons among specific cytosolic or mitochondrial redox-centers. We propose that specific redox agents with mild redox potential (-0.1 V; 0.1 V) improve mitochondrial function because they can readily donate or accept electrons in biological systems, thus they enhance metabolic activity and prevent reactive oxygen species (ROS) production. These agents are likely to lack toxic effects because they lack the risk of inhibiting electron transfer in redox centers. This is different from redox agents with strong negative (-0.4 V; -0.2 V) or positive (0.2 V; 0.4 V) redox potentials who alter the redox status of redox-centers (i.e., become permanently reduced or oxidized). This view has been demonstrated by testing the effect of several redox active agents on cellular senescence. Methylene blue (MB, redox potential ≅10 mV) appears to readily cycle between the oxidized and reduced forms using specific mitochondrial and cytosolic redox centers. MB is most effective in delaying cell senescence and enhancing mitochondrial function in vivo and in vitro. Mild-redox agents can alter the biochemical activity of specific mitochondrial components, which then in response alters the expression of nuclear and mitochondrial genes. We present the concept of mitochondrial electron-carrier bypass as a potential result of mild-redox agents, a method to prevent ROS production, improve mitochondrial function, and delay cellular aging. Thus, mild-redox agents may prevent/delay mitochondria-driven disorders. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Modulating the Biologic Activity of Mesenteric Lymph after Traumatic Shock Decreases Systemic Inflammation and End Organ Injury.

PubMed

Langness, Simone; Costantini, Todd W; Morishita, Koji; Eliceiri, Brian P; Coimbra, Raul

2016-01-01

Trauma/hemorrhagic shock (T/HS) causes the release of pro-inflammatory mediators into the mesenteric lymph (ML), triggering a systemic inflammatory response and acute lung injury (ALI). Direct and pharmacologic vagal nerve stimulation prevents gut barrier failure and alters the biologic activity of ML after injury. We hypothesize that treatment with a pharmacologic vagal agonist after T/HS would attenuate the biologic activity of ML and prevent ALI. ML was collected from male Sprague-Dawley rats after T/HS, trauma-sham shock (T/SS) or T/HS with administration of the pharmacologic vagal agonist CPSI-121. ML samples from each experimental group were injected into naïve mice to assess biologic activity. Blood samples were analyzed for changes in STAT3 phosphorylation (pSTAT3). Lung injury was characterized by histology, permeability and immune cell recruitment. T/HS lymph injected in naïve mice caused a systemic inflammatory response characterized by hypotension and increased circulating monocyte pSTAT3 activity. Injection of T/HS lymph also resulted in ALI, confirmed by histology, lung permeability and increased recruitment of pulmonary macrophages and neutrophils to lung parenchyma. CPSI-121 attenuated T/HS lymph-induced systemic inflammatory response and ALI with stable hemodynamics and similar monocyte pSTAT3 levels, lung histology, lung permeability and lung immune cell recruitment compared to animals injected with lymph from T/SS. Treatment with CPSI-121 after T/HS attenuated the biologic activity of the ML and decreased ALI. Given the superior clinical feasibility of utilizing a pharmacologic approach to vagal nerve stimulation, CPSI-121 is a potential treatment strategy to limit end organ dysfunction after injury.

Systems Biology Graphical Notation: Entity Relationship language Level 1 Version 2.

PubMed

Sorokin, Anatoly; Le Novère, Nicolas; Luna, Augustin; Czauderna, Tobias; Demir, Emek; Haw, Robin; Mi, Huaiyu; Moodie, Stuart; Schreiber, Falk; Villéger, Alice

2015-09-04

The Systems Biological Graphical Notation (SBGN) is an international community effort for standardized graphical representations of biological pathways and networks. The goal of SBGN is to provide unambiguous pathway and network maps for readers with different scientific backgrounds as well as to support efficient and accurate exchange of biological knowledge between different research communities, industry, and other players in systems biology. Three SBGN languages, Process Description (PD), Entity Relationship (ER) and Activity Flow (AF), allow for the representation of different aspects of biological and biochemical systems at different levels of detail. The SBGN Entity Relationship language (ER) represents biological entities and their interactions and relationships within a network. SBGN ER focuses on all potential relationships between entities without considering temporal aspects. The nodes (elements) describe biological entities, such as proteins and complexes. The edges (connections) provide descriptions of interactions and relationships (or influences), e.g., complex formation, stimulation and inhibition. Among all three languages of SBGN, ER is the closest to protein interaction networks in biological literature and textbooks, but its well-defined semantics offer a superior precision in expressing biological knowledge.

[Biological activity of fungi from the phyllosphere of weeds and wild herbaceous plants].

PubMed

Berestitskiĭ, A O; Gasich, E L; Poluéktova, E V; Nikolaeva, E V; Sokornova, S V; Khlopunova, L B

2014-01-01

Antimicrobial, phytotoxic, and insecticidal activity of 30 fungal isolates obtained from leaves of weeds and wild herbaceous plants was assessed. Antibacterial, antifungal, phytotoxic, and insecticidal activity was found in over 50, 40, 47, and 40% of the isolates, respectively. These findings may be important for toxicological assessment of potential mycoherbicides, as well as provide a basis for investigation of the patterns of development of phyllosphere communities affected by fungal metabolites.

Surface grafting of zwitterionic polymers onto dye doped AIE-active luminescent silica nanoparticles through surface-initiated ATRP for biological imaging applications

NASA Astrophysics Data System (ADS)

Mao, Liucheng; Liu, Xinhua; Liu, Meiying; Huang, Long; Xu, Dazhuang; Jiang, Ruming; Huang, Qiang; Wen, Yuanqing; Zhang, Xiaoyong; Wei, Yen

2017-10-01

Aggregation-induced emission (AIE) dyes have recently been intensively explored for biological imaging applications owing to their outstanding optical feature as compared with conventional organic dyes. The AIE-active luminescent silica nanoparticles (LSNPs) are expected to combine the advantages both of silica nanoparticles and AIE-active dyes. Although the AIE-active LSNPs have been prepared previously, surface modification of these AIE-active LSNPs with functional polymers has not been reported thus far. In this work, we reported a rather facile and general strategy for preparation of polymers functionalized AIE-active LSNPs through the surface-initiated atom transfer radical polymerization (ATRP). The AIE-active LSNPs were fabricated via direct encapsulation of AIE-active dye into silica nanoparticles through a non-covalent modified Stöber method. The ATRP initiator was subsequently immobilized onto these AIE-active LSNPs through amidation reaction between 3-aminopropyl-triethoxy-silane and 2-bromoisobutyryl bromide. Finally, the zwitterionic 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) was selected as model monomer and grafted onto MSNs through ATRP. The characterization results suggested that LSNPs can be successfully modified with poly(MPC) through surface-initiated ATRP. The biological evaluation results demonstrated that the final SNPs-AIE-pMPC composites possess low cytotoxicity, desirable optical properties and great potential for biological imaging. Taken together, we demonstrated that AIE-active LSNPs can be fabricated and surface modified with functional polymers to endow novel functions and better performance for biomedical applications. More importantly, this strategy developed in this work could also be extended for fabrication of many other LSNPs polymer composites owing to the good monomer adoptability of ATRP.

Identification of Novel Activators of Constitutive Androstane Receptor from FDA-approved Drugs by Integrated Computational and Biological Approaches

PubMed Central

Lynch, Caitlin; Pan, Yongmei; Li, Linhao; Ferguson, Stephen S.; Xia, Menghang; Swaan, Peter W.; Wang, Hongbing

2012-01-01

Purpose The constitutive androstane receptor (CAR, NR1I3) is a xenobiotic sensor governing the transcription of numerous hepatic genes associated with drug metabolism and clearance. Recent evidence suggests that CAR also modulates energy homeostasis and cancer development. Thus, identification of novel human (h) CAR activators is of both clinical importance and scientific interest. Methods Docking and ligand-based structure-activity models were used for virtual screening of a database containing over 2000 FDA-approved drugs. Identified lead compounds were evaluated in cell-based reporter assays to determine hCAR activation. Potential activators were further tested in human primary hepatocytes (HPHs) for the expression of the prototypical hCAR target gene CYP2B6. Results Nineteen lead compounds with optimal modeling parameters were selected for biological evaluation. Seven of the 19 leads exhibited moderate to potent activation of hCAR. Five out of the seven compounds translocated hCAR from the cytoplasm to the nucleus of HPHs in a concentration-dependent manner. These compounds also induce the expression of CYP2B6 in HPHs with rank-order of efficacies closely resembling that of hCAR activation. Conclusion These results indicate that our strategically integrated approaches are effective in the identification of novel hCAR modulators, which may function as valuable research tools or potential therapeutic molecules. PMID:23090669

Genetic and Biological Analysis of Colombian Phthorimaea operculella Granulovirus Isolated from Tecia solanivora (Lepidoptera: Gelechiidae)▿

PubMed Central

Espinel-Correal, Carlos; Léry, Xavier; Villamizar, Laura; Gómez, Juliana; Zeddam, Jean Louis; Cotes, Alba Marina; López-Ferber, Miguel

2010-01-01

Tecia solanivora (Lepidoptera: Gelechiidae) is an invasive potato pest of the north of South America that recently colonized zones where Phthorimaea operculella (Lepidoptera: Gelechiidae), a taxonomically related insect, was established. Nowadays, both species can be found in most areas in different proportions. The Phthorimaea operculella granulovirus (PhopGV) was found to efficiently control P. operculella and was used as a biopesticide in storage conditions. However, no appropriate biological control methods exist for T. solanivora, and the use of granulovirus isolates would provide a solution. The Colombian Corporation for Agricultural Research (CORPOICA) carried out several T. solanivora larva samplings in Colombia with the aim of finding potential isolates. Five geographical granulovirus isolates from T. solanivora (VG001, VG002, VG003, VG004, and VG005) were found, and molecular analysis by REN profiles shows three different genotypic variants in Colombia. Analysis of their genomes revealed their relatedness to PhopGV. Two isolates exhibited submolar bands in their REN patterns, suggesting a mixture of viral genotypes. These data were confirmed by PCR amplification and sequencing of particular regions of the viral genomes. Their biological activity was assayed on both hosts, T. solanivora and P. operculella. A significantly higher pathogenicity in both hosts was observed with isolates VG001 and VG005 than with isolate VG003 or a Peruvian isolate (from P. operculella) used as a reference in the bioassay. Based on their molecular and biological activity characteristics, VG001 and VG005 isolates should be selected for further analysis in order to establish their potential as biological control agents. PMID:20870793

Synthesis, characterization and biological activity of Rhein-cyclodextrin conjugate

NASA Astrophysics Data System (ADS)

Liu, Manshuo; Lv, Pin; Liao, Rongqiang; Zhao, Yulin; Yang, Bo

2017-01-01

Cyclodextrin conjugate complexation is a useful method to enhance the solubility and absorption of poorly soluble drugs. A series of new Rhein-β-cyclodextrin conjugates (Rh-CD conjugates) have been synthesized and examined. Rhein is covalently linked with the β-CD by amido linkage in a 1:1 molar ratio. The conjugates were characterized by 1H NMR, 13C NMR, HRMS, powder X-ray diffraction (powder XRD) as well as thermogravimetric analysis (TGA). The results reveal that incorporation of β-CD could improve the aqueous solubility of Rhein and the cytotoxicity against hepatocellular carcinoma (HepG2) cell line as well as antibacterial activity against three organisms. The improved biological activity and the satisfactory water solubility of the conjugates will be potentially useful for developing novel drug-cyclodextrin conjugates, such as herbal medicine.

Organocatalytic atroposelective synthesis of axially chiral styrenes

NASA Astrophysics Data System (ADS)

Zheng, Sheng-Cai; Wu, San; Zhou, Qinghai; Chung, Lung Wa; Ye, Liu; Tan, Bin

2017-05-01

Axially chiral compounds are widespread in biologically active compounds and are useful chiral ligands or organocatalysts in asymmetric catalysis. It is well-known that styrenes are one of the most abundant and principal feedstocks and thus represent excellent prospective building blocks for chemical synthesis. Driven by the development of atroposelective synthesis of axially chiral styrene derivatives, we discovered herein the asymmetric organocatalytic approach via direct Michael addition reaction of substituted diones/ketone esters/malononitrile to alkynals. The axially chiral styrene compounds were produced with good chemical yields, enantioselectivities and almost complete E/Z-selectivities through a secondary amine-catalysed iminium activation strategy under mild conditions. Such structural motifs are important precursors for further transformations into biologically active compounds and synthetic useful intermediates and may have potential applications in asymmetric synthesis as olefin ligands or organocatalysts.

A review on acridinylthioureas and its derivatives: biological and cytotoxic activity.

PubMed

Kožurková, Mária; Sabolová, Danica; Kristian, Pavol

2017-10-01

Acridines possess two characteristics that have led many researchers to consider the agents interesting targets for future development as potential farmacophores: the planar acridine skeleton, which is able to intercalate into DNA, and the intense fluorescence of the agents. This review offers a study of the multifunctional character of acridines and the synthesis of novel acridine derivatives, with particular focus being placed on isothiocyanates and their congeners, e.g. thioureas, isothioureas, quaternary ammonium salts and platinum/gold conjugates. The review provides an overview of the structure, spectral properties, DNA binding and biological activity of acridinylthiourea congeners. These acridinylthiourea derivatives display significant cytotoxic activities against different types of cancer cell lines at micromolar concentrations. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Synthesis, Characterization and Biological Activities of Creatinine Amides and Creatinine Schiff Bases.

PubMed

Mumtaz, Amara; Zahoor, Fareeha; Zaib, Sumera; Nawaz, Muhammad Azhar H; Saeed, Aamer; Waseem, Amir; Khan, Afsar; Hussain, Izhar; Iqbal, Jamshed

2017-01-30

In spite of substantial progress in scientific cognizance and medical technology, still infectious diseases are among the leading cause of morbidity and mortality. Creatinine and Schiff bases are well known for their diverse range of biological activities and thought to be emerging and useful therapeutic target for the treatment of several diseases. The present work was aimed to illustrate the influence of substitution of amides and Schiff bases on creatinine and their antimicrobial, antioxidant and anti-urease effectiveness was determined. Creatinine substituted amides (1-2) and creatinine Schiff bases (3-7) were synthesized and characterized by NMR and IR spectral data in combination with elemental analysis. All the compounds (1-7) were investigated on Jack bean urease for their urease inhibitory potential. Investigation of antimicrobial activity of the compounds was made by the agar dilution method. Moreover, 1,1-diphenyl-2- picrylhydrazyl (DPPH) method was used to determine their antioxidant potential. Molecular docking studies were also carried out to elucidate their relationship with the binding pockets of the enzyme. The compounds were found to be potent inhibitors of urease. The synthesized derivatives exhibited significant inhibition against Gram-positive and Gram-negative bacterial strains, as compared to standard, ciprofloxacin. Creatinine based derivatives exhibited potential antifungal activity when tested on infectious and pathogenic fungal strains. Similarly, most of the compounds exhibited good antioxidant activity. These derivatives may serve as a source of potential antioxidants and also help to retard microbial growth in food industry. Similarly, the studies provide a basis for further research to develop more potent urease inhibitory compounds of medicinal /agricultural interest. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Algae as promising organisms for environment and health

PubMed Central

2011-01-01

Algae, like other plants, produce a variety of remarkable compounds collectively referred to as secondary metabolites. They are synthesized by these organisms at the end of the growth phase and/or due to metabolic alterations induced by environmental stress conditions. Carotenoids, phenolic compounds, phycobiliprotein pigments, polysaccharides and unsaturated fatty acids are same of the algal natural products, which were reported to have variable biological activities, including antioxidant activity, anticancer activity, antimicroabial activity against bacteria-virus-algae-fungi, organic fertilizer and bioremediation potentials. PMID:21862867

Antioxidant and Antiplasmodial Activities of Bergenin and 11-O-Galloylbergenin Isolated from Mallotus philippensis

PubMed Central

Khan, Hamayun; Amin, Hazrat; Ullah, Asad; Saba, Sumbal; Rafique, Jamal; Khan, Khalid; Ahmad, Nasir; Badshah, Syed Lal

2016-01-01

Two important biologically active compounds were isolated from Mallotus philippensis. The isolated compounds were characterized using spectroanalytical techniques and found to be bergenin (1) and 11-O-galloylbergenin (2). The in vitro antioxidant and antiplasmodial activities of the isolated compounds were determined. For the antioxidant potential, three standard analytical protocols, namely, DPPH radical scavenging activity (RSA), reducing power assay (RPA), and total antioxidant capacity (TAC) assay, were adopted. The results showed that compound 2 was found to be more potent antioxidant as compared to 1. Fascinatingly, compound 2 displayed better EC50 results as compared to α-tocopherol while being comparable with ascorbic acid. The antiplasmodial assay data showed that both the compound exhibited good activity against chloroquine sensitive strain of Plasmodium falciparum (D10) and IC50 values were found to be less than 8 μM. The in silico molecular docking analyses were also performed for the determination of binding affinity of the isolated compounds using P. falciparum proteins PfLDH and Pfg27. The results showed that compound 2 has high docking score and binding affinity to both protein receptors as compared to compound 1. The demonstrated biological potentials declared that compound 2 could be the better natural antioxidant and antiplasmodial candidate. PMID:26998192

First-Year and Non-First-Year Student Expectations Regarding In-Class and Out-of-Class Learning Activities in Introductory Biology †

PubMed Central

Brown, Tanya L.; Brazeal, Kathleen R.; Couch, Brian A.

2017-01-01

National calls for teaching transformation build on a constructivist learning theory and propose that students learn by actively engaging in course activities and interacting with other students. While interactive pedagogies can improve learning, they also have the potential to challenge traditional norms regarding class participation and learning strategies. To better understand the potential openness of students to interactive teaching practices, we administered a survey during the first week of two sections of an introductory biology course to characterize how students envisioned spending time during class as well as what activities they expected to complete outside of class during non-exam weeks and in preparation for exams. Additionally, we sought to test the hypothesis that the expectations of first-year students differed from those of non-first-year students. Analyses of closed-ended and open-ended questions revealed that students held a wide range of expectations and that most students expressed expectations consistent with some degree of transformed teaching. Furthermore, first-year students expected more active learning in class, more out-of-class coursework during non-exam weeks, and more social learning strategies than non-first-year students. We discuss how instructor awareness of incoming student expectations might be used to promote success in introductory science courses. PMID:28512514

Design, synthesis, and biological evaluation of novel EF24 and EF31 analogs as potential IκB kinase β inhibitors for the treatment of pancreatic cancer.

PubMed

Xie, Xuemeng; Tu, Jinfu; You, Heyi; Hu, Bingren

2017-01-01

Given the important role that inhibitory kappa B (IκB) kinase β (IKKβ) plays in pancreatic cancer (PC) development and progression, inhibitors targeting IKKβ are believed to be increasingly popular as novel anti-PC therapies. Two synthetic molecules, named EF24 and EF31 , exhibited favorable potential in terms of inhibition of both IKKβ activity and PC cell proliferation. Aiming to enhance their cellular efficacy and to analyze their structure-activity relationship, four series of EF24 and EF31 analogs were designed and synthesized. Through kinase activity and vitality screening of cancer cells, D6 displayed excellent inhibition of both IKKβ activity and PC cell proliferation. Additionally, multiple biological evaluations showed that D6 was directly bound to IKKβ and significantly suppressed the activation of the IKKβ/nuclear factor κB pathway induced by tumor necrosis factor-α, as well as effectively inducing cancer cell apoptosis. Moreover, molecular docking and molecular dynamics simulation analysis indicated that the dominant force between D6 and IKKβ comprised hydrophobic interactions. In conclusion, D6 may be a promising therapeutic agent for PC treatment and it also provides a structural lead for the design of novel IKKβ inhibitors.

Design, synthesis, and biological evaluation of novel EF24 and EF31 analogs as potential IκB kinase β inhibitors for the treatment of pancreatic cancer

PubMed Central

Xie, Xuemeng; Tu, Jinfu; You, Heyi; Hu, Bingren

2017-01-01

Given the important role that inhibitory kappa B (IκB) kinase β (IKKβ) plays in pancreatic cancer (PC) development and progression, inhibitors targeting IKKβ are believed to be increasingly popular as novel anti-PC therapies. Two synthetic molecules, named EF24 and EF31, exhibited favorable potential in terms of inhibition of both IKKβ activity and PC cell proliferation. Aiming to enhance their cellular efficacy and to analyze their structure–activity relationship, four series of EF24 and EF31 analogs were designed and synthesized. Through kinase activity and vitality screening of cancer cells, D6 displayed excellent inhibition of both IKKβ activity and PC cell proliferation. Additionally, multiple biological evaluations showed that D6 was directly bound to IKKβ and significantly suppressed the activation of the IKKβ/nuclear factor κB pathway induced by tumor necrosis factor-α, as well as effectively inducing cancer cell apoptosis. Moreover, molecular docking and molecular dynamics simulation analysis indicated that the dominant force between D6 and IKKβ comprised hydrophobic interactions. In conclusion, D6 may be a promising therapeutic agent for PC treatment and it also provides a structural lead for the design of novel IKKβ inhibitors. PMID:28553074

Catalytically and biologically active silver nanoparticles synthesized using essential oil

NASA Astrophysics Data System (ADS)

Vilas, Vidya; Philip, Daizy; Mathew, Joseph

2014-11-01

There are numerous reports on phytosynthesis of silver nanoparticles and various phytochemicals are involved in the reduction and stabilization. Pure explicit phytosynthetic protocol for catalytically and biologically active silver nanoparticles is of importance as it is an environmentally benign green method. This paper reports the use of essential oil of Myristica fragrans enriched in terpenes and phenyl propenes in the reduction and stabilization. FTIR spectra of the essential oil and the synthesized biogenic silver nanoparticles are in accordance with the GC-MS spectral analysis reports. Nanosilver is initially characterized by an intense SPR band around 420 nm, followed by XRD and TEM analysis revealing the formation of 12-26 nm sized, highly pure, crystalline silver nanoparticles. Excellent catalytic and bioactive potential of the silver nanoparticles is due to the surface modification. The chemocatalytic potential of nanosilver is exhibited by the rapid reduction of the organic pollutant, para nitro phenol and by the degradation of the thiazine dye, methylene blue. Significant antibacterial activity of the silver colloid against Gram positive, Staphylococcus aureus (inhibition zone - 12 mm) and Gram negative, Escherichia coli (inhibition zone - 14 mm) is demonstrated by Agar-well diffusion method. Strong antioxidant activity of the biogenic silver nanoparticles is depicted through NO scavenging, hydrogen peroxide scavenging, reducing power, DPPH and total antioxidant activity assays.

Nanoelectronics Meets Biology: From Novel Nanoscale Devices for Live Cell Recording to 3D Innervated Tissues†

PubMed Central

Duan, Xiaojie; Lieber, Charles M.

2013-01-01

High spatio-temporal resolution interfacing between electrical sensors and biological systems, from single live cells to tissues, is crucial for many areas, including fundamental biophysical studies as well as medical monitoring and intervention. This focused review summarizes recent progresses in the development and application of novel nanoscale devices for intracellular electrical recordings of action potentials, and the effort of merging electronic and biological systems seamlessly in three dimension using macroporous nanoelectronic scaffolds. The uniqueness of these nanoscale devices for minimally invasive, large scale, high spatial resolution, and three dimensional neural activity mapping will be highlighted. PMID:23946279

Brain network involved in visual processing of movement stimuli used in upper limb robotic training: an fMRI study.

PubMed

Nocchi, Federico; Gazzellini, Simone; Grisolia, Carmela; Petrarca, Maurizio; Cannatà, Vittorio; Cappa, Paolo; D'Alessio, Tommaso; Castelli, Enrico

2012-07-24

The potential of robot-mediated therapy and virtual reality in neurorehabilitation is becoming of increasing importance. However, there is limited information, using neuroimaging, on the neural networks involved in training with these technologies. This study was intended to detect the brain network involved in the visual processing of movement during robotic training. The main aim was to investigate the existence of a common cerebral network able to assimilate biological (human upper limb) and non-biological (abstract object) movements, hence testing the suitability of the visual non-biological feedback provided by the InMotion2 Robot. A visual functional Magnetic Resonance Imaging (fMRI) task was administered to 22 healthy subjects. The task required observation and retrieval of motor gestures and of the visual feedback used in robotic training. Functional activations of both biological and non-biological movements were examined to identify areas activated in both conditions, along with differential activity in upper limb vs. abstract object trials. Control of response was also tested by administering trials with congruent and incongruent reaching movements. The observation of upper limb and abstract object movements elicited similar patterns of activations according to a caudo-rostral pathway for the visual processing of movements (including specific areas of the occipital, temporal, parietal, and frontal lobes). Similarly, overlapping activations were found for the subsequent retrieval of the observed movement. Furthermore, activations of frontal cortical areas were associated with congruent trials more than with the incongruent ones. This study identified the neural pathway associated with visual processing of movement stimuli used in upper limb robot-mediated training and investigated the brain's ability to assimilate abstract object movements with human motor gestures. In both conditions, activations were elicited in cerebral areas involved in visual perception, sensory integration, recognition of movement, re-mapping on the somatosensory and motor cortex, storage in memory, and response control. Results from the congruent vs. incongruent trials revealed greater activity for the former condition than the latter in a network including cingulate cortex, right inferior and middle frontal gyrus that are involved in the go-signal and in decision control. Results on healthy subjects would suggest the appropriateness of an abstract visual feedback provided during motor training. The task contributes to highlight the potential of fMRI in improving the understanding of visual motor processes and may also be useful in detecting brain reorganisation during training.

Evaluation of antioxidant, antibacterial, and antidiabetic potential of two traditional medicinal plants of India: Swertia cordata and Swertia chirayita.

PubMed

Roy, Priyanka; Abdulsalam, Fatima I; Pandey, D K; Bhattacharjee, Aniruddha; Eruvaram, Naveen Reddy; Malik, Tabarak

2015-06-01

Swertia cordata and Swertia chirayita are temperate Himalayan medicinal plants used as potent herbal drugs in Indian traditional systems of medicine (Ayurvedic, Unani and Siddha). Assessment of Antioxidant, antibacterial, and antidiabetic potential of Swertia cordata and Swertia chirayita. Phytochemicals of methanolic and aqueous extracts of the two Swertia species were analyzed. The antioxidant potential of all the extracts was assessed by measuring total phenolic content, total flavonoid content and free radical scavenging potential was assessed by 1,1-diphenyl-2-picrilhydrazyl (DPPH) assay, antibacterial activity was assessed against various pathogenic and nonpathogenic bacteria in vitro by Kirby-Bauer agar well diffusion method and antidiabetic activity was assessed by α-amylase inhibition. Methanolic leaf extracts of both the species of Swertia contain significant antibacterial as well as anti-diabetic potential, whereas methanolic root extracts of both species were found to have potential antioxidant activity. However, Swertia chirayita showed better activities than Swertia cordata although both species have good reputation in traditional Indian medicine. Both the species are having high medicinal potential in terms of their antioxidant, antibacterial and antidiabetic activities. Studies are required to further elucidate antioxidant, anti-diabetic and antibacterial potentials using various in-vitro, in-vivo biochemical and molecular biology techniques.

Evaluation of antioxidant, antibacterial, and antidiabetic potential of two traditional medicinal plants of India: Swertia cordata and Swertia chirayita

PubMed Central

Roy, Priyanka; Abdulsalam, Fatima I.; Pandey, D. K.; Bhattacharjee, Aniruddha; Eruvaram, Naveen Reddy; Malik, Tabarak

2015-01-01

Background: Swertia cordata and Swertia chirayita are temperate Himalayan medicinal plants used as potent herbal drugs in Indian traditional systems of medicine (Ayurvedic, Unani and Siddha). Objective: Assessment of Antioxidant, antibacterial, and antidiabetic potential of Swertia cordata and Swertia chirayita. Materials and Methods: Phytochemicals of methanolic and aqueous extracts of the two Swertia species were analyzed. The antioxidant potential of all the extracts was assessed by measuring total phenolic content, total flavonoid content and free radical scavenging potential was assessed by 1,1-diphenyl-2-picrilhydrazyl (DPPH) assay, antibacterial activity was assessed against various pathogenic and nonpathogenic bacteria in vitro by Kirby-Bauer agar well diffusion method and antidiabetic activity was assessed by α-amylase inhibition. Results: Methanolic leaf extracts of both the species of Swertia contain significant antibacterial as well as anti-diabetic potential, whereas methanolic root extracts of both species were found to have potential antioxidant activity. However, Swertia chirayita showed better activities than Swertia cordata although both species have good reputation in traditional Indian medicine. Conclusion: Both the species are having high medicinal potential in terms of their antioxidant, antibacterial and antidiabetic activities. Studies are required to further elucidate antioxidant, anti-diabetic and antibacterial potentials using various in-vitro, in-vivo biochemical and molecular biology techniques. PMID:26109789

Isolation and biological evaluation of jatrophane diterpenoids from Euphorbia dendroides.

PubMed

Aljancić, Ivana S; Pesić, Milica; Milosavljević, Slobodan M; Todorović, Nina M; Jadranin, Milka; Milosavljević, Goran; Povrenović, Dragan; Banković, Jasna; Tanić, Nikola; Marković, Ivanka D; Ruzdijić, Sabera; Vajs, Vlatka E; Tesević, Vele V

2011-07-22

From the Montenegrin spurge Euphorbia dendroides, seven new diterpenoids [jatrophanes (1-6) and a tigliane (7)] were isolated and their structures elucidated by spectroscopic techniques. The biological activity of the new compounds was studied against four human cancer cell lines. The most effective jatrophane-type compound (2) and its structurally closely related derivative (1) were evaluated for their interactions with paclitaxel and doxorubicin using a multi-drug-resistant cancer cell line. Both compounds exerted a strong reversal potential resulting from inhibition of P-glycoprotein transport.

Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase.

PubMed

Abrahim, Noor Nazirahanie; Kanthimathi, M S; Abdul-Aziz, Azlina

2012-11-15

Breast cancer is the most common form of cancer and the focus on finding chemotherapeutic agents have recently shifted to natural products. Piper betle is a medicinal plant with various biological activities. However, not much data is available on the anti-cancer effects of P. betle on breast cancer. Due to the current interest in the potential effects of antioxidants from natural products in breast cancer treatment, we investigated the antioxidant activities of the leaves of P. betle and its inhibitory effect on the proliferation of the breast cancer cell line, MCF-7. The leaves of P. betle were extracted with solvents of varying polarities (water, methanol, ethyl acetate and hexane) and their phenolic and flavonoid content were determined using colorimetric assays. Phenolic composition was characterized using HPLC. Antioxidant activities were measured using FRAP, DPPH, superoxide anion, nitric oxide and hyroxyl radical scavenging assays. Biological activities of the extracts were analysed using MTT assay and antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase) assays in MCF-7 cells. Overall, the ethyl acetate extract showed the highest ferric reducing activity and radical scavenging activities against DPPH, superoxide anion and nitric oxide radicals. This extract also contained the highest phenolic content implying the potential contribution of phenolics towards the antioxidant activities. HPLC analyses revealed the presence of catechin, morin and quercetin in the leaves. The ethyl acetate extract also showed the highest inhibitory effect against the proliferation of MCF-7 cells (IC50=65 μg/ml). Treatment of MCF-7 cells with the plant extract increased activities of catalase and superoxide dismutase. Ethyl acetate is the optimal solvent for the extraction of compounds with antioxidant and anti-proliferative activities. The increased activities of catalase and superoxide dismutase in the treated cells could alter the antioxidant defense system, potentially contributing towards the anti-proliferative effect. There is great potential for the ethyl acetate extract of P. betle leaf as a source of natural antioxidants and to be developed as therapeutics in cancer treatment.

Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase

PubMed Central

2012-01-01

Background Breast cancer is the most common form of cancer and the focus on finding chemotherapeutic agents have recently shifted to natural products. Piper betle is a medicinal plant with various biological activities. However, not much data is available on the anti-cancer effects of P. betle on breast cancer. Due to the current interest in the potential effects of antioxidants from natural products in breast cancer treatment, we investigated the antioxidant activities of the leaves of P. betle and its inhibitory effect on the proliferation of the breast cancer cell line, MCF-7. Methods The leaves of P. betle were extracted with solvents of varying polarities (water, methanol, ethyl acetate and hexane) and their phenolic and flavonoid content were determined using colorimetric assays. Phenolic composition was characterized using HPLC. Antioxidant activities were measured using FRAP, DPPH, superoxide anion, nitric oxide and hyroxyl radical scavenging assays. Biological activities of the extracts were analysed using MTT assay and antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase) assays in MCF-7 cells. Results Overall, the ethyl acetate extract showed the highest ferric reducing activity and radical scavenging activities against DPPH, superoxide anion and nitric oxide radicals. This extract also contained the highest phenolic content implying the potential contribution of phenolics towards the antioxidant activities. HPLC analyses revealed the presence of catechin, morin and quercetin in the leaves. The ethyl acetate extract also showed the highest inhibitory effect against the proliferation of MCF-7 cells (IC50=65 μg/ml). Treatment of MCF-7 cells with the plant extract increased activities of catalase and superoxide dismutase. Conclusions Ethyl acetate is the optimal solvent for the extraction of compounds with antioxidant and anti-proliferative activities. The increased activities of catalase and superoxide dismutase in the treated cells could alter the antioxidant defense system, potentially contributing towards the anti-proliferative effect. There is great potential for the ethyl acetate extract of P. betle leaf as a source of natural antioxidants and to be developed as therapeutics in cancer treatment. PMID:23153283

The relevance of nanoscale biological fragments for ice nucleation in clouds

NASA Astrophysics Data System (ADS)

O‧Sullivan, D.; Murray, B. J.; Ross, J. F.; Whale, T. F.; Price, H. C.; Atkinson, J. D.; Umo, N. S.; Webb, M. E.

2015-01-01

Most studies of the role of biological entities as atmospheric ice-nucleating particles have focused on relatively rare supermicron particles such as bacterial cells, fungal spores and pollen grains. However, it is not clear that there are sufficient numbers of these particles in the atmosphere to strongly influence clouds. Here we show that the ice-nucleating activity of a fungus from the ubiquitous genus Fusarium is related to the presence of nanometre-scale particles which are far more numerous, and therefore potentially far more important for cloud glaciation than whole intact spores or hyphae. In addition, we quantify the ice-nucleating activity of nano-ice nucleating particles (nano-INPs) washed off pollen and also show that nano-INPs are present in a soil sample. Based on these results, we suggest that there is a reservoir of biological nano-INPs present in the environment which may, for example, become aerosolised in association with fertile soil dust particles.

Click Chemistry Mediated Functionalization of Vertical Nanowires for Biological Applications.

PubMed

Vutti, Surendra; Schoffelen, Sanne; Bolinsson, Jessica; Buch-Månson, Nina; Bovet, Nicolas; Nygård, Jesper; Martinez, Karen L; Meldal, Morten

2016-01-11

Semiconductor nanowires (NWs) are gaining significant importance in various biological applications, such as biosensing and drug delivery. Efficient and controlled immobilization of biomolecules on the NW surface is crucial for many of these applications. Here, we present for the first time the use of the Cu(I) -catalyzed alkyne-azide cycloaddition and its strain-promoted variant for the covalent functionalization of vertical NWs with peptides and proteins. The potential of the approach was demonstrated in two complementary applications of measuring enzyme activity and protein binding, which is of general interest for biological studies. The attachment of a peptide substrate provided NW arrays for the detection of protease activity. In addition, green fluorescent protein was immobilized in a site-specific manner and recognized by antibody binding to demonstrate the proof-of-concept for the use of covalently modified NWs for diagnostic purposes using minute amounts of material. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of Carbocyanine Dyes for PRMT Inhibition and Imaging

PubMed Central

Sinha, Sarmistha Halder; Owens, Eric A.; Feng, You; Yang, Yutao; Xie, Yan; Tu, Yaping; Henary, Maged; Zheng, Yujun George

2014-01-01

Summary Protein arginine methylation regulates multiple biological processes. Deregulation of protein arginine methyltransferase (PRMT) activities has been observed in many disease phenotypes. Small molecule probes that target PRMTs with strong affinity and selectivity can be used as valuable tools to dissect biological mechanisms of arginine methylation and establish the role of PRMT proteins in a disease process. In this work, we report synthesis and evaluation of a class of carbocyanine compounds containing indolium, benz[e]indolium or benz[c,d]indolium heterocyclic moieties that bind to the predominant arginine methyltransferase PRMT1 and inhibit its methyltransferase activity at low micromolar potencies. In particular, the developed molecules have long wavelength colorimetric and fluorometric photoactivities, which can be used for optical and near-infrared fluorescence imaging in cells or biological tissues. Together, these new chemical probes have potential application in PRMT studies both as enzyme inhibitors and as fluorescent dyes for microscope imaging. PMID:22749641

Biosafety Manual

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, Bruce W.

2010-05-18

Work with or potential exposure to biological materials in the course of performing research or other work activities at Lawrence Berkeley National Laboratory (LBNL) must be conducted in a safe, ethical, environmentally sound, and compliant manner. Work must be conducted in accordance with established biosafety standards, the principles and functions of Integrated Safety Management (ISM), this Biosafety Manual, Chapter 26 (Biosafety) of the Health and Safety Manual (PUB-3000), and applicable standards and LBNL policies. The purpose of the Biosafety Program is to protect workers, the public, agriculture, and the environment from exposure to biological agents or materials that may causemore » disease or other detrimental effects in humans, animals, or plants. This manual provides workers; line management; Environment, Health, and Safety (EH&S) Division staff; Institutional Biosafety Committee (IBC) members; and others with a comprehensive overview of biosafety principles, requirements from biosafety standards, and measures needed to control biological risks in work activities and facilities at LBNL.« less

The relevance of nanoscale biological fragments for ice nucleation in clouds.

PubMed

O'Sullivan, D; Murray, B J; Ross, J F; Whale, T F; Price, H C; Atkinson, J D; Umo, N S; Webb, M E

2015-01-28

Most studies of the role of biological entities as atmospheric ice-nucleating particles have focused on relatively rare supermicron particles such as bacterial cells, fungal spores and pollen grains. However, it is not clear that there are sufficient numbers of these particles in the atmosphere to strongly influence clouds. Here we show that the ice-nucleating activity of a fungus from the ubiquitous genus Fusarium is related to the presence of nanometre-scale particles which are far more numerous, and therefore potentially far more important for cloud glaciation than whole intact spores or hyphae. In addition, we quantify the ice-nucleating activity of nano-ice nucleating particles (nano-INPs) washed off pollen and also show that nano-INPs are present in a soil sample. Based on these results, we suggest that there is a reservoir of biological nano-INPs present in the environment which may, for example, become aerosolised in association with fertile soil dust particles.

Phenformin inhibits cell proliferation and induces cell apoptosis and autophagy in cholangiocarcinoma.

PubMed

Hu, Shuyang; Ouyang, Qing; Cheng, Qingbao; Wang, Jinghan; Feng, Feiling; Qiao, Liang; Gan, Wei; Shi, Yang; Wu, Demin; Jiang, Xiaoqing

2018-04-01

Cholangiocarcinoma (CCA) is an aggressive malignant tumor and the prognosis of patients with advanced stage disease remains poor. Therefore, the identification of novel treatment agents for CCA is required. In the present study, the biological effects of the diabetes therapeutic agent, phenformin, in CCA cell lines was investigated. Cell Counting Kit‑8 cell viability, cellular clone formation and subcutaneous tumor formation assays were performed, which revealed that phenformin inhibited CCA cell proliferation and growth both in vitro and in vivo. In addition, phenformin induced CCA cell apoptosis and autophagy. Phenformin partly activated the liver kinase B1 (LKB1)/5' AMP‑activated protein kinase signaling pathway to exert its biological effects on CCA cell lines, as demonstrated by knockdown of LKB1, which reversed these effects. In conclusion, the present study demonstrated the biological effects of phenformin in CCA and suggested that phenformin may be a potential novel agent for CCA treatment.

Invasive species in agriculture

USDA-ARS?s Scientific Manuscript database

Agricultural production of food, feed, fiber or fuel is a local human activity with global ecological impacts, including the potential to foster invasions. Agriculture plays an unusual role in biological invasions, in that it is both a source of non-indigenous invasive species (NIS) and especially s...

Applications of high throughput screening to identify profiles of biological activity relevant to carcinogenesis

EPA Science Inventory

ToxCast, the United States Environmental Protection Agency’s chemical prioritization research program, is developing methods for utilizing computational chemistry and bioactivity profiling to predict potential for toxicity and prioritize limited testing resources (www.epa.gov/toc...

Significant Correlation between TLR2 Agonist Activity and TNF-α Induction in J774.A1 Macrophage Cells by Different Medicinal Mushroom Products.

PubMed

Coy, Catherine; Standish, Leanna J; Bender, Geoff; Lu, Hailing

2015-01-01

In the US market, there is a variety of mushroom preparations available, even within the same species of mushroom. Nonetheless, little is known about whether species or the various extraction methods affect biological activity and potency of the immune modulatory activity of mushroom extracts. After discovering that protein-bound polysaccharide-K, a hot water extract from Trametes versicolor, was a potent Toll-like receptor (TLR)-2 agonist that stimulates both innate and adaptive immunity, this study was initiated to evaluate whether other medicinal mushroom products also have TLR2 agonist activity and immune-enhancing potential as measured by the induction of tumor necrosis factor (TNF)-α in J774.A1 murine macrophage cells. Furthermore, the products were divided by extraction method and species to determine whether these factors affect their immunomodulatory activity. The results showed that the majority (75%) of mushroom products tested had TLR2 agonist activity and that there was a significant correlation between TLR2 agonist activity and TNF-α induction potential in the mushroom products analyzed. In addition, the data demonstrated that hot water mushroom extracts are more potent than ground mushroom products in activating TLR2 and inducing TNF-α. These data provide evidence that extraction methods may affect the biological activity of mushroom products; thus, further studies are warranted to investigate the structural differences between various mushroom products.

Potential applications of silk sericin, a natural protein from textile industry by-products.

PubMed

Aramwit, Pornanong; Siritientong, Tippawan; Srichana, Teerapol

2012-03-01

Silk is composed of two major proteins, fibroin (fibrous protein) and sericin (globular, gumming protein). Fibroin has been used in textile manufacturing and for several biomaterial applications, whereas sericin is considered a waste material in the textile industry. Sericin has recently been found to activate the proliferation of several cell-lines and has also shown various biological activities. Sericin can form a gel by itself; however, after mixing with other polymers and cross-linking it can form a film or a scaffold with good characteristics that can be used in the cosmetic and pharmaceutical industries. Sericin is proven to cause no immunological responses, which has resulted in a more acceptable material for biological applications.

Proteome profile and biological activity of caprine, bovine and human milk fat globules.

PubMed

Spertino, Stefano; Cipriani, Valentina; De Angelis, Chiara; Giuffrida, Maria Gabriella; Marsano, Francesco; Cavaletto, Maria

2012-04-01

Upon combining bidimensional electrophoresis with monodimensional separation, a more comprehensive analysis of the milk fat globule membrane has been obtained. The proteomic profile of caprine milk fat globules revealed the presence of butyrophilin, lactadherin and perilipin as the major proteins, they were also associated to bovine and human milk fat globule membranes. Xanthine dehydrogenase/oxidase has been detected only in monodimensional gels. Biological activity of milk fat globules has been evaluated in Caco2-cells, as a representative model of the intestinal barrier. The increase of cell viability was indicative of a potential nutraceutical role for the whole milk fat globule, suggesting a possible employment in milk formula preparation.

Discovery and biological relevance of 3,4-didehydroretinol (vitamin A2) in small indigenous fish species and its potential as a dietary source for addressing vitamin A deficiency.

PubMed

La Frano, Michael R; Cai, Yimeng; Burri, Betty J; Thilsted, Shakuntala H

2018-05-01

Discovered in the late 1920s, 3,4-didehydroretinol (DROL, vitamin A 2 ) plays a significant biological role in freshwater fish. The functions of this vitamin have been investigated but to a far lesser extent than those of retinol (ROL, vitamin A 1 ). A recent study indicating all-trans DROL has 119-127% vitamin A biological activity compared to that of all-trans ROL suggests the significance of DROL for addressing vitamin A deficiency (VAD) in comparison to ROL may be currently overlooked. Freshwater fish such as small indigenous fish species (SIS), with high DROL content can be a promising dietary source for reducing VAD in areas where SIS are readily available and consumed. In this paper, the discovery and biological relevance of DROL are reviewed and furthermore, the vast potential of production and consumption of DROL-rich SIS in food-based strategies to combat VAD in Bangladesh and other developing countries with high prevalence of VAD is highlighted.

Behavioral, biological, and chemical perspectives on targeting CRF1 receptor antagonists to treat alcoholism

PubMed Central

Zorrilla, Eric P.; Heilig, Markus; de Wit, Harriet; Shaham, Yavin

2013-01-01

Background Alcohol use disorders are chronic disabling conditions for which existing pharmacotherapies have only modest efficacy. In the present review, derived from the 2012 Behavior, Biology and Chemistry “Translational Research in Addiction” symposium, we summarize the anti-relapse potential of corticotropin-releasing factor type 1 (CRF1) receptor antagonists to reduce negative emotional symptoms of acute and protracted alcohol withdrawal and stress-induced relapse to alcohol seeking. Methods We review the biology of CRF1 systems, the activity of CRF1 receptor antagonists in animal models of anxiolytic and antidepressant activity, and experimental findings in alcohol addiction models. We also update the clinical trial status of CRF1 receptor antagonists, including pexacerfont (BMS-562086), emicerfont (GW876008), verucerfont (GSK561679), CP316311, SSR125543A, R121919/NBI30775, R317573/19567470/CRA5626, and ONO-2333Ms. Finally, we discuss the potential heterogeneity and pharmacogenomics of CRF1 receptor pharmacotherapy for alcohol dependence. Results The evidence suggests that brain penetrant-CRF1 receptor antagonists have therapeutic potential for alcohol dependence. Lead compounds with clinically desirable pharmacokinetic properties now exist, and longer receptor residence rates (i.e., slow dissociation) may predict greater CRF1 receptor antagonist efficacy. Functional variants in genes that encode CRF system molecules, including polymorphisms in Crhr1 (rs110402, rs1876831, rs242938) and Crhbp genes (rs10055255, rs3811939) may promote alcohol seeking and consumption by altering basal or stress-induced CRF system activation. Conclusions Ongoing clinical trials with pexacerfont and verucerfont in moderately to highly severe dependent anxious alcoholics may yield insight as to the role of CRF1 receptor antagonists in a personalized medicine approach to treat drug or alcohol dependence. PMID:23294766

Murabutide revisited: a review of its pleiotropic biological effects.

PubMed

Jakopin, Žiga

2013-01-01

Despite the great efforts put into their development, the list of clinically approved immunological adjuvants is still very short. Evolution of the knowledge of the immune system has enabled for rational design of novel adjuvants and has led to the conclusion that more than one type of adjuvant will be required. Derivatives of muramyl dipeptide (MDP), the minimal immunomodulatory structure of bacterial cell wall peptidoglycan, have gained considerable attention in the past decades, because of their potent adjuvant effects. Murabutide is a safe derivative of MDP, which interacts with cells of the immune system, both innate and adaptive, and exerts its effect through activation of Nod2. The transcriptional response of murabutide-stimulated macrophages revealed enhanced expression of genes coding for various proteins such as immune mediators and their receptors, transcription factors and kinases, ion channels/transporters and proteins involved in cell metabolic activity, thus reflecting a broad spectrum of biological effects. In addition to its well recognized adjuvant effect, murabutide has also been shown to enhance the host's resistance against microbial infections, nonspecific resistance against tumors and the induction of cytokines and chemokines implicated in enhancing the immune response and hematopoesis. This article provides an insight into the mechanism of action of murabutide and its interactions with the cells of the immune system in vitro and in vivo. On account of its numerous biological effects, murabutide has been the subject of several clinical studies. Many of these have confirmed its potential to synergize with cytokines of therapeutic interest in potentiating the tumoricidal activity of macrophages or targeting chronic viral diseases, as well as reducing the cytokine dosage needed to achieve a therapeutic effect. This review covers the findings of all relevant studies and focuses on the role of murabutide and its potential in the treatment of several microbial diseases.

Extracellular palladium-catalysed dealkylation of 5-fluoro-1-propargyl-uracil as a bioorthogonally activated prodrug approach

PubMed Central

Weiss, Jason T.; Dawson, John C.; Macleod, Kenneth G.; Rybski, Witold; Fraser, Craig; Torres-Sánchez, Carmen; Patton, E. Elizabeth; Bradley, Mark; Carragher, Neil O.; Unciti-Broceta, Asier

2014-01-01

A bioorthogonal organometallic reaction is a biocompatible transformation undergone by a synthetic material exclusively through the mediation of a non-biotic metal source; a selective process used to label biomolecules and activate probes in biological environs. Here we report the in vitro bioorthogonal generation of 5-fluorouracil from a biologically inert precursor by heterogeneous Pd0 catalysis. Although independently harmless, combined treatment of 5-fluoro-1-propargyl-uracil and Pd0-functionalized resins exhibits comparable antiproliferative properties to the unmodified drug in colorectal and pancreatic cancer cells. Live-cell imaging and immunoassay studies demonstrate that the cytotoxic activity of the prodrug/Pd0-resin combination is due to the in situ generation of 5-fluorouracil. Pd0-resins can be carefully implanted in the yolk sac of zebrafish embryos and display excellent biocompatibility and local catalytic activity. The in vitro efficacy shown by this masking/activation strategy underlines its potential to develop a bioorthogonally activated prodrug approach and supports further in vivo investigations. PMID:24522696

Synthesis and biological evaluation of 6-substituted-5-fluorouridine ProTides.

PubMed

Slusarczyk, Magdalena; Ferla, Salvatore; Brancale, Andrea; McGuigan, Christopher

2018-02-01

A new family of thirteen phosphoramidate prodrugs (ProTides) of different 6-substituted-5-fluorouridine nucleoside analogues were synthesized and evaluated as potential anticancer agents. In addition, antiviral activity against Chikungunya (CHIKV) virus was evaluated using a cytopathic effect inhibition assay. Although a carboxypeptidase Y assay supported a putative mechanism of activation of ProTides built on 5-fluorouridine with such C6-modifications, the Hint docking studies revealed a compromised substrate-activity for the Hint phosphoramidase-type enzyme that is likely responsible for phosphoramidate bioactivation through P-N bond cleavage and free nucleoside 5'-monophosphate delivery. Our observations may support and explain to some extent the poor in vitro biological activity generally demonstrated by the series of 6-substituted-5-fluorouridine phosphoramidates (ProTides) and will be of guidance for the design of novel phosphoramidate prodrugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fluid dynamics in biological active nematics

NASA Astrophysics Data System (ADS)

Tan, Amanda; Hirst, Linda

We use biological materials to form a self-mixing active system that consists of microtubules driven by kinesin clusters. Microtubules are rigid biopolymers that are a part of the cytoskeleton. Kinesin motors are molecular motors that walk along microtubules to transport cellular cargo. In this system, microtubules are bundled together, and as the kinesin clusters walk along the filaments, the microtubule bundles move relative to each other. As microtubules shear against each other, they extend, bend, buckle and fracture. When confined in a 2D water-oil interface, the system becomes an active nematic that self-mixes due to the buckling and fracturing. To quantify this self-mixing, we attached beads to the microtubules, and tracked their motion. We quantify the quality of mixing using the bead trajectories. This new active material has potential applications as a self-mixing solvent. CCBM NSF-CREST, UC Merced Health Science Research Institute.

Yucca Mountain Biological Resources Monitoring Program; Annual report, FY91

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1992-01-01

The US Department of Energy (DOE) is required by the Nuclear Waste Policy Act of 1982 (as amended in 1987) to study and characterize Yucca Mountain as a possible site for a geologic repository for high-level nuclear waste. During site characterization, the DOE will conduct a variety of geotechnical, geochemical, geological, and hydrological studies to determine the suitability of Yucca Mountain as a repository. To ensure that site characterization activities (SCA) do not adversely affect the Yucca Mountain area, an environmental program has been implemented to monitor and mitigate potential impacts and to ensure that activities comply with applicable environmentalmore » regulations. This report describes the activities and accomplishments during fiscal year 1991 (FY91) for six program areas within the Terrestrial Ecosystem component of the YMP environmental program. The six program areas are Site Characterization Activities Effects, Desert Tortoises, Habitat Reclamation, Monitoring and Mitigation, Radiological Monitoring, and Biological Support.« less

Temporal and spatial variability of soil biological activity at European scale

NASA Astrophysics Data System (ADS)

Mallast, Janine; Rühlmann, Jörg

2015-04-01

The CATCH-C project aims to identify and improve the farm-compatibility of Soil Management Practices including to promote productivity, climate change mitigation and soil quality. The focus of this work concentrates on turnover conditions for soil organic matter (SOM). SOM is fundamental for the maintenance of quality and functions of soils while SOM storage is attributed a great importance in terms of climate change mitigation. The turnover conditions depend on soil biological activity characterized by climate and soil properties. Soil biological activity was investigated using two model concepts: a) Re_clim parameter within the ICBM (Introductory Carbon Balance Model) (Andrén & Kätterer 1997) states a climatic factor summarizing soil water storage and soil temperature and its influence on soil biological activity. b) BAT (biological active time) approach derived from model CANDY (CArbon and Nitrogen Dynamic) (Franko & Oelschlägel 1995) expresses the variation of soil moisture, soil temperature and soil aeration as a time scale and an indicator of biological activity for soil organic matter (SOM) turnover. During an earlier stage both model concepts, Re_clim and BAT, were applied based on a monthly data to assess spatial variability of turnover conditions across Europe. This hampers the investigation of temporal variability (e.g. intra-annual). The improved stage integrates daily data of more than 350 weather stations across Europe presented by Klein Tank et al. (2002). All time series data (temperature, precipitation and potential evapotranspiration and soil texture derived from the European Soil Database (JRC 2006)), are used to calculate soil biological activity in the arable layer. The resulting BAT and Re_clim values were spatio-temporal investigated. While "temporal" refers to a long-term trend analysis, "spatial" includes the investigation of soil biological activity variability per environmental zone (ENZ, Metzger et al. 2005 representing similar conditions for precipitation, temperature and relief) to identify ranges and hence turnover conditions for each ENZ. We will discuss the analyzed results of both concepts to assess SOM turnover conditions across Europe for historical weather data and for Spain focusing on climate scenarios. Both concepts help to separate different turnover activities and to indicate organic matter input in order to maintain the given SOM. The assessment could provide recommendations for adaptations of soil management practices. CATCH-C is funded within the 7th Framework Programme for Research, Technological Development and Demonstration, Theme 2 - Biotechnologies, Agriculture & Food (Grant Agreement N° 289782).

Hysteresis in voltage-gated channels.

PubMed

Villalba-Galea, Carlos A

2017-03-04

Ion channels constitute a superfamily of membrane proteins found in all living creatures. Their activity allows fast translocation of ions across the plasma membrane down the ion's transmembrane electrochemical gradient, resulting in a difference in electrical potential across the plasma membrane, known as the membrane potential. A group within this superfamily, namely voltage-gated channels, displays activity that is sensitive to the membrane potential. The activity of voltage-gated channels is controlled by the membrane potential, while the membrane potential is changed by these channels' activity. This interplay produces variations in the membrane potential that have evolved into electrical signals in many organisms. These signals are essential for numerous biological processes, including neuronal activity, insulin release, muscle contraction, fertilization and many others. In recent years, the activity of the voltage-gated channels has been observed not to follow a simple relationship with the membrane potential. Instead, it has been shown that the activity of voltage-gated channel displays hysteresis. In fact, a growing number of evidence have demonstrated that the voltage dependence of channel activity is dynamically modulated by activity itself. In spite of the great impact that this property can have on electrical signaling, hysteresis in voltage-gated channels is often overlooked. Addressing this issue, this review provides examples of voltage-gated ion channels displaying hysteretic behavior. Further, this review will discuss how Dynamic Voltage Dependence in voltage-gated channels can have a physiological role in electrical signaling. Furthermore, this review will elaborate on the current thoughts on the mechanism underlying hysteresis in voltage-gated channels.

Bothriurus bonariensis scorpion venom activates voltage-dependent sodium channels in insect and mammalian nervous systems.

PubMed

Dos Santos, Douglas Silva; Carvalho, Evelise Leis; de Lima, Jeferson Camargo; Breda, Ricardo Vaz; Oliveira, Raquel Soares; de Freitas, Thiago Carrazoni; Salamoni, Simone Denise; Domingues, Michelle Flores; Piovesan, Angela Regina; Boldo, Juliano Tomazzoni; de Assis, Dênis Reis; da Costa, Jaderson Costa; Dal Belo, Cháriston André; Pinto, Paulo Marcos

2016-10-25

Animal venoms have been widely recognized as a major source of biologically active molecules. Bothriurus bonariensis, popularly known as black scorpion, is the arthropod responsible for the highest number of accidents involving scorpion sting in Southern Brazil. Here we reported the first attempt to investigate the neurobiology of B. bonariensis venom (BBV) in the insect and mammalian nervous system. BBV (32 μg/g) induced a slow neuromuscular blockade in the in vivo cockroach nerve-muscle preparations (70 ± 4%, n = 6, p < 0.001), provoking repetitive twitches and significantly decreasing the frequency of spontaneous leg action potentials (SNCAPs) from 82 ± 3 min(-1) to 36 ± 1.3 min(-1) (n = 6, p < 0.05), without affecting the amplitude. When tested in primary cultures of rat hippocampal cells, BBV induced a massive increase of Ca(2+) influx (250 ± 1% peak increase, n = 3, p < 0.0001). The disturbance of calcium homeostasis induced by BBV on the mammalian central nervous system was not accompanied by cellular death and was prevented by the co-treatment of the hippocampal cells with tetrodotoxin, a selective sodium channel blocker. The results suggest that the biological activity of BBV is mostly related to a modulation of sodium channels function. Our biological activity survey suggests that BBV may have a promising insecticidal and therapeutic potential. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Research in Biological and Medical Sciences Including Biochemistry, Communicable Disease and Immunology, Internal Medicine, Physiology, Psychiatry, Surgery, and Veterinary Medicine. Volume 1

DTIC Science & Technology

1979-09-01

and R.P. MacDermott. Antibody-dependent cell-mediated antibacterial activity of human mononuclear cells. I. K-lymphocytes and monocytes are effective...malaria research. During the reporting period, research activities have included analyses of: 1) a hemagglutination inhibition test for early detection of...radioiodination or sodium borohydride reduction. Evaluate the potential roles of activity for each protein isolated. Compare the composition of isolated

Assessing the Biological Safety Profession's Evaluation and Control of Risks Associated with the Field Collection of Potentially Infectious Specimens.

PubMed

Patlovich, Scott J; Emery, Robert J; Whitehead, Lawrence W; Brown, Eric L; Flores, Rene

2015-03-01

Because the origins of the biological safety profession are rooted in the control and prevention of laboratory-associated infections, the vocation focuses primarily on the safe handling of specimens within the laboratory. But in many cases, the specimens and samples handled in the lab are originally collected in the field where a broader set of possible exposure considerations may be present, each with varying degrees of controllability. The failure to adequately control the risks associated with collecting biological specimens in the field may result in illness or injury, and could have a direct impact on laboratory safety, if infectious specimens were packaged or transported inappropriately, for example. This study developed a web-based survey distributed to practicing biological safety professionals to determine the prevalence of and extent to which biological safety programs consider and evaluate field collection activities. In cases where such issues were considered, the data collected characterize the types of controls and methods of oversight at the institutional level that are employed. Sixty-one percent (61%) of the survey respondents indicated that research involving the field collection of biological specimens is conducted at their institutions. A majority (79%) of these field collection activities occur at academic institutions. Twenty-seven percent (27%) of respondents indicated that their safety committees do not consider issues related to biological specimens collected in the field, and only 25% with an oversight committee charged to review field collection protocols have generated a field research-specific risk assessment form to facilitate the assembly of pertinent information for a project risk assessment review. The results also indicated that most biosafety professionals (73% overall; 71% from institutions conducting field collection activities) have not been formally trained on the topic, but many (64% overall; 87% from institutions conducting field collection activities) indicated that training on field research safety issues would be helpful, and even more (71% overall; 93% from institutions conducting field collection activities) would consider participation in such a training course. Results obtained from this study can be used to develop a field research safety toolkit and associated training curricula specifically targeted to biological safety professionals.

Privileged scaffolds or promiscuous binders: a glance of pyrrolo[2,1-f][1,2,4]triazines and related bridgehead nitrogen heterocycles in medicinal chemistry.

PubMed

Song, Yu'ning; Zhan, Peng; Zhang, Qingzhu; Liu, Xinyong

2013-01-01

Pyrrolo[2,1-f][1,2,4]triazine template, a unique bridgehead nitrogen heterocycle, certainly deserves the title of "privileged scaffold" in the drug discovery field because of the versatility and potential to yield derivatives with a wide range of biological activities, such as anti-anaplastic lymphoma kinase (ALK), Janus kinase 2 (JAK2), VEGFR-2, EGFR and/or HER2, Met kinase, p38α mitogen-activated protein (MAP) kinase and insulin-like growth factor receptor (IGF-1R) kinase activities, etc. These different biological properties of pyrrolo[2,1-f][1,2,4]triazine derivatives have motivated new studies in searching for novel derivatives with improved activity and also other applications in pharmaceutical field. However, no systematic review is available in the literature on the pyrrolo[2,1- f][1,2,4]triazine derivatives concerning the design of potent drug-like compounds. Owing to the importance of this heterocyclic system, the present paper is an attempt to the pharmacological activities, structural modifications and the structure-activity relationship (SAR) reported for bridgehead nitrogen heterocycles in the current literature, making an effort to highlight the importance and therapeutic potentials of the pyrrolo[2,1-f][1,2,4]triazine scaffold and its bridgehead nitrogen bioisosters as heterocyclic privileged medicinal scaffolds.

Synthesis, biological evaluation and molecular docking of novel 5-phenyl-1H-pyrazol derivatives as potential BRAF(V600E) inhibitors.

PubMed

Dong, Jing-Jun; Li, Qing-Shan; Wang, Shu-Fu; Li, Cui-Yun; Zhao, Xin; Qiu, Han-Yue; Zhao, Meng-Yue; Zhu, Hai-Liang

2013-10-07

The RAF-MEK-ERK cascade appears to be intimately involved in the regulation of cell cycle progression and apoptosis. The BRAF(V600E) mutant results in constitutive activation of the ERK pathway, which can lead to cellular growth dysregulation. A series of 5-phenyl-1H-pyrazol derivatives (3a-5e) have been designed and synthesized, and their biological activities were evaluated as potential BRAF(V600E) inhibitors. All the compounds were reported for the first time except 3e, and compound 1-(4-bromo-2-hydroxybenzyl)-3-phenyl-1-(5-phenyl-1H-pyrazol-3-yl)urea (5c) displayed the most potent inhibitory activity (BRAF(V600E) IC50 = 0.19 μM). Antiproliferative assay results indicated that compound 5c possessed high antiproliferative activity against cell lines WM266.4 and A375 in vitro, with IC50 values of 1.50 and 1.32 μM, respectively, which were comparable with the positive control vemurafenib. Docking simulations showed that compound 5c binds tightly to the BRAF(V600E) active site and acts as BRAF(V600E) inhibitor. A 3D-QSAR model was also built to provide more pharmacophore understanding towards designing new agents with more potent BRAF(V600E) inhibitory activity.

hERG1/Kv11.1 activation stimulates transcription of p21waf/cip in breast cancer cells via a calcineurin-dependent mechanism.

PubMed

Perez-Neut, Mathew; Rao, Vidhya R; Gentile, Saverio

2016-09-13

The function of Kv11.1 is emerging in breast cancer biology, as a growing body of evidence indicates that the hERG1/Kv11.1 potassium channel is aberrantly expressed in several cancer types including breast cancers.The biological effects of Kv11.1 channel blockers and their associated side effects are very well known but the potential use of Kv11.1 activators as an anticancer strategy are still unexplored. In our previous work, we have established that stimulation of the Kv11.1 potassium channel activates a senescent-like program that is characterized by a significant increase in tumor suppressor protein levels, such as p21waf/cip and p16INK4A. In this study we investigated the mechanism linking Kv11.1 stimulation to augmentation of p21waf/cip protein level. We have demonstrated that the Kv11.1 channel activator NS1643 activates a calcineurin-dependent transcription of p21waf/cip and that this event is fundamental for the inhibitory effect of NS1643 on cell proliferation. Our results reveal a novel mechanism by which stimulation of Kv11.1 channel leads to transcription of a potent tumor suppressor and suggest a potential therapeutic use for Kv11.1 channel activators.

hERG1/Kv11.1 activation stimulates transcription of p21waf/cip in breast cancer cells via a calcineurin-dependent mechanism

PubMed Central

Perez-Neut, Mathew; Rao, Vidhya R.; Gentile, Saverio

2016-01-01

The function of Kv11.1 is emerging in breast cancer biology, as a growing body of evidence indicates that the hERG1/Kv11.1 potassium channel is aberrantly expressed in several cancer types including breast cancers. The biological effects of Kv11.1 channel blockers and their associated side effects are very well known but the potential use of Kv11.1 activators as an anticancer strategy are still unexplored. In our previous work, we have established that stimulation of the Kv11.1 potassium channel activates a senescent-like program that is characterized by a significant increase in tumor suppressor protein levels, such as p21waf/cip and p16INK4A. In this study we investigated the mechanism linking Kv11.1 stimulation to augmentation of p21waf/cip protein level. We have demonstrated that the Kv11.1 channel activator NS1643 activates a calcineurin-dependent transcription of p21waf/cip and that this event is fundamental for the inhibitory effect of NS1643 on cell proliferation. Our results reveal a novel mechanism by which stimulation of Kv11.1 channel leads to transcription of a potent tumor suppressor and suggest a potential therapeutic use for Kv11.1 channel activators. PMID:25945833

Enzymatically Active Microgels from Self-Assembling Protein Nanofibrils for Microflow Chemistry.

PubMed

Zhou, Xiao-Ming; Shimanovich, Ulyana; Herling, Therese W; Wu, Si; Dobson, Christopher M; Knowles, Tuomas P J; Perrett, Sarah

2015-06-23

Amyloid fibrils represent a generic class of protein structure associated with both pathological states and with naturally occurring functional materials. This class of protein nanostructure has recently also emerged as an excellent foundation for sophisticated functional biocompatible materials including scaffolds and carriers for biologically active molecules. Protein-based materials offer the potential advantage that additional functions can be directly incorporated via gene fusion producing a single chimeric polypeptide that will both self-assemble and display the desired activity. To succeed, a chimeric protein system must self-assemble without the need for harsh triggering conditions which would damage the appended functional protein molecule. However, the micrometer to nanoscale patterning and morphological control of protein-based nanomaterials has remained challenging. This study demonstrates a general approach for overcoming these limitations through the microfluidic generation of enzymatically active microgels that are stabilized by amyloid nanofibrils. The use of scaffolds formed from biomaterials that self-assemble under mild conditions enables the formation of catalytic microgels while maintaining the integrity of the encapsulated enzyme. The enzymatically active microgel particles show robust material properties and their porous architecture allows diffusion in and out of reactants and products. In combination with microfluidic droplet trapping approaches, enzymatically active microgels illustrate the potential of self-assembling materials for enzyme immobilization and recycling, and for biological flow-chemistry. These design principles can be adopted to create countless other bioactive amyloid-based materials with diverse functions.

Understanding sources of contaminants of emerging concern in a mixed use watershed

USDA-ARS?s Scientific Manuscript database

Contaminants of emerging concern (CECs) have been detected in surface waters worldwide and include biologically active compounds originating from agricultural, residential, and industrial sources that may result in potential ecological and health effects. The objectives of this research were to dete...

Green Infrastructure Benefits for Communities Managing Nitrate in their Drinking Water Sources

EPA Science Inventory

Nitrate in water moving through the “biologically active soil zone” of riparian zones, wetlands and streams may undergo denitrification. Therefore GI techniques such as conservation and restoration of riparian zones, wetlands and streams (daylighting) have the potential to remov...

Plant defense activators as elicitors of oat avenanthramide biosynthesis

USDA-ARS?s Scientific Manuscript database

Oats produce a group of phenolic secondary metabolites termed “avenanthramides”. Among food crops these metabolites are unique to oat. In addition to their biological role as phytoalexins, the avenanthramides are potent antioxidants in vitro and have potential as nutraceuticals. In cellular assays ...

Unsupervised Analysis of the Effects of a Wastewater Treatment Plant Effluent on the Fathead Minnow Ovarian Transcriptome

EPA Science Inventory

Wastewater treatment plant (WWTP) effluents contain complex mixtures of chemicals, potentially including endocrine active chemicals (EACs), pharmaceuticals, and other contaminants of emerging concern (CECs). Due to the complex and variable nature of effluents, biological monitori...

NCT and Culture-Conscious Developmental Science

ERIC Educational Resources Information Center

Downing-Wilson, Deborah; Pelaprat, Etienne; Rosero, Ivan; Vadeboncoeur, Jennifer; Packer, Martin; Cole, Michael

2013-01-01

The authors share the belief that there is great potential for developmental science in bringing the ideas of Niche Construction Theory (NCT), as developed in evolutionary biology, into conversation with Vygotskian-inspired theories such as cultural-historical and activity theories, distributed cognition, and embodied cognition, although from…

Can biosolids reduce wind erosion of agricultural soils?

USDA-ARS?s Scientific Manuscript database

The application of biosolids to agricultural land has the potential to improve soil health and crop production. In addition, organic material contained in biosolids may enhance biological activity, retention of soil water, and soil aggregation. Thus, there is a likelihood that biosolids applied to s...

High-throughput screening, predictive modeling and computational embryology

EPA Science Inventory

High-throughput screening (HTS) studies are providing a rich source of data that can be applied to profile thousands of chemical compounds for biological activity and potential toxicity. EPA’s ToxCast™ project, and the broader Tox21 consortium, in addition to projects worldwide,...

An Upper Bound for Population Exposure Variability (SOT)

EPA Science Inventory

Tools for the rapid assessment of exposure potential are needed in order to put the results of rapidly-applied tools for assessing biological activity, such as ToxCast® and other high throughput methodologies, into a quantitative exposure context. The ExpoCast models (Wambaugh et...

Electromagnetic information transfer through aqueous system.

PubMed

Foletti, Alberto; Ledda, Mario; Lolli, Maria Grazia; Grimaldi, Settimio; Lisi, Antonella

2017-01-01

Several beneficial effects of the electromagnetic information transfer through aqueous system (EMITTAS) procedure have previously been reported in vitro. The clinical potential of this procedure has also started to be evaluated. Information flow in biological systems can be investigated through chemical and molecular approaches or by a biophysical approach focused on endogenous electrodynamic activities. Electromagnetic signals are endogenously generated at different levels of the biological organization and, likely, play an active role in synchronizing internal cell function or local/systemic adaptive response. Consequently, each adaptive response can be described by its specific electromagnetic pattern and, therefore, correlates with a unique and specific electromagnetic signature. A biophysical procedure synchronously integrating the EMITTAS procedure has already been applied for the treatment of articular pain, low-back pain, neck pain and mobility, fluctuating asymmetry, early-stage chronic kidney disease, refractory gynecological infections, minor anxiety and depression disorders. This clinical strategy involves a single treatment, since the EMITTAS procedure allows the patient to continue his/her own personal treatment at home by means of self-administration of the recorded aqueous system. A significant and long-lasting improvement has been reported, showing a potential beneficial use of this biophysical procedure in the management of common illnesses in an efficient, effective and personalized way. Data from recent studies suggest that aqueous systems may play a key role in providing the basis for recording, storing, transferring and retrieving clinically effective quanta of biological information. These features likely enable to trigger local and systemic self-regulation and self-regeneration potential of the organism.

Anticancer and antioxidant activity of bread enriched with broccoli sprouts.

PubMed

Gawlik-Dziki, Urszula; Świeca, Michał; Dziki, Dariusz; Sęczyk, Łukasz; Złotek, Urszula; Różyło, Renata; Kaszuba, Kinga; Ryszawy, Damian; Czyż, Jarosław

2014-01-01

This study is focused on antioxidant and anticancer capacity of bread enriched with broccoli sprouts (BS) in the light of their potential bioaccessibility and bioavailability. Generally, bread supplementation elevated antioxidant potential of product (both nonenzymatic and enzymatic antioxidant capacities); however, the increase was not correlated with the percent of BS. A replacement up to 2% of BS gives satisfactory overall consumers acceptability and desirable elevation of antioxidant potential. High activity was especially found for extracts obtained after simulated digestion, which allows assuming their protective effect for upper gastrointestinal tract; thus, the anticancer activity against human stomach cancer cells (AGS) was evaluated. A prominent cytostatic response paralleled by the inhibition of AGS motility in the presence of potentially mastication-extractable phytochemicals indicates that phenolic compounds of BS retain their biological activity in bread. Importantly, the efficient phenolics concentration was about 12 μM for buffer extract, 13 μM for extracts after digestion in vitro, and 7 μM for extract after absorption in vitro. Our data confirm chemopreventive potential of bread enriched with BS and indicate that BS comprise valuable food supplement for stomach cancer chemoprevention.

Retro-inverso forms of gastrin5-12 are as biologically active as glycine-extended gastrin in vitro but not in vivo.

PubMed

Marshall, Kathryn M; Laval, Marie; Sims, Ioulia; Shulkes, Arthur; Baldwin, Graham S

2015-12-01

Non-amidated gastrin peptides such as glycine-extended gastrin (Ggly) are biologically active in vitro and in vivo and have been implicated in the development of gastric and colonic cancers. Previous studies have shown that the truncated form of Ggly, the octapeptide LE5AY, was still biologically active in vitro, and that activity was dependent on ferric ion binding but independent of binding to the cholecystokinin 2 (CCK2) receptor. The present work was aimed at creating more stable gastrin-derived 'super agonists' using retro-inverso technology. The truncated LE5AY peptide was synthesized using end protecting groups in three forms with l-amino acids (GL), d-amino acids (GD) or retro-inverso (reverse order with d-amino acids; GRI). All of these peptides bound ferric ions with a 2:1 (Fe: peptide) ratio. As predicted, Ggly, GL and GRI were biologically active in vitro and increased cell proliferation in mouse gastric epithelial (IMGE-5) and human colorectal cancer (DLD-1) cell lines, and increased cell migration in DLD-1 cells. These activities were likely via the same mechanism as Ggly since no CCK1 or CCK2 binding was identified, and GD remained inactive in all assays. Surprisingly, unlike Ggly, GL and GRI were not active in vivo. While Ggly stimulated colonic crypt height and proliferation rates in gastrin knockout mice, GL and GRI did not. The apparent lack of activity may be due to rapid clearance of these smaller peptides. Nevertheless further work designing and testing retro-inverso gastrins is warranted, as it may lead to the generation of super agonists that could potentially be used to treat patients with gastrointestinal disorders with reduced mucosal function. Copyright © 2015 Elsevier Inc. All rights reserved.

Protein Neddylation: Beyond Cullin-RING Ligases

PubMed Central

Enchev, Radoslav I.; Schulman, Brenda A.; Peter, Matthias

2016-01-01

NEDD8 is a ubiquitin-like protein that activates the largest ubiquitin E3 ligase family, the cullin RING ligases. Many non-cullin neddylation targets have been proposed in recent years. However, overexpression of exogenous NEDD8 can trigger NEDD8 conjugation through the ubiquitylation machinery, which makes validating potential NEDD8 targets challenging. Here we re-evaluate these studies in light of the current understanding of the neddylation pathway, and suggest criteria for the identification of genuine neddylation substrates under homeostatic conditions. We describe the biological processes that might be regulated by non-cullin neddylation, and the utility of neddylation inhibitors for research and as potential therapies. Understanding the biological significance of non-cullin neddylation is an exciting research prospect primed to reveal fundamental insights. PMID:25531226

SPR Biosensors in Direct Molecular Fishing: Implications for Protein Interactomics.

PubMed

Florinskaya, Anna; Ershov, Pavel; Mezentsev, Yuri; Kaluzhskiy, Leonid; Yablokov, Evgeniy; Medvedev, Alexei; Ivanov, Alexis

2018-05-18

We have developed an original experimental approach based on the use of surface plasmon resonance (SPR) biosensors, applicable for investigation of potential partners involved in protein⁻protein interactions (PPI) as well as protein⁻peptide or protein⁻small molecule interactions. It is based on combining a SPR biosensor, size exclusion chromatography (SEC), mass spectrometric identification of proteins (LC-MS/MS) and direct molecular fishing employing principles of affinity chromatography for isolation of potential partner proteins from the total lysate of biological samples using immobilized target proteins (or small non-peptide compounds) as ligands. Applicability of this approach has been demonstrated within the frame of the Human Proteome Project (HPP) and PPI regulation by a small non-peptide biologically active compound, isatin.

A model to estimate the oestrogen receptor mediated effects from exposure to soy isoflavones in food.

PubMed

Safford, Bob; Dickens, Andrea; Halleron, Nadine; Briggs, David; Carthew, Philip; Baker, Valerie

2003-10-01

The advantages that regular consumption of a diet containing soy may have on human health have been enshrined in a major health claim that has been approved by the Food and Drug Administration in the USA, regarding potential protection from heart disease by soy. This could have a major influence on the dietary consumption patterns of soy for consumers and lead to the development of soy enriched foods to enable consumers to achieve the benefits thought to be associated with increased soy consumption in a Western diet. If an increase in soy consumption is beneficial to particular disease conditions, there is always the possibility that there will be effects other than those that are desirable. For soy-containing foods there has been concern that the phytoestrogen content of soy, which is composed of several isoflavones, could be a separate health issue, due to the oestrogen-like activity of isoflavones. To address this, a method has been developed to estimate, relative to 17-beta oestradiol, the activity of the common isoflavones present in soy phytoestrogens, based on their binding to and transcriptional activation of the major oestrogen receptor sub-types alpha and beta. Using this approach, the additional oestrogen-like activity that would be expected from inclusion of soy supplemented foodstuffs in a Western diet, can be determined for different sub-populations, who may have different susceptibilities to the potential for the unwanted biological effects occurring with consumption of soy enriched foods. Because of the theoretical nature of this model, and the controversy over the nature of whether some of the oestrogen-like effects of phytoestrogens are adverse, the biological effects of soy isoflavones and their potential for adverse effects in man, is also reviewed. The question that is critical to the long term safe use of foods enriched in soy is, which observed biological effects in animal studies are likely to also occur in man and whether these would have an adverse effect on human health.

Modifications of the chemical structure of phenolics differentially affect physiological activities in pulvinar cells of Mimosa pudica L. II. Influence of various molecular properties in relation to membrane transport.

PubMed

Rocher, Françoise; Roblin, Gabriel; Chollet, Jean-François

2017-03-01

Early prediction of compound absorption by cells is of considerable importance in the building of an integrated scheme describing the impact of a compound on intracellular biological processes. In this scope, we study the structure-activity relationships of several benzoic acid-related phenolics which are involved in many plant biological phenomena (growth, flowering, allelopathy, defense processes). Using the partial least squares (PLS) regression method, the impact of molecular descriptors that have been shown to play an important role concerning the uptake of pharmacologically active compounds by animal cells was analyzed in terms of the modification of membrane potential, variations in proton flux, and inhibition of the osmocontractile reaction of pulvinar cells of Mimosa pudica leaves. The hydrogen bond donors (HBD) and hydrogen bond acceptors (HBA), polar surface area (PSA), halogen ratio (Hal ratio), number of rotatable bonds (FRB), molar volume (MV), molecular weight (MW), and molar refractivity (MR) were considered in addition to two physicochemical properties (logD and the amount of non-dissociated form in relation to pKa). HBD + HBA and PSA predominantly impacted the three biological processes compared to the other descriptors. The coefficient of determination in the quantitative structure-activity relationship (QSAR) models indicated that a major part of the observed seismonasty inhibition and proton flux modification can be explained by the impact of these descriptors, whereas this was not the case for membrane potential variations. These results indicate that the transmembrane transport of the compounds is a predominant component. An increasing number of implicated descriptors as the biological processes become more complex may reflect their impacts on an increasing number of sites in the cell. The determination of the most efficient effectors may lead to a practical use to improve drugs in the control of microbial attacks on plants.

Urine: Waste product or biologically active tissue?

PubMed

2018-03-01

Historically, urine has been viewed primarily as a waste product with little biological role in the overall health of an individual. Increasingly, data suggest that urine plays a role in human health beyond waste excretion. For example, urine might act as an irritant and contribute to symptoms through interaction with-and potential compromise of-the urothelium. To explore the concept that urine may be a vehicle for agents with potential or occult bioactivity and to discuss existing evidence and novel research questions that may yield insight into such a role, the National Institute of Diabetes and Digestive and Kidney Disease invited experts in the fields of comparative evolutionary physiology, basic science, nephrology, urology, pediatrics, metabolomics, and proteomics (among others) to a Urinology Think Tank meeting on February 9, 2015. This report reflects ideas that evolved from this meeting and current literature, including the concept of urine quality, the biological, chemical, and physical characteristics of urine, including the microbiota, cells, exosomes, pH, metabolites, proteins, and specific gravity (among others). Additionally, the manuscript presents speculative, and hopefully testable, ideas about the functional roles of urine constituents in health and disease. Moving forward, there are several questions that need further understanding and pursuit. There were suggestions to consider actively using various animal models and their biological specimens to elaborate on basic mechanistic information regarding human bladder dysfunction. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Simple Biological Systems for Assessing the Activity of Superoxide Dismutase Mimics

PubMed Central

Tovmasyan, Artak; Reboucas, Julio S.

2014-01-01

Abstract Significance: Half a century of research provided unambiguous proof that superoxide and species derived from it—reactive oxygen species (ROS)—play a central role in many diseases and degenerative processes. This stimulated the search for pharmaceutical agents that are capable of preventing oxidative damage, and methods of assessing their therapeutic potential. Recent Advances: The limitations of superoxide dismutase (SOD) as a therapeutic tool directed attention to small molecules, SOD mimics, that are capable of catalytically scavenging superoxide. Several groups of compounds, based on either metal complexes, including metalloporphyrins, metallocorroles, Mn(II) cyclic polyamines, and Mn(III) salen derivatives, or non-metal based compounds, such as fullerenes, nitrones, and nitroxides, have been developed and studied in vitro and in vivo. Very few entered clinical trials. Critical Issues and Future Directions: Development of SOD mimics requires in-depth understanding of their mechanisms of biological action. Elucidation of both molecular features, essential for efficient ROS-scavenging in vivo, and factors limiting the potential side effects requires biologically relevant and, at the same time, relatively simple testing systems. This review discuses the advantages and limitations of genetically engineered SOD-deficient unicellular organisms, Escherichia coli and Saccharomyces cerevisiae as tools for investigating the efficacy and mechanisms of biological actions of SOD mimics. These simple systems allow the scrutiny of the minimal requirements for a functional SOD mimic: the association of a high catalytic activity for superoxide dismutation, low toxicity, and an efficient cellular uptake/biodistribution. Antioxid. Redox Signal. 20, 2416–2436. PMID:23964890

Nrf2 and HSF-1 Pathway Activation via Hydroquinone-Based Proelectrophilic Small Molecules Is Regulated by Electrochemical Oxidation Potential

PubMed Central

Stalder, Romain; McKercher, Scott R.; Williamson, Robert E.; Roth, Gregory P.; Lipton, Stuart A.

2015-01-01

Activation of the Kelch-like ECH-associated protein 1/nuclear factor (erythroid-derived 2)-like 2 and heat-shock protein 90/heat-shock factor-1 signal-transduction pathways plays a central role in combatting cellular oxidative damage and related endoplasmic reticulum stress. Electrophilic compounds have been shown to be activators of these transcription-mediated responses through S-alkylation of specific regulatory proteins. Previously, we reported that a prototype compound (D1, a small molecule representing a proelectrophilic, para-hydroquinone species) exhibited neuroprotective action by activating both of these pathways. We hypothesized that the para-hydroquinone moiety was critical for this activation because it enhanced transcription of these neuroprotective pathways to a greater degree than that of the corresponding ortho-hydroquinone isomer. This notion was based on the differential oxidation potentials of the isomers for the transformation of the hydroquinone to the active, electrophilic quinone species. Here, to further test this hypothesis, we synthesized a pair of para- and ortho-hydroquinone-based proelectrophilic compounds and measured their redox potentials using analytical cyclic voltammetry. The redox potential was then compared with functional biological activity, and the para-hydroquinones demonstrated a superior neuroprotective profile. PMID:26243592

Nrf2 and HSF-1 Pathway Activation via Hydroquinone-Based Proelectrophilic Small Molecules is Regulated by Electrochemical Oxidation Potential.

PubMed

Satoh, Takumi; Stalder, Romain; McKercher, Scott R; Williamson, Robert E; Roth, Gregory P; Lipton, Stuart A

2015-01-01

Activation of the Kelch-like ECH-associated protein 1/nuclear factor (erythroid-derived 2)-like 2 and heat-shock protein 90/heat-shock factor-1 signal-transduction pathways plays a central role in combatting cellular oxidative damage and related endoplasmic reticulum stress. Electrophilic compounds have been shown to be activators of these transcription-mediated responses through S-alkylation of specific regulatory proteins. Previously, we reported that a prototype compound (D1, a small molecule representing a proelectrophilic, para-hydroquinone species) exhibited neuroprotective action by activating both of these pathways. We hypothesized that the para-hydroquinone moiety was critical for this activation because it enhanced transcription of these neuroprotective pathways to a greater degree than that of the corresponding ortho-hydroquinone isomer. This notion was based on the differential oxidation potentials of the isomers for the transformation of the hydroquinone to the active, electrophilic quinone species. Here, to further test this hypothesis, we synthesized a pair of para- and ortho-hydroquinone-based proelectrophilic compounds and measured their redox potentials using analytical cyclic voltammetry. The redox potential was then compared with functional biological activity, and the para-hydroquinones demonstrated a superior neuroprotective profile. © The Author(s) 2015.

The dual role of tumor necrosis factor (TNF) in cancer biology.

PubMed

Bertazza, Loris; Mocellin, Simone

2010-01-01

Tumor necrosis factor (TNF) is a cytokine with well known anticancer properties and is being utilized as anticancer agent for the treatment of patients with locally advanced solid tumors. However, TNF role in cancer biology is debated. In fact, in spite of the wealth of evidence supporting its antitumor activity, the cascade of molecular events underlying TNF-mediated tumor regression observed in vivo is still incompletely elucidated. Furthermore, some preclinical findings suggest that TNF may even promote cancer development and progression. With this work we intend to summarize the molecular biology of TNF (with particular regard to its tumor-related activities) and review the experimental and clinical evidence currently available describing the complex and sometime apparently conflicting relationship between this cytokine, cancer biology and antitumor therapy. We also propose a model to explain the dual effect of TNF based on the exposure time and cytokine levels reached within the tumor microenvironment. Finally, we overview recent research findings that might lead to new ways for exploiting the anticancer potential of TNF in the clinical setting.

Biomaterials-Based Electronics: Polymers and Interfaces for Biology and Medicine

PubMed Central

Muskovich, Meredith; Bettinger, Christopher J.

2012-01-01

Advanced polymeric biomaterials continue to serve as a cornerstone of new medical technologies and therapies. The vast majority of these materials, both natural and synthetic, interact with biological matter without direct electronic communication. However, biological systems have evolved to synthesize and employ naturally-derived materials for the generation and modulation of electrical potentials, voltage gradients, and ion flows. Bioelectric phenomena can be interpreted as potent signaling cues for intra- and inter-cellular communication. These cues can serve as a gateway to link synthetic devices with biological systems. This progress report will provide an update on advances in the application of electronically active biomaterials for use in organic electronics and bio-interfaces. Specific focus will be granted to the use of natural and synthetic biological materials as integral components in technologies such as thin film electronics, in vitro cell culture models, and implantable medical devices. Future perspectives and emerging challenges will also be highlighted. PMID:23184740

PPAR Ligands Function as Suppressors That Target Biological Actions of HMGB1

PubMed Central

Chen, Tianhui

2016-01-01

High mobility group box 1 (HMGB1), which has become one of the most intriguing molecules in inflammatory disorders and cancers and with which ligand-activated peroxisome proliferator-activated receptors (PPARs) are highly associated, is considered as a therapeutic target. Of particular interest is the fact that certain PPAR ligands have demonstrated their potent anti-inflammatory activities and potential anticancer effects. In this review article we summarize recent experimental evidence that PPAR ligands function as suppressors that target biological actions of HMGB1, including intracellular expression, receptor signaling cascades, and extracellular secretion of HMGB1 in cell lines and/or animal models. We also propose the possible mechanisms underlying PPAR involvement in inflammatory disorders and discuss the future therapeutic value of PPAR ligands targeting HMGB1 molecule for cancer prevention and treatment. PMID:27563308

Inhibition of angiogenic attributes by decursin in endothelial cells and ex vivo rat aortic ring angiogenesis model.

PubMed

Bhat, Tariq A; Moon, Jung S; Lee, Sookyeon; Yim, Dongsool; Singh, Rana P

2011-11-01

The present study was undertaken to observe the inhibition of angiogenesis by decursin. It was the first time to show that decursin offered strong anti-angiogenic activities under the biologically relevant growth (with serum) conditions. Decursin significantly inhibited human umbilical vein endothelial cell (HUVEC) proliferation concomitant with G1 phase cell cycle arrest. Decursin also inhibited HUVEC-capillary tube formation and invasion/migration in a dose-dependant manner which was associated with the suppression of matrix metalloproteinase (MMP) -2 and -9 activities. Decursin suppressed angiogenesis in ex vivo rat aortic ring angiogenesis model where it significantly inhibited blood capillary-network sprouting from rat aortic sections. Taken together, these findings suggested anti-angiogenic activity of decursin in biologically relevant condition, and warrants further pre-clinical studies for its potential clinical usefulness.

Sandalwood Album Oil as a Botanical Therapeutic in Dermatology.

PubMed

Moy, Ronald L; Levenson, Corey

2017-10-01

Many skin conditions and diseases are characterized by inflammation, infection, and hyperplasia. Safe and effective topical treatment options that can be used long-term are needed. Traditional botanical medicines, which are often complex mixtures that exert their biological activities via multiple mechanisms of action, are being studied as potential new active ingredients in dermatology. Sandalwood album oil (SAO), also known as East Indian sandalwood oil (EISO), is an essential oil distilled from the Santalum album tree and has demonstrated biological activity as an anti-inflammatory, anti-microbial, and anti-proliferative agent. Sandalwood album oil has also shown promise in clinical trials for treatment of acne, psoriasis, eczema, common warts, and molluscum contagiosum. The favorable safety profile, ease of topical use, and recent availability of pharmaceutical-grade sandalwood album oil support its broader use as the basis of novel therapies in dermatology.

Methods used to characterize the chemical composition and biological activity of environmental waters throughout the United States, 2012-14

USGS Publications Warehouse

Romanok, Kristin M.; Reilly, Timothy J.; Barber, Larry B.; Boone, J. Scott; Buxton, Herbert T.; Foreman, William T.; Furlong, Edward T.; Hladik, Michelle; Iwanowicz, Luke R.; Journey, Celeste A.; Kolpin, Dana W.; Kuivila, Kathryn; Loftin, Keith A.; Mills, Marc A.; Meyer, Michael T.; Orlando, James L.; Smalling, Kelly L.; Villeneuve, Daniel L.; Bradley, Paul M.

2017-03-22

A vast array of chemical compounds are in wide commercial use in the United States, and the potential ecological and human-health effect of exposure to chemical mixtures has been identified as a high priority in environment health science. Awareness of the potential effects of low-level chemical exposures is rising. The U.S. Geological Survey, in cooperation with the U.S. Environmental Protection Agency, conducted a study in which samples were collected from 38 streams in 25 States to provide an overview of contaminants found in stream water across the Nation. Additionally, biological screening assays were used to help determine any potential ecological and human-health effects of these chemical mixtures and to prioritize target chemicals for future toxicological studies. This report describes the site locations and the sampling and analytical methods and quality-assurance procedures used in the study.

Potential control of multiple sclerosis by cannabis and the endocannabinoid system.

PubMed

Pryce, Gareth; Baker, David

2012-08-01

For many years, multiple sclerosis (MS) patients have been self-medicating with illegal street cannabis to alleviate symptoms associated with MS. Data from animal models of MS and clinical studies have supported the anecdotal data that cannabis can improve symptoms such as limb spasticity, which are commonly associated with progressive MS, by the modulation of excessive neuronal signalling. This has lead to cannabis-based medicines being approved for the treatment of pain and spasticity in MS for the first time. Experimental studies into the biology of the endocannabinoid system have revealed that cannabinoids have activity, not only in symptom relief but also potentially in neuroprotective strategies which may slow disease progression and thus delay the onset of symptoms such as spasticity. This review appraises the current knowledge of cannabinoid biology particularly as it pertains to MS and outlines potential future therapeutic strategies for the treatment of disease progression in MS.

Effect of biologically active fraction of Nardostachys jatamansi on cerulein-induced acute pancreatitis

PubMed Central

Bae, Gi-Sang; Kim, Min-Sun; Park, Kyoung-Chel; Koo, Bon Soon; Jo, Il-Joo; Choi, Sun Bok; Lee, Dong-Sung; Kim, Youn-Chul; Kim, Tae-Hyeon; Seo, Sang-Wan; Shin, Yong Kook; Song, Ho-Joon; Park, Sung-Joo

2012-01-01

AIM: To determine if the fraction of Nardostachys jatamansi (NJ) has the potential to ameliorate the severity of acute pancreatitis (AP). METHODS: Mice were administered the biologically active fraction of NJ, i.e., the 4th fraction (NJ4), intraperitoneally, and then injected with the stable cholecystokinin analogue cerulein hourly for 6 h. Six hours after the last cerulein injection, the pancreas, lung, and blood were harvested for morphological examination, measurement of cytokine expression, and examination of neutrophil infiltration. RESULTS: NJ4 administration attenuated the severity of AP and lung injury associated with AP. It also reduced cytokine production and neutrophil infiltration and resulted in the in vivo up-regulation of heme oxygenase-1 (HO-1). Furthermore, NJ4 and its biologically active fraction, NJ4-2 inhibited the cerulein-induced death of acinar cells by inducing HO-1 in isolated pancreatic acinar cells. CONCLUSION: These results suggest that NJ4 may be a candidate fraction offering protection in AP and NJ4 might ameliorate the severity of pancreatitis by inducing HO-1 expression. PMID:22783046

The Biological Activities of Oleocanthal from a Molecular Perspective.

PubMed

Pang, Kok-Lun; Chin, Kok-Yong

2018-05-06

Oleocanthal is a minor constituent of olive oil with strong anti-inflammatory activities. Since the pathogenesis of many chronic diseases involves inflammatory and oxidative components, oleocanthal is a promising agent to prevent these conditions. This review aimed to summarise the current beneficial health effects of oleocanthal and the molecular basis of its biological actions. The anti-inflammatory, antioxidative, antimicrobial, anticancer and neuroprotective activities of oleocanthal have been examined by previous studies. Of these, studies on the anticancer effects have been the most extensive. Oleocanthal was reported to suppress melanoma, breast, liver, and colon cancer cells. Neurological studies focused on the effects of oleocanthal against Alzheimer’s disease. Oleocanthal improved clearance of the amyloid beta protein from neurons and reduced the inflammation of astrocytes. Despite the positive results, validation of the biological effects of oleocanthal in animal disease models is limited and should be emphasized in the future. As a conclusion, oleocanthal may act together with other bioactive compounds in olive oil to achieve its therapeutic potential. The use of oleocanthal alone as a single therapeutic measure awaits validation from future studies.

The Biological Activities of Oleocanthal from a Molecular Perspective

PubMed Central

Pang, Kok-Lun; Chin, Kok-Yong

2018-01-01

Oleocanthal is a minor constituent of olive oil with strong anti-inflammatory activities. Since the pathogenesis of many chronic diseases involves inflammatory and oxidative components, oleocanthal is a promising agent to prevent these conditions. This review aimed to summarise the current beneficial health effects of oleocanthal and the molecular basis of its biological actions. The anti-inflammatory, antioxidative, antimicrobial, anticancer and neuroprotective activities of oleocanthal have been examined by previous studies. Of these, studies on the anticancer effects have been the most extensive. Oleocanthal was reported to suppress melanoma, breast, liver, and colon cancer cells. Neurological studies focused on the effects of oleocanthal against Alzheimer’s disease. Oleocanthal improved clearance of the amyloid beta protein from neurons and reduced the inflammation of astrocytes. Despite the positive results, validation of the biological effects of oleocanthal in animal disease models is limited and should be emphasized in the future. As a conclusion, oleocanthal may act together with other bioactive compounds in olive oil to achieve its therapeutic potential. The use of oleocanthal alone as a single therapeutic measure awaits validation from future studies. PMID:29734791

Perspectives in active liquid crystals

PubMed Central

Majumdar, Apala; Cristina, Marchetti M.; Virga, Epifanio G.

2014-01-01

Active soft matter is a young, growing field, with potential applications to a wide variety of systems. This Theme Issue explores this emerging new field by highlighting active liquid crystals. The collected contributions bridge theory to experiment, mathematical theories of passive and active nematics, spontaneous flows to defect dynamics, microscopic to continuum levels of description, spontaneous activity to biological activation. While the perspectives offered here only span a small part of this rapidly evolving field, we trust that they might provide the interested reader with a taste for this new class of non-equilibrium systems and their rich behaviour. PMID:25332386

Synthesis: Small library of hybrid scaffolds of benzothiazole having hydrazone and evaluation of their β-glucuronidase activity.

PubMed

Taha, Muhammad; Arbin, Mastura; Ahmat, Norizan; Imran, Syahrul; Rahim, Fazal

2018-04-01

Due to the great biological importance of β-glucuronidase inhibitors, here in this study, we have synthesized a library of novel benzothiazole derivatives (1-30), characterized by different spectroscopic methods and evaluated for β-glucuronidase inhibitory potential. Among the series sixteen compounds i.e.1-6, 8, 9, 11, 14, 15, 20-23 and 26 showed outstanding inhibitory potential with IC 50 value ranging in between 16.50 ± 0.26 and 59.45 ± 1.12 when compared with standard d-Saccharic acid 1,4-lactone (48.4 ± 1.25 µM). Except compound 8 and 23 all active analogs showed better potential than the standard. Structure activity relationship has been established. Copyright © 2018 Elsevier Inc. All rights reserved.

Bisphosphonates as potential adjuvants for patients with cancers of the digestive system.

PubMed

Ang, Celina; Doyle, Erin; Branch, Andrea

2016-01-21

Best known for their anti-resorptive activity in bone, bisphosphonates (BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antiangiogenic and immune-modulating properties. Clinical studies in multiple malignancies suggest that BPs may be active in the prevention or treatment of cancer. Digestive tract malignancies represent a large and heterogeneous disease group, and the activity of BPs in these cancers has not been extensively studied. Recent data showing that some BPs inhibit human epidermal growth factor receptor (HER) signaling highlight a potential therapeutic opportunity in digestive cancers, many of which have alterations in the HER axis. Herein, we review the available evidence providing a rationale for the repurposing of BPs as a therapeutic adjunct in the treatment of digestive malignancies, especially in HER-driven subgroups.

Influences of NOM composition and bacteriological characteristics on biological stability in a full-scale drinking water treatment plant.

PubMed

Park, Ji Won; Kim, Hyun-Chul; Meyer, Anne S; Kim, Sungpyo; Maeng, Sung Kyu

2016-10-01

The influences of natural organic matter (NOM) and bacteriological characteristics on the biological stability of water were investigated in a full-scale drinking water treatment plant. We found that prechlorination decreased the hydrophobicity of the organic matter and significantly increased the high-molecular-weight (MW) dissolved organic matter, such as biopolymers and humic substances. High-MW organic matter and structurally complex compounds are known to be relatively slowly biodegradable; however, because of the prechlorination step, the indigenous bacteria could readily utilise these fractions as assimilable organic carbon. Sequential coagulation and sedimentation resulted in the substantial removal of biopolymer (74%), humic substance (33%), bacterial cells (79%), and assimilable organic carbon (67%). Rapid sand and granular activated carbon filtration induced an increase in the low-nucleic-acid content bacteria; however, these bacteria were biologically less active in relation to enzymatic activity and ATP. The granular activated carbon step was essential to securing biological stability (the ability to prevent bacterial growth) by removing the residual assimilable organic carbon that had formed during the ozone treatment. The growth potential of Escherichia coli and indigenous bacteria were found to differ in respect to NOM characteristics. In comparison with E. coli, the indigenous bacteria utilised a broader range of NOM as a carbon source. Principal component analysis demonstrated that the measured biological stability of water could differ, depending on the NOM characteristics, as well as on the bacterial inoculum selected for the analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-Throughput Models for Exposure-Based Chemical Prioritization in the ExpoCast Project

EPA Science Inventory

The United States Environmental Protection Agency (U.S. EPA) must characterize potential risks to human health and the environment associated with manufacture and use of thousands of chemicals. High-throughput screening (HTS) for biological activity allows the ToxCast research pr...

High-Throughput Exposure Potential Prioritization for ToxCast Chemicals

EPA Science Inventory

The U.S. EPA must consider lists of hundreds to thousands of chemicals when prioritizing research resources in order to identify risk to human populations and the environment. High-throughput assays to identify biological activity in vitro have allowed the ToxCastTM program to i...

Inflammatory Cytokine Response to Ambient Particles Varies due to Field Collection Procedures

EPA Science Inventory

In-vitro assays of biological activity induced by particulate matter (PM) are a tool for investigating mechanisms of PM health effects. They have potential application to exposure assessment in chronic disease epidemiology. However, there has been little reporting of the impact o...

Pathway Profiling and Tissue Modeling of Developmental Toxicity

EPA Science Inventory

High-throughput and high-content screening (HTS-HCS) studies are providing a rich source of data that can be applied to in vitro profiling of chemical compounds for biological activity and potential toxicity. EPA’s ToxCast™ project, and the broader Tox21 consortium, in addition t...

VIRTUAL EMBRYO: SYSTEMS MODELING IN DEVELOPMENTAL TOXICITY - Symposium: SOT 2012

EPA Science Inventory

High-throughput screening (HTS) studies are providing a rich source of data that can be applied to in vitro profiling of chemical compounds for biological activity and potential toxicity. Chemical profiling in ToxCast covered 965 drugs-chemicals in over 500 diverse assays testing...

Virtual Embryo: Systems Modeling in Developmental Toxicity

EPA Science Inventory

High-throughput and high-content screening (HTS-HCS) studies are providing a rich source of data that can be applied to in vitro profiling of chemical compounds for biological activity and potential toxicity. EPA’s ToxCast™ project, and the broader Tox21 consortium, in addition t...

Characterizing a novel strain of Bacillus amyloliquefaciens BAC03 for potential biological control application

USDA-ARS?s Scientific Manuscript database

Aims: Identify and characterize a bacterial strain from suppressive soil, BAC03, evaluate its antimicrobial activity against Streptomyces scabies and other microorganisms, and characterize an antimicrobial substance produced by this strain. Methods and Results: Bacterial strain BAC03 (isolated from ...

Biological activity of peanut (Arachis hypogaea) phytoalexins and selected natural and synthetic stilbenoids

USDA-ARS?s Scientific Manuscript database

The peanut plant (Arachis hypogaea L.), when infected by a microbial pathogen, is capable of producing stilbene-derived compounds that are considered antifungal phytoalexins. In addition, the potential health benefits of other stilbenoids from peanuts, including resveratrol and pterostilbene have be...

Chromanyl-isoxazolidines as Antibacterial agents: Synthesis, Biological Evaluation, Quantitative Structure Activity Relationship, and Molecular Docking Studies.

PubMed

Singh, Gagandeep; Sharma, Anuradha; Kaur, Harpreet; Ishar, Mohan Paul S

2016-02-01

Regio- and stereoselective 1,3-dipolar cycloadditions of C-(chrom-4-one-3-yl)-N-phenylnitrones (N) with different mono-substituted, disubstituted, and cyclic dipolarophiles were carried out to obtain substituted N-phenyl-3'-(chrom-4-one-3-yl)-isoxazolidines (1-40). All the synthesized compounds were assayed for their in vitro antibacterial activity and display significant inhibitory potential; in particular, compound 32 exhibited good inhibitory activity against Salmonella typhymurium-1 & Salmonella typhymurium-2 with minimum inhibitory concentration value of 1.56 μg/mL and also showed good potential against methicillin-resistant Staphylococcus aureus with minimum inhibitory concentration 3.12 μg/mL. Quantitative structure activity relationship investigations with stepwise multiple linear regression analysis and docking simulation studies have been performed for validation of the observed antibacterial potential of the investigated compounds for determination of the most important parameters regulating antibacterial activities. © 2015 John Wiley & Sons A/S.

Biotic and abiotic degradation of CL-20 and RDX in soils.

PubMed

Crocker, Fiona H; Thompson, Karen T; Szecsody, James E; Fredrickson, Herbert L

2005-01-01

The caged cyclic nitramine 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) is a new explosive that has the potential to replace existing military explosives, but little is known about its environmental toxicity, transport, and fate. We quantified and compared the aerobic environmental fate of CL-20 to the widely used cyclic nitramine explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in surface and subsurface soil microcosms. Soil-free controls and biologically attenuated soil controls were used to separate abiotic processes from biologically mediated processes. Both abiotic and biological processes significantly degraded CL-20 in all soils examined. Apparent abiotic, first-order degradation rates (k) for CL-20 were not significantly different between soil-free controls (0.018 < k < 0.030 d(-1)) and biologically attenuated soil controls (0.003 < k < 0.277 d(-1)). The addition of glucose to biologically active soil microcosms significantly increased CL-20 degradation rates (0.068 < k < 1.22 d(-1)). Extents of mineralization of (14)C-CL-20 to (14)CO(2) in biologically active soil microcosms were 41.1 to 55.7%, indicating that the CL-20 cage was broken, since all carbons are part of the heterocyclic cage. Under aerobic conditions, abiotic degradation rates of RDX were generally slower (0 < k < 0.032 d(-1)) than abiotic CL-20 degradation rates. In biologically active soil microcosms amended with glucose aerobic RDX degradation rates varied between 0.010 and 0.474 d(-1). Biodegradation was a key factor in determining the environmental fate of RDX, while a combination of biotic and abiotic processes was important with CL-20. Our data suggest that CL-20 should be less recalcitrant than RDX in aerobic soils.

Antibacterial Free Fatty Acids and Monoglycerides: Biological Activities, Experimental Testing, and Therapeutic Applications

PubMed Central

Yoon, Bo Kyeong; Jackman, Joshua A.; Valle-González, Elba R.

2018-01-01

Antimicrobial lipids such as fatty acids and monoglycerides are promising antibacterial agents that destabilize bacterial cell membranes, causing a wide range of direct and indirect inhibitory effects. The goal of this review is to introduce the latest experimental approaches for characterizing how antimicrobial lipids destabilize phospholipid membranes within the broader scope of introducing current knowledge about the biological activities of antimicrobial lipids, testing strategies, and applications for treating bacterial infections. To this end, a general background on antimicrobial lipids, including structural classification, is provided along with a detailed description of their targeting spectrum and currently understood antibacterial mechanisms. Building on this knowledge, different experimental approaches to characterize antimicrobial lipids are presented, including cell-based biological and model membrane-based biophysical measurement techniques. Particular emphasis is placed on drawing out how biological and biophysical approaches complement one another and can yield mechanistic insights into how the physicochemical properties of antimicrobial lipids influence molecular self-assembly and concentration-dependent interactions with model phospholipid and bacterial cell membranes. Examples of possible therapeutic applications are briefly introduced to highlight the potential significance of antimicrobial lipids for human health and medicine, and to motivate the importance of employing orthogonal measurement strategies to characterize the activity profile of antimicrobial lipids. PMID:29642500

Limiting the protein corona: A successful strategy for in vivo active targeting of anti-HER2 nanobody-functionalized nanostars.

PubMed

D'Hollander, Antoine; Jans, Hilde; Velde, Greetje Vande; Verstraete, Charlotte; Massa, Sam; Devoogdt, Nick; Stakenborg, Tim; Muyldermans, Serge; Lagae, Liesbet; Himmelreich, Uwe

2017-04-01

Gold nanoparticles hold great promise as anti-cancer theranostic agents against cancer by actively targeting the tumor cells. As this potential has been supported numerously during in vitro experiments, the effective application is hampered by our limited understanding and control of the interactions within complex in vivo biological systems. When these nanoparticles are exposed to a biological environment, their surfaces become covered with proteins and biomolecules, referred to as the protein corona, reducing the active targeting capabilities. We demonstrate a chemical strategy to overcome this issue by reducing the protein corona's thickness by blocking the active groups of the self-assembled monolayer on gold nanostars. An optimal blocking agent, 2-mercapto ethanol, has been selected based on charge and length of the carbon chain. By using a nanobody as a biological ligand of the human epidermal growth factor 2 receptor (HER2), the active targeting is demonstrated in vitro and in vivo in an experimental tumor model by using darkfield microscopy and photoacoustic imaging. In this study, we have established gold nanostars as a conceivable theranostic agent with a specificity for HER2-positive tumors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional inclusion bodies produced in the yeast Pichia pastoris.

PubMed

Rueda, Fabián; Gasser, Brigitte; Sánchez-Chardi, Alejandro; Roldán, Mònica; Villegas, Sandra; Puxbaum, Verena; Ferrer-Miralles, Neus; Unzueta, Ugutz; Vázquez, Esther; Garcia-Fruitós, Elena; Mattanovich, Diethard; Villaverde, Antonio

2016-10-01

Bacterial inclusion bodies (IBs) are non-toxic protein aggregates commonly produced in recombinant bacteria. They are formed by a mixture of highly stable amyloid-like fibrils and releasable protein species with a significant extent of secondary structure, and are often functional. As nano structured materials, they are gaining biomedical interest because of the combination of submicron size, mechanical stability and biological activity, together with their ability to interact with mammalian cell membranes for subsequent cell penetration in absence of toxicity. Since essentially any protein species can be obtained as IBs, these entities, as well as related protein clusters (e.g., aggresomes), are being explored in biocatalysis and in biomedicine as mechanically stable sources of functional protein. One of the major bottlenecks for uses of IBs in biological interfaces is their potential contamination with endotoxins from producing bacteria. To overcome this hurdle, we have explored here the controlled production of functional IBs in the yeast Pichia pastoris (Komagataella spp.), an endotoxin-free host system for recombinant protein production, and determined the main physicochemical and biological traits of these materials. Quantitative and qualitative approaches clearly indicate the formation of IBs inside yeast, similar in morphology, size and biological activity to those produced in E. coli, that once purified, interact with mammalian cell membranes and penetrate cultured mammalian cells in absence of toxicity. Structurally and functionally similar from those produced in E. coli, the controlled production of IBs in P. pastoris demonstrates that yeasts can be used as convenient platforms for the biological fabrication of self-organizing protein materials in absence of potential endotoxin contamination and with additional advantages regarding, among others, post-translational modifications often required for protein functionality.

Nanoelectronics meets biology: from new nanoscale devices for live-cell recording to 3D innervated tissues.

PubMed

Duan, Xiaojie; Lieber, Charles M

2013-10-01

High spatiotemporal resolution interfaces between electrical sensors and biological systems, from single live cells to tissues, is crucial for many areas, including fundamental biophysical studies as well as medical monitoring and intervention. Herein, we summarize recent progress in the development and application of novel nanoscale devices for intracellular electrical recording of action potentials and the effort of merging electronic and biological systems seamlessly in three dimensions by using macroporous nanoelectronic scaffolds. The uniqueness of these nanoscale devices for minimally invasive, large-scale, high spatial resolution, and three-dimensional neural activity mapping are highlighted. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization of 2,3-diarylxanthones by electrospray mass spectrometry: gas-phase chemistry versus known antioxidant activity properties.

PubMed

Silva, Eduarda M P; Barros, Cristina M R F; Santos, Clementina M M; Barros, António S; Domingues, M Rosário M; Silva, Artur M S

2016-10-30

Xanthones (XH) are a class of heterocyclic compounds widely distributed in nature that hold numerous noteworthy biological and antioxidant activities. Therefore, it is of utmost importance to achieve relevant detailed structural information to understand and assist prediction of their biological properties. The potential relationship between radical-mediated xanthone chemistry in the gas phase and their promising antioxidant activities has not been previously explored. Protonated xanthones XH1-9 were generated in the gas phase by electrospray ionization (ESI) and the main fragmentation pathways of the protonated XH1-9 formed due to collision-induced dissociation (CID) were investigated. In the CID-MS/MS spectra of [M+H](+) ions of XH1, XH2 and XH4 the product ions formed due to H2 O elimination corresponding to the base peak of the spectra. For the remaining six xanthones (XH3, XH5-9), showing the most promising biological profile, the product ion produced with the highest relative abundance (RA) corresponded to the one formed through concomitant loss of H2 O plus CO. Indicative of an inexistent or lower biological activity is the combined loss of CO plus O unique to the CID-MS/MS spectra of XH1, XH2, XH4, and XH5. The product ion formed by loss of 64 Da (concomitant loss of two molecules of H2 O plus CO) is only observed for xanthones containing a catechol unit (XH3 and XH6-9). This product ion has the highest RA for the most potent scavenger of reactive oxygen and nitrogen species XH9 that contains two of these catechol moieties. A strong relationship between some of the biological activities of the studied 2,3-diarylxanthones and their ESI-MS/MS fragmentation spectra was found. The multivariate statistical analysis results suggest that the selected MS features are related to the important biological features. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The antioxidant activity and nitric oxide production of extracts obtained from the leaves of Chenopodium quinoa Willd

PubMed Central

Chen, Hsiao-Ling; Lan, Xiang-Zhen; Wu, Yan-Yi; Ou, Yu-Wen; Chen, Tsung Chi; Wu, Wen-Tzu

2017-01-01

Background: Most reports have indicated the antioxidant capacity of quinoa seeds. However, the leaves of Quinoa (Chenopodium quinoa Willd.) are usually worthless and little known about their biological activities. In this study, the antioxidant and immunomodulatory potential of the quinoa leaf extracts were explored. Methods: The crude leaf extracts of quinoa were extracted using water, 50% ethanol or 95% ethanol as solvent, denoted WQL, 50% EQL and 95% EQL, respectively. The antioxidant activities of quinoa leaf extracts were assessed by the ability of 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging and iron chelating. The total phenolic content was determined. Inhibition of nitric oxide (NO) production in the lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells was examined to gauge the anti-inflammatory activity. Results: The 95% EQL showed a higher level of total phenolic content (569.5 mg GAE/g extract) and better DPPH scavenging activity. The WQL exhibited a better iron chelating capacity (28.9% at 10 mg/ml). The iron chelating activity of the 95% EQL increased in a concentration-dependent manner, which ranged from 10.9% up to 53.9%. The 50% EQL and 95% EQL significantly inhibited NO production in the LPSstimulated RAW 264.7 cells. Conclusion: We demonstrate that the extracts of quinoa leaves possess the biological activities of antioxidant and anti-inflammatory. Our finding suggests that the leaf extract of quinoa has potential to be utilized for natural health products. PMID:29130449

Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping

PubMed Central

Nicolau, Carolina Alves; Prorock, Alyson; Bao, Yongde; Neves-Ferreira, Ana Gisele da Costa; Fox, Jay William

2018-01-01

Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components) are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map) approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7) followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic), and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1) antimicrobial activity; (2) treatment of neuropsychiatric illnesses (Parkinson’s disease, schizophrenia, depression, and epilepsy); (3) treatment of cardiovascular diseases, and (4) anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic) and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents. PMID:29415440

New Potential Pharmaceutical Applications of Hypericum Species.

PubMed

Marrelli, Mariangela; Statti, Giancarlo; Conforti, Filomena; Menichini, Francesco

2016-01-01

The genus Hypericum includes more than 450 species distributed in Europe, North America, North Africa and West Asia. These plants are widely used in folk medicine for the treatment of inflammation, bacterial and viral infections, burns and gastric disorders. The use for alleviating inflammation and promoting wound healing is well known for H. Perforatum L. (St. John's wort) and other species. Because of its pharmacological activity, H. perforatum L. is one of the most important species of this genus. This plant has been largely utilized for its efficacy in the treatment of mild to moderate depression. However, some other species have been utilized in traditional medicine and have been studied for their phytochemical composition and for their biological activities to date. Hypericum species contain biologically active secondary metabolites belonging to at least ten different classes, with prevalence of naphthodianthrones (hypericin and pseudohypericin), phloroglucinols (hyperforin), flavonoids (rutin, hyperoside, isoquercitrin, quercitrin, quercetin, amentoflavone) and phenylpropanoids (chlorogenic acid). However, great variations in contents have been reported for wild populations worldwide. The purpose of this review is to provide an overview of most recent studies about potential pharmaceutical applications of plants belonging to Hypericum genus. The most interesting isolated active principles and both in vitro and in vivo effects of Hypericum extracts are presented and discussed.

Anti-cancer, anti-diabetic and other pharmacologic and biological activities of penta-galloyl-glucose

PubMed Central

Zhang, Jinhui; Li, Li; Kim, Sung-Hoon; Hagerman, Ann E.; Lü, Junxuan

2010-01-01

1, 2, 3, 4, 6-penta-O-galloyl-β-D-glucose (PGG) is a polyphenolic compound highly enriched in a number of medicinal herbals. Several in vitro and a handful of in vivo studies have shown that PGG exhibits multiple biological activities which implicate a great potential for PGG in the therapy and prevention of several major diseases including cancer and diabetes. Chemically and functionally, PGG appears to be distinct from its constituent gallic acid or tea polyphenols. For anti-cancer activity, three published in vivo preclinical cancer model studies with PGG support promising efficacy to selectively inhibit malignancy without host toxicity. Potential mechanisms include anti-angiogenesis, anti-proliferative actions through inhibition of DNA replicative synthesis and S-phase arrest and also G1 arrest, induction of apoptosis, anti-inflammation and anti-oxidation. Putative molecular targets include p53, Stat3, Cox-2, VEGFR1, AP-1, SP-1, Nrf-2 and MMP-9. For anti-diabetic activity, PGG and analogues appear to improve glucose uptake. However, very little is known about the absorption, pharmacokinetics and metabolism of PGG, nor its toxicity profile. The lack of large quantity of highly pure PGG has been a bottleneck limiting in vivo validation of cancer preventive and therapeutic efficacies in clinically relevant models. PMID:19575286

Extract from the Zooxanthellate Jellyfish Cotylorhiza tuberculata Modulates Gap Junction Intercellular Communication in Human Cell Cultures

PubMed Central

Leone, Antonella; Lecci, Raffaella Marina; Durante, Miriana; Piraino, Stefano

2013-01-01

On a global scale, jellyfish populations in coastal marine ecosystems exhibit increasing trends of abundance. High-density outbreaks may directly or indirectly affect human economical and recreational activities, as well as public health. As the interest in biology of marine jellyfish grows, a number of jellyfish metabolites with healthy potential, such as anticancer or antioxidant activities, is increasingly reported. In this study, the Mediterranean “fried egg jellyfish” Cotylorhiza tuberculata (Macri, 1778) has been targeted in the search forputative valuable bioactive compounds. A medusa extract was obtained, fractionated, characterized by HPLC, GC-MS and SDS-PAGE and assayed for its biological activity on breast cancer cells (MCF-7) and human epidermal keratinocytes (HEKa). The composition of the jellyfish extract included photosynthetic pigments, valuable ω-3 and ω-6 fatty acids, and polypeptides derived either from jellyfish tissues and their algal symbionts. Extract fractions showed antioxidant activity and the ability to affect cell viability and intercellular communication mediated by gap junctions (GJIC) differentially in MCF-7and HEKa cells. A significantly higher cytotoxicity and GJIC enhancement in MCF-7 compared to HEKa cells was recorded. A putative action mechanism for the anticancer bioactivity through the modulation of GJIC has been hypothesized and its nutraceutical and pharmaceutical potential was discussed. PMID:23697954

Extract from the zooxanthellate jellyfish Cotylorhiza tuberculata modulates gap junction intercellular communication in human cell cultures.

PubMed

Leone, Antonella; Lecci, Raffaella Marina; Durante, Miriana; Piraino, Stefano

2013-05-22

On a global scale, jellyfish populations in coastal marine ecosystems exhibit increasing trends of abundance. High-density outbreaks may directly or indirectly affect human economical and recreational activities, as well as public health. As the interest in biology of marine jellyfish grows, a number of jellyfish metabolites with healthy potential, such as anticancer or antioxidant activities, is increasingly reported. In this study, the Mediterranean "fried egg jellyfish" Cotylorhiza tuberculata (Macri, 1778) has been targeted in the search forputative valuable bioactive compounds. A medusa extract was obtained, fractionated, characterized by HPLC, GC-MS and SDS-PAGE and assayed for its biological activity on breast cancer cells (MCF-7) and human epidermal keratinocytes (HEKa). The composition of the jellyfish extract included photosynthetic pigments, valuable ω-3 and ω-6 fatty acids, and polypeptides derived either from jellyfish tissues and their algal symbionts. Extract fractions showed antioxidant activity and the ability to affect cell viability and intercellular communication mediated by gap junctions (GJIC) differentially in MCF-7 and HEKa cells. A significantly higher cytotoxicity and GJIC enhancement in MCF-7 compared to HEKa cells was recorded. A putative action mechanism for the anticancer bioactivity through the modulation of GJIC has been hypothesized and its nutraceutical and pharmaceutical potential was discussed.

Phytochemical and biological evaluation of some Sargassum species from Persian Gulf

PubMed Central

Mehdinezhad, Negin; Ghannadi, Alireza; Yegdaneh, Afsaneh

2016-01-01

Sea algae are widely consumed in the world. There are several seaweeds including brown algae which are authorized for human consumption. These plants contain important phytochemical constituents and have various potential biological activities. The present study investigated the presence of phytochemical constituents and total phenolic quantity of the seaweeds Sargassum angustifolium, Sargassum oligocystum and Sargassum boveanum. Cytotoxicity of seaweeds was tested against HT-29, HeLa and MCF-7 cell lines. Antioxidant potential of these 3 Sargassum species was also analyzed. Cytotoxicity was characterized by IC50 of human cancer cell lines using sulforhodamine assay. Antioxidant activities were evaluated using 2,2-diphenyl-1- picrylhydrazil. The analysis revealed that tannins, saponins, sterols and triterpenes were the most abundant compounds in these Sargassum species while cyanogenic and cardiac glycosides were the least ones. Sargassum angustifolium had the highest content of total phenolics (0.061 mg/g) and showed the highest antioxidant activity (IC50 = 0.231). Cytotoxic results showed that all species could inhibit cell growth effectively, especially MCF-7 cell line (IC50 = 67.3, 56.9, 60.4 for S. oligocystum, S. angustifolium and S. boveanum respectively). Considerable phytochemicals and moderate cytotoxic activity of S. angustifolium, S. oligocystum and S. boveanum make them appropriate candidate for further studies and identification of their bioactive principles. PMID:27499794

Phytochemical and biological evaluation of some Sargassum species from Persian Gulf.

PubMed

Mehdinezhad, Negin; Ghannadi, Alireza; Yegdaneh, Afsaneh

2016-01-01

Sea algae are widely consumed in the world. There are several seaweeds including brown algae which are authorized for human consumption. These plants contain important phytochemical constituents and have various potential biological activities. The present study investigated the presence of phytochemical constituents and total phenolic quantity of the seaweeds Sargassum angustifolium, Sargassum oligocystum and Sargassum boveanum. Cytotoxicity of seaweeds was tested against HT-29, HeLa and MCF-7 cell lines. Antioxidant potential of these 3 Sargassum species was also analyzed. Cytotoxicity was characterized by IC50 of human cancer cell lines using sulforhodamine assay. Antioxidant activities were evaluated using 2,2-diphenyl-1- picrylhydrazil. The analysis revealed that tannins, saponins, sterols and triterpenes were the most abundant compounds in these Sargassum species while cyanogenic and cardiac glycosides were the least ones. Sargassum angustifolium had the highest content of total phenolics (0.061 mg/g) and showed the highest antioxidant activity (IC50 = 0.231). Cytotoxic results showed that all species could inhibit cell growth effectively, especially MCF-7 cell line (IC50 = 67.3, 56.9, 60.4 for S. oligocystum, S. angustifolium and S. boveanum respectively). Considerable phytochemicals and moderate cytotoxic activity of S. angustifolium, S. oligocystum and S. boveanum make them appropriate candidate for further studies and identification of their bioactive principles.

Antimicrobial Compounds from Marine Invertebrates-Derived Microorganisms.

PubMed

Liu, Juan; Jung, Jee H; Liu, Yonghong

2016-01-01

It is known that marine invertebrates, including sponges, tunicates, cnidaria or mollusks, host affluent and various communities of symbiotic microorganisms. The microorganisms associated with the invertebrates metabolized various biologically active compounds, which could be an important resource for the discovery and development of potentially novel drugs. In this review, the new compounds with antimicrobial activity isolated from marine invertebrate-derived microorganisms in the last decade (2004-2014) will be presented, with focus on the relevant antimicrobial activities, origin of isolation, and information of strain species. New compounds without antimicrobial activity were not revealed.

Natural products and biological activity of the pharmacologically active cauliflower mushroom Sparassis crispa.

PubMed

Kimura, Takashi

2013-01-01

Sparassis crispa, also known as cauliflower mushroom, is an edible mushroom with medicinal properties. Its cultivation became popular in Japan about 10 years ago, a phenomenon that has been attributed not only to the quality of its taste, but also to its potential for therapeutic applications. Herein, I present a comprehensive summary of the pharmacological activities and mechanisms of action of its bioactive components, such as beta-glucan, and other physiologically active substances. In particular, the immunomodulatory mechanisms of the beta-glucan components are presented herein in detail.

Prioritizing human pharmaceuticals for ecological risks in the freshwater environment of Korea.

PubMed

Ji, Kyunghee; Han, Eun Jeong; Back, Sunhyoung; Park, Jeongim; Ryu, Jisung; Choi, Kyungho

2016-04-01

Pharmaceutical residues are potential threats to aquatic ecosystems. Because more than 3000 active pharmaceutical ingredients (APIs) are in use, identifying high-priority pharmaceuticals is important for developing appropriate management options. Priority pharmaceuticals may vary by geographical region, because their occurrence levels can be influenced by demographic, societal, and regional characteristics. In the present study, the authors prioritized human pharmaceuticals of potential ecological risk in the Korean water environment, based on amount of use, biological activity, and regional hydrologic characteristics. For this purpose, the authors estimated the amounts of annual production of 695 human APIs in Korea. Then derived predicted environmental concentrations, using 2 approaches, to develop an initial candidate list of target pharmaceuticals. Major antineoplastic drugs and hormones were added in the initial candidate list regardless of their production amount because of their high biological activity potential. The predicted no effect concentrations were derived for those pharmaceuticals based on ecotoxicity information available in the literature or by model prediction. Priority lists of human pharmaceuticals were developed based on ecological risks and availability of relevant information. Those priority APIs identified include acetaminophen, clarithromycin, ciprofloxacin, ofloxacin, metformin, and norethisterone. Many of these pharmaceuticals have been neither adequately monitored nor assessed for risks in Korea. Further efforts are needed to improve these lists and to develop management decisions for these compounds in Korean water. © 2015 SETAC.

Stevia rebaudiana Bert. leaf extracts as a multifunctional source of natural antioxidants.

PubMed

Gaweł-Bęben, Katarzyna; Bujak, Tomasz; Nizioł-Łukaszewska, Zofia; Antosiewicz, Beata; Jakubczyk, Anna; Karaś, Monika; Rybczyńska, Kamila

2015-03-27

The aim of the presented study was to characterize the content and biological activity of extracts prepared from dried Stevia rebaudiana leaves with potential application in the food or cosmetic industry. Aqueous (A), ethanolic (E) and glycol-aqueous (GA) extracts were analyzed for the content of polyphenols and proteins, showing that the highest amount of phenols (15.50 mg/g) and flavonoids (3.85 mg/g) contained GA. All extracts contained significant amount of protein (69.40-374.67 mg/g). Between analyzed stevia extracts (HPLC) GA contained the highest amount of polyphenols, especially ferulic (5.50 mg/g) and rozmaric (4.95 mg/g) acids derivates. The highest antiradical activity against DPPH• and ABTS•+ was noted for GA and E (IC50 = 0.38 and 0.71 µg flavonoids/mL). The highest ability to chelate Fe2+ was observed for E (IC50 = 2.08 µg flavonoids/mL). Stevia extracts were also analyzed for their cytotoxicity and fibroblast irritation potential in vitro. E and GA were the most cytotoxic and irritating, probably due to the high content of biologically active phytochemicals. On the other hand, a extract was the most tolerable by the cells. To summarize, the presented study evaluated the potential application of A, E and GA stevia extracts as natural source of antioxidants in the food and cosmetic industry.

Early hematological and immunological alterations in gasoline station attendants exposed to benzene.

PubMed

Moro, Angela M; Brucker, Natália; Charão, Mariele F; Sauer, Elisa; Freitas, Fernando; Durgante, Juliano; Bubols, Guilherme; Campanharo, Sarah; Linden, Rafael; Souza, Ana P; Bonorino, Cristina; Moresco, Rafael; Pilger, Diogo; Gioda, Adriana; Farsky, Sandra; Duschl, Albert; Garcia, Solange C

2015-02-01

Elucidation of effective biomarkers may provide tools for the early detection of biological alterations caused by benzene exposure and may contribute to the reduction of occupational diseases. This study aimed to assess early alterations on hematological and immunological systems of workers exposed to benzene. Sixty gasoline station attendants (GSA group) and 28 control subjects were evaluated. Environmental and biological monitoring of benzene exposure was performed in blood and urine. The potential effect biomarkers evaluated were δ-aminolevulinate dehydratase (ALA-D) activity, CD80 and CD86 expression in lymphocytes and monocytes, and serum interleukin-8 (IL-8). The influence of confounding factors and toluene co-exposure were considered. Although exposures were below ACGIH (American Conference of Governmental Industrial Hygienists) limits, reduced ALA-D activity, decreased CD80 and CD86 expression in monocytes and increased IL-8 levels were found in the GSA group compared to the control subjects. Furthermore, according to multiple linear regression analysis, benzene exposure was associated to a decrease in CD80 and CD86 expression in monocytes. These findings suggest, for the first time, a potential effect of benzene exposure on ALA-D activity, CD80 and CD86 expression, IL-8 levels, which could be suggested as potential markers for the early detection of benzene-induced alterations. Copyright © 2014 Elsevier Inc. All rights reserved.

WormClassroom.org: An Inquiry-rich Educational Web Portal for Research Resources of Caenorhabditis elegans

PubMed Central

Lu, Fong-Mei; Stewart, James; White, John G.

2007-01-01

The utilization of biology research resources, coupled with a “learning by inquiry” approach, has great potential to aid students in gaining an understanding of fundamental biological principles. To help realize this potential, we have developed a Web portal for undergraduate biology education, WormClassroom.org, based on current research resources of a model research organism, Caenorhabditis elegans. This portal is intended to serve as a resource gateway for students to learn biological concepts using C. elegans research material. The driving forces behind the WormClassroom website were the strengths of C. elegans as a teaching organism, getting researchers and educators to work together to develop instructional materials, and the 3 P's (problem posing, problem solving, and peer persuasion) approach for inquiry learning. Iterative assessment is an important aspect of the WormClassroom site development because it not only ensures that content is up-to-date and accurate, but also verifies that it does, in fact, aid student learning. A primary assessment was performed to refine the WormClassroom website utilizing undergraduate biology students and nonstudent experts such as C. elegans researchers; results and comments were used for site improvement. We are actively encouraging continued resource contributions from the C. elegans research and education community for the further development of WormClassroom. PMID:17548872

Biosimilars for psoriasis: worldwide overview of regulatory guidelines, uptake and implications for dermatology clinical practice.

PubMed

Cohen, A D; Wu, J J; Puig, L; Chimenti, S; Vender, R; Rajagopalan, M; Romiti, R; de la Cruz, C; Skov, L; Zachariae, C; Young, H S; Foley, P; van der Walt, J M; Naldi, L; Prens, E P; Blauvelt, A

2017-12-01

The introduction of biological drugs for the treatment of patients with psoriasis has revolutionized treatment paradigms and enabled numerous patients to achieve disease control with an acceptable safety profile. However, the high cost of biologics limits access to these medications for the majority of patients worldwide. In recent years, the introduction of biosimilars for inflammatory diseases has become a fast evolving field. The future use of biosimilars offers the potential for decreased cost and increased access to biologics for patients with psoriasis. For approval of biosimilars, different regulatory agencies use highly variable methods for definition, production, approval, marketing and postmarketing surveillance. Due to potential interchangeability between biologics and biosimilars, traceability and pharmacovigilance are required to collect accurate data about adverse events in patients with psoriasis; spontaneous reporting, registries and use of 'big data' should facilitate this process on a global basis. The current article describes biosimilar regulatory guidelines and examples of biosimilar uptake in clinical practice in several countries around the world. As it is apparent that biological therapy treatment decisions may become more physician independent, the International Psoriasis Council recommends that dermatologists should take an active role in the development of biosimilar prescribing policies with their respective healthcare settings and government agencies. © 2017 British Association of Dermatologists.

Assessment of biological leaf tissue using biospeckle laser imaging technique

NASA Astrophysics Data System (ADS)

Ansari, M. Z.; Mujeeb, A.; Nirala, A. K.

2018-06-01

We report on the application of an optical imaging technique, the biospeckle laser, as a potential tool to assess biological and medicinal plant leaves. The biospeckle laser technique is a non-invasive and non-destructive optical technique used to investigate biological objects. Just after their removal from plants, the torn leaves were used for biospeckle laser imaging. Quantitative evaluation of the biospeckle data using the inertia moment (IM) of the time history speckle pattern, showed that the IM can be utilized to provide a biospeckle signature to the plant leaves. It showed that leaves from different plants can have their own characteristic IM values. We further investigated the infected regions of the leaves that display a relatively lower biospeckle activity than the healthy tissue. It was easy to discriminate between the infected and healthy regions of the leaf tissue. The biospeckle technique can successfully be implemented as a potential tool for the taxonomy of quality leaves. Furthermore, the technique can help boost the quality of ayurvedic medicines.

The Rise of Radicals in Bioinorganic Chemistry.

PubMed

Gray, Harry B; Winkler, Jay R

2016-10-01

Prior to 1950, the consensus was that biological transformations occurred in two-electron steps, thereby avoiding the generation of free radicals. Dramatic advances in spectroscopy, biochemistry, and molecular biology have led to the realization that protein-based radicals participate in a vast array of vital biological mechanisms. Redox processes involving high-potential intermediates formed in reactions with O 2 are particularly susceptible to radical formation. Clusters of tyrosine (Tyr) and tryptophan (Trp) residues have been found in many O 2 -reactive enzymes, raising the possibility that they play an antioxidant protective role. In blue copper proteins with plastocyanin-like domains, Tyr/Trp clusters are uncommon in the low-potential single-domain electron-transfer proteins and in the two-domain copper nitrite reductases. The two-domain muticopper oxidases, however, exhibit clusters of Tyr and Trp residues near the trinuclear copper active site where O 2 is reduced. These clusters may play a protective role to ensure that reactive oxygen species are not liberated during O 2 reduction.

Peptide B12: emerging trends at the interface of inorganic chemistry, chemical biology and medicine.

PubMed

Zelder, Felix; Zhou, Kai; Sonnay, Marjorie

2013-01-28

The sophisticated and efficient delivery of vitamin B(12) ("B(12)") into cells offers promise for B(12)-bioconjugates in medicinal diagnosis and therapy. It is therefore surprising that rather little attention is presently paid to an alternative strategy in drug design: the development of structurally perfect, but catalytically inactive semi-artificial B(12) surrogates. Vitamin B(12) cofactors catalyse important biological transformations and are indispensible for humans and most other forms of life. This strong metabolic dependency exhibits enormous medicinal opportunities. Inhibitors of B(12) dependent enzymes are potential suppressors of fast proliferating cancer cells. This perspective article focuses on the design and study of backbone modified B(12) derivatives, particularly on peptide B(12) derivatives. Peptide B(12) is a recently introduced class of biomimetic cobalamins bearing an artificial peptide backbone with adjustable coordination and redox-properties. Pioneering biological studies demonstrated reduced catalytic activity, combined with inhibitory potential that is encouraging for future efforts in turning natural cofactors into new anti-proliferative agents.

Propolis: A Complex Natural Product with a Plethora of Biological Activities That Can Be Explored for Drug Development

PubMed Central

Silva-Carvalho, Ricardo; Baltazar, Fátima; Almeida-Aguiar, Cristina

2015-01-01

The health industry has always used natural products as a rich, promising, and alternative source of drugs that are used in the health system. Propolis, a natural resinous product known for centuries, is a complex product obtained by honey bees from substances collected from parts of different plants, buds, and exudates in different geographic areas. Propolis has been attracting scientific attention since it has many biological and pharmacological properties, which are related to its chemical composition. Several in vitro and in vivo studies have been performed to characterize and understand the diverse bioactivities of propolis and its isolated compounds, as well as to evaluate and validate its potential. Yet, there is a lack of information concerning clinical effectiveness. The goal of this review is to discuss the potential of propolis for the development of new drugs by presenting published data concerning the chemical composition and the biological properties of this natural compound from different geographic origins. PMID:26106433

Determinants Affecting Physical Activity Levels In Animal Models

NASA Technical Reports Server (NTRS)

Tou, Janet C. L.; Wade, Charles E.; Dalton, Bonnie P. (Technical Monitor)

2001-01-01

Weight control is dependent on energy balance. Reduced energy expenditure (EE) associated with decreased physical activity is suggested to be a major underlying cause in the increasing prevalence of weight gain and obesity. Therefore, a better understanding of the biological determinants involved in the regulation of physical activity is essential. To facilitate interpretation in humans, it is helpful to consider the evidence from animal studies. This review focuses on animal studies examining the biological determinants influencing activity and potential implications to human. It appears that physical activity is influenced by a number of parameters. However, regardless of the parameter involved, body weight appears to play all underlying role in the regulation of activity. Furthermore, the regulation of activity associated with body weight appears to occur only after the animal achieves a critical weight. This suggests that activity levels are a consequence rather than a contributor to weight control. However, the existence of an inverse weight-activity relationship remains inconclusive. Confounding the results are the multi-factorial nature of physical activity and the lack of appropriate measuring devices. Furthermore, many determinants of body weight are closely interlocked making it difficult to determine whether a single, combination or interaction of factors is important for the regulation of activity. For example, diet-induced obesity, aging, lesions to tile ventral medial hypothalamus and genetics all produce hypoactivity. Providing a better understanding of the biological determinants involved in the regulation of activity has important implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population.

Determinants affecting physical activity levels in animal models

NASA Technical Reports Server (NTRS)

Tou, Janet C L.; Wade, Charles E.

2002-01-01

Weight control is dependent on energy balance. Reduced energy expenditure (EE) associated with decreased physical activity is suggested to be a major underlying cause in the increasing prevalence of weight gain and obesity. Therefore, a better understanding of the biological determinants involved in the regulation of physical activity is essential. To facilitate interpretation in humans, it is helpful to consider the evidence from animal studies. This review focuses on animal studies examining the biological determinants influencing activity and potential implications to human. It appears that physical activity is influenced by a number of parameters. However, regardless of the parameter involved, body weight appears to play an underlying role in the regulation of activity. Furthermore, the regulation of activity associated with body weight appears to occur only after the animal achieves a critical weight. This suggests that activity levels are a consequence rather than a contributor to weight control. However, the existence of an inverse weight-activity relationship remains inconclusive. Confounding the results are the multifactorial nature of physical activity and the lack of appropriate measuring devices. Furthermore, many determinants of body weight are closely interlocked, making it difficult to determine whether a single, combination, or interaction of factors is important for the regulation of activity. For example, diet-induced obesity, aging, lesions to the ventral medial hypothalamus, and genetics all produce hypoactivity. Providing a better understanding of the biological determinants involved in the regulation of activity has important implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population.

Aqua mediated synthesis of bio-active compounds.

PubMed

Panda, Siva S

2013-05-01

Recently the aqueous medium has attracted the interest of organic chemists, and many. Moreover, in the past 20 years, the drug-discovery process has undergone extraordinary changes, and high-throughput biological screening of potential drug candidates has led to an ever-increasing demand for novel drug-like compounds. Noteworthy advantages were observed during the course of study on aqua mediated synthesis of compounds of medicinal importance. The established advantages of water as a solvent for reactions are, water is the most abundant and available resource on the planet and many biochemical processes occur in aqueous medium. This review will focus on describing new developments in the application of water in medicinal chemistry for the synthesis of bio-active compounds possessing various biological properties.

Maize Bioactive Peptides against Cancer

NASA Astrophysics Data System (ADS)

Díaz-Gómez, Jorge L.; Castorena-Torres, Fabiola; Preciado-Ortiz, Ricardo E.; García-Lara, Silverio

2017-06-01

Cancer is one of the main chronic degenerative diseases worldwide. In recent years, consumption of whole-grain cereals and their derived food products has been associated with reduction risks of various types of cancer. Cereals main biomolecules includes proteins, peptides, and amino acids present in different quantities within the grain. The nutraceutical properties associated with peptides exerts biological functions that promote health and prevent this disease. In this review, we report the current status and advances on maize peptides regarding bioactive properties that have been reported such as antioxidant, antihypertensive, hepatoprotective, and anti-tumour activities. We also highlighted its biological potential through which maize bioactive peptides exert anti-cancer activity. Finally, we analyse and emphasize the possible areas of application for maize peptides.

Structures and properties of naturally occurring polyether antibiotics.

PubMed

Rutkowski, Jacek; Brzezinski, Bogumil

2013-01-01

Polyether ionophores represent a large group of natural, biologically active substances produced by Streptomyces spp. They are lipid soluble and able to transport metal cations across cell membranes. Several of polyether ionophores are widely used as growth promoters in veterinary. Polyether antibiotics show a broad spectrum of bioactivity ranging from antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Recently, it has been shown that some of these compounds are able to selectively kill cancer stem cells and multidrug-resistant cancer cells. Thus, they are recognized as new potential anticancer drugs. The biological activity of polyether ionophores is strictly connected with their molecular structure; therefore, the purpose of this paper is to present an overview of their formula, molecular structure, and properties.

Structures and Properties of Naturally Occurring Polyether Antibiotics

PubMed Central

Rutkowski, Jacek; Brzezinski, Bogumil

2013-01-01

Polyether ionophores represent a large group of natural, biologically active substances produced by Streptomyces spp. They are lipid soluble and able to transport metal cations across cell membranes. Several of polyether ionophores are widely used as growth promoters in veterinary. Polyether antibiotics show a broad spectrum of bioactivity ranging from antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Recently, it has been shown that some of these compounds are able to selectively kill cancer stem cells and multidrug-resistant cancer cells. Thus, they are recognized as new potential anticancer drugs. The biological activity of polyether ionophores is strictly connected with their molecular structure; therefore, the purpose of this paper is to present an overview of their formula, molecular structure, and properties. PMID:23586016

The pancreatic stellate cell: a star on the rise in pancreatic diseases

PubMed Central

Omary, M. Bishr; Lugea, Aurelia; Lowe, Anson W.; Pandol, Stephen J.

2007-01-01

Pancreatic stellate cells (PaSCs) are myofibroblast-like cells found in the areas of the pancreas that have exocrine function. PaSCs are regulated by autocrine and paracrine stimuli and share many features with their hepatic counterparts, studies of which have helped further our understanding of PaSC biology. Activation of PaSCs induces them to proliferate, to migrate to sites of tissue damage, to contract and possibly phagocytose, and to synthesize ECM components to promote tissue repair. Sustained activation of PaSCs has an increasingly appreciated role in the fibrosis that is associated with chronic pancreatitis and with pancreatic cancer. Therefore, understanding the biology of PaSCs offers potential therapeutic targets for the treatment and prevention of these diseases. PMID:17200706

Shortcut nitrification-denitrification by means of autochthonous halophilic biomass in an SBR treating fish-canning wastewater.

PubMed

Capodici, Marco; Corsino, Santo Fabio; Torregrossa, Michele; Viviani, Gaspare

2018-02-15

Autochthonous halophilic biomass was cultivated in a sequencing batch reactor (SBR) aimed at analyzing the potential use of autochthonous halophilic activated sludge in treating saline industrial wastewater. Despite the high salt concentration (30 g NaCl L -1 ), biological oxygen demand (BOD) and total suspended solids (TSS), removal efficiencies were higher than 90%. More than 95% of the nitrogen was removed via a shortcut nitrification-denitrification process. Both the autotrophic and heterotrophic biomass samples exhibited high biological activity. The use of autochthonous halophilic biomass led to high-quality effluent and helped to manage the issues related to nitrogen removal in saline wastewater treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cooperative Learning in Industrial-sized Biology Classes

PubMed Central

Chang, Shu-Mei; Brickman, Marguerite

2007-01-01

This study examined the impact of cooperative learning activities on student achievement and attitudes in large-enrollment (>250) introductory biology classes. We found that students taught using a cooperative learning approach showed greater improvement in their knowledge of course material compared with students taught using a traditional lecture format. In addition, students viewed cooperative learning activities highly favorably. These findings suggest that encouraging students to work in small groups and improving feedback between the instructor and the students can help to improve student outcomes even in very large classes. These results should be viewed cautiously, however, until this experiment can be replicated with additional faculty. Strategies for potentially improving the impact of cooperative learning on student achievement in large courses are discussed. PMID:17548878

Cooperative learning in industrial-sized biology classes.

PubMed

Armstrong, Norris; Chang, Shu-Mei; Brickman, Marguerite

2007-01-01

This study examined the impact of cooperative learning activities on student achievement and attitudes in large-enrollment (>250) introductory biology classes. We found that students taught using a cooperative learning approach showed greater improvement in their knowledge of course material compared with students taught using a traditional lecture format. In addition, students viewed cooperative learning activities highly favorably. These findings suggest that encouraging students to work in small groups and improving feedback between the instructor and the students can help to improve student outcomes even in very large classes. These results should be viewed cautiously, however, until this experiment can be replicated with additional faculty. Strategies for potentially improving the impact of cooperative learning on student achievement in large courses are discussed.

Structures, biological activities, and industrial applications of the polysaccharides from Hericium erinaceus (Lion's Mane) mushroom: A review.

PubMed

He, Xirui; Wang, Xiaoxiao; Fang, Jiacheng; Chang, Yu; Ning, Ning; Guo, Hao; Huang, Linhong; Huang, Xiaoqiang; Zhao, Zefeng

2017-04-01

Hericium erinaceus (Bull.) Pers., also known as Yamabushitake, Houtou and Lion's Mane, is capable of fortifying the spleen and nourishing the stomach, tranquilizing the mind, and fighting cancer. Over the past decade, it has been demonstrated that H. erinaceus polysaccharides possess various promising bioactivities, including antitumor and immunomodulation, anti-gastric ulcer, neuroprotection and neuroregeneration, anti-oxidation and hepatoprotection, anti-hyperlipidemia, anti-hyperglycemia, anti-fatigue and anti-aging. The purpose of the present review is to provide systematically reorganized information on extraction and purification, structure characteristics, biological activities, and industrial applications of H. erinaceus polysaccharides to support their therapeutic potentials and sanitarian functions. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization and Comparison of the Structural Features, Immune-Modulatory and Anti-Avian Influenza Virus Activities Conferred by Three Algal Sulfated Polysaccharides

PubMed Central

Song, Lin; Chen, Xiaolin; Liu, Xiaodong; Zhang, Fubo; Hu, Linfeng; Yue, Yang; Li, Kecheng; Li, Pengcheng

2015-01-01

Three marine macroalgae, i.e., Grateloupia filicina, Ulva pertusa and Sargassum qingdaoense, were selected as the deputies of Rhodophyta, Chlorophyta and Ochrophyta for comparative analysis of the molecular structures and biological activities of sulfated polysaccharides (SP). The ratio of water-soluble polysaccharides, the monosaccharide composition and the sulfated contents of three extracted SPs were determined, and their structures were characterized by Fourier transformation infrared spectroscopy. In addition, biological activity analysis showed that all three SPs had immune-modulatory activity both in vitro and in vivo, and SPs from S. qingdaoense had the best effect. Further bioassays showed that three SPs could not only enhance the immunity level stimulated by inactivated avian influenza virus (AIV) in vivo but also significantly inhibited the activity of activated AIV (H9N2 subtype) in vitro. G. filicina SP exhibited the strongest anti-AIV activity. These results revealed the variations in structural features and bioactivities among three SPs and indicated the potential adjuvants for immune-enhancement and anti-AIV. PMID:26729137

In Vitro Dermo-Cosmetic Evaluation of Bark Extracts from Common Temperate Trees.

PubMed

Hubert, Jane; Angelis, Apostolis; Aligiannis, Nektarios; Rosalia, Michalea; Abedini, Amin; Bakiri, Ali; Reynaud, Romain; Nuzillard, Jean-Marc; Gangloff, Sophie C; Skaltsounis, Alexios-Leandros; Renault, Jean-Hugues

2016-10-01

Wood residues produced from forestry activities represent an interesting source of biologically active, high value-added secondary metabolites. In this study, 30 extracts from 10 barks of deciduous and coniferous tree species were investigated for their potential dermo-cosmetic use. The extracts were obtained from Fagus sylvatica, Quercus robur, Alnus glutinosa, Prunus avium, Acer pseudoplatanus, Fraxinus excelsior, Populus robusta, Larix decidua, Picea abies , and Populus tremula after three successive solid/liquid extractions of the barks with n- heptane, methanol, and methanol/water. All extracts were evaluated for their radical scavenging capacity, for their elastase, collagenase, and tyrosinase inhibitory activities, as well as for their antibacterial activity against gram-positive Staphylococcus aureus . In parallel, the global metabolite profiles of all extracts were established by 1D and 2D NMR and related to their biological activity. The results showed that the methanol extracts of Q. robur, A. glutinosa, L. decidua , and P. abies barks exhibit particularly high activities on most bioassays, suggesting their promising use as active ingredients in the dermo-cosmetic industry. Georg Thieme Verlag KG Stuttgart · New York.

Biological Activity of Conventional and Organic Pomegranate Juices: Antioxidant and Antimutagenic Potential.

PubMed

Cano-Lamadrid, M; Marhuenda-Egea, F C; Hernández, F; Rosas-Burgos, E C; Burgos-Hernández, A; Carbonell-Barrachina, A A

2016-12-01

None of the health claims about pomegranate juices has been approved yet by European Food Safety Authority (EFSA). There is a general perception among consumers that organic foods are healthier, tastier, and more nutritive than the conventional products. The aim of this research was to study the differences in the biological activity between ready-for-consumption juices obtained from pomegranates fruits grown under conventional and organic agricultural practices. Antioxidant activity has been evaluated by three methods (DPPH • , ABTS + , and FRAP), together with the total contents of phenolics and punicalagin (HPLC-DAD); besides, the Ames test was used to evaluate the antimutagenic potential of the juices. Pomegranate juice, either from conventionally or organically grown fruits, was antimutagenic (mean of 51 and 90 % for Salmonella typhimurium TA100 and TA98, respectively) and it was capable of protecting DNA from both, base-pair or frame-shift type of mutations. In fact, the antimutagenicity of conventional pomegranate juice was higher than that achieved by the organic sample; this finding was linked to a higher punicalagin content (201 and 104 mg L -1 for conventional and organic juices, respectively).

Impact of origin and biological source on chemical composition, anticholinesterase and antioxidant properties of some St. John's wort species (Hypericum spp., Hypericaceae) from the Central Balkans.

PubMed

Božin, Biljana; Kladar, Nebojša; Grujić, Nevena; Anačkov, Goran; Samojlik, Isidora; Gavarić, Neda; Conić, Branislava Srđenović

2013-09-25

The study shows the influence of the origin of plant material and biological source on the in vitro antioxidant (neutralization of DPPH and OH radical, nitric oxide, and inhibition of lipid peroxidation) and anticholinesterase activity of chemically characterized and quantified ethanol extracts of ten St. John's wort samples. The investigated samples were: five Hypericum perforatum species representatives collected at different localities, one commercial sample of Hyperici herba purchased at a local market and four Hypericum species autochtonous to the Balkan Peninsula (H. maculatum subsp. immaculatum, H. olympicum, H. richeri subsp. grisebachii and H. barbatum). All the examined extracts exhibited notable antioxidant potential, but in most of the cases indigenous Hypericum species expressed stronger effects compared to the original source of the drug, H. perforatum. The changes in the content of phenolic compounds, especially flavonoids, hyperforin and hypericin, related to the source of the drug affected the investigated activities. Since all of the investigated species have shown prominent inhibition of acetylcholinesterase in vitro activity, they could be further investigated as potential substances in preventing of Alzheimer's disease.

Activity of the nematophagous fungi Pochonia chlamydosporia, Duddingtonia flagrans and Monacrosporium thaumasium on egg capsules of Dipylidium caninum.

PubMed

Araujo, Juliana Milani; de Araújo, Jackson Victor; Braga, Fabio Ribeiro; Carvalho, Rogério Oliva; Ferreira, Sebastião Rodrigo

2009-12-03

Nematophagous fungi are potential biological control agents of helminths. The in vitro ovicidal effect of four isolates of the nematophagous fungi Pochonia chlamydosporia (VC1 and VC4), Duddingtonia flagrans (AC001) and Monacrosporium thaumasium (NF34) was evaluated on egg capsules of Dipylidium caninum, a cestode parasite of dogs, cats and humans. One thousand egg capsules of D. caninum were plated on 2% water-agar with the grown isolates and control without fungus. The ovicidal activity of these fungi was evaluated 5, 10 and 15 days after incubation. Only P. chlamydosporia showed ovicidal activity (p<0.05) on D. caninum egg capsules, of 19.6% (VC1) and 20% (VC4) on the 5th day; 44.2% (VC1) and 31.5% (VC4) on the 10th day; and 49.2% (VC1) and 41.9% (VC4) on the 15th day. D. flagrans and M. thaumasium caused no morphological damage to egg capsules. The results demonstrated that P. chlamydosporia was in vitro effective against capsules and eggs of D. caninum, and can be considered as a potential biological control agent for this helminth.

Creating biological nanomaterials using synthetic biology.

PubMed

Rice, MaryJoe K; Ruder, Warren C

2014-02-01

Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

Quantitative determination of biological activity of botulinum toxins utilizing compound muscle action potentials (CMAP), and comparison of neuromuscular transmission blockage and muscle flaccidity among toxins.

PubMed

Torii, Yasushi; Goto, Yoshitaka; Takahashi, Motohide; Ishida, Setsuji; Harakawa, Tetsuhiro; Sakamoto, Takashi; Kaji, Ryuji; Kozaki, Shunji; Ginnaga, Akihiro

2010-01-01

The biological activity of various types of botulinum toxin has been evaluated using the mouse intraperitoneal LD(50) test (ip LD(50)). This method requires a large number of mice to precisely determine toxin activity, and so has posed a problem with regard to animal welfare. We have used a direct measure of neuromuscular transmission, the compound muscle action potential (CMAP), to evaluate the effect of different types of botulinum neurotoxin (NTX), and we compared the effects of these toxins to evaluate muscle relaxation by employing the digit abduction scoring (DAS) assay. This method can be used to measure a broad range of toxin activities the day after administration. Types A, C, C/D, and E NTX reduced the CMAP amplitude one day after administration at below 1 ip LD(50), an effect that cannot be detected using the mouse ip LD(50) assay. The method is useful not only for measuring toxin activity, but also for evaluating the characteristics of different types of NTX. The rat CMAP test is straightforward, highly reproducible, and can directly determine the efficacy of toxin preparations through their inhibition of neuromuscular transmission. Thus, this method may be suitable for pharmacology studies and the quality control of toxin preparations. Copyright 2009 Elsevier Ltd. All rights reserved.

Biosynthesis, degradation and pharmacological importance of the fatty acid amides.

PubMed

Farrell, Emma K; Merkler, David J

2008-07-01

The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologically occurring fatty acid amides. In this review, we will outline which fatty acid amides have been isolated from mammalian sources, detail what is known about how these molecules are made and degraded in vivo, and highlight their potential for the development of novel therapeutics.

Biosynthesis, degradation, and pharmacological importance of the fatty acid amides

PubMed Central

Farrell, Emma K.; Merkler, David J.

2008-01-01

The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologically-occurring fatty acid amides. In this review, we will outline which fatty acid amides have been isolated from mammalian sources, detail what is known about how these molecules are made and degraded in vivo, and highlight their potential for the development of novel therapeutics. PMID:18598910

Laser Interferometry Method as a Novel Tool in Endotoxins Research.

PubMed

Arabski, Michał; Wąsik, Sławomir

2017-01-01

Optical properties of chemical substances are widely used at present for assays thereof in a variety of scientific disciplines. One of the measurement techniques applied in physical sciences, with a potential for novel applications in biology, is laser interferometry. This method enables to record the diffusion properties of chemical substances. Here we describe the novel application of laser interferometry in chitosan interactions with lipopolysaccharide by detection of colistin diffusion. The proposed model could be used in simple measurements of polymer interactions with endotoxins and/or biological active compounds, like antibiotics.

Appraisal of phytochemical and in vitro biological attributes of an unexplored folklore: Rhus Punjabensis Stewart.

PubMed

Tabassum, Saira; Ahmed, Madiha; Mirza, Bushra; Naeem, Muhammad; Zia, Muhammad; Shanwari, Zabta Khan; Khan, Gul Majid

2017-03-09

The role of plants for discovery of therapeutic potential accentuates the need to know their biological attributes. The present study aims to comprehend the biological attributes of Rhus punjabensis, an unexplored traditional medicinal plant. Leaf and stem extracts of R. punjabensis prepared in 11 different organic solvents are evaluated for multimode antioxidant potential, total phenolic and flavonoid contents were determined through colorimetric assays, HPLC-DAD analysis was carried out for quantification of various polyphenols in extracts. Brine shrimp lethality, SRB and MTT assays were used to elucidate plant's cytotoxic and antileishmanial potentials. Disc diffusion assay was used to elucidate the protein kinase inhibitory, antibacterial and antifungal spectrum. Ethanol + ethyl acetate yielded maximum extract recovery from leaf (6.11 ± 1.09% w/w), total phenolic content (80.5 ± 2.18 μg GAE/mg extract) and reducing power potential (165.4 ± 2.29 μg AAE/mg extract). Maximum flavonoid content (30.50 ± 1.11 μg QE/mg extract) and highest DPPH based free radical scavenging activity (IC 50 11.4 ± 2.07) was exhibited by the methanol + chloroform leaf extract. The methanol extract showed maximum total antioxidant capacity (74.5 ± 2.25 μg AAE/mg DW), protein kinase inhibitory (12.5 ± 1.10 bald phenotype at 100 μg/disc) and antifungal (MIC = 25 μg/disc against Aspergillus flavus) potential. Reverse phase HPLC-DAD based quantification reveals presence of gallic acid, apigenin, rutin and catechin in various extracts. Brine shrimp lethality assay demonstrated most extracts as highly cytotoxic (LC 50  < 50 μg/mL) whereas chloroform extract of leaf demonstrated maximuminhibition against human leukemia cell line (IC 50 7.80 ± 0.01 μg/mL). A significant activity against leishmanial promastigotes was demonstrated by n-hexane leaf extract (IC 50  = 15.78 ± 0.15 μg/mL). A better antibacterial activity,by the extracts, against Gram positive strains as compared to Gram negative was observed. Results recommend multiple-solvent system as a critical factor to sumptuous the biological prospective of R. punjabensis and propose it to be a useful natural hub for the discovery of novel antioxidant, anticancer, antileishmanial and antimicrobial agents.

Application of Nanoparticle Technology to Reduce the Anti-Microbial Resistance through β-Lactam Antibiotic-Polymer Inclusion Nano-Complex.

PubMed

Salamanca, Constain H; Yarce, Cristhian J; Roman, Yony; Davalos, Andrés F; Rivera, Gustavo R

2018-02-10

Biocompatible polymeric materials with potential to form functional structures in association with different therapeutic molecules have a high potential for biological, medical and pharmaceutical applications. Therefore, the capability of the inclusion of nano-Complex formed between the sodium salt of poly(maleic acid- alt -octadecene) and a β-lactam drug (ampicillin trihydrate) to avoid the chemical and enzymatic degradation and enhance the biological activity were evaluated. PAM-18Na was produced and characterized, as reported previously. The formation of polymeric hydrophobic aggregates in aqueous solution was determined, using pyrene as a fluorescent probe. Furthermore, the formation of polymer-drug nano-complexes was characterized by Differential Scanning Calorimetry-DSC, viscometric, ultrafiltration/centrifugation assays, zeta potential and size measurements were determined by dynamic light scattering-DLS. The PAM-18Na capacity to avoid the chemical degradation was studied through stress stability tests. The enzymatic degradation was evaluated from a pure β-lactamase, while the biological degradation was determined by different β-lactamase producing Staphylococcus aureus strains. When ampicillin was associated with PAM-18Na, the half-life time in acidic conditions increased, whereas both the enzymatic degradation and the minimum inhibitory concentration decreased to a 90 and 75%, respectively. These results suggest a promissory capability of this polymer to protect the β-lactam drugs against chemical, enzymatic and biological degradation.

Application of Nanoparticle Technology to Reduce the Anti-Microbial Resistance through β-Lactam Antibiotic-Polymer Inclusion Nano-Complex

PubMed Central

Yarce, Cristhian J.; Roman, Yony; Davalos, Andrés F.; Rivera, Gustavo R.

2018-01-01

Biocompatible polymeric materials with potential to form functional structures in association with different therapeutic molecules have a high potential for biological, medical and pharmaceutical applications. Therefore, the capability of the inclusion of nano-Complex formed between the sodium salt of poly(maleic acid-alt-octadecene) and a β-lactam drug (ampicillin trihydrate) to avoid the chemical and enzymatic degradation and enhance the biological activity were evaluated. PAM-18Na was produced and characterized, as reported previously. The formation of polymeric hydrophobic aggregates in aqueous solution was determined, using pyrene as a fluorescent probe. Furthermore, the formation of polymer-drug nano-complexes was characterized by Differential Scanning Calorimetry-DSC, viscometric, ultrafiltration/centrifugation assays, zeta potential and size measurements were determined by dynamic light scattering-DLS. The PAM-18Na capacity to avoid the chemical degradation was studied through stress stability tests. The enzymatic degradation was evaluated from a pure β-lactamase, while the biological degradation was determined by different β-lactamase producing Staphylococcus aureus strains. When ampicillin was associated with PAM-18Na, the half-life time in acidic conditions increased, whereas both the enzymatic degradation and the minimum inhibitory concentration decreased to a 90 and 75%, respectively. These results suggest a promissory capability of this polymer to protect the β-lactam drugs against chemical, enzymatic and biological degradation. PMID:29439391

Hysteresis in voltage-gated channels

PubMed Central

2017-01-01

ABSTRACT Ion channels constitute a superfamily of membrane proteins found in all living creatures. Their activity allows fast translocation of ions across the plasma membrane down the ion's transmembrane electrochemical gradient, resulting in a difference in electrical potential across the plasma membrane, known as the membrane potential. A group within this superfamily, namely voltage-gated channels, displays activity that is sensitive to the membrane potential. The activity of voltage-gated channels is controlled by the membrane potential, while the membrane potential is changed by these channels' activity. This interplay produces variations in the membrane potential that have evolved into electrical signals in many organisms. These signals are essential for numerous biological processes, including neuronal activity, insulin release, muscle contraction, fertilization and many others. In recent years, the activity of the voltage-gated channels has been observed not to follow a simple relationship with the membrane potential. Instead, it has been shown that the activity of voltage-gated channel displays hysteresis. In fact, a growing number of evidence have demonstrated that the voltage dependence of channel activity is dynamically modulated by activity itself. In spite of the great impact that this property can have on electrical signaling, hysteresis in voltage-gated channels is often overlooked. Addressing this issue, this review provides examples of voltage-gated ion channels displaying hysteretic behavior. Further, this review will discuss how Dynamic Voltage Dependence in voltage-gated channels can have a physiological role in electrical signaling. Furthermore, this review will elaborate on the current thoughts on the mechanism underlying hysteresis in voltage-gated channels. PMID:27689426

In vitro study on the effect of doxycycline on the microbial activity of soil determined by redox-potential measuring system.

PubMed

Szakmár, Katalin; Reichart, Olivér; Szatmári, István; Erdősi, Orsolya; Szili, Zsuzsanna; László, Noémi; Székely Körmöczy, Péter; Laczay, Péter

2014-09-01

The potential effect of doxycycline on the microbial activity was investigated in three types of soil. Soil samples were spiked with doxycycline, incubated at 25°C and tested at 0, 2, 4 and 6 days after treatment. The microbiological activity of the soil was characterized by the viable count determined by plate pouring and by the time necessary to reach a defined rate of the redox-potential decrease termed as time to detection (TTD).The viable count of the samples was not changed during the storage. The TTD values, however exhibited a significant increase in the 0.2-1.6 mg/kg doxycycline concentration range compared to the untreated samples indicating concentration-dependent inhibitory effect on microbial activity. The potency of the effect was different in the 3 soil types. To describe the combined effect of the doxycycline concentration and time on the biological activity of one type of soil a mathematical model was constructed and applied.The change of microbial metabolic rate could be measured also without (detectable) change of microbial count when the traditional microbiological methods are not applicable. The applied new redox potential measurement-based method is a simple and useful procedure for the examination of microbial activity of soil and its potential inhibition by antibiotics.

Real-Time Growth Kinetics Measuring Hormone Mimicry for ToxCast Chemicals in T‑47D Human Ductal Carcinoma Cells

EPA Science Inventory

High-throughput screening (HTS) assays capable of profiling thousands of environmentally relevant chemicals for in vitro biological activity provide useful information on the potential for disrupting endocrine pathways. Disruption of the estrogen signaling pathway has been implic...

A systems biology approach to investigate the antimicrobial activity of oleuropein

USDA-ARS?s Scientific Manuscript database

Oleuropein and its hydrolysis products are olive phenolic compounds that have antimicrobial effects on a variety of pathogens, with the potential to be utilized in food and pharmaceutical products. While the existing research is mainly focused on individual genes or enzymes that are regulated by ole...

Using ToxCast data to reconstruct dynamic cell state trajectories and estimate toxicological points of departure

EPA Science Inventory

AbstractBackground. High-throughput in vitro screening is an important tool for evaluating the potential biological activity of the thousands of existing chemicals in commerce and the hundreds more introduced each year. Among the assay technologies available, high-content imaging...

Managing hazardous waste in the clinical laboratory.

PubMed

Hoeltge, G A

1989-09-01

Clinical laboratories generate wastes that present chemical and biologic hazards. Ignitable, corrosive, reactive, toxic, and infectious potentials must be contained and minimized. A summary of these problems and an overview of the applicable regulations are presented. A checklist of activities to facilitate the annual review of the hazardous waste program is provided.

FATE OF PAH COMPOUNDS IN TWO SOIL TYPES: INFLUENCE OF VOLATILIZATION, ABIOTIC LOSS, AND BIOLOGICAL ACTIVITY

EPA Science Inventory

The fate of 14 polycyclic aromatic hydrocarbon (PAH) compounds was evaluated with regard to interphase transfer potential and mechanisms of treatment in soil under unsaturated conditions. Volatilization and abiotic and biotic fate of the PAHs were determined using two soils not p...

Microwave Digestion and Furnace Atomic Absorption Method for the Quantification of Nano-scale TiO2 in Aqueous Samples

EPA Science Inventory

Many nanomaterials posses physical, and potentially biological, activity that is unique relative to their macro-scaled or soluble forms. One such property is surface plasmon resonance; a phenomenon that can generate or facilitate photoreactivity. Optimization of these properties ...

Development of a quail embryo model for the detection of botulinum neurotoxin activity

USDA-ARS?s Scientific Manuscript database

Clostridium botulinum is a ubiquitous microorganism that under anaerobic conditions produces botulinum neurotoxins. In regards to both food-borne illness and the potential use of botulinum toxin as a biological weapon, the capability to assess the amount of toxin in a food or environmental sample e...

Can phylogeny predict chemical diversity and potential medicinal activity of plants? A case study of Amaryllidaceae

USDA-ARS?s Scientific Manuscript database

During evolution, plants and other organisms have developed a diversity of chemical defences, leading to the evolution of various groups of specialized metabolites selected for their endogenous biological function. A correlation between phylogeny and biosynthetic pathways could offer a predictive ap...

Biologic Activity of Lycopene Metabolites: Implications for Cancer Prevention

USDA-ARS?s Scientific Manuscript database

While early studies focused on the potential roles in health and disease of provitamin A carotenoids, such as beta-carotene, research over the past decade has provided a framework for our understanding of the functions of non-provitamin A carotenoids such as lycopene, especially in regards to its as...

Influence of spacer length on heparin coupling efficiency and fibrinogen adsorption of modified titanium surfaces

PubMed Central

Tebbe, David; Thull, Roger; Gbureck, Uwe

2007-01-01

Background Chemical bonding of the drug onto surfaces by means of spacer molecules is accompanied with a reduction of the biological activity of the drug due to a constricted mobility since normally only short spacer molecule like aminopropyltrimethoxysilane (APMS) are used for drug coupling. This work aimed to study covalent attachment of heparin to titanium(oxide) surfaces by varying the length of the silane coupling agent, which should affect the biological potency of the drug due to a higher mobility with longer spacer chains. Methods Covalent attachment of heparin to titanium metal and TiO2 powder was carried out using the coupling agents 3-(Trimethoxysilyl)-propylamine (APMS), N- [3-(Trimethoxysilyl)propyl]ethylenediamine (Diamino-APMS) and N1- [3-(Trimethoxy-silyl)-propyl]diethylenetriamine (Triamino-APMS). The amount of bound coupling agent and heparin was quantified photometrically by the ninhydrin reaction and the tolidine-blue test. The biological potency of heparin was determined photometrically by the chromogenic substrate Chromozym TH and fibrinogen adsorption to the modified surfaces was researched using the QCM-D (Quartz Crystal Microbalance with Dissipation Monitoring) technique. Results Zeta-potential measurements confirmed the successful coupling reaction; the potential of the unmodified anatase surface (approx. -26 mV) shifted into the positive range (> + 40 mV) after silanisation. Binding of heparin results in a strongly negatively charged surface with zeta-potentials of approx. -39 mV. The retaining biological activity of heparin was highest for the spacer molecule Triamino-APMS. QCM-D measurements showed a lower viscosity for adsorbed fibrinogen films on heparinised surfaces by means of Triamino-APMS. Conclusion The remaining activity of heparin was found to be highest for the covalent attachment with Triamino-APMS as coupling agent due to the long chain of this spacer molecule and therefore the highest mobility of the drug. Furthermore, the adsorption of fibrinogen on the differently heparinised surfaces in real time demonstrated that with longer spacer chains the ΔD/Δf ratios became higher, which is also associated with better biocompatible properties of the substrates in contact with a biosystem. PMID:17640335

Biologic Activity of Porphyromonas endodontalis complex lipids

PubMed Central

Mirucki, Christopher S.; Abedi, Mehran; Jiang, Jin; Zhu, Qiang; Wang, Yu-Hsiung; Safavi, Kamran E.; Clark, Robert B.; Nichols, Frank C.

2014-01-01

Introduction Periapical infections secondary to pulpal necrosis are associated with bacterial contamination of the pulp. Porphyromonas endodontalis, a Gram-negative organism, is considered to be a pulpal pathogen. P. gingivalis is phylogenetically related to P. endodontalis and synthesizes several classes of novel complex lipids that possess biological activity, including the capacity to promote osteoclastogenesis and osteoclast activation. The purpose of this study was to extract and characterize constituent lipids of P. endodontalis, and evaluate their capacity to promote pro-inflammatory secretory responses in the macrophage cell line, RAW 264.7, as well as their capacity to promote osteoclastogenesis and inhibit osteoblast activity. Methods Constituent lipids of both organisms were fractionated by HPLC and were structurally characterized using electrospray-mass spectrometry (ESI-MS) or ESI-MS/MS. The virulence potential of P. endodontalis lipids was then compared with known biologically active lipids isolated from P. gingivalis. Results P. endodontalis total lipids were shown to promote TNF-α secretion from RAW 264.7 cells and the serine lipid fraction appeared to account for the majority of this effect. P. endodontalis lipid preparations also increased osteoclast formation from RAW 264.7 cells but osteoblast differentiation in culture was inhibited and appeared to be dependent on TLR2 expression. Conclusions These effects underscore the importance of P. endodontalis lipids in promoting inflammatory and bone cell activation processes that could lead to periapical pathology. PMID:25146013

Biological and molecular characterization of cellular differentiation in Tetrahymena vorax: a potential biocontrol protozoan.

PubMed

Green, M M; LeBoeuf, R D; Churchill, P F

2000-01-01

Tetrahymena vorax (T. vorax) is an indigenous fresh water protozoan with the natural biological potential to maintain a specific aquatic microbial flora by ingesting and eliminating specific microorganism. To investigate the molecular mechanisms controlling Tetrahymena vorax (T. vorax) cellular differentiation from a small-mouth vegetative cell to a voracious large-mouth carnivore capable of ingesting prey ciliates and bacteria from aquatic environments, we use DNA subtraction and gene discovery techniques to identify and isolate T. vorax differentiation-specific genes. The physiological necessity for one newly discovered gene, SUBII-TG, was determined in vivo using an antisense oligonucleotide directed against the 5' SUBII-TG DNA sequence. The barriers to delivering antisense oligonucleotides to the cytoplasm of T. vorax were circumvented by employing a new but simple procedure of processing the oligonucleotide with the differentiation stimulus, stomatin. In these studies, the antisense oligonucleotide down-regulated SUBII-TG mRNA expression, and blocked differentiation and ingestion of prey ciliates. The ability to down-regulate SUBII-TG expression with the antisense oligonucleotide suggests that the molecular mechanisms controlling the natural biological activities of T. vorax can be manipulated to further study its cellular differentiation and potential as a biocontrol microorganism.

Aspirin Enhances Osteogenic Potential of Periodontal Ligament Stem Cells (PDLSCs) and Modulates the Expression Profile of Growth Factor-Associated Genes in PDLSCs.

PubMed

Abd Rahman, Fazliny; Mohd Ali, Johari; Abdullah, Mariam; Abu Kasim, Noor Hayaty; Musa, Sabri

2016-07-01

This study investigates the effects of aspirin (ASA) on the proliferative capacity, osteogenic potential, and expression of growth factor-associated genes in periodontal ligament stem cells (PDLSCs). Mesenchymal stem cells (MSCs) from PDL tissue were isolated from human premolars (n = 3). The MSCs' identity was confirmed by immunophenotyping and trilineage differentiation assays. Cell proliferation activity was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Polymerase chain reaction array was used to profile the expression of 84 growth factor-associated genes. Pathway analysis was used to identify the biologic functions and canonic pathways activated by ASA treatment. The osteogenic potential was evaluated through mineralization assay. ASA at 1,000 μM enhances osteogenic potential of PDLSCs. Using a fold change (FC) of 2.0 as a threshold value, the gene expression analyses indicated that 19 genes were differentially expressed, which includes 12 upregulated and seven downregulated genes. Fibroblast growth factor 9 (FGF9), vascular endothelial growth factor A (VEGFA), interleukin-2, bone morphogenetic protein-10, VEGFC, and 2 (FGF2) were markedly upregulated (FC range, 6 to 15), whereas pleotropin, FGF5, brain-derived neurotrophic factor, and Dickkopf WNT signaling pathway inhibitor 1 were markedly downregulated (FC 32). Of the 84 growth factor-associated genes screened, 35 showed high cycle threshold values (≥35). ASA modulates the expression of growth factor-associated genes and enhances osteogenic potential in PDLSCs. ASA upregulated the expression of genes that could activate biologic functions and canonic pathways related to cell proliferation, human embryonic stem cell pluripotency, tissue regeneration, and differentiation. These findings suggest that ASA enhances PDLSC function and may be useful in regenerative dentistry applications, particularly in the areas of periodontal health and regeneration.

Polyhydroxyalkanoate (PHA) accumulation potential and PHA-accumulating microbial communities in various activated sludge processes of municipal wastewater treatment plants.

PubMed

Sakai, K; Miyake, S; Iwama, K; Inoue, D; Soda, S; Ike, M

2015-01-01

To clarify the polyhydroxyalkanoate (PHA) accumulation potential and the PHA-accumulating microbial community structure in activated sludge in municipal wastewater treatment plants (WWTPs) and to identify their influential factors. Nine activated sludge samples were collected from municipal WWTPs employing various biological treatment processes. In acetate-fed 24-h batch experiments under aerobic and nitrogen- and phosphorus-limited conditions, polyhydroxybutyrate (PHB) content of activated sludge increased from 0-1·3 wt% to 7·9-24 wt%, with PHB yields of 0·22-0·50 C-mol 3-hydroxybutyrate (C-mol acetate)(-1). Microbial community analyses found that activated sludge samples that accumulated >20 wt% of PHB after 24-h PHA accumulation experiments had >5·0 × 10(8) copies g(-1)-mixed liquor-suspended solid of phaC genes. Results indicated that (i) activated sludge in municipal WWTPs can accumulate up to approx. 20 wt% of PHA without enrichment processes, (ii) PHA accumulation potential of activated sludge varied depending on the operational conditions (treatment processes) of WWTPs, and (iii) phaC gene number can provide a simple indication of PHA accumulation potential. This is the first study to compare the PHA accumulation potential and PHA-accumulating microbial communities in activated sludge of various treatment processes. Our findings may be useful for enhancing the resource recovery potential of wastewater treatment systems. © 2014 The Society for Applied Microbiology.

Synthetic Biology and Personalized Medicine

PubMed Central

Jain, K.K.

2013-01-01

Synthetic biology, application of synthetic chemistry to biology, is a broad term that covers the engineering of biological systems with structures and functions not found in nature to process information, manipulate chemicals, produce energy, maintain cell environment and enhance human health. Synthetic biology devices contribute not only to improve our understanding of disease mechanisms, but also provide novel diagnostic tools. Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs. The potential of synthetic genome, using an expanded genetic code that is designed for specific drug synthesis as well as delivery and activation of the drug in vivo by a pathological signal, was already pointed out during a lecture delivered at Kuwait University in 2005. Of two approaches to synthetic biology, top-down and bottom-up, the latter is more relevant to the development of personalized medicines as it provides more flexibility in constructing a partially synthetic cell from basic building blocks for a desired task. PMID:22907209

Electron Bifurcation: Thermodynamics and Kinetics of Two-Electron Brokering in Biological Redox Chemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Peng; Yuly, Jonathon L.; Lubner, Carolyn E.

How can proteins drive two electrons from a redox active donor onto two acceptors at very different potentials and distances? And how can this transaction be conducted without dissipating very much energy or violating the laws of thermodynamics? Nature appears to have addressed these challenges by coupling thermodynamically uphill and downhill electron transfer reactions, using two-electron donor cofactors that have very different potentials for the removal of the first and second electron. Although electron bifurcation is carried out with near perfection from the standpoint of energy conservation and electron delivery yields, it is a biological energy transduction paradigm that hasmore » only come into focus recently. This Account provides an exegesis of the biophysical principles that underpin electron bifurcation.« less