Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has...Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.展开更多
The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing ...The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.展开更多
Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS)is a severe clinical disorder characterized by widespread inflammation,diffuse alveolar damage,and pulmonary edema,often leading to respiratory failure a...Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS)is a severe clinical disorder characterized by widespread inflammation,diffuse alveolar damage,and pulmonary edema,often leading to respiratory failure and death.Despite significant advances in clinical care,ALI/ARDS remains the leading cause of death among intensive care unit patients.Sepsis is the primary risk factor for the development of ALI/ARDS,as excessive inflammatory responses contribute to organ injury and high mortality in critically ill patients.展开更多
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
BACKGROUND Constipation,a highly prevalent functional gastrointestinal disorder,induces a significant burden on the quality of patients'life and is associated with substantial healthcare expenditures.Therefore,ide...BACKGROUND Constipation,a highly prevalent functional gastrointestinal disorder,induces a significant burden on the quality of patients'life and is associated with substantial healthcare expenditures.Therefore,identifying efficient therapeutic modalities for constipation is of paramount importance.Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms.Consequently,we postulate that hydrogen therapy,an emerging and promising intervention,can serve as a safe and efficacious treatment for constipation.AIM To determine whether hydrogen-rich water(HRW)alleviates constipation and its potential mechanism.METHODS Constipation models were established by orally loperamide to Sprague-Dawley rats.Rats freely consumed HRW,and were recorded their 24 h total stool weight,fecal water content,and charcoal propulsion rate.Fecal samples were subjected to 16S rDNA gene sequencing.Serum non-targeted metabolomic analysis,malondialdehyde,and superoxide dismutase levels were determined.Colonic tissues were stained with hematoxylin and eosin,Alcian blue-periodic acid-Schiff,reactive oxygen species(ROS)immunofluorescence,and immunohistochemistry for cell growth factor receptor kit(c-kit),PGP 9.5,sirtuin1(SIRT1),nuclear factor-erythroid-2-related factor 2(Nrf2),and heme oxygenase-1(HO-1).Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1,Nrf2 and HO-1.A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor,EX527,into constipated rats.NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression.RESULTS HRW alleviated constipation symptoms by improving the total amount of stool over 24 h,fecal water content,charcoal propulsion rate,thickness of the intestinal mucus layer,c-kit expression,and the number of intestinal neurons.HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism.HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway.This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats.The serum metabolites,β-leucine(β-Leu)and traumatic acid,were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1.CONCLUSION HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway,modulating gut microbiota and serum metabolites.β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.展开更多
背景:牙周炎是以牙菌斑生物膜为主要致病物质的炎症性、破坏性疾病,发生于牙龈、牙周膜、牙槽骨和牙骨质。细菌复合体的抗原及其分泌的毒素、酶等直接导致牙周组织的破坏,并引发宿主的免疫反应,使机体组织受到间接损害。沉默信息调节因...背景:牙周炎是以牙菌斑生物膜为主要致病物质的炎症性、破坏性疾病,发生于牙龈、牙周膜、牙槽骨和牙骨质。细菌复合体的抗原及其分泌的毒素、酶等直接导致牙周组织的破坏,并引发宿主的免疫反应,使机体组织受到间接损害。沉默信息调节因子(Sirtuins,SIRTs)在抗衰老、抗氧化应激、调节炎症、介导细胞自噬等方面发挥重要作用,与牙周炎的发生和发展也有着密切的关系。目的:针对Sirtuins在牙周炎中的研究概况做一综述。方法:由第一作者应用计算机在PubMed、Web of Science、中国知网和万方数据库检索涉及Sirtuins在牙周炎中的相关研究,以“Sirtuins,Sirtuin1-7,periodontitis”为英文检索词,“沉默信息调节因子,沉默信息调节因子1-7,牙周炎”为中文检索词,经过筛选后纳入57篇文献进行综述分析。结果与结论:①SIRT1、SIRT2、SIRT3、SIRT6参与调控了牙周炎的发生与发展;②SIRT1:抑制SIRT1表达可能是牙周炎治疗靶点;SIRT1的过表达对牙周炎症有抑制作用,保护牙周组织;SIRT1的激活剂可减轻牙周组织的炎症,并可改善牙周炎引起的全身组织病变;③SIRT2:参与烟酰胺磷酸核糖转移酶介导的牙周炎症,SIRT2在牙周疾病的治疗和转归中发挥一定的作用;④SIRT3:可改善年龄相关的牙周病;天麻素可通过SIRT3的上调促进牙周膜干细胞成骨分化;SIRT3的激活剂通过调节细胞自噬水平,降低牙周炎对牙周和肾脏组织的破坏程度;⑤SIRT6:可抑制牙周组织炎症反应,抑制成牙骨质细胞的分化和矿化;SIRT6对根尖周炎的预后有利;⑥SIRT4、SIRT5、SIRT7与牙周炎的关系鲜有报道。展开更多
Sirtuins蛋白家族具有ADP-核糖基转移酶活性和NAD+依赖性的组蛋白去乙酰基转移酶等多种酶活性,其家族包括Sirtuin1-7,是有名的长寿蛋白大家族,具有控制能量代谢、DNA修复、细胞活性、组织再生、炎症、神经元信号传递等多种生物学功能,...Sirtuins蛋白家族具有ADP-核糖基转移酶活性和NAD+依赖性的组蛋白去乙酰基转移酶等多种酶活性,其家族包括Sirtuin1-7,是有名的长寿蛋白大家族,具有控制能量代谢、DNA修复、细胞活性、组织再生、炎症、神经元信号传递等多种生物学功能,同时在结直肠癌发生发展过程中作为不可替代的调控因素之一。Sirtuin1-7属于同一家族,但Sirtuin1-7表达对结肠癌的发生发展却有不同的影响,与患者预后也存在一定的相关性。本文综述了Sirtuins家族成员概述、在结直肠癌发生发展过程中所表达的生物学功能、作用机制及预后。Sirtuins protein family has various enzyme activities such as ADP-ribosyl transferase activity and NAD+ dependent histone deacetyl transferase activity. Its family includes Sirtuin1-7, which is a well-known family of long-lived proteins. It has various biological functions such as controlling energy metabolism, DNA repair, cell activity, tissue regeneration, inflammation, neuronal signal transmission, etc., and serves as one of the irreplaceable regulatory factors in the occurrence and development of colorectal cancer. Sirtuin1-7 belongs to the same family, but the expression of Sirtuin1-7 has different effects on the occurrence and development of colon cancer, and has a certain correlation with the prognosis of patients. In this review, Sirtuins family members, biological functions, mechanisms of action and prognosis of colorectal cancer were summarized.展开更多
基金funded by FEDER/Ministerio de Ciencia,Innovación y Universidades Agencia Estatal de Investigación/Project(PID2020-119729GB-100,REF/AEI/10.13039/501100011033)(to EP)a predoctoral fellowship from the Spanish Ministry of Universities(FPU)and Amigos de la Universidad de Navarra(to NSS)“Programa MRR Investigo 2023”(to MGB and MMD)。
文摘Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.
基金supported by the Science&Technology Department of Sichuan Province(No.2019YFS0040)the Improvement Plan of“Xinglin Scholar”Scientific Research Talent,Chengdu University of Traditional Chinese Medicine(No.XKTD2022002)。
文摘The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.
基金supported by National Natural Science Foundation of China(82471792,82270004,81870061,82202382,31770945)Beijing Municipal Natural Science Foundation(7242135)Zhejiang Provincial Natural Science Foundation(LY20H010003).
文摘Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS)is a severe clinical disorder characterized by widespread inflammation,diffuse alveolar damage,and pulmonary edema,often leading to respiratory failure and death.Despite significant advances in clinical care,ALI/ARDS remains the leading cause of death among intensive care unit patients.Sepsis is the primary risk factor for the development of ALI/ARDS,as excessive inflammatory responses contribute to organ injury and high mortality in critically ill patients.
基金Supported by National Natural Science Foundation of China,No.82060123Doctoral Start-up Fund of Affiliated Hospital of Guizhou Medical University,No.gysybsky-2021-28+1 种基金Fund Project of Guizhou Provincial Science and Technology Department,No.[2020]1Y299Guizhou Provincial Health Commission,No.gzwjk2019-1-082。
文摘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.
基金Supported by National Natural Science Foundation of China,No.82374449China Postdoctoral Science Foundation,No.2023M731782+1 种基金Jiangsu Funding Program for Excellent Postdoctoral Talent,No.2022ZB806Jiangsu Province Postgraduate Scientific Research and Innovation Plan,No.KYCX23_2136.
文摘BACKGROUND Constipation,a highly prevalent functional gastrointestinal disorder,induces a significant burden on the quality of patients'life and is associated with substantial healthcare expenditures.Therefore,identifying efficient therapeutic modalities for constipation is of paramount importance.Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms.Consequently,we postulate that hydrogen therapy,an emerging and promising intervention,can serve as a safe and efficacious treatment for constipation.AIM To determine whether hydrogen-rich water(HRW)alleviates constipation and its potential mechanism.METHODS Constipation models were established by orally loperamide to Sprague-Dawley rats.Rats freely consumed HRW,and were recorded their 24 h total stool weight,fecal water content,and charcoal propulsion rate.Fecal samples were subjected to 16S rDNA gene sequencing.Serum non-targeted metabolomic analysis,malondialdehyde,and superoxide dismutase levels were determined.Colonic tissues were stained with hematoxylin and eosin,Alcian blue-periodic acid-Schiff,reactive oxygen species(ROS)immunofluorescence,and immunohistochemistry for cell growth factor receptor kit(c-kit),PGP 9.5,sirtuin1(SIRT1),nuclear factor-erythroid-2-related factor 2(Nrf2),and heme oxygenase-1(HO-1).Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1,Nrf2 and HO-1.A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor,EX527,into constipated rats.NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression.RESULTS HRW alleviated constipation symptoms by improving the total amount of stool over 24 h,fecal water content,charcoal propulsion rate,thickness of the intestinal mucus layer,c-kit expression,and the number of intestinal neurons.HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism.HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway.This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats.The serum metabolites,β-leucine(β-Leu)and traumatic acid,were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1.CONCLUSION HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway,modulating gut microbiota and serum metabolites.β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.
文摘背景:牙周炎是以牙菌斑生物膜为主要致病物质的炎症性、破坏性疾病,发生于牙龈、牙周膜、牙槽骨和牙骨质。细菌复合体的抗原及其分泌的毒素、酶等直接导致牙周组织的破坏,并引发宿主的免疫反应,使机体组织受到间接损害。沉默信息调节因子(Sirtuins,SIRTs)在抗衰老、抗氧化应激、调节炎症、介导细胞自噬等方面发挥重要作用,与牙周炎的发生和发展也有着密切的关系。目的:针对Sirtuins在牙周炎中的研究概况做一综述。方法:由第一作者应用计算机在PubMed、Web of Science、中国知网和万方数据库检索涉及Sirtuins在牙周炎中的相关研究,以“Sirtuins,Sirtuin1-7,periodontitis”为英文检索词,“沉默信息调节因子,沉默信息调节因子1-7,牙周炎”为中文检索词,经过筛选后纳入57篇文献进行综述分析。结果与结论:①SIRT1、SIRT2、SIRT3、SIRT6参与调控了牙周炎的发生与发展;②SIRT1:抑制SIRT1表达可能是牙周炎治疗靶点;SIRT1的过表达对牙周炎症有抑制作用,保护牙周组织;SIRT1的激活剂可减轻牙周组织的炎症,并可改善牙周炎引起的全身组织病变;③SIRT2:参与烟酰胺磷酸核糖转移酶介导的牙周炎症,SIRT2在牙周疾病的治疗和转归中发挥一定的作用;④SIRT3:可改善年龄相关的牙周病;天麻素可通过SIRT3的上调促进牙周膜干细胞成骨分化;SIRT3的激活剂通过调节细胞自噬水平,降低牙周炎对牙周和肾脏组织的破坏程度;⑤SIRT6:可抑制牙周组织炎症反应,抑制成牙骨质细胞的分化和矿化;SIRT6对根尖周炎的预后有利;⑥SIRT4、SIRT5、SIRT7与牙周炎的关系鲜有报道。
文摘Sirtuins蛋白家族具有ADP-核糖基转移酶活性和NAD+依赖性的组蛋白去乙酰基转移酶等多种酶活性,其家族包括Sirtuin1-7,是有名的长寿蛋白大家族,具有控制能量代谢、DNA修复、细胞活性、组织再生、炎症、神经元信号传递等多种生物学功能,同时在结直肠癌发生发展过程中作为不可替代的调控因素之一。Sirtuin1-7属于同一家族,但Sirtuin1-7表达对结肠癌的发生发展却有不同的影响,与患者预后也存在一定的相关性。本文综述了Sirtuins家族成员概述、在结直肠癌发生发展过程中所表达的生物学功能、作用机制及预后。Sirtuins protein family has various enzyme activities such as ADP-ribosyl transferase activity and NAD+ dependent histone deacetyl transferase activity. Its family includes Sirtuin1-7, which is a well-known family of long-lived proteins. It has various biological functions such as controlling energy metabolism, DNA repair, cell activity, tissue regeneration, inflammation, neuronal signal transmission, etc., and serves as one of the irreplaceable regulatory factors in the occurrence and development of colorectal cancer. Sirtuin1-7 belongs to the same family, but the expression of Sirtuin1-7 has different effects on the occurrence and development of colon cancer, and has a certain correlation with the prognosis of patients. In this review, Sirtuins family members, biological functions, mechanisms of action and prognosis of colorectal cancer were summarized.
