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Sustained activation of the SIRT3-NLRP3 inflammasome has been associated with worse outcomes after ischemic stroke. The objective of this study was to examine the potential mechanism by which the SIRT3-NLRP3 inflammasome affects neural stem and progenitor cells (NSPCs) after transient middle cerebral artery occlusion (tMCAO) in rats. Following tMCAO, significantly elevated levels of NLRP3, ASC, cleaved caspase 1, IL-1β, and IL-18 were observed in the ischemic subventricular zone. Moreover, tMCAO increased NLRP3 expression while decreasing SIRT3 levels, suggesting a connection between these two processes. Furthermore, we discovered that inflammation induced by the NLRP3 inflammasome impaired post-stroke hippocampal and subventricular neurogenesis, while nestin (a marker for NSPCs) and Sox2 (a marker for stem cell pluripotency) were downregulated after tMCAO. However, systemic administration of MCC950 reduced inflammatory signaling and effectively restored neurogenesis. Overall, our results suggest that protecting NSPCs and neurogenesis in the ischemically damaged brain by mitigating the impact of the SIRT3-NLRP3 inflammasome may be a feasible treatment strategy for ischemic stroke., Competing Interests: Declaration of Competing Interest AABR is inventor of intellectual property (WO2016131098, WO2017140778, WO2018215818), granted in multiple jurisdictions, which discloses NLRP3 inhibitors for treatment of inflammatory diseases. These patents are licensed to Inflazome Ltd., which sold to Roche in 2020, and the compounds disclosed are progressing through clinical trials., (Copyright © 2025 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Compound K (CK), an active ingredient in ginseng, has anti-cancer, anti-inflammatory, and antioxidant properties. However, its effects on thermogenesis and mitochondrial dynamics in white adipose tissue (WAT) adipocytes are not well understood. This study explores CK's impact on thermogenesis and mitochondrial metabolism in cold-exposed mice and mouse stromal vascular fraction (SVF) cells. CK increased the expression of UCP1 and other brown/beige adipocyte markers (Cd137, Cytb, Letm1, Pgc1α, Prdm16, Tbp1, Tbx1, Uqcrc1) and mitochondrial biogenesis/dynamics factors (Cidea, Cox8b, Cycs, Dio2, Drp1, Fis1, Fgf21, Nrf1, Sirt3, Tfam) in 3T3-L1/iWAT SVF cells. CK enhanced mitochondrial respiration, reduced mitochondrial ROS levels, and restored MMP in iWAT SVF cells, leading to the differentiation of WAT into beige adipocytes, and that was also observed in cold-exposed subcutaneous tissue. CK administration to cold-exposed mice reduced fat droplet size and increased the number of mitochondria. Additionally, CK stimulated non-shivering thermogenesis, indicated by the upregulation of thermogenic and mitochondrial division proteins. The browning effect of CK was nullified by SIRT3 knockdown, suggesting that CK induces beige remodeling of WAT by regulating mitochondrial dynamics and SIRT3 expression. These findings suggest CK's potential as a therapeutic agent for obesity and metabolic disorders that promotes the transformation of WAT into a metabolically active beige phenotype., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Albumin has a variety of biological functions, such as immunomodulatory and antioxidant activity, which depends largely on its thiol activity. However, in clinical trials, the treatment of albumin by injection of commercial human serum albumin (HSA) did not achieve the desired results. Here, we constructed reduced modified albumin (SH-Alb) for in vivo and in vitro experiments to investigate the reasons why HSA did not achieve the expected effects. SH-Alb was found to delay the progression of liver fibrosis in mice by alleviating liver inflammation and oxidative stress. Although R-Alb also has some of the above roles, the effect of SH-Alb is more remarkable. Mechanism studies have shown that SH-Alb reduces the release of pro-inflammatory and pro-fibrotic cytokine through the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, SH-Alb deacetylates SOD2, a key enzyme of mitochondrial reactive oxygen species (ROS) production, by promoting the expression of SIRT3, thereby reducing the accumulation of ROS. Finally, macrophages altered by R-Alb or SH-Alb can inhibit the activation of hepatic stellate cells and endothelial cells, further delaying the progression of liver fibrosis. These results indicate that SH-Alb can remodel the phenotype of macrophages, thereby affecting the intrahepatic microenvironment and delaying the process of liver fibrosis. It provides a good foundation for the application of albumin in clinical treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024. Published by Elsevier Masson SAS.)

Ischemic heart disease invariably leads to devastating damage to human health. Nicotinamide ribose (NR), as one of the precursors of NAD + synthesis, has been discovered to exert a protective role in various neurological and cardiovascular disorders. Our findings demonstrated that pretreatment with 200 mg/kg NR for 3 h significantly reduced myocardial infarct area, decreased levels of CK-MB and LDH in serum, and improved cardiac function in the rats during myocardial ischemia-reperfusion (I/R) injury. Meanwhile, 0.5 mM NR also effectively increased the viability and decreased the LDH release of H9c2 cells during OGD/R. We had provided evidence that NR pretreatment could decrease mitochondrial reactive oxygen species (mtROS) production and MDA content, and enhance SOD activity, thereby mitigating mitochondrial damage and inhibiting apoptosis during myocardial I/R injury. Further investigations revealed that NR increased NAD + content and upregulated SIRT3 protein expression in myocardium. Through using of SIRT3 small interfering RNA and the SIRT3 deacetylase activity inhibitor 3-TYP, we had confirmed that the cardioprotective effect of NR on cardiomyocytes was largely dependent on the inhibition of mitochondrial oxidative stress via SIRT3-SOD2 axis. Overall, our study suggested that exogenous supplementation with NR mitigated mitochondrial damage and inhibited apoptosis during myocardial I/R injury by reducing mitochondrial oxidative stress via SIRT3-SOD2-mtROS pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Increasing global overweight and obesity rates not only increase the prevalence of myocardial infarction (MI), but also exacerbate ischemic injury and result in worsened prognosis. Currently, there are no drugs that can reverse myocardial damage once MI has occurred, therefore discovering drugs that can potentially limit the extent of ischemic damage to the myocardium is critical. Resveratrol is a polyphenol known for its antioxidant properties, however whether prolonged daily intake of resveratrol during obesity can protect against MI-induced damage remains unexplored., Methods: We established murine models of obesity via high-fat/high-fructose diet, along with daily administrations of resveratrol or vehicle, then performed surgical MI to examine the effects and mechanisms of resveratrol in protecting against myocardial ischemic injury., Results: Daily administration of resveratrol in obese mice robustly protected against myocardial ischemic injury and improved post-MI cardiac function. Resveratrol strongly inhibited oxidative and DNA damage via activating SIRT3/FOXO3a-dependent antioxidant enzymes following MI, which were completely prevented upon administration of 3-TYP, a selective SIRT3 inhibitor. Hence, the cardioprotective effects of prolonged resveratrol intake in protecting obese mice against myocardial ischemic injury was due to reestablishment of intracellular redox homeostasis through activation of SIRT3/FOXO3a signaling pathway., Conclusion: Our findings provide important new evidence that supports the daily intake of resveratrol, especially in those overweight or obese, which can robustly decrease the extent of ischemic damage following MI. Our study therefore provides new mechanistic insight and suggests the therapeutic potential of resveratrol as an invaluable drug in the treatment of ischemic heart diseases., Competing Interests: Declaration of Competing Interest The authors confirm that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Chronic Liver fibrosis may progress to liver cirrhosis and hepatocellular carcinoma (HCC), hence cause a substantial global burden. However, effective therapies for blocking fibrosis are still lacking. Although mesenchymal stem cells (MSCs) have been proven beneficial to liver regeneration after damage, the underlying mechanism of their therapeutic effects are not fully understood. Oxidative stress and mitochondrial functionality alteration directly contributes to the hepatocyte apoptosis and development of liver fibrosis. This study aims to elucidate the mechanism by which hUC-MSC alleviates liver fibrosis and mitochondrial dysfunction. RNA-sequencing was performed to characterize the transcriptomic changes after implantation of hUC-MSCs in mice with liver fibrosis. Next, western blot, RT-PCR, immunohistochemical and immunofluorescence staining were used to evaluate the expression of different genes in vitro and in vivo. Additionally, mitochondrial morphological and dynamic changes, ROS content, and ATP production were examined. Slc25a47, a newly identified liver-specific mitochondrial NAD + transporter, was notably reduced in CCl 4 -treated mice and H 2 O 2 -stimulated hepatocytes. Conversely, hUC-MSCs increased the Slc25a47 expression and NAD + level within mitochondria, thereby enhanced Sirt3 protein activity and alleviated mitochondrial dysfunction in the liver. Furthermore, Slc25a47 knockdown could partially abrogate the protective effects of hUC-MSCs on H 2 O 2 -induced mitochondrial fission and oxidative stress in hepatocytes. Our study illustrates that Slc25a47 is a key molecular for hUC-MSCs to improve liver fibrosis and regulates mitochondrial function through Sirt3 for the first time, and providing a theoretical basis for the clinical translation of hUC-MSCs transplantation in the treatment of patients with liver fibrosis/cirrhosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Dysregulation of mitochondrial homeostasis is common to all types of cardiovascular diseases. SIRT3 regulates apoptosis and autophagy, material and energy metabolism, mitochondrial oxidative stress, inflammation, and fibrosis. As an important mediator and node in the network of mechanisms, SIRT3 is essential to many activities. This review explains how SIRT3 regulates mitochondrial homeostasis and the tricarboxylic acid cycle to treat common cardiovascular diseases. A novel description of the impact of lifestyle factors on SIRT3 expression from the angles of nutrition, exercise, and temperature is provided., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Cyclovirobuxine D (CVB-D) is a natural alkaloid that exhibits multiple pharmacological activities, such as anti-inflammatory, anti-oxidative stress, and anti-cancer properties. However, its specific protective mechanism of action for myocardial hypertrophy remains unresolved., Purpose: This work was to investigate the ameliorative impact of CVB-D in myocardial hypertrophy, and to elucidate aldosterone (ALD)-induced myocardial hypertrophy by inhibiting the SIRT3 mediated Nrf2 activation., Methods: The myocardial hypertrophy model was reproduced by ALD both in vitro and in vivo, and the protective effect of CVB-D on myocardium and mitochondria was evaluated by TEM, H&E, qPCR, Western blot and ChIP. An immunoprecipitation experiment was adopted to evaluate the acetylation level of Nrf2 and the binding between SIRT3 and Nrf2. Additionally, bardoxolone-methyl (BAR, an Nrf2 agonist), ML385 (an Nrf2 inhibitor), resveratrol (RES, a SIRT3 agonist), and 3-TYP (a SIRT3 inhibitor) were used to confirm the molecular mechanism of CVB-D. Lastly, a molecular docking technique was employed to predict the binding site of SIRT3 and Nrf2 proteins., Results: Our findings suggested that CVB-D improved mitochondrial function, leading to a reduction in ALD-induced cardiomyocyte hypertrophy. By CVB-D treatment, there was an activation of mutual regulation between Nrf2 and SIRT3. Specifically, CVB-D resulted in the increase of Nrf2 protein in the nucleus and activated Nrf2 signaling pathway, thus up-regulating SIRT3. The activation of SIRT3 and the protective action of mitochondrion disappeared because of the intervention of ML385. After CVB-D activated SIRT3, the acetylation level of Nrf2 decreased, followed by activating the Nrf2 pathway. The activation of Nrf2 and mitochondrial protection by CVB-D were reversed by 3-TYP. Our results are also supported by Co-IP and molecular docking analysis, revealing that CVB-D promotes SIRT3-mediated Nrf2 activation., Conclusion: Thus, CVB-D ameliorates ALD-induced myocardial hypertrophy by recovering mitochondrial function by activating the mutual regulation of Nrf2 and SIRT3. Thus, CVB-D could be a beneficial drug for myocardial hypertrophy., Competing Interests: Declaration of Competing Interest Please declare any financial or personal interests that might be potentially viewed to influence the work presented. Interests could include consultancies, honoraria, patent ownership or other. If there are none state ‘there are none’., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Aim: To examine the protective effect of vitamin B12 against myocardial ischemia/reperfusion (I/R) injury and elucidate its underlying mechanism of action., Methods: Mice were subjected to myocardial I/R injury by left anterior descending coronary artery (LAD) occlusion followed by 24 h reperfusion. Cardiac function and injury were evaluated by echocardiography, triphenyl tetrazolium chloride (TTC) and cardiac troponin T (cTnT) staining, and measuring lactate dehydrogenase (LDH) levels. In addition, various molecular and biochemical methods, as well as RNA sequencing were used to determine the effects and mechanism of action of vitamin B12 on I/R injury., Results: We found that high doses of vitamin B12 inhibited myocardial I/R injury. Furthermore, our data indicated that vitamin B12 supplementation alleviated cardiac dysfunction and injury by mitigating oxidative stress and apoptosis through downregulation of Nox2, the Ac-SOD2/SOD2 and Bax/Bcl-2 ratios and cleaved caspase-3 expression, and upregulation of SIRT3 expression and AMPK activity. However, these effects were largely reversed following treatment with the SIRT3 inhibitor, 3-TYP. Our RNA-sequencing data further demonstrated that vitamin B12 supplementation reduced inflammation during I/R injury., Conclusion: High doses of vitamin B12 supplements improved myocardial I/R injury by suppressing the accumulation of reactive oxygen species and apoptosis of myocardial tissue through modulation of the SIRT3/AMPK signaling pathway, while reducing inflammation. Our findings suggested that vitamin B12 administered at high doses could be a potential therapy for myocardial I/R damage., Competing Interests: Declaration of Competing Interest No conflict of interest, (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Vascular calcification (VC) is induced by a decrease in sirtuin 3 (SIRT3) and superoxide dismutase (SOD)2 and increases mitochondrial reactive oxygen species (mtROS), eventually leading to mitochondrial dysfunction and phenotype alterations in vascular smooth muscle cells (VSMCs) into osteoblast-like cells in hypertension. Ecklonia cava extract (ECE) is known to increase peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) and SOD2. In this study, we evaluated the effect of ECE on decreasing VC by increasing PGC-1α which increased SOD2 activity and decreased mtROS in an in vitro VSMC model of treating serums from Wistar Kyoto (WKY), spontaneous hypertensive rats (SHRs), and ECE-treated SHRs. Furthermore, the decreasing effect of ECE on VC was evaluated with an in vivo SHR model. PGC-1α expression, SIRT3 expression, and SOD2 activity were decreased by the serum from the SHRs and increased by the serum from the ECE-treated SHRs in the VSMCs. PGC-1α silencing eliminated those increases. mtROS generation and mitochondrial DNA (mtDNA) damage increased in the SHRs but decreased with ECE. Mitochondrial fission increased in the SHRs but decreased by ECE. Mitochondrial fusion, mitophagy, and mitochondrial biogenesis were decreased in the SHRs but increased by ECE. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and calcium deposition in the medial layer of the aorta increased in the SHRs but decreased with ECE. Therefore, ECE decreases VC via the upregulation of PGC-1α and SIRT3, which increases SOD2 activity. Activated SOD2 decreases mtDNA damage and mtROS generation, which sequentially decreases NADPH oxidase activity and changes the mitochondrial dynamics, thereby decreasing VC., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier Masson SAS.)

Glioblastoma (GBM) is the most prevalent type of adult primary brain tumor and chemotherapy of GBM was limited by drug-resistance. Fraxinellone is a tetrahydro-benzofuranone derivative with various pharmacological activities. However, the pharmacological effects of fraxinellone on GBM remains largely unknown. Here, we found that fraxinellone inhibited the proliferation and growth of GBM cells in a dose-dependent manner in vitro. Subsequently, we found that fraxinellone suppressed the migration and induced apoptosis of GBM cells in vitro. Using western blot and immunostaining, we further found that fraxinellone downregulated the expressions of sirtuin 3 (SIRT3), and superoxide dismutase 2 (SOD2), a downstream of SIRT3 in GBM cells. Meanwhile, reactive oxygen species (ROS) were increased in these fraxinellone-treated GBM cells. Interestingly, overexpression of SIRT3 (SIRT3-OE) indeed partially restored the inhibition of both cell proliferation and migration of GBM cells induced by fraxinellone. Finally, we found that fraxinellone could inhibit the growth of GBM in xenograft model through the inactivation of SIRT3 signaling pathway. Taken together, these results suggest that fraxinellone suppressed the growth and migration of GBM cells by downregulating SIRT3 signaling in vitro, and inhibited the tumorigenesis of GBMs in vivo., Competing Interests: Conflict of interest statement The authors declare that they have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Despite the fact that the initial hypertrophic response to ventricular pressure overload is thought to be compensatory, prolonged stress often leads to heart failure. Previous studies have shown that the Fufang-Zhenzhu-Tiaozhi (FTZ) formula is beneficial for the treatment of dyslipidemia and hyperglycemia. However, the effects of FTZ on cardiac hypertrophy remain unclear., Objective: The aim of this study is to evaluate the protective effects of FTZ on cardiac hypertrophy and determine the underlying mechanisms., Methods: TAC was utilized to establish a cardiac hypertrophy animal model, and FTZ was given via gavage for four weeks. Next, echocardiographic measurements were made. The morphology of mouse cardiomyocytes was examined using H&E and WGA staining. In vitro, the neonatal cardiomyocytes were stimulated with angiotensin Ⅱ (Ang Ⅱ). In addition to measuring the size of cardiomyocytes, qRT-PCR and western blotting were conducted to measure cardiac stress markers and pathway., Results: According to our findings, FTZ alleviated cardiac hypertrophy in mice and cell models. Furthermore, expression of miR-214 was down-regulated following FTZ, whereas the effect of FTZ therapy was reversed using miR-214 transfection. Furthermore, the expression of Sirtuin 3 (SIRT3) was decreased in Ang Ⅱ-induced oxidative damage, which was associated with a reduction in SOD-1, GPX1, and HO-1 and an increase in MDA, while SIRT3 expression was restored following FTZ treatment., Conclusions: Collectively, these findings indicate that FTZ is a protective factor for cardiac hypertrophy due to its regulation of the miR-214-SIRT3 axis, which suggests that FTZ may be a therapeutic target for cardiac hypertrophy., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Sirtuin-3 (SIRT3) is a NAD + -dependent protein deacetylase that is located in mitochondria, regulating mitochondrial proteins and maintaining cellular antioxidant status. Increasing evidence demonstrates that SIRT3 plays a role in degenerative disorders including Parkinson's disease (PD), which is a devastating nervous system disease currently with no effective treatments available. Although the etiology of PD is still largely ambiguous, substantial evidence indicates that mitochondrial dysfunction and oxidative stress play major roles in the pathogenesis of PD. The imbalance of reactive oxygen species (ROS) production and detoxification leads to oxidative stress that can accelerate the progression of PD. By causing conformational changes in the deacetylated proteins SIRT3 modulates the activities and biological functions of a variety of proteins involved in mitochondrial antioxidant defense and various mitochondrial functions. Increasingly more studies have suggested that upregulation of SIRT3 confers beneficial effect on neuroprotection in various PD models. This review discusses the mechanism by which SIRT3 regulates intracellular oxidative status and mitochondrial function with an emphasis in discussing in detail the regulation of SIRT3 on each component of the five complexes of the mitochondrial respiratory chain and mitochondrial antioxidant defense, as well as the pharmacological regulation of SIRT3 in light of therapeutic strategies for PD., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Berberine improves insulin sensitivity and ovulation function in PCOS patients. However, the mechanism by which berberine initiates glucose metabolism-related signaling pathways in ovarian cells remains unknown. This study unveiled a new mechanism by which berberine promotes ovarian cell glucose uptake, and demonstrated that SIRT3 ubiquitination is involved in the insulin sensitizing effect of berberine., Methods: Berberine was used at different concentrations to treat cultured KGN cells. Then, cell viability, cell apoptosis, intracellular ROS levels, mitochondrial depolarization and activation of related signaling pathways were evaluated., Results: Berberine administration led to mitochondrial depolarization and AMP accumulation by promoting SIRT3 ubiquitination. We confirmed that AMP accumulation activated AMPK signaling and further promoted glucose uptake. Meanwhile, berberine reduced the activity of mitochondrial complex I in a dose-depended manner, but not that of mitochondrial complex II. Furthermore, intracellular ROS levels and the expression of mitochondrial apoptosis pathway related factors increased with berberine concentration. Berberine caused significant SIRT3 ubiquitination and degradation by activating the AMPK pathway and increasing intracellular ROS levels. Interestingly, berberine induced ubiquitination paralleled the increased FOXO3a phosphorylation and FOXO3a/Parkin pathway activation., Conclusions: Berberine promotes glucose uptake and inhibits mitochondrial function by promoting SIRT3 ubiquitination, and is likely to regulate autophagy related function in ovarian cells by activating the AMPK pathway. These findings may provide novel insights into the development of drugs for the treatment of abnormal reproductive functions of the ovary., (Copyright © 2019. Published by Elsevier Masson SAS.)

Background: Subarachnoid hemorrhage (SAH) results in many brain dysfunctions and the neuroprotective function of puerarin after brain damage has been demonstrated in several studies. But whether puerarin can reduce brain nerve damage after SAH is not clear.In this study, we hypothesized that puerarin had the neuroprotective effect after SAH, and this protection could be mediated by bothBcl-2/Bax/Cleaved caspase-3 and SIRT3/SOD2 apoptotic signaling pathways., Methods: First, we used neurological score, brain water content and so on to detect the neurological deficits after SAH. Then apoptosis neuron rate was detected by TUNEL staining. Western blot was carried out to explore the alteration of Blc-2, Bax, cleaved caspase-3 and Sirt3.Also, ROS acitivity and As-lysine level of SOD2 should be detected with assays., Results: We demonstrate that puerarin attenuated the neurological deficits, effectively relieves cerebral edema, and reduce BBB disruption in SAH mice.And we revealed that a reduced rate of apoptosis neuron has been found out in puerarin treatment after SAH. In addition, obviously higher ratio of Blc-2/Bax and decreased expression of cleaved caspase-3 in puerarin-treated SAH micecomparing with vehicle-treated SAH animals had been found. Furthermore, puerarin effectively reversed these alterations in expression and inhibits ROSproduction induced by SAH. Also, puerarin can increase SOD activation after SAH and protect the expression of Sirt3 after SAH., Conclusions: In coclusion, puerarin can provide potential neuroprotection from the SAH damages, and can be act as a novel therapy for SAH., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The recent investigations have extensively focused on the importance of sirtuins, as a highly conserved family of gene products, particularly SIRT3 in various biological and pathological processes. SIRT3, the mitochondrial NAD+-dependent deacetylase has been demonstrated to target a broad range of proteins involved in the oxidative stress, ischemia-reperfusion injury, mitochondrial metabolism homeostasis and cellular death. The critical function of SIRT3 in myocardial infarction (MI), which is one of the complex phenotype of coronary artery disease and a result of interaction between various genetic and environmental factors, as well as in cardiac repair and remodeling post-MI have attracted more attention in the recent years. Therefore, in this review, we will summarize important literature about the involvement of SIRT3 in cardiac remodeling/repair following MI and its potential underlying mechanisms., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

GLP-1 analogue exendin-4, a glucagon-like peptide 1 receptor (GLP-1R) agonist which shares 53% sequence with GLP-1, plays an essential role in human tumors. However, the function and mechanisms underlying the effects of exendin-4 on glioma cell migration, invasion and epithelial-to-mesenchymal transition are still obscure. Firstly, we demonstrated that GLP-1R was expressed in all glioma cell lines including U87, U251, U373 and A172. Exendin-4 treatment inhibited glioma cell survival, proliferation, migration and invasion. Also, exendin-4 inhibited epithelial-to-mesenchymal transition through positively regulating the expression of E-cadherin (epithelial marker), and negatively regulating the level of Vimentin (mesenchymal marker). Interestingly, we next demonstrated that exendin-4 elevated sirt3 expression dependent on the high level of GLP-1R in U87 and 251 cells. Finally, we confirmed that depletion the level of GLP-1R or sirt3 both reversed the inhibitory action of exendin-4 on glioma cell migration and invasion. These findings demonstrate that exendin-4 treatment suppressed the migration and invasion of glioma cells through GLP-1R/sirt3 pathway and exendin-4 plays an inhibitory effect on glioblastoma cell migration and invasion., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Sirtuin-3 (Sirt3), a sub-family member of the nicotinamide adenine dinucleotide-dependent histone deacetylases, has been reported to be involved in mitochondrial oxidative stress regulation, mitochondrial calcium management, mitophagy activation, and mitochondrial energy metabolism. The aim of our study was to explore the functional role of Sirt3 in colorectal cancer stress, focusing particularly on its effects on mitochondrial fission. Our study demonstrated that Sirt3 was highly upregulated in colorectal cancer cells compared to normal rectal mucosa cells. However, the genetic ablation of Sirt3 reduced colorectal cancer cell viability, mobility and proliferation. At the molecular level, we found that Sirt3 knockdown suppressed the expression of adhesive factors and cyclins. Furthermore, Sirt3 deletion was also associated with mitochondrial membrane potential reduction, ROS overproduction, mPTP opening, mitochondrial pro-apoptotic upregulation, and caspase-9-related death programme activation. Furthermore, we determined that Sirt3 regulated the colorectal cancer stress response by modulating mitochondrial fission. The loss of Sirt3 triggered fatal mitochondrial fission by suppressing the Akt/PTEN pathway. Re-activation of the Akt/PTEN pathway combatted mitochondrial fission and promoted colorectal cancer mobility, survival, and growth. Altogether, these findings provide an additional rationale for the function of Sirt3 in supporting the growth and survival of colorectal cancer., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Cerebral ischemia-reperfusion (I/R) injury is a key contributing factor to the pathogenic mechanisms involved in ischemic stroke. The present study was designed to explore the effects of icariside II (ICS II) on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced PC12 cell oxidative injury. The results showed that ICS II ameliorated OGD/R-induced PC12 cell injury at the concentrations of 12.5, 25, and 50 μM, as evidenced by both the increase of cell viability and the decrease of LDH leakage from 33.96% ± 0.48% to 16.78% ± 0.78%, 13.12% ± 0.17%, 12.96% ± 0.10%, respectively. Moreover, ICS II not only attenuated the reactive oxygen species (ROS) from 212.2% ± 5.45%, 168.6% ± 5.29%, 148.7% ± 9.37%, 142.7% ± 7.76%, respectively, but also decreased the overproduction of mitochondrial ROS, as well as recovered the mitochondrial membrane potential (MMP) from 60.68% ± 7.90% to 76.71% ± 2.87%, 93.69% ± 4.41%, 95.92% ± 3.97%, respectively. Furthermore, OGD/R accelerated neuronal oxidative injury and apoptosis along with reduced nucleus-Nrf2, NQO-1, HO-1, Bcl-2 protein expressions, and increased Keap1, Bax and cleaved caspase-3 contents, whereas ICS II significantly reversed the abovementioned changes. Interestingly, ICS II also restrained the OGD/R-induced decrease in SIRT3 and IDH2 expressions. In conclusion, this study indicates that ICS II alleviates OGD/R-induced oxidative injury in PC12 cells, and its underlying mechanisms are due to the regulation of Nrf2/SIRT3 signaling pathway., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

{2-[1-(3-Methoxycarbonylmethyl-1H-indol-2-yl)-1-methyl-ethyl]-1H-indol-3-yl}-acetic acid methyl ester (MIAM) is a novel indole compound. Our previous studies showed that MIAM possessed activity against many cancers xenografted in mice without significant toxicity. In this study, we determined the effect of MIAM on human hepatocellular carcinoma (HCC) by both in vitro and in vivo assays. In in vitro assay, the experiments were performed in the hypoxic incubator. MIAM inhibited HCC growth with dose-dependent manner. The effects of MIAM on HCC might be due to its activities in induction of apoptosis, arrest of cell cycle in G0/G1 phase. Further studies showed that MIAM might exert its actions through multiple mechanisms. MIAM could reduce intracellular ATP, increase levels of p53/p21 and SIRT3/SOD2/Bax. MIAM also had the activity of reducing HIF1α and hexokinase II (HK II) in HCC. MIAM had the activity of increasing cellular reactive oxygen species (ROS) in HCC. However, the increase of ROS might not be its main mechanism in inhibition of HCC. MIAM might inhibit HepG2 growth through induction of apoptosis. We determined the relationship between level of SIRT3 and cell viability in the MIAM-treated cells. MIAM treatment resulted in increase of SIRT3 in HCC. Further, HepG2 cells infected with human SIRT3 were more sensitive to MIAM than the cells without infection of SIRT3. These results suggested that MIAM might inhibit HCC growth through upregulation of SIRT3. Importantly, the effect of MIAM was confirmed in the HepG2 xenografts bearing in mice. MIAM treatment did not induce significant toxicology to mice. Together, MIAM could be developed as potential agent for treatment of HCC., (Copyright © 2014. Published by Elsevier Masson SAS.)