Developing Laryngeal Muscle of Xenopus laevis as a Model System: Androgen-Driven Myogenesis Controls Fiber Type Transformation

PubMed Central

Nasipak, Brian; Kelley, Darcy B.

2014-01-01

The developmental programs that contribute to myogenic stem cell proliferation and muscle fiber differentiation control fiber numbers and twitch type. In this study, we describe the use of an experimental model system—androgen-regulated laryngeal muscle of juvenile clawed frogs, Xenopus laevis—to examine the contribution of proliferation by specific populations of myogenic stem cells to expression of the larynx-specific myosin heavy chain isoform, LM. Androgen treatment of juveniles (Stage PM0) resulted in up-regulation of an early (Myf-5) and a late (myogenin) myogenic regulatory factor; the time course of LM up-regulation tracked that of myogenin. Myogenic stem cells stimulated to proliferate by androgen include a population that expresses Pax-7, a marker for the satellite cell myogenic stem cell population. Since androgen can switch muscle fiber types from fast to slow even in denervated larynges, we developed an ex vivo culture system to explore the relation between proliferation and LM expression. Cultured whole larynges maintain sensitivity to androgen, increasing in size and LM expression. Blockade of cell proliferation with cis-platin prevents the switch from slow to fast twitch muscle fibers as assayed by ATPase activity. Blockade of cell proliferation in vivo also resulted in inhibition of LM expression. Thus, both in vivo and ex vivo, inhibition of myogenic stem cell proliferation blocks androgen-induced LM expression and fiber type switching in juveniles. PMID:21954146

Solidification Technologies for Radioactive and Chemical Liquid Waste Treatment - Final CRADA Report

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

Castiglioni, Andrew J.; Gelis, Artem V.

This project, organized under DOE/NNSA's Global Initiatives for Proliferation Prevention program, joined Russian and DOE scientists in developing more effective solidification and storage technologies for liquid radioactive waste. Several patent applications were filed by the Russian scientists (Russia only) and in 2012, the technology developed was approved by Russia's Federal State Unitary Enterprise RADON for application throughout Russia in cleaning up and disposing of radioactive waste.

Nuclear Terrorism - Dimensions, Options, and Perspectives in Moldova

NASA Astrophysics Data System (ADS)

Vaseashta, Ashok; Susmann, P.; Braman, Eric W.; Enaki, Nicolae A.

Securing nuclear materials, controlling contraband and preventing proliferation is an international priority to resolve using technology, diplomacy, strategic alliances, and if necessary, targeted military exercises. Nuclear security consists of complementary programs involving international legal and regulatory structure, intelligence and law enforcement agencies, border and customs forces, point and stand-off radiation detectors, personal protection equipment, preparedness for emergency and disaster, and consequence management teams. The strategic goal of UNSCR 1540 and the GICNT is to prevent nuclear materials from finding their way into the hands of our adversaries. This multi-jurisdictional and multi-agency effort demands tremendous coordination, technology assessment, policy development and guidance from several sectors. The overall goal envisions creating a secured environment that controls and protects nuclear materials while maintaining the free flow of commerce and individual liberty on international basis. Integral to such efforts are technologies to sense/detect nuclear material, provide advance information of nuclear smuggling routes, and other advanced means to control nuclear contraband and prevent proliferation. We provide an overview of GICNT and several initiatives supporting such efforts. An overview is provided of technological advances in support of point and stand-off detection and receiving advance information of nuclear material movement from perspectives of the Republic of Moldova.

Global threat reduction initiative Russian nuclear material removal progress

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

Cummins, Kelly; Bolshinsky, Igor

2008-07-15

In December 1999 representatives from the United States, the Russian Federation, and the International Atomic Energy Agency (IAEA) started discussing a program to return to Russia Soviet- or Russian-supplied highly enriched uranium (HEU) fuel stored at the Russian-designed research reactors outside Russia. Trilateral discussions among the United States, Russian Federation, and the International Atomic Energy Agency (IAEA) have identified more than 20 research reactors in 17 countries that have Soviet- or Russian-supplied HEU fuel. The Global Threat Reduction Initiative's Russian Research Reactor Fuel Return Program is an important aspect of the U.S. Government's commitment to cooperate with the other nationsmore » to prevent the proliferation of nuclear weapons and weapons-usable proliferation-attractive nuclear materials. To date, 496 kilograms of Russian-origin HEU have been shipped to Russia from Serbia, Latvia, Libya, Uzbekistan, Romania, Bulgaria, Poland, Germany, and the Czech Republic. The pilot spent fuel shipment from Uzbekistan to Russia was completed in April 2006. (author)« less

E-counseling as an emerging preventive strategy for hypertension.

PubMed

Nolan, Robert P; Liu, Sam; Payne, Ada Y M

2014-07-01

Lifestyle counseling that includes exercise training, diet modification, and medication adherence is critical to hypertension management. This article summarizes the efficacy of lifestyle counseling interventions in face-to-face, telehealth, and e-counseling settings. It also discusses the therapeutic potential of e-counseling as a preventive strategy for hypertension. The recent proliferation of telehealth and e-counseling programs increases the reach of preventive counseling for patients with cardiovascular disorders. Blood pressure reduction following these interventions is comparable to face-to-face interventions. However, the effectiveness of e-counseling varies depending on the design features of the core protocol. An evidence-based guideline needs to be established that identifies e-counseling components which are independently associated with blood pressure reduction. As the Internet becomes more sophisticated, e-counseling is demonstrating a therapeutic advantage in comparison with other telehealth interventions. Current evidence supports further development of preventive e-counseling programs for hypertension. A pressing challenge for investigators is to specify key evidence-based components of e-counseling that are essential to the core protocol. In order to achieve this goal, it will be necessary to ensure that e-counseling programs are also clinically organized, in order to guide patients through the process of initiating and sustaining therapeutic behavior change.

Proliferation of nuclear weapons: opportunities for control and abolition.

PubMed

Sidel, Victor W; Levy, Barry S

2007-09-01

Nuclear weapons pose a particularly destructive threat. Prevention of the proliferation and use of nuclear weapons is urgently important to public health. "Horizontal" proliferation refers to nation-states or nonstate entities that do not have, but are acquiring, nuclear weapons or developing the capability and materials for producing them. "Vertical" proliferation refers to nation-states that do possess nuclear weapons and are increasing their stockpiles of these weapons, improving the technical sophistication or reliability of their weapons, or developing new weapons. Because nation-states or other entities that wish to use or threaten to use nuclear weapons need methods for delivering those weapons, proliferation of delivery mechanisms must also be prevented. Controlling proliferation--and ultimately abolishing nuclear weapons--involves national governments, intergovernmental organizations, nongovernmental and professional organizations, and society at large.

U.S. Department of Energy's initiatives for proliferation prevention program: solidification technologies for radioactive waste treatment in Russia

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

Pokhitonov, Y.; Kelley, D.

Large amounts of liquid radioactive waste have existed in the U.S. and Russia since the 1950's as a result of the Cold War. Comprehensive action to treat and dispose of waste products has been lacking due to insufficient funding, ineffective technologies or no proven technologies, low priority by governments among others. Today the U.S. and Russian governments seek new, more reliable methods to treat liquid waste, in particular the legacy waste streams. A primary objective of waste generators and regulators is to find economical and proven technologies that can provide long-term stability for repository storage. In 2001, the V.G. Khlopinmore » Radium Institute (Khlopin), St. Petersburg, Russia, and Pacific Nuclear Solutions (PNS), Indianapolis, Indiana, began extensive research and test programs to determine the validity of polymer technology for the absorption and immobilization of standard and complex waste streams. Over 60 liquid compositions have been tested including extensive irradiation tests to verify polymer stability and possible degradation. With conclusive scientific evidence of the polymer's effectiveness in treating liquid waste, both parties have decided to enter the Russian market and offer the solidification technology to nuclear sites for waste treatment and disposal. In conjunction with these efforts, the U.S. Department of Energy (DOE) will join Khlopin and PNS to explore opportunities for direct application of the polymers at predetermined sites and to conduct research for new product development. Under DOE's 'Initiatives for Proliferation Prevention'(IPP) program, funding will be provided to the Russian participants over a three year period to implement the program plan. This paper will present details of U.S. DOE's IPP program, the project structure and its objectives both short and long-term, training programs for scientists, polymer tests and applications for LLW, ILW and HLW, and new product development initiatives. (authors)« less

Leo Szilard Lectureship Award: Science Matters - Technical Dimensions of Arms Control and Non-Proliferation Agreements

NASA Astrophysics Data System (ADS)

Timbie, James

2017-01-01

Agreements to reduce nuclear arms and prevent proliferation of nuclear weapons are technical as well as political documents. They must be both technically sound and politically acceptable. This presentation illustrates technical aspects of arms control and non-proliferation agreements, with examples from SALT I, INF, the HEU Agreement, START, and the Iran nuclear negotiations, drawing on 44 years of personal experience in the negotiation of these agreements. The lecture is designed to convey an appreciation of the role that individuals with technical training can play in diplomatic efforts to reduce nuclear forces and prevent nuclear proliferation.

On The Export Control Of High Speed Imaging For Nuclear Weapons Applications

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

Watson, Scott Avery; Altherr, Michael Robert

Since the Manhattan Project, the use of high-speed photography, and its cousins flash radiography1 and schieleren photography have been a technological proliferation concern. Indeed, like the supercomputer, the development of high-speed photography as we now know it essentially grew out of the nuclear weapons program at Los Alamos2,3,4. Naturally, during the course of the last 75 years the technology associated with computers and cameras has been export controlled by the United States and others to prevent both proliferation among non-P5-nations and technological parity among potential adversaries among P5 nations. Here we revisit these issues as they relate to high-speed photographicmore » technologies and make recommendations about how future restrictions, if any, should be guided.« less

Legionella pneumophila prevents proliferation of its natural host Acanthamoeba castellanii

PubMed Central

Mengue, Luce; Régnacq, Matthieu; Aucher, Willy; Portier, Emilie; Héchard, Yann; Samba-Louaka, Ascel

2016-01-01

Legionella pneumophila is a ubiquitous, pathogenic, Gram-negative bacterium responsible for legionellosis. Like many other amoeba-resistant microorganisms, L. pneumophila resists host clearance and multiplies inside the cell. Through its Dot/Icm type IV secretion system, the bacterium injects more than three hundred effectors that modulate host cell physiology in order to promote its own intracellular replication. Here we report that L. pneumophila prevents proliferation of its natural host Acanthamoeba castellanii. Infected amoebae could not undergo DNA replication and no cell division was observed. The Dot/Icm secretion system was necessary for L. pneumophila to prevent the eukaryotic proliferation. The absence of proliferation was associated with altered amoebal morphology and with a decrease of mRNA transcript levels of CDC2b, a putative regulator of the A. castellanii cell cycle. Complementation of CDC28-deficient Saccharomyces cerevisiae by the CDC2b cDNA was sufficient to restore proliferation of CDC28-deficient S. cerevisiae and suggests for the first time that CDC2b from A. castellanii could be functional and a bona fide cyclin-dependent kinase. Hence, our results reveal that L. pneumophila impairs proliferation of A. castellanii and this effect could involve the cell cycle protein CDC2b. PMID:27805070

RNA-binding protein HuR sequesters microRNA-21 to prevent translation repression of proinflammatory tumor suppressor gene programmed cell death 4.

PubMed

Poria, D K; Guha, A; Nandi, I; Ray, P S

2016-03-31

Translation control of proinflammatory genes has a crucial role in regulating the inflammatory response and preventing chronic inflammation, including a transition to cancer. The proinflammatory tumor suppressor protein programmed cell death 4 (PDCD4) is important for maintaining the balance between inflammation and tumorigenesis. PDCD4 messenger RNA translation is inhibited by the oncogenic microRNA, miR-21. AU-rich element-binding protein HuR was found to interact with the PDCD4 3'-untranslated region (UTR) and prevent miR-21-mediated repression of PDCD4 translation. Cells stably expressing miR-21 showed higher proliferation and reduced apoptosis, which was reversed by HuR expression. Inflammatory stimulus caused nuclear-cytoplasmic relocalization of HuR, reversing the translation repression of PDCD4. Unprecedentedly, HuR was also found to bind to miR-21 directly, preventing its interaction with the PDCD4 3'-UTR, thereby preventing the translation repression of PDCD4. This suggests that HuR might act as a 'miRNA sponge' to regulate miRNA-mediated translation regulation under conditions of stress-induced nuclear-cytoplasmic translocation of HuR, which would allow fine-tuned gene expression in complex regulatory environments.

Manufacturing and Characterization of Ultra Pure Ferrous Alloys Final Report CRADA No. TC02069.0

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

Lesuer, D.; McGreevy, T. E.

This CRADA was a.collaborative effort between the Lawrence Livermore National Security LLC (formerly University of California)/Lawrence Livermore National Laboratory (LLNL),and Caterpillar Inc. (CaterpiHar), to further advance levitation casting techniques (developed at the Central Research Institute for Material (CRIM) in St. Petersburg, Russia) for use in manufacturing high purity metal alloys. This DOE Global Initiatives for Proliferation Prevention Program (IPP) project was to develop and demonstrate the levitation casting technology for producing ultra-pure alloys.

Colon Cancer Chemoprevention by Sage Tea Drinking: Decreased DNA Damage and Cell Proliferation.

PubMed

Pedro, Dalila F N; Ramos, Alice A; Lima, Cristovao F; Baltazar, Fatima; Pereira-Wilson, Cristina

2016-02-01

Salvia officinalis and some of its isolated compounds have been found to be preventive of DNA damage and increased proliferation in vitro in colon cells. In the present study, we used the azoxymethane model to test effects of S. officinalis on colon cancer prevention in vivo. The results showed that sage treatment reduced the number of ACF formed only if administered before azoxymethane injection, demonstrating that sage tea drinking has a chemopreventive effect on colorectal cancer. A decrease in the proliferation marker Ki67 and in H2 O2 -induced and azoxymethane-induced DNA damage to colonocytes and lymphocytes were found with sage treatment. This confirms in vivo the chemopreventive effects of S. officinalis. Taken together, our results show that sage treatment prevented initiation phases of colon carcinogenesis, an effect due, at least in part, to DNA protection, and reduced proliferation rates of colon epithelial cell that prevent mutations and their fixation through cell replication. These chemopreventive effects of S. officinalis on colon cancer add to the many health benefits attributed to sage and encourage its consumption. Copyright © 2015 John Wiley & Sons, Ltd.

H. R. 3743: This Act may be cited as the Iran Nuclear Proliferation Prevention Act of 1998, Introduced in the House of Representatives, One Hundred Fifth Congress, Second Session, April 29, 1998

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

Not Available

1998-04-29

The purpose of this bill is to withhold voluntary proportional assistance for programs and projects of the International Atomic Energy Agency relating to the development and completion of the Bushehr nuclear power plant in Iran, and for other purposes. This bill is divided into the following sections: Section 1. Short Title; Section 2. Findings; Section 3. Withholding of voluntary contributions to the International Atomic Energy Agency for programs and projects in Iran. Section 4. Annual review by Secretary of State of programs and projects of the International Atomic Energy Agency; United States opposition to programs and projects of the Agencymore » in Iran; Section 5. Reporting Requirements; and Section 7. Sense of the Congress.« less

Proliferation of Nuclear Weapons: Opportunities for Control and Abolition

PubMed Central

Sidel, Victor W.; Levy, Barry S.

2007-01-01

Nuclear weapons pose a particularly destructive threat. Prevention of the proliferation and use of nuclear weapons is urgently important to public health. “Horizontal” proliferation refers to nation-states or nonstate entities that do not have, but are acquiring, nuclear weapons or developing the capability and materials for producing them. “Vertical” proliferation refers to nation-states that do possess nuclear weapons and are increasing their stockpiles of these weapons, improving the technical sophistication or reliability of their weapons, or developing new weapons. Because nation-states or other entities that wish to use or threaten to use nuclear weapons need methods for delivering those weapons, proliferation of delivery mechanisms must also be prevented. Controlling proliferation—and ultimately abolishing nuclear weapons—involves national governments, intergovernmental organizations, nongovernmental and professional organizations, and society at large. PMID:17666690

Reproductive history and breast cancer prevention.

PubMed

Russo, Jose

2016-07-01

The hormonal milieu of an early full-term pregnancy induces lobular development, completing the cycle of differentiation of the breast. This process induces a specific genomic signature in the mammary gland that is represented by the stem cell containing a heterochomatin condensed nucleus (HTN). Even though differentiation significantly reduces cell proliferation in the mammary gland, the mammary epithelium remains capable of responding with proliferation to given stimuli, such as a new pregnancy. The stem cell HTN is able to metabolize the carcinogen and repair the induced DNA damage more efficiently than the stem cell containing an euchromatinic structure (EUN), as it has been demonstrated in the rodent experimental system. The basic biological concept is that pregnancy shifts the stem cell EUN to the stem cell HTN that is refractory to carcinogenesis. Data generated by the use of cDNA micro array techniques have allowed to demonstrate that while lobular development regressed after pregnancy and lactation, programmed cell death genes, DNA repair genes, chromatin remodeling, transcription factors and immune-surveillance gene transcripts all of these genes are upregulated and are part of the genomic signature of pregnancy that is associated with the preventive effect of this physiological process.

The influence of arachidonic acid metabolites on cell division in the intestinal epithelium and in colonic tumors.

PubMed

Petry, F M; Tutton, P J; Barkla, D H

1984-09-01

Various metabolites of arachidonic acid are now known to influence cell division. In this paper the effects on cell proliferation of arachidonic acid, some inhibitors of arachidonic acid metabolism and some analogs of arachidonic acid metabolites is described. The epithelial cell proliferation rate in the jejunum, in the descending colon and in dimethylhydrazine-induced tumors of rat colon was measured using a stathmokinetic technique. Administration of arachidonic acid resulted in retardation of cell proliferation in each of the tissues examined. A cyclooxygenase inhibitor (Flurbiprofen) prevented this effect of arachidonic acid in the jejunal crypts and in colonic tumors, but not in colonic crypts. In contrast, inhibitors of both cyclooxygenase and lipoxygenase (Benoxaprofen and BW755c) prevented the effect of arachidonic acid in the colonic crypts and reduced its effect on colonic tumours but did not alter its effect on the jejunum. An inhibitor of thromoboxane A2 synthetase (U51,605) was also able to prevent the inhibitory effect of arachidonic acid on colonic tumors. Treatment with 16,16-dimethyl PGE2 inhibited cell proliferation in jejunal crypts and in colonic tumors, as did a thromboxane A2 mimicking agent, U46619. Nafazatrom, an agent that stimulates prostacyclin synthesis and inhibits lypoxygenase, promoted cell proliferation in the jejunal crypts and colonic crypts, but inhibited cell proliferation in colonic tumours.

Norms in Conflict: Statecraft, Preventive Force, and Counter Proliferation

DTIC Science & Technology

2016-12-01

power. Finally, the ethical character of norms offers a framework for the attacking state to justify its actions to the international community ...national identity, sanctions, and ethics play in counter-proliferation strategies. Finally, it concludes by offering policy recommendations for...role that national identity, sanctions, and ethics play in counter-proliferation strategies. Finally, it concludes by offering policy

Liganded Peroxisome Proliferator-Activated Receptors (PPARs) Preserve Nuclear Histone Deacetylase 5 Levels in Endothelin-Treated Sprague-Dawley Rat Cardiac Myocytes

PubMed Central

Zhang, Haining; Shao, Zongjun; Alibin, Caroline P.; Acosta, Crystal; Anderson, Hope D.

2014-01-01

Ligand activation of peroxisome proliferator-activated receptors (PPARs) prevents cardiac myocyte hypertrophy, and we previously reported that diacylglycerol kinase zeta (DGKζ) is critically involved. DGKζ is an intracellular lipid kinase that catalyzes phosphorylation of diacylglycerol; by attenuating DAG signaling, DGKζ suppresses protein kinase C (PKC) and G-protein signaling. Here, we investigated how PPAR-DGKζ signaling blocks activation of the hypertrophic gene program. We focused on export of histone deacetylase 5 (HDAC5) from the nucleus, a key event during hypertrophy, since crosstalk occurs between PPARs and other members of the HDAC family. Using cardiac myocytes isolated from Sprague-Dawley rats, we determined that liganded PPARs disrupt endothelin-1 (ET1)-induced nuclear export of HDAC5 in a manner that is dependent on DGKζ. When DGKζ-mediated PKC inhibition was circumvented using a constitutively-active PKCε mutant, PPARs failed to block ET1-induced nuclear retention of HDAC5. Liganded PPARs also prevented (i) activation of protein kinase D (the downstream effector of PKC), (ii) HDAC5 phosphorylation at 14-3-3 protein chaperone binding sites (serines 259 and 498), and (iii) physical interaction between HDAC5 and 14-3-3, all of which are consistent with blockade of nucleo-cytoplasmic shuttling of HDAC5. Finally, the ability of PPARs to prevent neutralization of HDAC5 activity was associated with transcriptional repression of hypertrophic genes. This occurred by first, reduced MEF2 transcriptional activity and second, augmented deacetylation of histone H3 associated with hypertrophic genes expressing brain natriuretic peptide, β-myosin heavy chain, skeletal muscle α-actin, and cardiac muscle α-actin. Our findings identify spatial regulation of HDAC5 as a target for liganded PPARs, and to our knowledge, are the first to describe a mechanistic role for nuclear DGKζ in cardiac myocytes. In conclusion, these results implicate modulation of HDAC5 as a mechanism by which liganded PPARs suppress the hypertrophic gene program. PMID:25514029

Prostate cancer chemoprevention agent development: the National Cancer Institute, Division of Cancer Prevention portfolio.

PubMed

Parnes, Howard L; House, Margaret G; Kagan, Jacob; Kausal, David J; Lieberman, Ronald

2004-02-01

We describe the current National Cancer Institute chemoprevention agent development program and provide a summary of the intermediate end points used. The National Cancer Institute is currently sponsoring a wide range of studies of promising chemoprevention agents in a variety of informative cohorts, eg high grade prostatic intraepithelial neoplasia, positive family history of cancer, increased prostate specific antigen with negative biopsies, prostate cancer followed expectantly, prostate cancer awaiting definitive therapy and the general population. The rationale for each agent under investigation is derived from epidemiological observations, prostate cancer treatment trials, secondary analyses of large cancer prevention studies, an understanding of cancer biology and prostate carcinogenesis, and/or experimental animal models. Carcinogenesis is a multistep process occurring over decades which is characterized by disruption of the normal regulatory pathways controlling cellular proliferation, programmed cell death and differentiation. Administration of agents to reverse, inhibit or slow this process of malignant transformation is known as chemoprevention. Chemoprevention represents a promising approach to reducing the morbidity and mortality of prostate cancer. A variety of agents are currently being studied in phase 2 clinical trials, some of which may warrant subsequent evaluation in phase 3 trials with definitive cancer end points. Two large phase 3 trials, the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, which are ongoing, are also sponsored by the National Cancer Institute.

Russian Contract Procurement Document

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

Tobin, J G

2010-03-29

This contract supports the enhancement of physical protection or nuclear material control and accounting systems at institutes or enterprises of the newly independent states under the material protection control and accounting (MPC&A) program. The contract is entered into pursuant to the MPC&A Program, a gratuitous technical assistance program, in accordance with the bilateral Agreements between the Russian Federation and the United States of America concerning the Safe and Secure Transportation, Storage and Destruction of Weapons and the Prevention of Weapons Proliferation of June 1992, as extended and amended by Protocol signed of June 1999, Agreement between the Government of themore » Russian Federation regarding Cooperation in the Area of Nuclear Materials Physical Protection, Control and Accounting of October 1999 and the Russian Federation law of May 1999 on the taxation exemption of gratuitous technical assistance with Russian Federation under registration No.DOE001000.« less

Tea Polysaccharide Prevents Colitis-Associated Carcinogenesis in Mice by Inhibiting the Proliferation and Invasion of Tumor Cells

PubMed Central

Liu, Li-Qiao; Li, Hai-Shan; Shen, Ming-Yue; Hu, Jie-Lun; Xie, Ming-Yong

2018-01-01

The imbalance between cell proliferation and apoptosis can lead to tumor progression, causing oncogenic transformation, abnormal cell proliferation and cell apoptosis suppression. Tea polysaccharide (TPS) is the major bioactive component in green tea, it has showed antioxidant, antitumor and anti-inflammatory bioactivities. In this study, the chemoprophylaxis effects of TPS on colitis-associated colon carcinogenesis, especially the cell apoptosis activation and inhibition effects on cell proliferation and invasion were analyzed. The azoxymethane/dextran sulfate sodium (AOM/DSS) was used to induce the colorectal carcinogenesis in mice. Results showed that the tumor incidence was reduced in TPS-treated AOM/DSS mice compared to AOM/DSS mice. TUNEL staining and Ki-67 immunohistochemistry staining showed that the TPS treatment increased significantly the cell apoptosis and decreased cell proliferation among AOM/DSS mice. Furthermore, TPS reduced the expression levels of the cell cycle protein cyclin D1, matrix metalloproteinase (MMP)-2, and MMP-9. In addition, in vitro studies showed that TPS, suppressed the proliferation and invasion of the mouse colon cancer cells. Overall, our findings demonstrated that TPS could be a potential agent in the treatment and/or prevention of colon tumor, which promoted the apoptosis and suppressed the proliferation and invasion of the mouse colon cancer cells via arresting cell cycle progression. PMID:29419740

TGFbeta receptor saxophone non-autonomously regulates germline proliferation in a Smox/dSmad2-dependent manner in Drosophila testis.

PubMed

Li, Chun-Yan; Guo, Zheng; Wang, Zhaohui

2007-09-01

Elucidating the regulatory mechanism of cell proliferation is central to the understanding of cancer development or organ size control. Drosophila spermatogenesis provides an excellent model to study cell proliferation since the germline cells mitotically amplify in a precise manner. However, the underlying molecular mechanism remains elusive. Germ cells derived from each gonialblast develop synchronously as one unit encapsulated by two somatic support cells (called cyst cells). Components of TGFbeta pathway have previously been found to restrict germ cell proliferation via their functions in cyst cells. Here we report that saxophone (sax), a TGFbeta type I receptor, is required in somatic cells to prevent the mitotically dividing spermatogonia from over-amplifying. Using various approaches, we demonstrate that Mad (Mothers against Dpp), a receptor-Smad usually associated with Sax-mediated TGFbeta/BMP signaling, is dispensable in this process. Instead, Smox (Smad on X, Drosophila Smad2), the other receptor-Smad formerly characterized in TGFbeta/activin signaling, is necessary for the precise mitotic divisions of spermatogonia. Furthermore, over-expressing Smox in cyst cells can partially rescue the proliferation phenotype induced by sax mutation. We propose that Smox acts downstream of Sax to prevent spermatogonial over-proliferation in Drosophila.

Gingerol Inhibits Serum-Induced Vascular Smooth Muscle Cell Proliferation and Injury-Induced Neointimal Hyperplasia by Suppressing p38 MAPK Activation.

PubMed

Jain, Manish; Singh, Ankita; Singh, Vishal; Maurya, Preeti; Barthwal, Manoj Kumar

2016-03-01

Gingerol inhibits growth of cancerous cells; however, its role in vascular smooth muscle cell (VSMC) proliferation is not known. The present study investigated the effect of gingerol on VSMC proliferation in cell culture and during neointima formation after balloon injury. Rat VSMCs or carotid arteries were harvested at 15 minutes, 30 minutes, 1, 6, 12, and 24 hours of fetal bovine serum (FBS; 10%) stimulation or balloon injury, respectively. Gingerol prevented FBS (10%)-induced proliferation of VSMCs in a dose-dependent manner (50 μmol/L-400 μmol/L). The FBS-induced proliferating cell nuclear antigen (PCNA) upregulation and p27(Kip1) downregulation were also attenuated in gingerol (200 μmol/L) pretreated cells. Fetal bovine serum-induced p38 mitogen-activated protein kinase (MAPK) activation, PCNA upregulation, and p27(Kip1) downregulation were abrogated in gingerol (200 μmol/L) and p38 MAPK inhibitor (SB203580, 10 μmol/L) pretreated cells. Balloon injury induced time-dependent p38 MAPK activation in the carotid artery. Pretreatment with gingerol (200 μmol/L) significantly attenuated injury-induced p38 MAPK activation, PCNA upregulation, and p27(Kip1) downregulation. After 14 days of balloon injury, intimal thickening, neointimal proliferation, and endothelial dysfunction were significantly prevented in gingerol pretreated arteries. In isolated organ bath studies, gingerol (30 nmol/L-300 μmol/L) inhibited phenylephrine-induced contractions and induced dose-dependent relaxation of rat thoracic aortic rings in a partially endothelium-dependent manner. Gingerol prevented FBS-induced VSMC proliferation and balloon injury-induced neointima formation by regulating p38 MAPK. Vasodilator effect of gingerol observed in the thoracic aorta was partially endothelium dependent. Gingerol is thus proposed as an attractive agent for modulating VSMC proliferation, vascular reactivity, and progression of vascular proliferative diseases. © The Author(s) 2015.

Inhibition of Vascular Smooth Muscle Cell Proliferation by Gentiana lutea Root Extracts

PubMed Central

Kesavan, Rushendhiran; Potunuru, Uma Rani; Nastasijević, Branislav; T, Avaneesh; Joksić, Gordana; Dixit, Madhulika

2013-01-01

Gentiana lutea belonging to the Gentianaceae family of flowering plants are routinely used in traditional Serbian medicine for their beneficial gastro-intestinal and anti-inflammatory properties. The aim of the study was to determine whether aqueous root extracts of Gentiana lutea consisting of gentiopicroside, gentisin, bellidifolin-8-O-glucoside, demethylbellidifolin-8-O-glucoside, isovitexin, swertiamarin and amarogentin prevents proliferation of aortic smooth muscle cells in response to PDGF-BB. Cell proliferation and cell cycle analysis were performed based on alamar blue assay and propidium iodide labeling respectively. In primary cultures of rat aortic smooth muscle cells (RASMCs), PDGF-BB (20 ng/ml) induced a two-fold increase in cell proliferation which was significantly blocked by the root extract (1 mg/ml). The root extract also prevented the S-phase entry of synchronized cells in response to PDGF. Furthermore, PDGF-BB induced ERK1/2 activation and consequent increase in cellular nitric oxide (NO) levels were also blocked by the extract. These effects of extract were due to blockade of PDGF-BB induced expression of iNOS, cyclin D1 and proliferating cell nuclear antigen (PCNA). Docking analysis of the extract components on MEK1, the upstream ERK1/2 activating kinase using AutoDock4, indicated a likely binding of isovitexin to the inhibitor binding site of MEK1. Experiments performed with purified isovitexin demonstrated that it successfully blocks PDGF-induced ERK1/2 activation and proliferation of RASMCs in cell culture. Thus, Gentiana lutea can provide novel candidates for prevention and treatment of atherosclerosis. PMID:23637826

Inhibition of vascular smooth muscle cell proliferation by Gentiana lutea root extracts.

PubMed

Kesavan, Rushendhiran; Potunuru, Uma Rani; Nastasijević, Branislav; T, Avaneesh; Joksić, Gordana; Dixit, Madhulika

2013-01-01

Gentiana lutea belonging to the Gentianaceae family of flowering plants are routinely used in traditional Serbian medicine for their beneficial gastro-intestinal and anti-inflammatory properties. The aim of the study was to determine whether aqueous root extracts of Gentiana lutea consisting of gentiopicroside, gentisin, bellidifolin-8-O-glucoside, demethylbellidifolin-8-O-glucoside, isovitexin, swertiamarin and amarogentin prevents proliferation of aortic smooth muscle cells in response to PDGF-BB. Cell proliferation and cell cycle analysis were performed based on alamar blue assay and propidium iodide labeling respectively. In primary cultures of rat aortic smooth muscle cells (RASMCs), PDGF-BB (20 ng/ml) induced a two-fold increase in cell proliferation which was significantly blocked by the root extract (1 mg/ml). The root extract also prevented the S-phase entry of synchronized cells in response to PDGF. Furthermore, PDGF-BB induced ERK1/2 activation and consequent increase in cellular nitric oxide (NO) levels were also blocked by the extract. These effects of extract were due to blockade of PDGF-BB induced expression of iNOS, cyclin D1 and proliferating cell nuclear antigen (PCNA). Docking analysis of the extract components on MEK1, the upstream ERK1/2 activating kinase using AutoDock4, indicated a likely binding of isovitexin to the inhibitor binding site of MEK1. Experiments performed with purified isovitexin demonstrated that it successfully blocks PDGF-induced ERK1/2 activation and proliferation of RASMCs in cell culture. Thus, Gentiana lutea can provide novel candidates for prevention and treatment of atherosclerosis.

Intrauterine programming of lipid metabolic alterations in the heart of the offspring of diabetic rats is prevented by maternal diets enriched in olive oil.

PubMed

Capobianco, Evangelina; Pelesson, Magalí; Careaga, Valeria; Fornes, Daiana; Canosa, Ivana; Higa, Romina; Maier, Marta; Jawerbaum, Alicia

2015-10-01

Maternal diabetes can program metabolic and cardiovascular diseases in the offspring. The aim of this work was to address whether an olive oil supplemented diet during pregnancy can prevent lipid metabolic alterations in the heart of the offspring of mild diabetic rats. Control and diabetic Wistar rats were fed during pregnancy with either a standard diet or a 6% olive oil supplemented diet. The heart of adult offspring from diabetic rats showed increases in lipid concentrations (triglycerides in males and phospholipids, cholesterol, and free fatty acids in females), which were prevented with the maternal diets enriched in olive oil. Maternal olive oil supplementation increased the content of unsaturated fatty acids in the hearts of both female and male offspring from diabetic rats (possibly due to a reduction in lipoperoxidation), increased the expression of Δ6 desaturase in the heart of male offspring from diabetic rats, and increased the expression of peroxisome proliferator activated receptor α in the hearts of both female and male offspring from diabetic rats. Relevant alterations in cardiac lipid metabolism were evident in the adult offspring of a mild diabetic rat model, and regulated by maternal diets enriched in olive oil. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Targeting the Epigenome with Bioactive Food Components for Cancer Prevention

PubMed Central

Ong, Thomas Prates; Moreno, Fernando Salvador; Ross, Sharon Ann

2012-01-01

Epigenetic processes participate in cancer development and likely influence cancer prevention. Global DNA hypomethylation, gene promoter hypermethylation and aberrant histone post-translational modifications are hallmarks of neoplastic cells which have been associated with genomic instability and altered gene expression. Because epigenetic deregulation occurs early in carcinogenesis and is potentially reversible, intervention strategies targeting the epigenome have been proposed for cancer prevention. Bioactive food components (BFCs) with anticancer potential, including folate, polyphenols, selenium, retinoids, fatty acids, isothiocyanates and allyl compounds, influence DNA methylation and histone modification processes. Such activities have been shown to affect the expression of genes involved in cell proliferation, death and differentiation that are frequently altered in cancer. Although the epigenome represents a promising target for cancer prevention with BFCs, few studies have addressed the influence of dietary components on these mechanisms in vivo, particularly on the phenotype of humans, and thus the exact mechanisms whereby diet mediates an effect on cancer prevention remains unclear. Primary factors that should be elucidated include the effective doses and dose timing of BFCs to attain epigenetic effects. Because diet-epigenome interactions are likely to occur in utero, the impact of early-life nutrition on cancer risk programming should be further investigated. PMID:22353664

Genistein effects on stromal cells determines epithelial proliferation in endometrial co-cultures.

PubMed

Sampey, Brante P; Lewis, Terrence D; Barbier, Claire S; Makowski, Liza; Kaufman, David G

2011-06-01

Estrogen is the leading etiologic factor for endometrial cancer. Estrogen-induced proliferation of endometrial epithelial cells normally requires paracrine growth factors produced by stromal cells. Epidemiologic evidence indicates that dietary soy prevents endometrial cancer, and implicates the phytoestrogen genistein in this effect. However, results from previous studies are conflicting regarding the effects of genistein on hormone responsive cancers. The effects of estrogen and genistein on proliferation of Ishikawa (IK) endometrial adenocarcinoma cells were examined in co-cultures of IK cells with endometrial stromal cells, recapitulating the heterotypic cell-to-cell interactions observed in vivo. The roles of estrogen receptor (ER)α and ERβ were evaluated using ERα and ERβ specific agonists. ER activation and cell proliferation in the IK epithelial cells were determined by alkaline phosphatase assay and Coulter counter enumeration, respectively. Both estrogen and genistein increased estrogen receptor-induced gene activity in IK cells over a range of concentrations. Estrogen alone but not genistein increased IK proliferation in co-cultures. When primed by estrogen treatment, increasing concentrations of genistein produced a biphasic effect on IK proliferation: nM concentrations inhibited estrogen-induced proliferation while μM concentrations increased proliferation. Studies with an ERβ-specific agonist produced similar results. Genistein did not influence the effects of estrogen on IK proliferation in monoculture. Our study indicates that nutritionally relevant concentrations (nM) of genistein inhibit the proliferative effects of estrogen on endometrial adenocarcinoma cells presumably through activation of stromal cell ERβ. We believe that sub-micromolar concentrations of genistein may represent a novel adjuvant for endometrial cancer treatment and prevention. Copyright © 2011 Elsevier Inc. All rights reserved.

Identification of cancer genes that are independent of dominant proliferation and lineage programs

PubMed Central

Selfors, Laura M.; Stover, Daniel G.; Harris, Isaac S.; Brugge, Joan S.; Coloff, Jonathan L.

2017-01-01

Large, multidimensional cancer datasets provide a resource that can be mined to identify candidate therapeutic targets for specific subgroups of tumors. Here, we analyzed human breast cancer data to identify transcriptional programs associated with tumors bearing specific genetic driver alterations. Using an unbiased approach, we identified thousands of genes whose expression was enriched in tumors with specific genetic alterations. However, expression of the vast majority of these genes was not enriched if associations were analyzed within individual breast tumor molecular subtypes, across multiple tumor types, or after gene expression was normalized to account for differences in proliferation or tumor lineage. Together with linear modeling results, these findings suggest that most transcriptional programs associated with specific genetic alterations in oncogenes and tumor suppressors are highly context-dependent and are predominantly linked to differences in proliferation programs between distinct breast cancer subtypes. We demonstrate that such proliferation-dependent gene expression dominates tumor transcriptional programs relative to matched normal tissues. However, we also identified a relatively small group of cancer-associated genes that are both proliferation- and lineage-independent. A subset of these genes are attractive candidate targets for combination therapy because they are essential in breast cancer cell lines, druggable, enriched in stem-like breast cancer cells, and resistant to chemotherapy-induced down-regulation. PMID:29229826

Muscle progenitor cells proliferation doesn't sufficiently contribute to maintaining stretched soleus muscle mass during gravitational unloading

NASA Astrophysics Data System (ADS)

Tarakina, M. V.; Turtikova, O. V.; Nemirovskaya, T. L.; Kokontcev, A. A.; Shenkman, B. S.

Skeletal muscle work hypertrophy is usually connected with muscle progenitor satellite cells (SC) activation with subsequent incorporation of their nuclei into myofibers. Passive stretch of unloaded muscle was earlier established to prevent atrophic processes and is accompanied by enhanced protein synthesis. We hypothesized that elimination of SC proliferation capacity by γ-irradiation would partly avert stretched muscle fiber capability to maintain their size under the conditions of gravitational unloading. To assess the role of muscle progenitor (satellite) cells in development of passive stretch preventive effect SC proliferation was suppressed by local exposing to ionized radiation (2500 rad), subsequent hindlimb suspension or hindlimb suspension with concomitant passive stretch were carried out. Reduction of myofiber cross-sectional area and decrease in myonuclei number accompanying unloaded muscle atrophy were completely abolished by passive stretch both in irradiated and sham-treated animals. We conclude that SC did not make essential contribution to passive stretch preventive action under the conditions of simulated weightlessness.

Reversible effect of all-trans-retinoic acid on AML12 hepatocyte proliferation and cell cycle progression

EPA Science Inventory

The role of all-trans-retinoic acid (atRA) in the regulation of cellular proliferation and differentiation is well documented. Numerous studies have established the cancer preventive propertiesofatRAwhichfunctionstoregulate levels ofcellcycleproteinsessentialfortheGliS transition...

78 FR 58859 - Provision of Defense Articles and Services to Vetted Members of the Syrian Opposition for Use in...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-25

... Use in Syria To Prevent the Use or Proliferation of Chemical Weapons and Related Materials... proliferation of Syria's chemical weapons, is essential to the national security interests of the United States...

Trans, trans-2,4-decadienal induced cell proliferation via p27 pathway in human bronchial epithelial cells

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

Chang, Y.-C.; Lin Pinpin

2008-04-01

Lung cancer is the leading cause of cancer deaths worldwide. Epidemiological studies have shown that exposure to cooking oil fumes (COF) is a risk factor for lung cancer. Trans, trans-2,4-decadienal (tt-DDE), a dienaldehyde, is abundant in heated oils and COF. Previously, we found that long-term exposure (45 days) to a sub-lethal dose (1 {mu}M) of tt-DDE significantly increased growth of human bronchial epithelial cells (BEAS-2B). Aims of this study are to understand the mechanism of tt-DDE-induced cell proliferation and possible protective effects of antioxidant, vitamin C and N-acetylcysteine (NAC) in BEAS-2B cells. Utilizing the real-time RT-PCR and Western immunoblotting, wemore » found that p27 mRNA and protein levels were significantly increased by 1 {mu}M tt-DDE treatment. Co-treatment with vitamin C or NAC partially prevented tt-DDE-induced cell proliferation. In addition, the downstream targets of p27, including CDK4, cyclin D{sub 1} and phosphorylated-Rb proteins, increased in 1 {mu}M tt-DDE-treated cells and these changes were prevented by NAC co-treatment. Therefore, these results suggest that tt-DDE increased cell proliferation via inhibition of p27 expression, increase in CDK4/cyclin D{sub 1} protein accumulation and enhancement of Rb phosphorylation. Increased cell proliferation is considered as the early stages of lung carcinogenesis. Administration of antioxidants may prevent COF-associated lung carcinogenesis.« less

Inhibition of mitochondrial fission prevents hypoxia-induced metabolic shift and cellular proliferation of pulmonary arterial smooth muscle cells.

PubMed

Parra, Valentina; Bravo-Sagua, Roberto; Norambuena-Soto, Ignacio; Hernández-Fuentes, Carolina P; Gómez-Contreras, Andrés G; Verdejo, Hugo E; Mellado, Rosemarie; Chiong, Mario; Lavandero, Sergio; Castro, Pablo F

2017-11-01

Chronic hypoxia exacerbates proliferation of pulmonary arterial smooth muscle cells (PASMC), thereby reducing the lumen of pulmonary arteries. This leads to poor blood oxygenation and cardiac work overload, which are the basis of diseases such as pulmonary artery hypertension (PAH). Recent studies revealed an emerging role of mitochondria in PAH pathogenesis, as key regulators of cell survival and metabolism. In this work, we assessed whether hypoxia-induced mitochondrial fragmentation contributes to the alterations of both PASMC death and proliferation. In previous work in cardiac myocytes, we showed that trimetazidine (TMZ), a partial inhibitor of lipid oxidation, stimulates mitochondrial fusion and preserves mitochondrial function. Thus, here we evaluated whether TMZ-induced mitochondrial fusion can prevent human PASMC proliferation in an in vitro hypoxic model. Using confocal fluorescence microscopy, we showed that prolonged hypoxia (48h) induces mitochondrial fragmentation along with higher levels of the mitochondrial fission protein DRP1. Concomitantly, both mitochondrial potential and respiratory rates decreased, indicative of mitochondrial dysfunction. In accordance with a metabolic shift towards non-mitochondrial ATP generation, mRNA levels of glycolytic markers HK2, PFKFB2 and GLUT1 increased during hypoxia. Incubation of PASMC with TMZ, prior to hypoxia, prevented all these changes and precluded the increase in PASMC proliferation. These findings were also observed using Mdivi-1 (a pharmacological DRP1 inhibitor) or a dominant negative DRP1 K38A as pre-treatments. Altogether, our data indicate that TMZ exerts a protective role against hypoxia-induced PASMC proliferation, by preserving mitochondrial function, thus highlighting DRP1-dependent morphology as a novel therapeutic approach for diseases such as PAH. Copyright © 2017 Elsevier B.V. All rights reserved.

A Meta-Analysis of the Impact of Universal and Indicated Preventive Technology-Delivered Interventions for Higher Education Students.

PubMed

Conley, Colleen S; Durlak, Joseph A; Shapiro, Jenna B; Kirsch, Alexandra C; Zahniser, Evan

2016-08-01

The uses of technology-delivered mental health treatment options, such as interventions delivered via computer, smart phone, or other communication or information devices, as opposed to primarily face-to-face interventions, are proliferating. However, the literature is unclear about their effectiveness as preventive interventions for higher education students, a population for whom technology-delivered interventions (TDIs) might be particularly fitting and beneficial. This meta-analytic review examines technological mental health prevention programs targeting higher education students either without any presenting problems (universal prevention) or with mild to moderate subclinical problems (indicated prevention). A systematic literature search identified 22 universal and 26 indicated controlled interventions, both published and unpublished, involving 4763 college, graduate, or professional students. As hypothesized, the overall mean effect sizes (ESs) for both universal (0.19) and indicated interventions (0.37) were statistically significant and differed significantly from each other favoring indicated interventions. Skill-training interventions, both universal (0.21) and indicated (0.31), were significant, whereas non-skill-training interventions were only significant among indicated (0.25) programs. For indicated interventions, better outcomes were obtained in those cases in which participants had access to support during the course of the intervention, either in person or through technology (e.g., email, online contact). The positive findings for both universal and indicated prevention are qualified by limitations of the current literature. To improve experimental rigor, future research should provide detailed information on the level of achieved implementation, describe participant characteristics and intervention content, explore the impact of potential moderators and mechanisms of success, collect post-intervention and follow-up data regardless of intervention completion, and use analysis strategies that allow for inclusion of cases with partially missing data.

Lipoic acid prevents suppression of connective tissue proliferation in the rat liver induced by n-3 PUFAs. A pilot study.

PubMed

Arend, A; Zilmer, M; Vihalemm, T; Selstam, G; Sepp, E

2000-01-01

As previously shown, dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) suppress connective tissue proliferation in the rat liver wound concurrent with an elevated level of lipid peroxidation. The present study was undertaken to investigate the influence of alpha-lipoic acid (LA), a natural anti-oxidant, on these effects of n-3 PUFAs. Rats were fed with a commercial pellet diet (control group) or with diets enriched with 10% of sunflower oil (n-6 group) or 10% of fish oil (n-3 group) for 8 weeks followed by addition of LA to the same diets for 10 days. Then a liver thermic wound was induced and the administration of LA was continued for 6 days. The proliferation of the connective tissue, the level of lipid peroxidation and their peroxidizability and the content of prostaglandins E2 and F2alpha were measured in the liver wounds. LA prevented the suppression of connective tissue proliferation in the healing wound induced by n-3 PUFAs, avoided the increase in peroxidation of lipids, reduced peroxidizability of lipids and modulated the decrease in PGE2 and PGF2alpha. The results indicate that dietary LA may prevent the suppression of liver wound healing induced by n-3 PUFAs.

Regulation of the Mevalonate Pathway for the Prevention of Breast Cancer

DTIC Science & Technology

2003-08-01

eicosapentaenoic acid (EPA) as well as the dietary isoprenoid geraniol that inhibit cell proliferation, are inhibitors of HMG-CoA reductase activity in...breast cancer cells. The inhibitory effects of EPA and geraniol on cell proliferation, however, are independent of mevalonate. DHA, on the other hand

Effects of donor proliferation in development aid for health on health program performance: A conceptual framework.

PubMed

Pallas, Sarah Wood; Ruger, Jennifer Prah

2017-02-01

Development aid for health increased dramatically during the past two decades, raising concerns about inefficiency and lack of coherence among the growing number of global health donors. However, we lack a framework for how donor proliferation affects health program performance to inform theory-based evaluation of aid effectiveness policies. A review of academic and gray literature was conducted. Data were extracted from the literature sample on study design and evidence for hypothesized effects of donor proliferation on health program performance, which were iteratively grouped into categories and mapped into a new conceptual framework. In the framework, increases in the number of donors are hypothesized to increase inter-donor competition, transaction costs, donor poaching of recipient staff, recipient control over aid, and donor fragmentation, and to decrease donors' sense of accountability for overall development outcomes. There is mixed evidence on whether donor proliferation increases or decreases aid volume. These primary effects in turn affect donor innovation, information hoarding, and aid disbursement volatility, as well as recipient country health budget levels, human resource capacity, and corruption, and the determinants of health program performance. The net effect of donor proliferation on health will vary depending on the magnitude of the framework's competing effects in specific country settings. The conceptual framework provides a foundation for improving design of aid effectiveness practices to mitigate negative effects from donor proliferation while preserving its potential benefits. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cancer prevention and therapy through the modulation of the tumor microenvironment

PubMed Central

Casey, Stephanie C.; Amedei, Amedeo; Aquilano, Katia; Benencia, Fabian; Bhakta, Dipita; Boosani, Chandra S.; Chen, Sophie; Ciriolo, Maria Rosa; Crawford, Sarah; Fujii, Hiromasa; Georgakilas, Alexandros G.; Guha, Gunjan; Halicka, Dorota; Helferich, William G.; Heneberg, Petr; Honoki, Kanya; Kerkar, Sid P.; Mohammed, Sulma I.; Niccolai, Elena; Nowsheen, Somaira; Rupasinghe, H. P. Vasantha; Samadi, Abbas; Singh, Neetu; Talib, Wamidh H.; Venkateswaran, Vasundara; Whelan, Richard; Yang, Xujuan; Felsher, Dean W.

2015-01-01

Cancer arises in the context of an in vivo tumor microenvironment. This microenvironment is both a cause and consequence of tumorigenesis. Tumor and host cells co-evolve dynamically through indirect and direct cellular interactions, eliciting multiscale effects on many biological programs, including cellular proliferation, growth, and metabolism, as well as angiogenesis and hypoxia and innate and adapative immunity. Here we highlight specific biological processes that could be exploited as targets for the prevention and therapy of cancer. Specifically, we describe how inhibition of targets such as cholesterol synthesis and metabolites, reactive oxygen species and hypoxia, macrophage activation and conversion, indoleamine 2, 3-dioxygenase regulation of dendritic cells, vascular endothelial growth factor regulation of angiogenesis, fibrosis inhibition, endoglin, and Janus kinase signaling emerge as examples of important potential nexuses in the regulation of tumorigenesis and the tumor microenvironment that can be targeted. We have also identified therapeutic agents as approaches, in particular natural products such as berberine, resveratrol, onionin A, epigallocatechin gallate, genistein, curcumin, naringenin, desoxyrhapontigenin, piperine, and zerumbone, that may warrant further investigation to target the tumor microenvironment for the treatment and/or prevention of cancer. PMID:25865775

Different fibroblast subpopulations of the eye: a therapeutic target to prevent postoperative fibrosis in glaucoma therapy.

PubMed

Stahnke, Thomas; Löbler, Marian; Kastner, Christian; Stachs, Oliver; Wree, Andreas; Sternberg, Katrin; Schmitz, Klaus-Peter; Guthoff, Rudolf

2012-07-01

The aim of this study is the characterization of fibroblasts mainly responsible for fibrosis processes associated with trabeculectomy or microstent implantation for glaucoma therapy. Therefore we isolated human primary fibroblasts from choroidea, sclera, Tenon capsule, and orbital fat tissues. These fibroblast subpopulations were analysed in vitro for expression of the extracellular matrix components which are responsible for postoperative scarring in glaucoma therapy. For scarring the proteins of the collagen family are predominant and so we focused on the expression of collagen I, collagen III and collagen VI in every fibroblast subpopulation. Also, the extracellular matrix protein fibronectin which crosslinks collagen fibres or other extracellular matrix components and cell surfaces, was analyzed. Collagen I, III and VI were prominent in every fibroblast subpopulation. The highest amounts of collagen III were found in hCF and hOF, whereas the signal in hSF and hTF was negligible. Additionally, there is a link between scarring processes and proliferating potential of fibroblasts, in case of microstent implantation triggered through the infiltration of inflammatory cells. Thus we analyzed fibroblast subpopulations for the presence of TGF-β1 which is one of the most important cytokines involved in proliferation processes. TGF-β1 was prominent in all fibroblast subpopulations with lowest expression in hCF cultures. To prevent postoperative fibroblast proliferation we analyzed in vitro the proliferation-inhibitors paclitaxel and mitomycin C which are potential candidates in drug eluting drainage systems on ocular fibroblast subpopulations. These inhibitors arrest fibroblast proliferation and viability, being, however, not very specific and have a cytotoxic potential also on healthy tissues surrounding the microstent outflow area. Significant differences in protein synthesis of fibroblasts subpopulations which could be specific targets for inhibition may help to find out fibroblast specific inhibitors to prevent postoperative scarring and could prevent patients from secondary surgery after microstent implantation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A2A receptor-dependent manner: A2A receptor blockade prevents BDNF release and proliferation of microglia

PubMed Central

2013-01-01

Background Brain-derived neurotrophic factor (BDNF) has been shown to control microglial responses in neuropathic pain. Since adenosine A2A receptors (A2ARs) control neuroinflammation, as well as the production and function of BDNF, we tested to see if A2AR controls the microglia-dependent secretion of BDNF and the proliferation of microglial cells, a crucial event in neuroinflammation. Methods Murine N9 microglial cells were challenged with lipopolysaccharide (LPS, 100 ng/mL) in the absence or in the presence of the A2AR antagonist, SCH58261 (50 nM), as well as other modulators of A2AR signaling. The BDNF cellular content and secretion were quantified by Western blotting and ELISA, A2AR density was probed by Western blotting and immunocytochemistry and cell proliferation was assessed by BrdU incorporation. Additionally, the A2AR modulation of LPS-driven cell proliferation was also tested in primary cultures of mouse microglia. Results LPS induced time-dependent changes of the intra- and extracellular levels of BDNF and increased microglial proliferation. The maximal LPS-induced BDNF release was time-coincident with an LPS-induced increase of the A2AR density. Notably, removing endogenous extracellular adenosine or blocking A2AR prevented the LPS-mediated increase of both BDNF secretion and proliferation, as well as exogenous BDNF-induced proliferation. Conclusions We conclude that A2AR activation plays a mandatory role controlling the release of BDNF from activated microglia, as well as the autocrine/paracrine proliferative role of BDNF. PMID:23363775

Improved Technology To Prevent Nuclear Proliferation And Counter Nuclear Terrorism

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

Richardson, J; Yuldashev, B; Labov, S

2006-06-12

As the world moves into the 21st century, the possibility of greater reliance on nuclear energy will impose additional technical requirements to prevent proliferation. In addition to proliferation resistant reactors, a careful examination of the various possible fuel cycles from cradle to grave will provide additional technical and nonproliferation challenges in the areas of conversion, enrichment, transportation, recycling and waste disposal. Radiation detection technology and information management have a prominent role in any future global regime for nonproliferation. As nuclear energy and hence nuclear materials become an increasingly global phenomenon, using local technologies and capabilities facilitate incorporation of enhanced monitoringmore » and detection on the regional level. Radiation detection technologies are an important tool in the prevention of proliferation and countering radiological/nuclear terrorism. A variety of new developments have enabled enhanced performance in terms of energy resolution, spatial resolution, passive detection, predictive modeling and simulation, active interrogation, and ease of operation and deployment in the field. For example, various gamma ray imaging approaches are being explored to combine spatial resolution with background suppression in order to enhance sensitivity many-fold at reasonable standoff distances and acquisition times. New materials and approaches are being developed in order to provide adequate energy resolution in field use without the necessity for liquid nitrogen. Different detection algorithms enable fissile materials to be distinguished from other radioisotopes.« less

Pyruvate kinase isoform expression alters nucleotide synthesis to impact cell proliferation

PubMed Central

Lunt, Sophia Y.; Muralidhar, Vinayak; Hosios, Aaron M.; Israelsen, William J.; Gui, Dan Y.; Newhouse, Lauren; Ogrodzinski, Martin; Hecht, Vivian; Xu, Kali; Acevedo, Paula N. Marín; Hollern, Daniel P.; Bellinger, Gary; Dayton, Talya L.; Christen, Stefan; Elia, Ilaria; Dinh, Anh T.; Stephanopoulos, Gregory; Manalis, Scott R.; Yaffe, Michael B.; Andrechek, Eran R.; Fendt, Sarah-Maria; Heiden, Matthew G. Vander

2014-01-01

SUMMARY Metabolic regulation influences cell proliferation. The influence of pyruvate kinase isoforms on tumor cells has been extensively studied, but whether PKM2 is required for normal cell proliferation is unknown. We examine how PKM2-deletion affects proliferation and metabolism in non-transformed, non-immortalized PKM2-expressing primary cells. We find that deletion of PKM2 in primary cells results in PKM1 expression and proliferation arrest. PKM1 expression, rather than PKM2 loss, is responsible for this effect, and proliferation arrest cannot be explained by cell differentiation, senescence, death, changes in gene expression, or prevention of cell growth. Instead, PKM1 expression impairs nucleotide production and the ability to synthesize DNA and progress through the cell cycle. Nucleotide biosynthesis is limiting, as proliferation arrest is characterized by severe thymidine depletion, and supplying exogenous thymine rescues both nucleotide levels and cell proliferation. Thus, PKM1 expression promotes a metabolic state that is unable to support DNA synthesis. PMID:25482511

[Biological experiments on "Kosmos-1887"].

PubMed

Alpatov, A M; I'lin, E A; Antipov, V V; Tairbekov, M G

1989-01-01

In the 13-ray space flight on Kosmos-1887 various experiments in the field of cell biology, genetics, biorhythm, developmental biology and regeneration were performed using bacteria, protozoa, plants, worms, insects, fish and amphibia. Paramecia showed enhanced cell proliferation, spheroidization and diminished protein content. Experiments on fruit-flies, newt oocytes and primate lymphocytes confirmed involvement of the cell genetic apparatus in responses to microgravity. Beetles exhibited a reduction of the length of the spontaneous period of freely running circadian rhythms. Carausius morosus developed latent changes in early embryogenesis which manifested at later stages of ontogenesis. Exposure to microgravity did not prevent recovery of injured tissues; moreover their regeneration may be accelerated after recovery. Biology research programs in future biosatellite flights are discussed.

Cholinergic system modulates growth, apoptosis, and secretion of cholangiocytes from bile duct-ligated rats.

PubMed

LeSagE, G; Alvaro, D; Benedetti, A; Glaser, S; Marucci, L; Baiocchi, L; Eisel, W; Caligiuri, A; Phinizy, J L; Rodgers, R; Francis, H; Alpini, G

1999-07-01

To investigate the role of the cholinergic system in regulation of cholangiocyte functions, we evaluated the effects of vagotomy on cholangiocyte proliferation and secretion in rats that underwent bile duct ligation (BDL rats). After bile duct ligation (BDL), the vagus nerve was resected; 7 days later, expression of M3 acetylcholine receptor was evaluated. Cholangiocyte proliferation was assessed by morphometry and measurement of DNA synthesis. Apoptosis was evaluated by light microscopy and annexin-V staining. Ductal secretion was evaluated by measurement of secretin-induced choleresis, secretin receptor (SR) gene expression, and cyclic adenosine 3',5'-monophosphate (cAMP) levels. Vagotomy decreased the expression of M3 acetylcholine receptors in cholangiocytes. DNA synthesis and ductal mass were markedly decreased, whereas cholangiocyte apoptosis was increased by vagotomy. Vagotomy decreased ductal secretion. Forskolin treatment prevented the decrease in cAMP levels induced by vagotomy, maintained cholangiocyte proliferation, and decreased cholangiocyte apoptosis caused by vagotomy in BDL rats. Cholangiocyte secretion was also maintained by forskolin. Vagotomy impairs cholangiocyte proliferation and enhances apoptosis, leading to decreased ductal mass in response to BDL. Secretin-induced choleresis of BDL rats was virtually eliminated by vagotomy in association with decreased cholangiocyte cAMP levels. Maintenance of cAMP levels by forskolin administration prevents the effects of vagotomy on cholangiocyte proliferation, apoptosis, and secretion.

Protective effects of anisodamine on cigarette smoke extract-induced airway smooth muscle cell proliferation and tracheal contractility

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

Xu, Guang-Ni; Yang, Kai; Xu, Zu-Peng

2012-07-01

Anisodamine, an antagonist of muscarinic acetylcholine receptors (mAChRs), has been used therapeutically to improve smooth muscle function, including microvascular, intestinal and airway spasms. Our previous studies have revealed that airway hyper-reactivity could be prevented by anisodamine. However, whether anisodamine prevents smoking-induced airway smooth muscle (ASM) cell proliferation remained unclear. In this study, a primary culture of rat ASM cells was used to evaluate an ASM phenotype through the ability of the cells to proliferate and express contractile proteins in response to cigarette smoke extract (CSE) and intervention of anisodamine. Our results showed that CSE resulted in an increase in cyclinmore » D1 expression concomitant with the G0/G1-to-S phase transition, and high expression of M2 and M3. Functional studies showed that tracheal hyper-contractility accompanied contractile marker α-SMA high-expression. These changes, which occur only after CSE stimulation, were prevented and reversed by anisodamine, and CSE-induced cyclin D1 expression was significantly inhibited by anisodamine and the specific inhibitor U0126, BAY11-7082 and LY294002. Thus, we concluded that the protective and reversal effects and mechanism of anisodamine on CSE-induced events might involve, at least partially, the ERK, Akt and NF-κB signaling pathways associated with cyclin D1 via mAChRs. Our study validated that anisodamine intervention on ASM cells may contribute to anti-remodeling properties other than bronchodilation. -- Highlights: ► CSE induces tracheal cell proliferation, hyper-contractility and α-SMA expression. ► Anisodamine reverses CSE-induced tracheal hyper-contractility and cell proliferation. ► ERK, PI3K, and NF-κB pathways and cyclin D1 contribute to the reversal effect.« less

Systemic application of sirolimus prevents neointima formation not via a direct anti-proliferative effect but via its anti-inflammatory properties.

PubMed

Daniel, Jan-Marcus; Dutzmann, Jochen; Brunsch, Hannes; Bauersachs, Johann; Braun-Dullaeus, Rüdiger; Sedding, Daniel G

2017-07-01

Systemic treatment with sirolimus, as used for immunosuppression in transplant patients, results in markedly low rates of in-stent restenosis. Since the underlying mechanisms remain obscure, we aimed to determine the molecular and cellular effects of systemic sirolimus treatment on vascular remodeling processes. Systemic sirolimus treatment significantly reduced smooth muscle cell (SMC) proliferation 14days after wire-induced injury and neointima formation 28days after injury in C57BL/6 mice, while simultaneously impairing re-endothelialization. Interestingly, in vitro, sirolimus had no direct effect on the proliferation of SMC or endothelial cells (EC) at serum concentrations observed after systemic application. In contrast, sirolimus reduced the adhesion of leukocytes (CD45 + ) and bone marrow-derived progenitor cells (CD34 + ) to activated EC by down-regulating the adhesion molecules ICAM-1 and VCAM-1. In addition, sirolimus treatment also significantly reduced the upregulation of ICAM-1 and VCAM-1 and the recruitment of monocytic cells (MOMA-2 + ) in neointimal lesions in vivo. Our findings show that systemic sirolimus treatment effectively prevents SMC and EC proliferation in vivo without directly affecting these cells. Instead, sirolimus prevents neointima formation and re-endothelialization by attenuating the inflammatory response after injury with secondary effects on SMC and EC proliferation. Thus, despite a similar net effect, the mechanisms of systemic sirolimus treatment are largely different from the local effects achieved after application of sirolimus-eluting stents. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Everolimus Inhibits Anti-HLA I Antibody-Mediated Endothelial Cell Signaling, Migration and Proliferation More Potently than Sirolimus

PubMed Central

Jin, Yi-Ping; Valenzuela, Nicole M.; Ziegler, Mary E.; Rozengurt, Enrique; Reed, Elaine F.

2017-01-01

Antibody (Ab) crosslinking of HLA I molecules on the surface of endothelial cells triggers proliferative and pro-survival intracellular signaling, which is implicated in the process of chronic allograft rejection, also known as transplant vasculopathy. The purpose of this study was to investigate the role of mammalian target of rapamycin (mTOR) in HLA I antibody-induced signaling cascades. Everolimus provides a tool to establish how the mTOR signal network regulates HLA I-mediated migration, proliferation, and survival. We found that everolimus inhibits mTORC1 by disassociating Raptor from mTOR, thereby preventing class I-induced phosphorylation of mTOR, p70S6K, S6RP, and 4E-BP1, and resultant class I-stimulated cell migration and proliferation. Furthermore, we found that everolimus inhibits class I-mediated mTORC2 activation (1) by disassociating Rictor and Sin1 from mTOR; (2) by preventing class I-stimulated Akt phosphorylation; and (3) by preventing class I-mediated ERK phosphorylation. These results suggest that everolimus is more effective than sirolimus at antagonizing both mTORC1 and mTORC2, the latter of which is critical in endothelial cell functional changes leading to transplant vasculopathy in solid organ transplantation after HLA I crosslinking. Our findings point to a potential therapeutic effect of everolimus in prevention of chronic antibody-mediated rejection. PMID:24580843

DIOL Triterpenes Block Profibrotic Effects of Angiotensin II and Protect from Cardiac Hypertrophy

PubMed Central

Jurado-López, Raquel; Martínez-Martínez, Ernesto; Gómez-Hurtado, Nieves; Delgado, Carmen; Visitación Bartolomé, Maria; San Román, José Alberto; Cordova, Claudia; Lahera, Vicente; Nieto, Maria Luisa; Cachofeiro, Victoria

2012-01-01

Background The natural triterpenes, erythrodiol and uvaol, exert anti-inflammatory, vasorelaxing and anti-proliferative effects. Angiotensin II is a well-known profibrotic and proliferative agent that participates in the cardiac remodeling associated with different pathological situations through the stimulation and proliferation of cardiac fibroblasts. Therefore, the aim of the study was to investigate the preventive effects of the natural triterpenes erythrodiol and uvaol on the proliferation and collagen production induced by angiotensin II in cardiac myofibroblasts. Their actions on cardiac hypertrophy triggered by angiotensin II were also studied. Methodology/Principal Findings The effect of erythrodiol and uvaol on angiotensin II-induced proliferation was evaluated in cardiac myofibroblasts from adult rats in the presence or the absence of the inhibitors of PPAR-γ, GW9662 or JNK, SP600125. The effect on collagen levels induced by angiotensin II was evaluated in cardiac myofibroblasts and mouse heart. The presence of low doses of both triterpenes reduced the proliferation of cardiac myofibroblasts induced by angiotensin II. Pretreatment with GW9662 reversed the effect elicited by both triterpenes while SP600125 did not modify it. Both triterpenes at high doses produced an increase in annexing-V binding in the presence or absence of angiotensin II, which was reduced by either SP600125 or GW9662. Erythrodiol and uvaol decreased collagen I and galectin 3 levels induced by angiotensin II in cardiac myofribroblasts. Finally, cardiac hypertrophy, ventricular remodeling, fibrosis, and increases in myocyte area and brain natriuretic peptide levels observed in angiotensin II-infused mice were reduced in triterpene-treated animals. Conclusions/Significance Erythrodiol and uvaol reduce cardiac hypertrophy and left ventricle remodeling induced by angiotensin II in mice by diminishing fibrosis and myocyte area. They also modulate growth and survival of cardiac myofibroblasts. They inhibit the angiotensin II-induced proliferation in a PPAR-γ-dependent manner, while at high doses they activate pathways of programmed cell death that are dependent on JNK and PPAR-γ. PMID:22844495

Telomerase Inhibition by Everolimus Suppresses Smooth Muscle Cell Proliferation and Neointima Formation Through Epigenetic Gene Silencing.

PubMed

Aono, Jun; Ruiz-Rodriguez, Ernesto; Qing, Hua; Findeisen, Hannes M; Jones, Karrie L; Heywood, Elizabeth B; Bruemmer, Dennis

2016-01-01

The present study sought to investigate the mechanisms underlying the mitogenic function of telomerase and to test the hypothesis that everolimus, commonly used on drug-eluting stents, suppresses smooth muscle cells (SMC) proliferation by targeting telomerase. Proliferation of SMC during neointima formation is prevented by drug-eluting stents. Although the replicative capacity of mammalian cells is enhanced by telomerase expression, the contribution of telomerase to the proliferative response underlying neointima formation and its potential role as a pharmacological target remain to be investigated. We first employed constitutive expression of telomerase reverse transcriptase (TERT) in cell systems to study transcriptional mechanisms by which telomerase activates a mitogenic program. Second, overexpression of telomerase in mice provided a model to study the role of telomerase as a drug target for the antiproliferative efficacy of everolimus. Inhibition of neointima formation by everolimus is lost in mice overexpressing TERT, indicating that repression of telomerase confers the antiproliferative efficacy of everolimus. Everolimus reduces TERT expression in SMC through an Ets-1-dependent inhibition of promoter activation. The inhibition of TERT-dependent SMC proliferation by everolimus occurred in the absence of telomere shortening but rather as a result of a G1→S phase arrest. Although everolimus failed to inhibit phosphorylation of the retinoblastoma protein as the gatekeeper of S-phase entry, it potently repressed downstream target genes. Using chromatin immunoprecipitation assays, we finally demonstrate that TERT induces E2F binding to S-phase gene promoters and supports histone acetylation, effects that are inhibited by everolimus and mediate its antiproliferative activity. These results characterize telomerase as a previously unrecognized target for the antiproliferative activity of everolimus. Our studies further identify a novel mitogenic pathway in SMC, which depends on the epigenetic activation of S-phase gene promoters by TERT.

The molecular responses of skeletal muscle satellite cells to continuous expression of IGF-1: implications for the rescue of induced muscular atrophy in aged rats

NASA Technical Reports Server (NTRS)

Chakravarthy, M. V.; Booth, F. W.; Spangenburg, E. E.

2001-01-01

Approximately 50% of humans older than 85 years have physical frailty due to weak skeletal muscles. This indicates a need for determining mechanisms to combat this problem. A critical cellular factor for postnatal muscle growth is a population of myogenic precursor cells called satellite cells. Given the complex process of sarcopenia, it has been postulated that, at some point in this process, a limited satellite cell proliferation potential could become rate-limiting to the regrowth of old muscles. It is conceivable that if satellite cell proliferative capacity can be maintained or enhanced with advanced age, sarcopenia could potentially be delayed or prevented. Therefore, the purposes of this paper are to describe whether IGF-I can prevent muscular atrophy induced by repeated cycles of hindlimb immobilization, increase the in vitro proliferation in satellite cells from these muscles and, if so, the molecular mechanisms by which IGF-I mediates this increased proliferation. Our results provide evidence that IGF-I can enhance aged muscle regrowth possibly through increased satellite cell proliferation. The results also suggest that IGF-I enhances satellite cell proliferation by decreasing the cell cycle inhibitor, p27Kip1, through the PI3'-K/Akt pathway. These data provide molecular evidence for IGF-I's rescue effect upon aging-associated skeletal muscle atrophy.

DOE-NE Proliferation and Terrorism Risk Assessment: FY12 Plans Update

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

Sadasivan, Pratap

2012-06-21

This presentation provides background information on FY12 plans for the DOE Office of Nuclear Energy Proliferation and Terrorism Risk Assessment program. Program plans, organization, and individual project elements are described. Research objectives are: (1) Develop technologies and other solutions that can improve the reliability, sustain the safety, and extend the life of current reactors; (2) Develop improvements in the affordability of new reactors to enable nuclear energy; (3) Develop Sustainable Nuclear Fuel Cycles; and (4) Understand and minimize the risks of nuclear proliferation and terrorism - Goal is to enable the use of risk information to inform NE R&D programmore » planning.« less

Fluoxetine prevents the memory deficits and reduction in hippocampal cell proliferation caused by valproic acid.

PubMed

Welbat, Jariya Umka; Sangrich, Preeyanuch; Sirichoat, Apiwat; Chaisawang, Pornthip; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanun; Wigmore, Peter

2016-12-01

Valproic acid (VPA), a commonly used antiepileptic drug, has been reported to cause cognitive impairments in patients. In a previous study, using a rodent model, we showed that VPA treatment impaired cognition which was associated with a reduction in the cell proliferation required for hippocampal neurogenesis. The antidepressant fluoxetine has been shown to increase hippocampal neurogenesis and to reverse the memory deficits found in a number of pathological conditions. In the present study we investigated the protective effects of fluoxetine treatment against the impairments in memory and hippocampal cell proliferation produced by VPA. Male Sprague Dawley rats received daily treatment with fluoxetine (10mg/kg) by oral gavage for 21days. Some rats were co-administered with VPA (300mg/kg, twice daily i.p. injections) for 14days from day 8 to day 21 of the fluoxetine treatment. Spatial memory was tested using the novel object location (NOL) test. The number of proliferating cells present in the sub granular zone of the dentate gyrus was quantified using Ki67 immunohistochemistry at the end of the experiment. Levels of the receptor Notch1, the neurotrophic factor BDNF and the neural differentiation marker DCX were determined by Western blotting. VPA-treated rats showed memory deficits, a decrease in the number of proliferating cells in the sub granular zone and decreases in the levels of Notch1 and BDNF but not DCX compared to control animals. These changes in behavior, cell proliferation and Notch1 and BDNF were prevented in animals which had received both VPA and fluoxetine. Rats receiving fluoxetine alone did not show a significant difference in the number of proliferating cells or behavior compared to controls. These results demonstrated that the spatial memory deficits and reduction of cell proliferation produced by VPA can be ameliorated by the simultaneous administration of the antidepressant fluoxetine. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Drug checking: a potential solution to the opioid overdose epidemic?

PubMed

Bardwell, Geoff; Kerr, Thomas

2018-05-25

North America is experiencing an overdose epidemic driven in part by the proliferation of illicitly-manufactured fentanyl and related analogues. In response, communities are scaling up novel overdose prevention interventions. Included are drug checking technologies. Drug checking technologies aim to identify the contents of illicit drugs. These technologies vary considerably in terms of cost, accuracy, and usability, and while efforts are now underway to implement drug checking programs for people who inject drugs, there remains a lack of rigorous evaluation of their impacts. Given the ongoing overdose crisis and the urgent need for effective responses, research on drug checking should be prioritized. However, while such research should be supported, it should be completed before these technologies are widely implemented.

Effects of phytoestrogens on the trophoblast tumour cell lines BeWo and Jeg3.

PubMed

Plessow, D; Waldschläger, J; Richter, D U; Jeschke, U; Bruer, G; Briese, V; Friese, K

2003-01-01

Phytoestrogens are a diverse group of nonsteroidal plant compounds that occur naturally in many plants. Because they possess a ring system similar to estrogens they are able to bind to estrogen receptors in humans. With this study we tested the effects of the phytoestrogens genistein and daidzein in cell proliferation and the production of progesterone and hCG in trophoblast tumour cells of the cell lines BeWo and Jeg3. The phytoestrogens genistein and daidzein were incubated in different concentrations with trophoblast tumour cells. Untreated cells were used as controls. At designated times, aliquots were removed and tested for progesterone and hCG. In addition we tested the effects of phytoestrogens on cell proliferation. Different concentrations of genistein and daidzein were cultivated with trophoblast tumour cells. After designated times, 1 microCi thymidin-(methyl-3H) was added. Methyl-3H thymidin incorporation was tested and compared to incorporation results of untreated cells. With this study we could show that the production of the steroid hormone progesterone and the protein hormone hCG is influenced by the phytoestrogens genistein and daidzein in trophoblast tumour cells of the cell lines BeWo and Jeg3. We found a correlation between the effects on the proliferation and the production of progesterone and hCG at high concentrations of genistein and daidzein in the cell lines tested. With low concentrations of genistein and daidzein we observed a stimulation of the production of hCG and a weak inhibition of proliferation in both cell lines BeWo and Jeg3. The results obtained with this study suggest that only high doses of phytoestrogens (> 1 mumol/ml) can reduce the proliferation of trophoblast tumour cells significantly. Low doses of phytoestrogens induced a higher hCG production in both cell lines tested. Although high hCG production did not lead to a higher proliferation rate of the tumour cells tested, hCG is able to induce neovascularisation in tumour cells. In summary, with this in vitro study we showed that high doses of phytoestrogens inhibit proliferation and progesterone production in trophoblast tumour cells. High doses of phytoestrogens could be useful candidates for special diet programs for prevention and surgery for patients with this type of disease. In addition we found a useful cell culture model for the testing of new types of phytoestrogens.

Telomerase Reverse Transcriptase Deficiency Prevents Neointima Formation Through Chromatin Silencing of E2F1 Target Genes.

PubMed

Endorf, Elizabeth B; Qing, Hua; Aono, Jun; Terami, Naoto; Doyon, Geneviève; Hyzny, Eric; Jones, Karrie L; Findeisen, Hannes M; Bruemmer, Dennis

2017-02-01

Aberrant proliferation of smooth muscle cells (SMC) in response to injury induces pathological vascular remodeling during atherosclerosis and neointima formation. Telomerase is rate limiting for tissue renewal and cell replication; however, the physiological role of telomerase in vascular diseases remains to be determined. The goal of the present study was to determine whether telomerase reverse transcriptase (TERT) affects proliferative vascular remodeling and to define the molecular mechanism by which TERT supports SMC proliferation. We first demonstrate high levels of TERT expression in replicating SMC of atherosclerotic and neointimal lesions. Using a model of guidewire-induced arterial injury, we demonstrate decreased neointima formation in TERT-deficient mice. Studies in SMC isolated from TERT-deficient and TERT overexpressing mice with normal telomere length established that TERT is necessary and sufficient for cell proliferation. TERT deficiency did not induce a senescent phenotype but resulted in G1 arrest albeit hyperphosphorylation of the retinoblastoma protein. This proliferative arrest was associated with stable silencing of the E2F1-dependent S-phase gene expression program and not reversed by ectopic overexpression of E2F1. Finally, chromatin immunoprecipitation and accessibility assays revealed that TERT is recruited to E2F1 target sites and promotes chromatin accessibility for E2F1 by facilitating the acquisition of permissive histone modifications. These data indicate a previously unrecognized role for TERT in neointima formation through epigenetic regulation of proliferative gene expression in SMC. © 2016 American Heart Association, Inc.

Effects of functional β-glucan on proliferation, differentiation, metabolism and its anti-fibrosis properties in muscle cells.

PubMed

Li, Yan; Fan, Yihui; Pan, Haiou; Qian, Haifeng; Qi, Xiguang; Wu, Gangcheng; Zhang, Hui; Xu, Meijuan; Rao, Zhiming; Wang, Li; Ying, Hao

2018-05-26

Skeletal muscles plays a crucial role in metabolism and exercise. Fuctional β-glucan is polysaccharide that is found in the cell walls of cereal, which is known to reduce cholesterol and lipid, prevent diabetes, cancer and cardiovascular diseases. In an attempt to identify β-glucan that could promote skeletal muscle function, we analyzed the proliferation, differentiation, metabolism and anti-fibrotic properties of β-glucan in C2C12 muscle cells. Treatment of β-glucan in C2C12 myoblasts led to increased proliferation and differentiation. Besides that, we found that C2C12 myotubes treated with β-glucan displayed a fast-to-slow muscle fiber conversion and improved oxidative metabolism. Further study revealed that β-glucan treatment could prevent myotubes from becoming myofibroblasts. Together, our study suggests that functional β-glucan might have a therapeutic potential to improve skeletal muscle function, which might contribute to the development of β-glucan. Copyright © 2018. Published by Elsevier B.V.

Can apple antioxidants inhibit tumor cell proliferation? Generation of H(2)O(2) during interaction of phenolic compounds with cell culture media.

PubMed

Lapidot, Tair; Walker, Michael D; Kanner, Joseph

2002-05-22

It has recently been suggested that the ability of apple extracts to inhibit proliferation of tumor cells in vitro may be due to phenolic/flavonoid antioxidants. Our study demonstrates that this inhibition is caused indirectly by H(2)O(2) generated through interaction of the phenolics with the cell culture media. The results indicate that many previously reported effects of flavonoids and phenolic compounds on cultured cells may result from similar artifactual generation of oxidative stress. We suggest that in order to prevent such artifacts, the use of catalase and/or metmyoglobin in the presence of reducing agents should be considered as a method to decompose H(2)O(2) and prevent generation of other reactive oxygen species, which could affect cell proliferation. The use of tumor cells and "nontumor cells" in a bioassay to measure antioxidant activity, in this context, is potentially misleading and should be applied with caution.

The role of science in treaty verification.

PubMed

Gavron, Avigdor

2005-01-01

Technologically advanced nations are currently applying more science to treaty verification than ever before. Satellites gather a multitude of information relating to proliferation concerns using thermal imaging analysis, nuclear radiation measurements, and optical and radio frequency signals detection. Ground stations gather complementary signals such as seismic events and radioactive emissions. Export controls in many countries attempt to intercept materials and technical means that could be used for nuclear proliferation. Nevertheless, we have witnessed a plethora of nuclear proliferation episodes, that were undetected (or were belatedly detected) by these technologies--the Indian nuclear tests in 1998, the Libyan nuclear buildup, the Iranian enrichment program and the North Korea nuclear weapons program are some prime examples. In this talk, we will discuss some of the technologies used for proliferation detection. In particular, we will note some of the issues relating to nuclear materials control agreements that epitomize political difficulties as they impact the implementation of science and technology.

TC-1 Overexpression Promotes Cell Proliferation in Human Non-Small Cell Lung Cancer that Can Be Inhibited by PD173074

PubMed Central

Zhang, Na; Bai, Guangzhen; Zhong, Daixing; Su, Kai; Liu, Boya; Li, Xiaofei; Wang, Yunjie; Wang, Xiaoping

2014-01-01

Thyroid cancer-1 (TC-1), a natively disordered protein, is widely expressed in vertebrates and overexpressed in many kinds of tumors. However, its exact role and regulation mechanism in human non-small cell lung cancer (NSCLC) are still unclear. In the present study, we found that TC-1 is highly expressed in NSCLC and that its aberrant expression is strongly associated with NSCLC cell proliferation. Exogenous TC-1 overexpression promotes cell proliferation, accelerates the cell G1-to-S-phase transition, and reduces apoptosis in NSCLC. The knockdown of TC-1, however, inhibits NSCLC cell proliferation, cycle transition, and apoptosis resistance. Furthermore, we also demonstrated that PD173074, which functions as an inhibitor of the TC-1 in NSCLC, decreases the expression of TC-1 and inhibits TC-1 overexpression mediated cell proliferation in vitro and in vivo. Nevertheless, the inhibition function of PD173074 on NSCLC cell proliferation was eliminated in cells with TC-1 knockdown. These results suggest that PD173074 plays a significant role in TC-1 overexpression mediated NSCLC cell proliferation and may be a potential intervention target for the prevention of cell proliferation in NSCLC. PMID:24941347

Lunasin-aspirin combination against NIH/3T3 cells transformation induced by chemical carcinogens.

PubMed

Hsieh, Chia-Chien; Hernández-Ledesma, Blanca; de Lumen, Ben O

2011-06-01

Carcinogenesis is a multistage process involving a number of molecular pathways sensitive to intervention. Chemoprevention is defined as the use of natural and/or synthetic substances to block, reverse, or retard the process of carcinogenesis. To achieve greater inhibitory effects on cancer cells, combination of two or more chemopreventive agents is commonly considered as a better preventive and/or therapeutic strategy. Lunasin is a promising cancer preventive peptide identified in soybean and other seeds. Its efficacy has been demonstrated by both in vitro and in vivo models. This peptide has been found to inhibit human breast cancer MDA-MB-231 cells proliferation, suppressing cell cycle progress and inducing cell apoptosis. Moreover, lunasin potentiates the effects on these cells of different synthetic and natural compounds, such as aspirin and anacardic acid. This study explored the role of lunasin, alone and in combination with aspirin and anacardic acid on cell proliferation and foci formation of transformed NIH/3T3 cells induced by chemical carcinogens 7,12-dimethylbenz[a]anthracene or 3-methylcholanthrene. The results revealed that lunasin, acting as a single agent, inhibits cell proliferation and foci formation. When combined with aspirin, these effects were significantly increased, indicating that this combination might be a promising strategy to prevent/treat cancer induced by chemical carcinogens.

LPA Induces Colon Cancer Cell Proliferation through a Cooperation between the ROCK and STAT-3 Pathways.

PubMed

Leve, Fernanda; Peres-Moreira, Rubem J; Binato, Renata; Abdelhay, Eliana; Morgado-Díaz, José A

2015-01-01

Lysophosphatidic acid (LPA) plays a critical role in the proliferation and migration of colon cancer cells; however, the downstream signaling events underlying these processes remain poorly characterized. The aim of this study was to investigate the signaling pathways triggered by LPA to regulate the mechanisms involved in the progression of colorectal cancer (CRC). We have used three cell line models of CRC, and initially analyzed the expression profile of LPA receptors (LPAR). Then, we treated the cells with LPA and events related to their tumorigenic potential, such as migration, invasion, anchorage-independent growth, proliferation as well as apoptosis and cell cycle were evaluated. We used the Chip array technique to analyze the global gene expression profiling that occurs after LPA treatment, and we identified cell signaling pathways related to the cell cycle. The inhibition of these pathways verified the conclusions of the transcriptomic analysis. We found that the cell lines expressed LPAR1, -2 and -3 in a differential manner and that 10 μM LPA did not affect cell migration, invasion and anchorage-independent growth, but it did induce proliferation and cell cycle progression in HCT-116 cells. Although LPA in this concentration did not induce transcriptional activity of β-catenin, it promoted the activation of Rho and STAT-3. Moreover, ROCK and STAT-3 inhibitors prevented LPA-induced proliferation, but ROCK inhibition did not prevent STAT-3 activation. Finally, we observed that LPA regulates the expression of genes related to the cell cycle and that the combined inhibition of ROCK and STAT-3 prevented cell cycle progression and increased the LPA-induced expression of cyclins E1, A2 and B1 to a greater degree than either inhibitor alone. Overall, these results demonstrate that LPA increases the proliferative potential of colon adenocarcinoma HCT-116 cells through a mechanism involving cooperation between the Rho-ROCK and STAT3 pathways involved in cell cycle control.

Prevention of Autoimmune Diabetes and Induction of β-Cell Proliferation in NOD Mice by Hyperbaric Oxygen Therapy

PubMed Central

Faleo, Gaetano; Fotino, Carmen; Bocca, Nicola; Molano, R. Damaris; Zahr-Akrawi, Elsie; Molina, Judith; Villate, Susana; Umland, Oliver; Skyler, Jay S.; Bayer, Allison L.; Ricordi, Camillo; Pileggi, Antonello

2012-01-01

We evaluated the effects of hyperbaric oxygen therapy (HOT) on autoimmune diabetes development in nonobese diabetic (NOD) mice. Animals received no treatment or daily 60-min HOT 100% oxygen (HOT-100%) at 2.0 atmospheres absolute and were monitored for diabetes onset, insulitis, infiltrating cells, immune cell function, and β-cell apoptosis and proliferation. Cyclophosphamide-induced diabetes onset was reduced from 85.3% in controls to 48% after HOT-100% (P < 0.005) and paralleled by lower insulitis. Spontaneous diabetes incidence reduced from 85% in controls to 65% in HOT-100% (P = 0.01). Prediabetic mice receiving HOT-100% showed lower insulitis scores, reduced T-cell proliferation upon stimulation in vitro (P < 0.03), increased CD62L expression in T cells (P < 0.04), reduced costimulation markers (CD40, DC80, and CD86), and reduced major histocompatibility complex class II expression in dendritic cells (DCs) (P < 0.025), compared with controls. After autoimmunity was established, HOT was less effective. HOT-100% yielded reduced apoptosis (transferase-mediated dUTP nick-end labeling-positive insulin-positive cells; P < 0.01) and increased proliferation (bromodeoxyuridine incorporation; P < 0.001) of insulin-positive cells compared with controls. HOT reduces autoimmune diabetes incidence in NOD mice via increased resting T cells and reduced activation of DCs with preservation of β-cell mass resulting from decreased apoptosis and increased proliferation. The safety profile and noninvasiveness makes HOT an appealing adjuvant therapy for diabetes prevention and intervention trials. PMID:22566533

Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway

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

Zhang, Liang, E-mail: countryspring@sina.com; Ji, Yunxia, E-mail: 413499057@qq.com; Kang, Zechun, E-mail: davidjiangwl@163.com

An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play a key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-β1 (TGF-β1)-mediated epithelial–mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonarymore » fibrosis in vivo were investigated. PA treatment resulted in a reduction of EMT in A549 cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a reduction of HLF-1 proliferation with a decrease of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological scores and collagen deposition, and a lower FGF-2, PDGF, α-smooth muscle actin (α-SMA) and HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through the decrease of HGMB1 and the regulation of RAGE, PA reversed the EMT, inhibited HLF-1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary fibrosis in vivo. Collectively, our results demonstrate that PA prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. - Highlights: • PA prevents EMT, reduces the apoptosis of AT1 in vitro. • PA decreases proliferation of HLF-1, reduces PDGF and FGF expression in vitro. • PA prevents experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.« less

Overview of DOE-NE Proliferation and Terrorism Risk Assessment

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

Sadasivan, Pratap

2012-08-24

Research objectives are: (1) Develop technologies and other solutions that can improve the reliability, sustain the safety, and extend the life of current reactors; (2) Develop improvements in the affordability of new reactors to enable nuclear energy; (3) Develop Sustainable Nuclear Fuel Cycles; and (4) Understand and minimize the risks of nuclear proliferation and terrorism. The goal is to enable the use of risk information to inform NE R&D program planning. The PTRA program supports DOE-NE's goal of using risk information to inform R&D program planning. The FY12 PTRA program is focused on terrorism risk. The program includes a mixmore » of innovative methods that support the general practice of risk assessments, and selected applications.« less

Arginase Inhibition Suppresses Native Low-Density Lipoprotein-Stimulated Vascular Smooth Muscle Cell Proliferation by NADPH Oxidase Inactivation.

PubMed

Koo, Bon Hyeock; Yi, Bong Gu; Wang, Wi Kwang; Ko, In Young; Hoe, Kwang Lae; Kwon, Young Guen; Won, Moo Ho; Kim, Young Myeong; Lim, Hyun Kyo; Ryoo, Sungwoo

2018-05-01

Vascular smooth muscle cell (VSMC) proliferation induced by native low-density lipoprotein (nLDL) stimulation is dependent on superoxide production from activated NADPH oxidase. The present study aimed to investigate whether the novel arginase inhibitor limonin could suppress nLDL-induced VSMC proliferation and to examine related mechanisms. Isolated VSMCs from rat aortas were treated with nLDL, and cell proliferation was measured by WST-1 and BrdU assays. NADPH oxidase activation was evaluated by lucigenin-induced chemiluminescence, and phosphorylation of protein kinase C (PKC) βII and extracellular signal-regulated kinase (ERK) 1/2 was determined by western blot analysis. Mitochondrial reactive oxygen species (ROS) generation was assessed using MitoSOX-red, and intracellular L-arginine concentrations were determined by high-performance liquid chromatography (HPLC) in the presence or absence of limonin. Limonin inhibited arginase I and II activity in the uncompetitive mode, and prevented nLDL-induced VSMC proliferation in a p21Waf1/Cip1-dependent manner without affecting arginase protein levels. Limonin blocked PKCβII phosphorylation, but not ERK1/2 phosphorylation, and translocation of p47phox to the membrane was decreased, as was superoxide production in nLDL-stimulated VSMCs. Moreover, mitochondrial ROS generation was increased by nLDL stimulation and blocked by preincubation with limonin. Mitochondrial ROS production was responsible for the phosphorylation of PKCβII. HPLC analysis showed that arginase inhibition with limonin increases intracellular L-arginine concentrations, but decreases polyamine concentrations. L-Arginine treatment prevented PKCβII phosphorylation without affecting ERK1/2 phosphorylation. Increased L-arginine levels following limonin-dependent arginase inhibition prohibited NADPH oxidase activation in a PKCβII-dependent manner, and blocked nLDL-stimulated VSMC proliferation. © Copyright: Yonsei University College of Medicine 2018.

Arginase Inhibition Suppresses Native Low-Density Lipoprotein-Stimulated Vascular Smooth Muscle Cell Proliferation by NADPH Oxidase Inactivation

PubMed Central

Wang, Wi-Kwang; Ko, In-Young; Hoe, Kwang-Lae; Kwon, Young-Guen; Won, Moo-Ho; Kim, Young-Myeong

2018-01-01

Purpose Vascular smooth muscle cell (VSMC) proliferation induced by native low-density lipoprotein (nLDL) stimulation is dependent on superoxide production from activated NADPH oxidase. The present study aimed to investigate whether the novel arginase inhibitor limonin could suppress nLDL-induced VSMC proliferation and to examine related mechanisms. Materials and Methods Isolated VSMCs from rat aortas were treated with nLDL, and cell proliferation was measured by WST-1 and BrdU assays. NADPH oxidase activation was evaluated by lucigenin-induced chemiluminescence, and phosphorylation of protein kinase C (PKC) βII and extracellular signal-regulated kinase (ERK) 1/2 was determined by western blot analysis. Mitochondrial reactive oxygen species (ROS) generation was assessed using MitoSOX-red, and intracellular L-arginine concentrations were determined by high-performance liquid chromatography (HPLC) in the presence or absence of limonin. Results Limonin inhibited arginase I and II activity in the uncompetitive mode, and prevented nLDL-induced VSMC proliferation in a p21Waf1/Cip1-dependent manner without affecting arginase protein levels. Limonin blocked PKCβII phosphorylation, but not ERK1/2 phosphorylation, and translocation of p47phox to the membrane was decreased, as was superoxide production in nLDL-stimulated VSMCs. Moreover, mitochondrial ROS generation was increased by nLDL stimulation and blocked by preincubation with limonin. Mitochondrial ROS production was responsible for the phosphorylation of PKCβII. HPLC analysis showed that arginase inhibition with limonin increases intracellular L-arginine concentrations, but decreases polyamine concentrations. L-Arginine treatment prevented PKCβII phosphorylation without affecting ERK1/2 phosphorylation. Conclusion Increased L-arginine levels following limonin-dependent arginase inhibition prohibited NADPH oxidase activation in a PKCβII-dependent manner, and blocked nLDL-stimulated VSMC proliferation. PMID:29611398

Molecular Pathways: Gene-environment interactions regulating dietary fiber induction of proliferation and apoptosis via butyrate for cancer prevention

PubMed Central

Bultman, Scott J.

2013-01-01

Gene-environment interactions are so numerous and biologically complicated that it can be challenging to understand their role in cancer. However, dietary fiber and colorectal cancer prevention may represent a tractable model system. Fiber is fermented by colonic bacteria into short-chain fatty acids such as butyrate. One molecular pathway that has emerged involves butyrate having differential effects depending on its concentration and the metabolic state of the cell. Low-moderate concentrations, which are present near the base of colonic crypts, are readily metabolized in the mitochondria to stimulate cell proliferation via energetics. Higher concentrations, which are present near the lumen, exceed the metabolic capacity of the colonocyte. Unmetabolized butyrate enters the nucleus and functions as a histone deacetylase (HDAC) inhibitor that epigenetically regulates gene expression to inhibit cell proliferation and induce apoptosis as the colonocytes exfoliate into the lumen. Butyrate may therefore play a role in normal homeostasis by promoting turnover of the colonic epithelium. Because cancerous colonocytes undergo the Warburg effect, their preferred energy source is glucose instead of butyrate. Consequently, even moderate concentrations of butyrate accumulate in cancerous colonocytes and function as HDAC inhibitors to inhibit cell proliferation and induce apoptosis. These findings implicate a bacterial metabolite with metaboloepigenetic properties in tumor suppression. PMID:24270685

BETAINE PREVENTS MALLORY-DENK BODY FORMATION IN DRUG-PRIMED MICE BY EPIGENETIC MECHANISMS

PubMed Central

Oliva, Joan; Bardag-Gorce, Fawzia; Li, Jun; French, Barbara A; Nguyen, Sheila K.; Lu, Shelly C.; French, Samuel W.

2012-01-01

Previous studies showed that S-Adenosylmethionine (SAMe) prevented MDB formation and the hypomethylation of histones induced by DDC feeding. These results suggest that formation of MDBs is an epigenetic phenomenon. To further test this theory, drug-primed mice were fed the methyl donor, betaine, together with DDC, which was refed for 7 days. Betaine significantly reduced MDB formation, decreased the liver/body weight ratio and decreased the number of FAT10 positive liver cells when they proliferate in response to DDC refeeding. Betaine also significantly prevented the decreased expression of BHMT, AHCY, MAT1a and GNMT and the increased expression of MTHFR, caused by DDC refeeding. S-Adenosylhomocysteine (SAH) levels were reduced by DDC refeeding and this was prevented by betaine. The results support the concept that betaine donates methyl groups, increasing methionine available in the cell. SAMe metabolism was reduced by the decrease in GNMT expression, which prevented the conversion of SAMe to SAH. As a consequence, betaine prevented MDB formation and FAT10 positive cell proliferation by blocking the epigenetic memory expressed by hepatocytes. The results further support the concept that MDB formation is the result of an epigenetic phenomenon, where a change in methionine metabolism causes global gene expression changes in hepatocytes. PMID:19073172

Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis.

PubMed

Abdelsamed, Hossam A; Moustaki, Ardiana; Fan, Yiping; Dogra, Pranay; Ghoneim, Hazem E; Zebley, Caitlin C; Triplett, Brandon M; Sekaly, Rafick-Pierre; Youngblood, Ben

2017-06-05

Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell-mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA methylation programs. Whole-genome bisulfite sequencing of primary human naive, short-lived effector memory (T EM ), and longer-lived central memory (T CM ) and stem cell memory (T SCM ) CD8 T cells identified effector molecules with demethylated promoters and poised for expression. Effector-loci demethylation was heritably preserved during IL-7- and IL-15-mediated in vitro cell proliferation. Conversely, cytokine-driven proliferation of T CM and T SCM memory cells resulted in phenotypic conversion into T EM cells and was coupled to increased methylation of the CCR7 and Tcf7 loci. Furthermore, haploidentical donor memory CD8 T cells undergoing in vivo proliferation in lymphodepleted recipients also maintained their effector-associated demethylated status but acquired T EM -associated programs. These data demonstrate that effector-associated epigenetic programs are preserved during cytokine-driven subset interconversion of human memory CD8 T cells. © 2017 Abdelsamed et al.

Crocin prevents platelet‑derived growth factor BB‑induced vascular smooth muscle cells proliferation and phenotypic switch.

PubMed

Tong, Lijian; Qi, Guoxian

2018-06-01

The phenotypic switch of vascular smooth muscle cells (VSMCs) is a major initiating factor for atherosclerotic cardiovascular diseases. Platelet‑derived growth factor‑BB (PDGF‑BB) initiates a number of biological processes that contribute to VSMC proliferation and phenotypic switch. Crocin, a component of saffron, has been reported to inhibit atheromatous plaque formation. However, the effects of crocin on PDGF‑BB‑induced VSMC proliferation and phenotypic switch remain unclear. The aim of the present study was to investigate the role of crocin on PDGF‑BB‑induced VSMCs proliferation and phenotypic switch and its underlying mechanisms. Cell proliferation and markers of VSMCs phenotypic switch were measured using a Cell Counting Kit‑8 assay and western blot analysis, respectively. The signaling pathways involved in the effects of crocin on VSMCs were validated by western blot analysis with or without the use of specific pathway inhibitors. Crocin significantly inhibited PDGF‑BB‑induced VSMCs proliferation compared with the PDGF‑BB only group (P<0.05). In addition, crocin significantly abrogated the PDGF‑BB‑induced increase in contractile protein α‑smooth muscle actin, calponin and decrease in synthetic proteins osteopontin (OPN) in a concentration dependent manner (P<0.05). In addition, crocin slowed PDGF‑BB‑induced Janus kinase (JAK)‑signal transducer and activator of transcription 3 (STAT3) and extracellular signal‑regulated kinase (ERK)/Kruppel‑like factor 4 (KLF4) signaling activation in VSMCs. By applying the JAK inhibitor (AG490) and ERK1/2 inhibitor (U0126), the results suggested that the crocin inhibited PDGF‑BB‑induced VSMCs phenotypic switch through the JAK/STAT3 and ERK/KLF4 signaling pathways. These results suggested that crocin may effectively prevent PDGF‑BB‑induced VSMCs proliferation and phenotypic switch and may be a promising candidate for the therapy of atherosclerotic cardiovascular diseases.

Young People and Alcohol--Where's the Risk? Changing the Focus of School-Based Prevention Initiatives

ERIC Educational Resources Information Center

Petrie, Margaret

2017-01-01

Research statistics highlighting the social costs of widespread excessive alcohol consumption have led to a proliferation of school-based prevention programmes that aim to give young people the skills and knowledge necessary to resist social pressure to drink alcohol and avoid potentially "risky" consumption. Such interventions offer,…

Achieving Intelligence Proliferation: Policies and Programs for Leveraging Intelligence Support to State, Local and Tribal Law Enforcement

DTIC Science & Technology

2008-12-01

by the attacks of 9-11. Terrorism cuts across all levels of society through loss of life , economic chaos and inhibiting freedoms. The horrific loss of... life cannot be minimized or discounted, but the damage goes further and its effects are enduring. Estimates of the future economic impact of...PROLIFERATION: POLICIES AND PROGRAMS FOR LEVERAGING INTELLIGENCE SUPORT TO STATE, LOCAL AND TRIBAL LAW ENFORCEMENT James A. Dahl Captain, United

Regulation of oxidative stress responses by ataxia-telangiectasia mutated is required for T cell proliferation.

PubMed

Bagley, Jessamyn; Singh, Gyanesh; Iacomini, John

2007-04-15

Mutations in the gene encoding ataxia-telangiectasia (A-T) mutated (Atm) cause the disease A-T, characterized by immunodeficiency, the molecular basis of which is not known. Following stimulation through the TCR, Atm-deficient T cells and normal T cells in which Atm is inhibited undergo apoptosis rather than proliferation. Apoptosis is prevented by scavenging reactive oxygen species (ROS) during activation. Atm therefore plays a critical role in T cell proliferation by regulating responses to ROS generated following T cell activation. The inability of Atm-deficient T cells to control responses to ROS is therefore the molecular basis of immunodeficiency associated with A-T.

Ceramic High Efficiency Particulate Air (HEPA) Filter Final Report CRADA No. TC02102.0

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

Mitchell, M.; Morse, T.

This was a collaborative effort between Lawrence Livermore National Security, LLC (formerly The Regents of the University of California)/Lawrence Livermor e National Laboratory (LLNL) and Flanders-Precisionaire (Flanders), to develop ceramic HEP A filters under a Thrust II Initiative for Proliferation Prevention (IPP) project. The research was conducted via the IPP Program at Commonwe alth of Independent States (CIS) Institutes, which are handled under a separate agreement. The institutes (collectively referred to as "CIS Institutes") involved with this project were: Bochvar: Federal State Unitarian Enterprise All-Russia Scientific and Research Institute of Inorganic Materials (FSUE VNIINM); Radium Khlopin: Federal State Unitarian Enterprisemore » NPO Radium Institute named (FSUE NPO Radium Institute); and Bakor: Science and Technology Center Bakor (STC Bakor).« less

Water Treatment Using Advanced Ultraviolet Light Sources Final Report CRADA No. TC02089.0

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

Hoppes, W.; Oster, S.

This was a collaborative effort between Lawrence Livermore National Security, LLC as manager and operator of Lawrence Livermore National Laboratory (LLNL) and Teknichal Services, LLC (TkS), to develop water treatment systems using advanced ultraviolet light sources. The Russian institutes involved with this project were The High Current Electronics Institute (HCEI) and Russian Institute of Technical Physics-Institute of Experimental Physics (VNIIEF). HCEI and VNIIEF developed and demonstrated the potential commercial viability of short-wavelength ultraviolet excimer lamps under a Thrust 1 Initiatives for Proliferation Prevention (IPP) Program. The goals of this collaboration were to demonstrate both the commercial viability of excilampbased watermore » disinfection and achieve further substantial operational improvement in the lamps themselves; particularly in the area of energy efficiency.« less

Effect of zinc supplementation on neuronal precursor proliferation in the rat hippocampus after traumatic brain injury.

PubMed

Cope, Elise C; Morris, Deborah R; Gower-Winter, Shannon D; Brownstein, Naomi C; Levenson, Cathy W

2016-05-01

There is great deal of debate about the possible role of adult-born hippocampal cells in the prevention of depression and related mood disorders. We first showed that zinc supplementation prevents the development of the depression-like behavior anhedonia associated with an animal model of traumatic brain injury (TBI). This work then examined the effect of zinc supplementation on the proliferation of new cells in the hippocampus that have the potential to participate in neurogenesis. Rats were fed a zinc adequate (ZA, 30ppm) or zinc supplemented (ZS, 180ppm) diet for 4wk followed by TBI using controlled cortical impact. Stereological counts of EdU-positive cells showed that TBI doubled the density of proliferating cells 24h post-injury (p<0.05), and supplemental zinc significantly increased this by an additional 2-fold (p<0.0001). While the survival of these proliferating cells decreased at the same rate in ZA and in ZS rats after injury, the total density of newly born cells was approximately 60% higher in supplemented rats 1wk after TBI. Furthermore, chronic zinc supplementation resulted in significant increases in the density of new doublecortin-positive neurons one week post-TBI that were maintained for 4wk after injury (p<0.01). While the effect of zinc supplementation on neuronal precursor cells in the hippocampus was robust, use of targeted irradiation to eliminate these cells after zinc supplementation and TBI revealed that these cells are not the sole mechanism through which zinc acts to prevent depression associated with brain injury, and suggest that other zinc dependent mechanisms are needed for the anti-depressant effect of zinc in this model of TBI. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of in vitro biomimicked stem cell 'niche' for regulation of proliferation and differentiation of human bone marrow-derived mesenchymal stem cells to myocardial phenotypes: serum starvation without aid of chemical agents and prevention of spontaneous stem cell transformation enhanced by the matrix environment.

PubMed

Kim, Jae Hyung; Shin, Sang-Hyun; Li, Tian Zhu; Suh, Hwal

2016-01-01

Niche appears important for preventing the spontaneous differentiation or senescence that cells undergo during in vitro expansion. In the present study, it was revealed that human bone marrow-derived mesenchymal stem cells (hBM-MSCs) undergo senescence-related differentiation into the myocardial lineage in vitro without any induction treatment. This phenomenon occurred over the whole population of MCSs, much different from conventional differentiation with limited frequency of occurrence, and was accompanied by a change of morphology into large, flat cells with impeded proliferation, which are the representative indications of MSC senescence. By culturing MSCs under several culture conditions, it was determined that induction treatment with 5-azacytidine was not associated with the phenomenon, but the serum-starvation condition, under which proliferation is severely hampered, caused senescence progression and upregulation of cardiac markers. Nevertheless, MSCs gradually developed a myocardial phenotype under normal culture conditions over a prolonged culture period and heterogeneous populations were formed. In perspectives of clinical applications, this must be prevented for fair and consistent outcomes. Hence, the biomimetic 'niche' was constituted for hBM-MSCs by cultivating on a conventionally available extracellular matrix (ECM). Consequently, cells on ECM regained a spindle-shape morphology, increased in proliferation rate by two-fold and showed decreased expression of cardiac markers at both the mRNA and protein levels. In conclusion, the outcome indicates that progression of MSC senescence may occur via myocardial differentiation during in vitro polystyrene culture, and this can be overcome by employing appropriate ECM culture techniques. Copyright © 2013 John Wiley & Sons, Ltd.

Potential Molecular Targets of Statins in the Prevention of Hepatocarcinogenesis.

PubMed

Ridruejo, Ezequiel; Romero-Caími, Giselle; Obregón, María J; Kleiman de Pisarev, Diana; Alvarez, Laura

2018-04-09

Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins, may reduce the incidence of various tumors, including HCC. Antitumoral activities may be mediated by changes in transforming growth factor-beta (TGF-β1) and thyroid hormones (TH) regulation. The aim of our study is to establish the statins mechanism of action and the potential key molecules involved in an in vivo and in vitro HCC model. We used two models: in vivo (in rats) using diethylnitrosamine (DEN) and hexachlorobenzene (HCB) to develop HCC, we analyzed cell proliferation parameters (proliferating cell nuclear antigen, PCNA) and cholesterol metabolism (hydroxy-methylglutaryl-CoA reductase, HMGCoAR). In vitro (Hep-G2 cells) we evaluated the effects of different doses of Atorvastatin (AT) and Simvastatin (SM) on HCB induced proliferation and analyzed proliferative parameters, colesterol metabolism, TGF-β1 mRNA, c-Src and TH levels. In vivo, we observed that cell proliferation significantly increased as well as cholesterol serum levels in rats treated with HCB. In vitro, we observed the same results on PCNA as in vivo. The statins prevented the increase in HMG-CoAR mRNA levels induced by HCB, reaching levels similar to controls at máximum doses: AT (30 μM), and SM (20 μM). Increases in PCNA, TGF-β1, and pc-Src, and decreases in deiodinase I mRNA levels induced by HCB were not observed when cells were pre-treated with AT and SM at maximum doses. Statins can prevent the proliferative HCB effects on Hep-G2 cells. TGF-β1, c-Src and TH may be the statins molecular targets in hepatocarcinogenesis.

Role of magnolol in the proliferation of vascular smooth muscle cells.

PubMed

Wu, L; Zou, H; Xia, W; Dong, Q; Wang, L

2015-05-01

Proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of vascular remodeling. Recently, magnolol has been reported to have a potential role in regulating tumor necrosis factor α-induced proliferation of VSMCs. However, the role of magnolol in platelet-derived growth factor (PDGF)-induced proliferation of VSMCs remains unknown. Our purpose was to elucidate the effect of magnolol on the proliferation of VSMCs induced by PDGF-BB and to investigate the underlying molecular mechanisms. Our data demonstrated that magnolol inhibited rat VSMC proliferation and DNA synthesis stimulated by 20 ng/ml PDGF-BB without causing cell cytotoxicity. Flow cytometric analysis showed that magnolol inhibited S-phase entry of VSMCs. We also demonstrated that magnolol caused this effect by inhibiting the mRNA and protein expression of cyclin D1, cyclin E, and cyclin-dependent kinases 2 and 4 in PDGF-BB-stimulated VSMCs. Further analysis showed that the inhibitory effect of magnolol on the proliferation of VSMCs was associated with the inhibition of the PDGF-BB-stimulated production of intracellular reactive oxygen species (ROS) and Ras, MEK, and ERK1/2 activation. These results demonstrate that magnolol can block the proliferation of VSMCs through inhibition of intracellular ROS production and Ras-MEK-ERK1/2 pathways. Magnolol, therefore, has a potential application in preventing atherosclerosis and restenosis.

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

Rodriguez-Acebes, Sara; CIBER de Fisiopatologia de la Obesidad y Nutricion; Cueva, Paloma de la

We addressed the ability of native, oxidized and acetylated low-density lipoproteins (nLDL, oxLDL and acLDL, respectively) and desmosterol to act as sources of sterol for the proliferation of J774A.1 macrophages. Treatment with 0.5 {mu}M lovastatin and lipoprotein-deficient serum suppressed cell proliferation. This inhibition was effectively prevented by nLDL, but only to a lesser extent by oxLDL. AcLDL, despite its ability to deliver a higher amount of cholesterol to J774 macrophages than the other LDLs, was dependent on mevalonate supply to sustain cell proliferation. Similarly, exogenous desmosterol, which is not converted into cholesterol in J774 cells, required the simultaneous addition ofmore » mevalonate to support optimal cell growth. Expression of hydroxymethyl glutaryl coenzyme A reductase mRNA was potently down-regulated by acLDL and exogenous desmosterol, but the effect was weaker with other sterol sources. We conclude that nLDL is more efficient than modified LDL in sustaining macrophage proliferation. Despite the requirement of cholesterol or desmosterol for J774 cell proliferation, excessive provision of either sterol limits mevalonate availability, thus suppressing cell proliferation.« less

Paracrine influence of human perivascular cells on the proliferation of adenocarcinoma alveolar epithelial cells.

PubMed

Kim, Eunbi; Na, Sunghun; An, Borim; Yang, Se-Ran; Kim, Woo Jin; Ha, Kwon-Soo; Han, Eun-Taek; Park, Won Sun; Lee, Chang-Min; Lee, Ji Yoon; Lee, Seung-Joon; Hong, Seok-Ho

2017-03-01

Understanding the crosstalk mechanisms between perivascular cells (PVCs) and cancer cells might be beneficial in preventing cancer development and metastasis. In this study, we investigated the paracrine influence of PVCs derived from human umbilical cords on the proliferation of lung adenocarcinoma epithelial cells (A549) and erythroleukemia cells (TF-1α and K562) in vitro using Transwell® co-culture systems. PVCs promoted the proliferation of A549 cells without inducing morphological changes, but had no effect on the proliferation of TF-1α and K562 cells. To identify the factors secreted from PVCs, conditioned media harvested from PVC cultures were analyzed by antibody arrays. We identified a set of cytokines, including persephin (PSPN), a neurotrophic factor, and a key regulator of oral squamous cell carcinoma progression. Supplementation with PSPN significantly increased the proliferation of A549 cells. These results suggested that PVCs produced a differential effect on the proliferation of cancer cells in a cell-type dependent manner. Further, secretome analyses of PVCs and the elucidation of the molecular mechanisms could facilitate the discovery of therapeutic target(s) for lung cancer.

The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression

PubMed Central

He, Chunbo; Mao, Dagan; Hua, Guohua; Lv, Xiangmin; Chen, Xingcheng; Angeletti, Peter C; Dong, Jixin; Remmenga, Steven W; Rodabaugh, Kerry J; Zhou, Jin; Lambert, Paul F; Yang, Peixin; Davis, John S; Wang, Cheng

2015-01-01

The Hippo signaling pathway controls organ size and tumorigenesis through a kinase cascade that inactivates Yes-associated protein (YAP). Here, we show that YAP plays a central role in controlling the progression of cervical cancer. Our results suggest that YAP expression is associated with a poor prognosis for cervical cancer. TGF-α and amphiregulin (AREG), via EGFR, inhibit the Hippo signaling pathway and activate YAP to induce cervical cancer cell proliferation and migration. Activated YAP allows for up-regulation of TGF-α, AREG, and EGFR, forming a positive signaling loop to drive cervical cancer cell proliferation. HPV E6 protein, a major etiological molecule of cervical cancer, maintains high YAP protein levels in cervical cancer cells by preventing proteasome-dependent YAP degradation to drive cervical cancer cell proliferation. Results from human cervical cancer genomic databases and an accepted transgenic mouse model strongly support the clinical relevance of the discovered feed-forward signaling loop. Our study indicates that combined targeting of the Hippo and the ERBB signaling pathways represents a novel therapeutic strategy for prevention and treatment of cervical cancer. PMID:26417066

Cell death in neural precursor cells and neurons before neurite formation prevents the emergence of abnormal neural structures in the Drosophila optic lobe.

PubMed

Hara, Yusuke; Sudo, Tatsuya; Togane, Yu; Akagawa, Hiromi; Tsujimura, Hidenobu

2018-04-01

Programmed cell death is a conserved strategy for neural development both in vertebrates and invertebrates and is recognized at various developmental stages in the brain from neurogenesis to adulthood. To understand the development of the central nervous system, it is essential to reveal not only molecular mechanisms but also the role of neural cell death (Pinto-Teixeira et al., 2016). To understand the role of cell death in neural development, we investigated the effect of inhibition of cell death on optic lobe development. Our data demonstrate that, in the optic lobe of Drosophila, cell death occurs in neural precursor cells and neurons before neurite formation and functions to prevent various developmental abnormalities. When neuronal cell death was inhibited by an effector caspase inhibitor, p35, multiple abnormal neuropil structures arose during optic lobe development-e.g., enlarged or fused neuropils, misrouted neurons and abnormal neurite lumps. Inhibition of cell death also induced morphogenetic defects in the lamina and medulla development-e.g., failures in the separation of the lamina and medulla cortices and the medulla rotation. These defects were reproduced in the mutant of an initiator caspase, dronc. If cell death was a mechanism for removing the abnormal neuropil structures, we would also expect to observe them in mutants defective for corpse clearance. However, they were not observed in these mutants. When dead cell-membranes were visualized with Apoliner, they were observed only in cortices and not in neuropils. These results suggest that the cell death occurs before mature neurite formation. Moreover, we found that inhibition of cell death induced ectopic neuroepithelial cells, neuroblasts and ganglion mother cells in late pupal stages, at sites where the outer and inner proliferation centers were located at earlier developmental stages. Caspase-3 activation was observed in the neuroepithelial cells and neuroblasts in the proliferation centers. These results indicate that cell death is required for elimination of the precursor cells composing the proliferation centers. This study substantiates an essential role of early neural cell death for ensuring normal development of the central nervous system. Copyright © 2018 Elsevier Inc. All rights reserved.

Evolving perceptions of security - US National Security surveys 1993--1995. Progress report, September 30, 1995--November 14, 1995

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

Herron, K.G.; Jenkins-Smith, H.C.

This study analyzes findings from a national survey of 2,490 randomly selected members of the US public conducted between September 30 and November 14, 1995. It provides an over time comparison of public perceptions about nuclear weapons risks and benefits and key nuclear policy issues between 1993 and 1995. Other areas of investigation include policy preferences regarding nuclear proliferation, terrorism, US/Russian nuclear cooperation, and personal security. Public perceptions of post-cold war security were found to be evolving in unexpected ways. The perceived threat of nuclear conflict involving the US had not declined, and the threat of nuclear conflict between othermore » countries and fears of nuclear proliferation and terrorism had increased. Perceived risks associated with managing the US nuclear arsenal were also higher. Perceptions of external and domestic benefits from US nuclear weapons were not declining. Support was found for increasing funding for nuclear weapons safety, training, and maintenance, but most respondents favored decreasing funding for developing and testing new nuclear weapons. Strong support was evident for programs and funding to prevent nuclear proliferation and terrorism. Though skeptical that nuclear weapons can be eliminated, most respondents supported reducing the US nuclear arsenal, banning nuclear test explosions, and ending production of fissile materials to make nuclear weapons. Statistically significant relationships were found between perceptions of nuclear weapons risks and benefits and policy and spending preferences. Demographic variables and basic social and political beliefs were systematically related both to risk and benefit perceptions and policy and spending options.« less

Preventive effects of 125I seeds on benign restenosis following esophageal stent implantation in a dog model

PubMed Central

GAN, ZHEN; JING, JIAN; ZHU, GUANGYU; QIN, YONGLIN; TENG, GAOJUN; GUO, JINHE

2015-01-01

The present study aimed to evaluate the effects of iodine-125 (125I) seeds on the proliferation of primary esophageal fibroblasts in dogs, and to assess the safety and preventive efficacy of 125I seed-pre-loaded esophageal stents in benign restenosis following implantation. Primary fibroblasts were cultured with various 125I seed activities, which were then evaluated using cell proliferation and apoptosis assays as well as cell cycle analysis using Annexin V/propidium iodide (PI) double staining and PI staining. Prior to sacrification, animals were submitted to esophageal radiography under digital subtraction angiography. Esophageal tissues were collected and examined for macroscopic, microscopic and pathological alterations. The results demonstrated a significant and dose-dependent inhibition of fibroblast proliferation and increased apoptosis following exposure to 125I seeds. G0/G1 fibroblast populations increased in a dose-dependent manner following treatment with 125I seeds, in contrast to cells in S phase. Four weeks following implantation, α-smooth muscle actin and proliferating cell nuclear antigen expression levels in the experimental group were significantly lower compared with those in the control group; in addition, eight weeks following implantation, esophageal inner diameters were increased in the experimental group. 125I seeds inhibited proliferation of dog esophageal fibroblasts via cell cycle arrest and apoptosis. In conclusion, 125I seed-pre-loaded esophageal stents inhibited benign hyperplasia in the upper edge of the stent to a certain extent, which relieved benign restenosis following implantation with a good safety profile. PMID:25543838

Proliferation: Threat and Response

DTIC Science & Technology

2001-01-01

weapons program threatens Japan, South Korea, and U.S. forces and interests in the region. In North Africa and the Middle East, states of proliferation...fanatical terrorists or self-proclaimed apocalyptic prophets. The followers of Usama bin Laden have, in fact, already trained with toxic chemicals...18 SOUTH ASIA

Intentional, explicit, systematic: Implementation and scale-up of effective practices for supporting student mental well-being in Ontario schools

PubMed Central

Short, Kathryn H.

2016-01-01

Increasingly, the potential for school mental health programming to enhance the well-being of children and youth is being recognized and realized. When evidence-based practices in mental health promotion and prevention are adopted in a whole school manner, students show positive social emotional and academic benefits. These findings have stimulated a proliferation of mental well-being programming for Canadian schools, with variability across offerings in terms of supporting evidence, costs and ease of implementation. In the absence of coordination and guidance, there has been uneven uptake of high-quality programming, resulting in a patchwork of sometimes competing efforts across our country. In order to build cohesive and sustainable evidence-based programming, intentional, explicit and systematic effort must be afforded to matters of implementation and scale-up. In Canada, School Mental Health ASSIST has been developed to provide leadership, implementation support and embeddable resources to the province of Ontario’s 72 school districts, and 5000 schools, with a view to ensuring long-term sustainability of best-in-class school mental health practices. Key elements for uptake and scale-up are described, with an implementation science lens and an emphasis on aspects that are generalizable across jurisdictions. PMID:27019639

Nobel Laureate Mohamed ElBaradei: Preventing Nuclear Proliferation Peacefully

ERIC Educational Resources Information Center

Dufour, Joanne

2006-01-01

The 2005 Nobel Peace Prize was awarded 60 years after the first atomic bombs fell on the Japanese cities of Hiroshima and Nagasaki, killing more than 200,000 people; the peace prize raises the hopes of those working to rejuvenate global efforts to prevent the spread and development of nuclear arms. This article profiles the International Atomic…

Free fatty acids block glucose-induced β-cell proliferation in mice by inducing cell cycle inhibitors p16 and p18.

PubMed

Pascoe, Jordan; Hollern, Douglas; Stamateris, Rachel; Abbasi, Munira; Romano, Lia C; Zou, Baobo; O'Donnell, Christopher P; Garcia-Ocana, Adolfo; Alonso, Laura C

2012-03-01

Pancreatic β-cell proliferation is infrequent in adult humans and is not increased in type 2 diabetes despite obesity and insulin resistance, suggesting the existence of inhibitory factors. Free fatty acids (FFAs) may influence proliferation. In order to test whether FFAs restrict β-cell proliferation in vivo, mice were intravenously infused with saline, Liposyn II, glucose, or both, continuously for 4 days. Lipid infusion did not alter basal β-cell proliferation, but blocked glucose-stimulated proliferation, without inducing excess β-cell death. In vitro exposure to FFAs inhibited proliferation in both primary mouse β-cells and in rat insulinoma (INS-1) cells, indicating a direct effect on β-cells. Two of the fatty acids present in Liposyn II, linoleic acid and palmitic acid, both reduced proliferation. FFAs did not interfere with cyclin D2 induction or nuclear localization by glucose, but increased expression of inhibitor of cyclin dependent kinase 4 (INK4) family cell cycle inhibitors p16 and p18. Knockdown of either p16 or p18 rescued the antiproliferative effect of FFAs. These data provide evidence for a novel antiproliferative form of β-cell glucolipotoxicity: FFAs restrain glucose-stimulated β-cell proliferation in vivo and in vitro through cell cycle inhibitors p16 and p18. If FFAs reduce proliferation induced by obesity and insulin resistance, targeting this pathway may lead to new treatment approaches to prevent diabetes.

eHealth interventions for HIV prevention

PubMed Central

Noar, Seth M.; Willoughby, Jessica Fitts

2015-01-01

The rapidly changing media landscape and proliferation of new technologies creates vast new opportunities for HIV prevention. The fast growth of the relatively new eHealth field is a testament to the excitement and promise of these new technologies. eHealth interventions in HIV prevention tested to date include computer- and Internet-based interventions; chat room interventions; text messaging interventions; and social media. The current article provides a brief review of these types of interventions in HIV prevention, including their unique advantages and evidence of efficacy. Implications for future research in the eHealth HIV prevention field are discussed. PMID:22519523

Modulation of hepatic stellate cells and reversibility of hepatic fibrosis

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

Huang, Yu, E-mail: 1293363632@QQ.com; Deng, Xin, E-mail: Hendly@163.com; Liang, Jian, E-mail: lj99669@163.com

Hepatic fibrosis (HF) is the pathological component of a variety of chronic liver diseases. Hepatic stellate cells (HSC) are the main collagen-producing cells in the liver and their activation promotes HF. If HSC activation and proliferation can be inhibited, HF occurrence and development can theoretically be reduced and even reversed. Over the past ten years, a number of studies have addressed this process, and here we present a review of HSC modulation and HF reversal. - Highlights: • We present a review of the modulation of hepatic stellate cells (HSC) and reversibility of hepatic fibrosis (HF). • HSC are themore » foci of HF occurrence and development, HF could be prevented and treated by modulating HSC. • If HSC activation and proliferation can be inhibited, HF could theoretically be inhibited and even reversed. • Prevention or reversal of HSC activation, or promotion of HSC apoptosis, immune elimination, and senescence may prevent, inhibit or reverse HF.« less

Sildenafil Inhibits the Proliferation of Cultured Human Endothelial Cells

PubMed Central

Erdogan, Ali; Luedders, Doerte Wiebke; Muenz, Benedikt Manuel; Schaefer, Christian Alexander; Tillmanns, Harald; Wiecha, Johannes; Kuhlmann, Christoph Ruediger Wolfram

2007-01-01

The proliferation of endothelial cells plays a crucial role in the development of intraplaque angiogenesis (IPA). IPA is a major source of intraplaque hemorrhage and therefore contributes to the destabilization of atherosclerotic plaques. Therefore, the aim of the present study was to examine, whether sildenafil inhibits endothelial cell growth. The proliferation of human endothelial cells derived from umbilical cord veins (HUVEC) was examined on DNA level by measurements of (3H)-thymidine incorporation. Cell viability was analyzed using trypan blue staining. The proliferation of cultured human endothelial cells was significantly decreased by 1 μmol/l (-48.4%) and 10 μmol/l (-89.6%) sildenafil (n=10, p<0.05). This was not a cytotoxic effect, because cell viability was only reduced at sildenafil concentrations of 50 μmol/l or greater. In addition sildenafil significantly reduced endothelial proliferation induced by bFGF (n=10, p<0.05). The presented results demonstrate an antiangiogenic effect of sildenafil that might be useful in the prevention of atherosclerotic plaque vascularization. PMID:23675029

Paving Pathways: shaping the Public Health workforce through tertiary education.

PubMed

Bennett, Catherine M; Lilley, Kathleen; Yeatman, Heather; Parker, Elizabeth; Geelhoed, Elizabeth; Hanna, Elizabeth G; Robinson, Priscilla

2010-01-03

Public health educational pathways in Australia have traditionally been the province of Universities, with the Master of Public Health (MPH) recognised as the flagship professional entry program. Public health education also occurs within the fellowship training of the Faculty of Public Health Medicine, but within Australia this remains confined to medical graduates. In recent years, however, we have seen a proliferation of undergraduate degrees as well as an increasing public health presence in the Vocational Education and Training (VET) sector.Following the 2007 Australian Federal election, the new Labour government brought with it a refreshing commitment to a more inclusive and strategic style of government. An important example of this was the 2020 visioning process that identified key issues of public health concern, including an acknowledgment that it was unacceptable to allocate less than 2% of the health budget towards disease prevention. This led to the recommendation for the establishment of a national preventive health agency (Australia: the healthiest country by 2020 National Preventative Health Strategy, Prepared by the Preventative Health Taskforce 2009).The focus on disease prevention places a spotlight on the workforce that will be required to deliver the new investment in health prevention, and also on the role of public health education in developing and upskilling the workforce. It is therefore timely to reflect on trends, challenges and opportunities from a tertiary sector perspective. Is it more desirable to focus education efforts on selected lead issues such as the "obesity epidemic", climate change, Indigenous health and so on, or on the underlying theory and skills that build a flexible workforce capable of responding to a range of health challenges? Or should we aspire to both?This paper presents some of the key discussion points from 2008 - 2009 of the Public Health Educational Pathways workshops and working group of the Australian Network of Public Health Institutions. We highlight some of the competing tensions in public health tertiary education, their impact on public health training programs, and the educational pathways that are needed to grow, shape and prepare the public health workforce for future challenges.

Distinct cytoprotective roles of pyruvate and ATP by glucose metabolism on epithelial necroptosis and crypt proliferation in ischaemic gut

PubMed Central

Huang, Ching‐Ying; Kuo, Wei‐Ting; Huang, Chung‐Yen; Lee, Tsung‐Chun; Chen, Chin‐Tin; Peng, Wei‐Hao; Lu, Kuo‐Shyan; Yang, Chung‐Yi

2016-01-01

Key points Intestinal ischaemia causes epithelial death and crypt dysfunction, leading to barrier defects and gut bacteria‐derived septic complications.Enteral glucose protects against ischaemic injury; however, the roles played by glucose metabolites such as pyruvate and ATP on epithelial death and crypt dysfunction remain elusive.A novel form of necrotic death that involves the assembly and phosphorylation of receptor interacting protein kinase 1/3 complex was found in ischaemic enterocytes.Pyruvate suppressed epithelial cell death in an ATP‐independent manner and failed to maintain crypt function. Conversely, replenishment of ATP partly restored crypt proliferation but had no effect on epithelial necroptosis in ischaemic gut.Our data argue against the traditional view of ATP as the main cytoprotective factor by glucose metabolism, and indicate a novel anti‐necroptotic role of glycolytic pyruvate under ischaemic stress. Abstract Mesenteric ischaemia/reperfusion induces epithelial death in both forms of apoptosis and necrosis, leading to villus denudation and gut barrier damage. It remains unclear whether programmed cell necrosis [i.e. receptor‐interacting protein kinase (RIP)‐dependent necroptosis] is involved in ischaemic injury. Previous studies have demonstrated that enteral glucose uptake by sodium‐glucose transporter 1 ameliorated ischaemia/reperfusion‐induced epithelial injury, partly via anti‐apoptotic signalling and maintenance of crypt proliferation. Glucose metabolism is generally assumed to be cytoprotective; however, the roles played by glucose metabolites (e.g. pyruvate and ATP) on epithelial cell death and crypt dysfunction remain elusive. The present study aimed to investigate the cytoprotective effects exerted by distinct glycolytic metabolites in ischaemic gut. Wistar rats subjected to mesenteric ischaemia were enterally instilled glucose, pyruvate or liposomal ATP. The results showed that intestinal ischaemia caused RIP1‐dependent epithelial necroptosis and villus destruction accompanied by a reduction in crypt proliferation. Enteral glucose uptake decreased epithelial cell death and increased crypt proliferation, and ameliorated mucosal histological damage. Instillation of cell‐permeable pyruvate suppressed epithelial cell death in an ATP‐independent manner and improved the villus morphology but failed to maintain crypt function. Conversely, the administration of liposomal ATP partly restored crypt proliferation but did not reduce epithelial necroptosis and histopathological injury. Lastly, glucose and pyruvate attenuated mucosal‐to‐serosal macromolecular flux and prevented enteric bacterial translocation upon blood reperfusion. In conclusion, glucose metabolites protect against ischaemic injury through distinct modes and sites, including inhibition of epithelial necroptosis by pyruvate and the promotion of crypt proliferation by ATP. PMID:27121603

NF-κB Hyper-Activation by HTLV-1 Tax Induces Cellular Senescence, but Can Be Alleviated by the Viral Anti-Sense Protein HBZ

PubMed Central

Zhi, Huijun; Yang, Liangpeng; Kuo, Yu-Liang; Ho, Yik-Khuan; Shih, Hsiu-Ming; Giam, Chou-Zen

2011-01-01

Activation of I-κB kinases (IKKs) and NF-κB by the human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, is thought to promote cell proliferation and transformation. Paradoxically, expression of Tax in most cells leads to drastic up-regulation of cyclin-dependent kinase inhibitors, p21CIP1/WAF1 and p27KIP1, which cause p53-/pRb-independent cellular senescence. Here we demonstrate that p21CIP1/WAF1-/p27KIP1-mediated senescence constitutes a checkpoint against IKK/NF-κB hyper-activation. Senescence induced by Tax in HeLa cells is attenuated by mutations in Tax that reduce IKK/NF-κB activation and prevented by blocking NF-κB using a degradation-resistant mutant of I-κBα despite constitutive IKK activation. Small hairpin RNA-mediated knockdown indicates that RelA induces this senescence program by acting upstream of the anaphase promoting complex and RelB to stabilize p27KIP1 protein and p21CIP1/WAF1 mRNA respectively. Finally, we show that down-regulation of NF-κB by the HTLV-1 anti-sense protein, HBZ, delay or prevent the onset of Tax-induced senescence. We propose that the balance between Tax and HBZ expression determines the outcome of HTLV-1 infection. Robust HTLV-1 replication and elevated Tax expression drive IKK/NF-κB hyper-activation and trigger senescence. HBZ, however, modulates Tax-mediated viral replication and NF-κB activation, thus allowing HTLV-1-infected cells to proliferate, persist, and evolve. Finally, inactivation of the senescence checkpoint can facilitate persistent NF-κB activation and leukemogenesis. PMID:21552325

Hydrogen-rich saline attenuates vascular smooth muscle cell proliferation and neointimal hyperplasia by inhibiting reactive oxygen species production and inactivating the Ras-ERK1/2-MEK1/2 and Akt pathways.

PubMed

Chen, Yali; Jiang, Jinyao; Miao, Huibing; Chen, Xingjuan; Sun, Xuejun; Li, Yongjun

2013-03-01

Hydrogen-rich saline has been reported to prevent neointimal hyperplasia induced by carotid balloon injury. The purpose of the present study was to further investigate the molecular mechanisms underlying this phenomenon. Daily injection of a hydrogen-rich saline solution (HRSS) in rats was employed to study the effect of hydrogen on balloon injury-induced neointimal hyperplasia and the neointima/media ratio was assessed. HRSS significantly decreased the neointima area and neointima/media ratio in a dose-dependent manner. In vitro effects of hydrogen on fetal bovine serum (FBS)-induced vascular smooth muscle cell (VSMC) proliferation were also investigated. Hydrogen-rich medium (HRM) inhibited rat VSMC proliferation and migration induced by 10% FBS. FBS-induced reactive oxygen species (ROS) production and activation of intracellular Ras, MEK1/2, ERK1/2, proliferative cell nuclear antigen (PCNA), Akt were significantly inhibited by HRM. In addition, HRM blocked FBS-induced progression from the G0/G1 to the S-phase and increased the apoptosis rate of VSMCs. These results showed that hydrogen-rich saline was able to attenuate FBS-induced VSMC proliferation and neointimal hyperplasia by inhibiting ROS production and inactivating the Ras-ERK1/2-MEK1/2 and Akt pathways. Thus, HRSS may have potential therapeutic relevance for the prevention of human restenosis.

Geospatial Image Mining For Nuclear Proliferation Detection: Challenges and New Opportunities

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

Vatsavai, Raju; Bhaduri, Budhendra L; Cheriyadat, Anil M

2010-01-01

With increasing understanding and availability of nuclear technologies, and increasing persuasion of nuclear technologies by several new countries, it is increasingly becoming important to monitor the nuclear proliferation activities. There is a great need for developing technologies to automatically or semi-automatically detect nuclear proliferation activities using remote sensing. Images acquired from earth observation satellites is an important source of information in detecting proliferation activities. High-resolution remote sensing images are highly useful in verifying the correctness, as well as completeness of any nuclear program. DOE national laboratories are interested in detecting nuclear proliferation by developing advanced geospatial image mining algorithms. Inmore » this paper we describe the current understanding of geospatial image mining techniques and enumerate key gaps and identify future research needs in the context of nuclear proliferation.« less

Telomerase Inhibition by Everolimus Suppresses Smooth Muscle Cell Proliferation and Neointima Formation Through Epigenetic Gene Silencing

PubMed Central

Aono, Jun; Ruiz-Rodriguez, Ernesto; Qing, Hua; Findeisen, Hannes M.; Jones, Karrie L.; Heywood, Elizabeth B.; Bruemmer, Dennis

2016-01-01

Objectives The present study sought to investigate the mechanisms underlying the mitogenic function of telomerase and to test the hypothesis that everolimus, commonly used on drug-eluting stents, suppresses smooth muscle cells (SMC) proliferation by targeting telomerase. Background Proliferation of SMC during neointima formation is prevented by drug-eluting stents. Although the replicative capacity of mammalian cells is enhanced by telomerase expression, the contribution of telomerase to the proliferative response underlying neointima formation and its potential role as a pharmacological target remain to be investigated. Methods We first employed constitutive expression of telomerase reverse transcriptase (TERT) in cell systems to study transcriptional mechanisms by which telomerase activates a mitogenic program. Second, overexpression of telomerase in mice provided a model to study the role of telomerase as a drug target for the antiproliferative efficacy of everolimus. Results Inhibition of neointima formation by everolimus is lost in mice overexpressing TERT, indicating that repression of telomerase confers the antiproliferative efficacy of everolimus. Everolimus reduces TERT expression in SMC through an Ets-1–dependent inhibition of promoter activation. The inhibition of TERT-dependent SMC proliferation by everolimus occurred in the absence of telomere shortening but rather as a result of a G1→S phase arrest. Although everolimus failed to inhibit phosphorylation of the retinoblastoma protein as the gatekeeper of S-phase entry, it potently repressed downstream target genes. Using chromatin immunoprecipitation assays, we finally demonstrate that TERT induces E2F binding to S-phase gene promoters and supports histone acetylation, effects that are inhibited by everolimus and mediate its antiproliferative activity. Conclusions These results characterize telomerase as a previously unrecognized target for the antiproliferative activity of everolimus. Our studies further identify a novel mitogenic pathway in SMC, which depends on the epigenetic activation of S-phase gene promoters by TERT. PMID:27127803

Strengthening Biosecurity in Iraq: Development of a National Biorisk Management System

PubMed Central

Al Jewari, Mahdi F. H.; Koblentz, Gregory D.

2016-01-01

Since 2004, the Republic of Iraq has undertaken a concerted effort to comply with all of its international obligations to prevent the proliferation and the use of chemical, biological, radiological, and nuclear (CBRN) weapons. A centerpiece of this effort is Iraq’s development of a National Biorisk Management System. The Iraqi National Monitoring Authority (INMA), which is responsible for CBRN security and non-proliferation in Iraq, has played a key role in establishing this system. This article provides an overview of Iraq’s international non-proliferation commitments, describes the legal and organizational steps it has taken to implement these commitments, and examines current initiatives to strengthen Iraq’s biosecurity. PMID:26952002

Molecular role of TGF-beta, secreted from a new type of CD4+ suppressor T cell, NY4.2, in the prevention of autoimmune IDDM in NOD mice.

PubMed

Han, H S; Jun, H S; Utsugi, T; Yoon, J W

1997-06-01

A new type of CD4+ T cell clone (NY4.2) isolated from pancreatic islet-infiltrated lymphocytes of acutely diabetic non-obese diabetic (NOD) mice prevents the development of insulin-dependent diabetes mellitus (IDDM) in NOD mice, as well as the recurrence of autoimmune diabetes in syngeneic islet-transplanted NOD mice. It has been demonstrated that the cytokine TGF-beta, secreted from the cells of this clone, is the substance which prevents autoimmune IDDM. This investigation was initiated to determine the molecular role TGF-beta plays in the prevention of autoimmune IDDM by determining its effect on IL-2-induced signal transduction in Con A-activated NOD mouse splenocytes and HT-2 cells. First, we determined whether TGF-beta, secreted from NY4.2 T cells, inhibits IL-2-dependent T cell proliferation in HT-2 cells (IL-2-dependent T cell line) and NOD splenocytes. We found that TGF-beta suppresses IL-2-dependent T cell proliferation. Second, we determined whether TGF-beta inhibits the activation of Janus kinases (JAKs), as well as signal transducers and activators of transcription (STAT) proteins, involved in an IL-2-induced signalling pathway that normally leads to the proliferation of T cells. We found that TGF-beta inhibited tyrosine phosphorylation of JAK1, JAK3, STAT3 and STAT5 in Con A blasts from NOD splenocytes and HT-2 cells. Third, we examined whether TGF-beta inhibits the cooperation between STAT proteins and mitogen-activated protein kinase (MAPK), especially extracellular signal-regulated kinase 2 (ERK2). We found that TGF-beta inhibited the association of STAT3 and STAT5 with ERK2 in Con A blasts from NOD splenocytes and HT-2 cells. On the basis of these observations, we conclude that TGF-beta may interfere with signal transduction via inhibition of the IL-2-induced JAK/STAT pathway and inhibition of the association of STAT proteins with ERK2 in T cells from NOD splenocytes, resulting in the inhibition of IL-2-dependent T cell proliferation. TGF-beta-mediated suppression of T cell activation may be responsible for the prevention of effector T cell-mediated autoimmune IDDM in NOD mice by TGF-beta-producing CD4+ suppressor T cells.

The long noncoding RNA Wisper controls cardiac fibrosis and remodeling

PubMed Central

Micheletti, Rudi; Plaisance, Isabelle; Abraham, Brian J.; Sarre, Alexandre; Ting, Ching-Chia; Alexanian, Michael; Maric, Daniel; Maison, Damien; Nemir, Mohamed; Young, Richard A.; Schroen, Blanche; González, Arantxa; Ounzain, Samir; Pedrazzini, Thierry

2017-01-01

Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of cardiac development and disease. However, our understanding of the importance of these molecules in cardiac fibrosis is limited. Using an integrated genomic screen, we identified Wisper (Wisp2 super-enhancer–associated RNA) as a cardiac fibroblast–enriched lncRNA that regulates cardiac fibrosis after injury. Wisper expression was correlated with cardiac fibrosis both in a murine model of myocardial infarction (MI) and in heart tissue from human patients suffering from aortic stenosis. Loss-of-function approaches in vitro using modified antisense oligonucleotides (ASOs) demonstrated that Wisper is a specific regulator of cardiac fibroblast proliferation, migration, and survival. Accordingly, ASO-mediated silencing of Wisper in vivo attenuated MI-induced fibrosis and cardiac dysfunction. Functionally, Wisper regulates cardiac fibroblast gene expression programs critical for cell identity, extracellular matrix deposition, proliferation, and survival. In addition, its association with TIA1-related protein allows it to control the expression of a profibrotic form of lysyl hydroxylase 2, implicated in collagen cross-linking and stabilization of the matrix. Together, our findings identify Wisper as a cardiac fibroblast–enriched super-enhancer–associated lncRNA that represents an attractive therapeutic target to reduce the pathological development of cardiac fibrosis in response to MI and prevent adverse remodeling in the damaged heart. PMID:28637928

NR2B-containing NMDA receptors promote neural progenitor cell proliferation through CaMKIV/CREB pathway

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

Li, Mei, E-mail: limeihit@163.com; Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing; Zhang, Dong-Qing

2011-08-12

Highlights: {yields} The NR2B component of the NMDARs is important for the NSPC proliferation. {yields} pCaMKIV and pCREB exist in NSPCs. {yields} The CaMKIV/CREB pathway mediates NSPC proliferation. -- Abstract: Accumulating evidence indicates the involvement of N-methyl-D-aspartate receptors (NMDARs) in regulating neural stem/progenitor cell (NSPC) proliferation. Functional properties of NMDARs can be markedly influenced by incorporating the regulatory subunit NR2B. Here, we aim to analyze the effect of NR2B-containing NMDARs on the proliferation of hippocampal NSPCs and to explore the mechanism responsible for this effect. NSPCs were shown to express NMDAR subunits NR1 and NR2B. The NR2B selective antagonist, Romore » 25-6981, prevented the NMDA-induced increase in cell proliferation. Moreover, we demonstrated that the phosphorylation levels of calcium/calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein (CREB) were increased by NMDA treatment, whereas Ro 25-6981 decreased them. The role that NR2B-containing NMDARs plays in NSPC proliferation was abolished when CREB phosphorylation was attenuated by CaMKIV silencing. These results suggest that NR2B-containing NMDARs have a positive role in regulating NSPC proliferation, which may be mediated through CaMKIV phosphorylation and subsequent induction of CREB activation.« less

Decoy receptor 3 inhibits renal mononuclear leukocyte infiltration and apoptosis and prevents progression of IgA nephropathy in mice.

PubMed

Ka, Shuk-Man; Hsieh, Tai-Tzu; Lin, Shih-Hua; Yang, Sung-Sen; Wu, Chin-Chen; Sytwu, Huey-Kang; Chen, Ann

2011-12-01

The progression of IgA nephropathy (IgAN), the most frequent type of primary glomerulonephritis, is associated with high levels of mononuclear leukocyte infiltration into the kidney. These cells consist mainly of T cells and macrophages. Our previous study showed that a decoy receptor 3 (DCR3) gene therapy can prevent the development of a mouse autoimmune glomerulonephritis model by its potent immune modulating effects (Ka SM, Sytwu HK, Chang DM, Hsieh SL, Tsai PY, Chen A. J Am Soc Nephrol 18: 2473-2485, 2007). Here, we tested the hypothesis that DCR3 might prevent the progression of IgAN, an immune complex-mediated primary glomerulonephritis, by inhibiting T cell activation, renal T cell/macrophage infiltration, and protecting the kidney from apoptosis. We used a progressive IgAN (Prg-IgAN) model in B cell-deficient mice, because the mice are characterized by a dramatic proliferation of activated T cells systemically and progressive NF-κB activation in the kidney. We treated the animals with short-term gene therapy with DCR3 plasmids by hydrodynamics-based gene delivery. When the mice were euthanized on day 21, we found that, compared with empty vector-treated (disease control) Prg-IgAN mice, DCR3 gene therapy resulted in 1) systemic inhibition of T cell activation and proliferation; 2) lower serum levels of proinflammatory cytokines; 3) improved proteinuria, renal function, and renal pathology (inhibiting the development of marked glomerular proliferation, crescent formation, glomerulosclerosis, and interstitial inflammation); 5) suppression of T cell and macrophage infiltration into the periglomerular interstitium of the kidney; and 5) a reduction in apoptotic figures in the kidney. On the basis of these findings, DCR3 might be useful therapeutically in preventing the progression of IgAN.

The Credibility of America’s Extended Nuclear Deterrent: The Case of the Republic of Turkey

DTIC Science & Technology

2009-04-01

program. In his 2006 Foreign Affairs article, “After Proliferation: What to Do if More States Go Nuclear,” author Stephen Rosen used Turkey and Saudi...Endowment for International Peace, Washington, DC, 28 October 2008), 3-4. 4 Stephen Peter Rosen , “After Proliferation: What to do if More States Go...without an Adversary,” International Security 16, no 4 (Spring 1992); Stephen P. Rosen , After Proliferation: What to Do if More States Go Nuclear

Inhibitory Effects of Hydrogen on Proliferation and Migration of Vascular Smooth Muscle Cells via Down-Regulation of Mitogen/Activated Protein Kinase and Ezrin-Radixin-Moesin Signaling Pathways.

PubMed

Zhang, Ya-Xing; Xu, Jing-Ting; You, Xin-Chao; Wang, Chen; Zhou, Ke-Wen; Li, Ping; Sun, Peng; Wang, Ling; Wang, Ting-Huai

2016-02-29

Molecular hydrogen (H₂) has recently attracted considerable attention for the prevention of oxidative stress-related vascular diseases. The purpose of this study is to evaluate the effects of hydrogen on proliferation and migration of vascular smooth muscle cells (VSMCs) stimulated by angiotensin II (Ang II) in vitro, and on vascular hypertrophy induced by abdominal aortic coarctation (AAC) in vivo. Hydrogen-rich medium (0.6~0.9 ppm) was added 30 min before 10⁻⁷ M Ang II administration, then the proliferation and migration index were determined 24 h after Ang II stimulation. Hydrogen gas (99.999%) was given by intraperitoneal injection at the dose of 1 ml/100 g/day consecutively for one week before AAC and lasted for 6 weeks in vivo. Hydrogen inhibited proliferation and migration of VSMCs with Ang II stimulation in vitro, and improved the vascular hypertrophy induced by AAC in vivo. Treatment with hydrogen reduced Ang II- or AAC-induced oxidative stress, which was reflected by diminishing the induction of reactive oxygen species (ROS) in Ang II-stimulated VSMCs, inhibiting the levels of 3-nitrotyrosine (3-NT) in vascular and serum malondialdehyde (MDA). Hydrogen treatment also blocked Ang II-induced phosphorylation of the extracellular signal-regulated kinase1/2 (ERK1/2), p38 MAPK, c-Jun NH₂-terminal kinase (JNK) and the ezrin/radixin/moesin (ERM) in vitro. Taken together, our studies indicate that hydrogen prevents AAC-induced vascular hypertrophy in vivo, and inhibits Ang II-induced proliferation and migration of VSMCs in vitro possibly by targeting ROS-dependent ERK1/2, p38 MAPK, JNK and ERM signaling. It provides the molecular basis of hydrogen on inhibiting the abnormal proliferation and migration of VSMCs and improving vascular remodeling diseases.

The dual targeting of insulin and insulin-like growth factor 1 receptor enhances the mTOR inhibitor-mediated antitumor efficacy in hepatocellular carcinoma

PubMed Central

Pivonello, Claudia; Negri, Mariarosaria; De Martino, Maria Cristina; Napolitano, Maria; de Angelis, Cristina; Provvisiero, Donatella Paola; Cuomo, Gaia; Auriemma, Renata Simona; Simeoli, Chiara; Izzo, Francesco; Colao, Annamaria; Hofland, Leo J.; Pivonello, Rosario

2016-01-01

Deregulation of mTOR and IGF pathways is frequent in hepatocellular carcinoma (HCC), thus mTOR and IGF1R represent suitable therapeutic targets in HCC. The aim of this study was to evaluate the effects of mTOR inhibitors (mTORi) and OSI-906, blocker of IGF1R/IR, on HCC cell proliferation, viability, migration and invasion, and alpha-fetoprotein (α-FP) secretion. In HepG2 and HuH-7 we evaluated, the expression of mTOR and IGF pathway components; the effects of Sirolimus, Everolimus, Temsirolimus and OSI-906 on cell proliferation; the effects of Sirolimus, OSI-906, and their combination, on cell secretion, proliferation, viability, cell cycle, apoptosis, invasion and migration. Moreover, intracellular mechanisms underlying these cell functions were evaluated in both cell lines. Our results show that HepG2 and HuH-7 present with the same mRNA expression profile with high levels of IGF2. OSI-906 inhibited cell proliferation at high concentration, while mTORi suppressed cell proliferation in a dose-time dependent manner in both cell lines. The co-treatment showed an additive inhibitory effect on cell proliferation and viability. This effect was not related to induction of apoptosis, but to G0/G1 phase block. Moreover, the co-treatment prevented the Sirolimus-induced AKT activation as escape mechanism. Both agents demonstrated to be differently effective in inhibiting α-FP secretion. Sirolimus, OSI-906, and their combination, blocked cell migration and invasion in HuH-7. These findings indicate that, co-targeting of IGF1R/IR and mTOR pathways could be a novel therapeutic approach in the management of HCC, in order to maximize antitumoral effect and to prevent the early development of resistance mechanisms. PMID:26756219

[Glyburide prevents pulmonary artery smooth muscle cell proliferation and migration via inhibiting NLRP3 activation].

PubMed

Liu, Y F; Wang, W; Liu, T; Zhang, W; Liu, J; Wang, J

2017-06-12

Objective: To investigate whether glyburide prevents platelet-derived growth factor (PDGF) induced pulmonary artery smooth muscle cells(PASMCs) proliferation and migration via inhibiting nucleotide binding domain leucine-rich repeat-containing receptors protein 3(NLRP3) inflammasome activation. Methods: PASMCs were divided into 4 groups: control group, glyburide group, PDGF group and PDGF+ glyburide group. Cell proliferation and migration were assessed by MTT and Transwell respectively. The NLRP3 inflammasome activation was assessed by Western blot. Results: Compared with the control group, the protein expressions of NLRP3, caspase-1 and IL-1β in PASMCs were increased to (1.38±0.09, t =3.998, P <0.001), (1.32±0.1, t =3.268, P <0.01)and(1.43±0.19) ( t =2.096, P <0.05) folds in the PDGF group. Glyburide had no effect on NLRP3, caspase-1 and IL-1β expression as compared with the control group, while the NLRP3, caspase-1 and IL-1β were decreased by(20.49±7.6)% ( t =2.862, P <0.01), (32.94±3.44)% ( t =4.154, P <0.001) and (24.67±5.29)% ( t =2.335, P <0.05) in the PDGF+ glyburide group, respectively, as compared with the PDGF group. Compared with the control group, the PASMCs proliferation and migration in the PDGF group were significantly increased to (1.74±0.23, t =4.717, P <0.001) and (3.12±0.8, t =5.249, P <0.001) folds, respectively. Compared with the control group, glyburide had no effect on PASMCs proliferation and migration. In PDGF+ glyburide group, cell proliferation was reduced by (50.5±4.27)% ( t =4.462, P <0.001) and cell migration count was lower than in the PDGF group (42.77±2.84)% ( t =3.716, P <0.001). Conclusion: Glyburide could ameliorate PDGF-induced PASMCs proliferation and migration by inhibiting NLRP3 inflammasome activation.

A herbal medicine for Alzheimer’s disease and its active constituents promote neural progenitor proliferation

PubMed Central

Mao, Jianxin; Huang, Shichao; Liu, Shangfeng; Feng, Xiao-Lin; Yu, Miao; Liu, Junjun; Sun, Yi Eve; Chen, Guoliang; Yu, Yang; Zhao, Jian; Pei, Gang

2015-01-01

Aberrant neural progenitor cell (NPC) proliferation and self-renewal have been linked to age-related neurodegeneration and neurodegenerative disorders including Alzheimer’s disease (AD). Rhizoma Acori tatarinowii is a traditional Chinese herbal medicine against cognitive decline. In this study, we found that the extract of Rhizoma Acori tatarinowii (AT) and its active constituents, asarones, promote NPC proliferation. Oral administration of AT enhanced NPC proliferation and neurogenesis in the hippocampi of adult and aged mice as well as that of transgenic AD model mice. AT and its fractions also enhanced the proliferation of NPCs cultured in vitro. Further analysis identified α-asarone and β-asarone as the two active constituents of AT in promoting neurogenesis. Our mechanistic study revealed that AT and asarones activated extracellular signal-regulated kinase (ERK) but not Akt, two critical kinase cascades for neurogenesis. Consistently, the inhibition of ERK activities effectively blocked the enhancement of NPC proliferation by AT or asarones. Our findings suggest that AT and asarones, which can be orally administrated, could serve as preventive and regenerative therapeutic agents to promote neurogenesis against age-related neurodegeneration and neurodegenerative disorders. PMID:26010330

Lactate dehydrogenase-A is indispensable for vascular smooth muscle cell proliferation and migration.

PubMed

Kim, Ji-Hyun; Bae, Kwi-Hyun; Byun, Jun-Kyu; Lee, Sungwoo; Kim, Jung-Guk; Lee, In Kyu; Jung, Gwon-Soo; Lee, You Mie; Park, Keun-Gyu

2017-10-07

The proliferation and migration of vascular smooth muscle cells (VSMCs) have been implicated in the pathogenesis of atherosclerosis. Increased aerobic glycolysis is a key feature of cellular phenotypes including cancer and immune cells. However, the role of aerobic glycolysis in the atherogenic phenotype of VSMCs remains largely unknown. Here, we investigated the role of lactate dehydrogenase-A (LDHA), which is a key enzyme for glycolysis, in the proliferation and migration of VSMCs. Activation of primary rat VSMCs with fetal bovine serum (FBS) or platelet-derived growth factor (PDGF) increased their proliferation and migration, glycolytic activity, and expression of LDHA. Wound healing and transwell migration assays demonstrated that small interfering RNA-mediated knockdown of LDHA and pharmacological inhibition of LDHA by oxamate both effectively inhibited VSMC proliferation and migration. Inhibition of LDHA activity by oxamate reduced PDGF-stimulated glucose uptake, lactate production, and ATP production. Taken together, this study shows that enhanced glycolysis in PDGF- or FBS-stimulated VSMCs plays an important role in their proliferation and migration and suggests that LDHA is a potential therapeutic target to prevent vessel lumen constriction during the course of atherosclerosis and restenosis. Copyright © 2017 Elsevier Inc. All rights reserved.

A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation.

PubMed

Mao, Jianxin; Huang, Shichao; Liu, Shangfeng; Feng, Xiao-Lin; Yu, Miao; Liu, Junjun; Sun, Yi Eve; Chen, Guoliang; Yu, Yang; Zhao, Jian; Pei, Gang

2015-10-01

Aberrant neural progenitor cell (NPC) proliferation and self-renewal have been linked to age-related neurodegeneration and neurodegenerative disorders including Alzheimer's disease (AD). Rhizoma Acori tatarinowii is a traditional Chinese herbal medicine against cognitive decline. In this study, we found that the extract of Rhizoma Acori tatarinowii (AT) and its active constituents, asarones, promote NPC proliferation. Oral administration of AT enhanced NPC proliferation and neurogenesis in the hippocampi of adult and aged mice as well as that of transgenic AD model mice. AT and its fractions also enhanced the proliferation of NPCs cultured in vitro. Further analysis identified α-asarone and β-asarone as the two active constituents of AT in promoting neurogenesis. Our mechanistic study revealed that AT and asarones activated extracellular signal-regulated kinase (ERK) but not Akt, two critical kinase cascades for neurogenesis. Consistently, the inhibition of ERK activities effectively blocked the enhancement of NPC proliferation by AT or asarones. Our findings suggest that AT and asarones, which can be orally administrated, could serve as preventive and regenerative therapeutic agents to promote neurogenesis against age-related neurodegeneration and neurodegenerative disorders. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Effect of Pirfenidone on Vascular Proliferation, Inflammation and Fibrosis in an Abdominal Adhesion Rat Model.

PubMed

Hasdemir, Pinar Solmaz; Ozkut, Mahmud; Guvenal, Tevfik; Uner, Melis Aylin; Calik, Esat; Koltan, Semra Oruc; Koyuncu, Faik Mumtaz; Ozbilgin, Kemal

2017-02-01

To study the efficacy of pirfenidone for prevention of postoperative adhesion formation in an adhesion rat model. Eighteen female Wistar rats were subjected to right-sided parietal peritoneum and right uterine horn adhesion model. Rats were randomized into three groups: group 1 (control) (closure of midline abdominal incision without any agent administration), group 2 (closure of incision after intraperitoneal administration of pirfenidone), and group 3 (closure of incision and only oral administration of pirfenidone for 14 days). Relaparotomy was performed 14 days after the first surgery. Effect of pirfenidone on adhesion formation was assessed on light microscopy by scoring vascular proliferation, inflammation, fibrosis, and collagen formation in the scarred tissue. Effect of pirfenidone on inflammation was assessed by measurement of transforming growth factor-β and interleukin-17 levels in scarred tissue. The degree of vascular proliferation (1.32 ± 0.39 versus 2.34 ± 0.46, p < 0.001), inflammation (1.60 ± 0.70 versus 2.60 ± 0.52, p < 0.01), and fibrosis (1.50 ± 0.53 versus 2.40 ± 0.52, p < 0.01) were less prominent in group 2 compared to group 1, respectively. Only vascular proliferation was found to be less prominent in group 3 compared to group 1 (1.60 ± 0.42 versus 2.34 ± 0.46, p < 0.01). Intraperitoneal and oral administration of pirfenidone reduced tissue levels of inflammatory markers (TGF-β and IL-17) in parietal and visceral peritoneum compared to control group. Intraperitoneal administration of pirfenidone compared to oral administration was more effective in reducing tissue levels of inflammatory markers. Pirfenidone is an effective agent on the prevention of postoperative vascular proliferation, inflammation and fibrosis in scarred tissue particularly with intraperitoneal administration.

Orbital fluid shear stress promotes osteoblast metabolism, proliferation and alkaline phosphates activity in vitro

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

Aisha, M.D.; Nor-Ashikin, M.N.K.; DDH, Universiti Teknologi MARA, ShahAlam 40450, Selangor

Prolonged disuse of the musculoskeletal system is associated with reduced mechanical loading and lack of anabolic stimulus. As a form of mechanical signal, the multidirectional orbital fluid shear stress transmits anabolic signal to bone forming cells in promoting cell differentiation, metabolism and proliferation. Signals are channeled through the cytoskeleton framework, directly modifying gene and protein expression. For that reason, we aimed to study the organization of Normal Human Osteoblast (NHOst) cytoskeleton with regards to orbital fluid shear (OFS) stress. Of special interest were the consequences of cytoskeletal reorganization on NHOst metabolism, proliferation, and osteogenic functional markers. Cells stimulated at 250more » RPM in a shaking incubator resulted in the rearrangement of actin and tubulin fibers after 72 h. Orbital shear stress increased NHOst mitochondrial metabolism and proliferation, simultaneously preventing apoptosis. The ratio of RANKL/OPG was reduced, suggesting that orbital shear stress has the potential to inhibit osteoclastogenesis and osteoclast activity. Increase in ALP activity and OCN protein production suggests that stimulation retained osteoblast function. Shear stress possibly generated through actin seemed to hold an anabolic response as osteoblast metabolism and functional markers were enhanced. We hypothesize that by applying orbital shear stress with suitable magnitude and duration as a non-drug anabolic treatment can help improve bone regeneration in prolonged disuse cases. - Highlights: • OFS stress transmits anabolic signals to osteoblasts. • Actin and tubulin fibers are rearranged under OFS stress. • OFS stress increases mitochondrial metabolism and proliferation. • Reduced RANKL/OPG ratio in response to OFS inhibits osteoclastogenesis. • OFS stress prevents apoptosis and stimulates ALP and OCN.« less

Arginase inhibition reduces interleukin-1β-stimulated vascular smooth muscle cell proliferation by increasing nitric oxide synthase-dependent nitric oxide production

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

Yoon, Jeongyeon; Ryoo, Sungwoo, E-mail: ryoosw08@kangwon.ac.kr

2013-06-07

Highlights: •Arginase inhibition suppressed proliferation of IL-1β-stimulated VSMCs in dose-dependent manner. •NO production from IL-1β-induced iNOS expression was augmented by arginase inhibition, reducing VSMC proliferation. •Incubation with cGMP analogues abolished IL-1β-dependent proliferation of VSMCs. -- Abstract: We investigated whether arginase inhibition suppressed interleukin (IL)-1β-stimulated proliferation in vascular smooth muscle cells (VSMCs) and the possible mechanisms involved. IL-1β stimulation increased VSMC proliferation, while the arginase inhibitor BEC and transfection of the antisense (AS) oligonucleotide against arginase I decreased VSMC proliferation and was associated with increased protein content of the cell cycle regulator p21Waf1/Cip1. IL-1β incubation induced inducible nitric oxide synthase (iNOS)more » mRNA expression and protein levels in a dose-dependent manner, but did not affect arginase I and II expression. Consistent with this data, IL-1β stimulation resulted in increase in NO production that was significantly augmented by arginase inhibition. The specific iNOS inhibitor 1400W abolished IL-1β-mediated NO production and further accentuated IL-1β-stimulated cell proliferation. Incubation with NO donors GSNO and DETA/NO in the presence of IL-1β abolished VSMCs proliferation and increased p21Waf1/Cip1 protein content. Furthermore, incubation with the cGMP analogue 8-Br-cGMP prevented IL-1β-induced VSMCs proliferation. In conclusion, arginase inhibition augmented iNOS-dependent NO production that resulted in suppression of IL-1β-induced VSMCs proliferation in a cGMP-dependent manner.« less

Time-spatial model on the dynamics of the proliferation of Aedes aegypti

NASA Astrophysics Data System (ADS)

Gouvêa, Maury Meirelles, Jr.

2017-03-01

Some complex physical systems, such as cellular regulation, ecosystems, and societies, can be represented by local interactions between agents. Then, complex behaviors may emerge. A cellular automaton is a discrete dynamic system with these features. Among the several complex systems, epidemic diseases are given special attention by researchers with respect to their dynamics. Understanding the behavior of an epidemic may well benefit a society. For instance, different proliferation scenarios may be produced and a prevention policy set. This paper presents a new simulation method of the time-spatial spread of the Dengue mosquito with a cellular automaton. Thus, it will be possible to create different dissemination scenarios and preventive policies for these in several regions. Simulations were performed with different initial conditions and parameters as a result of which the behavior of the proposed method was characterized.

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

Murray, B.L.; Hallenbeck, R.A.; Gill, J.M.

This seminar provided an overview on the proliferation of nuclear, chemical and biological weapons as well as missiles and missile technology, and set the stage for subsequent seminar meetings of the 1993 program. A multiplicity of factors -- different nations, regions, and capabilities -- is making dealing with proliferation increasingly complicated. Additionally, recent or upcoming world events introduce further uncertainty into proliferation calculations. These proliferation accelerators and decelerators, will greatly shape and define the overall proliferation picture. These factors combine to raise a whole new series of stability issues which require new analyses and approaches for managing proliferation in themore » post-Cold War era. While technology cannot alone solve the proliferation problem, a particularly promising application is in new information technologies and interactive information management systems. A proliferation information network could be used to fuse large amounts of information and data on exports; license; treaty reporting, notifications, and other obligations; dual use technologies and related scientific advances; and others information of proliferation relevance. This type of network could use readily available technologies, would be simple to use and relatively inexpensive to create and maintain, and could be made available to almost of all of the nations of the world.« less

Proliferation of Masters Degrees in General Administration: Refocusing School Leadership Reform

ERIC Educational Resources Information Center

Gahungu, Athanase

2010-01-01

The proliferation of inappropriate master's degrees in educational administration is a tough challenge facing efforts to reform school leadership in the nation. In the state of Illinois alone, there are 26 universities and colleges offering 32 master's degree programs in educational leadership. In all, candidates enroll in 16 different types of…

The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression.

PubMed

He, Chunbo; Mao, Dagan; Hua, Guohua; Lv, Xiangmin; Chen, Xingcheng; Angeletti, Peter C; Dong, Jixin; Remmenga, Steven W; Rodabaugh, Kerry J; Zhou, Jin; Lambert, Paul F; Yang, Peixin; Davis, John S; Wang, Cheng

2015-11-01

The Hippo signaling pathway controls organ size and tumorigenesis through a kinase cascade that inactivates Yes-associated protein (YAP). Here, we show that YAP plays a central role in controlling the progression of cervical cancer. Our results suggest that YAP expression is associated with a poor prognosis for cervical cancer. TGF-α and amphiregulin (AREG), via EGFR, inhibit the Hippo signaling pathway and activate YAP to induce cervical cancer cell proliferation and migration. Activated YAP allows for up-regulation of TGF-α, AREG, and EGFR, forming a positive signaling loop to drive cervical cancer cell proliferation. HPV E6 protein, a major etiological molecule of cervical cancer, maintains high YAP protein levels in cervical cancer cells by preventing proteasome-dependent YAP degradation to drive cervical cancer cell proliferation. Results from human cervical cancer genomic databases and an accepted transgenic mouse model strongly support the clinical relevance of the discovered feed-forward signaling loop. Our study indicates that combined targeting of the Hippo and the ERBB signaling pathways represents a novel therapeutic strategy for prevention and treatment of cervical cancer. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

Caffeic Acid Inhibits Chronic UVB-Induced Cellular Proliferation Through JAK-STAT3 Signaling in Mouse Skin.

PubMed

Agilan, Balupillai; Rajendra Prasad, N; Kanimozhi, Govindasamy; Karthikeyan, Ramasamy; Ganesan, Muthusamy; Mohana, Shanmugam; Velmurugan, Devadasan; Ananthakrishnan, Dhanapalan

2016-05-01

Signal transducers and activators of transcription 3 (STAT3) play a critical role in inflammation, proliferation and carcinogenesis. Inhibition of JAK-STAT3 signaling is proved to be a novel target for prevention of UVB-induced skin carcinogenesis. In this study, chronic UVB irradiation (180 mJ cm(-2) ; weekly thrice for 30 weeks) induces the expression of IL-10 and JAK1 that eventually activates the STAT3 which leads to the transcription of proliferative and antiapoptotic markers such as PCNA, Cyclin-D1, Bcl2 and Bcl-xl, respectively. Caffeic acid (CA) inhibits JAK-STAT3 signaling, thereby induces apoptotic cell death by upregulating Bax, Cytochrome-C, Caspase-9 and Caspase-3 expression in mouse skin. Furthermore, TSP-1 is an antiangiogeneic protein, which is involved in the inhibition of angiogenesis and proliferation. Chronic UVB exposure decreased the expression of TSP-1 and pretreatment with CA prevented the UVB-induced loss of TSP-1 in UVB-irradiated mouse skin. Thus, CA offers protection against UVB-induced photocarcinogenesis probably through modulating the JAK-STAT3 in the mouse skin. © 2016 The American Society of Photobiology.

Use of Belatacept as Alternative Immunosuppression in Three Renal Transplant Patients with De Novo Drug-Induced Thrombotic Microangiopathy

PubMed Central

Cicora, Federico; Paz, Marta; Mos, Fernando; Roberti, Javier

2013-01-01

Thrombotic microangiopathy (TMA), a severe complication of renal transplantation, is a pathological process involving microvascular occlusion, thrombocytopenia, and microangiopathic hemolytic anemia. It generally appears within the first weeks after transplantation, when immunosuppressive drugs are used at high doses. De novo TMA may also be drug-induced when calcineurin inhibitors or proliferation signal inhibitors are used. We report three cases of de novo drug-induced TMA in renal transplant patients who were managed by replacing calcineurin inhibitors or proliferation signal inhibitors with belatacept, a primary maintenance immunosuppressive drug, which blocks the CD28 costimulation pathway, preventing the activation of T lymphocytes. To identify the cause of TMA, we ruled out HUS, hepatitis C serology, HIV serology, parvovirus B19, cytomegalovirus, anti-HLA antibodies, and prolonged activated partial thromboplastin time. We suspect that the TMA was caused by the calcineurin inhibitors or proliferation signal inhibitors. Belatacept treatment was initiated at a dose of 10 mg/kg on days 1, 5, 14, 28, 60, and 90; maintenance treatment was 5 mg/kg once a month for 1 year. Belatacept, in combination with other agents, prevented graft rejection in three patients. PMID:24198835

Neogenin, a regulator of adult hippocampal neurogenesis, prevents depressive-like behavior.

PubMed

Sun, Dong; Sun, Xiang-Dong; Zhao, Lu; Lee, Dae-Hoon; Hu, Jin-Xia; Tang, Fu-Lei; Pan, Jin-Xiu; Mei, Lin; Zhu, Xiao-Juan; Xiong, Wen-Cheng

2018-01-08

Adult neurogenesis in hippocampal dentate gyrus (DG) is a complex, but precisely controlled process. Dysregulation of this event contributes to multiple neurological disorders, including major depression. Thus, it is of considerable interest to investigate how adult hippocampal neurogenesis is regulated. Here, we present evidence for neogenin, a multifunctional transmembrane receptor, to regulate adult mouse hippocampal neurogenesis. Loss of neogenin in adult neural stem cells (NSCs) or neural progenitor cells (NPCs) impaired NSCs/NPCs proliferation and neurogenesis, whereas increased their astrocytic differentiation. Mechanistic studies revealed a role for neogenin to positively regulate Gli1, a crucial downstream transcriptional factor of sonic hedgehog, and expression of Gli1 into neogenin depleted NSCs/NPCs restores their proliferation. Further morphological and functional studies showed additional abnormities, including reduced dendritic branches and spines, and impaired glutamatergic neuro-transmission, in neogenin-depleted new-born DG neurons; and mice with depletion of neogenin in NSCs/NPCs exhibited depressive-like behavior. These results thus demonstrate unrecognized functions of neogenin in adult hippocampal NSCs/NPCs-promoting NSCs/NPCs proliferation and neurogenesis and preventing astrogliogenesis and depressive-like behavior, and suggest neogenin regulation of Gli1 signaling as a possible underlying mechanism.

Green Tea in Prevention and Therapy of Prostate Cancer

DTIC Science & Technology

2002-09-01

that polyphenols present in green tea especially its major constituent (-) epigallocatechin - 3- gallate ( EGCG ) possesses both cancer preventive and...androgen-sensitive 22Rv1 and androgen-insensitive PC-3 CaP cells. We found that intraperitoneal administration of EGCG resulted in significant inhibition...in tumor growth and serum PSA levels. Importantly, mice treated with EGCG exhibited a marked decrease in tumor proliferation along with significant

Targeting Aberrant p70S6K Activation for Estrogen Receptor-Negative Breast Cancer Prevention.

PubMed

Wang, Xiao; Yao, Jun; Wang, Jinyang; Zhang, Qingling; Brady, Samuel W; Arun, Banu; Seewaldt, Victoria L; Yu, Dihua

2017-11-01

The prevention of estrogen receptor-negative (ER-) breast cancer remains a major challenge in the cancer prevention field, although antiestrogen and aromatase inhibitors have shown adequate efficacy in preventing estrogen receptor-positive (ER + ) breast cancer. Lack of commonly expressed, druggable targets is a major obstacle for meeting this challenge. Previously, we detected the activation of Akt signaling pathway in atypical hyperplasic early-stage lesions of patients. In the current study, we found that Akt and the downstream 70 kDa ribosomal protein S6 kinase (p70S6K) signaling pathway was highly activated in ER - premalignant breast lesions and ER - breast cancer. In addition, p70S6K activation induced transformation of ER - human mammary epithelial cells (hMEC). Therefore, we explored the potential of targeting Akt/p70S6K in the p70S6K activated, ER - hMEC models and mouse mammary tumor models for the prevention of ER - breast cancer. We found that a clinically applicable Akt/p70S6K dual inhibitor, LY2780301, drastically decreased proliferation of hMECs with ErbB2-induced p70S6K activation via Cyclin B1 inhibition and cell-cycle blockade at G 0 -G 1 phase, while it did not significantly reverse the abnormal acinar morphology of these hMECs. In addition, a brief treatment of LY2780301 in MMTV- neu mice that developed atypical hyperplasia (ADH) and mammary intraepithelial neoplasia (MIN) lesions with activated p70S6K was sufficient to suppress S6 phosphorylation and decrease cell proliferation in hyperplasic MECs. In summary, targeting the aberrant Akt/p70S6K activation in ER - hMEC models in vitro and in the MMTV- neu transgenic mouse model in vivo effectively inhibited Akt/S6K signaling and reduced proliferation of hMECs in vitro and ADH/MIN lesions in vivo , indicating its potential in prevention of p70S6K activated ER - breast cancer. Cancer Prev Res; 10(11); 641-50. ©2017 AACR . ©2017 American Association for Cancer Research.

The cell proliferation antigen Ki-67 organises heterochromatin

PubMed Central

Sobecki, Michal; Mrouj, Karim; Camasses, Alain; Parisis, Nikolaos; Nicolas, Emilien; Llères, David; Gerbe, François; Prieto, Susana; Krasinska, Liliana; David, Alexandre; Eguren, Manuel; Birling, Marie-Christine; Urbach, Serge; Hem, Sonia; Déjardin, Jérôme; Malumbres, Marcos; Jay, Philippe; Dulic, Vjekoslav; Lafontaine, Denis LJ; Feil, Robert; Fisher, Daniel

2016-01-01

Antigen Ki-67 is a nuclear protein expressed in proliferating mammalian cells. It is widely used in cancer histopathology but its functions remain unclear. Here, we show that Ki-67 controls heterochromatin organisation. Altering Ki-67 expression levels did not significantly affect cell proliferation in vivo. Ki-67 mutant mice developed normally and cells lacking Ki-67 proliferated efficiently. Conversely, upregulation of Ki-67 expression in differentiated tissues did not prevent cell cycle arrest. Ki-67 interactors included proteins involved in nucleolar processes and chromatin regulators. Ki-67 depletion disrupted nucleologenesis but did not inhibit pre-rRNA processing. In contrast, it altered gene expression. Ki-67 silencing also had wide-ranging effects on chromatin organisation, disrupting heterochromatin compaction and long-range genomic interactions. Trimethylation of histone H3K9 and H4K20 was relocalised within the nucleus. Finally, overexpression of human or Xenopus Ki-67 induced ectopic heterochromatin formation. Altogether, our results suggest that Ki-67 expression in proliferating cells spatially organises heterochromatin, thereby controlling gene expression. DOI: http://dx.doi.org/10.7554/eLife.13722.001 PMID:26949251

Griffipavixanthone, a dimeric xanthone extracted from edible plants, inhibits tumor metastasis and proliferation via downregulation of the RAF pathway in esophageal cancer.

PubMed

Ding, Zhijie; Lao, Yuanzhi; Zhang, Hong; Fu, Wenwei; Zhu, Lunlun; Tan, Hongsheng; Xu, Hongxi

2016-01-12

Metastasis causes a large number of deaths among esophageal cancer patients. The activation of RAF family proteins elevates tumor metastasis and proliferation. In screen targeting the RAF protein, we identified that Griffipavixanthone (GPX), a dimeric xanthone isolated from Garcinia esculenta, is a B-RAF and C-RAF inhibitor against esophageal cancer cells. Using wound healing, transwell migration and matrigel invasion assays, we confirmed that GPX significantly inhibited cell migration and invasion. Furthermore, exposure to GPX rendered cell proliferation and induced G2/M cell cycle arrest. Our mechanistic study showed that GPX suppressed cancer metastasis and proliferation through downregulation of RAF-MEK-ERK cascades proteins as well as RAF mRNA levels. In a pulmonary metastasis model, the intraperitoneal injection of GPX significantly suppressed esophageal tumor metastasis and ERK protein level in vivo. In conclusion, our present study suggested that GPX could inhibit tumor migration, invasion and proliferation in vitro and in vivo, which indicated the potential of GPX for preventing and treating esophageal cancer.

MYB36 regulates the transition from proliferation to differentiation in the Arabidopsis root

PubMed Central

Liberman, Louisa M.; Sparks, Erin E.; Moreno-Risueno, Miguel A.; Petricka, Jalean J.; Benfey, Philip N.

2015-01-01

Stem cells are defined by their ability to self-renew and produce daughter cells that proliferate and mature. These maturing cells transition from a proliferative state to a terminal state through the process of differentiation. In the Arabidopsis thaliana root the transcription factors SCARECROW and SHORTROOT regulate specification of the bipotent stem cell that gives rise to cortical and endodermal progenitors. Subsequent progenitor proliferation and differentiation generate mature endodermis, marked by the Casparian strip, a cell-wall modification that prevents ion diffusion into and out of the vasculature. We identified a transcription factor, MYB DOMAIN PROTEIN 36 (MYB36), that regulates the transition from proliferation to differentiation in the endodermis. We show that SCARECROW directly activates MYB36 expression, and that MYB36 likely acts in a feed-forward loop to regulate essential Casparian strip formation genes. We show that myb36 mutants have delayed and defective barrier formation as well as extra divisions in the meristem. Our results demonstrate that MYB36 is a critical positive regulator of differentiation and negative regulator of cell proliferation. PMID:26371322

Loss of p53 induces cell proliferation via Ras-independent activation of the Raf/Mek/Erk signaling pathway

PubMed Central

Drosten, Matthias; Sum, Eleanor Y. M.; Lechuga, Carmen G.; Simón-Carrasco, Lucía; Jacob, Harrys K. C.; García-Medina, Raquel; Huang, Sidong; Beijersbergen, Roderick L.; Bernards, Rene; Barbacid, Mariano

2014-01-01

The Ras family of small GTPases constitutes a central node in the transmission of mitogenic stimuli to the cell cycle machinery. The ultimate receptor of these mitogenic signals is the retinoblastoma (Rb) family of pocket proteins, whose inactivation is a required step to license cell proliferation. However, little is known regarding the molecular events that connect Ras signaling with the cell cycle. Here, we provide genetic evidence to illustrate that the p53/p21 Cdk-interacting protein 1 (Cip1)/Rb axis is an essential component of the Ras signaling pathway. Indeed, knockdown of p53, p21Cip1, or Rb restores proliferative properties in cells arrested by ablation of the three Ras loci, H-, N- and K-Ras. Ras signaling selectively inactivates p53-mediated induction of p21Cip1 expression by inhibiting acetylation of specific lysine residues in the p53 DNA binding domain. Proliferation of cells lacking both Ras proteins and p53 can be prevented by reexpression of the human p53 ortholog, provided that it retains an active DNA binding domain and an intact lysine residue at position 164. These results unveil a previously unidentified role for p53 in preventing cell proliferation under unfavorable mitogenic conditions. Moreover, we provide evidence that cells lacking Ras and p53 proteins owe their proliferative properties to the unexpected retroactivation of the Raf/Mek/Erk cascade by a Ras-independent mechanism. PMID:25288756

Novel Mouse Xenograft Models Reveal a Critical Role of CD4+ T Cells in the Proliferation of EBV-Infected T and NK Cells

PubMed Central

Arai, Ayako; Nakazawa, Atsuko; Kawano, Fuyuko; Ichikawa, Sayumi; Shimizu, Norio; Yamamoto, Naoki; Morio, Tomohiro; Ohga, Shouichi; Nakamura, Hiroyuki; Ito, Mamoru; Miura, Osamu; Komano, Jun; Fujiwara, Shigeyoshi

2011-01-01

Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, ectopically infects T or NK cells to cause severe diseases of unknown pathogenesis, including chronic active EBV infection (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). We developed xenograft models of CAEBV and EBV-HLH by transplanting patients' PBMC to immunodeficient mice of the NOD/Shi-scid/IL-2Rγnull strain. In these models, EBV-infected T, NK, or B cells proliferated systemically and reproduced histological characteristics of the two diseases. Analysis of the TCR repertoire expression revealed that identical predominant EBV-infected T-cell clones proliferated in patients and corresponding mice transplanted with their PBMC. Expression of the EBV nuclear antigen 1 (EBNA1), the latent membrane protein 1 (LMP1), and LMP2, but not EBNA2, in the engrafted cells is consistent with the latency II program of EBV gene expression known in CAEBV. High levels of human cytokines, including IL-8, IFN-γ, and RANTES, were detected in the peripheral blood of the model mice, mirroring hypercytokinemia characteristic to both CAEBV and EBV-HLH. Transplantation of individual immunophenotypic subsets isolated from patients' PBMC as well as that of various combinations of these subsets revealed a critical role of CD4+ T cells in the engraftment of EBV-infected T and NK cells. In accordance with this finding, in vivo depletion of CD4+ T cells by the administration of the OKT4 antibody following transplantation of PBMC prevented the engraftment of EBV-infected T and NK cells. This is the first report of animal models of CAEBV and EBV-HLH that are expected to be useful tools in the development of novel therapeutic strategies for the treatment of the diseases. PMID:22028658

Novel mouse xenograft models reveal a critical role of CD4+ T cells in the proliferation of EBV-infected T and NK cells.

PubMed

Imadome, Ken-ichi; Yajima, Misako; Arai, Ayako; Nakazawa, Atsuko; Kawano, Fuyuko; Ichikawa, Sayumi; Shimizu, Norio; Yamamoto, Naoki; Morio, Tomohiro; Ohga, Shouichi; Nakamura, Hiroyuki; Ito, Mamoru; Miura, Osamu; Komano, Jun; Fujiwara, Shigeyoshi

2011-10-01

Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, ectopically infects T or NK cells to cause severe diseases of unknown pathogenesis, including chronic active EBV infection (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). We developed xenograft models of CAEBV and EBV-HLH by transplanting patients' PBMC to immunodeficient mice of the NOD/Shi-scid/IL-2Rγ(null) strain. In these models, EBV-infected T, NK, or B cells proliferated systemically and reproduced histological characteristics of the two diseases. Analysis of the TCR repertoire expression revealed that identical predominant EBV-infected T-cell clones proliferated in patients and corresponding mice transplanted with their PBMC. Expression of the EBV nuclear antigen 1 (EBNA1), the latent membrane protein 1 (LMP1), and LMP2, but not EBNA2, in the engrafted cells is consistent with the latency II program of EBV gene expression known in CAEBV. High levels of human cytokines, including IL-8, IFN-γ, and RANTES, were detected in the peripheral blood of the model mice, mirroring hypercytokinemia characteristic to both CAEBV and EBV-HLH. Transplantation of individual immunophenotypic subsets isolated from patients' PBMC as well as that of various combinations of these subsets revealed a critical role of CD4+ T cells in the engraftment of EBV-infected T and NK cells. In accordance with this finding, in vivo depletion of CD4+ T cells by the administration of the OKT4 antibody following transplantation of PBMC prevented the engraftment of EBV-infected T and NK cells. This is the first report of animal models of CAEBV and EBV-HLH that are expected to be useful tools in the development of novel therapeutic strategies for the treatment of the diseases.

Economic and Non-proliferation Policy Considerations of Uranium Enrichment in Brazil and Argentina

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

Short, Steven M.; Phillips, Jon R.; Weimar, Mark R.

2008-09-01

The nuclear development programs of both Argentina and Brazil have, since the 1970s, been premised on the desire for self-sufficiency and assurance of nuclear fuel supply. While military rivalry and mutual distrust led to nuclear weapons related development programs in the 1970s and 1980s, both countries have since terminated these programs. Furthermore, the governments of both countries have pledged their commitment to exclusively non-explosive use of nuclear energy and have signed the Non Proliferation Treaty (NPT). Utilizing rights provided for under the NPT, both Argentina and Brazil have nuclear fuel production facilities, with the notable exception of enrichment plants, thatmore » provide much of the current indigenous fuel requirements for their nuclear power plants. However, both countries are actively developing enrichment capability to fill this gap. The purpose of this report is to assess the economic basis and non-proliferation policy considerations for indigenous enrichment capability within the context of their desired self-sufficiency and to evaluate possible United States Government policy options.« less

Influence of Berry-Polyphenols on Receptor Signaling and Cell-Death Pathways: Implications for Breast Cancer Prevention

PubMed Central

Aiyer, Harini S; Warri, Anni M; Woode, Denzel R; Hilakivi-Clarke, Leena; Clarke, Robert

2012-01-01

Breast cancer is the most commonly diagnosed cancer among women worldwide. Many women have become more aware of the benefits of increasing fruit consumption, as part of a healthy lifestyle, for the prevention of cancer. The mechanisms by which fruits, including berries, prevent breast cancer can be partially explained by exploring their interactions with pathways known influence cell-proliferation and evasion of cell-death. Two receptor pathways- estrogen receptor (ER) and tyrosine kinase receptors, especially the epidermal growth factor receptor (EGFR) family- are drivers of cell-proliferation and play a significant role in the development of both primary and recurrent breast cancer. There is strong evidence to show that several phytochemicals present in berries such as cyanidin, delphinidin, quercetin, kaempferol, ellagic acid, resveratrol and pterostilbene, interact with and alter the effects of these pathways. Further, they also induce cell death (apoptosis and autophagy) via their influence on kinase signaling. In this review, we summarize in vitro data regarding the interaction of berry polyphenols with the specific receptors and the mechanisms by which they induce cell death. Further, we also present in vivo data of primary breast cancer prevention by individual compounds and whole berries. Finally, we present a possible role for berries and berry compounds in the prevention of breast cancer and our perspective on the areas that require further research. PMID:22300613

Plasma Rich in Growth Factors Induces Cell Proliferation, Migration, Differentiation, and Cell Survival of Adipose-Derived Stem Cells.

PubMed

Mellado-López, Maravillas; Griffeth, Richard J; Meseguer-Ripolles, Jose; Cugat, Ramón; García, Montserrat; Moreno-Manzano, Victoria

2017-01-01

Adipose-derived stem cells (ASCs) are a promising therapeutic alternative for tissue repair in various clinical applications. However, restrictive cell survival, differential tissue integration, and undirected cell differentiation after transplantation in a hostile microenvironment are complications that require refinement. Plasma rich in growth factors (PRGF) from platelet-rich plasma favors human and canine ASC survival, proliferation, and delaying human ASC senescence and autophagocytosis in comparison with serum-containing cultures. In addition, canine and human-derived ASCs efficiently differentiate into osteocytes, adipocytes, or chondrocytes in the presence of PRGF. PRGF treatment induces phosphorylation of AKT preventing ASC death induced by lethal concentrations of hydrogen peroxide. Indeed, AKT inhibition abolished the PRGF apoptosis prevention in ASC exposed to 100  μ M of hydrogen peroxide. Here, we show that canine ASCs respond to PRGF stimulus similarly to the human cells regarding cell survival and differentiation postulating the use of dogs as a suitable translational model. Overall, PRGF would be employed as a serum substitute for mesenchymal stem cell amplification to improve cell differentiation and as a preconditioning agent to prevent oxidative cell death.

ARQ-197, a small-molecule inhibitor of c-Met, reduces tumour burden and prevents myeloma-induced bone disease in vivo.

PubMed

Lath, Darren L; Buckle, Clive H; Evans, Holly R; Fisher, Matthew; Down, Jenny M; Lawson, Michelle A; Chantry, Andrew D

2018-01-01

The receptor tyrosine kinase c-Met, its ligand HGF, and components of the downstream signalling pathway, have all been implicated in the pathogenesis of myeloma, both as modulators of plasma cell proliferation and as agents driving osteoclast differentiation and osteoblast inhibition thus, all these contribute substantially to the bone destruction typically caused by myeloma. Patients with elevated levels of HGF have a poor prognosis, therefore, targeting these entities in such patients may be of substantial benefit. We hypothesized that ARQ-197 (Tivantinib), a small molecule c-Met inhibitor, would reduce myeloma cell growth and prevent myeloma-associated bone disease in a murine model. In vitro we assessed the effects of ARQ-197 on myeloma cell proliferation, cytotoxicity and c-Met protein expression in human myeloma cell lines. In vivo we injected NOD/SCID-γ mice with PBS (non-tumour bearing) or JJN3 cells and treated them with either ARQ-197 or vehicle. In vitro exposure of JJN3, U266 or NCI-H929 cells to ARQ-197 resulted in a significant inhibition of cell proliferation and an induction of cell death by necrosis, probably caused by significantly reduced levels of phosphorylated c-Met. In vivo ARQ-197 treatment of JJN3 tumour-bearing mice resulted in a significant reduction in tumour burden, tumour cell proliferation, bone lesion number, trabecular bone loss and prevented significant decreases in the bone formation rate on the cortico-endosteal bone surface compared to the vehicle group. However, no significant differences on bone parameters were observed in non-tumour mice treated with ARQ-197 compared to vehicle, implying that in tumour-bearing mice the effects of ARQ-197 on bone cells was indirect. In summary, these res ults suggest that ARQ-197 could be a promising therapeutic in myeloma patients, leading to both a reduction in tumour burden and an inhibition of myeloma-induced bone disease.

[6]-Shogaol attenuates inflammation, cell proliferation via modulate NF-κB and AP-1 oncogenic signaling in 7,12-dimethylbenz[a]anthracene induced oral carcinogenesis.

PubMed

Annamalai, Govindhan; Suresh, Kathiresan

2018-02-01

Nuclear factor-kappaB (NF-κB) and activator protein 1 (AP-1) is a major transcription factor which regulates many biological and pathological processes such as inflammation and cell proliferation, which are major implicates in cancer progression. [6]-Shogaol ([6]-SHO) is a major constituent of ginger, exhibits various biological properties such as anti-oxidants, anti-inflammation and anti-tumor. Recently, we proven that [6]-SHO prevents oral squamous cell carcinoma by activating proapoptotic factors in in vitro and in vivo experimental model. However, the preventive efficacy of [6]-SHO in 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis (HBP) has not been fully elucidated, so far. Hence, we aimed to investigate the effect of [6]-SHO on inflammation and cell proliferation by inhibiting the translocation of NF-κB and AP-1 in DMBA induced HBP carcinogenesis. In this study, we observed upregulation of inflammatory markers (COX-2, iNOS, TNF-α, interleukin-1 and -6), cell proliferative markers (Cyclin D1, PCNA and Ki-67) and aberrant activation of NF-κB, AP-1, IKKβ, c-jun, c-fos and decreased IκB-α in DMBA induced hamsters. Conversely, oral administration of [6]-SHO strongly inhibited constitutive phosphorylation and degradation of IκB and inhibit phosphorylation of c-jun, c-fos, resulting in inhibition of nuclear translocation of NF-κBp65 and AP-1. Thus, inhibition of NF-κB and AP-1 activation by [6]-SHO attenuates inflammation and cell proliferative response in DMBA induced hamsters. Our finding suggested that [6]-SHO is a novel functional agent capable of preventing DMBA induced inflammation and cell proliferation associated tumorigenesis by modulating multiple signalling molecules. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Get Well Care: Guidelines for Programs Serving Mildly Ill Children.

ERIC Educational Resources Information Center

Montanari, Ellen Orton, Ed.

Although child care programs for mildly ill children are proliferating around the country, very few states have developed regulations for these types of programs, and no states have developed standards or guidelines. Based upon this concern, a group of medical and early childhood professionals, parents, and directors of programs for mildly ill…

Teacher Performance Pay Programs and Necessary Communication Actions

ERIC Educational Resources Information Center

Heneman, Herbert G., III; Worth, Robin; Arrigoni, Jessica; Kimball, Steven M.; Milanowski, Anthony

2013-01-01

Teacher performance pay programs have proliferated across the country over the past 20 years. To aid in understanding their many variations, the seven major components of these programs are described. Three examples of teacher performance pay programs are provided for illustration: Denver ProComp, TAP, and Houston ASPIRE. Evidence is mixed on the…

Role of cellular bioenergetics in smooth muscle cell proliferation induced by platelet-derived growth factor.

PubMed

Perez, Jessica; Hill, Bradford G; Benavides, Gloria A; Dranka, Brian P; Darley-Usmar, Victor M

2010-05-13

Abnormal smooth muscle cell proliferation is a hallmark of vascular disease. Although growth factors are known to contribute to cell hyperplasia, the changes in metabolism associated with this response, particularly mitochondrial respiration, remain unclear. Given the increased energy requirements for proliferation, we hypothesized that PDGF (platelet-derived growth factor) would stimulate glycolysis and mitochondrial respiration and that this elevated bioenergetic capacity is required for smooth muscle cell hyperplasia. To test this hypothesis, cell proliferation, glycolytic flux and mitochondrial oxygen consumption were measured after treatment of primary rat aortic VSMCs (vascular smooth muscle cells) with PDGF. PDGF increased basal and maximal rates of glycolytic flux and mitochondrial oxygen consumption; enhancement of these bioenergetic pathways led to a substantial increase in the mitochondrial reserve capacity. Interventions with the PI3K (phosphoinositide 3-kinase) inhibitor LY-294002 or the glycolysis inhibitor 2-deoxy-D-glucose abrogated PDGF-stimulated proliferation and prevented augmentation of glycolysis and mitochondrial reserve capacity. Similarly, when L-glucose was substituted for D-glucose, PDGF-dependent proliferation was abolished, as were changes in glycolysis and mitochondrial respiration. Interestingly, LDH (lactate dehydrogenase) protein levels and activity were significantly increased after PDGF treatment. Moreover, substitution of L-lactate for D-glucose was sufficient to increase mitochondrial reserve capacity and cell proliferation after treatment with PDGF; these effects were inhibited by the LDH inhibitor oxamate. These results suggest that glycolysis, by providing substrates that enhance the mitochondrial reserve capacity, plays an essential role in PDGF-induced cell proliferation, underscoring the integrated metabolic response required for proliferation of VSMCs in the diseased vasculature.

Benign endometrial proliferations mimicking malignancies: a review of problematic entities in small biopsy specimens.

PubMed

Ip, Philip Pun-Ching

2018-02-14

Benign proliferations that mimic malignancies are commonly encountered during the course of assessment of small and fragmented endometrial samples. Although benign, endometrial epithelial metaplasias often coexist with premalignant or malignant lesions causing diagnostic confusion. The difficulty with mucinous metaplasia lies in its distinction from atypical mucinous glandular proliferations and mucinous carcinomas, which are associated with significant interobserver variability. Papillary proliferation of the endometrium is commonly associated with hormonal drugs and endometrial polyps and is characterised by papillae with fibrovascular cores covered by epithelial cells without cytologic atypia. They are classified into simple or complex papillary proliferations depending on the architectural complexity and extent of proliferation. Complex papillary proliferations are associated with a high risk of concurrent or subsequent hyperplasia with atypia/carcinoma. Papillary proliferations may have coexisting epithelial metaplasias and, most commonly, mucinous metaplasia and syncytial papillary change. Those with striking mucinous metaplasia overlap morphologically with papillary mucinous metaplasia. The latter has been proposed as a precursor of endometrial mucinous carcinoma. Misinterpreting the Arias-Stella reaction as a malignant or premalignant lesion is more likely to occur if the pathologist is unaware that the patient is pregnant or on hormonal drugs. Endometrial hyperplasia with secretory changes may occasionally be difficult to distinguish from the torturous and crowded glands of a late secretory endometrium. Endometrial polyps may have abnormal features that can be misinterpreted as endometrial hyperplasia or Mullerian adenosarcoma. Awareness of these benign endometrial proliferations and their common association with hormonal medication or altered endogenous hormonal levels will help prevent the over-diagnosis of premalignant and malignant lesions.

Cross talk between MMP2-Spm-Cer-S1P and ERK1/2 in proliferation of pulmonary artery smooth muscle cells under angiotensin II stimulation.

PubMed

Chowdhury, Animesh; Sarkar, Jaganmay; Pramanik, Pijush Kanti; Chakraborti, Tapati; Chakraborti, Sajal

2016-08-01

The aim of the present study is to establish the mechanism associated with the proliferation of PASMCs under ANG II stimulation. The results showed that treatment of PASMCs with ANG II induces an increase in cell proliferation and 100 nM was the optimum concentration for maximum increase in proliferation of the cells. Pretreatment of the cells with AT1, but not AT2, receptor antagonist inhibited ANG II induced cell proliferation. Pretreatment with pharmacological and genetic inhibitors of sphingomyelinase (SMase) and sphingosine kinase (SPHK) prevented ANG II-induced cell proliferation. ANG II has also been shown to induce SMase activity, SPHK phosphorylation and S1P production. In addition, ANG II caused an increase in proMMP-2 expression and activation, ERK1/2 phosphorylation and NADPH oxidase activation. Upon inhibition of MMP-2, SMase activity and S1P level were curbed leading to inhibition of cell proliferation. SPHK was phosphorylated by ERK1/2 during ET-1 stimulation of the cells. ANG II-induced ERK1/2 phosphorylation and proMMP-2 expression and activation in the cells were abrogated upon inhibition of NADPH oxidase activity. Overall, NADPH oxidase plays an important role in proMMP-2 expression and activation and that MMP-2 mediated SMC proliferation occurs through the involvement of Spm-Cer-S1P signaling axis under ANG II stimulation of PASMCs. Copyright © 2016 Elsevier Inc. All rights reserved.

40 CFR 68.170 - Prevention program/Program 2.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 15 2011-07-01 2011-07-01 false Prevention program/Program 2. 68.170 Section 68.170 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.170 Prevention program/Program...

40 CFR 68.170 - Prevention program/Program 2.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Prevention program/Program 2. 68.170 Section 68.170 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.170 Prevention program/Program...

Knockdown of AMPKα2 Promotes Pulmonary Arterial Smooth Muscle Cells Proliferation via mTOR/Skp2/p27Kip1 Signaling Pathway

PubMed Central

Ke, Rui; Liu, Lu; Zhu, Yanting; Li, Shaojun; Xie, Xinming; Li, Fangwei; Song, Yang; Yang, Lan; Gao, Li; Li, Manxiang

2016-01-01

It has been shown that activation of adenosine monophosphate-activated protein kinase (AMPK) suppresses proliferation of a variety of tumor cells as well as nonmalignant cells. In this study, we used post-transcriptional gene silencing with small interfering RNA (siRNA) to specifically examine the effect of AMPK on pulmonary arterial smooth muscle cells (PASMCs) proliferation and to further elucidate its underlying molecular mechanisms. Our results showed that knockdown of AMPKα2 promoted primary cultured PASMCs proliferation; this was accompanied with the elevation of phosphorylation of mammalian target of rapamycin (mTOR) and S-phase kinase-associated protein 2 (Skp2) protein level and reduction of p27Kip1. Importantly, prior silencing of mTOR with siRNA abolished AMPKα2 knockdown-induced Skp2 upregulation, p27Kip1 reduction as well as PASMCs proliferation. Furthermore, pre-depletion of Skp2 by siRNA also eliminated p27Kip1 downregulation and PASMCs proliferation caused by AMPKα2 knockdown. Taken together, our study indicates that AMPKα2 isoform plays an important role in regulation of PASMCs proliferation by modulating mTOR/Skp2/p27Kip1 axis, and suggests that activation of AMPKα2 might have potential value in the prevention and treatment of pulmonary arterial hypertension. PMID:27258250

Ghrelin inhibits proliferation and increases T-type Ca{sup 2+} channel expression in PC-3 human prostate carcinoma cells

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

Diaz-Lezama, Nundehui; Hernandez-Elvira, Mariana; Sandoval, Alejandro

Research highlights: {yields} Ghrelin decreases prostate carcinoma PC-3 cells proliferation. {yields} Ghrelin favors apoptosis in PC-3 cells. {yields} Ghrelin increase in intracellular free Ca{sup 2+} levels in PC-3 cells. {yields} Grelin up-regulates expression of T-type Ca{sup 2+} channels in PC-3 cells. {yields} PC-3 cells express T-channels of the Ca{sub V}3.1 and Ca{sub V}3.2 subtype. -- Abstract: Ghrelin is a multifunctional peptide hormone with roles in growth hormone release, food intake and cell proliferation. With ghrelin now recognized as important in neoplastic processes, the aim of this report is to present findings from a series of in vitro studies evaluating themore » cellular mechanisms involved in ghrelin regulation of proliferation in the PC-3 human prostate carcinoma cells. The results showed that ghrelin significantly decreased proliferation and induced apoptosis. Consistent with a role in apoptosis, an increase in intracellular free Ca{sup 2+} levels was observed in the ghrelin-treated cells, which was accompanied by up-regulated expression of T-type voltage-gated Ca{sup 2+} channels. Interestingly, T-channel antagonists were able to prevent the effects of ghrelin on cell proliferation. These results suggest that ghrelin inhibits proliferation and may promote apoptosis by regulating T-type Ca{sup 2+} channel expression.« less

Arab-American Hookah Smokers: Initiation, and Pros and Cons of Hookah Use.

PubMed

Kassem, Nada O F; Kassem, Noura O; Jackson, Sheila R; Daffa, Reem M; Liles, Sandy; Hovell, Melbourne F

2015-09-01

To examine initiation, pros and cons of hookah tobacco smoking among Arab Americans. In this descriptive cross-sectional study, we recruited a community-based convenience sample of 458 adult Arab-American hookah smokers, mean age 28.4 years, who completed self-administered questionnaires. Irrespective of sex, most participants initiated hookah tobacco use by young adulthood in private homes or hookah lounges influenced by friends and family. Women initiated hookah use later than men. Ever dual smokers (hookah smokers who ever smoked a cigarette) initiated hookah use later than cigarettes; however, early hookah initiators < 18 years initiated hookah and cigarettes concurrently. Participants enjoyed the flavors of hookah tobacco, and complained about coughing, dizziness, and headaches. Early and late initiation of hookah tobacco use warrant prevention programs targeting the youth and older adults in communities, colleges, and middle and high schools that include health education campaigns, and encouragement of voluntary smokefree home rules. Tobacco control policies aimed to prevent initiation of hookah use should include regulation of hookah tobacco flavors, and should target the physical environments in neighborhoods, especially around schools and colleges, to reduce the proliferation of hookah lounges. Dual hookah tobacco and cigarette use warrant continuous monitoring.

Pakistan’s Nuclear Weapons: Proliferation and Security Issues

DTIC Science & Technology

2009-10-15

and technical measures to prevent unauthorized or accidental use of nuclear weapons, as well as contribute to physical security of storage ...Talks On Nuclear Security,” The Boston Globe, May 5, 2009. 79 Abdul Mannan, “Preventing Nuclear Terrorism in Pakistan: Sabotage of a Spent Fuel Cask or...a Commercial Irradiation Source in Transport ,” in Pakistan’s Nuclear Future, 2008; Martellini, 2008. 80 Martellini, 2008. 81 For more information

Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet.

PubMed

Jin, Haiyan; Yamamoto, Naoki; Uchida, Koichi; Terai, Shuji; Sakaida, Isao

2007-12-28

Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor gamma activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions by down-regulating TGFbeta1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis.

Pharmacological doses of dietary curcumin increase colon epithelial cell proliferation in vivo in rats.

PubMed

Kim, Sylvia Jeewon; Hellerstein, Marc K

2007-10-01

Although curcumin has preventive actions in animal models of colon cancer, whether the mechanism of action is through anti-proliferation in normal environment is not clearly understood. Here, we studied the effects of chemopreventive doses of curcumin on the proliferation rate of colon epithelial cells (CEC), using a recently developed stable isotope-mass spectrometric method for measuring DNA synthesis rate. Adult male F344 rats were given diets containing 0, 2 and 4% curcumin for 5 weeks. 4% (2)H(2)O was given in drinking water to label DNA, after a priming bolus, for 4 days prior to sacrifice. The isotopic enrichment of the deoxyribose moiety of deoxyadenosine from DNA was measured by gas chromatography - mass spectrometry. Cell cycle analysis was performed after propidium iodide staining of CECs. Curcumin administration did not reduce but instead resulted in dose-dependent increases in CEC proliferation rate (p < 0.05) for 2% and 4% curcumin vs 0%). The length of the colon crypts and the fraction of cells in S-phase were also increased in the 2% and 4% curcumin groups (p < 0.05). Thus, pharmacological doses of curcumin increase CEC proliferation rate and pool size in normal rats. Reduction of CEC proliferation therefore cannot explain the proposed chemopreventive actions of curcumin in colon cancer.

Bisdemethoxycurcumin inhibits PDGF-induced vascular smooth muscle cell motility and proliferation

PubMed Central

Hua, Yinan; Dolence, Julia; Ramanan, Shalini; Ren, Jun; Nair, Sreejayan

2013-01-01

Scope A key event in the development of plaque in the arteries is the migration and proliferation of smooth muscle cells (SMCs) from the media to the intima of the blood vessel. This study was conducted to evaluate the effects of bisdemethoxycurcumin, a naturally occurring structural analog of curcumin, on PDGF-stimulated migration and proliferation of SMCs. Methods and results Demethoxycurcumin were synthesized by condensing vanillin and 4-hydroxybenzaldehyde. SMCs isolated from adult rat aorta were stimulated with PDGF in the presence or absence of curcumin or bisdemethoxycurcumin following which cell migration and proliferation were assessed by monolayer wound healing assay and [3H]-thymidine incorporation respectively. PDGF-induced phosphorylation of PDGF-receptor-β and its downstream effector Akt were assessed by Western blotting. Intracellular reactive oxygen species (ROS) was assessed using the fluorescent dye DCFDA. Bisdemethoxycurcumin elicited a concentration-dependent inhibition of PDGF-stimulated phosphorylation of PDGFR-β, Akt and Erk as well as the PDGF-stimulated SMC migration and proliferation. Bisdemethoxycurcumin was more potent than curcumin in inhibiting migration and proliferation and suppressing PDGF-signaling in SMCs. Both compounds were equipotent in inhibiting PDGF-stimulated intracellular ROS-generation. Conclusion Bisdemethoxycurcumin may be of potential use in the prevention or treatment of vascular disease. PMID:23554078

Potential advantages of treatment of transplanted saphenous vein aorto-coronary artery bypass grafts with beta irradiation to prevent graft occlusion.

PubMed

Smith, R G

1997-01-01

Intimal proliferation or Neointimal hyperplasia (NIH) is a vascular lesion that often arises in arteries after balloon angioplasty or other vessel wall injuries. FIH is a vascular lesion that develops in autologous saphenous vein grafts (SVG) after transplantation into the aorto-coronary circulation or the peripheral vascular circulation. FIH shares elements of smooth muscle migration, proliferation and fibrous tissue deposition in common with nibrointimal proliferation (NIH). Either NIH of a coronary artery or FIH of a SVG obstruct the vascular lumen and result in myocardial dysfunction. Local radiotherapy has been used for several decades to reduce the post-operative recurrence of the fibrovascular proliferations of pterygia and keloids. Similarly, in animal and human experiments, endovascular radiotherapy has been shown to reduce arterial smooth muscle proliferation. Consideration of the similarities of vascular smooth muscle cell proliferation in NIH and FIH leads one to suggest that endovascular beta irradiation can reduce FIH as well as it reduces NIH. The goal of such treatment is to achieve a clinically significant decrease in the morbidity and mortality resulting from SVG occlusions. The potential for large reduction of the consequences of SVG occlusion, the very large number of patients at risk, and the simplicity of the proposed intervention encourages prompt scientific evaluation of this technique.

Rho-associated kinases play an essential role in cardiac morphogenesis and cardiomyocyte proliferation.

PubMed

Zhao, Zhiyong; Rivkees, Scott A

2003-01-01

Rho-associated coiled-coil kinases (ROCKs), initially identified as effectors for Rho GTPases, play a role in cardiac cell physiology and are also expressed in the developing heart. However, their role in cardiac development is not known. To investigate the role of these kinases in cardiac development, we examined cardiac development in cultured murine embryos treated with the ROCK inhibitor Y27632. After inhibition of ROCK activity, we found disturbed cardiac chamber formation and trabeculation. To further examine the mechanisms by which ROCK blockade causes cardiac hypoplasia, we assessed programmed cell death and cell proliferation in the hearts. We found decreased cell proliferation in the Y27632-treated hearts, but no changes in programmed cell death. We further observed that ROCK inhibition decreased cardiac myocyte proliferation, suggesting that ROCK kinases regulate cardiomyocyte division. To identify factors involved in ROCK action in regulation of cardiac cell division, we examined expression of cell cycle proteins by using Western blot analysis. We found that ROCK blockade decreased expression of cell cycle proteins, cyclin D3, CDK6, and p27(KIP1) in the hearts and cardiomyocytes, which are required for initiation of cell cycle and G1/S phase transition. These observations show that ROCK kinases play a role in cardiac development and that ROCK kinases regulate cardiac cell proliferation and cell cycle protein expression. Copyright 2002 Wiley-Liss, Inc.

49 CFR 198.37 - State one-call damage prevention program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false State one-call damage prevention program. 198.37... REGULATIONS FOR GRANTS TO AID STATE PIPELINE SAFETY PROGRAMS Adoption of One-Call Damage Prevention Program § 198.37 State one-call damage prevention program. A State must adopt a one-call damage prevention...

Outcome Measures of Health Programs: What and How?

ERIC Educational Resources Information Center

Chen, Martin K.

With the proliferation of new health programs, such as Health Maintenance Organizations (HMO's) and Professional Service Review Organizations (PSRO's), the task of evaluating the impact of such programs on the health delivery systems and on the health of the American people becomes more urgent. Thus far no experimental or quasi-experimental…

The role of the cyclin-dependent kinase inhibitor p21 in apoptosis.

PubMed

Gartel, Andrei L; Tyner, Angela L

2002-06-01

Cancer develops when the balance between cell proliferation and cell death is disrupted, and the ensuing aberrant proliferation leads to tumor growth. The cyclin-dependent kinase inhibitor p21 is induced by both p53-dependent and -independent mechanisms following stress, and induction of p21 may cause cell cycle arrest. As a proliferation inhibitor, p21 is poised to play an important role in preventing tumor development. This notion is supported by data indicating that p21-null mice are more prone to spontaneous and induced tumorigenesis, and p21 synergizes with other tumor suppressors to protect against tumor progression in mice. However, a number of recent studies have pointed out that in addition to being an inhibitor of cell proliferation, p21 acts as an inhibitor of apoptosis in a number of systems, and this may counteract its tumor-suppressive functions as a growth inhibitor. In the current review, we discuss the role of p21 in regulating cell death and the potential relevance of its expression in cancer.

Vincristine modulates the expression of Ki67 and apoptosis in naturally occurring canine transmissible venereal tumor (TVT).

PubMed

Özalp, G R; Zik, B; Bastan, A; Peker, S; Özdemir-Salci, E S; Bastan, I; Darbaz, I; Salar, S; Karakas, K

2012-07-01

We investigated eight adult dogs that were brought to veterinary clinics with a history of transmissible venereal tumors (TVT). Our goal was to demonstrate the occurrence of apoptosis and the cessation of cell proliferation at every phase of scheduled chemotherapy for naturally occurring TVT. Tissue samples were collected immediately after weekly treatments with vincristine sulfate and processed for histological purposes. Sections 5 μm thick were stained by the TUNEL reaction for apoptosis and immunostained for Ki67 as a proliferation marker. We observed that after vincristine applications, tumor cell proliferation ceased and apoptosis increased. Ki67 HSCORE values were significantly lowered after the first and second treatments with the chemotherapeutic agent compared to controls, whereas TUNEL HSCORE values were significantly higher after two applications of vincristine compared to controls. Our results suggest that scheduled vincristine sulfate applications stabilize the induction of tumor regression by inducing apoptosis and preventing cell proliferation.

Pancreatic β-cell proliferation in obesity.

PubMed

Linnemann, Amelia K; Baan, Mieke; Davis, Dawn Belt

2014-05-01

Because obesity rates have increased dramatically over the past 3 decades, type 2 diabetes has become increasingly prevalent as well. Type 2 diabetes is associated with decreased pancreatic β-cell mass and function, resulting in inadequate insulin production. Conversely, in nondiabetic obesity, an expansion in β-cell mass occurs to provide sufficient insulin and to prevent hyperglycemia. This expansion is at least in part due to β-cell proliferation. This review focuses on the mechanisms regulating obesity-induced β-cell proliferation in humans and mice. Many factors have potential roles in the regulation of obesity-driven β-cell proliferation, including nutrients, insulin, incretins, hepatocyte growth factor, and recently identified liver-derived secreted factors. Much is still unknown about the regulation of β-cell replication, especially in humans. The extracellular signals that activate proliferative pathways in obesity, the relative importance of each of these pathways, and the extent of cross-talk between these pathways are important areas of future study. © 2014 American Society for Nutrition.

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

Inhibitory effects of OK-432 (Picibanil) on cellular proliferation and adhesive capacity of breast carcinoma cells.

PubMed

Horii, Yoshio; Iino, Yuichi; Maemura, Michio; Horiguchi, Jun; Morishita, Yasuo

2005-02-01

We investigated the potent inhibitory effects of OK-432 (Picibanil) on both cellular adhesion and cell proliferation of estrogen-dependent (MCF-7) or estrogen-independent (MDA-MB-231) breast carcinoma cells. Cellular proliferation of both MCF-7 and MDA-MB-231 cells was markedly inhibited in a dose-dependent manner, when the carcinoma cells were exposed to OK-432. Cell attachment assay demonstrated that incubation with OK-432 for 24 h reduced integrin-mediated cellular adhesion of both cell types. However, fluorescence activated cell sorter (FACS) analysis revealed that incubation with OK-432 for 24 h did not decrease the cell surface expressions of any integrins. These results suggest that the binding avidity of integrins is reduced by OK-432 without alteration of the integrin expression. We conclude that OK-432 inhibits integrin-mediated cellular adhesion as well as cell proliferation of breast carcinoma cells regardless of estrogen-dependence, and that these actions of OK-432 contribute to prevention or inhibition of breast carcinoma invasion and metastasis.

Separation of human bone marrow by counterflow centrifugation monitored by DNA-flowcytometry.

PubMed

de Witte, T; Plas, A; Koekman, E; Blankenborg, G; Salden, M; Wessels, J; Haanen, C

1984-10-01

Human bone marrow was fractionated by counterflow centrifugation into 16 fractions with increasing cell size. Three distinct subpopulations could be recognized: small lymphocytic cells, medium-sized nucleated erythroid cells and large myeloid elements. DNA-flowcytometry and 3H-thymidine uptake showed that within the erythroid and myeloid cell populations counterflow centrifugation separates each population according to the cell cycle phase. Hypotonic treatment of bone marrow for removal of the erythroid nucleated cells resulted in a complete abrogation of the proliferating erythroid cell population. Counterflow centrifugation also separates the small non-proliferating myeloid and erythroid committed stem cells from the larger proliferating stem cells. It appeared feasible to separate the small lymphocytic cells from the majority of BFU-E and CFU-GM, due to the larger size of the proliferating normoblasts and the committed progenitor cells. Elimination of the mature lymphocytes from the haematopoietic stem cells by counterflow centrifugation may offer an alternative approach to the prevention of graft versus host disease (GvHD).

Green vegetables, red meat and colon cancer: chlorophyll prevents the cytotoxic and hyperproliferative effects of haem in rat colon.

PubMed

de Vogel, Johan; Jonker-Termont, Denise S M L; van Lieshout, Esther M M; Katan, Martijn B; van der Meer, Roelof

2005-02-01

Diets high in red meat and low in green vegetables are associated with increased colon cancer risk. This association might be partly due to the haem content of red meat. In rats, dietary haem is metabolized in the gut to a cytotoxic factor that increases colonic cytotoxicity and epithelial proliferation. Green vegetables contain chlorophyll, a magnesium porphyrin structurally analogous to haem. We studied whether green vegetables inhibit the unfavourable colonic effects of haem. First, rats were fed a purified control diet or purified diets supplemented with 0.5 mmol haem/kg, spinach (chlorophyll concentration 1.2 mmol/kg) or haem plus spinach (n = 8/group) for 14 days. In a second experiment we also studied a group that received haem plus purified chlorophyll (1.2 mmol/kg). Cytotoxicity of faecal water was determined with a bioassay and colonic epithelial cell proliferation was quantified in vivo by [methyl-(3)H]thymidine incorporation into newly synthesized DNA. Exfoliation of colonocytes was measured as the amount of rat DNA in faeces. In both studies haem increased cytotoxicity of the colonic contents approximately 8-fold and proliferation of the colonocytes almost 2-fold. Spinach or an equimolar amount of chlorophyll supplement in the haem diet inhibited these haem effects completely. Haem clearly inhibited exfoliation of colonocytes, an effect counteracted by spinach and chlorophyll. Finally, size exclusion chromatography showed that chlorophyll prevented formation of the cytotoxic haem metabolite. We conclude that green vegetables may decrease colon cancer risk because chlorophyll prevents the detrimental, cytotoxic and hyperproliferative colonic effects of dietary haem.

High dose rate brachytherapy for prevention of restenosis after percutaneous transluminal coronary angioplasty: Preliminary dosimetric tests of a new source presentation

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

Popowski, Y.; Rouzaud, M.; Kurtz, J.M.

1995-08-30

Balloon dilatation of coronary artery stenosis has become a standard treatment of atherosclerotic heart disease. Restenosis due to excessive intimal cell proliferation, which subsequently occurs in 20-50% of patients, represents one of the major clinical problems in contemporary cardiology, and no satisfactory method for its prevention has thus far been found. Because modest doses of radiation have proved effective in preventing certain types of abnormal cellular proliferation resulting from surgical trauma, and brachytherapy has already been used successfully after dilatation of peripheral arteries, development of a radioactive source suitable for coronary artery applications would be of great interest. Doses obtainedmore » at the surface of the balloon, for a 2-min exposure for the 0.26 mm wire (balloon inflated with air) and the 0.15 mm wire (air or contrast), were 56.5 Gy, 17.8 Gy, 5.4 Gy, respectively. As expected for a beta emitter, the fall-off in dose as a function of depth was rapid. External irradiation from the beta source was negligible. Our experiments indicate that the dose rates attainable at the surface of the angioplasty balloon using this technique allow the doses necessary for the inhibition of intimal cell proliferation to be reached within a relatively short period of time. The thin yttrium-90 wires are very easy to handle, and their mechanical and radioactive properties are well suited to the requirements of the catheterization procedure. 16 refs., 4 figs., 1 tab.« less

Epidermal growth factor receptor inhibition with erlotinib ameliorates anti-Thy 1.1-induced experimental glomerulonephritis.

PubMed

Rintala, Jukka M; Savikko, Johanna; Rintala, Sini E; Palin, Niina; Koskinen, Petri K

2016-06-01

Mesangial proliferative glomerulonephritis is a common glomerular disorder that may lead to end-stage renal disease. Epidermal growth factor (EGF) plays an important role in the regulation of cell growth, proliferation, and differentiation and in the pathology of various renal diseases. Erlotinib is a novel, oral, highly selective tyrosine kinase inhibitor of the EGF receptor. It is clinically used to treat non-small cell lung and pancreatic cancers. Here, we investigated the effect of erlotinib on the progression of mesangioproliferative glomerulonephritis in an experimental model. Mesangial glomerulonephritis was induced with anti-rat Thy-1.1 antibody in male Wistar rats weighing 150-160 g. Rats were treated with erlotinib (10 mg/kg/day p.o.) or vehicle only (polyethylene glycol). Native Wistar rat kidneys were used as histological controls. Serum creatinine levels were measured at day 7. Kidneys were harvested 7 days after antibody administration for histology. Native controls showed no histological signs of glomerular pathology. In the vehicle group, intense glomerular inflammation developed after 7 days and prominent mesangial cell proliferation and glomerular matrix accumulation was seen. Erlotinib was well tolerated and there were no adverse effects during the follow-up period. Erlotinib significantly prevented progression of the glomerular inflammatory response and glomerular mesangial cell proliferation as well as matrix accumulation when compared with the vehicle group. Erlotinib also preserved renal function. These results indicate that erlotinib prevents the early events of experimental mesangial proliferative glomerulonephritis. Therefore, inhibition of the EGF receptor with erlotinib could prevent the progression of glomerulonephritis also in clinical nephrology.

T Cells Encountering Myeloid Cells Programmed for Amino Acid-dependent Immunosuppression Use Rictor/mTORC2 Protein for Proliferative Checkpoint Decisions*

PubMed Central

Van de Velde, Lee-Ann; Subramanian, Chitra; Smith, Amber M.; Barron, Luke; Qualls, Joseph E.; Neale, Geoffrey; Alfonso-Pecchio, Adolfo; Jackowski, Suzanne; Rock, Charles O.; Wynn, Thomas A.; Murray, Peter J.

2017-01-01

Modulation of T cell proliferation and function by immunoregulatory myeloid cells are an essential means of preventing self-reactivity and restoring tissue homeostasis. Consumption of amino acids such as arginine and tryptophan by immunoregulatory macrophages is one pathway that suppresses local T cell proliferation. Using a reduced complexity in vitro macrophage-T cell co-culture system, we show that macrophage arginase-1 is the only factor required by M2 macrophages to block T cells in G1, and this effect is mediated by l-arginine elimination rather than metabolite generation. Tracking how T cells adjust their metabolism when deprived of arginine revealed the significance of macrophage-mediated arginine deprivation to T cells. We found mTORC1 activity was unaffected in the initial G1 block. After 2 days of arginine deprivation, mTORC1 activity declined paralleling a selective down-regulation of SREBP target gene expression, whereas mRNAs involved in glycolysis, gluconeogenesis, and T cell activation were unaffected. Cell cycle arrest was reversible at any point by exogenous arginine, suggesting starved T cells remain poised awaiting nutrients. Arginine deprivation-induced cell cycle arrest was mediated in part by Rictor/mTORC2, providing evidence that this nutrient recognition pathway is a central component of how T cells measure environmental arginine. PMID:27903651

T Cells Encountering Myeloid Cells Programmed for Amino Acid-dependent Immunosuppression Use Rictor/mTORC2 Protein for Proliferative Checkpoint Decisions.

PubMed

Van de Velde, Lee-Ann; Subramanian, Chitra; Smith, Amber M; Barron, Luke; Qualls, Joseph E; Neale, Geoffrey; Alfonso-Pecchio, Adolfo; Jackowski, Suzanne; Rock, Charles O; Wynn, Thomas A; Murray, Peter J

2017-01-06

Modulation of T cell proliferation and function by immunoregulatory myeloid cells are an essential means of preventing self-reactivity and restoring tissue homeostasis. Consumption of amino acids such as arginine and tryptophan by immunoregulatory macrophages is one pathway that suppresses local T cell proliferation. Using a reduced complexity in vitro macrophage-T cell co-culture system, we show that macrophage arginase-1 is the only factor required by M2 macrophages to block T cells in G 1 , and this effect is mediated by l-arginine elimination rather than metabolite generation. Tracking how T cells adjust their metabolism when deprived of arginine revealed the significance of macrophage-mediated arginine deprivation to T cells. We found mTORC1 activity was unaffected in the initial G 1 block. After 2 days of arginine deprivation, mTORC1 activity declined paralleling a selective down-regulation of SREBP target gene expression, whereas mRNAs involved in glycolysis, gluconeogenesis, and T cell activation were unaffected. Cell cycle arrest was reversible at any point by exogenous arginine, suggesting starved T cells remain poised awaiting nutrients. Arginine deprivation-induced cell cycle arrest was mediated in part by Rictor/mTORC2, providing evidence that this nutrient recognition pathway is a central component of how T cells measure environmental arginine. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Developmental regulation of CYCA2s contributes to tissue-specific proliferation in Arabidopsis

PubMed Central

Vanneste, Steffen; Coppens, Frederik; Lee, EunKyoung; Donner, Tyler J; Xie, Zidian; Van Isterdael, Gert; Dhondt, Stijn; De Winter, Freya; De Rybel, Bert; Vuylsteke, Marnik; De Veylder, Lieven; Friml, Jiří; Inzé, Dirk; Grotewold, Erich; Scarpella, Enrico; Sack, Fred; Beemster, Gerrit T S; Beeckman, Tom

2011-01-01

In multicellular organisms, morphogenesis relies on a strict coordination in time and space of cell proliferation and differentiation. In contrast to animals, plant development displays continuous organ formation and adaptive growth responses during their lifespan relying on a tight coordination of cell proliferation. How developmental signals interact with the plant cell-cycle machinery is largely unknown. Here, we characterize plant A2-type cyclins, a small gene family of mitotic cyclins, and show how they contribute to the fine-tuning of local proliferation during plant development. Moreover, the timely repression of CYCA2;3 expression in newly formed guard cells is shown to require the stomatal transcription factors FOUR LIPS/MYB124 and MYB88, providing a direct link between developmental programming and cell-cycle exit in plants. Thus, transcriptional downregulation of CYCA2s represents a critical mechanism to coordinate proliferation during plant development. PMID:21772250

Role of Spm-Cer-S1P signalling pathway in MMP-2 mediated U46619-induced proliferation of pulmonary artery smooth muscle cells: protective role of epigallocatechin-3-gallate.

PubMed

Chowdhury, Animesh; Sarkar, Jaganmay; Chakraborti, Tapati; Chakraborti, Sajal

2015-10-01

During remodelling of pulmonary artery, marked proliferation of pulmonary artery smooth muscle cells (PASMCs) occurs, which contributes to pulmonary hypertension. Thromboxane A2 (TxA2) has been shown to produce pulmonary hypertension. The present study investigates the inhibitory effect of epigallocatechin-3-gallate (EGCG) on the TxA2 mimetic, U46619-induced proliferation of PASMCs. U46619 at a concentration of 10 nM induces maximum proliferation of bovine PASMCs. Both pharmacological and genetic inhibitors of p(38)MAPK, NF-κB and MMP-2 significantly inhibit U46619-induced cell proliferation. EGCG markedly abrogate U46619-induced p(38)MAPK phosphorylation, NF-κB activation, proMMP-2 expression and activation, and also the cell proliferation. U46619 causes an increase in the activation of sphingomyelinase (SMase) and sphingosine kinase (SPHK) and also increase sphingosine 1 phosphate (S1P) level. U46619 also induces phosphorylation of ERK1/2, which phosphorylates SPHK leading to an increase in S1P level. Both pharmacological and genetic inhibitors of SMase and SPHK markedly inhibit U46619-induced cell proliferation. Additionally, pharmacological and genetic inhibitors of MMP-2 markedly abrogate U46619-induced SMase activity and S1P level. EGCG markedly inhibit U46619-induced SMase activity, ERK1/2 and SPHK phosphorylation and S1P level in the cells. Overall, Sphingomyeline-Ceramide-Sphingosine-1-phosphate (Spm-Cer-S1P) signalling axis plays an important role in MMP-2 mediated U46619-induced proliferation of PASMCs. Importantly, EGCG inhibits U46619 induced increase in MMP-2 activation by modulating p(38)MAPK-NFκB pathway and subsequently prevents the cell proliferation. Copyright © 2015 John Wiley & Sons, Ltd.

oxLDL induces endothelial cell proliferation via Rho/ROCK/Akt/p27kip1 signaling: opposite effects of oxLDL and cholesterol loading.

PubMed

Zhang, Chongxu; Adamos, Crystal; Oh, Myung-Jin; Baruah, Jugajyoti; Ayee, Manuela A A; Mehta, Dolly; Wary, Kishore K; Levitan, Irena

2017-09-01

Oxidized modifications of LDL (oxLDL) play a key role in the development of endothelial dysfunction and atherosclerosis. However, the underlying mechanisms of oxLDL-mediated cellular behavior are not completely understood. Here, we compared the effects of two major types of oxLDL, copper-oxidized LDL (Cu 2+ -oxLDL) and lipoxygenase-oxidized LDL (LPO-oxLDL), on proliferation of human aortic endothelial cells (HAECs). Cu 2+ -oxLDL enhanced HAECs' proliferation in a dose- and degree of oxidation-dependent manner. Similarly, LPO-oxLDL also enhanced HAEC proliferation. Mechanistically, both Cu 2+ -oxLDL and LPO-oxLDL enhance HAEC proliferation via activation of Rho, Akt phosphorylation, and a decrease in the expression of cyclin-dependent kinase inhibitor 1B (p27 kip1 ). Both Cu 2+ -oxLDL or LPO-oxLDL significantly increased Akt phosphorylation, whereas an Akt inhibitor, MK2206, blocked oxLDL-induced increase in HAEC proliferation. Blocking Rho with C3 or its downstream target ROCK with Y27632 significantly inhibited oxLDL-induced Akt phosphorylation and proliferation mediated by both Cu 2+ - and LPO-oxLDL. Activation of RhoA was blocked by Rho-GDI-1, which also abrogated oxLDL-induced Akt phosphorylation and HAEC proliferation. In contrast, blocking Rac1 in these cells had no effect on oxLDL-induced Akt phosphorylation or cell proliferation. Moreover, oxLDL-induced Rho/Akt signaling downregulated cell cycle inhibitor p27 kip1 Preloading these cells with cholesterol, however, prevented oxLDL-induced Akt phosphorylation and HAEC proliferation. These findings provide a new understanding of the effects of oxLDL on endothelial proliferation, which is essential for developing new treatments against neovascularization and progression of atherosclerosis. Copyright © 2017 the American Physiological Society.

Combination chemoprevention: future direction of colorectal cancer prevention.

PubMed

Zhou, Ping; Cheng, Shao-Wen; Yang, Rong; Wang, Bing; Liu, Jian

2012-05-01

Recent research has drawn attention to protective effects of chemopreventive agents that reverse, suppress, or prevent the carcinogenic progression using pharmacological or nutritional agents. Aspirin and celecoxib are the promising preventive agents to effectively reduce the risk of colorectal cancer, but such agents are associated with severe gastrointestinal and cardiovascular side effects in long-term administration at high doses. Recently, the strategy that combinational use with several chemopreventive agents at low doses induces greater inhibition of carcinogenesis has become the focus. The nonsteroidal anti-inflammatory drugs (NSAIDs) may combine with ornithine decarboxylase inhibitors, hydroxymethylglutaryl-CoA reductase inhibitors, epidermal growth factor signaling inhibitors, peroxisome proliferator-activated receptor-γ ligands, and tumor necrosis factor-related apoptosis-inducing ligand, to magnify the chemoprophylactic effect. It is noteworthy that the phase III trial of difluoromethylornithine combination with sulidac has shown greater and effective preventive roles, which pave the way for the use of combinations of other agents. The long-term statins and low-dose NSAIDs have also been associated with risk reduction in vitro, in vivo, and in retrospective studies; however, the data are inconsistent. Epidermal growth factor signaling inhibitors, peroxisome proliferator-activated receptor-γ ligands and tumor necrosis factor-related apoptosis-inducing ligand have been demonstrated to potentiate the preventive effects of NSAIDs in vitro and in vivo, but these combinational regimens have not yet been applied to clinical research. The major goal of this study was to review combination chemoprevention for colorectal cancer by means of combining low doses of potential preventive agents to increase their chemoprophylaxis efficacy and to minimize toxicity.

FAK Is Required for Schwann Cell Spreading on Immature Basal Lamina to Coordinate the Radial Sorting of Peripheral Axons with Myelination

PubMed Central

Grove, Matthew

2014-01-01

Without Focal Adhesion Kinase (FAK), developing murine Schwann cells (SCs) proliferate poorly, sort axons inefficiently, and cannot myelinate peripheral nerves. Here we show that FAK is required for the development of SCs when their basal lamina (BL) is fragmentary, but not when it is mature in vivo. Mutant SCs fail to spread on fragmentary BL during development in vivo, and this is phenocopied by SCs lacking functional FAK on low laminin (LN) in vitro. Furthermore, SCs without functional FAK initiate differentiation prematurely, both in vivo and in vitro. In contrast to their behavior on high levels of LN, SCs lacking functional FAK grown on low LN display reduced spreading, proliferation, and indicators of contractility (i.e., stress fibers, arcs, and focal adhesions) and are primed to differentiate. Growth of SCs lacking functional FAK on increasing LN concentrations in vitro revealed that differentiation is not regulated by G1 arrest but rather by cell spreading and the level of contractile actomyosin. The importance of FAK as a critical regulator of the specific response of developing SCs to fragmentary BL was supported by the ability of adult FAK mutant SCs to remyelinate demyelinated adult nerves on mature BL in vivo. We conclude that FAK promotes the spreading and actomyosin contractility of immature SCs on fragmentary BL, thus maintaining their proliferation, and preventing differentiation until they reach high density, thereby promoting radial sorting. Hence, FAK has a critical role in the response of SCs to limiting BL by promoting proliferation and preventing premature SC differentiation. PMID:25274820

GLIS3 is indispensable for TSH/TSHR-dependent thyroid hormone biosynthesis and follicular cell proliferation

PubMed Central

Kang, Hong Soon; Kumar, Dhirendra; Liao, Grace; Lichti-Kaiser, Kristin; Gerrish, Kevin; Liao, Xiao-Hui; Refetoff, Samuel; Jothi, Raja; Jetten, Anton M.

2017-01-01

Deficiency in Krüppel-like zinc finger transcription factor GLI-similar 3 (GLIS3) in humans is associated with the development of congenital hypothyroidism. However, the functions of GLIS3 in the thyroid gland and the mechanism by which GLIS3 dysfunction causes hypothyroidism are unknown. In the current study, we demonstrate that GLIS3 acts downstream of thyroid-stimulating hormone (TSH) and TSH receptor (TSHR) and is indispensable for TSH/TSHR-mediated proliferation of thyroid follicular cells and biosynthesis of thyroid hormone. Using ChIP-Seq and promoter analysis, we demonstrate that GLIS3 is critical for the transcriptional activation of several genes required for thyroid hormone biosynthesis, including the iodide transporters Nis and Pds, both of which showed enhanced GLIS3 binding at their promoters. The repression of cell proliferation of GLIS3-deficient thyroid follicular cells was due to the inhibition of TSH-mediated activation of the mTOR complex 1/ribosomal protein S6 (mTORC1/RPS6) pathway as well as the reduced expression of several cell division–related genes regulated directly by GLIS3. Consequently, GLIS3 deficiency in a murine model prevented the development of goiter as well as the induction of inflammatory and fibrotic genes during chronic elevation of circulating TSH. Our study identifies GLIS3 as a key regulator of TSH/TSHR-mediated thyroid hormone biosynthesis and proliferation of thyroid follicular cells and uncovers a mechanism by which GLIS3 deficiency causes neonatal hypothyroidism and prevents goiter development. PMID:29083325

Photoprotective Properties of Isothiocyanate and Nitrile Glucosinolate Derivatives From Meadowfoam (Limnanthes alba) Against UVB Irradiation in Human Skin Equivalent

PubMed Central

Carpenter, Evan L.; Le, Mai N.; Miranda, Cristobal L.; Reed, Ralph L.; Stevens, Jan F.; Indra, Arup K.; Ganguli-Indra, Gitali

2018-01-01

Exposure to ultraviolet B (UVB) irradiation of the skin leads to numerous dermatological concerns including skin cancer and accelerated aging. Natural product glucosinolate derivatives, like sulforaphane, have been shown to exhibit chemopreventive and photoprotective properties. In this study, we examined meadowfoam (Limnanthes alba) glucosinolate derivatives, 3-methoxybenzyl isothiocyanate (MBITC) and 3-methoxyphenyl acetonitrile (MPACN), for their activity in protecting against the consequences of UV exposure. To that end, we have exposed human primary epidermal keratinocytes (HPEKs) and 3D human skin reconstructed in vitro (EpiDermTM FT-400) to UVB insult and investigated whether MBITC and MPACN treatment ameliorated the harmful effects of UVB damage. Activity was determined by the compounds’ efficacy in counteracting UVB-induced DNA damage, matrix-metalloproteinase (MMP) expression, and proliferation. We found that in monolayer cultures of HPEK, MBITC and MPACN did not protect against a UVB-induced loss in proliferation and MBITC itself inhibited cell proliferation. However, in human reconstructed skin-equivalents, MBITC and MPACN decrease epidermal cyclobutane pyrimidine dimers (CPDs) and significantly reduce total phosphorylated γH2A.X levels. Both MBITC and MPACN inhibit UVB-induced MMP-1 and MMP-3 expression indicating their role to prevent photoaging. Both compounds, and MPACN in particular, showed activity against UVB-induced proliferation as indicated by fewer epidermal PCNA+ cells and prevented UVB-induced hyperplasia as determined by a reduction in reconstructed skin epidermal thickness (ET). These data demonstrate that MBITC and MPACN exhibit promising anti-photocarcinogenic and anti-photoaging properties in the skin microenvironment and could be used for therapeutic interventions. PMID:29867483

Photoprotective Properties of Isothiocyanate and Nitrile Glucosinolate Derivatives From Meadowfoam (Limnanthes alba) Against UVB Irradiation in Human Skin Equivalent.

PubMed

Carpenter, Evan L; Le, Mai N; Miranda, Cristobal L; Reed, Ralph L; Stevens, Jan F; Indra, Arup K; Ganguli-Indra, Gitali

2018-01-01

Exposure to ultraviolet B (UVB) irradiation of the skin leads to numerous dermatological concerns including skin cancer and accelerated aging. Natural product glucosinolate derivatives, like sulforaphane, have been shown to exhibit chemopreventive and photoprotective properties. In this study, we examined meadowfoam ( Limnanthes alba ) glucosinolate derivatives, 3-methoxybenzyl isothiocyanate (MBITC) and 3-methoxyphenyl acetonitrile (MPACN), for their activity in protecting against the consequences of UV exposure. To that end, we have exposed human primary epidermal keratinocytes (HPEKs) and 3D human skin reconstructed in vitro (EpiDerm TM FT-400) to UVB insult and investigated whether MBITC and MPACN treatment ameliorated the harmful effects of UVB damage. Activity was determined by the compounds' efficacy in counteracting UVB-induced DNA damage, matrix-metalloproteinase (MMP) expression, and proliferation. We found that in monolayer cultures of HPEK, MBITC and MPACN did not protect against a UVB-induced loss in proliferation and MBITC itself inhibited cell proliferation. However, in human reconstructed skin-equivalents, MBITC and MPACN decrease epidermal cyclobutane pyrimidine dimers (CPDs) and significantly reduce total phosphorylated γH2A.X levels. Both MBITC and MPACN inhibit UVB-induced MMP-1 and MMP-3 expression indicating their role to prevent photoaging. Both compounds, and MPACN in particular, showed activity against UVB-induced proliferation as indicated by fewer epidermal PCNA+ cells and prevented UVB-induced hyperplasia as determined by a reduction in reconstructed skin epidermal thickness (ET). These data demonstrate that MBITC and MPACN exhibit promising anti-photocarcinogenic and anti-photoaging properties in the skin microenvironment and could be used for therapeutic interventions.

Sex Differences in Stress and Group Housing Effects on the Number of Newly Proliferated Cells and Neuroblasts in Middle-Aged Dentate Gyrus.

PubMed

Tzeng, Wen-Yu; Wu, Hsin-Hua; Wang, Ching-Yi; Chen, Jin-Chung; Yu, Lung; Cherng, Chianfang G

2016-01-01

Sex differences in stress and coping responses have been frequently documented in aged people, while whether such differences in aged people may appear at the middle age are unknown. This study was undertaken to study the impact of acute stress and social interaction on early neurogenesis in the dentate gyrus (DG) and hippocampus-related memory in two sexes of middle-aged mice. The number of newly proliferated cells, neuroblasts in DG, the object recognition and location memory in 9-month-old male and female C57BL/6N mice were assessed under baseline conditions as well as following an acute stressor regimen and group housing. Three conspecific companions, serving as "the housing group," were used to model the social interaction throughout the stressor regimen. Males had lower numbers of newly proliferated cells and neuroblasts under baseline conditions as compared to females. The stressor regimen caused rapid decreases in the number of newly proliferated cells and neuroblasts in female DG but no obvious changes were observed in male DG. Group housing, regardless of companions' age, prevented the stress-induced decreases in the number of newly proliferated cells and neuroblasts in female DG. In contrast, the presence of young or age-matched companions potentiated the stress effect in males by decreasing the number of newly proliferated cells and neuroblasts. Finally, neither the stressor regimen nor group housing affected mouse performances in the object recognition and location memory in either sex. These findings, taken together, provide evidence to support a notion that middle-aged females appear to demonstrate more stress susceptibility on early neurogenesis in DG as compared to middle-aged males, although the hippocampus-related memory performances are comparable and not affected by stress in these males and females. Experiencing stress, middle-aged females are more prone to benefit from social interaction as compared to middle-aged males in this regard. We suggest, accordingly, that involving social interaction may afford a therapeutic advance in preventing stress-produced decreases in early neurogenesis in middle-aged females' DG.

Simvastatin inhibits the proliferation of human prostate cancer PC-3 cells via down-regulation of the insulin-like growth factor 1 receptor

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

Sekine, Yoshitaka; Furuya, Yosuke; Nishii, Masahiro

2008-07-25

Recently, statins have been being studied for their proapoptic and antimetastatic effects. However, the exact mechanisms of their anticancer action are still unclear. Dolichyl phosphate is a nonsterol isoprenoid derivative in the mevalonate pathway that affects the expression of the Insulin-like growth factor 1 receptor (IGF-1R). IGF-1R activation is required for prostate cell proliferation; therefore, IGF-1R inhibitory agents may be of preventive and/or therapeutic value. In this study, the effects of simvastatin on IGF-1R signaling in prostate cancer PC-3 cells were examined. Simvastatin suppressed proliferation and induced apoptosis of PC-3, and the expression of IGF-1R was suppressed by simvastatin. Knockdownmore » of IGF-1R by siRNA led to inhibition of proliferation of PC-3. Simvastatin also inhibited IGF-1-induced activation of both ERK and Akt signaling and IGF-1-induced PC-3 cell proliferation. Our results suggest statins are potent inhibitors of the IGF-1/IGF-1R system in prostate cancer cells and may be beneficial in prostate cancer treatment.« less

Factors Affecting the Design of Short-Term Study-Abroad Programs: An Exploratory Study of Two Business Schools

ERIC Educational Resources Information Center

Ramakrishna, Hindupur; Sarkar, Avijit; Vijayaraman, Bindiganavale

2016-01-01

Study-abroad programs have played a significant role in globalization of business curricula over the years. Short-term study-abroad programs (STSAPs) are proliferating in business schools and provide a viable alternative of studying abroad to students who are unable to participate in programs of longer durations due to disruption in family, work,…

The effect of the immunophilin ligands rapamycin and FK506 on proliferation of mast cells and other hematopoietic cell lines.

PubMed Central

Hultsch, T; Martin, R; Hohman, R J

1992-01-01

The immunosuppressive drugs FK506 and cyclosporin A have an identical spectrum of activities with respect to IgE receptor (Fc epsilon RI)-mediated exocytosis from mast cells and T cell receptor-mediated transcription of IL-2. These findings suggest a common step in receptor-mediated signal transduction leading to exocytosis and transcription and imply that immunosuppressive drugs target specific signal transduction pathways, rather than specific cell types. This hypothesis is supported by studies on the effect of rapamycin on IL-3 dependent proliferation of the rodent mast cell line PT18. Rapamycin inhibits proliferation of PT18 cells, achieving a plateau of 80% inhibition at 1 nM. This inhibition is prevented in a competitive manner by FK506, a structural analogue of rapamycin. Proliferation of rat basophilic leukemia cells and WEHI-3 cells was also inhibited, at doses comparable to those shown previously to inhibit IL-2-dependent proliferation of cytotoxic T lymphocyte line (CTLL) cells. In contrast, proliferation of A-431 cells, a epidermoid cell line, was not affected by rapamycin. DNA histograms indicate that complexes formed between the rapamycin-FK506-binding protein (FKBP) and rapamycin arrest-proliferating PT18 cells in the G0/G1-phase. It is concluded that FKBP-rapamycin complexes may inhibit proliferative signals emanating from IL-3 receptors, resulting in growth arrest of cytokine-dependent, hematopoietic cells. PMID:1384815

Promising practices in the prevention of intimate partner violence among adolescents.

PubMed

De Grace, Alyssa; Clarke, Angela

2012-01-01

To inform practitioners and researchers interested in the prevention of intimate partner violence (IPV) among adolescents, 9 principles of effective prevention programs (Nation et al., 2003) were described and examples of how these principles have been incorporated into existing teen dating violence prevention programs were provided. An investigation of current prevention practices for adolescent IPV resulted in one noteworthy program that has successfully incorporated all 9 principles of effective prevention programming-Safe Dates (Substance Abuse and Mental Health Services Administration, National Registry of Evidence-based Programs and Practices [SAMHSA-NREPP], 2006). Although Safe Dates serves as a model teen dating violence prevention program, it may not be equally effective across contexts and diverse groups. Therefore, as researchers and practitioners continue to develop and refine programs to reduce adolescent IPV, the principles of effective prevention programs should serve as a guiding framework.

Novel strategy for prevention of esophageal stricture after endoscopic surgery.

PubMed

Mizutani, Taro; Tadauchi, Akimitsu; Arinobe, Manabu; Narita, Yuji; Kato, Ryuji; Niwa, Yasumasa; Ohmiya, Naoki; Itoh, Akihiro; Hirooka, Yoshiki; Honda, Hiroyuki; Ueda, Minoru; Goto, Hidemi

2010-01-01

Recently, novel endoscopic surgery, including endoscopic submucosal dissection (ESD), was developed to resect a large superficial gastrointestinal cancer. However, circumferential endoscopic surgery in the esophagus can lead to esophageal stricture that affects the patient's quality of life. This major complication is caused by scar formation, and develops during the two weeks after endoscopic surgery. We hypothesized that local administration of a controlled release anti-scarring agent can prevent esophageal stricture after endoscopic surgery. The aims of this study were to develop an endoscopically injectable anti-scarring drug delivery system, and to verify the efficacy of our strategy to prevent esophageal stricture. We focused on 5-Fluorouracil (5-FU) as an anti-scarring agent, which has already been shown to be effective not only for treatment of cancers, but also for treatment of hypertrophic skin scars. 5-FU was encapsulated by liposome, and then mixed with injectable 2% atelocollagen (5FLC: 5FU-liposome-collagen) to achieve sustained release. An in vitro 5-FU releasing test from 5FLC was performed using high-performance liquid chromatography (HPLC). Inhibition of cell proliferation was investigated using normal human dermal fibroblast cells (NHDF) with 5FLC. In addition, a canine esophageal mucosal resection was carried out, and 5FLC was endoscopically injected into the ulcer immediately after the operation, and compared with a similar specimen injected with saline as a control. 5-FU was gradually released from 5FLC for more than 2 weeks in vitro. The solution of 5-FU released from 5FLC inhibited NHDF proliferation more effectively than 5-FU alone. In the canine model, no findings of stricture were observed in the 5FLC-treated dog at 4 weeks after the operation and no vomiting occurred. In contrast, marked esophageal strictures were observed with repeated vomiting in the control group. Submucosal fibrosis was markedly reduced histologically in the 5FLC-treated dog compared with the control. 5FLC showed sustained release of 5-FU and decreased cell proliferation in vitro. The clinically relevant canine model demonstrated that local endoscopic injection of 5FLC can prevent post-operative esophageal stricture. These results suggest that our strategy may be useful for preventing post-operative esophageal stricture.

Prevention of posterior capsular opacification through cyclooxygenase-2 inhibition

PubMed Central

Barden, Curtis A; Lu, Ping; Kusewitt, Donna F.; Colitz, Carmen M. H.

2007-01-01

Purpose To determine if cyclooxygenase-2 (COX-2) is upregulated when lens epithelial cells (LEC) in clinical samples of cataracts and posterior capsule opacification (PCO) undergo epithelial-mesenchymal transition (EMT)-like changes. We also wanted to learn if inhibition of the enzymatic activity of COX-2 could prevent PCO formation. Methods To ensure that EMT-like changes were occurring in LEC, real-time RT-PCR was used to examine expression of EMT markers. Clinical samples of canine cataracts and PCO were examined for COX-2 expression using immunohistochemistry, western blot analysis, and real-time RT-PCR. The COX-2 inhibitors, rofecoxib and celecoxib, were used in an ex vivo model of PCO formation, and the effects on cellular migration, proliferation, and apoptosis were analyzed using immunohistochemistry and western blots. Prostaglandin E2 (PGE2) expression was examined with ELISA. Results Markers of EMT, such as lumican, Snail, Slug, and COX-2 were expressed in LEC. In clinical samples of cataracts and PCO, there was overexpression of COX-2 protein and mRNA. Both rofecoxib and celecoxib were effective at inhibiting PCO formation in our ex vivo model. Prevention of PCO with the COX-2 inhibitors appeared to work through decreased migration and proliferation, and increased apoptosis. Neither of the drugs had a toxic effect on confluent LEC and appeared to inhibit PCO through their pharmacologic action. Synthesis of PGE2 was inhibiting in the capsules treated with the COX-2 inhibiting drugs. Conclusions Extracapsular phacoemulsification cataract surgery is the most common surgical procedure performed in human and veterinary ophthalmology. The most frequent postoperative complication is PCO. The LEC that remain adhered to the lens capsule undergo EMT-like changes, proliferate, and migrate across the posterior lens capsule causing opacities. We have shown that COX-2, a protein associated with EMT, is upregulated in canine cataracts and PCO. Inhibiting the enzymatic activity effectively prevented EMT of LEC in our ex vivo model of PCO through pharmacologic action, and not acute toxicity. These findings indicate that using COX-2 inhibitors in vivo may be an effective technique in preventing PCO. PMID:17563718

Green Chemistry and Environmental Remediation

EPA Science Inventory

Abstract: Nutrient remediation and recovery is a growing concern for two key reasons: (i) the prevention of harmful algal bloom proliferation, and (ii) the recycling of nutrients (e.g., phosphates) as they are non-renewable resources which are quickly being depleted. A wide range...

Images of World Society: A Third World View.

ERIC Educational Resources Information Center

Gopal, Sarvepalli

1982-01-01

Discusses conditions in the Third World which prevent the development of a harmonious world society. The effects of nationalism, nuclear proliferation, racism, political and economic inequities, and social and religious conservatism on the growth of a global outlook are considered. (AM)

Sociodemographic Diversity and Distance Education: Who Drops out from Academic Programs and Why?

ERIC Educational Resources Information Center

Stoessel, Katharina; Ihme, Toni A.; Barbarino, Maria-Luisa; Fisseler, Björn; Stürmer, Stefan

2015-01-01

Current higher education is characterized by a proliferation of distance education programs and by an increasing inclusion of nontraditional students. In this study we investigated whether and to what extent nontraditional students are particularly at risk for attrition (vs. graduating) from distance education programs. We conducted a secondary…

BabeLO--An Extensible Converter of Programming Exercises Formats

ERIC Educational Resources Information Center

Queiros, R.; Leal, J. P.

2013-01-01

In the last two decades, there was a proliferation of programming exercise formats that hinders interoperability in automatic assessment. In the lack of a widely accepted standard, a pragmatic solution is to convert content among the existing formats. BabeLO is a programming exercise converter providing services to a network of heterogeneous…

On the role of subtype selective adenosine receptor agonists during proliferation and osteogenic differentiation of human primary bone marrow stromal cells.

PubMed

Costa, M Adelina; Barbosa, A; Neto, E; Sá-e-Sousa, A; Freitas, R; Neves, J M; Magalhães-Cardoso, T; Ferreirinha, F; Correia-de-Sá, P

2011-05-01

Purines are important modulators of bone cell biology. ATP is metabolized into adenosine by human primary osteoblast cells (HPOC); due to very low activity of adenosine deaminase, the nucleoside is the end product of the ecto-nucleotidase cascade. We, therefore, investigated the expression and function of adenosine receptor subtypes (A(1) , A(2A) , A(2B) , and A(3) ) during proliferation and osteogenic differentiation of HPOC. Adenosine A(1) (CPA), A(2A) (CGS21680C), A(2B) (NECA), and A(3) (2-Cl-IB-MECA) receptor agonists concentration-dependently increased HPOC proliferation. Agonist-induced HPOC proliferation was prevented by their selective antagonists, DPCPX, SCH442416, PSB603, and MRS1191. CPA and NECA facilitated osteogenic differentiation measured by increases in alkaline phosphatase (ALP) activity. This contrasts with the effect of CGS21680C which delayed HPOC differentiation; 2-Cl-IB-MECA was devoid of effect. Blockade of the A(2B) receptor with PSB603 prevented osteogenic differentiation by NECA. In the presence of the A(1) antagonist, DPCPX, CPA reduced ALP activity at 21 and 28 days in culture. At the same time points, blockade of A(2A) receptors with SCH442416 transformed the inhibitory effect of CGS21680C into facilitation. Inhibition of adenosine uptake with dipyridamole caused a net increase in osteogenic differentiation. The presence of all subtypes of adenosine receptors on HPOC was confirmed by immunocytochemistry. Data show that adenosine is an important regulator of osteogenic cell differentiation through the activation of subtype-specific receptors. The most abundant A(2B) receptor seems to have a consistent role in cell differentiation, which may be balanced through the relative strengths of A(1) or A(2A) receptors determining whether osteoblasts are driven into proliferation or differentiation. Copyright © 2010 Wiley-Liss, Inc.

Vinpocetine attenuates neointimal hyperplasia in diabetic rat carotid arteries after balloon injury.

PubMed

Wang, Ke; Wen, Li; Peng, Wenhui; Li, Hailing; Zhuang, Jianhui; Lu, Yuyan; Liu, Baoxin; Li, Xiankai; Li, Weiming; Xu, Yawei

2014-01-01

Diabetes exacerbates abnormal vascular smooth muscle cell (VSMC) accumulation in response to arterial wall injury. Vinpocetine has been shown to improve vascular remolding; however, little is known about the direct effects of vinpocetine on vascular complications mediated by diabetes. The objective of this study was to determine the effects of vinpocetine on hyperglycemia-facilitated neointimal hyperplasia and explore its possible mechanism. Nondiabetic and diabetic rats were subjected to balloon injury of the carotid artery followed by 3-week treatment with either vinpocetine (10 mg/kg/day) or saline. Morphological analysis and proliferating cell nuclear antigen (PCNA) immunostaining were performed on day 21. Rat VSMCs proliferation was determined with 5-ethynyl-20-deoxyuridine cell proliferation assays. Chemokinesis was monitored with scratch assays, and production of reactive oxygen species (ROS) was assessed using a 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) flow cytometric assay. Apoptosis was detected by annexin V-FITC/PI flow cytometric assay. Cell signaling was assessed by immunblotting. Vinpocetine prevented intimal hyperplasia in carotid arteries in both normal (I/M ratio: 93.83 ± 26.45% versus 143.2 ± 38.18%, P<0.05) and diabetic animals (I/M ratio: 120.5 ± 42.55% versus 233.46 ± 33.98%, P<0.05) when compared to saline. The in vitro study demonstrated that vinpocetine significantly inhibited VSMCs proliferation and chemokinesis as well as ROS generation and apoptotic resistance, which was induced by high glucose (HG) treatment. Vinpocetine significantly abolished HG-induced phosphorylation of Akt and JNK1/2 without affecting their total levels. For downstream targets, HG-induced phosphorylation of IκBα was significantly inhibited by vinpocetine. Vinpocetine also attenuated HG-enhanced expression of PCNA, cyclin D1 and Bcl-2. Vinpocetine attenuated neointimal formation in diabetic rats and inhibited HG-induced VSMCs proliferation, chemokinesis and apoptotic resistance by preventing ROS activation and affecting MAPK, PI3K/Akt, and NF-κB signaling.

Vinpocetine Attenuates Neointimal Hyperplasia in Diabetic Rat Carotid Arteries after Balloon Injury

PubMed Central

Peng, Wenhui; Li, Hailing; Zhuang, Jianhui; Lu, Yuyan; Liu, Baoxin; Li, Xiankai; Li, Weiming; Xu, Yawei

2014-01-01

Background Diabetes exacerbates abnormal vascular smooth muscle cell (VSMC) accumulation in response to arterial wall injury. Vinpocetine has been shown to improve vascular remolding; however, little is known about the direct effects of vinpocetine on vascular complications mediated by diabetes. The objective of this study was to determine the effects of vinpocetine on hyperglycemia-facilitated neointimal hyperplasia and explore its possible mechanism. Materials and Methods Nondiabetic and diabetic rats were subjected to balloon injury of the carotid artery followed by 3-week treatment with either vinpocetine (10 mg/kg/day) or saline. Morphological analysis and proliferating cell nuclear antigen (PCNA) immunostaining were performed on day 21. Rat VSMCs proliferation was determined with 5-ethynyl-20-deoxyuridine cell proliferation assays. Chemokinesis was monitored with scratch assays, and production of reactive oxygen species (ROS) was assessed using a 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) flow cytometric assay. Apoptosis was detected by annexin V-FITC/PI flow cytometric assay. Cell signaling was assessed by immunblotting. Results Vinpocetine prevented intimal hyperplasia in carotid arteries in both normal (I/M ratio: 93.83 ± 26.45% versus 143.2 ± 38.18%, P<0.05) and diabetic animals (I/M ratio: 120.5 ± 42.55% versus 233.46 ± 33.98%, P<0.05) when compared to saline. The in vitro study demonstrated that vinpocetine significantly inhibited VSMCs proliferation and chemokinesis as well as ROS generation and apoptotic resistance, which was induced by high glucose (HG) treatment. Vinpocetine significantly abolished HG-induced phosphorylation of Akt and JNK1/2 without affecting their total levels. For downstream targets, HG-induced phosphorylation of IκBα was significantly inhibited by vinpocetine. Vinpocetine also attenuated HG-enhanced expression of PCNA, cyclin D1 and Bcl-2. Conclusions Vinpocetine attenuated neointimal formation in diabetic rats and inhibited HG-induced VSMCs proliferation, chemokinesis and apoptotic resistance by preventing ROS activation and affecting MAPK, PI3K/Akt, and NF-κB signaling. PMID:24819198

Targeting CCl4 -induced liver fibrosis by RNA interference-mediated inhibition of cyclin E1 in mice.

PubMed

Bangen, Jörg-Martin; Hammerich, Linda; Sonntag, Roland; Baues, Maike; Haas, Ute; Lambertz, Daniela; Longerich, Thomas; Lammers, Twan; Tacke, Frank; Trautwein, Christian; Liedtke, Christian

2017-10-01

Initiation and progression of liver fibrosis requires proliferation and activation of resting hepatic stellate cells (HSCs). Cyclin E1 (CcnE1) is the regulatory subunit of the cyclin-dependent kinase 2 (Cdk2) and controls cell cycle re-entry. We have recently shown that genetic inactivation of CcnE1 prevents activation, proliferation, and survival of HSCs and protects from liver fibrogenesis. The aim of the present study was to translate these findings into preclinical applications using an RNA interference (RNAi)-based approach. CcnE1-siRNA (small interfering RNA) efficiently inhibited CcnE1 gene expression in murine and human HSC cell lines and in primary HSCs, resulting in diminished proliferation and increased cell death. In C57BL/6 wild-type (WT) mice, delivery of stabilized siRNA using a liposome-based carrier targeted approximately 95% of HSCs, 70% of hepatocytes, and 40% of CD45 + cells after single injection. Acute CCl 4 -mediated liver injury in WT mice induced endogenous CcnE1 expression and proliferation of surviving hepatocytes and nonparenchymal cells, including CD45 + leukocytes. Pretreatment with CcnE1-siRNA reverted CcnE1 induction to baseline levels of healthy mice, which was associated with reduced liver injury, diminished proliferation of hepatocytes and leukocytes, and attenuated overall inflammatory response. For induction of liver fibrosis, WT mice were challenged with CCl 4 for 4-6 weeks. Co-treatment with CcnE1-siRNA once a week was sufficient to continuously block CcnE1 expression and cell-cycle activity of hepatocytes and nonparenchymal cells, resulting in significantly ameliorated liver fibrosis and inflammation. Importantly, CcnE1-siRNA also prevented progression of liver fibrosis if applied after onset of chronic liver injury. Therapeutic targeting of CcnE1 in vivo using RNAi is feasible and has high antifibrotic activity. (Hepatology 2017;66:1242-1257). © 2017 by the American Association for the Study of Liver Diseases.

Epigenetic influences on sensory regeneration: histone deacetylases regulate supporting cell proliferation in the avian utricle.

PubMed

Slattery, Eric L; Speck, Judith D; Warchol, Mark E

2009-09-01

The sensory hair cells of the cochlea and vestibular organs are essential for normal hearing and balance function. The mammalian ear possesses a very limited ability to regenerate hair cells and their loss can lead to permanent sensory impairment. In contrast, hair cells in the avian ear are quickly regenerated after acoustic trauma or ototoxic injury. The very different regenerative abilities of the avian vs. mammalian ear can be attributed to differences in injury-evoked expression of genes that either promote or inhibit the production of new hair cells. Gene expression is regulated both by the binding of cis-regulatory molecules to promoter regions as well as through structural modifications of chromatin (e.g., methylation and acetylation). This study examined effects of histone deacetylases (HDACs), whose main function is to modify histone acetylation, on the regulation of regenerative proliferation in the chick utricle. Cultures of regenerating utricles and dissociated cells from the utricular sensory epithelia were treated with the HDAC inhibitors valproic acid, trichostatin A, sodium butyrate, and MS-275. All of these molecules prevent the enzymatic removal of acetyl groups from histones, thus maintaining nuclear chromatin in a "relaxed" (open) configuration. Treatment with all inhibitors resulted in comparable decreases in supporting cell proliferation. We also observed that treatment with the HDAC1-, 2-, and 3-specific inhibitor MS-275 was sufficient to reduce proliferation and that two class I HDACs--HDAC1 and HDAC2--were expressed in the sensory epithelium of the utricle. These results suggest that inhibition of specific type I HDACs is sufficient to prevent cell cycle entry in supporting cells. Notably, treatment with HDAC inhibitors did not affect the differentiation of replacement hair cells. We conclude that histone deacetylation is a positive regulator of regenerative proliferation but is not critical for avian hair cell differentiation.

Plasma Rich in Growth Factors Induces Cell Proliferation, Migration, Differentiation, and Cell Survival of Adipose-Derived Stem Cells

PubMed Central

Mellado-López, Maravillas; Griffeth, Richard J.; Meseguer-Ripolles, Jose; García, Montserrat

2017-01-01

Adipose-derived stem cells (ASCs) are a promising therapeutic alternative for tissue repair in various clinical applications. However, restrictive cell survival, differential tissue integration, and undirected cell differentiation after transplantation in a hostile microenvironment are complications that require refinement. Plasma rich in growth factors (PRGF) from platelet-rich plasma favors human and canine ASC survival, proliferation, and delaying human ASC senescence and autophagocytosis in comparison with serum-containing cultures. In addition, canine and human-derived ASCs efficiently differentiate into osteocytes, adipocytes, or chondrocytes in the presence of PRGF. PRGF treatment induces phosphorylation of AKT preventing ASC death induced by lethal concentrations of hydrogen peroxide. Indeed, AKT inhibition abolished the PRGF apoptosis prevention in ASC exposed to 100 μM of hydrogen peroxide. Here, we show that canine ASCs respond to PRGF stimulus similarly to the human cells regarding cell survival and differentiation postulating the use of dogs as a suitable translational model. Overall, PRGF would be employed as a serum substitute for mesenchymal stem cell amplification to improve cell differentiation and as a preconditioning agent to prevent oxidative cell death. PMID:29270200

Prevention of Intraabdominal Adhesions by Local and Systemic Administration of Immunosuppressive Drugs

PubMed Central

Peker, Kemal; Inal, Abdullah; Sayar, Ilyas; Sahin, Murat; Gullu, Huriye; Inal, Duriye Gul; Isik, Arda

2013-01-01

Background: Intraperitoneal adhesion formation is a serious postsurgical issue. Adhesions develop after damage to the peritoneum by surgery, irradiation, infection or trauma. Objectives: Using a rat model, we compared the effectiveness of systemic and intraperitoneally administered common immunosuppressive drugs for prevention of postoperative intraperitoneal adhesions. Materials and Methods: Peritoneal adhesions were induced in 98 female Wistar-Albino rats by cecal abrasion and peritoneal excision. Rats were randomly separated into seven groups, each containing fourteen rats, and the standard experimental model was applied to all of rats. 14 days later, rats were euthanized, intraperitoneal adhesions were scored and tissues were examined histologically using hematoxylin/eosin and Masson’s trichrome staining. Results: Throughout the investigation, no animal died during or after surgery. In all of experimental groups, decrease in fibrosis was statistically significant. Decrease in fibrosis was most prominently in intraperitoneal tacrolimus group (P = 0.000), and decrease was least in intraperitoneal cyclosporine group (P = 0.022). Vascular proliferation was significantly decreased in all experimental groups (P < 0.05) except for systemic tacrolimus group (P = 0.139). Most prominent reduction in vascular proliferation was in intraperitoneal tacrolimus group (P = 0.000). Conclusions: Administration of immunosuppressive drugs is effective for prevention of intraperitoneal adhesions. PMID:24693396

Protective effect of crocin on ultraviolet B‑induced dermal fibroblast photoaging.

PubMed

Deng, Mingwu; Li, Dong; Zhang, Yichen; Zhou, Guangdong; Liu, Wei; Cao, Yilin; Zhang, Wenjie

2018-06-11

Ultraviolet B (UVB) radiation induces the production of reactive oxygen species (ROS), resulting in the aging of dermal fibroblasts. Crocin, a bioactive constituent of Crocus sativus, possesses anti‑oxidation effects. The purpose of the present study was to evaluate the protective effect of crocin on UVB‑induced dermal fibroblast photoaging. Human dermal fibroblasts were isolated and cultured with different concentrations of crocin prior to and following exposure to UVB irradiation. The senescent phenotypes of cells were evaluated, including cell proliferation, cell cycle, senescence‑associated β‑galactosidase (SA‑β‑gal) expression, intracellular ROS, expression of antioxidant protein glutathione peroxidase 1 (GPX‑1) and extracellular matrix protein collagen type 1 (Col‑1). Crocin rescued the cell proliferation inhibited by UVB irradiation, prevented cell cycle arrest and markedly decreased the number of SA‑β‑gal‑positive cells. In addition, crocin reduced UVB‑induced ROS by increasing GPX‑1 expression and other direct neutralization effects. Furthermore, crocin promoted the expression of the extracellular matrix protein Col‑1. Crocin could effectively prevent UVB‑induced cell damage via the reduction of intracellular ROS; thus, it could potentially be used in the prevention of skin photoaging.

Delayed reendothelialization with rapamycin is rescued by the addition of nicorandil in balloon-injured rat carotid arteries.

PubMed

Zhang, Ying Qian; Tian, Feng; Chen, Jin Song; Chen, Yun Dai; Zhou, Ying; Li, Bo; Ma, Qiang; Zhang, Ying

2016-11-15

Rapamycin is an immunosuppressive agent that is added to drug eluting stents. It prevents restenosis, but it also impairs reendothelialization. Nicorandil is a hybrid agent with adenosine triphosphated (ATP)-sensitive K+ (KATP) channel opener and nitrate properties. It prevents oxidative stress and cell apoptosis induced by rapamycin in endothelial cells in vitro. However, whether nicorandil promotes reendothelialization after angioplasty delayed by rapamycin remains to be determined. Balloon injury model was established in SD rats. Nicorandil increased reendothelialization impaired by rapamycin, and it decreased xanthine oxidase (XO)-generated reactive oxygen species (ROS) induced by rapamycin. In addition, eNOS expression inhibited by rapamycin was increased by nicorandil in vivo. In vitro, rapamycin-impeded cardiac microvascular endothelial cells (CMECs) migration, proliferation and rapamycin-induced ROS production were reversed by nicorandil. Knockdown of XO partially inhibited rapamycin-induced ROS production and cell apoptosis in CMECs, and it promoted CMECs migration and proliferation suppressed by rapamycin. Knockdown of Akt partially prevents eNOS upregulation promoted by nicorandil. The beneficial effect of nicorandil is exhibited by inhibiting XO and up-regulating Akt pathway. Nicorandil combined with rapamycin in effect rescue the deficiencies of rapamycin alone in arterial healing after angioplasty.

Delayed reendothelialization with rapamycin is rescued by the addition of nicorandil in balloon-injured rat carotid arteries

PubMed Central

Zhang, Ying Qian; Tian, Feng; Chen, Jin Song; Chen, Yun Dai; Zhou, Ying; Li, Bo; Ma, Qiang; Zhang, Ying

2016-01-01

Rapamycin is an immunosuppressive agent that is added to drug eluting stents. It prevents restenosis, but it also impairs reendothelialization. Nicorandil is a hybrid agent with adenosine triphosphated (ATP)-sensitive K+ (KATP) channel opener and nitrate properties. It prevents oxidative stress and cell apoptosis induced by rapamycin in endothelial cells in vitro. However, whether nicorandil promotes reendothelialization after angioplasty delayed by rapamycin remains to be determined. Balloon injury model was established in SD rats. Nicorandil increased reendothelialization impaired by rapamycin, and it decreased xanthine oxidase (XO)-generated reactive oxygen species (ROS) induced by rapamycin. In addition, eNOS expression inhibited by rapamycin was increased by nicorandil in vivo. In vitro, rapamycin-impeded cardiac microvascular endothelial cells (CMECs) migration, proliferation and rapamycin-induced ROS production were reversed by nicorandil. Knockdown of XO partially inhibited rapamycin-induced ROS production and cell apoptosis in CMECs, and it promoted CMECs migration and proliferation suppressed by rapamycin. Knockdown of Akt partially prevents eNOS upregulation promoted by nicorandil. The beneficial effect of nicorandil is exhibited by inhibiting XO and up-regulating Akt pathway. Nicorandil combined with rapamycin in effect rescue the deficiencies of rapamycin alone in arterial healing after angioplasty. PMID:27713157

Anti-inflammatory effects of fish oil in ovaries of laying hens target prostaglandin pathways.

PubMed

Eilati, Erfan; Small, Carolynn C; McGee, Stacey R; Kurrey, Nawneet K; Hales, Dale Buchanan

2013-10-24

An effective way to control cancer is by prevention. Ovarian cancer is the most lethal gynecological malignancy. Progress in the treatment and prevention of ovarian cancer has been hampered due to the lack of an appropriate animal model and absence of effective chemo-prevention strategies. The domestic hens spontaneously develop ovarian adenocarcinomas that share similar histological appearance and symptoms such as ascites and metastasis with humans. There is a link between chronic inflammation and cancer. Prostaglandin E2 (PGE2) is the most pro-inflammatory ecoisanoid and one of the downstream products of two isoforms of cyclooxygenase (COX) enzymes: COX-1 and COX-2. PGE2 exerts its effects on target cells by coupling to four subtypes of receptors which have been classified as EP1-4. Fish oil is a source of omega-3 fatty acids (OM-3FAs) which may be effective in prevention of ovarian cancer. Our objective was to assess the potential impact of fish oil on expression of COX enzymes, PGE2 concentration, apoptosis and proliferation in ovaries of laying hens. 48 white Leghorn hens were fed 50, 100, 175, 375 and 700 mg/kg fish oil for 21 days. The OM3-FAs and omega-6 fatty acids contents of egg yolks were determined by Gas Chromatography. Proliferation, apoptosis, COX-1, COX-2 and prostaglandin receptor subtype 4 (EP4) protein and mRNA expression and PGE2 concentration in ovaries were measured by PCNA, TUNEL, Western blot, quantitative real-time qPCR and ELISA, respectively. Consumption of fish oil increased the incorporation of OM-3FAs into yolks and decreased both COX-1 and COX-2 protein and mRNA expression. In correlation with COXs down-regulation, fish oil significantly reduced the concentrations of PGE2 in ovaries. EP4 protein and mRNA expression in ovaries of hens was not affected by fish oil treatment. A lower dose of fish oil increased the egg laying frequency. 175 and 700 mg/kg fish oil reduced proliferation and 700 mg/kg increased apoptosis in hen ovaries. Our findings suggest that the lower doses of fish oil reduce inflammatory PG and may be an effective approach in preventing ovarian carcinogenesis. These findings may provide the basis for clinical trials utilizing fish oil as a dietary intervention targeting prostaglandin biosynthesis for the prevention and treatment of ovarian cancer.

Programmed hyperphagia secondary to increased hypothalamic SIRT1.

PubMed

Desai, Mina; Li, Tie; Han, Guang; Ross, Michael G

2014-11-17

Small for gestational age (SGA) offspring exhibit reduced hypothalamic neural satiety pathways leading to programmed hyperphagia and adult obesity. Appetite regulatory site, the hypothalamic arcuate nucleus (ARC) contains appetite (NPY/AgRP) and satiety (POMC) neurons. Using in vitro culture of hypothalamic neuroprogenitor cells (NPC) which form the ARC, we demonstrated that SGA offspring exhibit reduced NPC proliferation and neuronal differentiation. bHLH protein Hes1 promotes NPC self-renewal and inhibits differentiation by repressing neuronal differentiation genes (Mash1, neurogenin3). We hypothesized that Hes1/Mash1 and ultimately ARC neuronal differentiation and expression of NPY/POMC neurons are influenced by SIRT1 which is a nutrient sensor and a histone deacetylase. Control dams received ad libitum food, whereas study dams were 50% food-restricted from pregnancy day 10 to 21 (SGA). In vivo studies showed that SGA newborns and adult offspring had increased protein expression of hypothalamic/ARC SIRT1 and AgRP with decreased POMC. Additionally, SGA newborns had decreased expression of hypothalamic neurogenic factors with reduced in vivo NPC proliferation. In vitro culture of hypothalamic NPCs showed similar changes with elevated SIRT1 binding to Hes1 in SGA newborn. Silencing SIRT1 increased NPC proliferation and Hes1 and Tuj1expression in both Control and SGA NPCs. Although SGA NPC proliferation remained below that of Controls, it was higher than Control NPCs in the absence of SIRT1 siRNA. The direct impact of SIRT1 on NPC proliferation and differentiation were further confirmed with pharmacologic SIRT1 inhibitor and activator. Thus, in SGA newborns elevated SIRT1 induces premature differentiation of NPCs, reducing the NPC pool and cell proliferation. Copyright © 2014 Elsevier B.V. All rights reserved.

Programmed Hyperphagia secondary to Increased Hypothalamic SIRT1

PubMed Central

Desai, Mina; Li, Tie; Han, Guang; Ross, Michael G.

2014-01-01

Small for gestational age (SGA) offspring exhibit reduced hypothalamic neural satiety pathways leading to programmed hyperphagia and adult obesity. Appetite regulatory site, the hypothalamic arcuate nucleus (ARC) contains appetite (NPY/AgRP) and satiety (POMC) neurons. Using in vitro culture of hypothalamic neuroprogenitor cells (NPC) which form the ARC, we demonstrated that SGA offspring exhibit reduced NPC proliferation and neuronal differentiation. bHLH protein Hes1 promotes NPC self-renewal and inhibits differentiation by repressing neuronal differentiation genes (Mash1, neurogenin3). We hypothesized that Hes1/Mash1 and ultimately ARC neuronal differentiation and expression of NPY/POMC neurons are influenced by SIRT1 which is a nutrient sensor and a histone deacetylase. Control dams received ad libitum food, whereas study dams were 50% food-restricted from pregnancy day 10 to 21 (SGA). In vivo studies showed that SGA newborns and adult offspring had increased protein expression of hypothalamic/ARC SIRT1 and AgRP with decreased POMC. Additionally, SGA newborns had decreased expression of hypothalamic neurogenic factors with reduced in vivo NPC proliferation. In vitro culture of hypothalamic NPCs showed similar changes with elevated SIRT1 binding to Hes1 in SGA newborn. Silencing SIRT1 increased NPC proliferation and Hes1 and Tuj1expression in both Control and SGA NPCs. Although SGA NPC proliferation remained below that of Controls, it was higher than Control NPCs in the absence of SIRT1 siRNA. The direct impact of SIRT1 on NPC proliferation and differentiation were further confirmed with pharmacologic SIRT1 inhibitor and activator. Thus, in SGA newborns elevated SIRT1 induces premature differentiation of NPCs, reducing the NPC pool and cell proliferation. PMID:25245521

Construction of Expression Vector for Anti-Alpha-Fetoprotein Gene and Its Inhibition Effects on Alpha-Fetoprotein Positive Hepg2 Cells

NASA Astrophysics Data System (ADS)

Wang, Ze; Zhang, Hui

As research previously demonstrated, suppression of AFP expression or its biological activities might inhibit the proliferation of AFP positive human hepatocellular carcinoma cells. In this study, we constructed an anti-AFP gene vector and transfected it to HepG2 cells. RT-PCR showed AFP gene expression in the transfected cells was reduced. MTT assay suggested the proliferation of the transfected cells was also inhibited comparing with the untransfected cells. This result provides a new insight into AFP as the target for preventing and treating hepatocellular carcinoma.

[Advances in the effects of pH value of micro-environment on wound healing].

PubMed

Tian, Ruirui; Li, Na; Wei, Li

2016-04-01

Wound healing is a complex regeneration process, which is affected by lots of endogenous and exogenous factors. Researches have confirmed that acid environment could prevent wound infection and accelerate wound healing by inhibiting bacteria proliferation, promoting oxygen release, affecting keratinocyte proliferation and migration, etc. In this article, we review the literature to identify the potential relationship between the pH value of wound micro-environment and the progress of wound healing, and summarize the clinical application of variation of pH value of micro-environment in wound healing, thereby to provide new treatment strategy for wound healing.

Do diabetes and obesity affect the metabolic response to exercise?

PubMed

Plomgaard, Peter; Weigert, Cora

2017-07-01

Exercise is recommended as therapeutic intervention for people at risk to develop type 2 diabetes to prevent or treat the disease. Recent studies on the influence of obesity and type 2 diabetes on the outcome of exercise programs are discussed. Poor glycemic control before an intervention can be a risk factor of reduced therapeutic benefit from exercise. But the acute metabolic response to exercise and the transcriptional profile of the working muscle is similar in healthy controls and type 2 diabetic patients, including but not limited to intact activation of skeletal muscle AMP-activated kinase signaling, glucose uptake and expression of peroxisome proliferator-activated receptor gamma coactivator 1α. The increase in plasma acylcarnitines during exercise is not influenced by type 2 diabetes or obesity. The hepatic response to exercise is dependent on the glucagon/insulin ratio and the exercise-induced increase in hepatokines such as fibroblast growth factor 21 and follistatin is impaired in type 2 diabetes and obesity, but consequences for the benefit from exercise are unknown yet. Severe metabolic dysregulation can reduce the benefit from exercise, but the intact response of key metabolic regulators in exercising skeletal muscle of diabetic patients demonstrates the effectiveness of exercise programs to treat the disease.

Overview of gastrointestinal cancer prevention in Asia.

PubMed

Park, Jong-Min; Lee, Ho-Jae; Yoo, Jun Hwan; Ko, Weon Jin; Cho, Joo Young; Hahm, Ki Baik

2015-12-01

"War on cancer" was declared through the National Cancer Act by President Richard Nixon in 1971, but cancer statistics from the American Cancer Society and other sources indicated the failure of this war, suggesting instead focus on the message that a "prevention strategy" might be much more effective than cancer treatment. While cancer statistics notoriously showed sharp increases in incidence as well as in mortality concurrent with economic growth in Asia, fortunately Asian countries benefit from plentiful resources of natural compounds, which can prevent cancer. Just like cancer chemotherapeutics targeted to kill cancer cells in Western countries, natural agents activating molecular mechanisms for cancer prevention, reversion of premalignant tumors, and even ablation of cancer stem cells, are very abundant in Asia. Currently, these natural agents are under very active investigations targeting the hallmarks of cancer prevention, including selective induction of apoptosis in cancer cells, suppression of growth factors or their signaling, suppression of cell proliferation and of cancer-promoting angiogenesis, induction of mesenchymal-epithelial transition, and disruption of the tumor microenvironment, developing promising cancer preventive agents. However, Asia is the most populous continent in the world and some Asian countries do not have the resources to implement cancer screening programs for early detection or treatment. In addition, despite the excellent cancer preventive screening strategies in some Asian countries, well-designed clinical trials for cancer prevention are somewhat delayed compared to Western countries. In this review article, several phytochemicals/phytoceuticals produced and studied in different Asian countries will be introduced, including Korean red ginseng (pride of Korea), curcumin (Indian spice for life), black or green tea (popular in Japan/Sri Lanka), genistein from tofu (famous Chinese food), diallylsulfide or S-allylcysteine (garlic, popularly consumed as a food ingredient in many Asian countries), capsaicin, 6-gingerol, flavopiridol, and silymarin (abundant in various Asian foods). Whereas in Western countries cancer chemotherapeutics involve strategies not only to block the growth of the primary tumor, but also to inhibit its progression to metastatic disease, the endless pursuit of effective agents for cancer prevention may be a unique and featured strategy in Asia. More active efforts for clinical application of these principles should be supported. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Li, Guofeng; Xu, Jingren; Li, Zengchun, E-mail: lizc.2007@yahoo.com.cn

Highlights: Black-Right-Pointing-Pointer RAGE overexpression suppresses cell proliferation in MC3T3-E1 cells. Black-Right-Pointing-Pointer RAGE overexpression decreases Wnt/{beta}-catenin signaling. Black-Right-Pointing-Pointer RAGE overexpression decreases ERK and PI3K signaling. Black-Right-Pointing-Pointer Inhibition of Wnt signaling abolishes PI3K signaling restored by RAGE blockade. Black-Right-Pointing-Pointer Inhibition of Wnt signaling abolishes ERK signaling restored by RAGE blockade. -- Abstract: Expression of receptor for advanced glycation end products (RAGE) plays a crucial role in bone metabolism. However, the role of RAGE in the control of osteoblast proliferation is not yet evaluated. In the present study, we demonstrate that RAGE overexpression inhibits osteoblast proliferation in vitro. The negative regulation of RAGEmore » on cell proliferation results from suppression of Wnt, PI3K and ERK signaling, and is restored by RAGE neutralizing antibody. Prevention of Wnt signaling using Sfrp1 or DKK1 rescues RAGE-decreased PI3K and ERK signaling and cell proliferation, indicating that the altered cell growth in RAGE overexpressing cells is in part secondary to alterations in Wnt signaling. Consistently, RAGE overexpression inhibits the expression of Wnt targets cyclin D1 and c-myc, which is partially reversed by RAGE blockade. Overall, these results suggest that RAGE inhibits osteoblast proliferation via suppression of Wnt, PI3K and ERK signaling, which provides novel mechanisms by which RAGE regulates osteoblast growth.« less

A large shRNA library approach identifies lncRNA Ntep as an essential regulator of cell proliferation

PubMed Central

Beermann, Julia; Kirste, Dominique; Iwanov, Katharina; Lu, Dongchao; Kleemiß, Felix; Kumarswamy, Regalla; Schimmel, Katharina; Bär, Christian; Thum, Thomas

2018-01-01

The mammalian cell cycle is a complex and tightly controlled event. Myriads of different control mechanisms are involved in its regulation. Long non-coding RNAs (lncRNA) have emerged as important regulators of many cellular processes including cellular proliferation. However, a more global and unbiased approach to identify lncRNAs with importance for cell proliferation is missing. Here, we present a lentiviral shRNA library-based approach for functional lncRNA profiling. We validated our library approach in NIH3T3 (3T3) fibroblasts by identifying lncRNAs critically involved in cell proliferation. Using stringent selection criteria we identified lncRNA NR_015491.1 out of 3842 different RNA targets represented in our library. We termed this transcript Ntep (non-coding transcript essential for proliferation), as a bona fide lncRNA essential for cell cycle progression. Inhibition of Ntep in 3T3 and primary fibroblasts prevented normal cell growth and expression of key fibroblast markers. Mechanistically, we discovered that Ntep is important to activate P53 concomitant with increased apoptosis and cell cycle blockade in late G2/M. Our findings suggest Ntep to serve as an important regulator of fibroblast proliferation and function. In summary, our study demonstrates the applicability of an innovative shRNA library approach to identify long non-coding RNA functions in a massive parallel approach. PMID:29099486

Neuron-derived orphan receptor 1 promoted human pulmonary artery smooth muscle cells proliferation.

PubMed

Wang, Chang-Guo; Lei, Wei; Li, Chang; Zeng, Da-Xiong; Huang, Jian-An

2015-05-01

As a transcription factor of the nuclear receptor superfamily, neuron-derived orphan receptor 1 (NOR1) is induced rapidly in response to various extracellular stimuli. But, it is still unclear its role in pulmonary artery smooth muscle cells proliferation. Human PASMCs were cultured in vitro and stimulated by serum. The special antisense oligodeoxynucleotides (AS-ODNs) were used to knockdown human NOR1 gene expression. Real-time PCR and Western-blot were used to evaluate the gene expression and protein levels. Fetal bovine serum (FBS) induced human PASMCs proliferation in a dose dependent manner. Furthermore, FBS promoted NOR1 gene expression in a dose dependent manner and a time dependent manner. 10% FBS induced a maximal NOR1 mRNA levels at 2 h. FBS also induced a significant higher NOR1 protein levels as compared with control. The NOR1 over-expressed plasmid significantly promoted DNA synthesis and cells proliferation. Moreover, the special AS-ODNs against human NOR1 not only prevented NOR1 expression but also inhibited DNA synthesis and cells proliferation significantly. The NOR1 over-expression plasmid could up-regulate cyclin D1 expression markedly, but the AS-ODNs inhibited cyclin D1 expression significantly. So, we concluded that NOR1 could promote human PASMCs proliferation. Cyclin D1 might be involved in this process.

UAP56 is an important mediator of Angiotensin II/platelet derived growth factor induced vascular smooth muscle cell DNA synthesis and proliferation

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

Sahni, Abha; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555; Wang, Nadan

2013-02-15

Highlights: ► Knockdown of UAP56 inhibits Angiotensin II/PDGF induced vascular smooth muscle cell proliferation. ► UAP56 is a positive regulator of E2F transcriptional activation. ► UAP56 is present in the vessel wall of low flow carotid arteries. -- Abstract: Angiotensin (Ang) II and platelet-derived growth factor (PDGF) are important mediators of pathologic vascular smooth muscle cell (VSMC) proliferation. Identifying downstream mediators of Ang II and PDGF signaling may provide insights for therapies to improve vascular proliferative diseases. We have previously demonstrated that breakpoint cluster region (Bcr) is an important mediator of Ang II/PDGF signaling in VSMC. We have recently reportedmore » that the DExD/H box protein UAP56 is an interacting partner of Bcr in regulating VSMC DNA synthesis. We hypothesized that UAP56 itself is an important regulator of VSMC proliferation. In this report we demonstrate that knockdown of UAP56 inhibits Ang II/PDGF induced VSMC DNA synthesis and proliferation, and inhibits E2F transcriptional activity. In addition, we demonstrate that UAP56 is present in the vessel wall of low-flow carotid arteries. These findings suggest that UAP56 is a regulator of VSMC proliferation and identify UAP56 as a target for preventing vascular proliferative disease.« less

CXCL9 Is Important for Recruiting Immune T Cells into the Brain and Inducing an accumulation of the T Cells to the areas of tachyzoite proliferation to prevent reactivation of chronic cerebral infection with Toxoplasma gondii

USDA-ARS?s Scientific Manuscript database

T cells are required to maintain the latency of chronic infection with Toxoplasma gondii in the brain. In the present study, we examined the role of non-ELR (glutamic acid-leucine-arginine) CXC chemokine CXCL9 for T cell recruitment to prevent reactivation of infection with T. gondii. SCID mice were...

Propolis Augments Apoptosis Induced by Butyrate via Targeting Cell Survival Pathways

PubMed Central

Drago, Eric; Bordonaro, Michael; Lee, Seon; Atamna, Wafa; Lazarova, Darina L.

2013-01-01

Diet is one of the major lifestyle factors affecting incidence of colorectal cancer (CC), and despite accumulating evidence that numerous diet-derived compounds modulate CC incidence, definitive dietary recommendations are not available. We propose a strategy that could facilitate the design of dietary supplements with CC-preventive properties. Thus, nutrient combinations that are a source of apoptosis-inducers and inhibitors of compensatory cell proliferation pathways (e.g., AKT signaling) may produce high levels of programmed death in CC cells. Here we report the combined effect of butyrate, an apoptosis inducer that is produced through fermentation of fiber in the colon, and propolis, a honeybee product, on CC cells. We established that propolis increases the apoptosis of CC cells exposed to butyrate through suppression of cell survival pathways such as the AKT signaling. The programmed death of CC cells by combined exposure to butyrate and propolis is further augmented by inhibition of the JNK signaling pathway. Analyses on the contribution of the downstream targets of JNK signaling, c-JUN and JAK/STAT, to the apoptosis of butyrate/propolis-treated CC cells ascertained that JAK/STAT signaling has an anti-apoptotic role; whereas, the role of cJUN might be dependent upon regulatory cell factors. Thus, our studies ascertained that propolis augments apoptosis of butyrate-sensitive CC cells and re-sensitizes butyrate-resistant CC cells to apoptosis by suppressing AKT signaling and downregulating the JAK/STAT pathway. Future in vivo studies should evaluate the CC-preventive potential of a dietary supplement that produces high levels of colonic butyrate, propolis, and diet-derived JAK/STAT inhibitors. PMID:24023824

Lactobacillus salivarius Ren prevent the early colorectal carcinogenesis in 1, 2-dimethylhydrazine-induced rat model.

PubMed

Zhu, J; Zhu, C; Ge, S; Zhang, M; Jiang, L; Cui, J; Ren, F

2014-07-01

The objective of this study was to investigate the impact of Lactobacillus salivarius Ren (LS) on modulating colonic micro flora structure and influencing host colonic health in a rat model with colorectal precancerous lesions. Male F344 rats were injected with 1, 2-dimethylhydrazine (DMH) and treated with LS of two doses (5 × 10(8) and 1 × 10(10) CFU kg(-1) body weight) for 15 weeks. The colonic microflora profiles, luminal metabolites, epithelial proliferation and precancerous lesions [aberrant crypt foci (ACF)] were determined. A distinct segregation of colonic microflora structures was observed in LS-treated group. The abundance of one Prevotella-related strain was increased, and the abundance of one Bacillus-related strain was decreased by LS treatment. These changes were accompanied by increased short-chain fatty acid levels and decreased azoreductase activity. LS treatment also reduced the number of ACF by c. 40% and suppressed epithelial proliferation. Lactobacillus salivarius Ren improved the colonic microflora structures and the luminal metabolisms in addition preventing the early colorectal carcinogenesis in DMH-induced rat model. Colonic microflora is an important factor in colorectal carcinogenesis. Modulating the structural shifts of microflora may provide a novel option for preventing colorectal carcinogenesis. This study suggested a potential probiotic-based approach to modulate the intestinal microflora in the prevention of colorectal carcinogenesis. © 2014 The Society for Applied Microbiology.

9/11 Five Years Later: Successes and Challenges

DTIC Science & Technology

2006-09-01

Infrastructure Protection ........................................................................................... 10 Prevent Proliferation of Weapons of...20 Challenges to Combating the Violent Extremist Ideology ..................................................... 20 Challenges to Protecting the...message, agenda, and tactics of the violent extremist movement. • Before 9/11, the protection of civil liberties was not systematically and

75 FR 80734 - Chronic Beryllium Disease Prevention Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-23

... Disease Prevention Program AGENCY: Office of Health, Safety and Security, Department of Energy. ACTION... and comments on issues related to its current chronic beryllium disease prevention program. The... disease prevention program. DATES: All comments on the issues presented in this document must be received...

Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages

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

Kinoshita, Hiroyuki; Matsumura, Takeshi, E-mail: takeshim@gpo.kumamoto-u.ac.jp; Ishii, Norio

Highlights: ► We examined the anti-athrogenic effect of apocynin in atherosclerotic model mice. ► Apocynin prevented atherosclerotic lesion formation. ► Apocynin suppressed ROS production in aorta and in macrophages. ► Apocynin suppressed cytokine expression and cell proliferation in macrophages. ► Apocynin may be beneficial compound for the prevention of atherosclerosis. -- Abstract: Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages plays an important role in atherogenesis. Apocynin (4-hydroxy-3-methoxy-acetophenone), which is well known as a NADPH oxidase inhibitor, has anti-inflammatory effects including suppression of the generation of ROS. However, the suppressive effects of apocynin on the progressionmore » of atherosclerosis are not clearly understood. Thus, we investigated anti-atherosclerotic effects of apocynin using apolipoprotein E-deficient (apoE{sup –/–}) mice in vivo and in mouse peritoneal macrophages in vitro. In atherosclerosis-prone apoE{sup –/–} mice, apocynin suppressed the progression of atherosclerosis, decreased 4-hydroxynonenal-positive area in atherosclerotic lesions, and mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in aorta. In mouse peritoneal macrophages, apocynin suppressed the Ox-LDL-induced ROS generation, mRNA expression of MCP-1, IL-6 and granulocyte/macrophage colony-stimulating factor, and cell proliferation. Moreover, immunohistochemical studies revealed that apocynin decreased the number of proliferating cell nuclear antigen-positive macrophages in atherosclerotic lesions of apoE{sup –/–} mice. These results suggested that apocynin suppressed the formation of atherosclerotic lesions, at least in part, by inactivation of macrophages. Therefore, apocynin may be a potential therapeutic material to prevent the progression of atherosclerosis.« less

Melatonin promotes circadian rhythm-induced proliferation through Clock/histone deacetylase 3/c-Myc interaction in mouse adipose tissue.

PubMed

Liu, Zhenjiang; Gan, Lu; Luo, Dan; Sun, Chao

2017-05-01

Melatonin is synthesized in the pineal gland and controls circadian rhythm of peripheral adipose tissue, resulting in changes in body weight. Although core regulatory components of clock rhythmicity have been defined, insight into the mechanisms of circadian rhythm-mediated proliferation in adipose tissue is still limited. Here, we showed that melatonin (20 mg/kg/d) promoted circadian and proliferation processes in white adipose tissue. The circadian amplitudes of brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal1, P<.05) and circadian locomotor output cycles kaput (Clock, P<.05), period 2 (Per2, P<.05), cyclin E (P<.05), and c-Myc (P<.05) were directly increased by melatonin in adipose tissue. Melatonin also promoted cell cycle and increased cell numbers (P<.05), which was correlated with the Clock expression (P<.05). Further analysis demonstrated that Clock bound to the E-box elements in the promoter region of c-Myc and then directly stimulated c-Myc transcription. Moreover, Clock physically interacted with histone deacetylase 3 (HDAC3) and formed a complex with c-Myc to promote adipocyte proliferation. Melatonin also attenuated circadian disruption and promoted adipocyte proliferation in chronic jet-lagged mice and obese mice. Thus, our study found that melatonin promoted adipocyte proliferation by forming a Clock/HDAC3/c-Myc complex and subsequently driving the circadian amplitudes of proliferation genes. Our data reveal a novel mechanism that links circadian rhythm to cell proliferation in adipose tissue. These findings also identify a new potential means for melatonin to prevent and treat sleep deprivation-caused obesity. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro

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

Xu, Yang; Pang, Xiaoyan; Dong, Mei

Highlights: •Nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest. •Nesfatin-1 enhances HO-8910 cell apoptosis. •Nesfatin-1 inhibits HO-8910 cell proliferation via mTOR and RhoA/ROCK signaling pathway. •The first report of nesfatin-1-mediated proliferation in ovarian epithelial carcinoma. -- Abstract: Nesfatin-1, an 82-amino-acid peptide derived from a 396-amino-acid precursor protein nucleobindin 2 (NUCB2), was originally identified in hypothalamic nuclei involved in the regulation of food intake. It was recently reported that nesfatin-1 is a novel depot specific adipokine preferentially produced by subcutaneous tissue, with obesity- and food deprivation-regulated expression. Although a relation between ovarian cancer mortality and obesitymore » has been previously established, a role of nesfatin-1 in ovarian epithelial carcinoma remains unknown. The aim of the present study is to examine the effect of nesfatin-1 on ovary carcinoma cells proliferation. We found that nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, this inhibition could be abolished by nesfatin-1 neutralizing antibody. Nesfatin-1 enhances HO-8910 cell apoptosis, activation of mammalian target of rapamycin (mTOR) and RhoA/ROCK signaling pathway block the effects of nesfatin-1-induced apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation by nesfatin-1. In conclusion, the present study demonstrated that nesfatin-1 can inhibit the proliferation in human ovarian epithelial carcinoma cell line HO-8910 cells through inducing apoptosis via mTOR and RhoA/ROCK signaling pathway. This study provides a novel regulatory signaling pathway of nesfatin-1-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy, especially in obese patients.« less

Cosmetic Surgery Makeover Programs and Intentions to Undergo Cosmetic Enhancements: A Consideration of Three Models of Media Effects

ERIC Educational Resources Information Center

Nabi, Robin L.

2009-01-01

The recent proliferation of reality-based television programs highlighting cosmetic surgery has raised concerns that such programming promotes unrealistic expectations of plastic surgery and increases the desire of viewers to undergo such procedures. In Study 1, a survey of 170 young adults indicated little relationship between cosmetic surgery…

The One-to-One Tsunami: It's on the Horizon. Will You Be Ready?

ERIC Educational Resources Information Center

Livingston, Pamela

2007-01-01

In this article, the author discusses the proliferation of one-to-one programs. For educators, the key to one-to-one success is in a well-managed and thoughtfully approached classroom program. Despite a good body of anecdotal evidence on the success of one-to-one programs--increased student attendance and motivation, more collaborative…

Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat

PubMed Central

Blanco-Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodriguez de Fonseca, Fernando

2014-01-01

Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation. To this end, we examined whether pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg) or CB2 receptors (AM630, 3 mg/kg) would affect cell proliferation [the cells were labeled with 5-bromo-2′-deoxyuridine (BrdU)] in the subventricular zone (SVZ) of the lateral ventricle and the dentate subgranular zone (SGZ). Additionally, we measured cell apoptosis (as monitored by the expression of cleaved caspase-3) and glial activation [by analyzing the expression of glial fibrillary acidic protein (GFAP) and Iba-1] in the striatum and hippocampus during acute and repeated (4 days) cocaine administration (20 mg/kg). The results showed that acute cocaine exposure decreased the number of BrdU-immunoreactive (ir) cells in the SVZ and SGZ. In contrast, repeated cocaine exposure reduced the number of BrdU-ir cells only in the SVZ. Both acute and repeated cocaine exposure increased the number of cleaved caspase-3-, GFAP- and Iba1-ir cells in the hippocampus, and this effect was counteracted by AM630 or Rimonabant, which increased the number of BrdU-, GFAP-, and Iba1-ir cells in the hippocampus. These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned locomotion but not with the prevention of cocaine-induced sensitization. PMID:24409127

Sodium meta-arsenite prevents the development of autoimmune diabetes in NOD mice

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

Lee, Y.S.; Kim, D.; Lee, E.K.

Sodium meta-arsenite (SA) is an orally available arsenic compound. We investigated the effects of SA on the development of autoimmune type 1 diabetes. Female non-obese diabetic (NOD) mice were orally intubated with SA (5 mg/kg/day) from 8 weeks of age for 8 weeks. The cumulative incidence of diabetes was monitored until 30 weeks of age, islet histology was examined, and lymphocytes including T cells, B cells, CD4+ IFN-γ+ cells, CD8+ IFN-γ+ cells, CD4+ IL-4+ cells, and regulatory T cells were analyzed. We also investigated the diabetogenic ability of splenocytes using an adoptive transfer model and the effect of SA onmore » the proliferation, activation, and expression of glucose transporter 1 (Glut1) in splenocytes treated with SA in vitro and splenocytes isolated from SA-treated mice. SA treatment decreased the incidence of diabetes and delayed disease onset. SA treatment reduced the infiltration of immunocytes in islets, and splenocytes from SA-treated mice showed a reduced ability to transfer diabetes. The number of total splenocytes and T cells and both the number and the proportion of CD4+ IFN-γ+ and CD8+ IFN-γ+ T cells in the spleen were significantly reduced in SA-treated NOD mice compared with controls. The number, but not the proportion, of regulatory T cells was decreased in SA-treated NOD mice. Treatment with SA either in vitro or in vivo inhibited proliferation of splenocytes. In addition, the expression of Glut1 and phosphorylated ERK1/2 was decreased by SA treatment. These results suggest that SA reduces proliferation and activation of T cells, thus preventing autoimmune diabetes in NOD mice. - Highlights: • SA prevents the development of diabetes and delays the age of onset in NOD mice. • SA decreases the number but not the proportion of T lymphocytes in NOD mice. • SA reduces IFN-γ-producing T lymphocytes in NOD mice. • SA reduces proliferation and activation of T lymphocytes in vitro and in vivo. • SA reduces the expression of glucose transporter 1 (Glut1) in splenocytes.« less

An overview of the effectiveness and efficiency of HIV prevention programs.

PubMed Central

Holtgrave, D R; Qualls, N L; Curran, J W; Valdiserri, R O; Guinan, M E; Parra, W C

1995-01-01

Because of the enormity of the HIV-AIDS epidemic and the urgency for preventing transmission, HIV prevention programs are a high priority for careful and timely evaluations. Information on program effectiveness and efficiency is needed for decision-making about future HIV prevention priorities. General characteristics of successful HIV prevention programs, programs empirically evaluated and found to change (or not change) high-risk behaviors or in need of further empirical study, and economic evaluations of certain programs are described and summarized with attention limited to programs that have a behavioral basis. HIV prevention programs have an impact on averting or reducing risk behaviors, particularly when they are delivered with sufficient resources, intensity, and cultural competency and are based on a firm foundation of behavioral and social science theory and past research. Economic evaluations have found that some of these behaviorally based programs yield net economic benefits to society, and others are likely cost-effective (even if not cost-saving) relative to other health programs. Still, specific improvements should be made in certain HIV prevention programs. PMID:7630989

Dyon proliferation in interacting quantum spin Hall edges

NASA Astrophysics Data System (ADS)

Lee, Shu-Ping; Maciejko, Joseph

We show that a quantum spin Hall system with intra-edge multiparticle backscattering and inter-edge exchange interactions exhibits a modular invariant zero-temperature phase diagram. We establish this through mapping to a classical 2D Coulomb gas with electrically and magnetically charged particles; strong coupling phases in the quantum edge problem correspond to the proliferation of various dyons in the Coulomb gas. Distinct dyon proliferated phases can be accessed by tuning the edge Luttinger parameters, for example using a split gate geometry. This research was supported by NSERC Grant #RGPIN-2014-4608, the Canada Research Chair Program (CRC) and the Canadian Institute for Advanced Research (CIFAR).

Security implications of the proliferation of weapons of mass destruction in the Middle East. Final report

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

Hajjar, S.G.

1998-12-17

The author argues that the Arab-Israeli conflict, the Iran-Iraq rivalry, and the lack of progress in the peace process are strong incentives for nations in the region to acquire weapons of mass destruction (WMD). He documents Israeli, Iranian, and Arab WMD programs and capabilities, referencing use of WMD in the region. He discusses the reasons why the major regional powers seek WMD capabilities and examines the nature of the proliferation dynamic as well as nonproliferation and counterproliferation approaches applicable to the region. The author offers several recommendations designed to strengthen these efforts and deal more effectively with causes of proliferation.

Ion channels involved in cell volume regulation: effects on migration, proliferation, and programmed cell death in non adherent EAT cells and adherent ELA cells.

PubMed

Hoffmann, Else Kay

2011-01-01

This mini review outlines studies of cell volume regulation in two closely related mammalian cell lines: nonadherent Ehrlich ascites tumour cells (EATC) and adherent Ehrlich Lettre ascites (ELA) cells. Focus is on the regulatory volume decrease (RVD) that occurs after cell swelling, the volume regulatory ion channels involved, and the mechanisms (cellular signalling pathways) that regulate these channels. Finally, I shall also briefly review current investigations in these two cell lines that focuses on how changes in cell volume can regulate cell functions such as cell migration, proliferation, and programmed cell death. Copyright © 2011 S. Karger AG, Basel.

ZDHHC16 modulates FGF/ERK dependent proliferation of neural stem/progenitor cells in the zebrafish telencephalon.

PubMed

Shi, Wei; Chen, Xueran; Wang, Fen; Gao, Ming; Yang, Yang; Du, Zhaoxia; Wang, Chen; Yao, Yao; He, Kun; Hao, Aijun

2016-09-01

In vertebrates, neural stem/progenitor cells (NSPCs) maintenance is critical for nervous system development and homeostasis. However, the molecular mechanisms underlying the maintenance of NSPCs have not been fully elucidated. Here, we demonstrated that zebrafish ZDHHC16, a DHHC encoding protein, which was related to protein palmitoylation after translation, was expressed in the developing forebrain, and especially in the telencephalon. Loss- and gain-of-function studies showed that ZDHHC16 played a crucial role in the regualtion of NSPCs proliferation during zebrafish telencephalic development, via a mechanism dependent on its palmitoyltransferase activity. Further analyses showed that the inhibition of ZDHHC16 led to inactivation of the FGF/ERK signaling pathway during telencephalic NSPCs proliferation and maintenance. Taken together, our results suggest that ZDHHC16 activity is essential for early NSPCs proliferation where it acts to activate the FGF/ERK network, allowing for the initiation of proliferation -regulated gene expression programs. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1014-1028, 2016. © 2016 Wiley Periodicals, Inc.

An Evaluation of the Implementation Fidelity and Outcomes of the Olweus Bullying Prevention Program in Three Elementary Schools in Virginia

ERIC Educational Resources Information Center

Wood, Barbara F.

2013-01-01

Bullying continues to be a major concern in schools today. Many schools have implemented some type of bullying prevention program. The Olweus Bullying Prevention Program is one of these programs. Evaluation of the Olweus Bullying Prevention Program is typically done through the administration of the Olweus Bullying Questionnaire to students and…

New therapeutic possibilities for vein graft disease in the post-edifoligide era.

PubMed

Cai, Xinjiang; Freedman, Neil J

2006-07-01

Vein graft neointimal hyperplasia involves proliferation and migration of vascular smooth muscle cells into the vessel intima, and ultimately engenders accelerated atherosclerosis and vein graft failure. Since a myriad of stimuli provoke smooth muscle cell proliferation, molecular therapies for vein graft disease have targeted mechanisms fundamental to all cell proliferation - the 'cell-cycle' machinery. Preclinically, the most successful of these therapies has been edifoligide (E2F decoy), a double-stranded oligodeoxynucleotide that binds to the transcription factor known as E2F. Recently, PRoject of Ex vivo vein GRaft Engineering via Transfection (PREVENT) III and IV demonstrated that edifoligide failed to benefit human vein grafts employed to treat lower-extremity ischemia and coronary heart disease, respectively. The clinical failure of edifoligide calls into question previous models of vein graft disease and lends credence to recent animal studies demonstrating that vein graft arterialization substantially involves the immigration into the vein graft of a variety of vascular progenitor cells. Future vein graft disease therapies will likely target not only proliferation of graft-intrinsic cells, but also immigration of graft-extrinsic cells.

Omega-3 free fatty acids attenuate insulin-promoted breast cancer cell proliferation.

PubMed

Guo, Yang; Zhu, Sheng-Long; Wu, Yi-Kuan; He, Zhao; Chen, Yong-Quan

2017-06-01

High insulin levels in obese people are considered as a risk factor to induce breast carcinogenesis. And consumption of fish oils which mainly contain omega-3 fatty acids is associated with a reduced risk of breast cancer. However, whether omega-3 free fatty acids (FFAs) modulate insulin signaling pathway to prevent breast cancer is poorly understood. The current study tested the hypothesis that omega-3 FFAs attenuate insulin-induced breast cancer cell proliferation and regulate insulin signaling pathway. We show here that omega-3 FFAs attenuate MCF-7 cell proliferation and Akt and Erk1/2 phosphorylation levels stimulated by insulin. Knockdown Shp2 by siRNA resulted in significantly elevated omega-3 FFAs-activated Akt phosphorylation but failed to change insulin-stimulated Akt and Erk1/2 phosphorylation. And viable cell number was not affected by either downregulation of Shp2 expression or Erk1/2 inhibitor U0126 treatment. These observations indicated that omega-3 FFAs attenuate insulin-promoted breast cancer cell proliferation and insulin-activated Akt phosphorylation. Copyright © 2017 Elsevier Inc. All rights reserved.

Emodin prevents intima thickness via Wnt4/Dvl-1/β-catenin signaling pathway mediated by miR-126 in balloon-injured carotid artery rats

PubMed Central

Hua, Jun-yi; He, Yu-zhou; Xu, Yun; Jiang, Xu-hong; Ye, Wu; Pan, Zhi-min

2015-01-01

Neointimal proliferation after vascular injury is a key mechanism of restenosis, a major cause of percutaneous transluminal angioplasty failure and artery bypass occlusion. Emodin, an anthraquinone with multiple physiological activities, has been reported to inhibit proliferation of vascular smooth muscle cells (VSMCs) that might cause intimal arterial thickening. Thus, in this study, we established a rat model of balloon-injured carotid artery and investigated the therapeutic effect of emodin and its underlying mechanism. Intimal thickness was analyzed by hematoxylin and eosin staining. Expression of Wnt4, dvl-1, β-catenin and collagen was determined by immunohistochemistry and/or western blotting. The proliferation of VSMC was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and electron microscopy. MicroRNA levels were quantified by real-time quantitative PCR. Emodin relieved injury-induced artery intimal thickness. Results of western blots and immunohistochemistry showed that emodin suppressed expression of signaling molecules Wnt4/Dvl-1/β-catenin as well as collagen protein in the injured artery. In addition, emodin enhanced expression of an artery injury-related microRNA, miR-126. In vitro, MTT assay showed that emodin suppressed angiotensin II (AngII)-induced proliferation of VSMCs. Emodin reversed AngII-induced activation of Wnt4/Dvl-1/β-catenin signaling by increasing expression of miR-126 that was strongly supported by transfection of mimic or inhibitor for miR-126. Emodin prevents intimal thickening via Wnt4/Dvl-1/β-catenin signaling pathway mediated by miR-126 in balloon-injured carotid artery of rats. PMID:26113441

Melatonin prevents human pancreatic carcinoma cell PANC-1-induced human umbilical vein endothelial cell proliferation and migration by inhibiting vascular endothelial growth factor expression.

PubMed

Cui, Peilin; Yu, Minghua; Peng, Xingchun; Dong, Lv; Yang, Zhaoxu

2012-03-01

Melatonin is an important natural oncostatic agent, and our previous studies have found its inhibitory action on tumor angiogenesis, but the mechanism remains unclear. It is well known that vascular endothelial growth factor (VEGF) plays key roles in tumor angiogenesis and has become an important target for antitumor therapy. Pancreatic cancer is a representative of the most highly vascularized and angiogenic solid tumors, which responds poorly to chemotherapy and radiation. Thus, seeking new treatment strategies targeting which have anti-angiogenic capability is urgent in clinical practice. In this study, a co-culture system between human umbilical vein endothelial cells (HUVECs) and pancreatic carcinoma cells (PANC-1) was used to investigate the direct effect of melatonin on the tumor angiogenesis and its possible action on VEGF expression. We found HUVECs exhibited an increased cell proliferation and cell migration when co-cultured with PANC-1 cells, but the process was prevented when melatonin added to the incubation medium. Melatonin at concentrations of 1 μm and 1 mm inhibited the cell proliferation and migration of HUVECs and also decreased both the VEGF protein secreted to the cultured medium and the protein produced by the PANC-1 cells. In addition, the VEGF mRNA expression was also down-regulated by melatonin. Taken together, our present study shows that melatonin at pharmacological concentrations inhibited the elevated cell proliferation and cell migration of HUVECs stimulated by co-culturing them with PANC-1 cells; this was associated with a suppression of VEGF expression in PANC-1 cells. © 2011 John Wiley & Sons A/S.

TLX is an intrinsic regulator of the negative effects of IL-1β on proliferating hippocampal neural progenitor cells.

PubMed

Ó'Léime, Ciarán S; Kozareva, Danka A; Hoban, Alan E; Long-Smith, Caitriona M; Cryan, John F; Nolan, Yvonne M

2018-02-01

Hippocampal neurogenesis is a lifelong process whereby new neurons are produced and integrate into the host circuitry within the hippocampus. It is regulated by a multitude of extrinsic and intrinsic regulators and is believed to contribute to certain hippocampal-dependent cognitive tasks. Hippocampal neurogenesis and associated cognition have been demonstrated to be impaired after increases in the levels of proinflammatory cytokine IL-1β in the hippocampus, such as that which occurs in various neurodegenerative and psychiatric disorders. IL-1β also suppresses the expression of TLX (orphan nuclear receptor tailless homolog), which is an orphan nuclear receptor that functions to promote neural progenitor cell (NPC) proliferation and suppress neuronal differentiation; therefore, manipulation of TLX represents a potential strategy with which to prevent the antiproliferative effects of IL-1β. In this study, we assessed the mechanism that underlies IL-1β-induced changes in TLX expression and determined the protective capacity of TLX to mitigate the effects of IL-1β on embryonic rat hippocampal neurosphere expansion. We demonstrate that IL-1β activated the NF-κB pathway in proliferating NPCs and that this activation was responsible for IL-1β-induced changes in TLX expression. In addition, we report that enhancing TLX expression prevented the IL-1β-induced suppression of neurosphere expansion. Thus, we highlight TLX as a potential protective regulator of the antiproliferative effects of IL-1β on hippocampal neurogenesis.-Ó'Léime, C. S., Kozareva, D. A., Hoban, A. E., Long-Smith, C. M., Cryan, J. F., Nolan, Y. M. TLX is an intrinsic regulator of the negative effects of IL-1β on proliferating hippocampal neural progenitor cells.

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

Achanzar, William E.; Moyer, Carolyn F.; Marthaler, Laura T.

We previously reported prevention of urolithiasis and associated rat urinary bladder tumors by urine acidification (via diet acidification) in male rats treated with the dual peroxisome proliferator-activated receptor (PPAR){alpha}/{gamma} agonist muraglitazar. Because urine acidification could potentially alter PPAR signaling and/or cellular proliferation in urothelium, we evaluated urothelial cell PPAR{alpha}, PPAR{delta}, PPAR{gamma}, and epidermal growth factor receptor (EGFR) expression, PPAR signaling, and urothelial cell proliferation in rats fed either a normal or an acidified diet for 5, 18, or 33 days. A subset of rats in the 18-day study also received 63 mg/kg of the PPAR{gamma} agonist pioglitazone daily for themore » final 3 days to directly assess the effects of diet acidification on responsiveness to PPAR{gamma} agonism. Urothelial cell PPAR{alpha} and {gamma} expression and signaling were evaluated in the 18- and 33-day studies by immunohistochemical assessment of PPAR protein (33-day study only) and quantitative real-time polymerase chain reaction (qRT-PCR) measurement of PPAR-regulated gene expression. In the 5-day study, EGFR expression and phosphorylation status were evaluated by immunohistochemical staining and egfr and akt2 mRNA levels were assessed by qRT-PCR. Diet acidification did not alter PPAR{alpha}, {delta}, or {gamma} mRNA or protein expression, PPAR{alpha}- or {gamma}-regulated gene expression, total or phosphorylated EGFR protein, egfr or akt2 gene expression, or proliferation in urothelium. Moreover, diet acidification had no effect on pioglitazone-induced changes in urothelial PPAR{gamma}-regulated gene expression. These results support the contention that urine acidification does not prevent PPAR{gamma} agonist-induced bladder tumors by altering PPAR{alpha}, {gamma}, or EGFR expression or PPAR signaling in rat bladder urothelium.« less

IL-4-secreting eosinophils promote endometrial stromal cell proliferation and prevent Chlamydia-induced upper genital tract damage.

PubMed

Vicetti Miguel, Rodolfo D; Quispe Calla, Nirk E; Dixon, Darlene; Foster, Robert A; Gambotto, Andrea; Pavelko, Stephen D; Hall-Stoodley, Luanne; Cherpes, Thomas L

2017-08-15

Genital Chlamydia trachomatis infections in women typically are asymptomatic and do not cause permanent upper genital tract (UGT) damage. Consistent with this presentation, type 2 innate and T H 2 adaptive immune responses associated with dampened inflammation and tissue repair are elicited in the UGT of Chlamydia -infected women. Primary C. trachomatis infection of mice also causes no genital pathology, but unlike women, does not generate Chlamydia -specific T H 2 immunity. Herein, we explored the significance of type 2 innate immunity for restricting UGT tissue damage in Chlamydia -infected mice, and in initial studies intravaginally infected wild-type, IL-10 -/- , IL-4 -/- , and IL-4Rα -/- mice with low-dose C. trachomatis inoculums. Whereas Chlamydia was comparably cleared in all groups, IL-4 -/- and IL-4Rα -/- mice displayed endometrial damage not seen in wild-type or IL-10 -/- mice. Congruent with the aberrant tissue repair in mice with deficient IL-4 signaling, we found that IL-4Rα and STAT6 signaling mediated IL-4-induced endometrial stromal cell (ESC) proliferation ex vivo, and that genital administration of an IL-4-expressing adenoviral vector greatly increased in vivo ESC proliferation. Studies with IL-4-IRES-eGFP (4get) reporter mice showed eosinophils were the main IL-4-producing endometrial leukocyte (constitutively and during Chlamydia infection), whereas studies with eosinophil-deficient mice identified this innate immune cell as essential for endometrial repair during Chlamydia infection. Together, our studies reveal IL-4-producing eosinophils stimulate ESC proliferation and prevent Chlamydia -induced endometrial damage. Based on these results, it seems possible that the robust type 2 immunity elicited by Chlamydia infection of human genital tissue may analogously promote repair processes that reduce phenotypic disease expression.

α-Lipoic acid inhibits human lung cancer cell proliferation through Grb2-mediated EGFR downregulation.

PubMed

Yang, Lan; Wen, Ya; Lv, Guoqing; Lin, Yuntao; Tang, Junlong; Lu, Jingxiao; Zhang, Manqiao; Liu, Wen; Sun, Xiaojuan

2017-12-09

Alpha lipoic acid (α -LA) is a naturally occurring antioxidant and metabolic enzyme co-factor. Recently, α -LA has been reported to inhibit the growth of various cancer cells, but the precise signaling pathways that mediate the effects of α -LA on non-small cell lung cancer (NSCLC) development remain unclear. The CCK-8 assay was used to assess cell proliferation in NSCLC cell lines after α -LA treatment. The expression of growth factor receptor-bound protein 2 (Grb2), cyclin-dependent kinase (CDK)-2, CDK4, CDK6, Cyclin D3, Cyclin E1, Ras, c-Raf, epidermal growth factor receptor (EGFR), ERK1/2 and activated EGFR and ERK1/2 was evaluated by western blotting. Grb2 levels were restored in α-LA-treated cells by transfection of a plasmid carrying Grb2 and were reduced in NSCLC cells via specific siRNA-mediated knockdown. α -LA dramatically decreased NSCLC cell proliferation by downregulating Grb2; in contrast, Grb2 overexpression significantly prevented α-LA-induced decrease in cell growth in vitro. Western blot analysis indicated that α-LA decreased the levels of phospho-EGFR, CDK2/4/6, Cyclins D3 and E1, which are associated with the inhibition of G1/S-phase transition. Additional experiments indicated that Grb2 inhibition partially abolished EGF-induced phospho-EGFR and phospho-ERK1/2 activity. In addition, α-LA exerted greater inhibitory effects than gefitinib on NSCLC cells by preventing EGF-induced EGFR activation. For the first time, these findings provide the first evidence that α-LA inhibits cell proliferation through Grb2 by suppressing EGFR phosphorylation and that MAPK/ERK is involved in this pathway. Copyright © 2017. Published by Elsevier Inc.

Slow-cycling stem cells in hydra contribute to head regeneration

PubMed Central

Govindasamy, Niraimathi; Murthy, Supriya; Ghanekar, Yashoda

2014-01-01

ABSTRACT Adult stem cells face the challenge of maintaining tissue homeostasis by self-renewal while maintaining their proliferation potential over the lifetime of an organism. Continuous proliferation can cause genotoxic/metabolic stress that can compromise the genomic integrity of stem cells. To prevent stem cell exhaustion, highly proliferative adult tissues maintain a pool of quiescent stem cells that divide only in response to injury and thus remain protected from genotoxic stress. Hydra is a remarkable organism with highly proliferative stem cells and ability to regenerate at whole animal level. Intriguingly, hydra does not display consequences of high proliferation, such as senescence or tumour formation. In this study, we investigate if hydra harbours a pool of slow-cycling stem cells that could help prevent undesirable consequences of continuous proliferation. Hydra were pulsed with the thymidine analogue 5-ethynyl-2′-deoxyuridine (EdU) and then chased in the absence of EdU to monitor the presence of EdU-retaining cells. A significant number of undifferentiated cells of all three lineages in hydra retained EdU for about 8–10 cell cycles, indicating that these cells did not enter cell cycle. These label-retaining cells were resistant to hydroxyurea treatment and were predominantly in the G2 phase of cell cycle. Most significantly, similar to mammalian quiescent stem cells, these cells rapidly entered cell division during head regeneration. This study shows for the first time that, contrary to current beliefs, cells in hydra display heterogeneity in their cell cycle potential and the slow-cycling cells in this population enter cell cycle during head regeneration. These results suggest an early evolution of slow-cycling stem cells in multicellular animals. PMID:25432513

The Crataegus extract WS 1442 inhibits balloon catheter-induced intimal hyperplasia in the rat carotid artery by directly influencing PDGFR-beta.

PubMed

Fürst, Robert; Zirrgiebel, Ute; Totzke, Frank; Zahler, Stefan; Vollmar, Angelika M; Koch, Egon

2010-08-01

Effective systemic drugs against restenosis upon percutaneous transluminal coronary angioplasty (PTCA) are largely lacking. Polyphenols have been suggested to ameliorate post-angioplasty restenosis. Hawthorn (Crataegus spp.) extracts, which are among the most frequently used herbal medicinal products against mild forms of congestive heart failure, contain polyphenols, but have not been investigated in this context. We aimed to assess the potential of the hawthorn extract WS 1442 to prevent balloon catheter-induced intimal hyperplasia and to elucidate the underlying mechanisms. We analyzed the effects of WS 1442 on serum-induced vascular smooth muscle cell (VSMC) and endothelial cell (EC) growth and migration, growth factor-induced proliferation, growth factor receptor activity, and neointima formation in the rat carotid artery model. WS 1442 (100 microg/ml) decreased VSMC migration by 38% and proliferation by 44%, whereas EC migration and proliferation were unaltered. The extract inhibited VSMC DNA synthesis induced by platelet-derived growth factor (PDGF) (IC(50): 47 microg/ml), but not that of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Along this line, WS 1442 blocked recombinant human PDGF receptor (PDGFR)-beta kinase activity (IC(50): 1.4 microg/ml) and decreased PDGFR-beta activation and extracellular signal-regulated kinase (ERK) activation in VSMCs. In rats, orally administered WS 1442 significantly reduced neointima formation after balloon catheter dilatation of the carotid artery. WS 1442 inhibits migration and proliferation of VSMCs, but not of ECs, and reduces balloon catheter-evoked neointima formation probably through inhibition of PDGFR-beta. Thus, the present study suggests a novel adjunct pharmacological strategy to prevent angioplasty-related restenosis. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling

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

Son, Dong Ju; Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA; Kim, Soo Yeon

2012-10-19

Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murinemore » model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.« less

Age-related changes in select fecal bacteria in foals

USDA-ARS?s Scientific Manuscript database

Adult horses depend on the microbial community in the hindgut to produce VFAs that are utilized for energy. Microbial colonization in the gastrointestinal tract of foals is essential to develop a healthy symbiotic relationship and prevent proliferation of pathogenic bacteria. However, colonization i...

Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet

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

Jin Haiyan; Department of Gastroenterology and Hepatology, Yanbian University Hospital, Yanji, Jilin; Yamamoto, Naoki

2007-12-28

Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor {gamma} activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions bymore » down-regulating TGF{beta}1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis.« less

Local delivery of hormonal therapy with silastic tubing for prevention and treatment of breast cancer.

PubMed

Park, Jeenah; Thomas, Scott; Zhong, Allison Y; Wolfe, Alan R; Krings, Gregor; Terranova-Barberio, Manuela; Pawlowska, Nela; Benet, Leslie Z; Munster, Pamela N

2018-01-08

Broad use of germline testing has identified an increasing number of women at risk for breast cancer with a need for effective chemoprevention. We report a novel method to selectively deliver various anti-estrogens at high drug levels to the breast tissue by implanting a device comprised of silastic tubing. Optimized tubing properties allow elution of otherwise poorly bioavailable anti-estrogens, such as fulvestrant, into mammary tissue in vitro and in vivo with levels sufficient to inhibit estrogen receptor activation and tumor cell proliferation. Implantable silastic tubing delivers fulvestrant selectively to mouse mammary fat tissue for one year with anti-tumor effects similar to those achieved with systemic fulvestrant exposure. Furthermore, local delivery of fulvestrant significantly decreases cell proliferation, as assessed by Ki67 expression, most effectively in tumor sections adjacent to tubing. This approach may thereby introduce a potential paradigm shift and offer a promising alternative to systemic therapy for prevention and early interception of breast cancer.

Testosterone and breast cancer prevention.

PubMed

Glaser, R; Dimitrakakis, C

2015-11-01

Testosterone (T) is the most abundant biologically active hormone in women. Androgen receptors (AR) are located throughout the body including the breast where T decreases tissue proliferation. However, T can be aromatized to estradiol (E2), which increases proliferation and hence, breast cancer (BCA) risk. Increased aromatase expression and an imbalance in the ratio of stimulatory estrogens to protective androgens impacts breast homeostasis. Recent clinical data supports a role for T in BCA prevention. Women with symptoms of hormone deficiency treated with pharmacological doses of T alone or in combination with anastrozole (A), delivered by subcutaneous implants, had a reduced incidence of BCA. In addition, T combined with A effectively treated symptoms of hormone deficiency in BCA survivors and was not associated with recurrent disease. Most notably, T+A implants placed in breast tissue surrounding malignant tumors significantly reduced BCA tumor size, further supporting T direct antiproliferative, protective and therapeutic effect. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Microbial biofilm proliferation within sealer-root dentin interfaces is affected by sealer type and aging period.

PubMed

Roth, Karina A; Friedman, Shimon; Lévesque, Céline M; Basrani, Bettina R; Finer, Yoav

2012-09-01

Root canal fillings are intended to prevent microbial proliferation over time in the canal after treatment. The objective of this study was to assess biofilm proliferation within the sealer-dentin interfaces of 2 methacrylate resin-based systems, self-etch (SE) and total-etch (TE), and an epoxy resin-based sealer (EP), aged for up to 6 months. Standardized specimens (n = 45) comprising the coronal 5 mm of human roots were filled with the test materials and gutta-percha. Specimens were either not preincubated (control, n = 9) or were incubated in sterile saline for 1 week, 1 month, 3 months, or 6 months (n = 3/group). Monospecies biofilms of Enterococcus faecalis were grown on the specimens for 7 days in a chemostat-based biofilm fermentor mimicking pathogenic oral conditions. The extent of E. faecalis proliferation within the sealer-dentin interface for each material and incubation period group was assessed by using fluorescence microscopy of dihydroethidium-stained specimens. TE had less biofilm proliferation than both EP and SE (P < .01). Deeper biofilm proliferation was detected in SE and EP specimens aged for 1 and 3 months than those aged for 1 week or 6 months (P < .05). Maximum depth of biofilm penetration was recorded for SE at 1 month (P < .05). Within the test model used, the SE and EP sealers were more susceptible to interfacial biofilm proliferation than the TE restorative material. This susceptibility diminished after aging the materials' interfaces for 6 months. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Systematic review: internet-based program for youth smoking prevention and cessation.

PubMed

Park, Eunhee; Drake, Emily

2015-01-01

To review the characteristics and effects Internet-based youth smoking prevention and cessation programs. Systematic review of published articles in peer-reviewed journals in the past 10 years, focused on Internet-based youth smoking prevention and cessation programs. Twelve articles were selected based on the following criteria: studies reporting the outcomes of Internet-based smoking cessation or prevention intervention programs for adolescents who are younger than 24 years. The components of youth Internet-based smoking intervention programs are analyzed based on study features (i.e., sample, design, theoretical basis, analysis, outcome measures) and program characteristics (i.e., focus, setting, frequency, duration, intensity, and different components) that make the programs effective. The most common components of effective Internet-based programs are identified as the following: the use of multimedia, tailored approaches, personalized feedback, and interactive features. The characteristics and effects of the programs vary, but most programs show positive results in youth smoking prevention and cessation in spite of the studies' limitations. The evidence from this review provides useful information of recent efforts related to Internet-based youth smoking prevention and cessation programs, which can have significant clinical implications in developing future innovative youth smoking prevention and intervention programs. © 2014 Sigma Theta Tau International.

A systematic review of evaluated suicide prevention programs targeting indigenous youth.

PubMed

Harlow, Alyssa F; Bohanna, India; Clough, Alan

2014-01-01

Indigenous young people have significantly higher suicide rates than their non-indigenous counterparts. There is a need for culturally appropriate and effective suicide prevention programs for this demographic. This review assesses suicide prevention programs that have been evaluated for indigenous youth in Australia, Canada, New Zealand, and the United States. The databases MEDLINE and PsycINFO were searched for publications on suicide prevention programs targeting indigenous youth that include reports on evaluations and outcomes. Program content, indigenous involvement, evaluation design, program implementation, and outcomes were assessed for each article. The search yielded 229 articles; 90 abstracts were assessed, and 11 articles describing nine programs were reviewed. Two Australian programs and seven American programs were included. Programs were culturally tailored, flexible, and incorporated multiple-levels of prevention. No randomized controlled trials were found, and many programs employed ad hoc evaluations, poor program description, and no process evaluation. Despite culturally appropriate content, the results of the review indicate that more controlled study designs using planned evaluations and valid outcome measures are needed in research on indigenous youth suicide prevention. Such changes may positively influence the future of research on indigenous youth suicide prevention as the outcomes and efficacy will be more reliable.

Optimizing Implementation of Obesity Prevention Programs: A Qualitative Investigation Within a Large-Scale Randomized Controlled Trial.

PubMed

Kozica, Samantha L; Teede, Helena J; Harrison, Cheryce L; Klein, Ruth; Lombard, Catherine B

2016-01-01

The prevalence of obesity in rural and remote areas is elevated in comparison to urban populations, highlighting the need for interventions targeting obesity prevention in these settings. Implementing evidence-based obesity prevention programs is challenging. This study aimed to investigate factors influencing the implementation of obesity prevention programs, including adoption, program delivery, community uptake, and continuation, specifically within rural settings. Nested within a large-scale randomized controlled trial, a qualitative exploratory approach was adopted, with purposive sampling techniques utilized, to recruit stakeholders from 41 small rural towns in Australia. In-depth semistructured interviews were conducted with clinical health professionals, health service managers, and local government employees. Open coding was completed independently by 2 investigators and thematic analysis undertaken. In-depth interviews revealed that obesity prevention programs were valued by the rural workforce. Program implementation is influenced by interrelated factors across: (1) contextual factors and (2) organizational capacity. Key recommendations to manage the challenges of implementing evidence-based programs focused on reducing program delivery costs, aided by the provision of a suite of implementation and evaluation resources. Informing the scale-up of future prevention programs, stakeholders highlighted the need to build local rural capacity through developing supportive university partnerships, generating local program ownership and promoting active feedback to all program partners. We demonstrate that the rural workforce places a high value on obesity prevention programs. Our results inform the future scale-up of obesity prevention programs, providing an improved understanding of strategies to optimize implementation of evidence-based prevention programs. © 2015 National Rural Health Association.

The effects of selected drugs and dietary compounds on proliferation and apoptosis in colorectal carcinoma.

PubMed

Kiedrowski, Miroslaw; Mroz, Andrzej

2014-01-01

Like many malignancies, the development of colorectal carcinoma (CRC) can be considered as an imbalance between the compromised process of programmed cell death (apoptosis) and excessive, uncontrolled proliferation. Several mutations and epigenetic alterations are acquired during colorectal carcinogenesis. These are responsible for the cell cycle regulation, cellular sensitivity to pro- and antiapoptotic factors, cell proliferation, angiogenesis, invasiveness, as well as metastatic potential. The molecular alterations, along with their morphological expressions, have been recognised in detail, and most of the CRC cases can be attributed to either adenoma-carcinoma or serrated neoplasia pathways: in the first, the antiapoptotic features prevail; while in the second, the proliferative activity is of the utmost importance. The aim of the work is to discuss the influence of selected drugs and dietary compounds on the proliferation and apoptosis in CRC.

IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1

PubMed Central

Ruckerl, Dominik; Thomas, Graham D.; Hewitson, James P.; Duncan, Sheelagh; Brombacher, Frank; Maizels, Rick M.; Hume, David A.; Allen, Judith E.

2013-01-01

Macrophages (MΦs) colonize tissues during inflammation in two distinct ways: recruitment of monocyte precursors and proliferation of resident cells. We recently revealed a major role for IL-4 in the proliferative expansion of resident MΦs during a Th2-biased tissue nematode infection. We now show that proliferation of MΦs during intestinal as well as tissue nematode infection is restricted to sites of IL-4 production and requires MΦ-intrinsic IL-4R signaling. However, both IL-4Rα–dependent and –independent mechanisms contributed to MΦ proliferation during nematode infections. IL-4R–independent proliferation was controlled by a rise in local CSF-1 levels, but IL-4Rα expression conferred a competitive advantage with higher and more sustained proliferation and increased accumulation of IL-4Rα+ compared with IL-4Rα− cells. Mechanistically, this occurred by conversion of IL-4Rα+ MΦs from a CSF-1–dependent to –independent program of proliferation. Thus, IL-4 increases the relative density of tissue MΦs by overcoming the constraints mediated by the availability of CSF-1. Finally, although both elevated CSF1R and IL-4Rα signaling triggered proliferation above homeostatic levels, only CSF-1 led to the recruitment of monocytes and neutrophils. Thus, the IL-4 pathway of proliferation may have developed as an alternative to CSF-1 to increase resident MΦ numbers without coincident monocyte recruitment. PMID:24101381

IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1.

PubMed

Jenkins, Stephen J; Ruckerl, Dominik; Thomas, Graham D; Hewitson, James P; Duncan, Sheelagh; Brombacher, Frank; Maizels, Rick M; Hume, David A; Allen, Judith E

2013-10-21

Macrophages (MΦs) colonize tissues during inflammation in two distinct ways: recruitment of monocyte precursors and proliferation of resident cells. We recently revealed a major role for IL-4 in the proliferative expansion of resident MΦs during a Th2-biased tissue nematode infection. We now show that proliferation of MΦs during intestinal as well as tissue nematode infection is restricted to sites of IL-4 production and requires MΦ-intrinsic IL-4R signaling. However, both IL-4Rα-dependent and -independent mechanisms contributed to MΦ proliferation during nematode infections. IL-4R-independent proliferation was controlled by a rise in local CSF-1 levels, but IL-4Rα expression conferred a competitive advantage with higher and more sustained proliferation and increased accumulation of IL-4Rα(+) compared with IL-4Rα(-) cells. Mechanistically, this occurred by conversion of IL-4Rα(+) MΦs from a CSF-1-dependent to -independent program of proliferation. Thus, IL-4 increases the relative density of tissue MΦs by overcoming the constraints mediated by the availability of CSF-1. Finally, although both elevated CSF1R and IL-4Rα signaling triggered proliferation above homeostatic levels, only CSF-1 led to the recruitment of monocytes and neutrophils. Thus, the IL-4 pathway of proliferation may have developed as an alternative to CSF-1 to increase resident MΦ numbers without coincident monocyte recruitment.

Cell proliferation and apoptosis during histogenesis of the guinea pig and rabbit cerebellar cortex.

PubMed

Lossi, Laura; Coli, Alessandra; Giannessi, Elisabetta; Stornelli, Maria Rita; Marroni, Paolo

2002-01-01

Cell proliferation and apoptosis are essential for development of the nervous system. In this study we have investigated the histogenesis of the cerebellar cortex in guinea pig (a precocial species) and rabbit (an altricial species) at different stages of pregnancy and postnatal life. Proliferating cells were identified after labeling with antibodies against the proliferating cell nuclear antigen (PCNA) and/or the Ki-67 antigen. Apoptotic cells were visualized in situ by the TUNEL method and by immunodetection of cleaved caspase 3 and 9. In guinea pigs, both proliferating and apoptotic cells were detected during pre-natal life (E0-E40). Conversely, cell proliferation and apoptosis in rabbits were temporally restricted to early postnatal weeks (P0-P20). In both species cell proliferation was mainly linked to differentiation and migration of the granule cells. In both species, the majority of cells undergoing programmed cell death likely corresponded to granule cells. They were mainly detected in the external granular layer, and were by far more common than previously reported in other locations of the postnatal brain. This study shows that apoptosis is a shared process of cell death during cerebellar development in both altricial and precocial animals, and that there is a direct spatial and temporal correlation between cell proliferation and death in two mammals with different time tables in cerebellar maturation.

Substance use among Asian-American adolescents: perceptions of use and preferences for prevention programming.

PubMed

Fang, Lin; Barnes-Ceeney, Kevin; Lee, Rebecca A; Tao, John

2011-01-01

Rarely has substance use prevention programming targeted Asian-American adolescents. Using a focus group methodology, we explored perceptions of substance use and preferences for prevention programming among 31 Asian-American adolescents in New York City. Participants considered substance use common in the community. Factors contributing to substance use among Asian-American adolescents (e.g., peer pressure, pressure to achieve, family factors, and community influence) were identified, and the need for prevention programs tailored for the Asian-American community was highlighted. Participants discussed preferred program content, delivery settings, and recruitment and retention strategies. Despite the favorable attitude for family-based prevention programming, participants raised potential issues concerning the feasibility of such a program. Study findings facilitate understanding of Asian-American adolescents' substance use behavior and shed light on prevention program development for this underserved population.

Opposing effects of TIGAR- and RAC1-derived ROS on Wnt-driven proliferation in the mouse intestine

PubMed Central

Cheung, Eric C.; Lee, Pearl; Ceteci, Fatih; Nixon, Colin; Blyth, Karen; Sansom, Owen J.; Vousden, Karen H.

2016-01-01

Reactive oxygen species (ROS) participate in numerous cell responses, including proliferation, DNA damage, and cell death. Based on these disparate activities, both promotion and inhibition of ROS have been proposed for cancer therapy. However, how the ROS response is determined is not clear. We examined the activities of ROS in a model of Apc deletion, where loss of the Wnt target gene Myc both rescues APC loss and prevents ROS accumulation. Following APC loss, Myc has been shown to up-regulate RAC1 to promote proliferative ROS through NADPH oxidase (NOX). However, APC loss also increased the expression of TIGAR, which functions to limit ROS. To explore this paradox, we used three-dimensional (3D) cultures and in vivo models to show that deletion of TIGAR increased ROS damage and inhibited proliferation. These responses were suppressed by limiting damaging ROS but enhanced by lowering proproliferative NOX-derived ROS. Despite having opposing effects on ROS levels, loss of TIGAR and RAC1 cooperated to suppress intestinal proliferation following APC loss. Our results indicate that the pro- and anti-proliferative effects of ROS can be independently modulated in the same cell, with two key targets in the Wnt pathway functioning to integrate the different ROS signals for optimal cell proliferation. PMID:26679840

Aspirin therapy reduces the ability of platelets to promote colon and pancreatic cancer cell proliferation: Implications for the oncoprotein c-MYC

PubMed Central

Sylman, Joanna L.; Ngo, Anh T. P.; Pang, Jiaqing; Sears, Rosalie C.; Williams, Craig D.; McCarty, Owen J. T.

2017-01-01

Aspirin, an anti-inflammatory and antithrombotic drug, has become the focus of intense research as a potential anticancer agent owing to its ability to reduce tumor proliferation in vitro and to prevent tumorigenesis in patients. Studies have found an anticancer effect of aspirin when used in low, antiplatelet doses. However, the mechanisms through which low-dose aspirin works are poorly understood. In this study, we aimed to determine the effect of aspirin on the cross talk between platelets and cancer cells. For our study, we used two colon cancer cell lines isolated from the same donor but characterized by different metastatic potential, SW480 (nonmetastatic) and SW620 (metastatic) cancer cells, and a pancreatic cancer cell line, PANC-1 (nonmetastatic). We found that SW480 and PANC-1 cancer cell proliferation was potentiated by human platelets in a manner dependent on the upregulation and activation of the oncoprotein c-MYC. The ability of platelets to upregulate c-MYC and cancer cell proliferation was reversed by an antiplatelet concentration of aspirin. In conclusion, we show for the first time that inhibition of platelets by aspirin can affect their ability to induce cancer cell proliferation through the modulation of the c-MYC oncoprotein. PMID:27903583

A synthetic peptide derived from alpha-fetoprotein inhibits the estradiol-induced proliferation of mammary tumor cells in culture through the modulation of p21.

PubMed

Sierralta, Walter D; Epuñan, María J; Reyes, José M; Valladares, Luis E; Pino, Ana M

2008-01-01

A stable cyclized 9-mer peptide (cP) containing the active site of alpha-alpha fetoprotein (alphaFP) has been shown to be effective for prevention of estrogen-stimulated tumor cell proliferation in culture or of xenographt growth in immunodeficient mice. cP does not block 17beta-estradiol (E2) binding to its receptors, but rather appears to interfere with intracellular processing of the signal that supports growth. To obtain insight on that mechanism we studied the effect of cP on the proliferation of MCF-7 cells in culture. Proliferation in the presence of 2 microM E2 is decreased up to 40% upon addition of 2 microg ml(-1) cP to the medium; the presence of cP did not increase cell death, cP reduced also the proliferation of estrogen-dependent ZR75-1 cells but had no effect on autonomous MDA-MB-231 cells, cP did not modify the number of binding sites for labeled E2 or affected cell death. We detected increased nuclear p21Cip1 immunoreactivity after cP treatment. Our results suggest that cP acts via p21Cip1 to slow the process of MCF-7 cells through the cycle.

Claudin-18-mediated YAP activity regulates lung stem and progenitor cell homeostasis and tumorigenesis.

PubMed

Zhou, Beiyun; Flodby, Per; Luo, Jiao; Castillo, Dan R; Liu, Yixin; Yu, Fa-Xing; McConnell, Alicia; Varghese, Bino; Li, Guanglei; Chimge, Nyam-Osor; Sunohara, Mitsuhiro; Koss, Michael N; Elatre, Wafaa; Conti, Peter; Liebler, Janice M; Yang, Chenchen; Marconett, Crystal N; Laird-Offringa, Ite A; Minoo, Parviz; Guan, Kunliang; Stripp, Barry R; Crandall, Edward D; Borok, Zea

2018-03-01

Claudins, the integral tight junction (TJ) proteins that regulate paracellular permeability and cell polarity, are frequently dysregulated in cancer; however, their role in neoplastic progression is unclear. Here, we demonstrated that knockout of Cldn18, a claudin family member highly expressed in lung alveolar epithelium, leads to lung enlargement, parenchymal expansion, increased abundance and proliferation of known distal lung progenitors, the alveolar epithelial type II (AT2) cells, activation of Yes-associated protein (YAP), increased organ size, and tumorigenesis in mice. Inhibition of YAP decreased proliferation and colony-forming efficiency (CFE) of Cldn18-/- AT2 cells and prevented increased lung size, while CLDN18 overexpression decreased YAP nuclear localization, cell proliferation, CFE, and YAP transcriptional activity. CLDN18 and YAP interacted and colocalized at cell-cell contacts, while loss of CLDN18 decreased YAP interaction with Hippo kinases p-LATS1/2. Additionally, Cldn18-/- mice had increased propensity to develop lung adenocarcinomas (LuAd) with age, and human LuAd showed stage-dependent reduction of CLDN18.1. These results establish CLDN18 as a regulator of YAP activity that serves to restrict organ size, progenitor cell proliferation, and tumorigenesis, and suggest a mechanism whereby TJ disruption may promote progenitor proliferation to enhance repair following injury.

Higher Molecular Weight Polyethylene Glycol Increases Cell Proliferation While Improving Barrier Function in an In Vitro Colon Cancer Model

PubMed Central

Bharadwaj, Shruthi; Vishnubhotla, Ramana; Shan, Sun; Chauhan, Chinmay; Cho, Michael; Glover, Sarah C.

2011-01-01

Polyethylene glycol (PEG) has been previously shown to protect against enteric pathogens and prevent colon cancer invasion. To determine if PEG could indeed protect against previously observed pro-invasive effects of commensal E. coli and EPEC, Caco-2 cells grown in an in vitro model of colon cancer were infected with strains of human commensal E. coli or EPEC and treated with 10% PEG 3350, PEG 8000, and PEG 20,000, respectively. At 24 hours after infection, MMP-1 and MMP-13 activities, cell cluster thickness, depth of invasion, and proliferation were determined using standard molecular biology techniques and advanced imaging. We found that higher molecular weight PEG, especially PEG 8000 and 20,000, regardless of bacterial infection, increased proliferation and depth of invasion although a decrease in cellular density and MMP-1 activity was also noted. Maximum proliferation and depth of invasion of Caco-2 cells was observed in scaffolds treated with a combination of commensal E. coli strain, HS4 and PEG 8000. In conclusion, we found that PEG 8000 increased cell proliferation and led to the preservation of cell density in cells treated with commensal bacteria. This is important, because the preservation of a proliferative response in colon cancer results in a more chemo-responsive tumor. PMID:21976966

Higher molecular weight polyethylene glycol increases cell proliferation while improving barrier function in an in vitro colon cancer model.

PubMed

Bharadwaj, Shruthi; Vishnubhotla, Ramana; Shan, Sun; Chauhan, Chinmay; Cho, Michael; Glover, Sarah C

2011-01-01

Polyethylene glycol (PEG) has been previously shown to protect against enteric pathogens and prevent colon cancer invasion. To determine if PEG could indeed protect against previously observed pro-invasive effects of commensal E. coli and EPEC, Caco-2 cells grown in an in vitro model of colon cancer were infected with strains of human commensal E. coli or EPEC and treated with 10% PEG 3350, PEG 8000, and PEG 20,000, respectively. At 24 hours after infection, MMP-1 and MMP-13 activities, cell cluster thickness, depth of invasion, and proliferation were determined using standard molecular biology techniques and advanced imaging. We found that higher molecular weight PEG, especially PEG 8000 and 20,000, regardless of bacterial infection, increased proliferation and depth of invasion although a decrease in cellular density and MMP-1 activity was also noted. Maximum proliferation and depth of invasion of Caco-2 cells was observed in scaffolds treated with a combination of commensal E. coli strain, HS4 and PEG 8000. In conclusion, we found that PEG 8000 increased cell proliferation and led to the preservation of cell density in cells treated with commensal bacteria. This is important, because the preservation of a proliferative response in colon cancer results in a more chemo-responsive tumor.

N-Acetylcysteine prevents congenital heart defects induced by pregestational diabetes

PubMed Central

2014-01-01

Background Pregestational diabetes is a major risk factor of congenital heart defects (CHDs). Glutathione is depleted and reactive oxygen species (ROS) production is elevated in diabetes. In the present study, we aimed to examine whether treatment with N-acetylcysteine (NAC), which increases glutathione synthesis and inhibits ROS production, prevents CHDs induced by pregestational diabetes. Methods Female mice were treated with streptozotocin (STZ) to induce pregestational diabetes prior to breeding with normal males to produce offspring. Some diabetic mice were treated with N-acetylcysteine (NAC) in drinking water from E0.5 to the end of gestation or harvesting of the embryos. CHDs were identified by histology. ROS levels, cell proliferation and gene expression in the fetal heart were analyzed. Results Our data show that pregestational diabetes resulted in CHDs in 58% of the offspring, including ventricular septal defect (VSD), atrial septal defect (ASD), atrioventricular septal defects (AVSD), transposition of great arteries (TGA), double outlet right ventricle (DORV) and tetralogy of Fallot (TOF). Treatment with NAC in drinking water in pregestational diabetic mice completely eliminated the incidence of AVSD, TGA, TOF and significantly diminished the incidence of ASD and VSD. Furthermore, pregestational diabetes increased ROS, impaired cell proliferation, and altered Gata4, Gata5 and Vegf-a expression in the fetal heart of diabetic offspring, which were all prevented by NAC treatment. Conclusions Treatment with NAC increases GSH levels, decreases ROS levels in the fetal heart and prevents the development of CHDs in the offspring of pregestational diabetes. Our study suggests that NAC may have therapeutic potential in the prevention of CHDs induced by pregestational diabetes. PMID:24533448

Biotelemetry system for Epilepsy Seizure Control

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

Smith, LaCurtise; Bohnert, George W.

2009-07-02

The Biotelemetry System for Epilepsy Seizure Control Project developed and tested an automated telemetry system for use in an epileptic seizure prevention device that precisely controls localized brain temperature. This project was a result of a Department of Energy (DOE) Global Initiatives for Proliferation Prevention (GIPP) grant to the Kansas City Plant (KCP), Argonne National Laboratory (ANL), and Pacific Northwest National Laboratory (PNNL) to partner with Flint Hills Scientific, LLC, Lawrence, KS and Biophysical Laboratory Ltd (BIOFIL), Sarov, Russia to develop a method to help control epileptic seizures.

Remission of Collagen-Induced Arthritis through Combination Therapy of Microfracture and Transplantation of Thermogel-Encapsulated Bone Marrow Mesenchymal Stem Cells

PubMed Central

Liu, He; Ding, Jianxun; Wang, Jincheng; Wang, Yinan; Yang, Modi; Zhang, Yanbo; Chang, Fei; Chen, Xuesi

2015-01-01

The persistent inflammation of rheumatoid arthritis (RA) always leads to partial synovial hyperplasia and the destruction of articular cartilage. Bone marrow mesenchymal stem cells (BMMSCs) have been proven to possess immunosuppressive effects, and widely explored in the treatment of autoimmune diseases. However, poor inhibitory effect on local inflammatory state and limited capacity of preventing destruction of articular cartilage by systemic BMMSCs transplantation were observed. Herein, toward the classical type II collagen-induced arthritis in rats, the combination treatment of microfracture and in situ transplantation of thermogel-encapsulated BMMSCs was verified to obviously down-regulate the ratio of CD4+ to CD8+ T lymphocytes in peripheral blood. In addition, it resulted in the decreased levels of inflammatory cytokines, such as interleukin-1β, tumor necrosis factor-α and anti-collagen type II antibody, in the serum. Simultaneously, the combination therapy also could inhibit the proliferation of antigen specific lymphocytes and local joint inflammatory condition, and prevent the articular cartilage damage. The results indicated that the treatment programs could effectively stimulate the endogenous and exogenous BMMSCs to exhibit the immunosuppression and cartilage protection capability. This study provided a new therapeutic strategy for autoimmune inflammatory diseases, such as RA. PMID:25774788

Regulation of the proliferation of colon cancer cells by compounds that affect glycolysis, including 3-bromopyruvate, 2-deoxyglucose and biguanides.

PubMed

Lea, Michael A; Qureshi, Mehreen S; Buxhoeveden, Michael; Gengel, Nicolette; Kleinschmit, Jessica; Desbordes, Charles

2013-02-01

In previous studies performed by our group, we observed that 2-deoxyglucose blocked the acidification of the medium used for culture of colon cancer cells caused by incubation with biguanides and it had an additive inhibitory effect on growth. In the present work, we found that 3-bromopyruvate can also prevent the lowering of pH caused by biguanide treatment. 3-Bromopyruvate inhibited colonic cancer cell proliferation, but the effect was not always additive to that of biguanides and an additive effect was more notable in combined treatment with 3-bromopyruvate and 2-deoxyglucose. The induction of alkaline phosphatase activity by butyrate was not consistently affected by combination with other agents that modified glucose metabolism. The drug combinations that were examined inhibited proliferation of wild-type and p53-null cells and affected colonic cancer lines with different growth rates.

Regulation of the Proliferation of Colon Cancer Cells by Compounds that Affect Glycolysis, Including 3-Bromopyruvate, 2-Deoxyglucose and Biguanides

PubMed Central

Lea, Michael A.; Qureshi, Mehreen S.; Buxhoeveden, Michael; Gengel, Nicolette; Kleinschmit, Jessica; desBordes, Charles

2013-01-01

In previous studies we observed that 2-deoxyglucose blocked the acidification of the medium used for culture of colon cancer cells caused by incubation with biguanides and had an additive inhibitory effect on growth. In the present work, we found that 3-bromopyruvate can also prevent the lowering of pH caused by biguanide treatment. 3-Bromopyruvate inhibited colonic cancer cell proliferation but the effect was not always additive to that of biguanides and an additive effect was more notable in combined treatment with 3-bromopyruvate and 2-deoxyglucose. The induction of alkaline phosphatase activity by butyrate was not consistently affected by combination with other agents that modified glucose metabolism. The drug combinations that were examined inhibited proliferation of wild-type and P53 null cells and affected colonic cancer lines with different growth rates. PMID:23393330

Effects of Different Concentrations of Collagenous Peptide from Fish Scales on Osteoblast Proliferation and Osteoclast Resorption.

PubMed

Hu, Chung-Hsuan; Yao, Chun-Hsu; Chan, Tzu-Min; Huang, Teng-Le; Sen, Yang; Huang, Chih-Yang; Ho, Chien-Yi

2016-08-31

The incidence of osteoporosis has increased among the elderly population. Establishing a model of bone remodeling for screening new drugs is critical to identify safe and effective treatments for osteoporosis. In this study, we established a platform to investigate the therapeutic effects of collagenous peptides extracted from scales of two kinds of fish, namely, sparidae and chanos. These peptides were prepared using seven concentrations of collagenous peptide: 100, 80, 60, 40, 20, 10 and 1 mg/ml. Experimental results indicated that collagenous peptides promoted the proliferation of osteoblasts and inhibited the proliferation of mature osteoclasts; the effective concentration of collagenous peptide-sparidae was 10 mg/ml and that of collagenous peptide-chanos was 40 mg/ml. These findings demonstrate that, to a certain extent, collagenous peptides extracted from fish scales can be used to prevent osteoporosis to assist bone remodeling.

Nutlin-3 down-regulates retinoblastoma protein expression and inhibits muscle cell differentiation

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

Walsh, Erica M.; Niu, MengMeng; Bergholz, Johann

The p53 tumor suppressor gene plays a critical role in regulation of proliferation, cell death and differentiation. The MDM2 oncoprotein is a major negative regulator for p53 by binding to and targeting p53 for proteasome-mediated degradation. The small molecule inhibitor, nutlin-3, disrupts MDM2-p53 interaction resulting in stabilization and activation of p53 protein. We have previously shown that nutlin-3 activates p53, leading to MDM2 accumulation as concomitant of reduced retinoblastoma (Rb) protein stability. It is well known that Rb is important in muscle development and myoblast differentiation and that rhabdomyosarcoma (RMS), or cancer of the skeletal muscle, typically harbors MDM2 amplification.more » In this study, we show that nutlin-3 inhibited myoblast proliferation and effectively prevented myoblast differentiation, as evidenced by lack of expression of muscle differentiation markers including myogenin and myosin heavy chain (MyHC), as well as a failure to form multinucleated myotubes, which were associated with dramatic increases in MDM2 expression and decrease in Rb protein levels. These results indicate that nutlin-3 can effectively inhibit muscle cell differentiation. - Highlights: • Nutlin-3 inhibits myoblast proliferation and prevents differentiation into myotubes. • Nutlin-3 increases MDM2 expression and down-regulates Rb protein levels. • This study has implication in nutlin-3 treatment of rhabdomyosarcomas.« less

Heparin-binding EGF-like growth factor and enteric neural stem cell transplantation in the prevention of experimental necrotizing enterocolitis in mice.

PubMed

Wei, Jia; Zhou, Yu; Besner, Gail E

2015-07-01

Necrotizing enterocolitis (NEC) is associated with loss of neurons and glial cells in the enteric nervous system (ENS). Our goal was to determine whether enteric neural stem cell (NSC) transplantation, in conjunction with heparin-binding epidermal growth factor-like growth factor (HB-EGF), could protect against experimental NEC. In vitro, HB-EGF on NSC proliferation and migration, and the effects of receptors utilized by HB-EGF to exert these effects, were determined. In vivo, mouse pups were exposed to experimental NEC and treated with NSC alone, HB-EGF alone, NSC+HB-EGF, or HB-EGF overexpressing NSC. NSC engraftment and differentiation into neurons in the ENS, intestinal injury, intestinal permeability, and intestinal motility were determined. HB-EGF promoted NSC proliferation via ErbB-1 receptors and enhanced NSC migration via ErbB-1, ErbB-4, and Nardilysin receptors. HB-EGF significantly enhanced the engraftment of transplanted NSC into the ENS during NEC. NSC transplantation significantly reduced NEC incidence and improved gut barrier function and intestinal motility, and these effects were augmented by simultaneous administration of HB-EGF or by transplantation of HB-EGF overexpressing NSC. HB-EGF promotes NSC proliferation and migration. HB-EGF and NSC reduce intestinal injury and improve gut barrier function and intestinal motility in experimental NEC. Combined HB-EGF and NSC transplantation may represent a potential future therapy to prevent NEC.

Bee products prevent VEGF-induced angiogenesis in human umbilical vein endothelial cells.

PubMed

Izuta, Hiroshi; Shimazawa, Masamitsu; Tsuruma, Kazuhiro; Araki, Yoko; Mishima, Satoshi; Hara, Hideaki

2009-11-17

Vascular endothelial growth factor (VEGF) is a key regulator of pathogenic angiogenesis in diseases such as cancer and diabetic retinopathy. Bee products [royal jelly (RJ), bee pollen, and Chinese red propolis] from the honeybee, Apis mellifera, have been used as traditional health foods for centuries. The aim of this study was to investigate the anti-angiogenic effects of bee products using human umbilical vein endothelial cells (HUVECs). In an in vitro tube formation assay, HUVECs and fibroblast cells were incubated for 14 days with VEGF and various concentrations of bee products [RJ, ethanol extract of bee pollen, ethanol extract of Chinese red propolis and its constituent, caffeic acid phenethyl ester (CAPE)]. To clarify the mechanism of in vitro angiogenesis, HUVEC proliferation and migration were induced by VEGF with or without various concentrations of RJ, bee pollen, Chinese red propolis, and CAPE. RJ, bee pollen, Chinese red propolis, and CAPE significantly suppressed VEGF-induced in vitro tube formation in the descending order: CAPE > Chinese red propolis > bee pollen > RJ. RJ and Chinese red propolis suppressed both VEGF-induced HUVEC proliferation and migration. In contrast, bee pollen and CAPE suppressed only the proliferation. Among the bee products, Chinese red propolis and CAPE in particular showed strong suppressive effects against VEGF-induced angiogenesis. These findings indicate that Chinese red propolis and CAPE may have potential as preventive and therapeutic agents against angiogenesis-related human diseases.

Phosphodiesterase inhibitors suppress Lactobacillus casei cell-wall-induced NF-κB and MAPK activations and cell proliferation through protein kinase A--or exchange protein activated by cAMP-dependent signal pathway.

PubMed

Saito, Takekatsu; Sugimoto, Naotoshi; Ohta, Kunio; Shimizu, Tohru; Ohtani, Kaori; Nakayama, Yuko; Nakamura, Taichi; Hitomi, Yashiaki; Nakamura, Hiroyuki; Koizumi, Shoichi; Yachie, Akihiro

2012-01-01

Specific strains of Lactobacillus have been found to be beneficial in treating some types of diarrhea and vaginosis. However, a high mortality rate results from underlying immunosuppressive conditions in patients with Lactobacillus casei bacteremia. Cyclic AMP (cAMP) is a small second messenger molecule that mediates signal transduction. The onset and progression of inflammatory responses are sensitive to changes in steady-state cAMP levels. L. casei cell wall extract (LCWE) develops arteritis in mice through Toll-like receptor-2 signaling. The purpose of this study was to investigate whether intracellular cAMP affects LCWE-induced pathological signaling. LCWE was shown to induce phosphorylation of the nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways and cell proliferation in mice fibroblast cells. Theophylline and phosphodiesterase inhibitor increased intracellular cAMP and inhibited LCWE-induced cell proliferation as well as phosphorylation of NF-κB and MAPK. Protein kinase A inhibitor H89 prevented cAMP-induced MAPK inhibition, but not cAMP-induced NF-κB inhibition. An exchange protein activated by cAMP (Epac) agonist inhibited NF-κB activation but not MAPK activation. These results indicate that an increase in intracellular cAMP prevents LCWE induction of pathological signaling pathways dependent on PKA and Epac signaling.

Sustaining Teen Pregnancy Prevention Programs in Schools: Needs and Barriers Identified by School Leaders

ERIC Educational Resources Information Center

Craft, Lesley R.; Brandt, Heather M.; Prince, Mary

2016-01-01

Background: To reduce teen pregnancy rates, prevention programs must be consistently available to large numbers of youth. However, prevention efforts have been historically conducted with little emphasis on ensuring program sustainability. This study examined the needs and barriers to sustaining teen pregnancy prevention (TPP) programming in…

Developing Childhood Injury Prevention Programs: An Administrative Guide for State Maternal and Child Health (Title V) Programs.

ERIC Educational Resources Information Center

Birch & Davis Associates, Inc., Silver Spring, MD.

Based primarily on the experience of three childhood injury prevention demonstration projects, this manual provides state Title V program directors with an action guide for developing targeted childhood injury prevention programs. The manual is divided into four sections: background; program planning; program design; and program implementation and…

p21, an important mediator of quiescence during pituitary tumor formation, is dispensable for normal pituitary development during embryogenesis.

PubMed Central

Monahan, Pamela; Himes, Ashley D.; Parfieniuk, Agata; Raetzman, Lori T.

2011-01-01

A delicate balance between proliferation and differentiation must be maintained in the developing pituitary to ensure the formation of the appropriate number of hormone producing cells. In the adult, proliferation is actively restrained to prevent tumor formation. The cyclin dependent kinase inhibitors (CDKIs) of the CIP/KIP family, p21, p27 and p57, mediate cell cycle inhibition. Although p21 is induced in the pituitary upon loss of Notch signaling or initiation of tumor formation to halt cell cycle progression, its role in normal pituitary organogenesis has not been explored. In wildtype pituitaries, expression of p21 is limited to a subset of cells embryonically as well as during the postnatal proliferative phase. Mice lacking p21 do not have altered cell proliferation during early embryogenesis, but do show a slight delay in separation of proliferating progenitors from the oral ectoderm. By embryonic day 16.5, p21 mutants have an alteration in the spatial distribution of proliferating pituitary progenitors, however there is no overall change in proliferation. At postnatal day 21, there appears to be no change in proliferation, as assessed by cells expressing Ki67 protein. However, p21 mutant pituitaries have significantly less mRNA of Myc and the cyclins Ccnb1, Ccnd1, Ccnd2 and Ccne1 than wildtype pituitaries. Interestingly, unlike the redundant role in cell cycle inhibition uncovered in p27/p57 double mutants, the pituitary of p21/p27 double mutants has a similar proliferation profile to p27 single mutants at the time points examined. Taken together, these studies demonstrate that unlike p27 or p57, p21 does not play a major role in control of progenitor proliferation in the developing pituitary. However, p21 may be required to maintain normal levels of cell cycle components. PMID:22154697

ATG-Fresenius inhibits blood circulating cell proliferation in a dose-dependent manner: an experimental study.

PubMed

Werner, I; Seitz-Merwald, I; Kiessling, A H; Kur, F; Beiras-Fernandez, A

2014-11-01

Antithymocyte globulin (ATG)-Fresenius (Neovii-Biotech, Graefelfing, Germany), a highly purified rabbit polyclonal antihuman T-lymphocyte immunoglobulin resulting from immunization of rabbits with the Jurkat T-lymphoblast cell line, is currently used for the prevention of acute rejection in patients receiving solid organ transplants. Our aim was to investigate the in vitro activity of ATG-Fresenius regarding the proliferation of peripheral blood mononuclear cells (PBMCs), an important mechanism of rejection after solid organ transplantation. PBMCs were isolated from 6 healthy donors. Proliferation was assayed using [(3)H] thymidine incorporation. For analysis of mitogen-stimulated proliferation, the PBMCs were incubated at 37°C with various concentrations of ATG-Fresenius in the absence/presence of 40 μg/mL phytohemagglutinin. For analysis of the mixed lymphocyte reaction, PBMCs were incubated at 37°C with various concentrations of ATG-Fresenius for 3 days. On day 3, PBMCs (stimulator cells) from allogeneic donors were incubated with 25 μg/mL mitomycin C. The responder cells (preincubated with ATG-Fresenius) were then cultured at 37°C with the stimulator cells for 6 days. Groups were compared using ANOVA and the Tukey-Kramer multiple comparison test. Preincubation of PBMCs with ATG results in concentration-dependent inhibition of phytohemagglutinin-stimulated proliferation. The effect was more pronounced after 2 and 3 days of treatment with ATG compared with 1 day. There was a concentration-dependent decrease in the mixed lymphocyte reaction-induced proliferation (up to 80%) at ATG-Fresenius concentrations as low as 0.05 to 0.5 μg/mL. No further effect on proliferation at ATG-Fresenius concentrations of 0.5 to 50 μg/mL was seen, and higher concentrations (>100 μg/mL) totally inhibited proliferation. Our in vitro results provide more evidence of the beneficial effect of ATGs in the early phase of solid organ transplantation, by reducing effector cell proliferation.

The Influence of Physical Forces on Progenitor Cell Migration, Proliferation and Differentiation in Fracture Repair

DTIC Science & Technology

2009-11-01

The Influence of Physical Forces on Progenitor Cell Migration, Proliferation and Differentiation in Fracture Repair PRINCIPAL INVESTIGATOR...REPORT TYPE Final 3. DATES COVERED (From - To) 11/1/05 – 10/31/09 4. TITLE AND SUBTITLE The Influence of Physical Forces on Progenitor Cell Migration...SUPPLEMENTARY NOTES 14. ABSTRACT The goal of this program is to investigate the influence of controlled mechanical stimulation on the behavior of

A Test Bed for Detection of Botnet Infections in Low Data Rate Tactical Networks

DTIC Science & Technology

2009-09-01

perimeter, their effectiveness in preventing further proliferation within a LAN is almost non-existent. Conficker disables antivirus and firewall software...enable: Yes Disable “strict” capture filtering: no Fencelist location: /etc/fencelist.txt (IP addresses and CIDR blocks Enable Fencelist filtering

JPRS Report, Proliferation Issues

DTIC Science & Technology

1992-12-18

Tokai to Rokkasho in northeastern Honshu via the nearby port of Mutsu Ogawara. Guarded by riot police, 12 trucks began ferrying the 200-liter drums...the Mutsu Ogawara Port. To guard against collisions, the ship has two radars and is double hulled to prevent it from sinking. In June, a Maritime

Preventive and Therapeutic Effects of Chinese Herbal Compounds against Hepatocellular Carcinoma.

PubMed

Hu, Bing; An, Hong-Mei; Wang, Shuang-Shuang; Chen, Jin-Jun; Xu, Ling

2016-01-27

Traditional Chinese Medicines, unique biomedical and pharmaceutical resources, have been widely used for hepatocellular carcinoma (HCC) prevention and treatment. Accumulated Chinese herb-derived compounds with significant anti-cancer effects against HCC have been identified. Chinese herbal compounds are effective in preventing carcinogenesis, inhibiting cell proliferation, arresting cell cycle, inducing apoptosis, autophagy, cell senescence and anoikis, inhibiting epithelial-mesenchymal transition, metastasis and angiogenesis, regulating immune function, reversing drug resistance and enhancing the effects of chemotherapy in HCC. This paper comprehensively reviews these compounds and their effects on HCC. Finally, the perspectives and rational application of herbal compounds for HCC management are discussed.

The National Cross-Site Evaluation of High-Risk Youth Programs. Preventing Substance Abuse: Major Findings from the National Cross-Site Evaluation of High-Risk Youth Programs. Monograph Series.

ERIC Educational Resources Information Center

Springer, J. Fred; Sambrano, Soledad; Sale, Elizabeth; Kasim, Rafa; Herman, Jack

This multiple-site study assessed 48 prevention programs for high-risk youth funded by the Center for Substance Abuse Prevention, identifying program characteristics associated with strong substance abuse prevention outcomes. Data analysis indicated that substance abuse programs reduced rates of substance use, and the positive effects of program…

What Have We Learned about Preventing Child Abuse? An Overview of the "Community and Minority Group Action to Prevent Child Abuse and Neglect" Program. Prevention Focus Working Paper No. 009.

ERIC Educational Resources Information Center

Gray, Ellen

Results from the evaluation of 11 demonstration programs designed to prevent child abuse are summarized in this working paper. The programs were of three types: perinatal programs; community-wide education, information, and referral projects; and culturally relevant parent education efforts. The four perinatal programs focused on extended…

The new politics of missile proliferation

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

Karp, A.

1996-10-01

The author addresses the most consequential proliferation battle of the 1990s which occurred in Washington over the interpretation of the long-term threat to the United States from ballistic missiles. In the early 1970s, the stabilization of the US-Soviet strategic relationship led to new disputes over the other side`s future intentions, seen most graphically in Western debates over the implications of the Soviet SS-18 and SS-20 missile programs. Today, in much the same way, proliferation politics has matured to the point that surprises are few and the most challenging problem is anticipating the more distant future. Washington`s ballistic missile proliferation battlemore » was sparked by National Intelligence Estimate (NIE) 95-19, entitled {open_quotes}Emerging Threats to North America During the Next 15 Years,{close_quotes} released by the National Intelligence Council in November 1995. This document updated the evidence of regional missile programs reviewed in a similar report issued in 1993, and recapitulated the previous finding that {open_quotes}No country, other than the major declared nuclear powers, will develop or otherwise acquire a ballistic missile in the next 15 years that could threatened the contiguous 48 states or Canada.{close_quotes} The new report confirmed what several other studies of missile proliferation had already established: that besides the five nuclear-weapon states (the United States, Russia, China, France and Britain), only India, Israel and Japan are in a position to develop an ICBM during the foreseeable future, and while all have relevant capabilities, none are undertaking the steps necessary to develop an actual ICBM.« less

Epstein-Barr virus latency switch in human B-cells: a physico-chemical model.

PubMed

Werner, Maria; Ernberg, Ingemar; Zou, Jiezhi; Almqvist, Jenny; Aurell, Erik

2007-08-31

The Epstein-Barr virus is widespread in all human populations and is strongly associated with human disease, ranging from infectious mononucleosis to cancer. In infected cells the virus can adopt several different latency programs, affecting the cells' behaviour. Experimental results indicate that a specific genetic switch between viral latency programs, reprograms human B-cells between proliferative and resting states. Each of these two latency programs makes use of a different viral promoter, Cp and Qp, respectively. The hypothesis tested in this study is that this genetic switch is controlled by both human and viral transcription factors; Oct-2 and EBNA-1. We build a physico-chemical model to investigate quantitatively the dynamical properties of the promoter regulation and experimentally examine protein level variations between the two latency programs. Our experimental results display significant differences in EBNA-1 and Oct-2 levels between resting and proliferating programs. With the model we identify two stable latency programs, corresponding to a resting and proliferating cell. The two programs differ in robustness and transcriptional activity. The proliferating state is markedly more stable, with a very high transcriptional activity from its viral promoter. We predict the promoter activities to be mutually exclusive in the two different programs, and our relative promoter activities correlate well with experimental data. Transitions between programs can be induced, by affecting the protein levels of our transcription factors. Simulated time scales are in line with experimental results. We show that fundamental properties of the Epstein-Barr virus involvement in latent infection, with implications for tumor biology, can be modelled and understood mathematically. We conclude that EBNA-1 and Oct-2 regulation of Cp and Qp is sufficient to establish mutually exclusive expression patterns. Moreover, the modelled genetic control predict both mono- and bistable behavior and a considerable difference in transition dynamics, based on program stability and promoter activities. Both these phenomena we hope can be further investigated experimentally, to increase the understanding of this important switch. Our results also stress the importance of the little known regulation of human transcription factor Oct-2.

Peroxisome Proliferator-Activated Receptors Protect against Apoptosis via 14-3-3

PubMed Central

Wu, Kenneth K.

2010-01-01

Peroxisome proliferator-activated receptors (PPARs) were reported to prevent cells from stress-induced apoptosis and protect tissues against ischemia-reperfusion injury. The underlying transcriptional mechanism is unclear. Recent reports indicate that the antiapoptotic actions of ligand-activated PPARδ and PPARγ are mediated through enhanced binding of PPAR to the promoter of 14-3-3ε and upregulation of 14-3-3ε expression. We propose that ligand-activated PPARα exerts its anti-apoptotic actions via the identical pathway. The PPAR to 14-3-3 transcriptional axis plays an important role in protection of cell and tissue integrity and is a target for drug discovery. PMID:20862376

Military laser weapons: current controversies.

PubMed

Seet, B; Wong, T Y

2001-09-01

Military laser weapons systems are becoming indispensable in most modern armies. These lasers have undergone many stages of development, and have outpaced research on eye protection measures, which continue to have inherent limitations. Eye injuries caused by military lasers are increasingly reported, leading to speculation that these would become an important cause of blinding in modern conflicts. As part of the effort to ban inhumane weapons, international laws have been passed to restrict the proliferation of such blinding weapons. However, there are controversies concerning the interpretation, implementation and effectiveness of these laws. The ophthalmic community can play a greater role in highlighting ocular morbidity from military lasers, and in preventing their further proliferation.

14 CFR 91.1425 - CAMP: Maintenance, preventive maintenance, and alteration programs.

Code of Federal Regulations, 2010 CFR

2010-01-01

... RULES Fractional Ownership Operations Program Management § 91.1425 CAMP: Maintenance, preventive maintenance, and alteration programs. Each program manager who maintains program aircraft under a CAMP must... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false CAMP: Maintenance, preventive maintenance...

Reinterpreting Dissemination of Prevention Programs as Widespread Implementation with Effectiveness and Fidelity.

ERIC Educational Resources Information Center

Elias, Maurice J.

This article urges a reexamination of the concept of dissemination of health-related prevention programs. The article discusses factors that serve as sustaining conditions for dissemination of prevention programs including: (1) the nature of preventive intervention and parameters of effective community-based prevention praxis; (2) aspects of the…

A Meta-Analytic Review of Obesity Prevention Programs for Children and Adolescents: The Skinny on Interventions that Work

ERIC Educational Resources Information Center

Stice, Eric; Shaw, Heather; Marti, C. Nathan

2006-01-01

This meta-analytic review summarizes obesity prevention programs and their effects and investigates participant, intervention, delivery, and design features associated with larger effects. A literature search identified 64 prevention programs seeking to produce weight gain prevention effects, of which 21% produced significant prevention effects…

Proximate Effects of a Child Sexual Abuse Prevention Program in Elementary School Children.

ERIC Educational Resources Information Center

Hebert, Martine; Lavoie, Francine; Piche, Christiane; Poitras, Michele

2001-01-01

The effects of the sexual child abuse prevention program ESPACE were evaluated with 133 Canadian children (grades 1-3). Children participating in the prevention program showed greater preventive knowledge and skills relative to children not participating. Follow-up data showed knowledge gains were maintained while the preventive skill gains may…

10 CFR Appendix A to Part 850 - Chronic Beryllium Disease Prevention Program Informed Consent Form

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Chronic Beryllium Disease Prevention Program Informed Consent Form A Appendix A to Part 850 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Pt. 850, App. A Appendix A to Part 850—Chronic Beryllium Disease Prevention Program Informed...

10 CFR Appendix A to Part 850 - Chronic Beryllium Disease Prevention Program Informed Consent Form

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Chronic Beryllium Disease Prevention Program Informed Consent Form A Appendix A to Part 850 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Pt. 850, App. A Appendix A to Part 850—Chronic Beryllium Disease Prevention Program Informed...

"Helping Communities To Help Themselves." Twenty 1989 Exemplary Prevention Programs for Preventing Alcohol and Other Drug Abuse. Project Summaries.

ERIC Educational Resources Information Center

National Association of State Alcohol and Drug Abuse Directors, Inc.

Twenty exemplary substance abuse prevention programs are presented in this document. These programs are included: (1) Tuba City, Arizona, Fetal Alcohol Syndrome (FAS) Prevention Program; (2) Chemical Addiction Course, University of Arkansas; (3) "Teens Are Concerned" of Arkansas; (4) "Dare to be You of Colorado"; (5) Winyan…

10 CFR Appendix A to Part 850 - Chronic Beryllium Disease Prevention Program Informed Consent Form

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Chronic Beryllium Disease Prevention Program Informed Consent Form A Appendix A to Part 850 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Pt. 850, App. A Appendix A to Part 850—Chronic Beryllium Disease Prevention Program Informed...

10 CFR Appendix A to Part 850 - Chronic Beryllium Disease Prevention Program Informed Consent Form

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Chronic Beryllium Disease Prevention Program Informed Consent Form A Appendix A to Part 850 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Pt. 850, App. A Appendix A to Part 850—Chronic Beryllium Disease Prevention Program Informed...

10 CFR Appendix A to Part 850 - Chronic Beryllium Disease Prevention Program Informed Consent Form

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Chronic Beryllium Disease Prevention Program Informed Consent Form A Appendix A to Part 850 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Pt. 850, App. A Appendix A to Part 850—Chronic Beryllium Disease Prevention Program Informed...

A Drop-Out Prevention Program for High-Risk Inner-City Youth

ERIC Educational Resources Information Center

Lever, Nancy; Sander, Mark A.; Lombardo, Sylvie; Randall, Camille; Axelrod, Jennifer; Rubenstein, Michelle; Weist, Mark D.

2004-01-01

Inner-city youth are at high risk for dropping out of high school. Within this article, risk factors associated with dropout and strategies for effective prevention and intervention are reviewed. An example of a school-based drop-out prevention program is highlighted. The FUTURES Program is a school-based drop-out prevention program designed to…

Participation in Prevention Programs for Dating Violence: Beliefs about Relationship Violence and Intention to Participate

ERIC Educational Resources Information Center

Cornelius, Tara L.; Sullivan, Kieran T.; Wyngarden, Nicole; Milliken, Jennifer C.

2009-01-01

This study utilizes the Health Belief Model (HBM) to examine the factors related to the intention to participate in prevention programming for dating violence. Perceptions of susceptibility to future violence and the benefits of prevention programming appear to be the strongest predictors of participation in prevention programs. Perceptions of the…

Regulators of Intestinal Epithelial Migration in Sepsis.

PubMed

Meng, Mei; Klingensmith, Nathan J; Liang, Zhe; Lyons, John D; Fay, Katherine T; Chen, Ching-Wen; Ford, Mandy L; Coopersmith, Craig M

2018-02-08

The gut is a continuously renewing organ, with cell proliferation, migration and death occurring rapidly under basal conditions. Since the impact of critical illness on cell movement from crypt base to villus tip is poorly understood, the purpose of this study was to determine how sepsis alters enterocyte migration. Wild type, transgenic and knockout mice were injected with 5-bromo-2'deoxyuridine (BrdU) to label cells in S phase before and after the onset of cecal ligation and puncture and were sacrificed at pre-determined endpoints to determine distance proliferating cells migrated up the crypt-villus unit. Enterocyte migration rate was decreased from 24-96 hours following sepsis. BrdU was not detectable on villi 6 days after sham laparotomy, meaning all cells had migrated the length of the gut and been exfoliated into its lumen. However, BrdU positive cells were detectable on villi 10 days after sepsis. Multiple components of gut integrity altered enterocyte migration. Sepsis decreased crypt proliferation, which further slowed enterocyte transit as mice injected with BrdU after the onset of sepsis (decreased proliferation) had slower migration than mice injected with BrdU prior to the onset of sepsis (normal proliferation). Decreasing intestinal apoptosis via gut-specific overexpression of Bcl-2 prevented sepsis-induced slowing of enterocyte migration. In contrast, worsened intestinal hyperpermeability by genetic deletion of JAM-A increased enterocyte migration. Sepsis therefore significantly slows enterocyte migration, and intestinal proliferation, apoptosis and permeability all affect migration time, which can potentially be targeted both genetically and pharmacologically.

What's culture got to do with it? Prevention programs for African American adolescent girls.

PubMed

Corneille, Maya A; Ashcroft, Amie M; Belgrave, Faye Z

2005-11-01

This paper examines prevention programming for African American girls by placing the prevention process within the larger African and African American cultural context. We provide an overview of the theories and issues we consider most relevant to African American culture, including Africentric theory, ethnic identity, gender identity and relational theory, developmental issues, the community context, and historical considerations. Drawing from our own drug prevention work, we provide examples of how to incorporate culture into prevention programs to make them most relevant for the target population. We also summarize our own efforts to create culturally appropriate prevention interventions and their impact on the girls in our programs. We conclude with suggested directions for future research into culture-specific prevention programs.

Commentary on Foubert, Godin, & Tatum (2010): the evolution of sexual violence prevention and the urgency for effectiveness.

PubMed

Tharp, Andra Teten; DeGue, Sarah; Lang, Karen; Valle, Linda Anne; Massetti, Greta; Holt, Melissa; Matjasko, Jennifer

2011-11-01

Foubert, Godin, and Tatum describe qualitative effects among college men of The Men's Program, a one-session sexual violence prevention program. This article and the program it describes are representative of many sexual violence prevention programs that are in practice and provide an opportunity for a brief discussion of the development and evaluation of sexual violence prevention approaches. In this commentary, we will focus on two considerations for an evolving field: the adherence to the principles of prevention and the use of rigorous evaluation methods to demonstrate effectiveness. We argue that the problem of sexual violence has created urgency for effective prevention programs and that scientific and prevention standards provide the best foundation to meet this need.

Proliferation of epithelial cell rests, formation of apical cysts, and regression of apical cysts after periapical wound healing.

PubMed

Lin, Louis M; Huang, George T-J; Rosenberg, Paul A

2007-08-01

There is continuing controversy regarding the potential for inflammatory apical cysts to heal after nonsurgical endodontic therapy. Molecular cell biology may provide answers to a series of related questions. How are the epithelial cell rests of Malassez stimulated to proliferate? How are the apical cysts formed? How does the lining epithelium of apical cysts regress after endodontic therapy? Epithelial cell rests are induced to divide and proliferate by inflammatory mediators, proinflammatory cytokines, and growth factors released from host cells during periradicular inflammation. Quiescent epithelial cell rests can behave like restricted-potential stem cells if stimulated to proliferate. Formation of apical cysts is most likely caused by the merging of proliferating epithelial strands from all directions to form a three-dimensional ball mass. After endodontic therapy, epithelial cells in epithelial strands of periapical granulomas and the lining epithelium of apical cysts may stop proliferating because of a reduction in inflammatory mediators, proinflammatory cytokines, and growth factors. Epithelial cells will also regress because of activation of apoptosis or programmed cell death through deprivation of survival factors or by receiving death signals during periapical wound healing.

Alcohol, tobacco, and other drug use prevention programs in U.S. schools: a descriptive summary.

PubMed

Kumar, Revathy; O'Malley, Patrick M; Johnston, Lloyd D; Laetz, Virginia B

2013-12-01

This report identifies the prevalence of state, local, and commercially developed substance abuse prevention programs in middle and high schools from 2001 to 2007, using survey data from nationally representative samples of 1,206 schools. Based on school administrators' reports, schools and school districts offer students an average of 1.62 prevention programs during their school years from elementary through high school. Bivariate and multivariate regression analyses were conducted with school demographic characteristics public versus private, size, population density, region of the country, school race/ethnic composition, and socioeconomic status of the student body (SES) as predictors of total number of programs that students received and of the relative use of local, state, and commercial programs. Schools in the West had significantly fewer prevention programs than those in other regions of the country. Students in predominantly White and in higher SES schools received significantly more prevention programs than students in majority African American, majority Hispanic, or in lower SES affluent schools. The most frequently reported programs that students received were locally developed. D.A.R.E. was the most widely adopted prevention program. Findings from this study suggest that schools often develop their own curriculum to suit their students' needs, and students are exposed to multiple prevention programs through their school years, making it difficult to examine the effectiveness of any single program in preventing and reducing substance use among students.

High mobility group A1 protein modulates autophagy in cancer cells.

PubMed

Conte, Andrea; Paladino, Simona; Bianco, Gaia; Fasano, Dominga; Gerlini, Raffaele; Tornincasa, Mara; Renna, Maurizio; Fusco, Alfredo; Tramontano, Donatella; Pierantoni, Giovanna Maria

2017-11-01

High Mobility Group A1 (HMGA1) is an architectural chromatin protein whose overexpression is a feature of malignant neoplasias with a causal role in cancer initiation and progression. HMGA1 promotes tumor growth by several mechanisms, including increase of cell proliferation and survival, impairment of DNA repair and induction of chromosome instability. Autophagy is a self-degradative process that, by providing energy sources and removing damaged organelles and misfolded proteins, allows cell survival under stress conditions. On the other hand, hyper-activated autophagy can lead to non-apoptotic programmed cell death. Autophagy deregulation is a common feature of cancer cells in which has a complex role, showing either an oncogenic or tumor suppressor activity, depending on cellular context and tumor stage. Here, we report that depletion of HMGA1 perturbs autophagy by different mechanisms. HMGA1-knockdown increases autophagosome formation by constraining the activity of the mTOR pathway, a major regulator of autophagy, and transcriptionally upregulating the autophagy-initiating kinase Unc-51-like kinase 1 (ULK1). Consistently, functional experiments demonstrate that HMGA1 binds ULK1 promoter region and negatively regulates its transcription. On the other hand, the increase in autophagosomes is not associated to a proportionate increase in their maturation. Overall, the effects of HMGA1 depletion on autophagy are associated to a decrease in cell proliferation and ultimately impact on cancer cells viability. Importantly, silencing of ULK1 prevents the effects of HMGA1-knockdown on cellular proliferation, viability and autophagic activity, highlighting how these effects are, at least in part, mediated by ULK1. Interestingly, this phenomenon is not restricted to skin cancer cells, as similar results have been observed also in HeLa cells silenced for HMGA1. Taken together, these results clearly indicate HMGA1 as a key regulator of the autophagic pathway in cancer cells, thus suggesting a novel mechanism through which HMGA1 can contribute to cancer progression.

20 CFR 632.125 - Responsibilities of Native American grantees, subgrantees and contractors for preventing fraud...

Code of Federal Regulations, 2012 CFR

2012-04-01

..., subgrantees and contractors for preventing fraud and program abuse and for general program management. 632.125... and for general program management. (a) Each Native American grantee shall establish and use internal program management procedures sufficient to prevent fraud and program abuse, including subgrantee and...

20 CFR 632.125 - Responsibilities of Native American grantees, subgrantees and contractors for preventing fraud...

Code of Federal Regulations, 2011 CFR

2011-04-01

..., subgrantees and contractors for preventing fraud and program abuse and for general program management. 632.125... and for general program management. (a) Each Native American grantee shall establish and use internal program management procedures sufficient to prevent fraud and program abuse, including subgrantee and...

Title V Delinquency Prevention Program. Community Self-Evaluation Workbook.

ERIC Educational Resources Information Center

Caliber Associates, Fairfax, VA.

This workbook is designed to help communities and program administrators assess the success of their Title V delinquency prevention programs, but it may serve as an evaluation tool for other prevention efforts as well. It provides information and resource aids on program planning, conducting evaluations, tracking programs, describing activities,…

Building Gifted Education: One State at a Time

ERIC Educational Resources Information Center

Jolly, Jennifer L.

2014-01-01

The "Marland" Report was the impetus and structure to provide a more systematic approach to building state and regional gifted programs. One of the strategies used to proliferate the spread of programming for gifted students throughout the states was the National/State Leadership Training Institute on the Gifted and Talented…

Superintendents' Perceptions of Online Education for Principals

ERIC Educational Resources Information Center

Rutledge, David

2017-01-01

The proliferation of online educational leadership programs has led many aspiring principal candidates to complete their entire degree or licensure program online. While the online education is convenient and flexible for the learner, there is sparse research to determine the acceptability of online degrees in educational leadership, especially…

Assessment and Intervention for Adolescents with Anger and Aggression Difficulties in School Settings

ERIC Educational Resources Information Center

Feindler, Eva L.; Engel, Emily C.

2011-01-01

The development, implementation, and evaluation of anger management programs have proliferated over the past decade. The programs aim to moderate the intensity, frequency, and severity of anger expression, and facilitate alternative nonaggressive responses to conflict and frustration. Cognitive-behavioral theory highlights cognitive processes such…

Decreasing the Digital Divide: Technology Use for College Preparation Programs

ERIC Educational Resources Information Center

Center for Higher Education Policy Analysis, University of Southern California, 2006

2006-01-01

This paper examines the use of instructional technology for college preparation programs. Over the last decade, the proliferation of personal computers and internet access has led to the widespread adoption of instructional technology in all educational sectors. This paper provides a typology of instructional technology specific to college…

Quality Assurance--Best Practices for Assessing Online Programs

ERIC Educational Resources Information Center

Wang, Qi

2006-01-01

Educators have long sought to define quality in education. With the proliferation of distance education and online learning powered by the Internet, the tasks required to assess the quality of online programs become even more challenging. To assist educators and institutions in search of quality assurance methods to continuously improve their…

How Students Develop Online Learning Skills

ERIC Educational Resources Information Center

Roper, Alan R.

2007-01-01

More and more, adult learners are finding the convenience and flexibility of online learning a match for their learning goals and busy lifestyles. Online degree programs, courses, and virtual universities targeting adult learners have proliferated in the past decade. Although students can easily locate an online course or degree program that's…

Integrating Ethics in Community Colleges' Accounting Programs.

ERIC Educational Resources Information Center

Clarke, Clifton

1990-01-01

Argues that two-year college business programs need to provide moral guidance and leadership to students to help stem the proliferation of fraudulent and questionable financial reporting practices. Reviews amoral and moral unity theories of business ethics. Discusses barriers to ethical instruction in business curricula, and ways to overcome them.…

Factors That Influence the Attrition of Mentors in Rural Areas

ERIC Educational Resources Information Center

Givens, Sharon Leenese

2012-01-01

This research is a qualitative case study exploring the factors that influence the attrition of mentors in rural areas. Mentoring initiatives and programs have proliferated throughout schools in an effort to provide students with positive role models, increase graduation rates and improve overall performance Mentoring programs are an increasingly…

The Power of Integrators, Financiers, and Insurers to Reduce Proliferation Risks: Nuclear Dual-Use Goods

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

Weise, Rachel A.; Hund, Gretchen

2015-05-01

Globalization of manufacturing supply chains has changed the nature of nuclear proliferation. Before 1991, nonproliferation efforts focused almost exclusively on limiting the spread of materials and equipment specifically designed for nuclear use -- reactors, centrifuges, and fissile material. Dual-use items, those items with both nuclear and non-nuclear applications, were not closely scrutinized or controlled. However, in 1991 the international community discovered that Iraq had developed a fairly sophisticated nuclear weapons program by importing dual-use items; this discovery spurred the international community to increase controls on dual-use technologies. Despite these international efforts, dual-use items are still a challenge for those seekingmore » to limit proliferation.« less

Leflunomide/teriflunomide inhibit Epstein-Barr virus (EBV)- induced lymphoproliferative disease and lytic viral replication.

PubMed

Bilger, Andrea; Plowshay, Julie; Ma, Shidong; Nawandar, Dhananjay; Barlow, Elizabeth A; Romero-Masters, James C; Bristol, Jillian A; Li, Zhe; Tsai, Ming-Han; Delecluse, Henri-Jacques; Kenney, Shannon C

2017-07-04

EBV infection causes mononucleosis and is associated with specific subsets of B cell lymphomas. Immunosuppressed patients such as organ transplant recipients are particularly susceptible to EBV-induced lymphoproliferative disease (LPD), which can be fatal. Leflunomide (a drug used to treat rheumatoid arthritis) and its active metabolite teriflunomide (used to treat multiple sclerosis) inhibit de novo pyrimidine synthesis by targeting the cellular dihydroorotate dehydrogenase, thereby decreasing T cell proliferation. Leflunomide also inhibits the replication of cytomegalovirus and BK virus via both "on target" and "off target" mechanisms and is increasingly used to treat these viruses in organ transplant recipients. However, whether leflunomide/teriflunomide block EBV replication or inhibit EBV-mediated B cell transformation is currently unknown. We show that teriflunomide inhibits cellular proliferation, and promotes apoptosis, in EBV-transformed B cells in vitro at a clinically relevant dose. In addition, teriflunomide prevents the development of EBV-induced lymphomas in both a humanized mouse model and a xenograft model. Furthermore, teriflunomide inhibits lytic EBV infection in vitro both by preventing the initial steps of lytic viral reactivation, and by blocking lytic viral DNA replication. Leflunomide/teriflunomide might therefore be clinically useful for preventing EBV-induced LPD in patients who have high EBV loads yet require continued immunosuppression.

Green tea catechins: defensive role in cardiovascular disorders.

PubMed

Bhardwaj, Pooja; Khanna, Deepa

2013-07-01

Green tea, Camellia sinensis (Theaceae), a major source of flavonoids such as catechins, has recently shown multiple cardiovascular health benefits through various experimental and clinical studies. These studies suggest that green tea catechins prevent the incidence of detrimental cardiovascular events, and also lower the cardiovascular mortality rate. Catechins present in green tea have the ability to prevent atherosclerosis, hypertension, endothelial dysfunction, ischemic heart diseases, cardiomyopathy, cardiac hypertrophy and congestive heart failure by decreasing oxidative stress, preventing inflammatory events, reducing platelet aggregation and halting the proliferation of vascular smooth muscle cells. Catechins afford an anti-oxidant effect by inducing anti-oxidant enzymes, inhibiting pro-oxidant enzymes and scavenging free radicals. Catechins present anti-inflammatory activity through the inhibition of transcriptional factor NF-κB-mediated production of cytokines and adhesion molecules. Green tea catechins interfere with vascular growth factors and thus inhibit vascular smooth muscle cell proliferation, and also inhibit thrombogenesis by suppressing platelet adhesion. Additionally, catechins could protect vascular endothelial cells and enhance vascular integrity and regulate blood pressure. In this review various experimental and clinical studies suggesting the role of green tea catechins against the markers of cardiovascular disorders and the underlying mechanisms for these actions are discussed. Copyright © 2013 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Naringin, a natural dietary compound, prevents intestinal tumorigenesis in Apc (Min/+) mouse model.

PubMed

Zhang, Yu-Sheng; Li, Ye; Wang, Yan; Sun, Shi-Yue; Jiang, Tao; Li, Cong; Cui, Shu-Xiang; Qu, Xian-Jun

2016-05-01

Naringin is a natural dietary flavonoid compound. We aimed to evaluate the effects of naringin on intestinal tumorigenesis in the adenomatous polyposis coli multiple intestinal neoplasia (Apc (Min/+)) mouse model. Apc (Min/+) mice were given either naringin (150 mg/kg) or vehicle by p.o. gavage daily for 12 consecutive weeks. Mice were killed with ether, and blood samples were collected to assess the concentrations of IL-6 and PGE2. Total intestines were removed, and the number of polyps was examined. Tissue samples of intestinal polyps were subjected to the assays of histopathology, immunohistochemical analysis and Western blotting analysis. Apc (Min/+) mice fed with naringin developed less and smaller polyps in total intestines. Naringin prevented intestinal tumorigenesis without adverse effects. Histopathologic analysis revealed the reduction of dysplastic cells and dysplasia in the adenomatous polyps. The treatments' effects might arise from its anti-proliferation, induction of apoptosis and modulation of GSK-3β and APC/β-catenin signaling pathways. Naringin also exerted its effects on tumorigenesis through anti-chronic inflammation. Naringin prevented intestinal tumorigenesis likely through a collection of activities including anti-proliferation, induction of apoptosis, modulation of GSK-3β and APC/β-catenin pathways and anti-inflammation. Naringin is a potential chemopreventive agent for reducing the risk of colonic cancers.

Distinct gene regulatory programs define the inhibitory effects of liver X receptors and PPARG on cancer cell proliferation.

PubMed

Savic, Daniel; Ramaker, Ryne C; Roberts, Brian S; Dean, Emma C; Burwell, Todd C; Meadows, Sarah K; Cooper, Sara J; Garabedian, Michael J; Gertz, Jason; Myers, Richard M

2016-07-11

The liver X receptors (LXRs, NR1H2 and NR1H3) and peroxisome proliferator-activated receptor gamma (PPARG, NR1C3) nuclear receptor transcription factors (TFs) are master regulators of energy homeostasis. Intriguingly, recent studies suggest that these metabolic regulators also impact tumor cell proliferation. However, a comprehensive temporal molecular characterization of the LXR and PPARG gene regulatory responses in tumor cells is still lacking. To better define the underlying molecular processes governing the genetic control of cellular growth in response to extracellular metabolic signals, we performed a comprehensive, genome-wide characterization of the temporal regulatory cascades mediated by LXR and PPARG signaling in HT29 colorectal cancer cells. For this analysis, we applied a multi-tiered approach that incorporated cellular phenotypic assays, gene expression profiles, chromatin state dynamics, and nuclear receptor binding patterns. Our results illustrate that the activation of both nuclear receptors inhibited cell proliferation and further decreased glutathione levels, consistent with increased cellular oxidative stress. Despite a common metabolic reprogramming, the gene regulatory network programs initiated by these nuclear receptors were widely distinct. PPARG generated a rapid and short-term response while maintaining a gene activator role. By contrast, LXR signaling was prolonged, with initial, predominantly activating functions that transitioned to repressive gene regulatory activities at late time points. Through the use of a multi-tiered strategy that integrated various genomic datasets, our data illustrate that distinct gene regulatory programs elicit common phenotypic effects, highlighting the complexity of the genome. These results further provide a detailed molecular map of metabolic reprogramming in cancer cells through LXR and PPARG activation. As ligand-inducible TFs, these nuclear receptors can potentially serve as attractive therapeutic targets for the treatment of various cancers.

Youth empowerment solutions for violence prevention.

PubMed

Reischl, Thomas M; Zimmerman, Marc A; Morrel-Samuels, Susan; Franzen, Susan P; Faulk, Monique; Eisman, Andria B; Roberts, Everett

2011-12-01

The limited success of youth violence prevention interventions suggests that effective prevention needs to address causes at multiple levels of analysis and empower youth in developing and implementing prevention programs. In this article, we review published studies of youth violence prevention efforts that engage youth in developing or implementing violence prevention activities. The reviewed studies suggest the promise of youth empowerment strategies and the need for systematic outcome studies of empowerment programs. After reviewing empowerment theory applied to youth violence prevention programs, we present a case study of the Youth Empowerment Solutions (YES) for Peaceful Communities program. YES engages middle-school youth in an after-school and summer program that includes a culturally tailored character development curriculum and empowers the youth to plan and implement community improvement projects with assistance from adult neighborhood advocates. The case study focuses on outcome evaluation results and presents evidence of the YES program effects on community-level outcomes (eg, property improvements, violent crime incidents) and on individual-level outcomes (eg, conflict avoidance, victimization). The literature review and the case study suggest the promise of engaging and empowering youth to plan and implement youth violence prevention programs.

Feasibility and Acceptability of a Child Sexual Abuse Prevention Program for Childcare Professionals: Comparison of a Web-Based and In-Person Training

ERIC Educational Resources Information Center

Rheingold, Alyssa A.; Zajac, Kristyn; Patton, Meghan

2012-01-01

Recent prevention research has established the efficacy of some child sexual abuse prevention programs targeting adults; however, less is known about the feasibility of implementing such programs. The current study examines the feasibility and acceptability of a child sexual abuse prevention program for child care professionals provided in two…

Alterations of hepatocyte function with free radical generators and reparation or prevention with coffee polyphenols.

PubMed

Saidi Merzouk, Amel; Hafida, Merzouk; Medjdoub, Amel; Loukidi, Bouchra; Cherrak, Sabri; Merzouk, Sid Ahmed; Elhabiri, Mourad

2017-03-01

Liver diseases are linked in the majority of cases to oxidative stress that antioxidants could neutralize with reducing liver injury. Chlorogenic acid, a coffee polyphenol, possesses antioxidant prosperities. The aim of this study was to evaluate in vitro preventive and corrective effects of cholorogenic acid in hepatocyte toxicity induced by free radicals. Hepatocytes were isolated from adult male Wistar rats. To determine corrective effects and reparation, cells were first exposed to two free radical generators (hydrogen peroxide/iron sulfate for hydroxyl radical formation, and phenazine methosulfate/nicotinamide adenine dinucleotide for superoxide anion formation) for 12H and thereafter treated by chlorogenic acid (1 and 10 μM final concentration) for another 12H. To show preventive effects, cells were pretreated by chlorogenic acid and thereafter exposed to free radical generators. Hepatocyte proliferation, glucose uptake, ATP contents, membrane fluidity and integrity, and intracellular redox status were investigated after 24H culture. The results showed that chlorogenic acid reversed the decrease in cell proliferation, glucose uptake and ATP levels, the increased LDH release and the reduced membrane fluidity and restored the oxidant/antioxidant status under oxidative stress. When pre-treated with chlorogenic acid, hepatocytes became very resistant to oxidative conditions and cellular homeostasis was maintained. In conclusion, chlorogenic acid displayed not only corrective but also preventive effects in hepatocytes exposed to oxidative stress and could be beneficial in patients with or at risk of liver diseases.

Can we prevent BRCA1-associated breast cancer by RANKL inhibition?

PubMed

Kotsopoulos, Joanne; Singer, Christian; Narod, Steven A

2017-01-01

BRCA1 mutation carriers face a high lifetime risk of breast cancer, estimated at 60 % compared to 10 % in the general population. BRCA1 breast cancers typically have an aggressive course (i.e., high-grade, triple-negative) and are associated with a poor prognosis. At present, primary prevention is limited to prophylactic removal of the unaffected breasts. Effective chemopreventive strategies are not yet available. Emerging evidence suggests that BRCA1 mutation carriers have high circulating levels of progesterone which may play a role in their susceptibility to breast cancer. Recently, the RANK/RANKL system was found to be dysregulated in women with a BRCA1 mutation. Mutation carriers had significantly lower endogenous levels of osteoprotegerin (OPG) than women without a BRCA1 mutation. OPG is an endogenous decoy receptor for RANKL and inhibits RANKL-mediated signaling. RANKL binds to RANK on mammary epithelial cells and stimulates their proliferation and maturation. Low OPG levels may contribute to mammary tumorigenesis through increased proliferation and may explain in part the increased breast cancer risk in BRCA1 mutation carriers. Denosumab is an anti-RANKL monoclonal antibody which is approved to treat osteoporosis and to prevent skeletal damage caused by bone metastases. The emerging role of aberrant RANK-signaling in BRCA1 tumorigenesis suggests that targeting of RANKL may prevent breast cancer among women with germline BRCA1 mutations. Clinical investigations of denosumab are warranted and may lead to a novel chemopreventive approach for breast cancer for high-risk women.

Process Requirements for Achieving Full-Flow Disinfection of Recirculating Water Using Ozonation and UV Irradiation

USDA-ARS?s Scientific Manuscript database

A continuous water disinfection process can be used to prevent the introduction and accumulation of obligate and opportunistic fish pathogens in recirculating aquaculture systems (RAS), especially during a disease outbreak when the causative agent would otherwise proliferate within the system. To p...

Measuring Up? The Discursive Construction of Student Subjectivities in the Global Children's Challenge™

ERIC Educational Resources Information Center

Drew, Debbie L.; Gore, Jennifer M.

2016-01-01

International concern about "alarming" levels of childhood obesity has seen a proliferation of interventions filtering into school physical education programmes that are designed to influence children's health practices and attitudes. This article addresses one such obesity-prevention intervention, the Global Children's Challenge™, a…

Touryan Elected Chairman

Science.gov Websites

Touryan Elected Chairman of Proliferation Prevention Advisory Board For information contact: e:mail ) National Renewable Energy Laboratory (NREL) was elected chairman of the Inter-Laboratory Advisory Board for opportunities and a means of rapid commercialization of defense technologies. It creates a win-win situation for

Bidirectional Signaling of Mammary Epithelium and Stroma: Implications for Breast Cancer—Preventive Actions of Dietary Factors

USDA-ARS?s Scientific Manuscript database

The mammary gland is composed of two major cellular compartments: a highly dynamic epithelium that undergoes cycles of proliferation, differentiation, and apoptosis in response to local and endocrine signals and the underlying stroma comprised of fibroblasts, endothelial cells, and adipocytes that c...

Anti-Aging Medicine: Can Consumers Be Better Protected?

ERIC Educational Resources Information Center

Mehlman, Maxwell J.; Binstock, Robert H.; Juengst, Eric T.; Ponsaran, Roselle S.; Whitehouse, Peter J.

2004-01-01

The use of interventions claiming to prevent, retard, or reverse aging is proliferating. Some of these interventions can seriously harm older persons and aging baby boomers who consume them. Others that are merely ineffective may divert patients from participating in beneficial regimens and also cause them economic harm. "Free market…

[The development of an integrated suicide-violence prevention program for adolescents].

PubMed

Park, Hyun Sook

2008-08-01

The purpose of this study was to develop an integrated suicide-violence prevention program for adolescents. Another purpose was to evaluate the effects of the integrated suicide-violence prevention program on self-esteem, parent-child communication, aggression, and suicidal ideation in adolescents. The study employed a quasi-experimental design. Participants for the study were high school students, 24 in the experimental group and 25 in the control group. Data was analyzed by using the SPSS/WIN. 11.5 program with chi2 test, t-test, and 2-way ANOVA. Participants in the integrated suicide-violence prevention program reported increased self-esteem scores, which was significantly different from those in the control group. Participants in the integrated suicide-violence prevention program reported decreased aggression and suicidal ideation scores, which was significantly different from those in the control group. The integrated suicide-violence prevention program was effective in improving self-esteem and decreasing aggression and suicidal ideation for adolescents. Therefore, this approach is recommended as the integrated suicide-violence prevention strategy for adolescents.

A Clustered Randomized Controlled Trial of the Positive Prevention PLUS Adolescent Pregnancy Prevention Program.

PubMed

LaChausse, Robert G

2016-09-01

To determine the impact of Positive Prevention PLUS, a school-based adolescent pregnancy prevention program on delaying sexual intercourse, birth control use, and pregnancy. I randomly assigned a diverse sample of ninth grade students in 21 suburban public high schools in California into treatment (n = 2483) and control (n = 1784) groups that participated in a clustered randomized controlled trial. Between October 2013 and May 2014, participants completed baseline and 6-month follow-up surveys regarding sexual behavior and pregnancy. Participants in the treatment group were offered Positive Prevention PLUS, an 11-lesson adolescent pregnancy prevention program. The program had statistically significant impacts on delaying sexual intercourse and increasing the use of birth control. However, I detected no program effect on pregnancy rates at 6-month follow-up. The Positive Prevention PLUS program demonstrated positive impacts on adolescent sexual behavior. This suggests that programs that focus on having students practice risk reduction skills may delay sexual activity and increase birth control use.

Stem cell plasticity enables hair regeneration following Lgr5+ cell loss.

PubMed

Hoeck, Joerg D; Biehs, Brian; Kurtova, Antonina V; Kljavin, Noelyn M; de Sousa E Melo, Felipe; Alicke, Bruno; Koeppen, Hartmut; Modrusan, Zora; Piskol, Robert; de Sauvage, Frederic J

2017-06-01

Under injury conditions, dedicated stem cell populations govern tissue regeneration. However, the molecular mechanisms that induce stem cell regeneration and enable plasticity are poorly understood. Here, we investigate stem cell recovery in the context of the hair follicle to understand how two molecularly distinct stem cell populations are integrated. Utilizing diphtheria-toxin-mediated cell ablation of Lgr5 + (leucine-rich repeat-containing G-protein-coupled receptor 5) stem cells, we show that killing of Lgr5 + cells in mice abrogates hair regeneration but this is reversible. During recovery, CD34 + (CD34 antigen) stem cells activate inflammatory response programs and start dividing. Pharmacological attenuation of inflammation inhibits CD34 + cell proliferation. Subsequently, the Wnt pathway controls the recovery of Lgr5 + cells and inhibition of Wnt signalling prevents Lgr5 + cell and hair germ recovery. Thus, our study uncovers a compensatory relationship between two stem cell populations and the underlying molecular mechanisms that enable hair follicle regeneration.

Human replication protein Cdc6 is selectively cleaved by caspase 3 during apoptosis

PubMed Central

Pelizon, Cristina; d’Adda di Fagagna, Fabrizio; Farrace, Lorena; Laskey, Ronald A.

2002-01-01

In eukaryotes, the initiation of DNA replication involves the ordered assembly on chromatin of pre-replicative complexes (pre-RCs), including the origin recognition complex (ORC), Cdc6, Cdt1 and the minichromosome maintenance proteins (MCMs). In light of its indispensable role in the formation of pre-RCs, Cdc6 binding to chromatin represents a key step in the regulation of DNA replication and cell proliferation. Here, we study the human Cdc6 (HuCdc6) protein during programmed cell death (apoptosis). We find that HuCdc6, but not HuOrc2 (a member of the ORC) or HuMcm5 (one of the MCMs), is specifically cleaved in several human cell lines induced to undergo apoptosis by a variety of stimuli. Expression of caspase-uncleavable mutant HuCdc6 attenuates apoptosis, delaying cell death. Therefore, an important function for cleavage of HuCdc6 is to prevent a wounded cell from replicating and to facilitate death. PMID:12151338

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

Hooper, R.

Since the end of the Cold War the world has witnessed a remarkable series of events demonstrating that universal adherence to the principles of nuclear non-proliferation and disarmament are no longer utopian dreams. The author reviews the actions of various countries to terminate or reduce nuclear weapons programs and those that are resisting the non-proliferation efforts. The author addresses efforts of the International Atomic Energy Agency (IAEA) to safeguard declared nuclear material more cost-effectively and deal with the possibility of undeclared nuclear activities.

Selective Activation of a Perforin-Granzyme B Fusion Protein Toxin by PSA as Therapy for Metastatic Prostate Cancer

DTIC Science & Technology

2016-10-01

Prostate Cancer PRINCIPAL INVESTIGATOR: Samuel Denmeade RECIPIENT: Johns Hopkins University Baltimore, MD 21218 REPORT DATE: October 2016 TYPE...PSA as Therapy for Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0382 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Samuel R Denmeade...cytotoxic agent that can selectively kill both proliferating and non-proliferating prostate cancer cells within a metastatic site without significant host

Estradiol-17β-Induced Human Neural Progenitor Cell Proliferation Is Mediated by an Estrogen Receptor β-Phosphorylated Extracellularly Regulated Kinase Pathway

PubMed Central

Wang, Jun Ming; Liu, Lifei; Brinton, Roberta Diaz

2008-01-01

Estradiol-17β (E2) induces rodent hippocampal neural progenitor cell (NPC) proliferation in vitro, in vivo, and after brain injury. The purpose of the present investigation was to determine whether E2-induced proliferation observed in rodent model systems generalized to cells of human neural origin and the signaling pathway by which E2 promotes mitosis of human NPCs (hNPCs). Results of these analyses indicate that E2 induced a significant increase in hNPC proliferation in a time- and dose-dependent manner. E2-induced hNPC DNA replication was paralleled by elevated cell cycle protein expression and centrosome amplification, which was associated with augmentation of total cell number. To determine whether estrogen receptor (ER) and which ER subtype were required for E2-induced hNPC proliferation, ER expression was first determined by real-time RT-PCR, followed by Western blot analysis, and subsequently verified pharmacologically using ERα or β-selective ligands. Results of these analyses indicated that ERβ expression was predominant relative to ERα, which was barely detectable in hNPCs. Activation of ERβ by the ERβ-selective ligand, diarylpropionitrile, led to an increase in phosphorylated extracellular signal-regulated kinase, and subsequent centrosome amplification and hNPC proliferation, which were blocked by the MEKK antagonist, UO126, but not its inactive analog, UO124. These findings, for the first time, demonstrate the molecular cascade and related cell biology events involved in E2-induced hNPC proliferation in vitro. Therapeutic implications of these findings relevant to hormone therapy and prevention of neurodegenerative disease are discussed. PMID:17962344

Overexpression of human Hsp27 inhibits serum-induced proliferation in airway smooth muscle myocytes and confers resistance to hydrogen peroxide cytotoxicity.

PubMed

Salinthone, Sonemany; Ba, Mariam; Hanson, Lisa; Martin, Jody L; Halayko, Andrew J; Gerthoffer, William T

2007-11-01

Airway smooth muscle (ASM) hypertrophy and hyperplasia are characteristics of asthma that lead to thickening of the airway wall and obstruction of airflow. Very little is known about mechanisms underlying ASM remodeling, but in vascular smooth muscle, it is known that progression of atherosclerosis depends on the balance of myocyte proliferation and cell death. Small heat shock protein 27 (Hsp27) is antiapoptotic in nonmuscle cells, but its role in ASM cell survival is unknown. Our hypothesis was that phosphorylation of Hsp27 may regulate airway remodeling by modifying proliferation, cell survival, or both. To test this hypothesis, adenoviral vectors were used to overexpress human Hsp27 in ASM cells. Cells were infected with empty vector (Ad5) or wild-type Hsp27 (AdHsp27 WT), and proliferation and death were assessed. Overexpressing Hsp27 WT caused a 50% reduction in serum-induced proliferation and increased cell survival after exposure to 100 microM hydrogen peroxide (H(2)O(2)) compared with mock-infected controls. Overexpression studies utilizing an S15A, S78A, and S82A non-phosphorylation mutant (AdHsp27 3A) and an S15D, S78D, and S82D pseudo-phosphorylation mutant (AdHsp27 3D) showed phosphorylation of Hsp27 was necessary for regulation of ASM proliferation, but not survival. Hsp27 provided protection against H(2)O(2)-induced cytotoxicity by upregulating cellular glutathione levels and preventing necrotic cell death, but not apoptotic cell death. The results support the notion that ASM cells can be stimulated to undergo proliferation and death and that Hsp27 may regulate these processes, thereby contributing to airway remodeling in asthmatics.

Molecular basis for the interplay of apoptosis and proliferation mediated by Bcl-xL:Bim interactions in pancreatic cancer cells

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

Abrol, Ravinder, E-mail: abrol@wag.caltech.edu; Edderkaoui, Mouad; Goddard, William A.

2012-06-15

Highlights: Black-Right-Pointing-Pointer Direct role of Bcl-2 protein interactions in cell proliferation is not clear. Black-Right-Pointing-Pointer Designed Bcl-xL mutants show opposite effects on apoptosis and proliferation. Black-Right-Pointing-Pointer Disrupting Bcl-xL:Bim interaction increased apoptosis in pancreatic cancer. Black-Right-Pointing-Pointer Disrupting Bcl-xL:Bim interaction decreased proliferation in pancreatic cancer. Black-Right-Pointing-Pointer Bcl-xL:Bim interaction can control both apoptosis and proliferation. -- Abstract: A major mechanism through which cancer cells avoid apoptosis is by promoting the association of anti-apoptotic members of the pro-survival Bcl-2 protein family (like Bcl-2 and Bcl-xL) with BH{sub 3} domain-only proteins (like Bim and Bid). Apoptosis and cell proliferation have been shown to be linkedmore » for many cancers but the molecular basis for this link is far from understood. We have identified the Bcl-xL:Bim protein-protein interface as a direct regulator of proliferation and apoptosis in pancreatic cancer cells. We were able to predict and subsequently verify experimentally the effect of various Bcl-xL single-point mutants (at the position A142) on binding to Bim by structural analysis and computational modeling of the inter-residue interactions at the Bcl-xL:Bim protein-protein interface. The mutants A142N, A142Q, and A142Y decreased binding of Bim to Bcl-xL and A142S increased this binding. The Bcl-xL mutants, with decreased affinity for Bim, caused an increase in apoptosis and a corresponding decrease in cell proliferation. However, we could prevent these effects by introducing a small interfering RNA (siRNA) targeted at Bim. These results show a novel role played by the Bcl-xL:Bim interaction in regulating proliferation of pancreatic cancer cells at the expense of apoptosis. This study presents a physiologically relevant model of the Bcl-xL:Bim interface that can be used for rational therapeutic design for the inhibition of proliferation and cancer cell resistance to apoptosis.« less

Utility of Social Modeling for Proliferation Assessment - Preliminary Assessment

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

Coles, Garill A.; Gastelum, Zoe N.; Brothers, Alan J.

2009-06-01

This Preliminary Assessment draft report will present the results of a literature search and preliminary assessment of the body of research, analysis methods, models and data deemed to be relevant to the Utility of Social Modeling for Proliferation Assessment research. This report will provide: 1) a description of the problem space and the kinds of information pertinent to the problem space, 2) a discussion of key relevant or representative literature, 3) a discussion of models and modeling approaches judged to be potentially useful to the research, and 4) the next steps of this research that will be pursued based onmore » this preliminary assessment. This draft report represents a technical deliverable for the NA-22 Simulations, Algorithms, and Modeling (SAM) program. Specifically this draft report is the Task 1 deliverable for project PL09-UtilSocial-PD06, Utility of Social Modeling for Proliferation Assessment. This project investigates non-traditional use of social and cultural information to improve nuclear proliferation assessment, including nonproliferation assessment, proliferation resistance assessments, safeguards assessments and other related studies. These assessments often use and create technical information about the State’s posture towards proliferation, the vulnerability of a nuclear energy system to an undesired event, and the effectiveness of safeguards. This project will find and fuse social and technical information by explicitly considering the role of cultural, social and behavioral factors relevant to proliferation. The aim of this research is to describe and demonstrate if and how social science modeling has utility in proliferation assessment.« less

Anti-inflammatory effects of fish oil in ovaries of laying hens target prostaglandin pathways

PubMed Central

2013-01-01

Background An effective way to control cancer is by prevention. Ovarian cancer is the most lethal gynecological malignancy. Progress in the treatment and prevention of ovarian cancer has been hampered due to the lack of an appropriate animal model and absence of effective chemo-prevention strategies. The domestic hens spontaneously develop ovarian adenocarcinomas that share similar histological appearance and symptoms such as ascites and metastasis with humans. There is a link between chronic inflammation and cancer. Prostaglandin E2 (PGE2) is the most pro-inflammatory ecoisanoid and one of the downstream products of two isoforms of cyclooxygenase (COX) enzymes: COX-1 and COX-2. PGE2 exerts its effects on target cells by coupling to four subtypes of receptors which have been classified as EP1-4. Fish oil is a source of omega-3 fatty acids (OM-3FAs) which may be effective in prevention of ovarian cancer. Our objective was to assess the potential impact of fish oil on expression of COX enzymes, PGE2 concentration, apoptosis and proliferation in ovaries of laying hens. Methods 48 white Leghorn hens were fed 50, 100, 175, 375 and 700 mg/kg fish oil for 21 days. The OM3-FAs and omega-6 fatty acids contents of egg yolks were determined by Gas Chromatography. Proliferation, apoptosis, COX-1, COX-2 and prostaglandin receptor subtype 4 (EP4) protein and mRNA expression and PGE2 concentration in ovaries were measured by PCNA, TUNEL, Western blot, quantitative real-time qPCR and ELISA, respectively. Results Consumption of fish oil increased the incorporation of OM-3FAs into yolks and decreased both COX-1 and COX-2 protein and mRNA expression. In correlation with COXs down-regulation, fish oil significantly reduced the concentrations of PGE2 in ovaries. EP4 protein and mRNA expression in ovaries of hens was not affected by fish oil treatment. A lower dose of fish oil increased the egg laying frequency. 175 and 700 mg/kg fish oil reduced proliferation and 700 mg/kg increased apoptosis in hen ovaries. Conclusions Our findings suggest that the lower doses of fish oil reduce inflammatory PG and may be an effective approach in preventing ovarian carcinogenesis. These findings may provide the basis for clinical trials utilizing fish oil as a dietary intervention targeting prostaglandin biosynthesis for the prevention and treatment of ovarian cancer. PMID:24156238

Evaluation of Prevention Programs: A Basic Guide for Practitioners.

ERIC Educational Resources Information Center

Moberg, D. Paul

This guide is intended for professionals, laypersons, funding agents and others involved in planning and delivering local prevention services. Chapter 1 defines prevention, and differentiates between prevention strategies and programs targeted toward individuals or to general populations. Program evaluation and evaluation research are defined and…

Classroom Effects of a Hybrid Universal and Indicated Prevention Program for Preschool Children: A Comparative Analysis Based on Social and Emotional Competence Screening

ERIC Educational Resources Information Center

Stefan, Catrinel Alice; Miclea, Mircea

2012-01-01

Research Findings: The current study's main aim was to implement a multifocused, community-based intervention for preventing conduct problems in preschool children. Our assumption was that the same intervention program could be delivered concomitantly as a universal prevention program for all children as well as an indicated prevention program for…

Alcohol, Tobacco, and Other Drug Use Prevention Programs in U.S. Schools: A Descriptive Summary

PubMed Central

Kumar, Revathy; O’Malley, Patrick; Johnston, Lloyd; Laetz, Viginia

2013-01-01

This report identifies the relative prevalence and trends in state, local, and commercially developed substance abuse prevention programs in middle and high schools from 2001 to 2007, using survey data from nationally representative samples of 1,206 schools. Based on school administrators’ reports, schools and school districts offer students, on average 1.62 prevention programs during their school years from elementary through high school. Bivariate and multivariate regression analyses were conducted with school demographic characteristics (public versus private, size, population density, region of the country, school race/ethnic composition and socioeconomic status of the student body) as predictors of total number of weighted programs students received and of the relative use of local, state, and commercial programs. Schools in the West had significantly fewer prevention programs than those in all other regions of the country. Students in predominantly White and in more affluent schools received significantly more prevention programs than students in majority African American, majority Hispanic, or in less affluent schools. The most frequently reported programs that students received were locally developed. Of all the prevention programs, D.A.R.E. was the most widely adopted. Findings from this study suggest that schools often develop their own curriculum to suit their students’ needs, and students are exposed to multiple prevention programs through their school years, making it difficult to examine the effectiveness of any single program in preventing and reducing substance use among students. PMID:23404662

[Primary Prevention in General Medical Practice: A Survey].

PubMed

Holmberg, C; Muckelbauer, R; Sarganas, G; Braun, V; Heintze, C; Dini, L; Müller-Nordhorn, J

2016-09-16

Aim of the study: According to the German social insurance code §20 Sec. 1, statutory health insurance companies can reimburse up to 80% of costs incurred by primary prevention programs in physical activity, nutrition, stress management and drug consumption. Whether and how many general practitioners (GPs) provide their patients with information on such programs as part of their own practice is unknown. In this study, we investigate to which primary prevention programs primary care physicians refer their patients and whether they take into account reimbursability of programs. Methods: Between November 2010 and February 2011, all GPs with a practice in Berlin (n=1 168) received a questionnaire that assessed if patients were referred to prevention programs and the type of programs they were referred to, if they ensured they are reimbursable and if they themselves offered prevention programs. Descriptive statistics and multivariate logistic regression was used for analysis. Results: Of 474 respondents (response rate: 41%), 67% were female. Of the respondents, 22% offered reimbursable prevention programs and 42% at out-of-pocket expense. Patients were referred to reimbursable programs by 63%. GPs younger than 50 were twice as likely to offer reimbursable programs in their practice compared to those older than 50 (OR=1.7; 95% KI 1.1-2,8; p-value 0.025). Conclusion: A successful implementation of the new German prevention law needs awareness among GPs about reimbursable prevention programs, which may be lacking in some groups. © Georg Thieme Verlag KG Stuttgart · New York.

Youth exposure to violence prevention programs in a national sample.

PubMed

Finkelhor, David; Vanderminden, Jennifer; Turner, Heather; Shattuck, Anne; Hamby, Sherry

2014-04-01

This paper assesses how many children and youth have had exposure to programs aimed at preventing various kinds of violence perpetration and victimization. Based on a national sample of children 5-17, 65% had ever been exposed to a violence prevention program, 55% in the past year. Most respondents (71%) rated the programs as very or somewhat helpful. Younger children (5-9) who had been exposed to higher quality prevention programs had lower levels of peer victimization and perpetration. But the association did not apply to older youth or youth exposed to lower quality programs. Disclosure to authorities was also more common for children with higher quality program exposure who had experienced peer victimizations or conventional crime victimizations. The findings are consistent with possible benefits from violence prevention education programs. However, they also suggest that too few programs currently include efficacious components. Copyright © 2014 Elsevier Ltd. All rights reserved.

Integrating Health and Prevention Services in Syringe Access Programs: A Strategy to Address Unmet Needs in a High-Risk Population

PubMed Central

Storm, Deborah S.; Hoyt, Mary Jo; Dutton, Loretta; Berezny, Linda; Allread, Virginia; Paul, Sindy

2014-01-01

Injection drug users are at a high risk for a number of preventable diseases and complications of drug use. This article describes the implementation of a nurse-led health promotion and disease prevention program in New Jersey's syringe access programs. Initially designed to target women as part of a strategy to decrease missed opportunities for perinatal HIV prevention, the program expanded by integrating existing programs and funding streams available through the state health department. The program now offers health and prevention services to both men and women, with 3,488 client visits in 2011. These services extend the reach of state health department programs, such as adult vaccination and hepatitis and tuberculosis screening, which clients would have had to seek out at multiple venues. The integration of prevention, treatment, and health promotion services in syringe access programs reaches a vulnerable and underserved population who otherwise may receive only urgent and episodic care. PMID:24385646

Measuring sustainment of prevention programs and initiatives: a study protocol.

PubMed

Palinkas, Lawrence A; Spear, Suzanne E; Mendon, Sapna J; Villamar, Juan; Valente, Thomas; Chou, Chi-Ping; Landsverk, John; Kellam, Shepperd G; Brown, C Hendricks

2016-07-16

Sustaining prevention efforts directed at substance use and mental health problems is one of the greatest, yet least understood, challenges in the field of implementation science. A large knowledge gap exists regarding the meaning of the term "sustainment" and what factors predict or even measure sustainability of effective prevention programs and support systems. The U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) supports a diverse portfolio of prevention and treatment grant programs that aim to improve population and individual level behavioral health. This study focuses on four SAMHSA prevention grant programs, two of which target substance abuse prevention at the state or single community level, one targets suicide prevention, and one targets prevention of aggressive/disruptive behavior in elementary schools. An examination of all four grant programs simultaneously provides an opportunity to determine what is meant by the term sustainment and identify and support both the unique requirements for improving sustainability for each program as well as for developing a generalizable framework comprised of core components of sustainment across diverse prevention approaches. Based on an analysis of qualitative and quantitative data of 10 grantees supported by these four programs, we will develop a flexible measurement system, with both general and specific components, that can bring precision to monitoring sustainment of infrastructure, activities, and outcomes for each prevention approach. We will then transform this system for use in evaluating and improving the likelihood of achieving prevention effort sustainment. To achieve these goals, we will (1) identify core components of sustainment of prevention programs and their support infrastructures; (2) design a measurement system for monitoring and providing feedback regarding sustainment within the four SAMHSA's prevention-related grant programs; and (3) pilot test the predictability of this multilevel measurement system across these programs and the feasibility and acceptability of a measurement system to evaluate and improve the likelihood of sustainment. This project is intended to improve sustainment of the supporting prevention infrastructure, activities, and outcomes that are funded by federal, state, community, and foundation sources.

A wakeup call to the prevention field: are prevention programs for substance use effective for girls?

PubMed

Kumpfer, Karol L; Smith, Paula; Summerhays, Julia Franklin

2008-07-01

Substance misuse in adolescent girls has increased dramatically since 1992. This article reviews trends in use rates and etiological theories tested by gender that suggest that family protective factors have more influence on girls. Next, a literature review reveals that few prevention programs have published their outcomes by gender or developed gender-specific programs. Nationwide community coalition results found positive effects on boys but increased drug use in young girls. The most effective programs are family focused targeting family bonding, supervision, and communication. Recent gender-specific prevention programs with positive results address stress, depression, social assertiveness, and body image. The authors recommend additional research testing programs by gender and also gender-specific versus generic versions of evidence-based programs to determine how to improve prevention program effectiveness for girls.

Cost effectiveness of the MDOT preventive maintenance program.

DOT National Transportation Integrated Search

2013-04-01

The Michigan Department of Transportations (MDOT) pavement preservation program dates back to 1992. MDOTs pavement preservation strategy is primarily implemented through its capital preventive maintenance (CPM) program, in which preventive main...

Programs for Preventing the Causes of Mental Retardation.

ERIC Educational Resources Information Center

Oliphant, Peter S.; And Others

This monograph, which reports findings from the New Jersey Governor's Council on the Prevention of Mental Retardation, discusses the scope of mental retardation (MR), its causes, identification of people at risk, and prevention methods. The Council cites several cost-effective prevention programs, such as vaccination programs and prenatal care…

77 FR 73316 - Approval of Air Quality Implementation Plans; California; Eastern Kern, Imperial, Placer, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-10

... adopt and implement a SIP- approved Prevention of Significant Deterioration (PSD) permit program. We are...--Prevention of Significant Deterioration (PSD) Permit Program, PCAPCD Rule 518--Prevention of Significant Deterioration (PSD) Permit Program, and YSAQMD Rule 3.24-- Prevention of Significant Deterioration. The approval...

Connect: An Effective Community-Based Youth Suicide Prevention Program

ERIC Educational Resources Information Center

Bean, Gretchen; Baber, Kristine M.

2011-01-01

Youth suicide prevention is an important public health issue. However, few prevention programs are theory driven or systematically evaluated. This study evaluated Connect, a community-based youth suicide prevention program. Analysis of pre and posttraining questionnaires from 648 adults and 204 high school students revealed significant changes in…

Theoretical, Developmental & Cultural Orientations of School-Based Prevention Programs for Preschoolers

ERIC Educational Resources Information Center

Humphries, Marisha L.; Keenan, Kate E.

2006-01-01

Schools are the primary environment in which to conduct prevention programs for school-age children. Educators, policy makers, and psychologist argue that prevention efforts should begin as early as possible to maximize their effectiveness. Surprisingly, there are relatively few school-based prevention programs targeted for preschoolers. Given the…

Optimizing violence prevention programs: an examination of program effectiveness among urban high school students.

PubMed

Thompkins, Amanda C; Chauveron, Lisa M; Harel, Ofer; Perkins, Daniel F

2014-07-01

While demand for youth violence prevention programs increases, the ability of the school-day schedule to accommodate their time requirements has diminished. Viable school-based prevention programs must strike a balance between brevity and effectiveness. This article reports results from an effectiveness trial of a 12-session curriculum-based universal violence prevention program that promotes healthy conflict resolution skills among urban adolescents. Using a review of program record data and a multisite quasi-experimental study design, we examined the effectiveness of a New York City-based violence prevention program entitled the Violence Prevention project (VPP) optimized to meet school needs. We analyzed survey data from 1112 9th- and 10th-grade students in 13 New York City public high schools across 4 consecutive school years. Both participants and nonparticipants were surveyed. Review of program record data indicated that the program was implemented with acceptable fidelity to the core component structure, and that participant responsiveness to the model was high. Multilevel modeling indicated that VPP participation was protective for academic self-concept and promoted conflict resolution skills. Findings indicate that semester-long violence prevention programs optimized to meet the needs of a typical high school can be effective at promoting healthy conflict resolution skills in urban adolescents. © 2014, American School Health Association.

Teen Suicide in Nevada: The Problem, Effective Intervention & Prevention Programs, Status of Programs in Nevada Schools, Exemplary Programs, [and] Guidelines for Nevada School Programs.

ERIC Educational Resources Information Center

Smaby, Marlow H.; Downing, Jerry

The purpose of this paper is twofold: it reviews current national research on adolescent suicide and successful intervention/prevention programs and it surveys the 17 Nevada school districts to determine the presence of successful suicide intervention/prevention programs in the state. Findings include the following: (1) the popular…

Proliferation resistance design of a plutonium cycle (Proliferation Resistance Engineering Program: PREP)

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

Sorenson, R.J.; Roberts, F.P.; Clark, R.G.

1979-01-19

This document describes the proliferation resistance engineering concepts developed to counter the threat of proliferation of nuclear weapons in an International Fuel Service Center (IFSC). The basic elements of an International Fuel Service Center are described. Possible methods for resisting proliferation such as processing alternatives, close-coupling of facilities, process equipment layout, maintenance philosophy, process control, and process monitoring are discussed. Political and institutional issues in providing proliferation resistance for an International Fuel Service Center are analyzed. The conclusions drawn are (1) use-denial can provide time for international response in the event of a host nation takeover. Passive use-denial is moremore » acceptable than active use-denial, and acceptability of active-denial concepts is highly dependent on sovereignty, energy dependence and economic considerations; (2) multinational presence can enhance proliferation resistance; and (3) use-denial must be nonprejudicial with balanced interests for governments and/or private corporations being served. Comparisons between an IFSC as a national facility, an IFSC with minimum multinational effect, and an IFSC with maximum multinational effect show incremental design costs to be less than 2% of total cost of the baseline non-PRE concept facility. The total equipment acquisition cost increment is estimated to be less than 2% of total baseline facility costs. Personnel costs are estimated to increase by less than 10% due to maximum international presence. 46 figures, 9 tables.« less

Handbook for Evaluating Drug and Alcohol Prevention Programs: Staff/Team Evaluation of Prevention Programs (STEPP).

ERIC Educational Resources Information Center

Hawkins, J. David; Nederhood, Britt

This handbook was developed for the purpose of providing drug and alcohol prevention program managers with a comprehensive yet easy-to-use tool to help their evaluation efforts. The handbook emphasizes program staff members working together as a team. It provides instruments and activities for determining program effectiveness, as well as…

Attendance Improvement and Dropout Prevention (AIDP) Demonstration and Replication Program 1989. OREA Evaluation Section Report.

ERIC Educational Resources Information Center

New York City Board of Education, Brooklyn, NY. Office of Research, Evaluation, and Assessment.

Each of the 1989 dropout prevention programs funded under the New York City Attendance Improvement Dropout Prevention (AIDP) Demonstration and Replication Program was successful in meeting some of its objectives, and all of the programs were viewed as valuable by principals and teachers. The program encourages the design and implementation of…

Some theoretical models and constructs generic to substance abuse prevention programs for adolescents: possible relevance and limitations for problem gambling.

PubMed

Evans, Richard I

2003-01-01

For the past several years the author and his colleagues have explored the area of how social psychological constructs and theoretical models can be applied to the prevention of health threatening behaviors in adolescents. In examining the need for the development of gambling prevention programs for adolescents, it might be of value to consider the application of such constructs and theoretical models as a foundation to the development of prevention programs in this emerging problem behavior among adolescents. In order to provide perspective to the reader, the present paper reviews the history of various psychosocial models and constructs generic to programs directed at prevention of substance abuse in adolescents. A brief history of some of these models, possibly most applicable to gambling prevention programs, are presented. Social inoculation, reasoned action, planned behavior, and problem behavior theory, are among those discussed. Some deficits of these models, are also articulated. How such models may have relevance to developing programs for prevention of problem gambling in adolescents is also discussed. However, the inherent differences between gambling and more directly health threatening behaviors such as substance abuse must, of course, be seriously considered in utilizing such models. Most current gambling prevention programs have seldom been guided by theoretical models. Developers of gambling prevention programs should consider theoretical foundations, particularly since such foundations not only provide a guide for programs, but may become critical tools in evaluating their effectiveness.

Antidiabetic Effects of Chamomile Flowers Extract in Obese Mice through Transcriptional Stimulation of Nutrient Sensors of the Peroxisome Proliferator-Activated Receptor (PPAR) Family

PubMed Central

Weidner, Christopher; Wowro, Sylvia J.; Rousseau, Morten; Freiwald, Anja; Kodelja, Vitam; Abdel-Aziz, Heba; Kelber, Olaf; Sauer, Sascha

2013-01-01

Given the significant increases in the incidence of metabolic diseases, efficient strategies for preventing and treating of these common disorders are urgently needed. This includes the development of phytopharmaceutical products or functional foods to prevent or cure metabolic diseases. Plant extracts from edible biomaterial provide a potential resource of structurally diverse molecules that can synergistically interfere with complex disorders. In this study we describe the safe application of ethanolic chamomile (Matricaria recutita) flowers extract (CFE) for the treatment and prevention of type 2 diabetes and associated disorders. We show in vitro that this extract activates in particular nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) and its isotypes. In a cellular context, in human primary adipocytes CFE administration (300 µg/ml) led to specific expression of target genes of PPARγ, whereas in human hepatocytes CFE-induced we detected expression changes of genes that were regulated by PPARα. In vivo treatment of insulin-resistant high-fat diet (HFD)-fed C57BL/6 mice with CFE (200 mg/kg/d) for 6 weeks considerably reduced insulin resistance, glucose intolerance, plasma triacylglycerol, non-esterified fatty acids (NEFA) and LDL/VLDL cholesterol. Co-feeding of lean C57BL/6 mice a HFD with 200 mg/kg/d CFE for 20 weeks showed effective prevention of fatty liver formation and hepatic inflammation, indicating additionally hepatoprotective effects of the extract. Moreover, CFE treatment did not reveal side effects, which have otherwise been associated with strong synthetic PPAR-targeting molecules, such as weight gain, liver disorders, hemodilution or bone cell turnover. Taken together, modulation of PPARs and other factors by chamomile flowers extract has the potential to prevent or treat type 2 diabetes and related disorders. PMID:24265809

Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN.

PubMed

Kyte, S Lauren; Toma, Wisam; Bagdas, Deniz; Meade, Julie A; Schurman, Lesley D; Lichtman, Aron H; Chen, Zhi-Jian; Del Fabbro, Egidio; Fang, Xianjun; Bigbee, John W; Damaj, M Imad; Gewirtz, David A

2018-01-01

Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments. Our studies were designed to investigate whether nicotine can prevent and/or reverse paclitaxel-induced peripheral neuropathy in a mouse model of CIPN, while ensuring that nicotine will not stimulate lung tumor cell proliferation or interfere with the antitumor properties of paclitaxel. Male C57BL/6J mice received paclitaxel every other day for a total of four injections (8 mg/kg, i.p.). Acute (0.3-0.9 mg/kg, i.p.) and chronic (24 mg/kg per day, s.c.) administration of nicotine respectively reversed and prevented paclitaxel-induced mechanical allodynia. Blockade of the antinociceptive effect of nicotine with mecamylamine and methyllycaconitine suggests that the reversal of paclitaxel-induced mechanical allodynia is primarily mediated by the α 7 nicotinic acetylcholine receptor subtype. Chronic nicotine treatment also prevented paclitaxel-induced intraepidermal nerve fiber loss. Notably, nicotine neither promoted proliferation of A549 and H460 non-small cell lung cancer cells nor interfered with paclitaxel-induced antitumor effects, including apoptosis. Most importantly, chronic nicotine administration did not enhance Lewis lung carcinoma tumor growth in C57BL/6J mice. These data suggest that the nicotinic acetylcholine receptor-mediated pathways may be promising drug targets for the prevention and treatment of CIPN. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Treatment of whole blood with riboflavin plus ultraviolet light, an alternative to gamma irradiation in the prevention of transfusion-associated graft-versus-host disease?

PubMed

Fast, Loren D; Nevola, Martha; Tavares, Jennifer; Reddy, Heather L; Goodrich, Ray P; Marschner, Susanne

2013-02-01

Exposure of blood products to gamma irradiation is currently the standard of care in the prevention of transfusion-associated graft-versus-host disease (TA-GVHD). Regulatory, technical, and clinical challenges associated with the use of gamma irradiators are driving efforts to develop alternatives. Pathogen reduction methods were initially developed to reduce the risk of microbial transmission by blood components. Through modifications of nucleic acids, these technologies interfere with the replication of both pathogens and white blood cells (WBCs). To date, systems for pathogen and WBC inactivation of products containing red blood cells are less well established than those for platelets and plasma. In this study, the in vitro and in vivo function of WBCs present in whole blood after exposure to riboflavin plus ultraviolet light (Rb-UV) was examined and compared to responses of WBCs obtained from untreated or gamma-irradiated blood by measuring proliferation, cytokine production, activation, and antigen presentation and xenogeneic (X-)GVHD responses in an in vivo mouse model. In vitro studies demonstrated that treatment of whole blood with Rb-UV was as effective as gamma irradiation in preventing WBC proliferation, but was more effective in preventing antigen presentation, cytokine production, and T-cell activation. Consistent with in vitro findings, treatment with Rb-UV was as effective as gamma irradiation in preventing X-GVHD, a mouse model for TA-GVHD. The ability to effectively inactivate WBCs in fresh whole blood using Rb-UV, prior to separation into components, provides the transfusion medicine community with a potential alternative to gamma irradiation. © 2012 American Association of Blood Banks.

Antidiabetic effects of chamomile flowers extract in obese mice through transcriptional stimulation of nutrient sensors of the peroxisome proliferator-activated receptor (PPAR) family.

PubMed

Weidner, Christopher; Wowro, Sylvia J; Rousseau, Morten; Freiwald, Anja; Kodelja, Vitam; Abdel-Aziz, Heba; Kelber, Olaf; Sauer, Sascha

2013-01-01

Given the significant increases in the incidence of metabolic diseases, efficient strategies for preventing and treating of these common disorders are urgently needed. This includes the development of phytopharmaceutical products or functional foods to prevent or cure metabolic diseases. Plant extracts from edible biomaterial provide a potential resource of structurally diverse molecules that can synergistically interfere with complex disorders. In this study we describe the safe application of ethanolic chamomile (Matricaria recutita) flowers extract (CFE) for the treatment and prevention of type 2 diabetes and associated disorders. We show in vitro that this extract activates in particular nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) and its isotypes. In a cellular context, in human primary adipocytes CFE administration (300 µg/ml) led to specific expression of target genes of PPARγ, whereas in human hepatocytes CFE-induced we detected expression changes of genes that were regulated by PPARα. In vivo treatment of insulin-resistant high-fat diet (HFD)-fed C57BL/6 mice with CFE (200 mg/kg/d) for 6 weeks considerably reduced insulin resistance, glucose intolerance, plasma triacylglycerol, non-esterified fatty acids (NEFA) and LDL/VLDL cholesterol. Co-feeding of lean C57BL/6 mice a HFD with 200 mg/kg/d CFE for 20 weeks showed effective prevention of fatty liver formation and hepatic inflammation, indicating additionally hepatoprotective effects of the extract. Moreover, CFE treatment did not reveal side effects, which have otherwise been associated with strong synthetic PPAR-targeting molecules, such as weight gain, liver disorders, hemodilution or bone cell turnover. Taken together, modulation of PPARs and other factors by chamomile flowers extract has the potential to prevent or treat type 2 diabetes and related disorders.

The costs of prevention.

PubMed

Weinstein, M C

1990-01-01

A prevention program is cost-effective if it yields more health benefits than do alternative uses of health care resources. Some prevention programs meet this standard: either they actually save more health care resources than they utilize, or their net costs per healthy year of life gained are lower than those of alternatives such as curative or palliative medicine. Other prevention programs, however, are less cost-effective than are medical treatments for the same disease. One lesson for public policy is that generalizations about the cost-effectiveness of "prevention" are unwise. Another lesson is that prevention programs should not be subjected to a higher standard than other health programs: they should not be expected to save money, but they should be expected to yield improved health at a reasonable price.

Specific TRPC6 Channel Activation, a Novel Approach to Stimulate Keratinocyte Differentiation*S⃞

PubMed Central

Müller, Margarethe; Essin, Kirill; Hill, Kerstin; Beschmann, Heike; Rubant, Simone; Schempp, Christoph M.; Gollasch, Maik; Boehncke, W. Henning; Harteneck, Christian; Müller, Walter E.; Leuner, Kristina

2008-01-01

The protective epithelial barrier in our skin undergoes constant regulation, whereby the balance between differentiation and proliferation of keratinocytes plays a major role. Impaired keratinocyte differentiation and proliferation are key elements in the pathophysiology of several important dermatological diseases, including atopic dermatitis and psoriasis. Ca2+ influx plays an essential role in this process presumably mediated by different transient receptor potential (TRP) channels. However, investigating their individual role was hampered by the lack of specific stimulators or inhibitors. Because we have recently identified hyperforin as a specific TRPC6 activator, we investigated the contribution of TRPC6 to keratinocyte differentiation and proliferation. Like the endogenous differentiation stimulus high extracellular Ca2+ concentration ([Ca2+]o), hyperforin triggers differentiation in HaCaT cells and in primary cultures of human keratinocytes by inducing Ca2+ influx via TRPC6 channels and additional inhibition of proliferation. Knocking down TRPC6 channels prevents the induction of Ca2+- and hyperforin-induced differentiation. Importantly, TRPC6 activation is sufficient to induce keratinocyte differentiation similar to the physiological stimulus [Ca2+]o. Therefore, TRPC6 activation by hyperforin may represent a new innovative therapeutic strategy in skin disorders characterized by altered keratinocyte differentiation. PMID:18818211

Inhibition of FLT3 Expression by Green Tea Catechins in FLT3 Mutated-AML Cells

PubMed Central

Ly, Bui Thi Kim; Chi, Hoang Thanh; Yamagishi, Makoto; Kano, Yasuhiko; Hara, Yukihiko; Nakano, Kazumi; Sato, Yuko; Watanabe, Toshiki

2013-01-01

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by a block in differentiation and uncontrolled proliferation. FLT3 is a commonly mutated gene found in AML patients. In clinical trials, the presence of a FLT3-ITD mutation significantly correlates with an increased risk of relapse and dismal overall survival. Therefore, activated FLT3 is a promising molecular target for AML therapies. In this study, we have shown that green tea polyphenols including (−)-epigallocatechin-3-gallate (EGCG), (−)-epigallocatechin (EGC), and (−)-epicatechin-3-gallate (ECG) suppress the proliferation of AML cells. Interestingly, EGCG, EGC and ECG showed the inhibition of FLT3 expression in cell lines harboring FLT3 mutations. In the THP-1 cells harboring FLT3 wild-type, EGCG showed the suppression of cell proliferation but did not suppress the expression of FLT3 even at the concentration that suppress 100% cell proliferation. Moreover, EGCG-, EGC-and ECG-treated cells showed the suppression of MAPK, AKT and STAT5 phosphorylation. Altogether, we suggest that green tea polyphenols could serve as reagents for treatment or prevention of leukemia harboring FLT3 mutations. PMID:23840454

Overexpression of Striated Muscle Activator of Rho Signaling (STARS) Increases C2C12 Skeletal Muscle Cell Differentiation.

PubMed

Wallace, Marita A; Della Gatta, Paul A; Ahmad Mir, Bilal; Kowalski, Greg M; Kloehn, Joachim; McConville, Malcom J; Russell, Aaron P; Lamon, Séverine

2016-01-01

Skeletal muscle growth and regeneration depend on the activation of satellite cells, which leads to myocyte proliferation, differentiation and fusion with existing muscle fibers. Skeletal muscle cell proliferation and differentiation are tightly coordinated by a continuum of molecular signaling pathways. The striated muscle activator of Rho signaling (STARS) is an actin binding protein that regulates the transcription of genes involved in muscle cell growth, structure and function via the stimulation of actin polymerization and activation of serum-response factor (SRF) signaling. STARS mediates cell proliferation in smooth and cardiac muscle models; however, whether STARS overexpression enhances cell proliferation and differentiation has not been investigated in skeletal muscle cells. We demonstrate for the first time that STARS overexpression enhances differentiation but not proliferation in C2C12 mouse skeletal muscle cells. Increased differentiation was associated with an increase in the gene levels of the myogenic differentiation markers Ckm, Ckmt2 and Myh4, the differentiation factor Igf2 and the myogenic regulatory factors (MRFs) Myf5 and Myf6. Exposing C2C12 cells to CCG-1423, a pharmacological inhibitor of SRF preventing the nuclear translocation of its co-factor MRTF-A, had no effect on myotube differentiation rate, suggesting that STARS regulates differentiation via a MRTF-A independent mechanism. These findings position STARS as an important regulator of skeletal muscle growth and regeneration.

Burn Eschar Stimulates Fibroblast and Adipose Mesenchymal Stromal Cell Proliferation and Migration but Inhibits Endothelial Cell Sprouting

PubMed Central

Monsuur, Hanneke N.; van den Broek, Lenie J.; Jhingoerie, Renushka L.; Vloemans, Adrianus F. P. M.

2017-01-01

The majority of full-thickness burn wounds heal with hypertrophic scar formation. Burn eschar most probably influences early burn wound healing, since granulation tissue only forms after escharotomy. In order to investigate the effect of burn eschar on delayed granulation tissue formation, burn wound extract (BWE) was isolated from the interface between non-viable eschar and viable tissue. The influence of BWE on the activity of endothelial cells derived from dermis and adipose tissue, dermal fibroblasts and adipose tissue-derived mesenchymal stromal cells (ASC) was determined. It was found that BWE stimulated endothelial cell inflammatory cytokine (CXCL8, IL-6 and CCL2) secretion and migration. However, BWE had no effect on endothelial cell proliferation or angiogenic sprouting. Indeed, BWE inhibited basic Fibroblast Growth Factor (bFGF) induced endothelial cell proliferation and sprouting. In contrast, BWE stimulated fibroblast and ASC proliferation and migration. No difference was observed between cells isolated from dermis or adipose tissue. The inhibitory effect of BWE on bFGF-induced endothelial proliferation and sprouting would explain why excessive granulation tissue formation is prevented in full-thickness burn wounds as long as the eschar is still present. Identifying the eschar factors responsible for this might give indications for therapeutic targets aimed at reducing hypertrophic scar formation which is initiated by excessive granulation tissue formation once eschar is removed. PMID:28820426

β-Catenin Dosage Is a Critical Determinant of Tracheal Basal Cell Fate Determination

PubMed Central

Brechbuhl, Heather M.; Ghosh, Moumita; Smith, Mary Kathryn; Smith, Russell W.; Li, Bilan; Hicks, Douglas A.; Cole, Brook B.; Reynolds, Paul R.; Reynolds, Susan D.

2011-01-01

The purpose of this study was to determine whether β-catenin regulates basal cell fate determination in the mouse trachea. Analysis of TOPGal transgene reporter activity and Wnt/β-catenin pathway gene expression suggested a role for β-catenin in basal cell proliferation and differentiation after naphthalene-mediated Clara-like and ciliated cell depletion. However, these basal cell activities occurred simultaneously, limiting precise determination of the role(s) played by β-catenin. This issue was overcome by analysis of β-catenin signaling in tracheal air-liquid interface cultures. The cultures could be divided into two phases: basal cell proliferation and basal cell differentiation. A role for β-catenin in basal cell proliferation was indicated by activation of the TOPGal transgene on proliferation days 3 to 5 and by transient expression of Myc (alias c-myc). Another peak of TOPGal transgene activity was detected on differentiation days 2 to 10 and was associated with the expression of Axin 2. These results suggest a role for β-catenin in basal to ciliated and basal to Clara-like cell differentiation. Genetic stabilization of β-catenin in basal cells shortened the period of basal cell proliferation but had a minor effect on this process. Persistent β-catenin signaling regulated basal cell fate by driving the generation of ciliated cells and preventing the production of Clara-like cells. PMID:21703416

Toward the Development of a Sustainable Scientific Research Culture in Azerbaijan (2011-2015).

PubMed

Aliyeva, Saida; Flanagan, Peter; Johnson, April; Strelow, Lisa

2016-01-01

This review especially describes the dangerous pathogens research program in Azerbaijan (AJ) funded by the US Defense Threat Reduction Agency under the Cooperative Biological Engagement Program (CBEP) from 2011 through 2015. The objectives of the CBEP are to prevent the proliferation of biological weapons; to consolidate and secure collections of dangerous pathogens in central repositories; to strengthen biosafety and biosecurity of laboratory facilities; and to improve partner nations' ability to detect, diagnose, report, and respond to outbreaks of disease caused by especially dangerous pathogens. One of the missions of the CBEP is therefore to increase the research skills and proficiency of partner country scientists. The program aims to fulfill this mission by sponsoring scientific research projects that exercise the modern diagnostic techniques available in the CBEP-engaged laboratories and the enhanced disease surveillance/control programs. To strengthen the local scientists' ability to develop research ideas, write grant proposals, and conduct research independently, in-country CBEP integrating contractor personnel have mentored scientists across AJ and conducted workshops to address technical gaps. As a result of CBEP engagement, seven research projects developed and led by AJ scientists have been funded, and five projects are currently in various stages of implementation. The Defense Threat Reduction Agency has also sponsored AJ scientist participation at international scientific conferences to introduce and integrate them into the global scientific community. The efforts summarized in this review represent the first steps in an ongoing process that will ultimately provide AJ scientists with the skills and resources to plan and implement research projects of local and regional relevance.

Australian school-based prevention programs for alcohol and other drugs: a systematic review.

PubMed

Teesson, Maree; Newton, Nicola C; Barrett, Emma L

2012-09-01

To reduce the occurrence and costs related to substance use and associated harms it is important to intervene early. Although a number of international school-based prevention programs exist, the majority show minimal effects in reducing drug use and related harms. Given the emphasis on early intervention and prevention in Australia, it is timely to review the programs currently trialled in Australian schools. This paper reports the type and efficacy of Australian school-based prevention programs for alcohol and other drugs. Cochrane, PsychInfo and PubMed databases were searched. Additional materials were obtained from authors, websites and reference lists. Studies were selected if they described programs developed and trialled in Australia that address prevention of alcohol and other drug use in schools. Eight trials of seven intervention programs were identified. The programs targeted alcohol, cannabis and tobacco and most were based on social learning principles. All were universal. Five of the seven intervention programs achieved reductions in alcohol, cannabis and tobacco use at follow up. Existing school-based prevention programs have shown to be efficacious in the Australian context. However, there are only a few programs available, and these require further evaluative research. This is critical, given that substance use is such a significant public health problem. The findings challenge the commonly held view that school-based prevention programs are not effective. © 2012 Australasian Professional Society on Alcohol and other Drugs.

Universal PreKindergarten (UPK) Effects on Language Concept Acquisition and the Linkage to Classroom Practices and Quality

ERIC Educational Resources Information Center

Kemp, Karen A.

2014-01-01

The emergence and establishment of Universal PreKindergarten (UPK) programs in New York school districts have proliferated over the past ten years; nonetheless, limited attention has been paid to the "process quality" dimensions of these programs (Mashburn, Hamre, Downer, Barbarin, Bryant, Burchinal, Early, & Howes, 2008). Existing…

Early Commitment Financial Aid Programs: Promises, Practices, and Policies

ERIC Educational Resources Information Center

Blanco, Cheryl D.

2005-01-01

Student financial assistance has long been a means to promote access to postsecondary education and attainment of college degrees. Numerous types of financial aid programs have proliferated over the years, including a relatively new concept that specifically targets high-risk, low-income students, focusing not just on getting them to go to college…

The Politics of Higher Education During the Johnson Administration.

ERIC Educational Resources Information Center

Fullilove, John P.

The Johnson Administration produced a significant proliferation of programs designed specifically to aid higher education. That those programs did not represent an overall strategy of institutional aid does not lessen the clear fact that the President was deeply committed to the concept of aid. The Congress was highly receptive to the Presidential…

Human Service Administrator Perceptions of Online MSW Degree Programs

ERIC Educational Resources Information Center

Curran, Laura; Sanchez Mayers, Ray; Fulghum, Fontaine

2017-01-01

Online programs have proliferated rapidly in higher education, and this reality holds true for social work education as well. Employing a mixed methods design, this study looked at employer perceptions of online degrees compared to traditional degrees. Data was collected through an online survey that included Likert type and open-ended questions…

Navigating Social Networking and Social Media in School Psychology: Ethical and Professional Considerations in Training Programs

ERIC Educational Resources Information Center

Pham, Andy V.

2014-01-01

Social networking and social media have undoubtedly proliferated within the past decade, allowing widespread communication and dissemination of user-generated content and information. Some psychology graduate programs, including school psychology, have started to embrace social networking and media for instructional and training purposes; however,…

[Prevention among migrants: Participation, migrant sensitive strategies and programme characteristics].

PubMed

Brand, T; Kleer, D; Samkange-Zeeb, F; Zeeb, Hajo

2015-06-01

Health promotion and prevention can contribute to a long, healthy life in populations both with and without migrant background. This paper provides an overview on migrant participation in prevention programmes in Germany. Furthermore, we describe migrant sensitive prevention strategies and characteristics of prevention programmes for migrants in Germany. With regard to participation in prevention programmes, lower vaccination rates are found among children and adolescents who migrated to Germany after birth. Among adults with a migrant background, we found lower participation in general health check-ups, oral health check-ups, cancer screening programs and influenza vaccination. Migrant sensitive prevention strategies address the visual style of the material, a target group specific risk communication, language requirements, a systematic involvement of the target group, and the recognition of deeply rooted sociocultural practices and beliefs. On analyzing a large database on prevention programs in Germany, we found only a few programmes that were exclusively targeted to migrant groups (0.6%). In 16.6% of the programs migrants were addressed as the target group among others. Compared to general population programs, programs for migrants were more often exclusively directed towards girls or women. Moreover, programs for migrants used community-based approaches more often and addressed different age groups. Although information on migrant participation in prevention programs and utilization of migrant sensitive strategies is still incomplete, we can assume that there is a need for diversity-oriented, migrant sensitive prevention.

Comparative Study of the Mutant Prevention Concentrations of Moxifloxacin, Levofloxacin, and Gemifloxacin against Pneumococci▿ †

PubMed Central

Credito, Kim; Kosowska-Shick, Klaudia; McGhee, Pamela; Pankuch, Glenn A.; Appelbaum, Peter C.

2010-01-01

We tested the propensity of three quinolones to select for resistant Streptococcus pneumoniae mutants by determining the mutant prevention concentration (MPC) against 100 clinical strains, some of which harbored mutations in type II topoisomerases. Compared with levofloxacin and gemifloxacin, moxifloxacin had the lowest number of strains with MPCs above the susceptibility breakpoint (P < 0.001), thus representing a lower selective pressure for proliferation of resistant mutants. Only moxifloxacin gave a 50% MPC (MPC50) value (1 μg/ml) within the susceptible range. PMID:20008781

Comparative study of the mutant prevention concentrations of moxifloxacin, levofloxacin, and gemifloxacin against pneumococci.

PubMed

Credito, Kim; Kosowska-Shick, Klaudia; McGhee, Pamela; Pankuch, Glenn A; Appelbaum, Peter C

2010-02-01

We tested the propensity of three quinolones to select for resistant Streptococcus pneumoniae mutants by determining the mutant prevention concentration (MPC) against 100 clinical strains, some of which harbored mutations in type II topoisomerases. Compared with levofloxacin and gemifloxacin, moxifloxacin had the lowest number of strains with MPCs above the susceptibility breakpoint (P<0.001), thus representing a lower selective pressure for proliferation of resistant mutants. Only moxifloxacin gave a 50% MPC (MPC50) value (1 microg/ml) within the susceptible range.

Aerobic physical training does not condition against strenuous exercise-induced changes in immune function but modulates T cell proliferative responses.

PubMed

Patiño, Pablo J; Caraballo, Domingo I; Szewczyk, Katarzyna; Quintana, Juan C; Bedoya, Lady R; Ramírez, Beatriz E; Jaramillo, Andrés

2017-09-29

Exercise-induced stress induces considerable changes in the immune system. To better understand the mechanisms related to these immune changes during acute and chronic physical stress, we studied the effects of aerobic physical training (APT) on several parameters of the immune system. Previously untrained males (18-25 years of age) were divided into a group that was subjected to 6 months of APT (n=10) and a sedentary control group (n=7). The subjects performed a cardiopulmonary exercise test (CET) at 0, 3, and 6 months of the APT program. B cell (CD19+), T cell (CD4+ and CD8+), and natural killer cell (CD56+) levels, and mitogen-induced T cell proliferation and cytokine production (interleukin-1, interleukin-4, interleukin-12, and interferon-) were evaluated before and at 30 seconds and 24 hours after the CET. There was a significant increase in CD4+ T cells and natural killer cells and a significant reduction in T cell proliferation in both groups 30 seconds after the CET at 3 and 6 months of the APT program. Of note, the trained group showed significantly lower resting T cell proliferation (before and 24 hour after the CET) than the sedentary control group at 3 and 6 months of the APT program. There were no significant differences in cytokine production after the CET between both groups at any time point of the APT program. These data show that APT does not condition against strenuous exercise induced immune changes but significantly modulates T cell proliferative responses.

76 FR 31613 - NIOSH Fire Fighter Fatality Investigation and Prevention Program (FFFIPP)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... NIOSH-063B] NIOSH Fire Fighter Fatality Investigation and Prevention Program (FFFIPP) AGENCY: The... Fire Fighter Fatality Investigation and Prevention Program (FFFIPP). NIOSH is seeking stakeholder input on the FFFIPP to ensure that the program is meeting the needs and expectations of the U.S. fire...

19 CFR 122.171 - Description of program.

Code of Federal Regulations, 2010 CFR

2010-04-01

... TREASURY AIR COMMERCE REGULATIONS Air Carrier Smuggling Prevention Program § 122.171 Description of program. The Air Carrier Smuggling Prevention Program (ACSPP) is designed to enlist the cooperation of the air carriers, as defined in 19 U.S.C. 1584 note, in Customs efforts to prevent the smuggling of controlled...

40 CFR 68.175 - Prevention program/Program 3.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.175 Prevention program/Program... the most recent change that triggered management of change procedures and the date of the most recent review or revision of management of change procedures. (j) The date of the most recent pre-startup review...

Long-term prevalence and predictors of urinary incontinence among women in the Diabetes Prevention Program Outcomes Study.

PubMed

Phelan, Suzanne; Kanaya, Alka M; Ma, Yong; Vittinghoff, Eric; Barrett-Connor, Elizabeth; Wing, Rena; Kusek, John W; Orchard, Trevor J; Crandall, Jill P; Montez, Maria G; Brown, Jeanette S

2015-02-01

To examine the long-term prevalence and predictors of weekly urinary incontinence in the Diabetes Prevention Program Outcomes Study, a follow-up study of the Diabetes Prevention Program randomized clinical trial of overweight adults with impaired glucose tolerance. This analysis included 1778 female participants of the Diabetes Prevention Program Outcomes Study who had been randomly assigned during the Diabetes Prevention Program to intensive lifestyle intervention (n = 582), metformin (n = 589) or placebo (n = 607). The study participants completed semi-annual assessments after the final Diabetes Prevention Program visit and for 6 years until October 2008. At the study entry, the prevalence of weekly urinary incontinence was lower in the intensive lifestyle intervention group compared with the metformin and placebo groups (44.2% vs 51.8%, 48.0% urinary incontinence/week, P = 0.04); during the 6-year follow-up period, these lower rates in intensive lifestyle intervention were maintained (46.7%, 53.1%, 49.9% urinary incontinence/week; P = 0.03). Statistically adjusting for urinary incontinence prevalence at the end of the Diabetes Prevention Program, the treatment arm no longer had a significant impact on urinary incontinence during the Diabetes Prevention Program Outcomes Study. Independent predictors of lower urinary incontinence during the Diabetes Prevention Program Outcomes Study included lower body mass index (odds ratio 0.988, 95% confidence interval 0.982-0.994) and greater physical activity (odds ratio 0.999, 95% confidence interval 0.998-1.000) at the Diabetes Prevention Program Outcomes Study entry, and greater reductions in body mass index (odds ratio 0.75, 95% confidence interval 0.60-0.94) and waist circumference (odds ratio 0.998, 95% confidence interval 0.996-1.0) during the Diabetes Prevention Program Outcomes Study. Diabetes was not significantly related to urinary incontinence. Intensive lifestyle intervention has a modest positive and enduring impact on urinary incontinence, and should be considered for the long-term prevention and treatment of urinary incontinence in overweight/obese women with glucose intolerance. © 2014 The Japanese Urological Association.

Sexual assault prevention programs: current issues, future directions, and the potential efficacy of interventions with women.

PubMed

Yeater, E A; O'Donohue, W

1999-11-01

Current problems facing the primary prevention of sexual assault are reviewed. Effective sexual assault prevention programs for both males and females have been slow to develop due to the fact that the etiologies of sexual assault have not been identified. Although dissemination of prevention programs has become increasingly popular in recent years, few programs have evaluated the extent to which the constructs identified in the interventions are effective at decreasing rates of sexual assault. This article discusses previous studies in sexual assault prevention programs, methodological and conceptual problems that currently exist in the field, pragmatic difficulties regarding program implementation and evaluation, and recommendations for future research with an emphasis on interventions with female participants.

Beta-hydroxy-beta-methylbutyrate (HMB) stimulates myogenic cell proliferation, differentiation and survival via the MAPK/ERK and PI3K/Akt pathways.

PubMed

Kornasio, Reut; Riederer, Ingo; Butler-Browne, Gillian; Mouly, Vincent; Uni, Zehava; Halevy, Orna

2009-05-01

Beta-hydroxy-beta-methylbutyrate (HMB), a leucine catabolite, has been shown to prevent exercise-induced protein degradation and muscle damage. We hypothesized that HMB would directly regulate muscle-cell proliferation and differentiation and would attenuate apoptosis, the latter presumably underlying satellite-cell depletion during muscle degradation or atrophy. Adding various concentrations of HMB to serum-starved myoblasts induced cell proliferation and MyoD expression as well as the phosphorylation of MAPK/ERK. HMB induced differentiation-specific markers, increased IGF-I mRNA levels and accelerated cell fusion. Its inhibition of serum-starvation- or staurosporine-induced apoptosis was reflected by less apoptotic cells, reduced BAX expression and increased levels of Bcl-2 and Bcl-X. Annexin V staining and flow cytometry analysis showed reduced staurosporine-induced apoptosis in human myoblasts in response to HMB. HMB enhanced the association of the p85 subunit of PI3K with tyrosine-phosphorylated proteins. HMB elevated Akt phosphorylation on Thr308 and Ser473 and this was inhibited by Wortmannin, suggesting that HMB acts via Class I PI3K. Blocking of the PI3K/Akt pathway with specific inhibitors revealed its requirement in mediating the promotive effects of HMB on muscle cell differentiation and fusion. These direct effects of HMB on myoblast differentiation and survival resembling those of IGF-I, at least in culture, suggest its positive influence in preventing muscle wasting.

Chloride channels in stroke

PubMed Central

Zhang, Ya-ping; Zhang, Hao; Duan, Dayue Darrel

2013-01-01

Vascular remodeling of cerebral arterioles, including proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs), is the major cause of changes in the cross-sectional area and diameter of the arteries and sudden interruption of blood flow or hemorrhage in the brain, ie, stroke. Accumulating evidence strongly supports an important role for chloride (Cl−) channels in vascular remodeling and stroke. At least three Cl− channel genes are expressed in VSMCs: 1) the TMEM16A (or Ano1), which may encode the calcium-activated Cl− channels (CACCs); 2) the CLC-3 Cl− channel and Cl−/H+ antiporter, which is closely related to the volume-regulated Cl− channels (VRCCs); and 3) the cystic fibrosis transmembrane conductance regulator (CFTR), which encodes the PKA- and PKC-activated Cl− channels. Activation of the CACCs by agonist-induced increase in intracellular Ca2+ causes membrane depolarization, vasoconstriction, and inhibition of VSMC proliferation. Activation of VRCCs by cell volume increase or membrane stretch promotes the production of reactive oxygen species, induces proliferation and inhibits apoptosis of VSMCs. Activation of CFTR inhibits oxidative stress and may prevent the development of hypertension. In addition, Cl− current mediated by gamma-aminobutyric acid (GABA) receptor has also been implicated a role in ischemic neuron death. This review focuses on the functional roles of Cl− channels in the development of stroke and provides a perspective on the future directions for research and the potential to develop Cl− channels as new targets for the prevention and treatment of stroke. PMID:23103617

Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16(INK4a) gene in human colorectal carcinoma (Caco-2) cells.

PubMed

Naselli, Flores; Tesoriere, Luisa; Caradonna, Fabio; Bellavia, Daniele; Attanzio, Alessandro; Gentile, Carla; Livrea, Maria A

2014-07-18

Phytochemicals may exert chemo-preventive effects on cells of the gastro-intestinal tract by modulating epigenome-regulated gene expression. The effect of the aqueous extract from the edible fruit of Opuntia ficus-indica (OFI extract), and of its betalain pigment indicaxanthin (Ind), on proliferation of human colon cancer Caco-2 cells has been investigated. Whole extract and Ind caused a dose-dependent apoptosis of proliferating cells at nutritionally relevant amounts, with IC50 400±25 mg fresh pulp equivalents/mL, and 115±15 μM (n=9), respectively, without toxicity for post-confluent differentiated cells. Ind accounted for ∼80% of the effect of the whole extract. Ind did not cause oxidative stress in proliferating Caco-2 cells. Epigenomic activity of Ind was evident as de-methylation of the tumor suppressor p16(INK4a) gene promoter, reactivation of the silenced mRNA expression and accumulation of p16(INK4a), a major controller of cell cycle. As a consequence, decrease of hyper-phosphorylated, in favor of the hypo-phosphorylated retinoblastoma was observed, with unaltered level of the cycline-dependent kinase CDK4. Cell cycle showed arrest in the G2/M-phase. Dietary cactus pear fruit and Ind may have chemo-preventive potential in intestinal cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Inhibition of Notch3 prevents monocrotaline-induced pulmonary arterial hypertension.

PubMed

Zhang, Yonghong; Xie, Xinming; Zhu, Yanting; Liu, Lu; Feng, Wei; Pan, Yilin; Zhai, Cui; Ke, Rui; Li, Shaojun; Song, Yang; Fan, Yuncun; Fan, Fenling; Wang, Xiaochuang; Li, Fengjuan; Li, Manxiang

2015-01-01

It has been shown that activation of Notch3 signaling is involved in the development of pulmonary arterial hypertension (PAH) by stimulating pulmonary arteries remodeling, while the molecular mechanisms underlying this are still largely unknown. The aims of this study are to address these issues. Monocrotaline dramatically increased right ventricle systolic pressure to 39.0 ± 2.6 mmHg and right ventricle hypertrophy index to 53.4 ± 5.3% (P < 0.05 versus control) in rats, these were accompanied with significantly increased proliferation and reduced apoptosis of pulmonary vascular cells as well as pulmonary arteries remodeling. Treatment of PAH model with specific Notch inhibitor DAPT significantly reduced right ventricle systolic pressure to 26.6 ± 1.3 mmHg and right ventricle hypertrophy index to 33.5 ± 2.6% (P < 0.05 versus PAH), suppressed proliferation and enhanced apoptosis of pulmonary vascular cells as well as inhibited pulmonary arteries remodeling. Our results further indicated that level of Notch3 protein and NICD3 were increased in MCT-induced model of PAH, this was accompanied with elevation of Skp2 and Hes1 protein level and reduction of P27Kip1. Administration of rats with DAPT-prevented MCT induced these changes. Our results suggest that Notch3 signaling activation stimulated pulmonary vascular cells proliferation by Skp2-and Hes1-mediated P27Kip1 reduction, and Notch3 might be a new target to treat PAH.

Gallic acid sensitizes paclitaxel-resistant human ovarian carcinoma cells through an increase in reactive oxygen species and subsequent downregulation of ERK activation.

PubMed

Sánchez-Carranza, Jessica Nayelli; Díaz, J Fernando; Redondo-Horcajo, Mariano; Barasoain, Isabel; Alvarez, Laura; Lastres, Pedro; Romero-Estrada, Antonio; Aller, Patricio; González-Maya, Leticia

2018-06-01

Paclitaxel (PTX) is currently used as a front-line chemotherapeutic agent for several types of cancer, including ovarian carcinoma; however, PTX-resistance frequently arises through multiple mechanisms. The development of new strategies using natural compounds and PTX in combination has been the aim of several prior studies, in order to enhance the efficacy of chemotherapy. In this study, we found the following: (i) gallic acid (GA), a phenolic compound, potentiated the capacity of PTX to decrease proliferation and to cause G2/M cycle arrest in the PTX-resistant A2780AD ovarian cancer cell line; (ii) GA exerted a pro-oxidant action by increasing the production of reactive oxygen species (ROS), and co-treatment with the antioxidant agent N‑acetyl-L‑cysteine (NAC) prevented GA+PTX-induced cell proliferation inhibition and G2/M phase arrest; (iii) PTX stimulated ERK phosphorylation/activation, and co-treatment with the MEK/ERK inhibitor PD98049 potentiated the proliferation inhibition and G2/M phase arrest; (iv) and finally, GA abrogated the PTX-induced stimulation of ERK phosphorylation, a response that was prevented by co-treatment with NAC. Taken together, these results indicate that GA sensitizes PTX-resistant ovarian carcinoma cells via the ROS‑mediated inactivation of ERK, and suggest that GA could represent a useful co-adjuvant to PTX in ovarian carcinoma treatment.

Bee products prevent VEGF-induced angiogenesis in human umbilical vein endothelial cells

PubMed Central

2009-01-01

Background Vascular endothelial growth factor (VEGF) is a key regulator of pathogenic angiogenesis in diseases such as cancer and diabetic retinopathy. Bee products [royal jelly (RJ), bee pollen, and Chinese red propolis] from the honeybee, Apis mellifera, have been used as traditional health foods for centuries. The aim of this study was to investigate the anti-angiogenic effects of bee products using human umbilical vein endothelial cells (HUVECs). Methods In an in vitro tube formation assay, HUVECs and fibroblast cells were incubated for 14 days with VEGF and various concentrations of bee products [RJ, ethanol extract of bee pollen, ethanol extract of Chinese red propolis and its constituent, caffeic acid phenethyl ester (CAPE)]. To clarify the mechanism of in vitro angiogenesis, HUVEC proliferation and migration were induced by VEGF with or without various concentrations of RJ, bee pollen, Chinese red propolis, and CAPE. Results RJ, bee pollen, Chinese red propolis, and CAPE significantly suppressed VEGF-induced in vitro tube formation in the descending order: CAPE > Chinese red propolis >> bee pollen > RJ. RJ and Chinese red propolis suppressed both VEGF-induced HUVEC proliferation and migration. In contrast, bee pollen and CAPE suppressed only the proliferation. Conclusion Among the bee products, Chinese red propolis and CAPE in particular showed strong suppressive effects against VEGF-induced angiogenesis. These findings indicate that Chinese red propolis and CAPE may have potential as preventive and therapeutic agents against angiogenesis-related human diseases. PMID:19917137

25 CFR 63.32 - Under what authority are Indian child protection and family violence prevention program funds...

Code of Federal Regulations, 2010 CFR

2010-04-01

... family violence prevention program funds awarded? 63.32 Section 63.32 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR TRIBAL GOVERNMENT INDIAN CHILD PROTECTION AND FAMILY VIOLENCE PREVENTION Indian Child Protection and Family Violence Prevention Program § 63.32 Under what authority are Indian child...

School-Based Violence Prevention Programs: Systematic Review of Secondary Prevention Trials.

ERIC Educational Resources Information Center

Mytton, Julie A.; DiGuiseppi, Carolyn; Gough, David A.; Taylor, Rod S.; Logan, Stuart

2002-01-01

Conducted a systematic review and meta-analysis of randomized controlled secondary prevention trials to explore the effects of school-based violence prevention programs on aggressive and violent behavior in children at high risk for violence. Results indicated that such programs produced modest reductions in aggressive and violent behaviors in…

Bottling Proliferation of the Uranium Genie: Identifying and Monitoring Clandestine Enrichment Programs

DTIC Science & Technology

2007-04-01

Separation The first method used to enrich uranium on a significant scale was developed by the United States as part of the Manhattan Project during...there does not seem to be a easy way to enrich uranium. It has been over 60 years since the 33 Manhattan Project successfully enriched U-235 to...Proliferation, 91-3. 14 The cost of $5B dollars is adjusted to FY96 dollars. Brookings Institution, “The Costs of the Manhattan Project ,” Global Politics

Evidence-Based Prevention for Adolescent Substance Use.

PubMed

Harrop, Erin; Catalano, Richard F

2016-07-01

Due to the significant consequences of adolescent substance use behaviors, researchers have increasingly focused on prevention approaches. The field of prevention science is based on the identification of predictors of problem behaviors, and the development and testing of prevention programs that seek to change these predictors. As the field of prevention science moves forward, there are many opportunities for growth, including the integration of prevention programs into service systems and primary care, an expansion of program adaptations to fit the needs of local populations, and a greater emphasis on the development of programs targeted at young adult populations. Copyright © 2016 Elsevier Inc. All rights reserved.

Obesity prevention programs and policies: practitioner and policy-maker perceptions of feasibility and effectiveness.

PubMed

Cleland, Verity; McNeilly, Briohny; Crawford, David; Ball, Kylie

2013-09-01

The aims of this study were to map obesity prevention activity being implemented by government, non-government, and community-based organizations; to determine practitioner and policy-maker perceptions of the feasibility and effectiveness of a range of evidence-based obesity prevention strategies; and to determine practitioner and policy-maker perceptions of preferred settings for obesity prevention strategies. This study involved a cross-sectional survey of 304 public health practitioners and policy-makers from government, non-government, and community organizations across Victoria, Australia. Participants reported their organizations' current obesity prevention programs and policies, their own perceptions of the feasibility and effectiveness of strategies to prevent obesity and their preferred settings for obesity prevention. Thirty-nine percent had an obesity prevention policy, and 92% were implementing obesity prevention programs. The most common programs focused on education, skill-building, and increasing access to healthy eating/physical activity opportunities. School curriculum-based initiatives, social support for physical activity, and family-based programs were considered the most effective strategies, whereas curriculum-based initiatives, active after-school programs, and providing access to and information about physical activity facilities were deemed the most feasible strategies. Schools were generally perceived as the most preferred setting for obesity prevention. Many organizations had obesity prevention programs, but far fewer had obesity prevention policies. Current strategies and those considered feasible and effective are often mismatched with the empirical literature. Systems to ensure better alignment between researchers, practitioners, and policy-makers, and identifying effective methods of translating empirical evidence into practice and policy are required. Copyright © 2012 The Obesity Society.

Transforming growth factor-alpha stimulates enterocyte proliferation and accelerates intestinal recovery following methotrexate-induced intestinal mucositis in a rat and a cell culture model.

PubMed

Sukhotnik, Igor; Shteinberg, Dan; Ben Lulu, Shani; Bashenko, Yulia; Mogilner, Jorge G; Ure, Benno M; Shaoul, Ron; Shamian, Benhoor; Coran, Arnold G

2008-12-01

Recent evidence suggests that transforming growth factor-alpha (TGF-alpha) enhances enterocyte proliferation and exerts a gut trophic effect. The purpose of the present study was to evaluate the effect of TGF-alpha on enterocyte proliferation and intestinal recovery following methotrexate (MTX)-induced intestinal mucositis in rats and in Caco-2 cells. Nonpretreated Caco-2 cells and those pretreated with MTX were incubated with increasing concentrations of TGF-alpha. Cell proliferation was determined by FACS cytometry. Adult rats were divided into three groups: control rats treated with vehicle, MTX rats treated with one dose (20 microg/kg) of MTX given intraperitoneally, and MTX-TGF-alpha rats treated with one dose of MTX followed by two doses of TGF-alpha (75 microg/kg a day). Three days after MTX injection, rats were sacrificed. Intestinal mucosal damage (Park's score), mucosal structural changes, and enterocyte proliferation were measured at sacrifice. Western blotting was used to determine the level of extracellular signal-related kinase (ERK) protein, a marker of cell proliferation. A nonparametric Kruskal-Wallis ANOVA test was used for statistical analysis with P value less than 0.05 considered statistically significant. The in vitro experiment demonstrated that treatment with TGF-alpha of Caco-2 cells resulted in a significant stimulation of cell proliferation in a dose-dependent manner. The in vivo experiment showed that treatment with TGF-alpha resulted in a significant increase in bowel and mucosal weight, DNA and protein content in jejunum and ileum, villus height in jejunum and ileum, crypt depth in ileum, and increased cell proliferation in jejunum and ileum compared to the MTX group. MTX-TGF-alpha rats also had a significantly lower intestinal injury score in ileum when compared to MTX animals. The increase in levels of cell proliferation in MTX-TGF-alpha rats corresponded with the increase in ERK protein levels in intestinal mucosa. Treatment with TGF-alpha prevents mucosal injury, enhances ERK-induced enterocyte proliferation, and improves intestinal recovery following MTX-induced intestinal mucositis in rats. These findings correlated with the observation that TGF-alpha also caused a significant stimulation of cell proliferation in a Caco-2 cell culture model treated with MTX. These observations may have significant implications for the treatment of patients on chemotherapy who develop severe mucositis.

The Non-Proliferation Treaty review: An American perspective

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

Dunn, L.A.

1985-01-01

Since the entry into the force in March 1970, the Treaty on the Non-Proliferation of Nuclear Weapons (NPT) has played a central part in this decades-long endeavor. The Treaty's specific undertakings have been carefully crafted to serve its three major objectives. The first, which was the driving force behind the initial push for the NPT, is to prevent the further spread of nuclear weapons. The second is to foster peaceful nuclear cooperation under safeguards. The third objective, added during the multilateral negotiation of the NPT, is to encourage good faith negotiations to end the nuclear arms race with a viewmore » to general and complete disarmament.« less

Peroxisome proliferator-activated receptor α ligands and modulators from dietary compounds: Types, screening methods and functions.

PubMed

Yang, Haixia; Xiao, Lei; Wang, Nanping

2017-04-01

Peroxisome proliferator-activated receptor α (PPARα) plays a key role in lipid metabolism and glucose homeostasis and a crucial role in the prevention and treatment of metabolic diseases. Natural dietary compounds, including nutrients and phytochemicals, are PPARα ligands or modulators. High-throughput screening assays have been developed to screen for PPARα ligands and modulators in our diet. In the present review, we discuss recent advances in our knowledge of PPARα, including its structure, function, and ligand and modulator screening assays, and summarize the different types of dietary PPARα ligands and modulators. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Effects of exogenous vitamins A, C, and E and NADH supplementation on proliferation, cytokines release, and cell redox status of lymphocytes from healthy aged subjects.

PubMed

Bouamama, Samia; Merzouk, Hafida; Medjdoub, Amel; Merzouk-Saidi, Amel; Merzouk, Sid Ahmed

2017-06-01

Aging is an inevitable biological event that is associated with immune alterations. These alterations are related to increased cellular oxidative stress and micronutrient deficiency. Antioxidant supplementation could improve these age-related abnormalities. The aim of this study was to determine in vitro effects of vitamin A, vitamin C, vitamin E, and nicotinamide adenine dinucleotide (NADH) on T cell proliferation, cytokine release, and cell redox status in the elderly compared with young adults. Peripheral blood lymphocytes were isolated using a density gradient of Histopaque. They were cultured in vitro and stimulated with concanavalin A in the presence or absence of vitamins. Cell proliferation was determined by conducting MTT assays, and based on interleukin-2 and interleukin-4 secretions. Cell oxidant/antioxidant balance was assessed by assaying reduced glutathione (GSH), malondialdehyde, carbonyl protein levels, and catalase activity. The present study demonstrated that T-lymphocyte proliferation was decreased with aging and was associated with cytokine secretion alterations, GSH depletion, and intracellular oxidative stress. In the elderly, vitamin C, vitamin E, and NADH significantly improved lymphocyte proliferation and mitigated cellular oxidative stress, whereas vitamin A did not affect cell proliferation or cell redox status. In conclusion, vitamin C, vitamin E, and NADH supplementation improved T-lymphocytes response in the elderly, and could contribute to the prevention of age-related immune alterations. Consumption of food items containing these vitamins is recommended, and further investigation is necessary to evaluate the effect of vitamin supplementation in vivo.

Nucleolin inhibitor GroA triggers reduction in epidermal growth factor receptor activation: Pharmacological implication for glial scarring after spinal cord injury.

PubMed

Goldshmit, Yona; Schokoroy Trangle, Sari; Afergan, Fabian; Iram, Tal; Pinkas-Kramarski, Ronit

2016-09-01

Glial scarring, formed by reactive astrocytes, is one of the major impediments for regeneration after spinal cord injury (SCI). Reactive astrocytes become hypertrophic, proliferate and secrete chondroitin sulphate proteoglycans into the extracellular matrix (ECM). Many studies have demonstrated that epidermal growth factor receptors (EGFR) can mediate astrocyte reactivity after neurotrauma. Previously we showed that there is crosstalk between nucleolin and EGFR that leads to increased EGFR activation followed by increased cell proliferation. Treatment with the nucleolin inhibitor GroA (AS1411) prevented these effects in vitro and in vivo. In this study, we hypothesized that similar interactions may mediate astrogliosis after SCI. Our results demonstrate that nucleolin and EGFR interaction may play a pivotal role in mediating astrocyte proliferation and reactivity after SCI. Moreover, we demonstrate that treatment with GroA reduces EGFR activation, astrocyte proliferation and chondroitin sulphate proteoglycans secretion, therefore promoting axonal regeneration and sprouting into the lesion site. Our results identify, for the first time, a role for the interaction between nucleolin and EGFR in astrocytes after SCI, indicating that nucleolin inhibitor GroA may be used as a novel treatment after neurotrauma. A major barrier for axonal regeneration after spinal cord injury is glial scar created by reactive and proliferating astrocytes. EGFR mediate astrocyte reactivity. We showed that inhibition of nucleolin by GroA, reduces EGFR activation, which results in attenuation of astrocyte reactivity and proliferation in vivo and in vitro. EGFR, epidermal growth factor receptor. © 2016 International Society for Neurochemistry.

Free Fatty Acids Shift Insulin-induced Hepatocyte Proliferation towards CD95-dependent Apoptosis*

PubMed Central

Sommerfeld, Annika; Reinehr, Roland; Häussinger, Dieter

2015-01-01

Insulin is known to induce hepatocyte swelling, which triggers via integrins and c-Src kinase an activation of the epidermal growth factor receptor (EGFR) and subsequent cell proliferation (1). Free fatty acids (FFAs) are known to induce lipoapoptosis in liver cells in a c-Jun-NH2-terminal kinase (JNK)-dependent, but death receptor-independent way (2). As non-alcoholic steatohepatitis (NASH) is associated with hyperinsulinemia and increased FFA-blood levels, the interplay between insulin and FFA was studied with regard to hepatocyte proliferation and apoptosis in isolated rat and mouse hepatocytes. Saturated long chain FFAs induced apoptosis and JNK activation in primary rat hepatocytes, but did not activate the CD95 (Fas, APO-1) system, whereas insulin triggered EGFR activation and hepatocyte proliferation. Coadministration of insulin and FFAs, however, abolished hepatocyte proliferation and triggered CD95-dependent apoptosis due to a JNK-dependent association of the activated EGFR with CD95, subsequent CD95 tyrosine phosphorylation and formation of the death-inducing signaling complex (DISC). JNK inhibition restored the proliferative insulin effect in presence of FFAs and prevented EGFR/CD95 association, CD95 tyrosine phosphorylation and DISC formation. Likewise, in presence of FFAs insulin increased apoptosis in hepatocytes from wild type but not from Alb-Cre-FASfl/fl mice, which lack functional CD95. It is concluded that FFAs can shift insulin-induced hepatocyte proliferation toward hepatocyte apoptosis by triggering a JNK signal, which allows activated EGFR to associate with CD95 and to trigger CD95-dependent apoptosis. Such phenomena may contribute to the pathogenesis of NASH. PMID:25548285

The Proliferation Security Initiative: A Means to an End for the Operational Commander

DTIC Science & Technology

2009-05-04

The Reduced Enrichment for Research and Test Reactors ( RERTR ) Program develops technology necessary to enable the conversion of civilian...facilities using high enriched uranium (HEU) to low enriched uranium (LEU) fuels and targets. The RERTR Program was initiated by the U.S. Department of...processes have been developed for producing radioisotopes with LEU targets. The RERTR Program is managed by the Office of Nuclear Material Threat

The C.I.E.E. Summer Program in Leningrad: How Can They Study When the Nights Are White?

ERIC Educational Resources Information Center

Beyer, Thomas R., Jr.

Recently several persons involved with language study in the U.S.S.R. have publicly voiced concerns on the value of summer programs for American students there. The proliferation of these programs in the last ten years calls for a reexamination of what students who study in the Soviet Union are expected to achieve. By examining the expectations of…

The relative efficacy of pamphlets, CD-ROM, and the Internet for disseminating adolescent drug abuse prevention programs: an exploratory study.

PubMed

Di Noia, Jennifer; Schwinn, Traci M; Dastur, Zubin A; Schinke, Steven P

2003-12-01

Despite the availability of an increasing array of empirically validated adolescent drug abuse prevention programs, program materials and evaluation findings are poorly disseminated. CD-ROM and the Internet hold promise for disseminating this information to schools and agencies that directly serve youth, and to policy-making bodies that exercise control over funds to support adolescent drug abuse prevention programming. However, data on the relative efficacy of these newer technologies over conventional print means of dissemination are lacking. Recruited through schools, community agencies, and policy-making bodies, 188 professionals were randomized to receive prevention program materials via pamphlets (55 participants), CD-ROM (64 participants), and the Internet (69 participants). Participants completed pretest, posttest, and 6-month follow-up measures that assessed their access to prevention program materials; self-efficacy for identifying, obtaining, and recommending these programs; and their likelihood of requesting, implementing, and recommending prevention programs to their constituents. Participants exposed to dissemination via CD-ROM and the Internet evidenced the greatest short- and long-term gains on accessibility, self-efficacy, and behavioral intention variables. CD-ROM and the Internet are viable means for disseminating adolescent drug abuse prevention programs to schools, community agencies, and policy-making bodies, and should be increasingly used for dissemination purposes.

An example of international drug politics--the development and distribution of substance prevention programs directed at adolescents.

PubMed

Lilja, John; Giota, Joanna; Hamilton, David; Larsson, Sam

2007-01-01

Many substance use prevention programs directed at adolescents exist that have been developed by researchers in the United States and are intended to be used in school settings. Some of the problems associated with such programs are reviewed, including their accessibility, ease of use, copyright status, evaluation options, program scales, and ratings, together with an overall consideration of the factors and processes posited to be associated with substance use and non-use (posited "at-risk" and "protective" mechanisms). The authors contend that there is a great need to: (a) develop substance use prevention programs which are commercially available but are not protected by copyright, (b) assess empirically each component in a program separately, and (c) encourage funding bodies to be more active in supporting the production of manuals and evaluation instruments for substance use prevention programs directed at adolescents. We need more and better process evaluations that are also sensitive to both endogenous and exogenous forces in order to know the processes by which a successful prevention program achieves its effects, is prevented from doing so and which processes are irrelevant. A social competence framework might be used as both a goal and as a theoretical base to achieve a better understanding of the processes by which substance use prevention programs reach their effects.

The relative efficacy of pamphlets, CD-ROM, and the Internet for disseminating adolescent drug abuse prevention programs: an exploratory study⋆

PubMed Central

Di Noia, Jennifer; Schwinn, Traci M.; Dastur, Zubin A.; Schinke, Steven P.

2010-01-01

Background Despite the availability of an increasing array of empirically validated adolescent drug abuse prevention programs, program materials and evaluation findings are poorly disseminated. CD-ROM and the Internet hold promise for disseminating this information to schools and agencies that directly serve youth, and to policy-making bodies that exercise control over funds to support adolescent drug abuse prevention programming. However, data on the relative efficacy of these newer technologies over conventional print means of dissemination are lacking. Methods Recruited through schools, community agencies, and policy-making bodies, 188 professionals were randomized to receive prevention program materials via pamphlets (55 participants), CD-ROM (64 participants), and the Internet (69 participants). Participants completed pretest, posttest, and 6-month follow-up measures that assessed their access to prevention program materials; self-efficacy for identifying, obtaining, and recommending these programs; and their likelihood of requesting, implementing, and recommending prevention programs to their constituents. Results Participants exposed to dissemination via CD-ROM and the Internet evidenced the greatest short- and long-term gains on accessibility, self-efficacy, and behavioral intention variables. Conclusions CD-ROM and the Internet are viable means for disseminating adolescent drug abuse prevention programs to schools, community agencies, and policy-making bodies, and should be increasingly used for dissemination purposes. PMID:14636798

[Suicidal behavior prevention for children under age 13: A systematic review].

PubMed

Baux-Cazal, L; Gokalsing, E; Amadeo, S; Messiah, A

2017-05-01

Our objective was to review international literature on suicidal behavior prevention for children under age 13. We gathered all relevant articles on suicide prevention for children under 13. We researched all publications in the French and English languages in PubMed (MEDLINE), PsychINFO and SUDOC databases published until February 2014, with the keywords "child", "child preschool", "prevention and control", "suicide", and "suicide attempted". Publications were included if they described suicidal behavior prevention programs (suicide prevention programs, attempted-suicide prevention programs, suicidal ideation screening programs), and if the studies concerned children under age 13. We also included references cited in the articles if they were not already present in our searches but met inclusion criteria. Studies were excluded if they analyzed populations of children and adolescents without sub-analysis for children under age 13. A total of 350 potentially relevant articles were identified, 33 of which met the inclusion criteria, including 4 retrieved from articles' bibliography. Preventive measures against suicidal behavior for children under 13 exist and include: social programs, maltreatment prevention, curriculum-based suicide prevention programs, suicide screening in schools, gatekeepers, reduction of access of lethal means of suicide, suicide screening by primary care, and post-suicide intervention programs. Overall, the evidence was limited by methodological concerns, particularly a lack of RCTs. However, positive effects were found: school-based suicide prevention programs and gatekeepers increased knowledge about suicide and how to seek help, post-suicide programs helped to reduce psychological distress in the short term. One study showed a decreased risk of attempted-suicide after entry into the child welfare system. There are promising interventions but there is not enough scientific evidence to support any efficient preventive measure against suicidal behavior for children under 13, whether primary, secondary, tertiary or post-intervention. More research is needed. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Application of preventive medicine resources in the health insurance system.

PubMed

Oliveira, Karla Regina Dias de; Liberal, Márcia Mello Costa de; Zucchi, Paola

2015-01-01

To identify the financial resources and investments provided for preventive medicine programs by health insurance companies of all kinds. Data were collected from 30 large health insurance companies, with over 100 thousand individuals recorded, and registered at the Agência Nacional de Saúde Suplementar. It was possible to identify the percentage of participants of the programs in relation to the total number of beneficiaries of the health insurance companies, the prevention and promotion actions held in preventive medicine programs, the inclusion criteria for the programs, as well as the evaluation of human resources and organizational structure of the preventive medicine programs. Most of the respondents (46.7%) invested more than US$ 50,000.00 in preventive medicine program, while 26.7% invested more than US$ 500,000.00. The remaining, about 20%, invested less than US$ 50,000.00, and 3.3% did not report the value applied.

Dating Violence Prevention Programming: Directions for Future Interventions

PubMed Central

Shorey, Ryan C.; Zucosky, Heather; Brasfield, Hope; Febres, Jeniimarie; Cornelius, Tara L.; Sage, Chelsea; Stuart, Gregory L.

2012-01-01

Dating violence among college students is a widespread and destructive problem. The field of dating violence has seen a substantial rise in research over the past several years, which has improved our understanding of factors that increase risk for perpetration. Unfortunately, there has been less attention paid to dating violence prevention programming, and existing programs have been marred with methodological weaknesses and a lack of demonstrated effectiveness in reducing aggression. In hopes of sparking new research on dating violence prevention programs, the current review examines possible new avenues for dating violence prevention programming among college students. We discuss clinical interventions that have shown to be effective in reducing a number of problematic behaviors, including motivational interventions, dialectical behavior therapy, mindfulness, and bystander interventions, and how they could be applied to dating violence prevention. We also discuss methodological issues to consider when implementing dating violence prevention programs. PMID:22773916

Effectiveness of the surviving the Teens® suicide prevention and depression awareness program: an impact evaluation utilizing a comparison group.

PubMed

Strunk, Catherine M; King, Keith A; Vidourek, Rebecca A; Sorter, Michael T

2014-12-01

Youth suicide is a serious public health issue in the United States. It is currently the third leading cause of death for youth aged 10 to 19. School-based prevention programs may be an effective method of educating youth and enhancing their help-seeking. Most school-based suicide prevention programs have not been rigorously evaluated for their effectiveness. This evaluation employs a comparison group to measure whether program group participants differed significantly from comparison group participants on pretest-posttest measures while assessing the immediate impact of the Surviving the Teens® Suicide Prevention and Depression Awareness Program. Findings indicate several positive outcomes in program group students' suicide and depression knowledge, attitudes, confidence, and behavioral intentions compared with the comparison group. Suicide prevention specialists and prevention planners may benefit from study findings. © 2014 Society for Public Health Education.

Application of preventive medicine resources in the health insurance system

PubMed Central

de Oliveira, Karla Regina Dias; Liberal, Márcia Mello Costa De; Zucchi, Paola

2015-01-01

ABSTRACT Objective To identify the financial resources and investments provided for preventive medicine programs by health insurance companies of all kinds. Methods Data were collected from 30 large health insurance companies, with over 100 thousand individuals recorded, and registered at the Agência Nacional de Saúde Suplementar. Results It was possible to identify the percentage of participants of the programs in relation to the total number of beneficiaries of the health insurance companies, the prevention and promotion actions held in preventive medicine programs, the inclusion criteria for the programs, as well as the evaluation of human resources and organizational structure of the preventive medicine programs. Conclusion Most of the respondents (46.7%) invested more than US$ 50,000.00 in preventive medicine program, while 26.7% invested more than US$ 500,000.00. The remaining, about 20%, invested less than US$ 50,000.00, and 3.3% did not report the value applied. PMID:26761558

Yarning about fall prevention: community consultation to discuss falls and appropriate approaches to fall prevention with older Aboriginal and Torres Strait Islander people.

PubMed

Lukaszyk, Caroline; Coombes, Julieann; Turner, Norma Jean; Hillmann, Elizabeth; Keay, Lisa; Tiedemann, Anne; Sherrington, Cathie; Ivers, Rebecca

2017-08-01

Fall related injury is an emerging issue for older Indigenous people worldwide, yet few targeted fall prevention programs are currently available for Indigenous populations. In order to inform the development of a new Aboriginal-specific fall prevention program in Australia, we conducted community consultation with older Aboriginal people to identify perceptions and beliefs about falls, and to identify desired program elements. Yarning Circles were held with Aboriginal and Torres Strait Islander people aged 45 years and over. Each Yarning Circle was facilitated by an Aboriginal researcher who incorporated six indicative questions into each discussion. Questions explored the impact of falls on Yarning Circle participants, their current use of fall prevention services and investigated Yarning Circle participant's preferences regarding the design and mode of delivery of a fall prevention program. A total of 76 older Aboriginal people participated in ten Yarning Circles across six sites in the state of New South Wales. Participants associated falls with physical disability, a loss of emotional well-being and loss of connection to family and community. Many participants did not use existing fall prevention services due to a lack of availability in their area, having no referral provided by their GP and/or being unaware of fall prevention programs in general. Program elements identified as important by participants were that it be Aboriginal-specific, group-based, and on-going, with the flexibility to be tailored to specific communities, with free transport provided to and from the program. Older Aboriginal people reported falls to be a priority health issue, with a significant impact on their health and well-being. Few older Aboriginal people accessed prevention programs, suggesting there is an important need for targeted Aboriginal-specific programs. A number of important program elements were identified which if incorporated into prevention programs, may help to address the rising burden of falls.

Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation

USDA-ARS?s Scientific Manuscript database

Consumption of a high fat diet causes an increase in bile acid deoxycholic acid (DCA) in colon lumen and colon cancer risk while butyrate, an intestinal microbiota metabolite of dietary fiber, has been shown to exhibit colon cancer preventive effects. To distinguish these opposing effects of D...

HDL and Glut1 inhibition reverse a hypermetabolic state in mouse models of myeloproliferative disorders

PubMed Central

Gautier, Emmanuel L.; Westerterp, Marit; Bhagwat, Neha; Cremers, Serge; Shih, Alan; Abdel-Wahab, Omar; Lütjohann, Dieter; Randolph, Gwendalyn J.; Levine, Ross L.; Tall, Alan R.

2013-01-01

A high metabolic rate in myeloproliferative disorders is a common complication of neoplasms, but the underlying mechanisms are incompletely understood. Using three different mouse models of myeloproliferative disorders, including mice with defective cholesterol efflux pathways and two models based on expression of human leukemia disease alleles, we uncovered a mechanism by which proliferating and inflammatory myeloid cells take up and oxidize glucose during the feeding period, contributing to energy dissipation and subsequent loss of adipose mass. In vivo, lentiviral inhibition of Glut1 by shRNA prevented myeloproliferation and adipose tissue loss in mice with defective cholesterol efflux pathway in leukocytes. Thus, Glut1 was necessary to sustain proliferation and potentially divert glucose from fat storage. We also showed that overexpression of the human ApoA-I transgene to raise high-density lipoprotein (HDL) levels decreased Glut1 expression, dampened myeloproliferation, and prevented fat loss. These experiments suggest that inhibition of Glut-1 and HDL cholesterol–raising therapies could provide novel therapeutic approaches to treat the energy imbalance observed in myeloproliferative disorders. PMID:23319699

Hair-Loss Preventing Effect of Grateloupia elliptica

PubMed Central

Kang, Jung-Il; Kim, Sang-Cheol; Han, Sang-Chul; Hong, Hye-Jin; Jeon, You-Jin; Kim, Bora; Koh, Young-Sang; Yoo, Eun-Sook; Kang, Hee-Kyoung

2012-01-01

This study was conducted to evaluate the effect of Grateloupia elliptica, a seaweed native to Jeju Island, Korea, on the prevention of hair loss. When immortalized rat vibrissa dermal papilla cells were treated with extract of G. elliptica, the proliferation of dermal papilla cells significantly increased. In addition, the G. elliptica extract significantly inhibited the activity of 5α-reductase, which converts testosterone to dihydrotestosterone (DHT), a main cause of androgenetic alopecia. On the other hand, the G. elliptica extract promoted PGE2 production in HaCaT cells in a dose-dependent manner. The G. elliptica extract exhibited particularly high inhibitory effect on LPS-stimulated IL-12, IL-6, and TNF-α production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. The G. elliptica extract also showed inhibitory activity against Pityrosporum ovale, a main cause of dandruff. These results suggest that G. elliptica extract has the potential to treat alopecia via the proliferation of dermal papilla, 5α-reductase inhibition, increase of PGE2 production, decrease of LPS-stimulated pro-inflammatory cytokines and inhibitory activity against Pityrosporum ovale. PMID:24116284

Arsenic Induces p62 Expression to Form a Positive Feedback Loop with Nrf2 in Human Epidermal Keratinocytes: Implications for Preventing Arsenic-Induced Skin Cancer.

PubMed

Shah, Palak; Trinh, Elaine; Qiang, Lei; Xie, Lishi; Hu, Wen-Yang; Prins, Gail S; Pi, Jingbo; He, Yu-Ying

2017-01-24

Exposure to inorganic arsenic in contaminated drinking water poses an environmental public health threat for hundreds of millions of people in the US and around the world. Arsenic is a known carcinogen for skin cancer. However, the mechanism by which arsenic induces skin cancer remains poorly understood. Here, we have shown that arsenic induces p62 expression in an autophagy-independent manner in human HaCaT keratinocytes. In mouse skin, chronic arsenic exposure through drinking water increases p62 protein levels in the epidermis. Nrf2 is required for basal and arsenic-induced p62 up-regulation. p62 knockdown reduces arsenic-induced Nrf2 activity, and induces sustained p21 up-regulation. p62 induction is associated with increased proliferation in mouse epidermis. p62 knockdown had little effect on arsenic-induced apoptosis, while it decreased cell proliferation following arsenic treatment. Our findings indicate that arsenic induces p62 expression to regulate the Nrf2 pathway in human keratinocytes and suggest that targeting p62 may help prevent arsenic-induced skin cancer.

Effect of oral glutamine on enterocyte turnover during methotrexate-induced mucositis in rats.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Karry, Rahel; Shamian, Benhoor; Lurie, Michael; Kokhanovsky, Natalie; Ure, Benno M; Coran, Arnold G

2009-01-01

The objective of this study was to evaluate the effects of oral glutamine in preventing intestinal mucosal damage caused by methotrexate (MTX) in rats. Male Sprague-Dawley rats were divided into 3 experimental groups: control rats, rats treated intraperitoneally with MTX (MTX rats) and rats treated with oral glutamine in the drinking water (2%) 72 h following intraperitoneal injection of a single dose of MTX (MTX-glutamine rats). Intestinal mucosal damage (Park's injury score), mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 h following MTX injection. RT-PCR was used to determine Bax and Bcl-2 mRNA expression. MTX-glutamine rats demonstrated greater jejunal and ileal mucosal weight and mucosal DNA, greater ileal villus height and crypt depth, and a greater index of proliferation in the jejunum and ileum compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-glutamine rats (vs. MTX) was accompanied by decreased Bax and increased Bcl-2 mRNA expression. Treatment with oral glutamine prevents mucosal injury and improves intestinal recovery following MTX injury in the rat.

Administration of the peroxisomal proliferator-activated receptor {gamma} agonist pioglitazone during fractionated brain irradiation prevents radiation-induced cognitive impairment

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

Zhao Weiling; Payne, Valerie; Tommasi, Ellen

2007-01-01

Purpose: We hypothesized that administration of the anti-inflammatory peroxisomal proliferator-activated receptor {gamma} (PPAR{gamma}) agonist pioglitazone (Pio) to adult male rats would inhibit radiation-induced cognitive impairment. Methods and Materials: Young adult male F344 rats received one of the following: (1) fractionated whole brain irradiation (WBI); 40 or 45 Gy {gamma}-rays in 4 or 4.5 weeks, respectively, two fractions per week and normal diet; (2) sham-irradiation and normal diet; (3) WBI plus Pio (120 ppm) before, during, and for 4 or 54 weeks postirradiation; (4) sham-irradiation plus Pio; or (5) WBI plus Pio starting 24h after completion of WBI. Results: Administration ofmore » Pio before, during, and for 4 or 54 weeks after WBI prevented Radiation-induced cognitive impairment. Administration of Pio for 54 weeks starting after completion of fractionated WBI substantially but not significantly reduced Radiation-induced cognitive impairment. Conclusions: These findings offer the promise of improving the quality of life and increasing the therapeutic window for brain tumor patients.« less

6 CFR 5.2 - Public reading rooms.

Code of Federal Regulations, 2010 CFR

2010-01-01

... the non-proliferation and verification research and development program; (v) The life sciences..., Washington, DC 20472 (for regional offices, consult your phone book); (20) For the Federal Computer Incident...

6 CFR 5.2 - Public reading rooms.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the non-proliferation and verification research and development program; (v) The life sciences..., Washington, DC 20472 (for regional offices, consult your phone book); (20) For the Federal Computer Incident...

6 CFR 5.2 - Public reading rooms.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the non-proliferation and verification research and development program; (v) The life sciences..., Washington, DC 20472 (for regional offices, consult your phone book); (20) For the Federal Computer Incident...

6 CFR 5.2 - Public reading rooms.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the non-proliferation and verification research and development program; (v) The life sciences..., Washington, DC 20472 (for regional offices, consult your phone book); (20) For the Federal Computer Incident...

6 CFR 5.2 - Public reading rooms.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the non-proliferation and verification research and development program; (v) The life sciences..., Washington, DC 20472 (for regional offices, consult your phone book); (20) For the Federal Computer Incident...

Linking HIV-Negative Youth to Prevention Services in 12 U.S. Cities: Barriers and Facilitators to Implementing the HIV Prevention Continuum.

PubMed

Doll, Mimi; Fortenberry, J Dennis; Roseland, Denise; McAuliff, Kathleen; Wilson, Craig M; Boyer, Cherrie B

2018-04-01

Linkage of HIV-negative youth to prevention services is increasingly important with the development of effective pre-exposure prophylaxis that complements behavioral and other prevention-focused interventions. However, effective infrastructure for delivery of prevention services does not exist, leaving many programs to address HIV prevention without data to guide program development/implementation. The objective of this study was to provide a qualitative description of barriers and facilitators of linkage to prevention services among high-risk, HIV-negative youth. Thematic analysis of structured interviews with staff implementing linkage to prevention services programs for youth aged 12-24 years. Twelve adolescent medicine HIV primary care programs as part of larger testing research program focused on young sexual minority men of color. The study included staff implementing linkage to prevention services programs along with community-based HIV testing programs. The main outcomes of the study were key barriers/facilitators to linkage to prevention services. Eight themes summarized perspectives on linkage to prevention services: (1) relationships with community partners, (2) trust between providers and youth, (3) youth capacity to navigate prevention services, (4) pre-exposure prophylaxis specific issues, (5) privacy issues, (6) gaps in health records preventing tailored services, (7) confidentiality of care for youth accessing services through parents'/caretakers' insurance, and (8) need for health-care institutions to keep pace with models that prioritize HIV prevention among at-risk youth. Themes are discussed in the context of factors that facilitated/challenged linkage to prevention services. Several evidence-based HIV prevention tools are available; infrastructures for coordinated service delivery to high-risk youth have not been developed. Implementation of such infrastructures requires attention to community-, provider-, and youth-related issues. Copyright © 2017 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

The Process of Adoption of Evidence-based Tobacco Use Prevention Programs in California Schools

PubMed Central

Little, Melissa A.; Pokhrel, Pallav; Sussman, Steve; Rohrbach, Louise Ann

2014-01-01

Although there are a number of research-validated substance use prevention programs available for wide-scale dissemination, very little is known about the factors that influence adoption of evidence-based prevention programs in schools. We tested a model of the mechanisms of program adoption in schools that was guided by diffusion of innovations and social ecological theories. Cross-sectional data were collected from a sample of school district and county office of education tobacco use prevention education coordinators throughout California. Structural equation modeling was used to test the effects of community- and organizational variables on the adoption of prevention programs via school administrators’ beliefs and the organization’s receipt of funding for the program. Results supported the hypothesis that the process of adoption begins with forming beliefs about the program, leading to adoption through the receipt of funding. In addition, we found direct effects of various community- and organizational-level factors on beliefs, receipt of funding, and adoption. These results are likely to inform policies that affect school districts’ use of evidence-based substance use prevention programming, which should ultimately lead to reductions in negative health outcomes among adolescents. Specifically, this study identifies various factors that could be targeted for improvement to enhance evidence-based program adoption. To our knowledge, this is the first study to empirically elucidate the process of adoption of evidence-based tobacco prevention programs in schools. PMID:24398826

Prevention of alcohol and drug abuse: what works?

PubMed

Kumpfer, Karol L

2002-09-01

There is no single "best" prevention program, and no one program or approach will stop all drug use. There are many effective research-based programs; the best approach for any particular population requires selecting the best intervention for the target population on the basis of a knowledge of the risk and protective factors in that population. Unfortunately, the most highly marketed school or family programs are generally not those programs with the best outcomes. The best approach to prevention is to begin early to reduce emerging behavioral and emotional problems in youth. Longer-lasting effects should accrue from changing school, community, and family environmental conditions that promote and maintain drug problems in youth. More and more prevention specialists are considering moving from a focus on the individual to changes in total systems or the environmental contexts that promote or hinder drug use. On the basis of economic considerations, the "whole family" systems-change approach of family skills training classes is becoming popular even in the managed care environment. The greatest challenge facing the drug abuse prevention field is to get information out to practitioners and communities about the best prevention programs, approaches, and principles of effectiveness. Researchers and funding agencies must learn how to effectively market the most successful programs to bridge the gap between research and practice. We must become as effective at marketing drug prevention programs as drug dealers are at promoting and selling drugs. Communities need health care professionals who are knowledgeable about substance abuse prevention and who can advocate the implementation and ongoing improvement of prevention programs with known effectiveness.

Optimizing Violence Prevention Programs: An Examination of Program Effectiveness among Urban High School Students

ERIC Educational Resources Information Center

Thompkins, Amanda C.; Chauveron, Lisa M.; Harel, Ofer; Perkins, Daniel F.

2014-01-01

Background: While demand for youth violence prevention programs increases, the ability of the school-day schedule to accommodate their time requirements has diminished. Viable school-based prevention programs must strike a balance between brevity and effectiveness. This article reports results from an effectiveness trial of a 12-session…

Psychological Treatment as Part of Dropout Prevention: An Israeli Program

ERIC Educational Resources Information Center

Schwartz, Hava; Hain, Rebecca

2014-01-01

This article reports on the integration of psychotherapy in a comprehensive dropout prevention program developed at the Dean of Students' office of Ben-Gurion University of the Negev in Israel. The program's psychologists conducted psychotherapy with a subset of dropout prevention program participants who had reacted with emotional turmoil to the…

Reinforcing Alcohol Prevention (RAP) Program: A Secondary School Curriculum to Combat Underage Drinking and Impaired Driving

ERIC Educational Resources Information Center

Will, Kelli England; Sabo, Cynthia Shier

2010-01-01

The Reinforcing Alcohol Prevention (RAP) Program is an alcohol prevention curriculum developed in partnership with secondary schools to serve their need for a brief, evidence-based, and straightforward program that aligned with state learning objectives. Program components included an educational lesson, video, and interactive activities delivered…

Prevention in Action. 1991 Exemplary Alcohol and Other Drug Prevention Programs.

ERIC Educational Resources Information Center

National Association of State Alcohol and Drug Abuse Directors, Inc.

Eight exemplary programs for preventing alcohol and other drug abuse are presented in this document. These programs are summarized: (1) SUPER II Early Intervention Program, Atlanta, Georgia, which serves primarily inner-city youth ages 11-17 and their families through community agencies, juvenile courts, alternative schools, and public housing;…

The Juvenile and Adolescent Substance Abuse Prevention Program: An Evaluation

ERIC Educational Resources Information Center

Talpade, Medha; Lynch, Diane; Lattimore, Barbara; Graham, Ashlee

2008-01-01

The Juvenile and Adolescent Substance Abuse Prevention Program (JASAP) is a curriculum-based prevention and health promotion program for youth between the ages of 13 to 18 years in Fulton County, Georgia. The program was established in 2007 to promote healthy decision-making skills that would eventually lead to informed choices and decisions…

Feasibility of the Olweus Bullying Prevention Program in Low-Income Schools

ERIC Educational Resources Information Center

Hong, Jun S.

2009-01-01

This article examines school response to bullying and youth aggression in upper/middle-class and low socioeconomic neighborhoods, and the feasibility of successfully implementing the Olweus Bullying Prevention Program in schools located in impoverished communities. The Olweus Bullying Prevention Program is one of the few programs that has proven…

Evaluation of the Olweus Bullying Prevention Program in Nine Urban Schools: Effective Practices and next Steps

ERIC Educational Resources Information Center

Black, Sally; Washington, Ericka

2008-01-01

The Olweus Bullying Prevention Program (BPP) is an internationally recognized school-based bullying prevention program. This project sought to evaluate pilot implementation of the program in one urban district using fidelity of implementation, bullying incident density (BID), student surveys, and serious incident reports as process and outcome…

40 CFR 68.170 - Prevention program/Program 2.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the process. (c) The name(s) of the chemical(s) covered. (d) The date of the most recent review or... (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.170 Prevention program/Program... of completion of the most recent hazard review or update. (1) The expected date of completion of any...

40 CFR 68.170 - Prevention program/Program 2.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the process. (c) The name(s) of the chemical(s) covered. (d) The date of the most recent review or... (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.170 Prevention program/Program... of completion of the most recent hazard review or update. (1) The expected date of completion of any...

40 CFR 68.170 - Prevention program/Program 2.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the process. (c) The name(s) of the chemical(s) covered. (d) The date of the most recent review or... (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.170 Prevention program/Program... of completion of the most recent hazard review or update. (1) The expected date of completion of any...

Curbing Teen Dating Violence: Evidence from a School Prevention Program. RB-9194-CDC

ERIC Educational Resources Information Center

Jaycox, Lisa H.; McCaffrey, Daniel F.; Weidmer Ocampo, Beverly; Marshall, Grant N.; Collins, Rebecca L.; Hickman, Laura J.; Quigley, Denise D.

2006-01-01

This research brief summarizes a survey about the effectiveness of programs from Break the Cycle, a nonprofit organization dedicated to developing and fielding dating-violence prevention programs. The study evaluated "Ending Violence," a three-class-session prevention program. Developed by a Los Angeles-based nonprofit group called Break…

Design of a continuous quality improvement program to prevent falls among community-dwelling older adults in an integrated healthcare system.

PubMed

Ganz, David A; Yano, Elizabeth M; Saliba, Debra; Shekelle, Paul G

2009-11-16

Implementing quality improvement programs that require behavior change on the part of health care professionals and patients has proven difficult in routine care. Significant randomized trial evidence supports creating fall prevention programs for community-dwelling older adults, but adoption in routine care has been limited. Nationally-collected data indicated that our local facility could improve its performance on fall prevention in community-dwelling older people. We sought to develop a sustainable local fall prevention program, using theory to guide program development. We planned program development to include important stakeholders within our organization. The theory-derived plan consisted of 1) an initial leadership meeting to agree on whether creating a fall prevention program was a priority for the organization, 2) focus groups with patients and health care professionals to develop ideas for the program, 3) monthly workgroup meetings with representatives from key departments to develop a blueprint for the program, 4) a second leadership meeting to confirm that the blueprint developed by the workgroup was satisfactory, and also to solicit feedback on ideas for program refinement. The leadership and workgroup meetings occurred as planned and led to the development of a functional program. The focus groups did not occur as planned, mainly due to the complexity of obtaining research approval for focus groups. The fall prevention program uses an existing telephonic nurse advice line to 1) place outgoing calls to patients at high fall risk, 2) assess these patients' risk factors for falls, and 3) triage these patients to the appropriate services. The workgroup continues to meet monthly to monitor the progress of the program and improve it. A theory-driven program development process has resulted in the successful initial implementation of a fall prevention program.

Optimal Investment in HIV Prevention Programs: More Is Not Always Better

PubMed Central

Brandeau, Margaret L.; Zaric, Gregory S.

2008-01-01

This paper develops a mathematical/economic framework to address the following question: Given a particular population, a specific HIV prevention program, and a fixed amount of funds that could be invested in the program, how much money should be invested? We consider the impact of investment in a prevention program on the HIV sufficient contact rate (defined via production functions that describe the change in the sufficient contact rate as a function of expenditure on a prevention program), and the impact of changes in the sufficient contact rate on the spread of HIV (via an epidemic model). In general, the cost per HIV infection averted is not constant as the level of investment changes, so the fact that some investment in a program is cost effective does not mean that more investment in the program is cost effective. Our framework provides a formal means for determining how the cost per infection averted changes with the level of expenditure. We can use this information as follows: When the program has decreasing marginal cost per infection averted (which occurs, for example, with a growing epidemic and a prevention program with increasing returns to scale), it is optimal either to spend nothing on the program or to spend the entire budget. When the program has increasing marginal cost per infection averted (which occurs, for example, with a shrinking epidemic and a prevention program with decreasing returns to scale), it may be optimal to spend some but not all of the budget. The amount that should be spent depends on both the rate of disease spread and the production function for the prevention program. We illustrate our ideas with two examples: that of a needle exchange program, and that of a methadone maintenance program. PMID:19938440

The peroxisome proliferator-activated receptor (PPAR) β/δ agonist GW501516 inhibits IL-6-induced signal transducer and activator of transcription 3 (STAT3) activation and insulin resistance in human liver cells.

PubMed

Serrano-Marco, L; Barroso, E; El Kochairi, I; Palomer, X; Michalik, L; Wahli, W; Vázquez-Carrera, M

2012-03-01

IL-6 induces insulin resistance by activating signal transducer and activator of transcription 3 (STAT3) and upregulating the transcription of its target gene SOCS3. Here we examined whether the peroxisome proliferator-activated receptor (PPAR)β/δ agonist GW501516 prevented activation of the IL-6-STAT3-suppressor of cytokine signalling 3 (SOCS3) pathway and insulin resistance in human hepatic HepG2 cells. Studies were conducted with human HepG2 cells and livers from mice null for Pparβ/δ (also known as Ppard) and wild-type mice. GW501516 prevented IL-6-dependent reduction in insulin-stimulated v-akt murine thymoma viral oncogene homologue 1 (AKT) phosphorylation and in IRS-1 and IRS-2 protein levels. In addition, treatment with this drug abolished IL-6-induced STAT3 phosphorylation of Tyr⁷⁰⁵ and Ser⁷²⁷ and prevented the increase in SOCS3 caused by this cytokine. Moreover, GW501516 prevented IL-6-dependent induction of extracellular-related kinase 1/2 (ERK1/2), a serine-threonine protein kinase involved in serine STAT3 phosphorylation; the livers of Pparβ/δ-null mice showed increased Tyr⁷⁰⁵- and Ser⁷²⁷-STAT3 as well as phospho-ERK1/2 levels. Furthermore, drug treatment prevented the IL-6-dependent reduction in phosphorylated AMP-activated protein kinase (AMPK), a kinase reported to inhibit STAT3 phosphorylation on Tyr⁷⁰⁵. In agreement with the recovery in phospho-AMPK levels observed following GW501516 treatment, this drug increased the AMP/ATP ratio and decreased the ATP/ADP ratio. Overall, our findings show that the PPARβ/δ activator GW501516 prevents IL-6-induced STAT3 activation by inhibiting ERK1/2 phosphorylation and preventing the reduction in phospho-AMPK levels. These effects of GW501516 may contribute to the prevention of cytokine-induced insulin resistance in hepatic cells.

Activation of peroxisome proliferator-activated receptor-β/-δ (PPAR-β/-δ) ameliorates insulin signaling and reduces SOCS3 levels by inhibiting STAT3 in interleukin-6-stimulated adipocytes.

PubMed

Serrano-Marco, Lucía; Rodríguez-Calvo, Ricardo; El Kochairi, Ilhem; Palomer, Xavier; Michalik, Liliane; Wahli, Walter; Vázquez-Carrera, Manuel

2011-07-01

It has been suggested that interleukin (IL)-6 is one of the mediators linking obesity-derived chronic inflammation with insulin resistance through activation of STAT3, with subsequent upregulation of suppressor of cytokine signaling 3 (SOCS3). We evaluated whether peroxisome proliferator-activated receptor (PPAR)-β/-δ prevented activation of the IL-6-STAT3-SOCS3 pathway and insulin resistance in adipocytes. Adipocytes and white adipose tissue from wild-type and PPAR-β/-δ-null mice were used to evaluate the effect of PPAR-β/-δ on the IL-6-STAT3-SOCS3 pathway. First, we observed that the PPAR-β/-δ agonist GW501516 prevented both IL-6-dependent reduction in insulin-stimulated Akt phosphorylation and glucose uptake in adipocytes. In addition, this drug treatment abolished IL-6-induced SOCS3 expression in differentiated 3T3-L1 adipocytes. This effect was associated with the capacity of the drug to prevent IL-6-induced STAT3 phosphorylation on Tyr(705) and Ser(727) residues in vitro and in vivo. Moreover, GW501516 prevented IL-6-dependent induction of extracellular signal-related kinase (ERK)1/2, a serine-threonine-protein kinase involved in serine STAT3 phosphorylation. Furthermore, in white adipose tissue from PPAR-β/-δ-null mice, STAT3 phosphorylation (Tyr(705) and Ser(727)), STAT3 DNA-binding activity, and SOCS3 protein levels were higher than in wild-type mice. Several steps in STAT3 activation require its association with heat shock protein 90 (Hsp90), which was prevented by GW501516 as revealed in immunoprecipitation studies. Consistent with this finding, the STAT3-Hsp90 association was enhanced in white adipose tissue from PPAR-β/-δ-null mice compared with wild-type mice. Collectively, our findings indicate that PPAR-β/-δ activation prevents IL-6-induced STAT3 activation by inhibiting ERK1/2 and preventing the STAT3-Hsp90 association, an effect that may contribute to the prevention of cytokine-induced insulin resistance in adipocytes. © 2011 by the American Diabetes Association.

Parents-CARE: a suicide prevention program for parents of at-risk youth.

PubMed

Hooven, Carole

2013-02-01

Families play an important role in youth suicide prevention, as both a source of protection and a source of risk, and thus are an important target for adolescent suicide prevention programs. This article describes in detail Parents-CARE, a brief youth suicide prevention program for parents, for which effectiveness has been demonstrated. Engaging parents in preventive intervention can be challenging; therefore, the feasibility, acceptability, and relevance of the program to parents are examined. A total of 289 households participated in Parents-CARE. Parent attendance data and parent and interventionist process data are utilized to demonstrate the positive response by parents to the program. The Parents-CARE program was highly attended, and ratings demonstrate that parents were engaged in the program. Ratings show parents found the program both acceptable and relevant. Hence, the program described is promising for clinicians working with at-risk youth as they seek brief, accessible, and effective interventions that include parents in order to amplify the effects of an individual intervention approach. © 2013 Wiley Periodicals, Inc.

Translating evidence based violence and drug use prevention to obesity prevention: development and construction of the pathways program.

PubMed

Sakuma, Kari-Lyn K; Riggs, Nathaniel R; Pentz, Mary Ann

2012-04-01

Effective school-based obesity prevention programs are needed to prevent and reduce the growing obesity risk among youth. Utilizing the evidence-rich areas of violence and substance use prevention, translation science may provide an efficient means for developing curricula across multiple health behaviors. This paper introduces Pathways to Health, a school-based obesity prevention program that was developed by translating from evidence-based violence and drug use prevention programs, Promoting Alternative THinking Strategies and the Midwestern Prevention Project STAR (STAR). We illustrate how a hypothesized underlying behavior change mechanism in two domains of risk behavior, violence and substance use, can be applied to obesity prevention. A 4-step translational process is provided and may be relevant for use in developing other curricula to address multiple health risk behaviors. Practical application and decision points are also provided.

Translating evidence based violence and drug use prevention to obesity prevention: development and construction of the Pathways program

PubMed Central

Sakuma, Kari-Lyn K.; Riggs, Nathaniel R.; Pentz, Mary Ann

2012-01-01

Effective school-based obesity prevention programs are needed to prevent and reduce the growing obesity risk among youth. Utilizing the evidence-rich areas of violence and substance use prevention, translation science may provide an efficient means for developing curricula across multiple health behaviors. This paper introduces Pathways to Health, a school-based obesity prevention program that was developed by translating from evidence-based violence and drug use prevention programs, Promoting Alternative THinking Strategies and the Midwestern Prevention Project STAR (STAR). We illustrate how a hypothesized underlying behavior change mechanism in two domains of risk behavior, violence and substance use, can be applied to obesity prevention. A 4-step translational process is provided and may be relevant for use in developing other curricula to address multiple health risk behaviors. Practical application and decision points are also provided. PMID:21987475

25 CFR 63.33 - What must an application for Indian child protection and family violence prevention program funds...

Code of Federal Regulations, 2010 CFR

2010-04-01

... family violence prevention program funds include? 63.33 Section 63.33 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR TRIBAL GOVERNMENT INDIAN CHILD PROTECTION AND FAMILY VIOLENCE PREVENTION Indian Child Protection and Family Violence Prevention Program § 63.33 What must an application for Indian...

25 CFR 63.30 - What is the purpose of the Indian child protection and family violence prevention program?

Code of Federal Regulations, 2010 CFR

2010-04-01

... family violence prevention program? 63.30 Section 63.30 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR TRIBAL GOVERNMENT INDIAN CHILD PROTECTION AND FAMILY VIOLENCE PREVENTION Indian Child Protection and Family Violence Prevention Program § 63.30 What is the purpose of the Indian child protection...

The Efficacy of Sexual Violence Prevention Programs: Implications for Schools

ERIC Educational Resources Information Center

Adair, Jeannie

2006-01-01

Over the past decade researchers have begun to explore the prevalence, incidence, short and long term effects, and prevention of sexual violence. The purpose of this article was to provide a review of the literature related to the efficacy of sexual violence prevention programs. The review showed that there are many prevention programs yet few…

Title V Incentive Grants for Local Delinquency Prevention Programs. 2008 Report to Congress

ERIC Educational Resources Information Center

Office of Juvenile Justice and Delinquency Prevention, 2011

2011-01-01

The "2008 Title V Report to Congress" marks a departure from the past. Before 2008, the Office of Juvenile Justice and Delinquency Prevention (OJJDP) reported solely on the Community Prevention Grants program in its "Title V Report to Congress." This year, OJJDP is reporting on the four delinquency prevention programs that were…

Using a Domestic and Sexual Violence Prevention Advocate to Implement a Dating Violence Prevention Program with Athletes

ERIC Educational Resources Information Center

Jaime, M. C. D.; Stocking, M.; Freire, K.; Perkinson, L.; Ciaravino, S.; Miller, E.

2016-01-01

"Coaching Boys into Men" is an evidence-based dating violence prevention program for coaches to implement with male athletes. A common adaptation of this program is delivery by domestic violence and sexual violence prevention advocates instead of coaches. We explored how this implementer adaptation may influence athlete uptake of program…

Dropout Prevention: A Study of Prevention Programs Used by High Schools to Increase Graduation Rate

ERIC Educational Resources Information Center

Simmons, Christopher L.

2013-01-01

This mixed methods study focused on the relationship between dropout prevention programs and graduation rates in one school district in Florida during the 2010-2011 school year. The dropout prevention program data analyzed included high school principals' perceptions in regard to perceived effectiveness, fidelity of implementation, cost efficacy,…

An Ounce of Prevention, a Pound of Uncertainty: The Cost-Effectiveness of School-Based Drug Prevention Programs.

ERIC Educational Resources Information Center

Caulkins, Jonathan P.; Rydell, C. Peter; Everingham, Susan S.; Chiesa, James; Bushway, Shawn

This book describes an analysis of the cost-effectiveness of model school-based drug prevention programs at reducing cocaine consumption. It compares prevention's cost-effectiveness with that of several enforcement programs and with that of treating heavy cocaine users. It also assesses the cost of nationwide implementation of model prevention…

Antiprogestin-releasing intrauterine devices

PubMed Central

Nayak, NR; Slayden, OD; Mah, K; Chwalisz, K; Brenner, Robert M

2007-01-01

Intrauterine devices (IUDs) that release progestins are highly effective contraceptives, but they induce breakthrough bleeding that some women find unacceptable. Because progesterone (P) antagonists (AP) are known to suppress the endometrium, induce amenorrhea, and inhibit fertility, AP IUDs may provide an effective contraceptive that also controls endometrial bleeding. Here we assessed the effects of empty (blank) vs AP-releasing (ZK 230 211) IUDs on bleeding patterns and endometrial growth in ovariectomized, artificially cycled macaques. The AP IUDs (but not the blank controls) induced extended, frank menstruation when inserted during the late luteal phase, an indication of local AP action. Over time, endometrial glandular and arterial proliferation were inhibited, steroid receptors were elevated, spiral arteries showed degenerative changes, progesterone withdrawal bleeding was prevented and estradiol-dependent proliferation was suppressed by the AP IUDs. In sum, AP IUDs suppressed the effects of P on endometrial progestational development and blocked the effects of estradiol on endometrial proliferation as previously shown for systemic treatment with APs. Therefore, AP IUDs may provide novel contraceptive devices with minimal breakthrough bleeding. PMID:17531599

Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

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

Suzuki, Chihiro; Takahashi, Masafumi; Morimoto, Hajime

Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected bymore » MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH.« less

Molecular mechanism of central nervous system repair by the Drosophila NG2 homologue kon-tiki

PubMed Central

Harrison, Neale

2016-01-01

Neuron glia antigen 2 (NG2)–positive glia are repair cells that proliferate upon central nervous system (CNS) damage, promoting functional recovery. However, repair is limited because of the failure of the newly produced glial cells to differentiate. It is a key goal to discover how to regulate NG2 to enable glial proliferation and differentiation conducive to repair. Drosophila has an NG2 homologue called kon-tiki (kon), of unknown CNS function. We show that kon promotes repair and identify the underlying mechanism. Crush injury up-regulates kon expression downstream of Notch. Kon in turn induces glial proliferation and initiates glial differentiation by activating glial genes and prospero (pros). Two negative feedback loops with Notch and Pros allow Kon to drive the homeostatic regulation required for repair. By modulating Kon levels in glia, we could prevent or promote CNS repair. Thus, the functional links between Kon, Notch, and Pros are essential for, and can drive, repair. Analogous mechanisms could promote CNS repair in mammals. PMID:27551055

Curcumin Suppresses Proliferation and Migration of MDA-MB-231 Breast Cancer Cells through Autophagy-Dependent Akt Degradation

PubMed Central

Zhang, Yemin; Zhou, Yu; Li, Mingxin; Wang, Changhua

2016-01-01

Previous studies have evidenced that the anticancer potential of curcumin (diferuloylmethane), a main yellow bioactive compound from plant turmeric was mediated by interfering with PI3K/Akt signaling. However, the underlying molecular mechanism is still poorly understood. This study experimentally revealed that curcumin treatment reduced Akt protein expression in a dose- and time-dependent manner in MDA-MB-231 breast cancer cells, along with an activation of autophagy and suppression of ubiquitin-proteasome system (UPS) function. The curcumin-reduced Akt expression, cell proliferation, and migration were prevented by genetic and pharmacological inhibition of autophagy but not by UPS inhibition. Additionally, inactivation of AMPK by its specific inhibitor compound C or by target shRNA-mediated silencing attenuated curcumin-activated autophagy. Thus, these results indicate that curcumin-stimulated AMPK activity induces activation of the autophagy-lysosomal protein degradation pathway leading to Akt degradation and the subsequent suppression of proliferation and migration in breast cancer cell. PMID:26752181

HIV Programs for Sex Workers: Lessons and Challenges for Developing and Delivering Programs

PubMed Central

Wilson, David

2015-01-01

There is evidence that HIV prevention programs for sex workers, especially female sex workers, are cost-effective in several contexts, including many western countries, Thailand, India, the Democratic Republic of Congo, Kenya, and Zimbabwe. The evidence that sex worker HIV prevention programs work must not inspire complacency but rather a renewed effort to expand, intensify, and maximize their impact. The PLOS Collection “Focus on Delivery and Scale: Achieving HIV Impact with Sex Workers” highlights major challenges to scaling-up sex worker HIV prevention programs, noting the following: sex worker HIV prevention programs are insufficiently guided by understanding of epidemic transmission dynamics, situation analyses, and programmatic mapping; sex worker HIV and sexually transmitted infection services receive limited domestic financing in many countries; many sex worker HIV prevention programs are inadequately codified to ensure consistency and quality; and many sex worker HIV prevention programs have not evolved adequately to address informal sex workers, male and transgender sex workers, and mobile- and internet-based sex workers. Based on the wider collection of papers, this article presents three major clusters of recommendations: (i) HIV programs focused on sex workers should be prioritized, developed, and implemented based on robust evidence; (ii) national political will and increased funding are needed to increase coverage of effective sex worker HIV prevention programs in low and middle income countries; and (iii) comprehensive, integrated, and rapidly evolving HIV programs are needed to ensure equitable access to health services for individuals involved in all forms of sex work. PMID:26079267

HIV Programs for Sex Workers: Lessons and Challenges for Developing and Delivering Programs.

PubMed

Wilson, David

2015-06-01

There is evidence that HIV prevention programs for sex workers, especially female sex workers, are cost-effective in several contexts, including many western countries, Thailand, India, the Democratic Republic of Congo, Kenya, and Zimbabwe. The evidence that sex worker HIV prevention programs work must not inspire complacency but rather a renewed effort to expand, intensify, and maximize their impact. The PLOS Collection "Focus on Delivery and Scale: Achieving HIV Impact with Sex Workers" highlights major challenges to scaling-up sex worker HIV prevention programs, noting the following: sex worker HIV prevention programs are insufficiently guided by understanding of epidemic transmission dynamics, situation analyses, and programmatic mapping; sex worker HIV and sexually transmitted infection services receive limited domestic financing in many countries; many sex worker HIV prevention programs are inadequately codified to ensure consistency and quality; and many sex worker HIV prevention programs have not evolved adequately to address informal sex workers, male and transgender sex workers, and mobile- and internet-based sex workers. Based on the wider collection of papers, this article presents three major clusters of recommendations: (i) HIV programs focused on sex workers should be prioritized, developed, and implemented based on robust evidence; (ii) national political will and increased funding are needed to increase coverage of effective sex worker HIV prevention programs in low and middle income countries; and (iii) comprehensive, integrated, and rapidly evolving HIV programs are needed to ensure equitable access to health services for individuals involved in all forms of sex work.

Culturally Grounded Prevention for Minority Youth Populations: A Systematic Review of the Literature

PubMed Central

Lauricella, Michela; Valdez, Jessica K.; Okamoto, Scott K.; Helm, Susana; Zaremba, Colleen

2016-01-01

Contemporary prevention science has focused on the application of cultural adaptations of evidence-based prevention programs for minority youth populations. Far less is known about culturally grounded methods that are intended to organically develop prevention programs within specific populations and communities. This article systematically reviews recent literature on culturally grounded interventions used to prevent health disparities in ethnic minority youth populations. In this review, we assessed 31 peer-reviewed articles published in 2003 or later that fit inclusionary criteria pertaining to the development and evaluation of culturally grounded prevention programs. The evaluated studies indicated different approaches toward cultural grounding, as well as specific populations, geographic regions, and health issues that have been targeted. Specifically, the findings indicated that most of the studies focused on the development and evaluation of culturally grounded HIV/STI and substance abuse prevention programs for Mexican American, African American, and American Indian/Alaska Native youth residing in the South or Southwestern U.S. These studies largely relied on community-based participatory or qualitative research methods to develop programs from the “ground up.” This review has implications for the development of future culturally grounded and culturally adapted prevention programs targeting underserved minority youth populations and geographic regions. Specifically, it identifies populations and regions where culturally grounded prevention efforts are underdeveloped or non-existent, providing some scientific direction for the future development of these types of programs. PMID:26733384

Culturally Grounded Prevention for Minority Youth Populations: A Systematic Review of the Literature.

PubMed

Lauricella, Michela; Valdez, Jessica K; Okamoto, Scott K; Helm, Susana; Zaremba, Colleen

2016-02-01

Contemporary prevention science has focused on the application of cultural adaptations of evidence-based prevention programs for minority youth populations. Far less is known about culturally grounded methods that are intended to organically develop prevention programs within specific populations and communities. This article systematically reviews recent literature on culturally grounded interventions used to prevent health disparities in ethnic minority youth populations. In this review, we assessed 31 peer-reviewed articles published in 2003 or later that fit inclusionary criteria pertaining to the development and evaluation of culturally grounded prevention programs. The evaluated studies indicated different approaches toward cultural grounding, as well as specific populations, geographic regions, and health issues that have been targeted. Specifically, the findings indicated that most of the studies focused on the development and evaluation of culturally grounded HIV/STI and substance abuse prevention programs for Mexican-American, African American, and American Indian/Alaska Native youth residing in the South or Southwestern US. These studies largely relied on community-based participatory or qualitative research methods to develop programs from the "ground up." This review has implications for the development of future culturally grounded and culturally adapted prevention programs targeting underserved minority youth populations and geographic regions. Specifically, it identifies populations and regions where culturally grounded prevention efforts are underdeveloped or non-existent, providing some scientific direction for the future development of these types of programs.

Purinergic receptors contribute to early mesangial cell transformation and renal vessel hypertrophy during angiotensin II-induced hypertension

PubMed Central

Graciano, Miguel L.; Nishiyama, Akira; Jackson, Keith; Seth, Dale M.; Ortiz, Rudy M.; Prieto-Carrasquero, Minolfa C.; Kobori, Hiroyuki; Navar, L. Gabriel

2008-01-01

Chronic ANG II infusions lead to increases in intrarenal ANG II levels, hypertension, and tissue injury. Increased blood pressure also elicits increases in renal interstitial fluid (RIF) ATP concentrations that stimulate cell proliferation. We evaluated the contribution of purinergic receptor activation to ANG II-induced renal injury in rats by treating with clopidogrel, a P2Y12 receptor blocker, or with PPADS, a nonselective P2 receptor blocker. α-Actin expression in mesangial cells, afferent arteriolar wall thickness (AAWT), cortical cell proliferation, and macrophage infiltration were used as early markers of renal injury. Clopidogrel and PPADS did not alter blood pressure, renin or kidney ANG II content. α-Actin expression increased from control of 0.6 ± 0.4% of mesangial area to 6.3 ± 1.9% in ANG II-infused rats and this response was prevented by clopidogrel (0.4 ± 0.2%) and PPADS. The increase in AAWT from 4.7 ± 0.1 to 6.0 ± 0.1 mm in ANG II rats was also prevented by clopidogrel (4.8 ± 0.1 mm) and PPADS. ANG II infusion led to interstitial macrophage infiltration (105 ± 16 vs. 62 ± 4 cell/mm2) and tubular proliferation (71 ± 15 vs. 20 ± 4 cell/mm2) and these effects were prevented by clopidogrel (52 ± 4 and 36 ± 3 cell/mm2) and PPADS. RIF ATP levels were higher in ANG II-infused rats than in control rats (11.8 ± 1.9 vs. 5.6 ± 0.6 nmol/l, P < 0.05). The results suggest that activation of vascular and glomerular purinergic P2 receptors may contribute to the mesangial cell transformation, renal inflammation, and vascular hypertrophy observed in ANG II-dependent hypertension. PMID:17989111

Photochemical inactivation of lymphocytes by riboflavin with visible light for TA-GVHD prevention.

PubMed

Mo, Qin; Huang, Yuwen; Wang, Li; Cheng, Zhenzhen; Wu, Xiaofei; Jia, Yao; Wang, Xun; Zhang, Bo

2017-09-01

Transfusion-associated graft-versus-host disease (TA-GVHD) is a life-threatening complication caused by the input of a number of immunocompetent allogeneic lymphocytes. This study focus on the photochemical effects of riboflavin excited by visible light (RB+L) treatment on human lymphocytes, to study the feasibility of using RB+L treatment to prevent adverse immune reactions caused by transfused lymphocytes. 100μM riboflavin was added to lymphocyte suspensions. After exposure to 400-580nm visible light with a total energy of 40J/mL, cells were cultured and the ability of proliferation and cytokine secretion were assayed upon stimuli. Meanwhile, lymphocytes were also treated by gamma-irradiation as parallel to testify the inactivation effect of RB+L. Results showed that γ-irradiation and RB+L treated cells showed a decline in cell viability. After stimulation of phytohemagglutinin (PHA) or anti-CD3 together with anti-CD28, proliferative ability of RB+L treated cells was strongly inhibited when compared to untreated cells. The inhibitive rates of proliferation in RB+L group were also higher than those of cells treated by γ-irradiation. Results of CFSE assays also illustrated hardly any cell division of RB+L and γ-irradiation treated lymphocytes. Besides low level productions of IL-4 and IL-12, cytokine production of TNF-α, IFN-γ and IL-10 by incubation with PHA or IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α and IFN-γ stimulated by anti-CD3 plus anti-CD28 were suppressed after treatment of RB+L significantly. It was suggested that RB+L/γ-irradiation treatment induced cell apoptosis. These results indicated that RB+L treatment functionally inactivated lymphocytes by inhibiting cell proliferation and cytokine production. RB+L might be an alternative for TA-GVHD prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

Bovine mastitis prevention: humoral and cellular response of dairy cows inoculated with lactic acid bacteria at the dry-off period.

PubMed

Pellegrino, M; Berardo, N; Giraudo, J; Nader-Macías, M E F; Bogni, C

2017-08-24

The use of lactic acid bacteria (LAB) in animal feed, constitute an alternative tool for bovine mastitis prevention. Previously, two LAB strains were isolated from bovine milk and selected for their probiotics properties. So far, immune response of inoculating LAB in bovine udders at dry-off period has not been investigated. The immunoglobulin isotype levels and memory cell proliferation in blood and milk of animals inoculated with Lactobacillus lactis subsp. lactis CRL1655 and Lactobacillus perolens CRL1724 at dry-off period was studied. Ten animals were inoculated intramammarily with 10 6 cells of each LAB (IG) and 2 animals used as control (NIG). Milk and blood samples were taken before inoculation and 1, 2, 4, 6, 12 and 24 h and 7 and 14 days after inoculation. Somatic cell count (SCC) in milk, the presence of bovine mastitis pathogens, the levels of antibodies and lymphocyte proliferation were determined. In the IG, the SCC was <250,000 cells/ml up to 4 h after intramammary inoculation. Six and 12 h after inoculation, the SCC increased up to 600,000 and 2,000,000 cells/ml, respectively. In the NIG, the SCC reached the maximum value 7 days after inoculation. Microbiological analysis showed that all samples were negative for major bovine mastitis pathogens after 24-48 h of incubation. In general, LAB inoculation increased the amount of IgG isotypes in blood and milk, and these antibodies were able to recognise Staphylococcus aureus epitopes. Lymphocytes proliferation was significantly higher in the IG at all time points assayed, following LAB or S. aureus stimulation. The lymphocytes of animals inoculated with LAB do not react in vitro to the presence of S. aureus antigen.. The results showed that probiotic microorganisms could be a natural and effective alternative in the prevention of bovine mastitis at dry-off period and act as immunomodulatory stimulating local and systemic defence lines.

Low molecular weight fucan prevents transplant coronaropathy in rat cardiac allograft model.

PubMed

Alkhatib, Bassam; Freguin-Bouilland, Caroline; Lallemand, Françoise; Henry, Jean Paul; Litzler, Pierre-Yves; Marie, Jean Paul; Richard, Vincent; Thuillez, Christian; Plissonnier, Didier

2006-06-01

Transplant arteriosclerosis is the main cause of long-term failure after cardiac transplantation. Vascular rejection is thought to be due to intimal proliferation occurring in response to arterial wall immune-mediated injury. A low molecular weight fucan (LMWF) compound, a sulfated polysaccharide, has been demonstrated to increase plasma levels of stromal cell-derived factor 1 (SDF-1) and consequently to mobilize bone marrow-derived vascular progenitor cells (BMVPC). The aim of this study was to evaluate the capacity of LMWF to prevent coronary intimal proliferation in a rat cardiac allograft model. Heterotopic abdominal cardiac graftings were performed in Brown Norway (BN) and Lewis (LEW) rats. Animals were divided into 4 groups of 10 rats. Two groups were treated intramuscularly with LMWF (5 mg/kg/day) (one BN to BN isograft group, and one BN to LEW allograft group); and two control groups were LMWF-untreated (one BN to BN isograft group and one BN to LEW allograft group). All animals were treated by cyclosporin (15 mg/kg/day) sub-cutaneously and sacrificed at day 30. The cardiac grafts were assessed by morphometry of structural parameters and by histological and immunohistochemical analyses. All cardiac isografts were devoid of any coronary and parenchymal lesions. In contrast, the majority of untreated allografts developed coronary intimal proliferation in close association with intimal and adventitial inflammatory CD68(+) cell infiltration. Further, the parenchyma exhibited large areas of actin(+) cells (myofibroblasts) of recipient origin colocalized with the CD68(+) infiltrating cells. Interestingly, all LMWF-treated allografts were well protected against coronary and parenchymal lesions and the coronary arteries exhibited an intimal monolayer of flat cells, which however were CD34 negative. treatment with LMWF appeared very effective in this rat cardiac allograft model to prevent arterial and parenchymal lesions occurring in response to alloimmune injury. However this protective effect does not appear to depend on mobilization of bone marrow-derived cells.

Paradoxical effects of antioxidants on cancer.

PubMed

Mendelsohn, Andrew R; Larrick, James W

2014-06-01

Antioxidants have had a checkered history concerning their reported ability to prevent or treat cancer. Early studies that showed ascorbate had benefit in cancer were followed by more definitive studies that demonstrated no benefit. Recent work suggests that biological context may be key to predicting whether antioxidants impede or even promote tumorigenesis. In a recent report, the antioxidants N-acetylcysteine and vitamin E accelerated tumorigenesis of lung cancer in mice. antioxidants decrease reactive oxygen species (ROS) levels, which paradoxically increase the proliferation rate of lung cancer cells, resulting in greater tumor burdens and reduced survival. Increased proliferation rates result from decreased expression of the genomic watchdog protein p53. In mice lacking p53, neither anti-oxidant affects tumor growth. But antioxidants can be used to kill cancer, at least in rodents. High concentrations of the "antioxidant" ascorbate, achievable only by injection in vivo, result in the production of ascorbate radicals and hydrogen peroxide in the extracellular fluid that kills cancer cells, but not normal cells. In preliminary human trials, ascorbate reduced the toxicity of chemotherapy, but showed no statistical benefit on disease progression. Vitamin C is beneficial when it acts as an oxidant. These studies are consistent with others that suggest that even tumor suppressor genes, such as Nrf2, which stimulate innate cellular stress protection pathways that reduce ROS, can promote cancer progression. Nrf2 is required for the cancer preventive effects of compounds such as sulforaphane, but Nrf2 can help maintain an aggressive tumor phenotype by stimulating proliferation and offering protection from chemotherapy. Context determines whether a specific gene is a tumor enhancer or a suppressor. Such paradoxical behavior creates difficult problems for the development of conventional therapeutics to fight cancer. Personal genomic analysis may provide the means to identify context to avoid these paradoxes and obtain a successful outcome. However, cancer prevention may be more difficult than previously thought.

Lovastatin inhibits proliferation of anaplastic thyroid cancer cells through up-regulation of p27 by interfering with the Rho/ROCK-mediated pathway.

PubMed

Zhong, Wen-Bin; Hsu, Sung-Po; Ho, Pei-Yin; Liang, Yu-Chih; Chang, Tien-Chun; Lee, Wen-Sen

2011-12-01

Previously, we demonstrated that lovastatin, a HMG-CoA reductase inhibitor, induced apoptosis, differentiation, and inhibition of invasiveness of human anaplastic thyroid carcinoma cells (ATCs). Here, we further examined the effect of lovastatin on the growth of ARO cells. Lovastatin (0-20μM) concentration-dependently decreased cell number in cultured ATC and arrested the cell at the G0/G1 phase of the cell cycle. Western blot analysis revealed that lovastatin caused an increase of the protein level of p27 and cyclin-dependent kinase (CDK)4 and a decrease of the protein level of cyclin A2, cyclin D3, and phosphorylated Rb (pRb), but did not significantly change the protein levels of p21, cyclins D1 and E, and CDK2, in ARO cells. The formation of the CDK2-p27 complex was increased and the CDK2 activity was decreased in the lovastatin-treated ARO cells. Pretreatment of ARO cells with a p27, but not p21, antisense oligonucleotide prevented the lovastatin-induced G0/G1 arrest in ARO cells. The lovastatin-induced growth inhibition and translocation of RhoA and Rac1 in ARO cells were completely prevented by mevalonate and partially by geranylgeranyl pyrophosphate. Treatment of ARO cells with Y27632, an inhibitor of Rho-associated kinase, abolished the GGPP-mediated prevention of lovastatin-induced anti-proliferation and up-regulation and prolonged degradation of p27. Taken together, these data suggest that lovastatin treatment caused a reduction of Rho geranylgeranylation, which in turn increased the expression and stability of p27, and then inhibited ARO cell proliferation. These data suggest that lovastatin merits further investigation as multipotent therapy for treatment ATC. Copyright © 2011 Elsevier Inc. All rights reserved.

Complementary development of prevention and mental health promotion programs for Canadian children based on contemporary scientific paradigms.

PubMed

Breton, J J

1999-04-01

Confusion regarding definitions and standards of prevention and promotion programs is pervasive, as revealed by a review of such programs in Canada. This paper examines how a discussion of scientific paradigms can help clarify models of prevention and mental health promotion and proposes the complementary development of prevention and promotion programs. A paradigm shift in science contributed to the emergence of the transactional model, advocating multiple causes and dynamic transactions between the individual and the environment. Consequently, the view of prevention applying over a linear continuum and of single stressful events causing mental disorders may no longer be appropriate. It is the author's belief that the new science of chaos theory, which addresses processes involved in the development of systems, can be applied to child development and thus to the heart of prevention and promotion programs. Critical moments followed by transitions or near-chaotic behaviours lead to stable states better adapted to the environment. Prevention programs would focus on the critical moments and target groups at risk to reduce risk factors. Promotion programs would focus on stable states and target the general population to develop age-appropriate life skills. The concept of sensitive dependence on initial conditions and certain empirical studies suggest that the programs would have the greatest impact at the beginning of life. It is hoped that this effort to organize knowledge about conceptual models of prevention and mental health promotion programs will foster the development of these programs to meet the urgent needs of Canadian children.

Preventing the Onset of Child Sexual Abuse by Targeting Young Adolescents With Universal Prevention Programming

PubMed Central

Letourneau, Elizabeth J.; Schaeffer, Cindy M.; Bradshaw, Catherine P.; Feder, Kenneth A.

2017-01-01

Child sexual abuse (CSA) is a serious public health problem that increases risk for physical and mental health problems across the life course. Young adolescents are responsible for a substantial portion of CSA offending, yet to our knowledge, no validated prevention programs that target CSA perpetration by youth exist. Most existing efforts to address CSA rely on reactive criminal justice policies or programs that teach children to protect themselves; neither approach is well validated. Given the high rates of desistance from sexual offending following a youth’s first CSA-related adjudication, it seems plausible that many youth could be prevented from engaging in their first offense. The goal of this article is to examine how school-based universal prevention programs might be used to prevent CSA perpetrated by adolescents. We review the literature on risk and protective factors for CSA perpetration and identify several promising factors to target in an intervention. We also summarize the literature on programs that have been effective at preventing adolescent dating violence and other serious problem behaviors. Finally, we describe a new CSA prevention program under development and early evaluation and make recommendations for program design characteristics, including unambiguous messaging, parental involvement, multisession dosage, skills practice, and bystander considerations. PMID:28413921

Activation of peroxisome proliferator-activated receptor beta/delta inhibits lipopolysaccharide-induced cytokine production in adipocytes by lowering nuclear factor-kappaB activity via extracellular signal-related kinase 1/2.

PubMed

Rodríguez-Calvo, Ricardo; Serrano, Lucía; Coll, Teresa; Moullan, Norman; Sánchez, Rosa M; Merlos, Manuel; Palomer, Xavier; Laguna, Juan C; Michalik, Liliane; Wahli, Walter; Vázquez-Carrera, Manuel

2008-08-01

Chronic activation of the nuclear factor-kappaB (NF-kappaB) in white adipose tissue leads to increased production of pro-inflammatory cytokines, which are involved in the development of insulin resistance. It is presently unknown whether peroxisome proliferator-activated receptor (PPAR) beta/delta activation prevents inflammation in adipocytes. First, we examined whether the PPARbeta/delta agonist GW501516 prevents lipopolysaccharide (LPS)-induced cytokine production in differentiated 3T3-L1 adipocytes. Treatment with GW501516 blocked LPS-induced IL-6 expression and secretion by adipocytes and the subsequent activation of the signal transducer and activator of transcription 3 (STAT3)-Suppressor of cytokine signaling 3 (SOCS3) pathway. This effect was associated with the capacity of GW501516 to impede LPS-induced NF-kappaB activation. Second, in in vivo studies, white adipose tissue from Zucker diabetic fatty (ZDF) rats, compared with that of lean rats, showed reduced PPARbeta/delta expression and PPAR DNA-binding activity, which was accompanied by enhanced IL-6 expression and NF-kappaB DNA-binding activity. Furthermore, IL-6 expression and NF-kappaB DNA-binding activity was higher in white adipose tissue from PPARbeta/delta-null mice than in wild-type mice. Because mitogen-activated protein kinase-extracellular signal-related kinase (ERK)1/2 (MEK1/2) is involved in LPS-induced NF-kappaB activation in adipocytes, we explored whether PPARbeta/delta prevented NF-kappaB activation by inhibiting this pathway. Interestingly, GW501516 prevented ERK1/2 phosphorylation by LPS. Furthermore, white adipose tissue from animal showing constitutively increased NF-kappaB activity, such as ZDF rats and PPARbeta/delta-null mice, also showed enhanced phospho-ERK1/2 levels. These findings indicate that activation of PPARbeta/delta inhibits enhanced cytokine production in adipocytes by preventing NF-kappaB activation via ERK1/2, an effect that may help prevent insulin resistance.

Potential reach of effective smoking prevention programmes in vocational schools: determinants of school directors' intention to adopt these programmes.

PubMed

Veldwijk, J; Hoving, C; van Gelder, B M; Feenstra, T L

2012-04-01

Investigating the current, intended and potential reach of two effective smoking prevention programs in Dutch vocational schools and identifying determinants of school directors' intention to adopt these programs. Cross-sectional survey. Two questionnaires were developed based on the Diffusion of Innovation theory and the I-Change model, focussing on either the 'Healthy School and Stimulants program' (HSS program) or the 'Out-of-school Computer Tailoring program' (CT program). The questionnaires were distributed amongst all Dutch vocational school directors (n = 452) of which 34% completed the questionnaire. The potential reach of the HSS program was 29% whereas the potential reach of the CT program was 5%. Regression analyses revealed that being female, perceiving a higher percentage of smoking students in school, having a personality more open towards change, perceiving a low need for a smoking prevention program, fewer disadvantages of the program, a higher level of self-efficacy towards adopting the program and a more positive social norm towards adopting a smoking prevention program from other school directors resulted in a positive intention towards adopting either program. The present study showed that the reach of effective smoking prevention programs is fairly low. School-based smoking prevention efforts are likely to improve if schools choose to use programs that are proven to be effective, which can be encouraged by adapting existing and newly designed programs to school directors' characteristics and providing easy access to reliable information regarding available programs. Copyright © 2012 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

A selective cyclooxygenase-2 inhibitor (Etodolac) prevents spontaneous biliary tumorigenesis in a hamster bilioenterostomy model.

PubMed

Kitasato, Amane; Kuroki, Tamotsu; Adachi, Tomohiko; Ono, Shinichiro; Tanaka, Takayuki; Tsuneoka, Noritsugu; Hirabaru, Masataka; Takatsuki, Mitsuhisa; Eguchi, Susumu

2014-01-01

Secondary biliary carcinomas are associated with persistent reflux cholangitis after bilioenterostomy. Cyclooxygenase-2 (COX-2) has been a target for cancer prevention. The aim of this study was to evaluate the chemopreventive efficacy of long-term treatment with a selective COX-2 inhibitor medication during the natural course after bilioenterostomy without chemical induction. Syrian golden hamsters which underwent choledochojejunostomy were randomly divided into two groups: the control group (n = 31), which was fed a normal diet, and the etodolac group (n = 33), which was fed 0.01% etodolac (a selective COX-2 inhibitor) mixed in the meal. The hamsters were killed at the postoperative weeks 20-39, 40-59, 60-79, or 80-100. Biliary neoplasms, cholangitis, proliferating cell nuclear antigen labeling index (PCNA-LI) of the biliary epithelium, and prostaglandin E2 (PGE2) production were evaluated. The occurrence rates of biliary neoplasm were 43.8 and 15.2% in the control and etodolac groups, respectively (p < 0.05). The incidence of biliary neoplasm increased as time progressed in the control group, whereas it remained at a low level throughout the experimental period in the etodolac group. PGE2 products tended to be lower in the etodolac group, and PCNA-LI was significantly lower in the etodolac group (p < 0.01). These results suggest that the medication etodolac suppresses cell proliferation of the biliary epithelium, thereby preventing biliary carcinogenesis. Etodolac is expected to prevent secondary biliary carcinogenesis caused by persistent reflux cholangitis after bilioenterostomy. © 2014 S. Karger AG, Basel.

Inhibition of Thymic Adipogenesis by Caloric Restriction Is Coupled with Reduction in Age-Related Thymic Involution1

PubMed Central

Yang, Hyunwon; Youm, Yun-Hee; Dixit, Vishwa Deep

2009-01-01

Aging of thymus is characterized by reduction in naive T cell output together with progressive replacement of lymphostromal thymic zones with adipocytes. Determining how calorie restriction (CR), a prolongevity metabolic intervention, regulates thymic aging may allow identification of relevant mechanisms to prevent immunosenescence. Using a mouse model of chronic CR, we found that a reduction in age-related thymic adipogenic mechanism is coupled with maintenance of thymic function. The CR increased cellular density in the thymic cortex and medulla and preserved the epithelial signatures. Interestingly, CR prevented the age-related increase in epithelial-mesenchymal transition (EMT) regulators, FoxC2, and fibroblast-specific protein-1 (FSP-1), together with reduction in lipid-laden thymic fibroblasts. Additionally, CR specifically blocked the age-related elevation of thymic proadipogenic master regulator, peroxisome proliferator activated receptor γ (PPARγ), and its upstream activator xanthine-oxidoreductase (XOR). Furthermore, we found that specific inhibition of PPARγ in thymic stromal cells prevented their adipogenic transformation in an XOR-dependent mechanism. Activation of PPARγ-driven adipogenesis in OP9-DL1 stromal cells compromised their ability to support T cell development. Conversely, CR-induced reduction in EMT and thymic adipogenesis were coupled with elevated thymic output. Compared with 26-mo-old ad libitum fed mice, the T cells derived from age-matched CR animals displayed greater proliferation and higher IL-2 expression. Furthermore, CR prevented the deterioration of the peripheral TCR repertoire diversity in older animals. Collectively, our findings demonstrate that reducing proadipogenic signaling in thymus via CR may promote thymopoiesis during aging. PMID:19648267

A Chimeric Peptide Composed of a Dermaseptin Derivative and an RNA III-Inhibiting Peptide Prevents Graft-Associated Infections by Antibiotic-Resistant Staphylococci

PubMed Central

Balaban, Naomi; Gov, Yael; Giacometti, Andrea; Cirioni, Oscar; Ghiselli, Roberto; Mocchegiani, Federico; Orlando, Fiorenza; D'Amato, Giuseppina; Saba, Vittorio; Scalise, Giorgio; Bernes, Sabina; Mor, Amram

2004-01-01

Staphylococcal bacteria are a prevalent cause of infections associated with foreign bodies and indwelling medical devices. Bacteria are capable of escaping antibiotic treatment through encapsulation into biofilms. RNA III-inhibiting peptide (RIP) is a heptapeptide that inhibits staphylococcal biofilm formation by obstructing quorum-sensing mechanisms. K4-S4(1-13)a is a 13-residue dermaseptin derivative (DD13) believed to kill bacteria via membrane disruption. We tested each of these peptides as well as a hybrid construct, DD13-RIP, for their ability to inhibit bacterial proliferation and suppress quorum sensing in vitro and for their efficacy in preventing staphylococcal infection in a rat graft infection model with methicillin-resistant Staphylococcus aureus (MRSA) or S. epidermidis (MRSE). In vitro, proliferation assays demonstrated that RIP had no inhibitory effect, while DD13-RIP and DD13 were equally effective, and that the chimeric peptide but not DD13 was slightly more effective than RIP in inhibiting RNA III synthesis, a regulatory RNA molecule important for staphylococcal pathogenesis. In vivo, the three peptides reduced graft-associated bacterial load in a dose-dependent manner, but the hybrid peptide was most potent in totally preventing staphylococcal infections at the lowest dose. In addition, each of the peptides acted synergistically with antibiotics. The data indicate that RIP and DD13 act in synergy by attacking bacteria simultaneously by two different mechanisms. Such a chimeric peptide may be useful for coating medical devices to prevent drug-resistant staphylococcal infections. PMID:15215107

Opportunities for technology-based HIV prevention programming among high school students in Cape Town, South Africa

PubMed Central

Mwaba, Kelvin; Prescott, Tonya L.; Roman, Nicolette V.; Rooi, Bronwyn; Bull, Sheana

2014-01-01

One in three new cases of HIV in South Africa is among adolescents. Given that adolescents are particularly affected, scalable and cost-effective prevention programs are urgently needed. This study aims to identify opportunities to integrate technology into youth HIV prevention efforts. In 2012, 1,107 8th – 11th graders completed a paper-and-pencil survey. Respondents were enrolled in one of three public high schools in Langa. Because it is the closest black township to Cape Town, Langa has the highest density of people in the region. Eighty-nine percent of respondents have used text messaging (SMS) and 86% have gone online. If an HIV prevention program was offered online, 66% of youth would be somewhat or extremely likely to access it; slightly fewer (55%) felt the same about SMS-based programming. In comparison, 85% said they would be somewhat or extremely likely to access a school-based HIV prevention program. Interest in Internet-(60%) and SMS-based (54%) HIV prevention programming was similar for youth who had a self-appraised risk for HIV compared to youth who appraised their risk to be lower, as it was for youth who were tired of hearing messages about HIV prevention. Technology use is common – even among high school students who live in lower income communities. At the same time, these data reveal that it is not uncommon for youth to be tired of hearing messages about HIV prevention, and many of the typical topics key to HIV prevention have low interest levels among youth. HIV prevention researchers need to be mindful of the extent of existing programming that youth are exposed to. Technology-based programming may be especially amenable to meeting these requirements because of its novelty especially in developing countries, and because interactive functionality can be easily integrated into the program design. Given the preference for school- and Internet-based programming, it seems that a hybrid approach is likely feasible and acceptable. PMID:25022287

Opportunities for technology-based HIV prevention programming among high school students in Cape Town, South Africa.

PubMed

Ybarra, Michele L; Mwaba, Kelvin; Prescott, Tonya L; Roman, Nicolette V; Rooi, Bronwyn; Bull, Sheana

2014-01-01

One in three new cases of HIV in South Africa is among adolescents. Given that adolescents are particularly affected, scalable, and cost-effective prevention programs are urgently needed. This study aims to identify opportunities to integrate technology into youth HIV prevention efforts. In 2012, 1107 8th-11th graders completed a paper-and-pencil survey. Respondents were enrolled in one of three public high schools in Langa, a lower income community in Cape Town, South Africa. Eighty-nine percent of respondents have used text messaging (SMS) and 86% have gone online. If an HIV prevention program was offered online, 66% of youth would be somewhat or extremely likely to access it; slightly fewer (55%) felt the same about SMS-based programming. In comparison, 85% said they would be somewhat or extremely likely to access a school-based HIV prevention program. Interest in Internet- (60%) and SMS-based (54%) HIV prevention programming was similar for youth who had a self-appraised risk of HIV compared to youth who appraised their risk to be lower, as it was for youth who were tired of hearing messages about HIV prevention. Technology use is common - even among high school students who live in lower income communities. At the same time, these data reveal that it is not uncommon for youth to be tired of hearing messages about HIV prevention, and many of the typical topics key to HIV prevention have low interest levels among youth. HIV prevention researchers need to be mindful of the extent of existing programming that youth are exposed to. Technology-based programming may be especially amenable to meeting these requirements because of its novelty especially in developing countries, and because interactive functionality can be easily integrated into the program design. Given the preference for school- and Internet-based programming, it seems that a hybrid approach is likely feasible and acceptable.

Business Students' Choice of Short-Term or Long-Term Study Abroad Opportunities

ERIC Educational Resources Information Center

Fitzsimmons, Stacey R.; Flanagan, David J.; Wang, Xiaodan

2013-01-01

Recent years have seen a proliferation of short-term study abroad opportunities. Although they are both supplementing and replacing semester-long study abroad programs, research has focused primarily on semester (long-term) programs. We draw on the theory of planned behavior (TPB) to explore factors that predict why students choose long-term and…

Do Vouchers and Tax Credits Increase Private School Regulation? A Statistical Analysis

ERIC Educational Resources Information Center

Coulson, Andrew J.

2011-01-01

School voucher and education tax credit programs have proliferated in the United States over the past 2 decades. Advocates have argued that they will enable families to become active consumers in a free and competitive education marketplace, but some fear that these programs may bring a heavy regulatory burden that could stifle market forces.…

Online Reading Strategies at Work: What Teachers Think and What Students Do

ERIC Educational Resources Information Center

Huang, Hsin-Chou

2013-01-01

This study designed and developed a web-based reading strategy training program and investigated students' use of its features and EFL teachers' and students' perceptions of the program. The recent proliferation of online reading materials has made information easily available to L2 readers; however, L2 readers' ability to deal with them requires…

Women's perspectives on falls and fall prevention during pregnancy.

PubMed

Brewin, Dorothy; Naninni, Angela

2014-01-01

Falls are the leading cause of unintentional injury in women. During pregnancy, even a minor fall can result in adverse consequences. Evidence to inform effective and developmentally appropriate pregnancy fall prevention programs is lacking. Early research on pregnancy fall prevention suggests that exercise may reduce falls. However, acceptability and effectiveness of pregnancy fall prevention programs are untested. To better understand postpartum women's perspective and preferences on fall prevention strategies during pregnancy to formulate an intervention. Focus groups and individual interviews were conducted with 31 postpartum women using descriptive qualitative methodology. Discussion of falls during pregnancy and fall prevention strategies was guided by a focus group protocol and enhanced by 1- to 3-minute videos on proposed interventions. Focus groups were audio recorded, transcribed, and analyzed using NVivo 10 software. Emerging themes were environmental circumstances and physical changes of pregnancy leading to a fall, prevention strategies, barriers, safety concerns, and marketing a fall prevention program. Wet surfaces and inappropriate footwear commonly contributed to falls. Women preferred direct provider counseling and programs including yoga and Pilates. Fall prevention strategies tailored to pregnant women are needed. Perspectives of postpartum women support fall prevention through provider counseling and individual or supervised exercise programs.

Measurement in comparative effectiveness research.

PubMed

Chubak, Jessica; Rutter, Carolyn M; Kamineni, Aruna; Johnson, Eric A; Stout, Natasha K; Weiss, Noel S; Doria-Rose, V Paul; Doubeni, Chyke A; Buist, Diana S M

2013-05-01

Comparative effectiveness research (CER) on preventive services can shape policy and help patients, their providers, and public health practitioners select regimens and programs for disease prevention. Patients and providers need information about the relative effectiveness of various regimens they may choose. Decision makers need information about the relative effectiveness of various programs to offer or recommend. The goal of this paper is to define and differentiate measures of relative effectiveness of regimens and programs for disease prevention. Cancer screening is used to demonstrate how these measures differ in an example of two hypothetical screening regimens and programs. Conceptually and algebraically defined measures of relative regimen and program effectiveness also are presented. The measures evaluate preventive services that range from individual tests through organized, population-wide prevention programs. Examples illustrate how effective screening regimens may not result in effective screening programs and how measures can vary across subgroups and settings. Both regimen and program relative effectiveness measures assess benefits of prevention services in real-world settings, but each addresses different scientific and policy questions. As the body of CER grows, a common lexicon for various measures of relative effectiveness becomes increasingly important to facilitate communication and shared understanding among researchers, healthcare providers, patients, and policymakers. Copyright © 2013 American Journal of Preventive Medicine. All rights reserved.

Prevalence and Implementation Fidelity of Research-Based Prevention Programs in Public Schools. Final Report

ERIC Educational Resources Information Center

Crosse, Scott; Williams, Barbara; Hagen, Carol A.; Harmon, Michele; Ristow, Liam; DiGaetano, Ralph; Broene, Pamela; Alexander, Debbie; Tseng, Margaret; Derzon, James H.

2011-01-01

This report presents descriptive information about the prevalence and quality of implementation of research-based programs from the Study of the Implementation of Research-Based Programs to Prevent Youth Substance Abuse and School Crime. The study found that, while schools reported implementing a large number of prevention programs during the…

Evaluation of the Courtlink Auto Crime Prevention Program (CACPP) for Senior Elementary and Alternative School Students in British Columbia.

ERIC Educational Resources Information Center

Curtis, Charles K.; Meehan, George

This study evaluated the Courtlink Auto Crime Prevention Program (CACPP), a 13-hour curriculum for senior elementary school and secondary school alternative program at-risk students in British Columbia, Canada. The program provides students with information about automobile crime and its costs, consequences, and prevention. It promotes positive…

Adapting a Multifaceted U.S. HIV Prevention Education Program for Girls in Ghana

ERIC Educational Resources Information Center

Fiscian, Vivian Sarpomaa; Obeng, E. Kwame; Goldstein, Karen; Shea, Judy A.; Turner, Barbara J.

2009-01-01

We adapted a U.S. HIV prevention program to address knowledge gaps and cultural pressures that increase the risk of infection in adolescent Ghanaian girls. The theory-based nine-module HIV prevention program combines didactics and games, an interactive computer program about sugar daddies, and tie-and-dye training to demonstrate an economic…

3 CFR 8761 - Proclamation 8761 of November 30, 2011. National Impaired Driving Prevention Month, 2011

Code of Federal Regulations, 2012 CFR

2012-01-01

... take action by promoting rigorous enforcement measures and effective substance abuse prevention programs. During National Impaired Driving Prevention Month, we recommit to preventing tragedy before it... efforts, implement more effective legislation, and support successful, evidence-based prevention programs...

Personal Computers.

ERIC Educational Resources Information Center

Toong, Hoo-min D.; Gupta, Amar

1982-01-01

Describes the hardware, software, applications, and current proliferation of personal computers (microcomputers). Includes discussions of microprocessors, memory, output (including printers), application programs, the microcomputer industry, and major microcomputer manufacturers (Apple, Radio Shack, Commodore, and IBM). (JN)

Long non-coding RNA HOTTIP promotes prostate cancer cells proliferation and migration by sponging miR-216a-5p.

PubMed

Yang, Bin; Gao, Ge; Wang, Zhixin; Sun, Daju; Wei, Xin; Ma, Yanan; Ding, Youpeng

2018-06-08

Long non-coding RNAs (lncRNAs) are a class of ncRNAs with > 200 nucleotides in length that regulate gene expression. The HOXA transcript at the distal tip (HOTTIP) lncRNA plays an important role in carcinogenesis, however, the underlying role of HOTTIP in prostate cancer (PCa) remain unknown. The aim of the present study was to evaluate the expression and function of HOTTIP in PCa. In the present study, we analyzed HOTTIP expression levels of 86 PCa patients in tumor and adjacent normal tissue by real-time quantitative PCR. Knockdown or overexpression of HOTTIP was performed to explore its roles in cell proliferation, migration, invasion, and cell cycle. Furthermore, bioinformatics online programs predicted and luciferase reporter assay were used to validate the association of HOTTIP and miR-216a-5p in PCa cells. Our results found that HOTTIP was up-regulated in human primary PCa tissues with lymph node metastasis. Knockdown of HOTTIP inhibited PCa cell proliferation, migration and invasion. Overexpression of HOTTIP promoted cell proliferation, migration and invasion of PCa cells. Bioinformatics online programs predicted that HOTTIP sponge miR-216a-5p at 3'-UTR with complementary binding sites, which was validated using luciferase reporter assay. HOTTIP could negatively regulate the expression of miR-216a-5p in PCa cells. Above all, knockdown of HOTTIP could represent a rational therapeutic strategy for PCa. ©2018 The Author(s).

Chemical-biological defense remote sensing: what's happening

NASA Astrophysics Data System (ADS)

Carrico, John P.

1998-08-01

The proliferation of weapons of mass destruction (WMD) continues to be a serious threat to the security of the US. Proliferation of chemical and biological (CB) weapons is particularly disturbing, and the threats posed can be devastating. Critical elements of the US efforts to reduce and counter WMD proliferation include: (1) the location and characterization of WMD facilities and capabilities worldwide; (2) the ability to rapidly detect and identify the use of CB weapons for expeditious warning and reporting on the battlefield; and (3) the capability to mitigate deleterious consequences of a CB incident through effective protective and medical treatment measures. Remote sensing has been touted as a key technology in these efforts. Historically, the role of remote sensing in CB defense has been to provide early warning of an attack from an extended distance. However, additional roles for remote sensing in CB defense, as well as applications in related missions, are possible and should be pursued. This paper examines what has been happening in remote sensing over the past decade to address needs in this area. Accomplishments, emerging technologies, programmatic issues, and opportunities for the future are covered. The Department of Defence chemical- biological, the Department of Energy's Chemical Analysis by Laser Interrogation of Proliferation Effluents, and other agency related programs are examined. Also, the status of remote sensing in the commercial market arena for environmental monitoring, its relevance to the WMD counterproliferation program, and opportunities for technology transfer are discussed. A course of action for the future is recommended.

The action of a dietary retinoid on gene expression and cancer induction in electron-irradiated rat skin

NASA Technical Reports Server (NTRS)

Burns, Fredric J.; Chen, Shuaili; Xu, Guijuan; Wu, Feng; Tang, Moon-Shong

2002-01-01

Current models of radiation carcinogenesis generally assume that the DNA is damaged in a variety of ways by the radiation and that subsequent cell divisions contribute to the conversion of the damage to heritable mutations. Cancer may seem complex and intractable, but its complexity provides multiple opportunities for preventive interventions. Mitotic inhibitors are among the strongest cancer preventive agents, not only slowing the growth rate of preneoplasias but also increasing the fidelity of DNA repair processes. Ionizing radiation, including electrons, is a strong inducer of cancer in rat skin, and dietary retinoids have shown potent cancer preventive activity in the same system. A non-toxic dietary dose of retinyl acetate altered gene expression levels 24 hours after electron irradiation of rat skin. Of the 8740 genes on an Affymetrix rat expression array, the radiation significantly (5 fold or higher) altered 188, while the retinoid altered 231, including 16 radiation-altered genes that were reversely altered. While radiation strongly affected the expression of stress response, immune/inflammation and nucleic acid metabolism genes, the retinoid most strongly affected proliferation-related genes, including some significant reversals, such as, keratin 14, retinol binding protein, and calcium binding proteins. These results point to reversal of proliferation-relevant genes as a likely basis for the anti-radiogenic effects of dietary retinyl acetate.

mTOR Overactivation in Mesenchymal cells Aggravates CCl4- Induced liver Fibrosis.

PubMed

Shan, Lanlan; Ding, Yan; Fu, You; Zhou, Ling; Dong, Xiaoying; Chen, Shunzhi; Wu, Hongyuan; Nai, Wenqing; Zheng, Hang; Xu, Wanfu; Bai, Xiaochun; Jia, Chunhong; Dai, Meng

2016-11-07

Hepatic stellate cells are of mesenchymal cell type located in the space of Disse. Upon liver injury, HSCs transactivate into myofibroblasts with increase in expression of fibrillar collagen, especially collagen I and III, leading to liver fibrosis. Previous studies have shown mTOR signaling is activated during liver fibrosis. However, there is no direct evidence in vivo. The aim of this study is to examine the effects of conditional deletion of TSC1 in mesenchymal on pathogenesis of liver fibrosis. Crossing mice bearing the floxed TSC1 gene with mice harboring Col1α2-Cre-ER(T) successfully generated progeny with a conditional knockout of TSC1 (TSC1 CKO) in collagen I expressing mesenchymal cells. TSC1 CKO and WT mice were subjected to CCl 4 , oil or CCl 4 + rapamycin treatment for 8 weeks. TSC1 CKO mice developed pronounced liver fibrosis relative to WT mice, as examined by ALT, hydroxyproline, histopathology, and profibrogenic gene. Absence of TSC1 in mesenchymal cells induced proliferation and prevented apoptosis in activated HSCs. However, there were no significant differences in oil-treated TSC1 CKO and WT mice. Rapamycin, restored these phenotypic changes by preventing myofibroblasts proliferation and enhancing their apoptosis. These findings revealed mTOR overactivation in mesenchymal cells aggravates CCl 4 - induced liver fibrosis and the rapamycin prevent its occurance.