Myocardial ischemia/reperfusion (I/R) injury has high morbidity and mortality rates, posing a significant burden on society. There is an urgent need to understand its pathogenesis and develop effective treatments. Reactive oxygen species (ROS) are crucial for the development of myocardial I/R injury, and inhibiting ROS overproduction is one of the most critical ways to delay myocardial I/R injury. Sirtuins are a group of nicotinic adenine dinucleotide ( +)-dependent histone deacetylases whose members can regulate ROS by modulating various biological processes. Numerous studies have shown that Sirtuins play an essential role in the progression of myocardial I/R injury by regulating ROS. This study focuses on the relationship between myocardial I/R injury and ROS, Sirtuins and ROS, discusses the role of Sirtuins in regulating ROS in myocardial I/R, and summarizes the therapeutic modalities aimed at targeting Sirtuins to modulate ROS in myocardial I/R injury, thereby guiding future research endeavors.

To investigate the role of silencing information regulator 2 related enzyme 1 (SIRT1) and its small ubiquitin-like modifier (SUMO) modification (SUMOylation) in hyperoxia lung injury in preterm infants.

The roles of SIRT1 and its SUMOylation in hyperoxia-induced damage to HAECs were explored from the cellular level using CCK-8, MTT, scratch assay, reactive oxygen species (ROS), Mito SOX™, BeyoClick™ EdU-488, immunofluorescence and Western-blot, mitochondrial membrane potential, malondialdehyde and superoxide dismutase assays, MitoTracker® Red CMXRos, transmission electron microscopy, and SIRT1 activity assay. Type II alveolar epithelial cell-specific knockout SENP1 mice were constructed. The role of SUMOylation of SIRT1 in hyperoxia lung injury in mice was explored in vivo by HE staining, immunohistochemistry, immunofluorescence, Western-blot and transmission electron microscopy.

(1) Hyperoxia increased ROS in HAECs and decreased cell proliferation levels and survival, as well as reduced the expression of peroxisome-proliferator-γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), optic atrophy protein 1 (OPA1), mitofusins 1 (MFN1), and mitofusins 2 (MFN2) proteins. (2) N-Acetylcysteine inhibited SIRT1 nucleoplasmic shuttling and reversed the hyperoxia-induced decrease in SUMO1 and increase in SENP1. (3) SRT1720 reversed the hyperoxia-induced decrease of PGC-1α, NRF1, TFAM, MFN1, MFN2 and OPA1 proteins. (4) Overexpression of SUMO1 increased total SIRT1 and nuclear SIRT1 but decreased cytoplasmic SIRT1 protein expression levels, attenuated hyperoxia-induced mitochondrial injury. (5) On day 14 of hyperoxia exposure, type II alveolar epithelial cell-specific knockout SENP1 mice showed reduced lung injury, increased lung tissue total SIRT1 and nuclear SIRT1 but decreased cytoplasmic SIRT1 protein expression, and reduced mitochondrial injury.

Hyperoxia increases ROS levels to decrease SIRT1 and SUMO1 levels, thereby inhibiting mitochondrial biogenesis and fusion, and promotion of SIRT1 and its SUMOylation improves mitochondrial biogenesis and fusion, thereby attenuating hyperoxia lung injury.

Acute liver injury (ALI), which manifests as abnormal liver function and hepatocyte damage, lacks effective treatment modalities and is associated with a high mortality rate. Recent studies have revealed that hepatoprotection is related to polysaccharide components. In this study, we examined the effect and mechanism of Lycium ruthenicum Murray polysaccharides (LRMP) on liver injury induced by lipopolysaccharide (LPS). Male ICR mice were pre-administered LRMP (100 and 400 mg/kg BW) once daily for 21 days. A single injection of LPS (10 mg/kg BW) was administered on day 21 to induce ALI. The difference between the groups indicated that LRMP supplementation had no adverse effect on body weight. LRMP administration considerably alleviated liver injury, as evidenced by the decreased levels of aspartate transaminase and alanine transaminase, increased levels of albumin, and preservation of liver structural integrity. Moreover, LRMP reduced oxidative stress and inflammatory responses in the liver, maintained mitochondrial structure, regulated mitochondrial apoptotic pathway, and upregulated Sirtuin 1/peroxisome proliferator-activated receptor γ coactivator-1α signalling pathway involved in mitochondrial biogenesis. This study suggests the potential therapeutic application of LRMP in liver-related diseases, which will provide a basis for innovative strategies.

Vascular calcification is a complication that is frequently encountered in patients affected by atherosclerosis, diabetes, and chronic kidney disease (CKD), and that is characterized by the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). At present, there remains a pressing lack of any effective therapies that can treat this condition. The sodium-glucose transporter 2 (SGLT2) inhibitor dapagliflozin (DAPA) has shown beneficial effects in cardiovascular disease. The role of this inhibitor in the context of vascular calcification, however, remains largely uncharacterized. Our findings revealed that DAPA treatment was sufficient to alleviate in vitro and in vivo osteogenic transdifferentiation and vascular calcification. Interestingly, our study demonstrated that DAPA exerts its anti-calcification effects on VSMCs by directly targeting SGLT2, with the overexpression of SGLT2 being sufficient to attenuate these beneficial effects. DAPA was also able to limit the glucose levels and NAD+/NADH ratio in calcified VSMCs, upregulating sirtuin 1 (SIRT1) in a caloric restriction (CR)-dependent manner. The SIRT1-specific siRNA and the SIRT1 inhibitor EX527 attenuated the anti-calcification effects of DAPA treatment. DAPA was also to drive SIRT1-mediated deacetylation and consequent degradation of hypoxia-inducible factor-1α (HIF-1α). The use of cobalt chloride and proteasome inhibitor MG132 to preserve HIF-1α stability mitigated the anti-calcification activity of DAPA. These analyses revealed that the DAPA/SGLT2/SIRT1 axis may therefore represent a viable novel approach to treating vascular calcification, offering new insights into how SGLT2 inhibitors may help prevent and treat vascular calcification.

In this editorial, we comment on the article published in the recent issue of the World Journal of Gastroenterology. Acute liver failure (ALF) is a fatal disease that causes uncontrolled massive hepatocyte death and rapid loss of liver function. Ferroptosis and pyroptosis, cell death forms that can be initiated or blocked concurrently, can play significant roles in developing inflammation and various malignancies. However, their roles in ALF remain unclear. The article discovered the positive feedback between ferroptosis and pyroptosis in the progression of ALF, and revealed that the silent information regulator sirtuin 1 (SIRT1) inhibits both pathways through p53, dramatically reducing inflammation and protecting hepatocytes. This suggests the potential use of SIRT1 and its downstream molecules as therapeutics for ALF. Thus, we will discuss the role of ferroptosis and pyroptosis in ALF and the crosstalk between these cell death mechanisms. Additionally, we address potential treatments that could alleviate ALF by simultaneously inhibiting both cell death pathways, as well as examples of SIRT1 activators being used as disease treatment strategies, providing new insights into the therapy of ALF.

Triptolide (TP), known for its effectiveness in treating various rheumatoid diseases, is also associated with significant hepatotoxicity risks. This study explored Catalpol (CAT), an iridoid glycoside with antioxidative and anti-inflammatory effects, as a potential defense against TP-induced liver damage. In vivo and in vitro models of liver injury were established using TP in combination with different concentrations of CAT. Metabolomics analyses were conducted to assess energy metabolism in mouse livers. Additionally, a Seahorse XF Analyzer was employed to measure glycolysis rate, mitochondrial respiratory functionality, and real-time ATP generation rate in AML12 cells. The study also examined the expression of proteins related to glycogenolysis and gluconeogenesis. Using both in vitro SIRT1 knockout/overexpression and in vivo liver-specific SIRT1 knockout models, we confirmed SIRT1 as a mechanism of action for CAT. Our findings revealed that CAT could alleviate TP-induced liver injury by activating SIRT1, which inhibited lysine acetylation of hypoxia-inducible factor-1α (HIF-1α), thereby restoring the balance between glycolysis and oxidative phosphorylation. This action improved mitochondrial dysfunction and reduced glucose metabolism disorder and oxidative stress caused by TP. Taken together, these insights unveil a hitherto undocumented mechanism by which CAT ameliorates TP-induced liver injury, positioning it as a potential therapeutic agent for managing TP-induced hepatotoxicity.

This study aims to clarify the specific anti-fatigue components of Schizophyllum commune (S.commune) and analyze its potential anti-fatigue mechanism. The main anti-fatigue active ingredient of S.commune was locked in n-butanol extract (SPE-n) by activity evaluation. Twelve compounds were identified by high performance liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS). The anti-fatigue effect of morusin is the most predominant among these 12 ingredients. The determination of biochemical indices showed that morusin could increase liver glycogen reserves, improve the activity of antioxidant enzymes in liver, and reduce reactive oxygen species (ROS) content in muscle tissue, thereby reducing myocyte damage. Further studies revealed that morusin could reduce the level of oxidative stress by activating Nrf2/HO-1 pathway, thus alleviating the fatigue of mice caused by exhaustive exercise. The current findings provide a theoretical basis for the development of natural anti-fatigue functional food.

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies.