The role of silent information regulator in periodontitis / 中国组织工程研究

BACKGROUND:Periodontitis is an inflammatory and destructive disease with plaque biofilm as the main pathogenic material,which occurs in the gingiva,periodontal ligament,alveolar bone and cementum.The antigen of bacterial complex and its secreted toxin and enzyme directly lead to the destruction of periodontal tissue and trigger the host's immune response,causing indirect damage to the body tissue.Silence information regulatory factors(Sirtuins,SIRTs)play an important role in anti-aging,anti-oxidative stress,regulating inflammation,and mediating autophagy,and are closely related to the occurrence and development of periodontitis. OBJECTIVE:To review the research status of Sirtuins in periodontitis. METHODS:The first author used the computer to search the relevant research regarding the role of Sirtuins in periodontitis in PubMed,Web of Scene,CNKI and WanFang databases.The key words were"Sirtuins,Sirtuin1-7,periodontitis"in English and Chinese.After literature screening,57 articles were included for review and analysis. RESULTS AND CONCLUSION:SIRT1,SIRT2,SIRT3,and SIRT6 participate in regulating the occurrence and development of periodontitis.Inhibition of SIRT1 expression may be the target of periodontitis treatment,while overexpression of SIRT1 can inhibit periodontitis and protect periodontal tissue.The activator of SIRT1 can reduce the inflammation of periodontal tissue and improve the systemic pathological changes caused by periodontitis.SIRT2 is involved in nicotinamide phosphoribosyltransferase-mediated periodontal inflammation and plays a role in the treatment and prognosis of periodontal diseases.SIRT3 can improve age-related periodontal disease.Gastrodin promotes the osteogenic differentiation of periodontal ligament stem cells through the up-regulation of SIRT3.The activator of SIRT3 reduces the damage of periodontitis to periodontal and renal tissues by regulating the level of autophagy in the cells.SIRT6 can inhibit the inflammatory reaction of periodontal tissue and inhibit the differentiation and mineralization of cementoblasts.SIRT6 is beneficial to the prognosis of periapical periodontitis.The relationship between SIRT4,SIRT5,SIRT7 and periodontitis is rarely reported.

Expression changes of glucose transporters 1/4 and Sirtuins in the retina of diabetic rats / 眼科新进展

Objective To explore the changes in the expression of glucose transporters 1/4(GLUT1/4)and Sirtuins in the retina of rats with diabetes.Methods Twenty 8-week-old healthy male Sprague-Dawley rats were randomly divid-ed into normal control and diabetic groups.Rats in the diabetic group received a disposable intraperitoneal injection of 60 mg·kg-1 streptozotocin to induce the diabetes model,while rats in the normal control group were injected with an equiva-lent amount of solvent.Body weight and blood glucose were measured at 2-week intervals.At 12 weeks after modeling,color Doppler ultrasound was applied to detect blood flow parameters in the central retinal artery(CRA)of rats;after an-esthetizing rats with sodium pentobarbital,eyeballs were harvested,and the pathological changes of rat retinal tissue were observed by hematoxylin & eosin(HE)staining.The expression of messenger ribonucleic acid(mRNA)for GLUT 1/4 and Sirtuins in the retina of rats were detected by immunohistochemical staining,Western blot and quantitative of reverse tran-scription polymerase chain reaction(qRT-PCR),respectively.Results At 12 weeks after modeling,compared with the normal control group,peak systolic velocity and end diastolic velocity were significantly lower in CRA of rats in the diabetic group(both P＜0.001);there were no significant differences in resistance index and pulsatility index(both P＞0.05).The HE staining results at 12 weeks after modeling showed that rats in the normal control group had clear structure in each layer of retinal tissues,closely and regularly arranged cells,and no obvious pathological changes;rats in the diabetic group showed decreased retinal thickness,blurred boundary of each layer,disordered structure and reduced cell number.Immu-nohistochemical staining at 12 weeks after modeling showed that GLUT 1 was mainly located in the retinal pigment epithelial layer of rats,and GLUT 4 was located in the ganglion cell layer,inner plexiform layer and photoreceptor layer.Western blot results showed that the relative expression of GLUT1 and GLUT 4 protein in the diabetic group were lower than that in the normal control group(both P＜0.05),and the relative expression of SIRT1-SIRT7 protein in the retina of rats in the di-abetic group were lower than those of the normal control group(all P＜0.05).qRT-PCR showed a decreased relative ex-pression of SIRT1-SIRT7 mRNA in the retina of rats in the diabetic group compared with that of the normal control group(allP＜0.01).Conclusion Diabetes can cause altered expression of GLUT1/4 and Sirtuins in the retinal tissue of rats,and GLUT1/4 and Sirtuins may be involved in the occurrence and development of diabetic retinopathy.

Inhibition of Oxidative Stress of Sciatic Nerve in Diabetic Rats by Tangbikang Granules Regulating AMPK/PGC-1α/SIRT3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Tangbikang granules on oxidative stress of sciatic nerve in diabetic rats by regulating adenylate activated protein kinase/peroxisome proliferator-activated receptor γ coactivator-1α/mitochondrial Sirtuins 3 （AMPK/PGC-1α/SIRT3） signaling pathway. MethodThe spontaneous obesity type 2 diabetes model was established using ZDF rats. After modeling， they were randomly divided into high， medium， and low dose Tangbikang granule groups （2.5， 1.25， 0.625 g·kg-1·d-1） and lipoic acid group （0.026 8 g·kg-1·d-1）， and the normal group was set up. The rats were administered continuously for 12 weeks after modeling. The blood glucose of rats was detected before intervention and at 4， 8， 12 weeks after intervention. At the 12th week， motor nerve conduction velocity （MNCV）， sensory nerve conduction velocity （SNCV）， nerve blood flow velocity， mechanical pain threshold， and thermal pain threshold were detected. The sciatic nerve was taken for hematoxylin-eosin （HE） staining to observe the tissue morphology. The ultrastructure of the sciatic nerve was observed by transmission electron microscope. The expression levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in sciatic nerve were determined by enzyme-related immunosorbent assay （ELISA）. The mRNA expressions of AMPKα， AMPKβ， PGC-1α， and SIRT3 in sciatic nerve were determined by real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， fasting blood glucose in the model group was increased at each time point （P<0.01）. The mechanical pain threshold was decreased （P<0.05）， and the incubation time of the hot plate was extended （P<0.01）. MNCV， SNCV， and nerve blood flow velocity decreased （P<0.05）. The expression level of SOD was decreased （P<0.01）. The expression levels of MDA， IL-1β， and TNF-α were increased （P<0.01）. The mRNA expression levels of AMPKα， AMPKβ， PGC-1α， and SIRT3 were decreased （P<0.01）. The structure of sciatic nerve fibers in the model group was loose， and the arrangement was disordered. The demyelination change was obvious. Compared with the model group， the fasting blood glucose of rats in the high dose Tangbikang granule group was decreased after the intervention of eight weeks and 12 weeks （P<0.01）. The mechanical pain threshold increased （P<0.05）. The incubation time of the hot plate was shortened （P<0.01）. MNCV， SNCV， and Flux increased （P<0.05）. The expression level of SOD was increased （P<0.01）. The expression levels of MDA， IL-1β， and TNF-α were decreased （P<0.01）. The mRNA expression levels of AMPKα， AMPKβ， PGC-1α， and SIRT3 were increased （P<0.01）. The sciatic nerve fibers in the high-dose Tangbikang granule group were tighter and more neatly arranged， with only a few demyelinating changes. The high， medium， and low dose Tangbikang granule groups showed a significant dose-effect trend. ConclusionTangbikang granules may improve sciatic nerve function in diabetic rats by regulating AMPK/PGC-1α/SIRT3 signaling pathway partly to inhibit oxidative stress.

Association between deacetylase Sirtuins and radiation-induced liver disease / 临床肝胆病杂志

Radiation-induced liver disease （RILD）， also known as radiation hepatitis， is subacute liver injury induced by radiation. As the focus of senescence-related studies， the deacetylase family Sirtuins （SIRTs） have the molecular functions including DNA repair and chromatin regulation， which makes SIRTs a hub for regulating genome and epigenome stability. Radiation-induced hepatic DNA damage and reaction is the primary physiological and pathological process of RILD， which is similar to the function of SIRTs. This article briefly introduces the structure and function of the SIRTs protein family， elaborates on the basic concepts and progress of the physical physiology of radiation therapy， discusses the internal relationship between SIRTs and RILD from the perspective of radiobiology， and points out the possibility of SIRTs as a target for the prevention and treatment of RILD.

Expression of sirtuin 2 and 7 in placenta accreta spectrum

SUMMARY OBJECTIVE: This study aimed to investigate the expression levels of sirtuin 2 and sirtuin 7 in the placenta accreta spectrum to reveal their role in its pathogenesis. METHODS: A total of 30 placenta accreta spectrum, 20 placenta previa, and 30 controls were experienced. The sirtuin 2 and sirtuin 7 expression levels in the placentas of these groups were determined by Western blot. sirtuin 2 and sirtuin 7 serum levels in the maternal and fetal cord blood were examined by enzyme-linked immunosorbent assay. RESULTS: It was found that sirtuin 7 in placenta accreta spectrum was significantly lower in the placenta compared to the control and placenta previa groups (p<0.05). However, a significant difference was not observed between the sirtuin 2 and sirtuin 7 levels in the maternal and fetal cord serum samples of those three groups (p>0.05). CONCLUSION: Sirtuin 7 may play an important role in the formation of placenta accreta spectrum. The effect of decreased expression of sirtuin 7 might be tissue-dependent in the placenta accreta spectrum and needs to be investigated further.

Evaluación y caracterización de la sirtuina 2.3 de Giardia duodenalis (CdSir2.3)

La giardiasis es la enfermedad gastrointestinal de mayor incidencia mundial, causada por el protozoario Giardia duodenalis, para la cual no se cuenta con una vacuna o tratamiento eficiente. En aras de buscar nuevos blancos farmacológicos contra este parásito, se han estudiado las enzimas del metabolismo energético, como las sirtuinas, deacetilasas dependientes del dinucleótido de adenina y nicotinamida (NAD). Previamente se identificó a GdSir2.1 y GdSir2.2 como deacetilasas dependientes de NAD, con localizaciones subcelulares diferentes. En este trabajo se estudió otro candidato a sirtuina (GdSir2.3) mediante herramientas bioinformáticas para la identificación de características típicas de la familia sirtuina en la secuencia del candidato, y experimentales como la obtención de la proteína recombinante 6xHis-GdSir2.3 que demostró actividad deacetilasa dependiente de NAD y que sirvió como antígeno en la producción de los IgY - α -6xHis-GdSir2.3 para la localización subcelular de la proteína endógena en G. duodenalis. Lo anterior concuerda con otros estudios donde se señala a GdSir2.3 como un importante regulador de la enquistación, debido a su aumento de expresión durante esta etapa del ciclo de vida, constituyéndola como un blanco farmacológico promisorio para el control de esta parasitemia.

Giardiasis is the gastrointestinal disease with the highest incidence worldwide, caused by the protozoan Giardia duodenalis, for which there is no vaccine or efficient treatment. In order to find new pharmacological targets against this parasite, energy metabolism enzymes such as sirtuins, deacetylases dependent on the nicotinamide adenine dinucleotide (NAD), have been studied. GdSir2.1 and GdSir2.2 were previously identified as NAD-dependent deacetylases, with different subcellular locations. In this work, another candidate for sirtuin (GdSir2.3) was studied using bioinformatic tools for the identification of typical characteristics of the sirtuin family in the sequence of the candidate; and experimental ones such as obtaining the recombinant protein 6xHis-GdSir2.3 that demonstrated NAD-dependent deacetylase activity; and that it served as an antigen in the production of IgY - α - 6xHis-GdSir2.3 for the subcellular localization of the endogenous protein in G. duodenalis. The foregoing is consistent with other studies where GdSir2.3 is indicated as an important regulator of encyst due to its increased expression during this stage of the life cycle, constituting it as a promising drug target for the control of this parasitaemia.

A giardíase é a doença gastrointestinal de maior incidência no mundo, causada pelo protozoário Giardia duodenalis, para a qual não existe vacina ou tratamento eficaz. Com o objetivo de encontrar novos alvos farmacológicos contra esse parasita, têm sido estudadas enzimas do metabolismo energético, como as sirtuínas, desacetilases dependentes do dinucleotídeo adenina nicotinamida (NAD). GdSir2.1 e GdSir2.2 foram previamente identificados como desacetilases dependentes de NAD, com diferentes localizações subcelulares. Neste trabalho, outro candidato a sirtuin (GdSir2.3) foi estudado usando ferramentas de bioinformática para a identificação de características típicas da família sirtuin na sequência do candidato; e experimentais, como a obtenção da proteína recombinante 6xHis-GdSir2.3 que demonstrou atividade desacetilase dependente de NAD; e que serviu como antígeno na produção de IgY - α - 6xHis-GdSir2.3 para a localização subcelular da proteína endógena em G. duodenalis. O exposto é consistente com outros estudos em que o GdSir2.3 é apontado como um importante regulador de encisto devido à sua expressão aumentada durante esta fase do ciclo de vida, constituindo-se como um alvo promissor para o controle dessa parasitemia.

Roles of NAD / 中国生物化学与分子生物学报

Nicotinamide adenine dinucleotide (NAD

Metabolic choreography of gene expression: nutrient transactions with the epigenome

Eukaryotic complexity and thus their ability to respond to diverse cues are largely driven by varyingexpression of gene products, qualitatively and quantitatively. Protein adducts in the form of post-translationalmodifications, most of which are derived from metabolic intermediates, allow fine tuning of gene expressionat multiple levels. With the advent of high-throughput and high-resolution mapping technologies there hasbeen an explosion in terms of the kind of modifications on chromatin and other factors that govern geneexpression. Moreover, even the classical notion of acetylation and methylation dependent regulation oftranscription is now known to be intrinsically coupled to biochemical pathways, which were otherwiseregarded as ‘mundane’. Here we have not only reviewed some of the recent literature but also havehighlighted the dependence of gene regulatory mechanisms on metabolic inputs, both direct and indirect. Wehave also tried to bring forth some of the open questions, and how our understanding of gene expression haschanged dramatically over the last few years, which has largely become metabolism centric. Finally,metabolic regulation of epigenome and gene expression has gained much traction due to the increasedincidence of lifestyle and age-related diseases.

The role of Sirtuins in the study of eye diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#In a variety of eye diseases, such as glaucoma, macular degeneration and other diseases, the occurrence of oxidative stress is very common, oxidative stress can cause cell damage and apoptosis. The Sirtuins family(histone class III deacetylases), as regulators of a variety of cells, is widely expressed in various organs of the human body. Homologous genes of sirtuins(SIRT1)are also widely expressed in the eyes, and their expression and activation can play an anti-oxidative stress role, prevent cell senescence and damage, and thus prevent the progression of disease. This paper discusses the mechanism and expression of Sirtuins family in glaucoma, senile macular degeneration, optic neuritis and senile cataract.

Serum Sirtuin 1, 3 and 6 Levels in Acute Myocardial Infarction Patients / Níveis de Sirtuína 1, 3 e 6 em Pacientes com Infarto Agudo do Miocárdio

Abstract Background: Sirtuins may act in many cellular processes like apoptosis, DNA repair and lipid/glucose metabolism. Experimental studies suggested some sirtuin types may have protective effects against endothelial dysfunction, atherosclerosis, cardiac hypertrophy and reperfusion injury. Data about sirtuins in acute myocardial infarction (AMI) patients are scarce. Objectives: To investigate temporal changes of serum sirtuin 1,3 and 6 levels in AMI patients; to compare the serum sirtuin 1,3 and 6 levels between AMI patients and control subjects; and to investigate the association of serum sirtuin 1,3 and 6 levels with prognostic markers of AMI. Methods: Forty patients with AMI and 40 patients with normal coronary arteries were included. Left ventricular ejection fraction (LVEF), serum proBNP, CRP, sirtuin1, sirtuin 3 and sirtuin 6 levels were processed. Peak troponin T levels, GRACE score, first day / second day sirtuin levels were recorded of AMI patients. A p value < 0.05 was considered statistically significant. Results: Serum sirtuin 1,3 and 6 levels in AMI patients were similar to those in normal coronary patients. No temporal change in serum sirtuin 1,3 and 6 levels were found in AMI course. No correlation was evident between the sirtuin levels and the following parameters: proBNP, CRP, peak troponin and LVEF. Baseline sirtuin 1 and 6 levels were positively correlated with reperfusion duration. Baseline sirtuin 3 levels were negatively correlated with GRACE score. Conclusion: Serum sirtuin 1,3 and 6 levels in AMI patients were similar to those in normal coronary patients. This study does not represent evidence of the possible protective effects of sirtuin1, 3 and 6 in AMI patients.

Resumo Fundamento: As sirtuínas podem atuar em muitos processos celulares, como a apoptose, reparo de DNA e metabolismo de lipídios e de glicose. Estudos experimentais sugeriram que alguns tipos de sirtuínas possam ter efeitos protetores contra disfunção endotelial, aterosclerose, hipertrofia cardíaca e lesão decorrente de reperfusão. Dados sobre as sirtuínas em pacientes com infarto agudo do miocárdio (IAM) são escassos. Objetivos: Avaliar as mudanças temporais dos níveis de sirtuína 1, 3 e 6 entre pacientes com IAM e indivíduos controles; investigar a associação entre os níveis de sirtuína 1, 3 e 6 e marcadores prognósticos de IAM. Métodos: Quarenta pacientes com IAM e 40 pacientes com artérias coronárias normais foram incluídos. Foram avaliados fração de ejeção do ventrículo esquerdo (FEVE), concentrações séricas de pró-BNP, proteína C-reativa, sirtuína 1, sirtuína 3 e de sirtuína 6. Pico de troponina T, escore GRACE, concentrações de sirtuínas no primeiro e no segundo dia foram registrados dos pacientes com IAM. Um valor de p<0,05 foi considerado estatisticamente significativo. Resultados: Os níveis de sirtuína 1, 3 e 6 em pacientes com IAM foram similares aos de pacientes com coronária normal. Não foram observadas mudanças temporais nos níveis de sirtuína 1, 3 e 6 no curso do IAM. Nenhuma correlação evidente foi observada dos níveis de sirtuína com os seguintes parâmetros: pró-BNP, proteína C-reativa, pico de troponina e FEVE. Níveis basais de sirtuína 1 e 6 apresentaram correlação positiva com a duração da reperfusão. Os níveis basais de sirtuína 3 correlacionaram-se negativamente com o escore GRACE. Conclusão: Os níveis de sirtuína 1, 3 e 6 em pacientes com IAM foram similares aos de pacientes com artérias coronárias normais. Este estudo não apresenta evidência de possíveis efeitos protetores da sirtuína 1, 3 e 6 em pacientes com IAM.

Emodin exerts protective effect against palmitic acid-induced endoplasmic reticulum stress in HepG2 cells / 한국영양학회지

PURPOSE: Protein overloading in the endoplasmic reticulum (ER) leads to endoplasmic reticulum stress, which exacerbates various disease conditions. Emodin, an anthraquinone compound, is known to have several health benefits. The effect of emodin against palmitic acid (PA) - induced ER stress in HepG2 cells was investigated. METHODS: HepG2 cells were treated with varying concentrations of palmitic acid to determine the working concentration that induced ER stress. ER stress associated genes such as ATF4, XBP1s, CHOP and GRP78 were checked using RT- PCR. In addition, the expression levels of unfolded protein response (UPR) associated proteins such as IRE1α, eIF2α and CHOP were checked using immunoblotting to confirm the induction of ER stress. The effect of emodin on ER stress was analyzed by treating HepG2 cells with 750 µM palmitic acid and varying concentrations of emodin, then analyzing the expression of UPR associated genes. RESULTS: It was evident from the mRNA and protein expression results that palmitic acid significantly increased the expression of UPR associated genes and thereby induced ER stress. Subsequent treatment with emodin reduced the mRNA expression of ATF4, GRP78, and XBP1s. Furthermore, the protein levels of p-IRE1α, p-elF2α and CHOP were also reduced by the treatment of emodin. Analysis of sirtuin mRNA expression showed that emodin increased the levels of SIRT4 and SIRT7, indicating a possible role in decreasing the expression of UPR-related genes. CONCLUSION: Altogether, the results suggest that emodin could exert a protective effect against fatty acid-induced ER stress and could be an agent for the management of various ER stress related diseases.

Effects of Mitochondrial Dysfunction via AMPK/PGC-1 α Signal Pathway on Pathogenic Mechanism of Diabetic Peripheral Neuropathy and the Protective Effects of Chinese Medicine / 中国结合医学杂志

Diabetic peripheral neuropathy (DPN) is a progressive neurodegenerative disease of peripheral nervous system with high energy requirement. The adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor- γ coactivator 1 α (PGC-1 α) axis plays a key role in regulating mitochondrial energy metabolism. Increasing preclinical evidences have shown that inhibition of AMPK/PGC-1 α pathway leading to mitochondrial dysfunction in neurons or Schwann cells contributes to neuron apoptosis, distal axonopathy and nerve demyelination in DPN. Some Chinese medicine formulae or extracts from herbs may have potential neuroprotective effects on DPN via activating AMPK/PGC-1 α pathway and improving mitochondrial function.

Combatiendo el metabolismo de las células cancerosas mediante la activación de SIRT3 y el ejercicio físico / Combating tumor cells through SIRT3 activation and exercise

One of the main features of cancer is the high rate of cell proliferation and growth. To do this, cancer cells need to redirect their metabolism mainly towards anaerobic glycolysis and an increased mitochondrial glutamine energy metabolism. Sirtuins are cellular proteins with regulatory functions on metabolic pathways, genomic stability, apoptosis, longevity, inflammation, energy metabolism and oxidative stress. Sirtuins have emerged recently as a potential therapeutic option to treat several chronic diseases including cancer. This review summarizes the tumor suppressor function of Sirtuin 3 (SIRT3), highlighting its repressor effect on glycolytic metabolism, promoting mitochondrial metabolism and oxidative stress reduction. SIRT3 activation by exercise is particularly described since it may represent a potent tool for several types of cancer treatment.

Role of short-term starvation in alleviating hepatic ischemia-reperfusion injury in mice and possible mechanism of action / 中华肝脏病杂志

Objective@#To investigate the role of short-term starvation (STS) in alleviating hepatic ischemia-reperfusion injury in mice and possible mechanism of action.@*Methods@#Wild-type male C57BL/6 mice aged 8 weeks were randomly divided into 75% hepatic ischemia-reperfusion injury group (IR group), STS+75% hepatic ischemia-reperfusion injury group (STS group), and sirtinol+STS+75% hepatic ischemia-reperfusion injury group (SIR group), using a random number table, and sham-operation groups (IR-Sham group, STS-Sham group, and SIR-Sham group) were also established. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, and the histomorphological changes of the liver were observed, as well as the expression of Sirt1, LC3B, and P62 proteins in liver tissue and the results of LC3B fluorescence staining. An analysis of variance was used for comparison of data between multiple groups, and the t-test was used for comparison of data between two groups.@*Results@#Compared with the IR group, the STS group had significant reductions in the serum levels of ALT (3 152.7 ± 735.6 U/L vs 8 414.2 ± 1 052.2 U/L, P < 0.01) and AST (3 577.0 ± 714.0 U/L vs 10 845.8 ± 1 145.7 U/L, P < 0.01) and significant alleviation of liver pathological injury (Suzuki score: 1.50±0.55 vs 3.50±0.55, P < 0.01). Compared with the STS group, the SIR group had significant increases in the serum levels of ALT (7 002.7 ± 1 485.2 U/L vs 3 152.7 ± 735.6 U/L, P < 0.01) and AST (8 980.7 ± 1 739.1 U/L vs 3 577.0 ± 714.0 U/L, P < 0.01) and significant exacerbation of liver pathological injury (Suzuki score: 3.33 ± 0.52 vs 1.50 ± 0.55, P < 0.01). Compared with the IR group and the IR-Sham group, the STS group and the STS-Sham group had significant increases in the mRNA and protein expression of Sirt1 and the protein expression of LC3B and a significant reduction in the protein expression of P62, as well as a significant increase in the percentage of LC3B-positive cells in liver tissue (22.83% ± 5.19% / 22.17% ± 4.83% vs 10.16% ± 3.06% / 10.83% ± 1.94%, both P < 0.01). Compared with the STS group and the STS-Sham group, the SIR group and the SIR-Sham group had significant reductions in the expression of Sirt1 and LC3B proteins and a significant increase in the expression of P62 protein, as well as a significant reduction in the percentage of LC3B-positive cells in liver tissue (11.83% ± 9.24% / 14.67% ± 4.68% vs 22.83% ± 5.19% / 22.17% ± 4.83%, both P < 0.01).@*Conclusion@#STS can effectively alleviate hepatic ischemia-reperfusion injury, and its protective effect may be associated with increasing the expression of Sirt1, inducing and promoting hepatocyte autophagy, and reducing hepatocyte death.

Research progress of the relationship between Sirtuins and diabetic retinopathy / 中华实验眼科杂志

As one of the serious complications of diabetes melitus,diabetic retinopathy (DR) is one of the major causes of blindness.It is urgent to figure out the mechanism of DR and identify an effective therapeutic target to prevent it.Sirtuins is a major catabolic pathway involved in degrading and recycling damaged organelles and macromolecules to maintain intracellular homeostasis.The study of Sirtuins in mammalian systems has been advancing rapidly and revealed that Sirtuins is involved in the pathogenesis of various metabolic and age-related diseases.The study of Sirtuins in such diseases as tumors,diabetic nephropathy,has been currently under intense investigation.Moreover,there is also a close relationship between Sirtuins and DR related factors including hypoxia,oxidative stress,inflammation,and so on.In this paper,recent research progress in Sirtuins and its application in DR are reviewed,so as to provide a new perspective on pathogenesis and therapy of DR.

Relationship between SIRT1-ERK1∕2 pathway and chikusetsu saponin IVa-induced reduction of isoflurane-elicited neurotoxicity in fetal rats: an in vitro experiment / 中华麻醉学杂志

Objective To evaluate the relationship between silent information regulator 1 ( SIRT1)-extracellular-regulated kinase1∕2 ( ERK1∕2) pathway and chikusetsu saponin IVa-induced reduc-tion of isoflurane-elicited neurotoxicity in fetal rats in an in vitro experiment. Methods The hippocampal neurons isolated from rats at 16-18 days of gestation were primarily cultured for 7 days and divided into 3 groups ( n = 6 each) using a random number table method: control group ( Con group) , isoflurane group (Iso group) and chikusetsu saponin IVa plus isoflurane group (ChIV+Iso group). Hippocampal neurons were cultured routinely for 6 h in Con group. Hippocampal neurons were exposed to 1. 8％ isoflurane for 6 h in an incubator in Iso group. Chikusetsu saponin IVa 25μg∕ml was added to the culture medium, and hipp-ocampal neurons were incubated for 6 h and then exposed to 1. 8％ isoflurane for 6 h in an incubator in ChIV+Iso group. The supernatant was collected for determination of the amount of lactic dehydrogenase ( LDH) released, neuronal viability ( by CCK-8) and expression of SIRT1, ERK1∕2 and phosphorylated ERK1∕2 ( p-ERK1∕2) ( by Western blot) . Results Compared with Con group, the neuronal viability was significantly decreased, the amount of LDH released was increased, and the expression of SIRT1 and p-ERK1∕2 was down-regulated in Iso group ( P<0. 05) . Compared with Iso group, the neuronal viability was significantly increased, the amount of LDH released was decreased, and the expression of SIRT1 and p-ERK1∕2 was up-regulated in ChIV+Iso group ( P<0. 05) . Conclusion The mechanism by which chikuset-su saponin IVa reduces isoflurane-elicited neurotoxicity is related to activating SIRT1-ERK1∕2 pathway in fe-tal rats in an in vitro experiment.

Role of SIRT3∕FOXO3α signaling pathway in dexmedetomidine-induced reduction of hepatic ische-mia-reperfusion injury in mice / 中华麻醉学杂志

Objective To evaluate the role of sirtuin 3 ( SIRT3)∕forkhead box O3α ( FOXO3α) signaling pathway in dexmedetomidine-induced reduction of hepatic ischemia-reperfusion ( I∕R) injury in mice. Methods Forty clean-grade C57BL∕6 mice of both sexes, aged 2 weeks, weighing 6-8 g, were di-vided into 4 groups (n＝10 each) using a random number table method: sham operation group (group S), hepatic I∕R group ( group I∕R), dexmedetomidine group ( group D) and SIRT3 inhibitor 3-TYP plus dexmedetomidine group (group T+D). Portal vein and hepatic artery supplying left and middle lobes of the liver and biliary tract were clamped resulting in ischemia of 70% of the liver in anesthetized rats. Normal sa-line 0. 25 ml was intraperitoneally injected at 1 h before establishing model, and 30 min later dexmedetomi-dine 50 μg∕kg (diluted to 0. 25 ml in normal saline) was intraperitoneally injected in group D. In group T+D, 3-TYP 5 mg∕kg (diluted to 0. 25 ml in normal saline) was intraperitoneally injected at 1 h before estab-lishing model, and 30 min later dexmedetomidine 50 μg∕kg (diluted to 0. 25 ml in normal saline) was in-traperitoneally injected. Mice were selected at 6 h after reperfusion, blood samples were obtained through eyeball, and the mice were then sacrificed and kidneys were removed for determination of the serum concen-trations of creatinine (Cr) and blood urea nitrogen (BUN), cell apoptosis (by TUNEL), malondialdehyde (MDA) content (using thiobarbituric acid method), superoxide dismutase (SOD) activity (by xanthine oxidase method), and acetylation of FOXO3α in renal tissues (by using immunoprecipitation) and for ex-amination of the pathologic changes. The damage to renal tubules was scored. Apoptosis index ( AI) was calculated. Results Compared with group S, the renal tubular damage score and AI were significantly in-creased, serum concentrations of Cr and BUN were increased, the content of MDA was increased, the ac-tivity of SOD was decreased, and the acetylation of FOXO3α was decreased in I∕R, D and T+D groups ( P＜0. 05). Compared with group I∕R, the renal tubular damage score and AI were significantly decreased, serum concentrations of Cr and BUN were decreased, the content of MDA was decreased, the activity of SOD was increased, and the acetylation of FOXO3α was decreased in group D (P＜0. 05), and no signifi-cant change was found in the parameters mentioned above in group T+D (P＞0. 05). Compared with group D, the renal tubular damage score and AI were significantly increased, serum concentrations of Cr and BUN were increased, the content of MDA was increased, the activity of SOD was decreased, and the acetylation of FOXO3α was decreased in group T+D ( P＜0. 05). Conclusion Activation of SIRT3∕FOXO3α signaling pathway is involved in dexmedetomidine-induced reduction of hepatic I∕R injury in mice.

Silent information regulator protein 6 and autophagy in age-related macular degeneration / 中华眼底病杂志

Age-related macular degeneration is one of the major causes of blindness in the elderly.As an important pathway of cell metabolism,autophagy maintains intracellular homeostasis through the degradation and recycle of damaged organelles and macromolecules.Understanding its mechanism may promote discoveries to delay aging process,reduce the incidence of age-related diseases.In mammals,silent information regulator protein 6 (SIRT6) plays its deacetylase and ribonucleotransferase activity in multiple signaling pathways,including inhibition of cellular senescence,tumorigenesis,metabolic diseases,regulating cellular lifespan.It has a significant impact on the structure and function of tissues and organs.SIRT6 regulates intracellular autophagy mainly through the insulin-like growth factor-protein kinase B-mammalian target of rapamycin,reducing the accumulation of toxic metabolites and cellular senescence.The function of SIRT6 in age-related macular degeneration need to be combined with the genetic background,pathogenesis,clinical manifestations and other aspects of the disease,and it is expected to be further studied in subsequent studies.

Sirtuins in malignant progression of tumor / 药学学报

As a post-translational modification, protein acetylation plays an important role in the regulation of apoptosis, mitochondriopoiesis, lipid metabolism and cellular stress response. The imbalance of acetylation and deacetylation has been blamed for the tumorigenesis and malignant progression, which is gradually considered as a promising therapeutic target. Mammalian sirtuins, a NAD+ dependent class Ⅲ HDACs, are closely related to the development of aging, tumor, diabetes, obesity and neurodegenerative diseases. To provide a theoretical basis for the development of new anti-tumor drugs and the treatment of malignant tumors, this paper is prepared to focus on the irreplaceable role of sirtuins in tumor evolution:maintaining genomic stability, regulating energy metabolism, and facilitating tumor cells stemness. The modulator and pathways of sirtuins family and the research progress of agonists and inhibitors are also reviewed. The functions of SIRT2 in resistance, proliferation and metastasis have been highlighted.