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Article ; Online: Ovarian follicular function is not altered by SARS-Cov-2 infection or BNT162b2 mRNA Covid-19 vaccination.

Bentov, Yaakov / Beharier, Ofer / Moav-Zafrir, Arbel / Kabessa, Maor / Godin, Miri / Greenfield, Caryn / Ketzinel-Gilad, Mali / Esh Broder, Efrat / Holzer, Hananel / Wolf, Dana / Oiknine-Djian, Esther / Barghouti, Iyad / Goldman-Wohl, Debra / Yagel, Simcha / Walfisch, Asnat / Hershko Klement, Anat

medRxiv

Abstract: Importance: This is the first study to examine the impact of SARS-Cov-2 infection and COVID-19 vaccination on ovarian function. Objective: To characterize anti-COVID-19 antibodies in follicular fluid and compare ovarian follicle function in women ... ...

Abstract	Importance: This is the first study to examine the impact of SARS-Cov-2 infection and COVID-19 vaccination on ovarian function. Objective: To characterize anti-COVID-19 antibodies in follicular fluid and compare ovarian follicle function in women following confirmed SARS-CoV-2 infection, COVID-19 vaccination, and non-infected, unvaccinated controls. Design: This is a cohort study conducted between February 1 and March 10, 2021. Setting: A single university hospital-based IVF clinic. Participants: Consecutive sample of female patients undergoing oocyte retrieval. Interventions: Consenting patients were recruited and assigned to one of three study groups: recovering from confirmed COVID 19 (n=9); vaccinated (n=9); and uninfected, non-vaccinated controls (n=14). Serum and follicular fluid samples were taken and analyzed for anti-COVID IgG as well as estrogen, progesterone and HSPG2 concentration, as well as the number and maturity of aspirated oocytes and previous estrogen and progesterone measurements. Main outcome measures: Follicular function, including steroidogenesis, follicular response to the LH/hCG trigger, and oocyte quality biomarkers. Results: Both natural and vaccine elicited anti-COVID IgG antibodies were detected in the follicular fluid in levels proportional to the IgG serum concentration. No differences were detected in any of the surrogate ovarian follicle quality reporting parameters. Conclusions and relevance: Both SARS-COV-2 infection and vaccination with the BNT162b2 mRNA vaccine mediate IgG immunity that crosses into the follicular fluid. No detrimental effect on follicular function was detected.
Keywords	covid19
Language	English
Publishing date	2021-04-13
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.04.09.21255195
Database	COVID19

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Article: RNA interference for antiviral therapy.

Ketzinel-Gilad, Mali / Shaul, Yosef / Galun, Eithan

The journal of gene medicine

2006 Volume 8, Issue 8, Page(s) 933–950

Abstract: Silencing gene expression through a process known as RNA interference (RNAi) has been known in the plant world for many years. In recent years, knowledge of the prevalence of RNAi and the mechanism of gene silencing through RNAi has started to unfold. It ...

Abstract	Silencing gene expression through a process known as RNA interference (RNAi) has been known in the plant world for many years. In recent years, knowledge of the prevalence of RNAi and the mechanism of gene silencing through RNAi has started to unfold. It is now believed that RNAi serves in part as an innate response against invading viral pathogens and, indeed, counter silencing mechanisms aimed at neutralizing RNAi have been found in various viral pathogens. During the past few years, it has been demonstrated that RNAi, induced by specifically designed double-stranded RNA (dsRNA) molecules, can silence gene expression of human viral pathogens both in acute and chronic viral infections. Furthermore, it is now apparent that in in vitro and in some in vivo models, the prospects for this technology in developing therapeutic applications are robust. However, many key questions and obstacles in the translation of RNAi into a potential therapeutic platform still remain, including the specificity and longevity of the silencing effect, and, most importantly, the delivery of the dsRNA that induces the system. It is expected that for the specific examples in which the delivery issue could be circumvented or resolved, RNAi may hold promise for the development of gene-specific therapeutics.
MeSH term(s)	Animals ; Antiviral Agents/therapeutic use ; Gene Silencing ; Genetic Therapy ; Humans ; Models, Biological ; RNA Interference ; RNA, Double-Stranded/physiology ; Virus Diseases/drug therapy
Chemical Substances	Antiviral Agents ; RNA, Double-Stranded
Keywords	covid19
Language	English
Publishing date	2006-01-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1458024-x
ISSN	1521-2254 ; 1099-498X
ISSN (online)	1521-2254
ISSN	1099-498X
DOI	10.1002/jgm.929
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: AMP-activated protein kinase (AMPK) mediates nutrient regulation of thioredoxin-interacting protein (TXNIP) in pancreatic beta-cells.

Shaked, Maayan / Ketzinel-Gilad, Mali / Cerasi, Erol / Kaiser, Nurit / Leibowitz, Gil

PloS one

2011 Volume 6, Issue 12, Page(s) e28804

Abstract: Thioredoxin-interacting protein (TXNIP) regulates critical biological processes including inflammation, stress and apoptosis. TXNIP is upregulated by glucose and is a critical mediator of hyperglycemia-induced beta-cell apoptosis in diabetes. In contrast, ...

Abstract	Thioredoxin-interacting protein (TXNIP) regulates critical biological processes including inflammation, stress and apoptosis. TXNIP is upregulated by glucose and is a critical mediator of hyperglycemia-induced beta-cell apoptosis in diabetes. In contrast, the saturated long-chain fatty acid palmitate, although toxic to the beta-cell, inhibits TXNIP expression. The mechanisms involved in the opposing effects of glucose and fatty acids on TXNIP expression are unknown. We found that both palmitate and oleate inhibited TXNIP in a rat beta-cell line and islets. Palmitate inhibition of TXNIP was independent of fatty acid beta-oxidation or esterification. AMP-activated protein kinase (AMPK) has an important role in cellular energy sensing and control of metabolic homeostasis; therefore we investigated its involvement in nutrient regulation of TXNIP. As expected, glucose inhibited whereas palmitate stimulated AMPK. Pharmacologic activators of AMPK mimicked fatty acids by inhibiting TXNIP. AMPK knockdown increased TXNIP expression in presence of high glucose with and without palmitate, indicating that nutrient (glucose and fatty acids) effects on TXNIP are mediated in part via modulation of AMPK activity. TXNIP is transcriptionally regulated by carbohydrate response element-binding protein (ChREBP). Palmitate inhibited glucose-stimulated ChREBP nuclear entry and recruitment to the Txnip promoter, thereby inhibiting Txnip transcription. We conclude that AMPK is an important regulator of Txnip transcription via modulation of ChREBP activity. The divergent effects of glucose and fatty acids on TXNIP expression result in part from their opposing effects on AMPK activity. In light of the important role of TXNIP in beta-cell apoptosis, its inhibition by fatty acids can be regarded as an adaptive/protective response to glucolipotoxicity. The finding that AMPK mediates nutrient regulation of TXNIP may have important implications for the pathophysiology and treatment of diabetes.
MeSH term(s)	AMP-Activated Protein Kinases/antagonists & inhibitors ; AMP-Activated Protein Kinases/metabolism ; Animals ; Apoptosis/drug effects ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; Carrier Proteins/metabolism ; Cell Cycle Proteins ; Cell Nucleus/drug effects ; Cell Nucleus/metabolism ; Deoxyglucose/pharmacology ; Enzyme Activation/drug effects ; Enzyme Activators/pharmacology ; Gene Knockdown Techniques ; Glucose/pharmacology ; Humans ; Insulin-Secreting Cells/cytology ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/enzymology ; Isoenzymes/metabolism ; Metformin/pharmacology ; Oleic Acid/pharmacology ; Palmitic Acid/pharmacology ; Protein Transport/drug effects ; Rats ; Rats, Wistar
Chemical Substances	Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Carrier Proteins ; Cell Cycle Proteins ; Enzyme Activators ; Isoenzymes ; Mlxipl protein, rat ; TXNIP protein, rat ; Oleic Acid (2UMI9U37CP) ; Palmitic Acid (2V16EO95H1) ; Metformin (9100L32L2N) ; Deoxyglucose (9G2MP84A8W) ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2011-12-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0028804
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Correction

Maayan Shaked / Mali Ketzinel-Gilad / Erol Cerasi / Nurit Kaiser / Gil Leibowitz

PLoS ONE, Vol 7, Iss

AMP-Activated Protein Kinase (AMPK) Mediates Nutrient Regulation of Thioredoxin-Interacting Protein (TXNIP) in Pancreatic Beta-Cells

2012 Volume 1

Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Correction

Maayan Shaked / Mali Ketzinel-Gilad / Erol Cerasi / Nurit Kaiser / Gil Leibowitz

PLoS ONE, Vol 7, Iss

AMP-Activated Protein Kinase (AMPK) Mediates Nutrient Regulation of Thioredoxin-Interacting Protein (TXNIP) in Pancreatic Beta-Cells.

2012 Volume 1

Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Glucose amplifies fatty acid-induced endoplasmic reticulum stress in pancreatic beta-cells via activation of mTORC1.

Bachar, Etti / Ariav, Yafa / Ketzinel-Gilad, Mali / Cerasi, Erol / Kaiser, Nurit / Leibowitz, Gil

PloS one

2009 Volume 4, Issue 3, Page(s) e4954

Abstract: Background: Palmitate is a potent inducer of endoplasmic reticulum (ER) stress in beta-cells. In type 2 diabetes, glucose amplifies fatty-acid toxicity for pancreatic beta-cells, leading to beta-cell dysfunction and death. Why glucose exacerbates beta- ... ...

Abstract	Background: Palmitate is a potent inducer of endoplasmic reticulum (ER) stress in beta-cells. In type 2 diabetes, glucose amplifies fatty-acid toxicity for pancreatic beta-cells, leading to beta-cell dysfunction and death. Why glucose exacerbates beta-cell lipotoxicity is largely unknown. Glucose stimulates mTORC1, an important nutrient sensor involved in the regulation of cellular stress. Our study tested the hypothesis that glucose augments lipotoxicity by stimulating mTORC1 leading to increased beta-cell ER stress. Principal findings: We found that glucose amplifies palmitate-induced ER stress by increasing IRE1alpha protein levels and activating the JNK pathway, leading to increased beta-cell apoptosis. Moreover, glucose increased mTORC1 activity and its inhibition by rapamycin decreased beta-cell apoptosis under conditions of glucolipotoxicity. Inhibition of mTORC1 by rapamycin did not affect proinsulin and total protein synthesis in beta-cells incubated at high glucose with palmitate. However, it decreased IRE1alpha expression and signaling and inhibited JNK pathway activation. In TSC2-deficient mouse embryonic fibroblasts, in which mTORC1 is constitutively active, mTORC1 regulated the stimulation of JNK by ER stressors, but not in response to anisomycin, which activates JNK independent of ER stress. Finally, we found that JNK inhibition decreased beta-cell apoptosis under conditions of glucolipotoxicity. Conclusions/significance: Collectively, our findings suggest that mTORC1 mediates glucose amplification of lipotoxicity, acting through activation of ER stress and JNK. Thus, mTORC1 is an important transducer of ER stress in beta-cell glucolipotoxicity. Moreover, in stressed beta-cells mTORC1 inhibition decreases IRE1alpha protein expression and JNK activity without affecting ER protein load, suggesting that mTORC1 regulates the beta-cell stress response to glucose and fatty acids by modulating the synthesis and activity of specific proteins involved in the execution of the ER stress response. This novel paradigm may have important implications for understanding beta-cell failure in type 2 diabetes.
MeSH term(s)	Animals ; Antibiotics, Antineoplastic/pharmacology ; Apoptosis/drug effects ; Cell Line ; Cycloheximide/pharmacology ; Diabetes Mellitus, Type 2/metabolism ; Endoplasmic Reticulum/drug effects ; Endoplasmic Reticulum/metabolism ; Enzyme Activation ; Gerbillinae ; Glucose/metabolism ; Insulin-Secreting Cells/cytology ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/metabolism ; JNK Mitogen-Activated Protein Kinases/metabolism ; Male ; Mechanistic Target of Rapamycin Complex 1 ; Membrane Proteins/metabolism ; Mice ; Multiprotein Complexes ; Oxidative Stress/drug effects ; Oxidative Stress/physiology ; Palmitates/metabolism ; Palmitates/pharmacology ; Protein Synthesis Inhibitors/pharmacology ; Protein-Serine-Threonine Kinases/metabolism ; Proteins ; Signal Transduction/physiology ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Antibiotics, Antineoplastic ; Crtc1 protein, rat ; Membrane Proteins ; Multiprotein Complexes ; Palmitates ; Protein Synthesis Inhibitors ; Proteins ; Transcription Factors ; Cycloheximide (98600C0908) ; Ern2 protein, mouse (EC 2.7.1.-) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Glucose (IY9XDZ35W2) ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2009-03-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0004954
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: AMP-activated protein kinase (AMPK) mediates nutrient regulation of thioredoxin-interacting protein (TXNIP) in pancreatic beta-cells.

Maayan Shaked / Mali Ketzinel-Gilad / Erol Cerasi / Nurit Kaiser / Gil Leibowitz

PLoS ONE, Vol 6, Iss 12, p e

2011 Volume 28804

Abstract	Thioredoxin-interacting protein (TXNIP) regulates critical biological processes including inflammation, stress and apoptosis. TXNIP is upregulated by glucose and is a critical mediator of hyperglycemia-induced beta-cell apoptosis in diabetes. In contrast, the saturated long-chain fatty acid palmitate, although toxic to the beta-cell, inhibits TXNIP expression. The mechanisms involved in the opposing effects of glucose and fatty acids on TXNIP expression are unknown. We found that both palmitate and oleate inhibited TXNIP in a rat beta-cell line and islets. Palmitate inhibition of TXNIP was independent of fatty acid beta-oxidation or esterification. AMP-activated protein kinase (AMPK) has an important role in cellular energy sensing and control of metabolic homeostasis; therefore we investigated its involvement in nutrient regulation of TXNIP. As expected, glucose inhibited whereas palmitate stimulated AMPK. Pharmacologic activators of AMPK mimicked fatty acids by inhibiting TXNIP. AMPK knockdown increased TXNIP expression in presence of high glucose with and without palmitate, indicating that nutrient (glucose and fatty acids) effects on TXNIP are mediated in part via modulation of AMPK activity. TXNIP is transcriptionally regulated by carbohydrate response element-binding protein (ChREBP). Palmitate inhibited glucose-stimulated ChREBP nuclear entry and recruitment to the Txnip promoter, thereby inhibiting Txnip transcription. We conclude that AMPK is an important regulator of Txnip transcription via modulation of ChREBP activity. The divergent effects of glucose and fatty acids on TXNIP expression result in part from their opposing effects on AMPK activity. In light of the important role of TXNIP in beta-cell apoptosis, its inhibition by fatty acids can be regarded as an adaptive/protective response to glucolipotoxicity. The finding that AMPK mediates nutrient regulation of TXNIP may have important implications for the pathophysiology and treatment of diabetes.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: A hepatocellular carcinoma cell line producing mature hepatitis B viral particles.

Fellig, Yakov / Almogy, Gidon / Galun, Eithan / Ketzinel-Gilad, Mali

Biochemical and biophysical research communications

2004 Volume 321, Issue 2, Page(s) 269–274

Abstract: Current in vitro models for hepatitis B virus (HBV) are based on human hepatoblastoma cell lines transfected with HBV genome. The objective of this work was to develop an in vitro, hepatocellular carcinoma (HCC)-based system supporting HBV full ... ...

Abstract	Current in vitro models for hepatitis B virus (HBV) are based on human hepatoblastoma cell lines transfected with HBV genome. The objective of this work was to develop an in vitro, hepatocellular carcinoma (HCC)-based system supporting HBV full replication and producing mature viral particles. The FLC4 human HCC cell line was stably transfected with a plasmid carrying a head-to-tail dimer of the adwHBV genome. One of the clones, FLC4A10II, exhibited prolonged expression of HBV, as was demonstrated by secreted levels of HBsAg, HBeAg, and HBV DNA in the culture medium of the growing cells. Furthermore, the cells produced HBV particles that were detected by a cesium chloride density gradient performed on the culture medium. Analysis by Southern blot revealed that HBV DNA has integrated into the FLC4A10II cell genome. The presence of HBV in the FLC4A10II cells did not cause alterations in cell morphology and the cells continued to resemble mature hepatocytes. They do exhibit a high mitotic activity. The new HBV stably transfected cell line, FLC4A10II, can serve as an important tool for further exploration of HBV host-pathogen interaction, viral life cycle, and for assessing new antiviral agents.
MeSH term(s)	Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/virology ; Cell Line, Tumor ; Culture Media ; DNA, Viral/analysis ; DNA, Viral/genetics ; DNA, Viral/secretion ; Gene Expression Regulation, Viral ; Hepatitis B Surface Antigens/genetics ; Hepatitis B Surface Antigens/metabolism ; Hepatitis B virus/chemistry ; Hepatitis B virus/genetics ; Hepatitis B virus/physiology ; Humans ; Kinetics ; RNA, Viral/genetics ; RNA, Viral/metabolism ; Transfection ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Virion/chemistry ; Virion/genetics ; Virion/physiology ; Virus Assembly ; Virus Integration
Chemical Substances	Culture Media ; DNA, Viral ; Hepatitis B Surface Antigens ; RNA, Viral ; Viral Proteins
Language	English
Publishing date	2004-08-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2004.06.148
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Zs.A 116: Show issues

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Article ; Online: Glucose amplifies fatty acid-induced endoplasmic reticulum stress in pancreatic beta-cells via activation of mTORC1.

Etti Bachar / Yafa Ariav / Mali Ketzinel-Gilad / Erol Cerasi / Nurit Kaiser / Gil Leibowitz

PLoS ONE, Vol 4, Iss 3, p e

2009 Volume 4954

Abstract: BACKGROUND: Palmitate is a potent inducer of endoplasmic reticulum (ER) stress in beta-cells. In type 2 diabetes, glucose amplifies fatty-acid toxicity for pancreatic beta-cells, leading to beta-cell dysfunction and death. Why glucose exacerbates beta- ... ...

Abstract	BACKGROUND: Palmitate is a potent inducer of endoplasmic reticulum (ER) stress in beta-cells. In type 2 diabetes, glucose amplifies fatty-acid toxicity for pancreatic beta-cells, leading to beta-cell dysfunction and death. Why glucose exacerbates beta-cell lipotoxicity is largely unknown. Glucose stimulates mTORC1, an important nutrient sensor involved in the regulation of cellular stress. Our study tested the hypothesis that glucose augments lipotoxicity by stimulating mTORC1 leading to increased beta-cell ER stress. PRINCIPAL FINDINGS: We found that glucose amplifies palmitate-induced ER stress by increasing IRE1alpha protein levels and activating the JNK pathway, leading to increased beta-cell apoptosis. Moreover, glucose increased mTORC1 activity and its inhibition by rapamycin decreased beta-cell apoptosis under conditions of glucolipotoxicity. Inhibition of mTORC1 by rapamycin did not affect proinsulin and total protein synthesis in beta-cells incubated at high glucose with palmitate. However, it decreased IRE1alpha expression and signaling and inhibited JNK pathway activation. In TSC2-deficient mouse embryonic fibroblasts, in which mTORC1 is constitutively active, mTORC1 regulated the stimulation of JNK by ER stressors, but not in response to anisomycin, which activates JNK independent of ER stress. Finally, we found that JNK inhibition decreased beta-cell apoptosis under conditions of glucolipotoxicity. CONCLUSIONS/SIGNIFICANCE: Collectively, our findings suggest that mTORC1 mediates glucose amplification of lipotoxicity, acting through activation of ER stress and JNK. Thus, mTORC1 is an important transducer of ER stress in beta-cell glucolipotoxicity. Moreover, in stressed beta-cells mTORC1 inhibition decreases IRE1alpha protein expression and JNK activity without affecting ER protein load, suggesting that mTORC1 regulates the beta-cell stress response to glucose and fatty acids by modulating the synthesis and activity of specific proteins involved in the execution of the ER stress response. This novel ...
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2009-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Small interfering RNA inhibits hepatitis B virus replication in mice.

Giladi, Hilla / Ketzinel-Gilad, Mali / Rivkin, Ludmila / Felig, Yaakov / Nussbaum, Ofer / Galun, Eithan

Molecular therapy : the journal of the American Society of Gene Therapy

2003 Volume 8, Issue 5, Page(s) 769–776

Abstract: Current therapies for chronic hepatitis B virus (HBV) infection are limited in their effect on viral gene expression and replication. Recent reports have shown that RNA interference can be induced in mammalian cells by short interfering RNA duplexes ( ... ...

Abstract	Current therapies for chronic hepatitis B virus (HBV) infection are limited in their effect on viral gene expression and replication. Recent reports have shown that RNA interference can be induced in mammalian cells by short interfering RNA duplexes (siRNA). Here we studied the effects of an HBV-specific 21-bp siRNA targeted to the surface antigen region (HBsAg), where three major viral mRNAs overlap, on HBV gene expression and replication both in a cell culture system and in a mouse model for HBV replication. Transfection of siRNA into HepG2.2.15 cells, which constitutively produce HBV particles, caused a significant reduction in viral RNA production that was accompanied by a >80% drop in the secretion of viral HBsAg and HBeAg into the medium. The effect of RNAi was tested in vivo in a mouse model that we have developed for HBV infection, which entails hydrodynamic injection of a plasmid bearing the HBV genome into tail veins of mice. Injection of the HBV plasmid induces viral replication and generation of HBV viral particles detectable in the mouse sera. Co-injection of the HBV plasmid together with siRNA caused a significant inhibition in the level of viral transcripts, viral antigens, and viral DNA detected in the livers and sera of the treated mice relative to control animals. Results suggest that siRNA is capable of inhibiting HBV replication in vivo and thus may constitute a new therapeutic strategy for HBV infection.
MeSH term(s)	Animals ; Blotting, Northern ; Blotting, Southern ; Cell Line ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Hepatitis B virus/genetics ; Hepatitis B virus/physiology ; Humans ; Immunohistochemistry ; Kinetics ; Liver/metabolism ; Mice ; Mice, Inbred BALB C ; Plasmids/metabolism ; Polymerase Chain Reaction ; RNA Interference ; RNA, Messenger/metabolism ; RNA, Small Interfering/metabolism ; Time Factors ; Transfection ; Virus Replication
Chemical Substances	RNA, Messenger ; RNA, Small Interfering
Language	English
Publishing date	2003-11-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/s1525-0016(03)00244-2
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