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Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis 被引量:6
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作者 Xing-Nian Zhou Quan Zhang +6 位作者 Hong Peng Yu-Jie Qin Yu-Hong Liu Lu Wang Ming-Liang Cheng Xin-Hua Luo Hong Li 《World Journal of Gastroenterology》 SCIE CAS 2024年第11期1588-1608,共21页
BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple b... BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF. 展开更多
关键词 silent information regulator sirtuin 1 Ferroptosis PYROPTOSIS p53/glutathione peroxidase 4/gasdermin D Acute liver failure
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Panax notoginseng Saponins Protect Kidney from Diabetes by Up-regulating Silent Information Regulator 1 and Activating Antioxidant Proteins in Rats 被引量:11
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作者 杜月光 汪丽佩 +2 位作者 钱俊文 章科娜 柴可夫 《Chinese Journal of Integrative Medicine》 SCIE CAS CSCD 2016年第12期910-917,共8页
Objective: To explore the mechanism of the protective effects of Panax notoginseng saponins(PNS) on kidney in diabetic rats. Methods: Diabetic rat model was obtained by intravenous injection of alloxan, and the ra... Objective: To explore the mechanism of the protective effects of Panax notoginseng saponins(PNS) on kidney in diabetic rats. Methods: Diabetic rat model was obtained by intravenous injection of alloxan, and the rats were divided into model, PNS-100 mg/(kg·day) and PNS-200 mg/(kg·day) groups, 10 each. Another 10 rats injected with saline were served as control. Periodic acid-Schiff staining and immunological histological chemistry were used to observe histomorphology and tissue expression of bone morphogenetic protein-7(BMP-7). Silent information regulator 1(SIRT1) was silenced in rat mesangial cells by RNA interference. The mR NA expressions of SIRT-1, monocyte chemoattractant protein-1(MCP-1), transforming growth factor β1(TGF-β1) and plasminogen activator inhibitor-1(PAI-1) were analyzed by reverse transcription polymerase chain reaction. The protein expressions of SIRT1 and the acetylation of nuclear factor κB(NF-κB) P65 were determined by western blotting. The concentration of MCP-1, TGF-β1 and malondialdehyde(MDA) in culture supernatant were detected by enzyme-linked immuno sorbent assay. The activity of superoxide dismutase(SOD) was detected by the classical method of nitrogen and blue four. Results: In diabetic model rats, PNS could not only reduce blood glucose and lipid(P〈0.01), but also increase protein level of BMP-7 and inhibit PAI-1 expression for suppressing fibrosis of the kidney. In rat mesangial cells, PNS could up-regulate the expression of SIRT1(P〈0.01) and in turn suppress the transcription of TGF-β1(P〈0.05) and MCP-1(P〈0.05). PNS could also reverse the increased acetylation of NF-κB p65 by high glucose. In addition, redox regulation factor MDA was down-regulated(P〈0.05) and SOD was up-regulated(P〈0.01), which were both induced by SIRT1 up-regulation. Conclusions: PNS could protect kidney from diabetes with the possible mechanism of up-regulating SIRT1, therefore inhibiting inflammation through decreasing the induction of inflammatory cytokines and TGF-β1, as well as activating antioxidant proteins. 展开更多
关键词 Panax notoginseng saponins diabetic nephropathy inflammation nuclear factor κB silent information regulator 1 Chinese medicine
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Protective Effect of Silent Mating Type Information Regulation 2 Homolog 1 on TGF-β1 Pathway via mTOR in Diabetic Nephropathy
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作者 Yanting Gu Dechun Jiang +1 位作者 Pengcheng Xu Yanchun Wang 《Journal of Biosciences and Medicines》 CAS 2023年第2期194-207,共14页
Objective: To demonstrate whether the expression of silent mating type information regulation 2 homolog 1 (SIRT1) affects the level of TGF-β1 and Smad3 in HEK293 cells through regulating mTOR. Methods: First, recombi... Objective: To demonstrate whether the expression of silent mating type information regulation 2 homolog 1 (SIRT1) affects the level of TGF-β1 and Smad3 in HEK293 cells through regulating mTOR. Methods: First, recombinant plasmids DNA (rSIRT1) and siRNA targeting SIRT1 were constructed which were transfected into Human Embryonic Kidney 293 cell (HEK293) cells, respectively. Then, the generation of intracellular ROS in cells was examined by flow cytometry using the oxidation-sensitive probe. Last, the expressions of TGF-β1, smad3, P53, mTOR, p-mTOR, LC3-I and LC3-II in cells were detected to observe the effect of SIRT1 on TGF-β1 Pathway by western blot analysis. Results: We demonstrated that overexpressing of SIRT1 may decrease TGF-β1 and Smad3 expression in HEK293 cells through regulating mTOR. In addition, the result is the opposite when SIRT1 was silent in HEK293 cells. Conclusions: SIRT1 is closely related to TGF-β1/Smad3 pathway that correlates with the regulation of mTOR and ROS generation and causes diabetic nephropathy. The available evidence implies that SIRT1 has great potential as a clinical target for the prevention and treatment of renal fibrosis in the development of DN. 展开更多
关键词 silent Mating Type information Regulation 2 Homolog 1 MTOR Diabetic Nephropathy AUTOPHAGY Oxidative Stress
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Regulation role of miR-204 on SIRT1/VEGF in metabolic memory induced by high glucose in human retinal pigment epithelial cells
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作者 Qiao-Ling Lai Ting Xie +1 位作者 Wei-Dong Zheng Yan Huang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第7期1232-1237,共6页
AIM:To examine the regulatory role of microRNA-204(miR-204)on silent information regulator 1(SIRT1)and vascular endothelial growth factor(VEGF)under highglucose-induced metabolic memory in human retinal pigment epithe... AIM:To examine the regulatory role of microRNA-204(miR-204)on silent information regulator 1(SIRT1)and vascular endothelial growth factor(VEGF)under highglucose-induced metabolic memory in human retinal pigment epithelial(hRPE)cells.METHODS:Cells were cultured with either normal(5 mmol/L)or high D-glucose(25 mmol/L)concentrations for 8d to establish control and high-glucose groups,respectively.To induce metabolic memory,cells were cultured with 25 mmol/L D-glucose for 4d followed by culture with 5 mmol/L D-glucose for 4d.In addition,exposed in 25 mmol/L D-glucose for 4d and then transfected with 100 nmol/L miR-204 control,miR-204 inhibitor or miR-204 mimic in 5 mmol/L D-glucose for 4d.Quantitative reverse transcription-polymerase chain reaction(RT-qPCR)was used to detect miR-204 mRNA levels.SIRT1 and VEGF protein levels were assessed by immunohistochemical and Western blot.Flow cytometry was used to investigate apoptosis rate.RESULTS:It was found that high glucose promoted miR-204 and VEGF expression,and inhibited SIRT1 activity,even after the return to normal glucose culture conditions.Upregulation of miR-204 promoted apoptosis inhibiting SIRT1 and increasing VEGF expression.However,downregulation of miR-204 produced the opposite effects.CONCLUSION:The study identifies that miR-204 is the upstream target of SIRT1and VEGF,and that miR-204 can protect hRPE cells from the damage caused by metabolic memory through increasing SIRT1 and inhibiting VEGF expression. 展开更多
关键词 human retinal pigment epithelial metabolic memory microRNA-204 silent information regulator 1 vascular endothelial growth factor high-glucose
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The potential of herbal drugs to treat heart failure:The roles of Sirt1/AMPK
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作者 Tao Zhang Lei Xu +5 位作者 Xiaowei Guo Honglin Tao Yue Liu Xianfeng Liu Yi Zhang Xianli Meng 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2024年第2期157-176,共20页
Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden.In addition to cardiac myocyte oxidative stress and apopto... Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden.In addition to cardiac myocyte oxidative stress and apoptosis,which are considered mechanisms for the development of HF,alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately HF.Silent information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases and phosphorylated kinases,respectively.They play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α),protein 38 mitogen-activated protein kinase(p38 MAPK),peroxisome proliferator-activated receptors(PPARs),and mammalian target of rapamycin(mTOR).We summarized the synergistic effects of Sirt1 and AMPK in the heart,and listed the traditional Chinese medicine(TCM)that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway,to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases(CVDs). 展开更多
关键词 Heart failure silent information regulator 1 Adenosine monophosphate-activated protein kinase Traditional Chinese medicine
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miR-211 promotes lens epithelial cells apoptosis by targeting silent mating-type information regulation 2 homolog 1 in age-related cataracts 被引量:10
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作者 Bo Lu Ian T.Christensen +6 位作者 Li-Wei Ma Xin-Ling Wang Ling-Feng Jiang Chun-Xia Wang Li Feng Jin-Song Zhang Qi-Chang Yan 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2018年第2期201-207,共7页
AIM: To detect the expression of miR-211 in age-related cataract tissue, explore the effects of miR-211 on lens epithelial cell proliferation and apoptosis, and identify its target gene.METHODS: This study used real... AIM: To detect the expression of miR-211 in age-related cataract tissue, explore the effects of miR-211 on lens epithelial cell proliferation and apoptosis, and identify its target gene.METHODS: This study used real-time quantitative polymerase chain reaction(RT-q PCR) to measure the expression of miR-211 and its predicted target gene [silent matingtype information regulation 2 homolog 1(SIRT1)] in 46 anterior lens capsules collected from age-related cataract patients. Human lens epithelial cell line(SRA01/04) cells were transfected with either miR-211 mimics, mimic controls, miR-211 inhibitors or inhibitor controls, 72 h after transfection, miR NA and protein expression of SIRT1 were measured using RT-qP CR and Western blotting; then cells were exposed to 200 μmol/L H2O2 for 1h, whereupon cell viability was measured by MTS assay, caspase-3 assay was performed. Dual luciferase reporter assay was performed to verify the relationship between miR-211 of SIRT1.RESULTS: Compared to the control group, expression of miR-211 was significantly increased(P〈0.001), the miR NA and protein expression of SIRT1 were significantly decreased(P〈0.001) in the anterior lens capsules of patients with age-related cataracts. Relative to the control group, SIRT1 miR NA and protein levels in the miR-211 mimic group were significantly reduced, cell proliferation activity significantly decreased, and caspase-3 activity was significantly increased(P〈0.001). In the miR-211 inhibitor group, SIRT1 miRNA and protein expression were significantly increased, cell proliferation activity significantly increased, and caspase-3 activity was significantly decreased(P〈0.001). A dual luciferase reporter assay confirmed that SIRT1 is a direct target of miR-211.CONCLUSION: miR-211 is highly expressed in the anterior lens capsules of patients with age-related cataracts. By negatively regulating the expression of SIRT1, miR-211 promotes lens epithelial cell apoptosis and inhibits lens epithelial cell proliferation. 展开更多
关键词 miR-211 silent mating-type information regulation 2 homolog 1 cataract apoptosis proliferation
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Sirtuin 1 in regulating the p53/glutathione peroxidase 4/gasdermin D axis in acute liver failure
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作者 Swati Katoch Vikram Patial 《World Journal of Gastroenterology》 SCIE CAS 2024年第34期3850-3855,共6页
In this editorial,we comment on the article by Zhou et al.The study reveals the connection between ferroptosis and pyroptosis and the effect of silent information regulator sirtuin 1(SIRT1)activation in acute liver fa... In this editorial,we comment on the article by Zhou et al.The study reveals the connection between ferroptosis and pyroptosis and the effect of silent information regulator sirtuin 1(SIRT1)activation in acute liver failure(ALF).ALF is characterized by a sudden and severe liver injury resulting in significant hepatocyte damage,often posing a high risk of mortality.The predominant form of hepatic cell death in ALF involves apoptosis,ferroptosis,autophagy,pyroptosis,and necroptosis.Glutathione peroxidase 4(GPX4)inhibition sensitizes the cell to ferroptosis and triggers cell death,while Gasdermin D(GSDMD)is a mediator of pyroptosis.The study showed that ferroptosis and pyroptosis in ALF are regulated by blocking the p53/GPX4/GSDMD pathway,bridging the gap between the two processes.The inhibition of p53 elevates the levels of GPX4,reducing the levels of inflammatory and liver injury markers,ferroptotic events,and GSDMDN protein levels.Reduced p53 expression and increased GPX4 on deletion of GSDMD indicated ferroptosis and pyroptosis interaction.SIRT1 is a NAD-dependent deacetylase,and its activation attenuates liver injury and inflammation,accompanied by reduced ferroptosis and pyroptosis-related proteins in ALF.SIRT1 activation also inhibits the p53/GPX4/GSDMD axis by inducing p53 acetylation,attenuating LPS/D-GalN-induced ALF. 展开更多
关键词 Acute liver failure Ferroptosis Gasdermin D PYROPTOSIS P53 silent information regulator sirtuin 1
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SIRT1 inhibits apoptosis of human lens epithelial cells through suppressing endoplasmic reticulum stress in vitro and in vivo
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作者 Hui Cui Di Sun +3 位作者 Sheng Meng Tian-Ju Ma Zi Ye Zhao-Hui Li 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第7期1205-1216,共12页
AIM:To explore the effect of silent information regulator factor 2-related enzyme 1(SIRT1)on modulating apoptosis of human lens epithelial cells(HLECs)and alleviating lens opacification of rats through suppressing end... AIM:To explore the effect of silent information regulator factor 2-related enzyme 1(SIRT1)on modulating apoptosis of human lens epithelial cells(HLECs)and alleviating lens opacification of rats through suppressing endoplasmic reticulum(ER)stress.METHODS:HLECs(SRA01/04)were treated with varying concentrations of tunicamycin(TM)for 24h,and the expression of SIRT1 and C/EBP homologous protein(CHOP)was assessed using real-time quantitative polymerase chain reaction(RT-PCR),Western blotting,and immunofluorescence.Cell morphology and proliferation was evaluated using an inverted microscope and cell counting kit-8(CCK-8)assay,respectively.In the SRA01/04 cell apoptosis model,which underwent siRNA transfection for SIRT1 knockdown and SRT1720 treatment for its activation,the expression levels of SIRT1,CHOP,glucose regulated protein 78(GRP78),and activating transcription factor 4(ATF4)were examined.The potential reversal of SIRT1 knockdown effects by 4-phenyl butyric acid(4-PBA;an ER stress inhibitor)was investigated.In vivo,age-related cataract(ARC)rat models were induced by sodium selenite injection,and the protective role of SIRT1,activated by SRT1720 intraperitoneal injections,was evaluated through morphology observation,hematoxylin and eosin(H&E)staining,Western blotting,and RT-PCR.RESULTS:SIRT1 expression was downregulated in TMinduced SRA01/04 cells.Besides,in SRA01/04 cells,both cell apoptosis and CHOP expression increased with the rising doses of TM.ER stress was stimulated by TM,as evidenced by the increased GRP78 and ATF4 in the SRA01/04 cell apoptosis model.Inhibition of SIRT1 by siRNA knockdown increased ER stress activation,whereas SRT1720 treatment had opposite results.4-PBA partly reverse the adverse effect of SIRT1 knockdown on apoptosis.In vivo,SRT1720 attenuated the lens opacification and weakened the ER stress activation in ARC rat models.CONCLUSION:SIRT1 plays a protective role against TM-induced apoptosis in HLECs and slows the progression of cataract in rats by inhibiting ER stress.These findings suggest a novel strategy for cataract treatment focused on targeting ER stress,highlighting the therapeutic potential of SIRT1 modulation in ARC development. 展开更多
关键词 silent information regulator factor 2-related enzyme 1 endoplasmic reticulum stress APOPTOSIS human lens epithelial cells CATARACT
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Cardiovascular and nonalcoholic fatty liver disease:Sharing common ground through SIRT1 pathways
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作者 Kenneth Maiese 《World Journal of Cardiology》 2024年第11期632-643,共12页
As a non-communicable disease,cardiovascular disorders have become the lea-ding cause of death for men and women.Of additional concern is that cardio-vascular disease is linked to chronic comorbidity disorders that in... As a non-communicable disease,cardiovascular disorders have become the lea-ding cause of death for men and women.Of additional concern is that cardio-vascular disease is linked to chronic comorbidity disorders that include nonal-coholic fatty liver disease(NAFLD).NAFLD,also termed metabolic-dysfunction-associated steatotic liver disease,is the greatest cause of liver disease throughout the world,increasing in prevalence concurrently with diabetes mellitus(DM),and can progress to nonalcoholic steatohepatitis that leads to cirrhosis and liver fi-brosis.Individuals with metabolic disorders,such as DM,are more than two times likely to experience cardiac disease,stroke,and liver disease that includes NAFLD when compared individuals without metabolic disorders.Interestingly,cardiovascular disorders and NAFLD share a common underlying cellular me-chanism for disease pathology,namely the silent mating type information regu-lation 2 homolog 1(SIRT1;Saccharomyces cerevisiae).SIRT1,a histone deacetylase,is linked to metabolic pathways through nicotinamide adenine dinucleotide and can offer cellular protection though multiple avenues,including trophic factors such as erythropoietin,stem cells,and AMP-activated protein kinase.Translating SIRT1 pathways into clinical care for cardiovascular and hepatic disease can offer significant hope for patients,but further insights into the complexity of SIRT1 pathways are necessary for effective treatment regimens. 展开更多
关键词 AMP-activated protein kinase Cardiovascular disease Diabetes mellitus ERYTHROPOIETIN Metabolic-dysfunction-associated steatotic liver disease NICOTINAMIDE Nicotinamide adenine dinucleotide Nonalcoholic fatty liver disease silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae) Stem cells
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Understanding the molecular crossroads in acute liver failure:A pathway to new therapies 被引量:1
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作者 Chun-Yao Cheng Wen-Rui Hao Tzu-Hurng Cheng 《World Journal of Gastroenterology》 SCIE CAS 2024年第23期2931-2933,共3页
In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ d... In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ dysfunction,and it often necessitates liver transplant to ensure patient survival.Recent research has eluci-dated the involvement of distinct cell death pathways,namely ferroptosis and pyroptosis,in the pathogenesis of ALF.Ferroptosis is driven by iron-dependent lipid peroxidation,whereas pyroptosis is an inflammatory form of cell death;both pathways contribute to hepatocyte death and exacerbate tissue damage.This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF,highlighting the role of key regulators such as silent information regulator sirtuin 1.Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways.Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition. 展开更多
关键词 silent information regulator sirtuin 1 Ferroptosis PYROPTOSIS P53/glutathione peroxidase 4/gasdermin D Acute liver failure
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Resveratrol inhibits collagen Ⅰ synthesis by suppressing IGF-1R activation in intestinal fibroblasts 被引量:6
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作者 Ping Li Mei-Lan Liang +4 位作者 Ying Zhu Yao-Yao Gong Yun Wang Ding Heng Lin Lin 《World Journal of Gastroenterology》 SCIE CAS 2014年第16期4648-4661,共14页
AIM: To investigate whether resveratrol (3,4,5-trihydroxy-trans-stilbene) inhibits collagen&#x02005;I&#x02005;synthesis induced by insulin growth factor-1 (IGF-1) in intestinal fibroblasts, and to explore the ... AIM: To investigate whether resveratrol (3,4,5-trihydroxy-trans-stilbene) inhibits collagen&#x02005;I&#x02005;synthesis induced by insulin growth factor-1 (IGF-1) in intestinal fibroblasts, and to explore the possible molecular mechanisms. 展开更多
关键词 Intestinal fibrosis Insulin-like growth factor-1 RESVERATROL silent information regulator 1 FIBROBLASTS
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Prognostic and Clinical Value of Sirt1 Expression in Gastric Cancer:A Systematic Meta-Analysis 被引量:3
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作者 姜斌 陈锦皇 +5 位作者 袁文正 纪金童 刘正义 吴亮 唐强 舒晓刚 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2016年第2期278-284,共7页
Many studies have reported that the expression of silent information regulator 1(Sirt1) is associated with the clinical features and prognosis of patients with gastric cancer, but the exact function remains controve... Many studies have reported that the expression of silent information regulator 1(Sirt1) is associated with the clinical features and prognosis of patients with gastric cancer, but the exact function remains controversial. We conducted this study to illustrate the clinical and prognostic value of Sirt1 in gastric cancer. The related publications before December 2015 were searched in the databases including Pubmed, Cochrane Library, Embase and China National Knowledge Infrastructure(CNKI). The studies were included and excluded according to the inclusion criteria and exclusion criteria. The 3- and 5-year overall survival(OS) and clinical features such as age, T stage, N stage and differentiation were analyzed by software Rev Man 5.3. A total of 1650 patients in 7 studies were included according to the inclusion criteria and exclusion criteria. The high expression of Sirt1 was found in 58.4% cases by immunohistochemistry. High expression of Sirt1 was closely linked with the 3-year OS(OR=0.25, 95% CI: 0.16–0.39, P0.00001, fixed), patient's age(≥60 years old vs. 〈60 years old; OR=1.43, 95% CI: 1.06–1.93, P=0.02, fixed), T stage(T3+T4 vs. T1+T2; OR=1.45, 95% CI: 1.08–1.94, P=0.01, fixed), N stage(N1+N2+N3 vs. N0; OR=3.47, 95% CI: 2.39–5.05, P〈0.00001, fixed) and tumor differentiation(G1+G2 vs. G3; OR=0.50, 95% CI: 0.35–0.69, P〈0.0001, fixed). Nevertheless, it seemed that high expression of Sirt1 was not associated with 5-year OS(OR=0.44, 95% CI: 0.15–1.28, P=0.13, random). It was suggested that the high expression of Sirt1 implies a poor prognosis of gastric cancer patients in a relatively short period(3 years), but not in a long time(≥5 years). The expression of Sirt1 is also linked with patients' age, T stage, N stage and tumor differentiation. 展开更多
关键词 gastric cancer silent information regulator 1 clinicopathological characteristics PROGNOSIS
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Targeting both ferroptosis and pyroptosis may represent potential therapies for acute liver failure
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作者 Zhong-Yuan Xing Chuan-Jie Zhang Li-Juan Liu 《World Journal of Gastroenterology》 SCIE CAS 2024年第33期3791-3798,共8页
In this editorial,we comment on the article published in the recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a fatal disease that causes uncontrolled massive hepatocyte death and rapid... In this editorial,we comment on the article published in the recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a fatal disease that causes uncontrolled massive hepatocyte death and rapid loss of liver function.Ferroptosis and pyroptosis,cell death forms that can be initiated or blocked concurrently,can play significant roles in developing inflammation and various malignancies.However,their roles in ALF remain unclear.The article discovered the positive feedback between ferroptosis and pyroptosis in the progression of ALF,and revealed that the silent information regulator sirtuin 1(SIRT1)inhibits both pathways through p53,dramatically reducing inflammation and protecting hepatocytes.This suggests the potential use of SIRT1 and its downstream molecules as therapeutics for ALF.Thus,we will discuss the role of ferroptosis and pyroptosis in ALF and the crosstalk between these cell death mechanisms.Additionally,we address potential treatments that could alleviate ALF by simultaneously inhibiting both cell death pathways,as well as examples of SIRT1 activators being used as disease treatment strategies,providing new insights into the therapy of ALF. 展开更多
关键词 Acute liver failure Ferroptosis PYROPTOSIS CROSSTALK silent information regulator sirtuin 1 P53 Glutathione peroxidase 4 Gasdermin D Treatment
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Novel insights into autophagy in gastrointestinal pathologies,mechanisms in metabolic dysfunction-associated fatty liver disease and acute liver failure
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作者 Tsvetelina Velikova Milena Gulinac 《World Journal of Gastroenterology》 SCIE CAS 2024年第27期3273-3277,共5页
In this editorial,we comment on three articles published in a recent issue of World Journal of Gastroenterology.There is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and al... In this editorial,we comment on three articles published in a recent issue of World Journal of Gastroenterology.There is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and also novel insights into some liver conditions,such as metabolic dysfunction-associated fatty liver disease(MAFLD)and acute liver failure(ALF).Despite advancements,understanding autophagy's intricate mechanisms and implications in these diseases remains incomplete.Moreover,MAFLD's pathogenesis,encompassing hepatic steatosis and metabolic dysregulation,require further elucidation.Similarly,the mechanisms underlying ALF,a severe hepatic dysfunction,are poorly understood.Innovative studies exploring the interplay between autophagy and GI disorders,as well as defined mechanisms of MAFLD and ALF,are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases. 展开更多
关键词 Gastrointestinal diseases AUTOPHAGY Metabolic dysfunction-associated fatty liver disease High-normal alanine aminotransferase level silent information regulator sirtuin 1 Acute liver failure
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Targeting the core of neurodegeneration:FoxO,mTOR,and SIRT1 被引量:8
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作者 Kenneth Maiese 《Neural Regeneration Research》 SCIE CAS CSCD 2021年第3期448-455,共8页
The global increase in lifespan noted not only in developed nations,but also in large developing countries parallels an observed increase in a significant number of noncommunicable diseases,most notable neurodegenerat... The global increase in lifespan noted not only in developed nations,but also in large developing countries parallels an observed increase in a significant number of noncommunicable diseases,most notable neurodegenerative disorders.Neurodegenerative disorders present a number of challenges for treatment options that do not resolve disease progression.Furthermore,it is believed by the year 2030,the services required to treat cognitive disorders in the United States alone will exceed$2 trillion annually.Mammalian forkhead transcription factors,silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae),the mechanistic target of rapamycin,and the pathways of autophagy and apoptosis offer exciting avenues to address these challenges by focusing upon core cellular mechanisms that may significantly impact nervous system disease.These pathways are intimately linked such as through cell signaling pathways involving protein kinase B and can foster,sometimes in conjunction with trophic factors,enhanced neuronal survival,reduction in toxic intracellular accumulations,and mitochondrial stability.Feedback mechanisms among these pathways also exist that can oversee reparative processes in the nervous system.However,mammalian forkhead transcription factors,silent mating type information regulation 2 homolog 1,mechanistic target of rapamycin,and autophagy can lead to cellular demise under some scenarios that may be dependent upon the precise cellular environment,warranting future studies to effectively translate these core pathways into successful clinical treatment strategies for neurodegenerative disorders. 展开更多
关键词 Alzheimer's disease apoptosis autophagy ERYTHROPOIETIN FORKHEAD FOXO mechanistic target of rapamycin silent mating type information regulation 2 homolog 1
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Urolithin a alleviates oxidative stress-induced senescence in nucleus pulposus-derived mesenchymal stem cells through SIRT1/PGC-1α pathway 被引量:3
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作者 Peng-Zhi Shi Jun-Wu Wang +6 位作者 Ping-Chuan Wang Bo Han Xu-Hua Lu Yong-Xin Ren Xin-Min Feng Xiao-Fei Cheng Liang Zhang 《World Journal of Stem Cells》 SCIE 2021年第12期1928-1946,共19页
BACKGROUND In degenerative intervertebral disc(IVD),an unfavorable IVD environment leads to increased senescence of nucleus pulposus(NP)-derived mesenchymal stem cells(NPMSCs)and the inability to complete the differen... BACKGROUND In degenerative intervertebral disc(IVD),an unfavorable IVD environment leads to increased senescence of nucleus pulposus(NP)-derived mesenchymal stem cells(NPMSCs)and the inability to complete the differentiation from NPMSCs to NP cells,leading to further aggravation of IVD degeneration(IDD).Urolithin A(UA)has been proven to have obvious effects in delaying cell senescence and resisting oxidative stress.AIM To explore whether UA can alleviate NPMSCs senescence and to elucidate the underlying mechanism.METHODS In vitro,we harvested NPMSCs from rat tails,and divided NPMSCs into four groups:the control group,H2O2 group,H2O2+UA group,and H2O2+UA+SR-18292 group.Senescence-associatedβ-Galactosidase(SA-β-Gal)activity,cell cycle,cell proliferation ability,and the expression of senescence-related and silent information regulator of transcription 1/PPAR gamma coactivator-1α(SIRT1/PGC-1α)pathway-related proteins and mRNA were used to evaluate the protective effects of UA.In vivo,an animal model of IDD was constructed,and Xrays,magnetic resonance imaging,and histological analysis were used to assess whether UA could alleviate IDD in vivo.RESULTS We found that H2O2 can cause NPMSCs senescence changes,such as cell cycle arrest,reduced cell proliferation ability,increased SA-β-Gal activity,and increased expression of senescence-related proteins and mRNA.After UA pretreatment,the abovementioned senescence indicators were significantly alleviated.To further demonstrate the mechanism of UA,we evaluated the mitochondrial membrane potential and the SIRT1/PGC-1αpathway that regulates mitochondrial function.UA protected mitochondrial function and delayed NPMSCs senescence by activating the SIRT1/PGC-1αpathway.In vivo,we found that UA treatment alleviated an animal model of IDD by assessing the disc height index,Pfirrmann grade and the histological score.CONCLUSION In summary,UA could activate the SIRT1/PGC-1αsignaling pathway to protect mitochondrial function and alleviate cell senescence and IDD in vivo and vitro. 展开更多
关键词 Urolithin A Mitochondrial function Oxidative stress SENESCENCE Nucleus pulposus-derived Mesenchymal stem cells The silent information regulator of transcription 1/PPAR gamma coactivator-1αpathway
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Recent therapeutic targets for the prevention and management of diabetic complications 被引量:1
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作者 Md Shahidul Islam Lu Cai Michael Horowitz 《World Journal of Diabetes》 SCIE 2023年第9期1330-1333,共4页
Diabetes and associated complications represent major global public health issues which are associated with impaired quality of life and premature death.Although some diabetic complications have decreased in the devel... Diabetes and associated complications represent major global public health issues which are associated with impaired quality of life and premature death.Although some diabetic complications have decreased in the developed world,the majority are still prevalent,with an increasing trend in the developing world.Currently used therapies are mainly‘glucocentric’,focusing on the optimization of glycemic control to prevent,delay or manage diabetes-associated complications-other common comorbidities,such as dyslipidemia and hypertension are often underestimated.Although a number of novel therapeutic approaches have been reported recently,some of them have not received comparable attention in relation to either further studies or potential clinical implementation.This editorial briefly discusses some recent therapeutic approaches to the prevention and management of diabetes and its associated complications,as well as potential directions for future research and development in this area. 展开更多
关键词 Diabetic complications Oxidative stress PHYTOCHEMICALS ZINC silent information regulator 1 FOXO Micro RNA
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沉默信号调节因子在慢性鼻-鼻窦炎中的表达及炎性因子对其调节作用 被引量:3
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作者 王继国 王虹园 李婷 《中国耳鼻咽喉头颈外科》 CSCD 2021年第4期257-260,共4页
目的探讨沉默信号调节因子1(silent information regulator 1,Sirt1)在慢性鼻-鼻窦炎(chronic rhinosinusitis,CRS)中的表达及炎性因子对其调节作用。方法 2017年3月~2019年3月于北京大学滨海医院接受鼻内镜手术治疗的30例CRS患者鼻筛... 目的探讨沉默信号调节因子1(silent information regulator 1,Sirt1)在慢性鼻-鼻窦炎(chronic rhinosinusitis,CRS)中的表达及炎性因子对其调节作用。方法 2017年3月~2019年3月于北京大学滨海医院接受鼻内镜手术治疗的30例CRS患者鼻筛窦黏膜上皮组织,对照组来源于行鼻中隔偏曲矫正术的患者。HE染色、免疫组化法检测各组患者鼻黏膜组织病理学改变以及Sirt1的表达;提取对照组筛窦黏膜的上皮细胞,进行离体培养。以浓度为0、1、10、100 ng/ml的白细胞介素5(IL-5)、干扰素γ(IFN-γ)处理细胞24 h后,实时荧光定量聚合酶链式反应(qRT-PCR)和Western blot检测细胞中Sirt1 mRNA和蛋白的表达。结果对照组患者鼻黏膜组织结构完整,CRS组患者鼻黏膜组织中炎性细胞大量浸润。与对照组患者相比,CRS组Sirt1的表达量明显降低(P<0.05);Sirt1蛋白和mRNA的表达随IL-5、IFN-γ浓度的升高而明显降低(P<0.05),并且具有浓度依赖性(P<0.05)。结论 Sirt1在CRS患者鼻黏膜组织中表达明显下降,炎性因子可导致Sirt1表达下降,且具有剂量依赖性,推断Sirt1可能参与CRS的炎性应激过程。 展开更多
关键词 鼻窦炎(Sinusitis) 白细胞介素5(Interleukin-5) 干扰素γ(Interferon-gamma) 沉默信号调节因子1(silent information regulator 1)
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Fermented Chinese formula Shuan-Tong-Ling attenuates ischemic stroke by inhibiting inflammation and apoptosis 被引量:22
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作者 Zhi-gang Mei Ling-jing Tan +3 位作者 Jin-feng Wang Xiao-li Li Wei-feng Huang Hua-jun Zhou 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第3期425-432,共8页
The fermented Chinese formula Shuan-Tong-Ling is composed of radix puerariae(Gegen),salvia miltiorrhiza(Danshen),radix curcuma(Jianghuang),hawthorn(Shanzha),salvia chinensis(Shijianchuan),sinapis alba(Baiji... The fermented Chinese formula Shuan-Tong-Ling is composed of radix puerariae(Gegen),salvia miltiorrhiza(Danshen),radix curcuma(Jianghuang),hawthorn(Shanzha),salvia chinensis(Shijianchuan),sinapis alba(Baijiezi),astragalus(Huangqi),panax japonicas(Zhujieshen),atractylodes macrocephala koidz(Baizhu),radix paeoniae alba(Baishao),bupleurum(Chaihu),chrysanthemum(Juhua),rhizoma cyperi(Xiangfu) and gastrodin(Tianma),whose aqueous extract was fermented with lactobacillus,bacillus aceticus and saccharomycetes.ShuanTong-Ling is a formula used to treat brain diseases including ischemic stroke,migraine,and vascular dementia.Shuan-Tong-Ling attenuated H_2O_2-induced oxidative stress in rat microvascular endothelial cells.However,the potential mechanism involved in these effects is poorly understood.Rats were intragastrically treated with 5.7 or 17.2 m L/kg Shuan-Tong-Ling for 7 days before middle cerebral artery occlusion was induced.The results indicated Shuan-Tong-Ling had a cerebral protective effect by reducing infarct volume and increasing neurological scores.Shuan-Tong-Ling also decreased tumor necrosis factor-α and interleukin-1β levels in the hippocampus on the ischemic side.In addition,Shuan-Tong-Ling upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of acetylated-protein 53 and Bax.Injection of 5 mg/kg silent information regulator 1(SIRT1) inhibitor EX527 into the subarachnoid space once every 2 days,four times,reversed the above changes.These results demonstrate that Shuan-Tong-Ling might benefit cerebral ischemia/reperfusion injury by reducing inflammation and apoptosis through activation of the SIRT1 signaling pathway. 展开更多
关键词 nerve regeneration traditional Chinese medicine ferment Shuan-Tong-Ling middle cerebral artery occlusion cerebral ischemia/reperfusion silent information regulator 1 INFLAMMATION APOPTOSIS tumor necrosis factor-alpha interleukin-1 beta Bcl-2 Bax acetylated-protein 53 neural regeneration
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Zhizhu Decoction Alleviates Intestinal Barrier Damage via Regulating SIRT1/FoxO1 Signaling Pathway in Slow Transit Constipation Model Mice 被引量:3
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作者 WEN Yong ZHAN Yu +4 位作者 TANG Shi-yu LIU Fang WANG Qiu-xiao KONG Peng-fei TANG Xue-gui 《Chinese Journal of Integrative Medicine》 SCIE CAS CSCD 2023年第9期809-817,共9页
Objective:To explore the possible effects and mechanism of Zhizhu Decoction(ZZD)on the pathophysiology of slow transit constipation(STC).Methods A total of 54 C57BL/6 mice was randomly divided into the following 6 gro... Objective:To explore the possible effects and mechanism of Zhizhu Decoction(ZZD)on the pathophysiology of slow transit constipation(STC).Methods A total of 54 C57BL/6 mice was randomly divided into the following 6 groups by a random number table,including control,STC model(model),positive control,and low-,medium-and high-doses ZZD treatment groups(5,10,20 g/kg,namely L,M-,and H-ZZD,respectively),9 mice in each group.Following 2-week treatment,intestinal transport rate(ITR)and fecal water content were determined,and blood and colon tissue samples were collected.Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate the morphology of colon tissues and calculate the number of goblet cells.To determine intestinal permeability,serum levels of lipopolysaccharide(LPS),low-density lipoprotein(LDL)and mannose were measured using enzyme-linked immunosorbent assay(ELISA).Western blot analysis was carried out to detect the expression levels of intestinal tight junction proteins zona-occludens-1(ZO-1),claudin-1,occludin and recombinant mucin 2(MUC2).The mRNA expression levels of inflammatory cytokines including tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,IL-4,IL-10 and IL-22 were determined using reverse transcription-quantitative reverse transcription reaction.Colon indexes of oxidative stress were measured by ELISA,and protein expression levels of colon silent information regulator 1/forkhead box O transcription factor 1(SIRT1/FoxO1)antioxidant signaling pathway were detected by Western blot.Results Compared with the model group,ITR and fecal moisture were significantly enhanced in STC mice in the M-ZZD and H-ZZD groups(P<0.01).Additionally,ZZD treatment notably increased the thickness of mucosal and muscular tissue,elevated the number of goblet cells in the colon of STC mice,reduced the secretion levels of LPS,LDL and mannose,and upregulated ZO-1,claudin-1,occludin and MUC2 expressions in the colon in a dose-dependent manner,compared with the model group(P<0.05 or P<0.01).In addition,ZZD significantly attenuated intestinal inflammation and oxidative stress and activated the SIRT1/FoxO1 signaling pathway(P<0.05 or P<0.01).Conclusion ZZD exhibited beneficial effects on the intestinal system of STC mice and alleviated intestinal inflammation and oxidative stress via activating SIRT1/FoxO1 antioxidant signaling pathway in the colon. 展开更多
关键词 ZhizhuDecoction intestinal barrier slow transit constipation oxidative stress silent information regulator 1/forkhead box O transcription factor1signalingpathway
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