BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
Humans ; Female ; Polycystic Ovary Syndrome/metabolism* ; Endometrium/metabolism* ; Sirtuin 3/genetics* ; Oxidative Stress/genetics* ; Adult ; Animals ; Mice ; Apoptosis/physiology* ; Immunohistochemistry ; Cell Proliferation/physiology*

Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). These mechanisms are vital for spermatogenesis, especially to maintain the normal function of testicular Sertoli cells and germ cells. The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility. In addition, we also briefly outline the current treatment of spermatogenic malfunction caused by mitochondrial OXPHOS disorders. However, relevant treatments have not been fully elucidated. Therefore, targeting mitochondrial OXPHOS disorders in Sertoli cells and germ cells is a research direction worthy of attention. We believe this review will provide new and more accurate ideas for treating male infertility.
Male ; Humans ; Infertility, Male/metabolism* ; Oxidative Phosphorylation ; Mitochondria/metabolism* ; Spermatogenesis/physiology* ; Sertoli Cells/metabolism* ; Oxidative Stress/physiology* ; Animals ; Reactive Oxygen Species/metabolism*

Oxidative stress due to aberrant metabolism is considered as a crucial contributor to diabetes and its complications. Hyperglycemia and hyperlipemia boost excessive reactive oxygen species generation by elevated mitochondrial respiration, increased nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced pro-oxidative processes, including protein kinase C pathways, hexosamine, polyol, and advanced glycation endproducts, which exacerbate oxidative stress. Oxidative stress plays a significant role in the onset of diabetes and its associated complications by impairing insulin production, increasing insulin resistance, maintaining hyperglycemic memory, and inducing systemic inflammation. A more profound comprehension of the molecular processes that link oxidative stress to diabetes is crucial to new preventive and therapeutic strategies. Therefore, this review discusses the mechanisms underlying how oxidative stress contributes to diabetes mellitus and its complications. We also summarize the current approaches for prevention and treatment by targeting the oxidative stress pathways in diabetes.
Oxidative Stress/physiology* ; Humans ; Diabetes Mellitus/physiopathology* ; Diabetes Complications/metabolism* ; Reactive Oxygen Species/metabolism* ; Glycation End Products, Advanced/metabolism* ; Animals

Vascular aging (VA) is a common etiology of various chronic diseases and represents a major public health concern. Intermittent hypoxia (IH) associated with obstructive sleep apnea-hypopnea syndrome (OSAHS) is a primary pathological and physiological driver of OSAHS-induced systemic complications. A substantial proportion of OSAHS patients, estimated to be between 40% and 80%, have comorbidities such as hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, aneurysm, and stroke, all of which are closely associated with VA. This review examines the molecular and cellular features common to both OSAHS and VA, highlighting decreased melatonin secretion, impaired autophagy, increased apoptosis, increased inflammation and pyroptosis, increased oxidative stress, accelerated telomere shortening, accelerated stem cell depletion, metabolic disorders, imbalanced protein homeostasis, epigenetic alterations, and dysregulated neurohormonal signaling. The accumulation and combination of these features may underlie the pathophysiological link between OSAHS and VA, but the exact mechanisms by which OSAHS affects VA may require further investigation. Taken together, these findings suggest that OSAHS may serve as a novel risk factor for VA and related vascular disorders, and that targeting these features may offer therapeutic potential to mitigate the vascular risks associated with OSAHS.
Humans ; Sleep Apnea, Obstructive/pathology* ; Aging/physiology* ; Oxidative Stress/physiology* ; Animals

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons and the accumulation of Lewy bodies, leading to motor and nonmotor symptoms. While both genetic and environmental factors contribute to PD, recent studies highlight the crucial role of lipid metabolism disturbances in disease progression. Altered lipid homeostasis promotes protein aggregation and oxidative stress, with significant changes in lipid classes such as sphingolipids and glycerolipids observed in patients with PD. These disturbances are involved in key pathological processes, such as α-synuclein aggregation, organelle dysfunction, lipid-mediated neuroinflammation, and impaired lipid homeostasis. This review examines the relationship between lipid species and PD progression, focusing on the physiological roles of lipids in the central nervous system. It explores the mechanistic links between lipid metabolism and PD pathology, along with lipid-related genetic risk factors. Furthermore, this review discusses lipid-targeting therapeutic strategies to mitigate PD progression, emphasizing the potential of lipid modulation for effective treatment development.
Humans ; Parkinson Disease/metabolism* ; Lipid Metabolism/physiology* ; Animals ; Oxidative Stress/physiology* ; alpha-Synuclein/metabolism*

Extracellular vesicles (EVs), defined as cell-secreted nanoscale vesicles that carry bioactive molecules, have emerged as a promising therapeutic strategy in tumor and tissue regeneration. Their potential in repairing intervertebral disc degeneration (IDD) through multidimensional regulatory mechanisms is a rapidly advancing field of research. This paper provided an overview of the mechanisms of EVs in IDD repair, thoroughly reviewed recent literature on EVs for IDD, domestically and internationally, and summarized their therapeutic mechanisms. In IDD repair, EVs could act through different mechanisms at the molecular, cellular, and tissue levels. At the molecular level, EVs could treat IDD by inhibiting inflammatory reactions, suppressing oxidative stress, and regulating the synthesis and decomposition of extracellular matrix. At the cellular level, EVs could treat IDD by inhibiting cellular pyroptosis, ferroptosis, and apoptosis and promoting cell proliferation and differentiation. At the tissue level, EVs could treat IDD by inhibiting neovascularization. EVs have a strong potential for clinical application in the treatment of IDD and deserve more profound study.
Extracellular Vesicles/physiology* ; Humans ; Intervertebral Disc Degeneration/therapy* ; Apoptosis ; Cell Proliferation ; Oxidative Stress ; Cell Differentiation ; Extracellular Matrix/metabolism* ; Animals ; Pyroptosis

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
Humans ; Male ; Prostatitis/blood* ; Adult ; Pelvic Pain/blood* ; Metabolomics ; Prostate/metabolism* ; Middle Aged ; Chronic Pain/blood* ; Metabolome ; Case-Control Studies ; Tryptophan/blood* ; Depression/blood* ; Oxidative Stress/physiology* ; Chronic Disease ; Lipid Metabolism/physiology*

Varicocele, the most common and treatable cause of male infertility, significantly impacts fertility. The pathophysiological mechanisms of varicocele have not been fully understood yet. Recent studies have focused on the pathophysiology of varicocele-induced infertility, highlighting inflammation and oxidative stress as key contributing factors. We reviewed recent research on the roles of inflammation and oxidative stress in the pathophysiology of varicocele and found that they negatively impact semen parameters, spermatogenesis, and testicular and epididymal function. In addition, this article summarizes the related factors of inflammation and oxidative stress caused by varicocele. Finally, a brief consideration on the treatments to address inflammation and oxidative stress is proposed. This review may provide treatment options and targets for varicocele-induced infertility. However, the relationship between inflammation and oxidative stress in varicocele still needs further study.
Varicocele/physiopathology* ; Humans ; Oxidative Stress/physiology* ; Infertility, Male/metabolism* ; Male ; Inflammation/physiopathology* ; Spermatogenesis/physiology*

Reactive oxygen species (ROS) play a dual role in mammalian spermatozoa. At high levels, they are detrimental to sperm function since they can promote oxidative stress that produces oxidation of protein, lipids, and sperm DNA. This oxidative damage is associated with male infertility. On the other hand, when ROS are produced at low levels, they participate in the redox signaling necessary for sperm capacitation. Capacitation-associated ROS are produced by the sperm oxidase, whose identity is still elusive, located in the plasma membrane of the spermatozoon. ROS, such as superoxide anion, hydrogen peroxide, nitric oxide, and peroxynitrite, activate protein kinases and inactivate protein phosphatases with the net increase of specific phosphorylation events. Peroxiredoxins (PRDXs), antioxidant enzymes that fight against oxidative stress, regulate redox signaling during capacitation. Among them, PRDX6, which possesses peroxidase and calcium-independent phospholipase A 2 (iPLA 2 ) activities, is the primary regulator of redox signaling and the antioxidant response in human spermatozoa. The lysophosphatidic acid signaling is essential to maintain sperm viability by activating the phosphatidylinositol 3-kinase/protein kinase (PI3K/AKT) pathway, and it is regulated by PRDX6 iPLA 2 , protein kinase C (PKC), and receptor-type protein tyrosine kinase. The understanding of redox signaling is crucial to pave the way for novel diagnostic tools and treatments of male infertility.
Humans ; Male ; Spermatozoa/physiology* ; Signal Transduction/physiology* ; Oxidation-Reduction ; Peroxiredoxins/physiology* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress/physiology* ; Sperm Capacitation/physiology* ; Infertility, Male/metabolism*

A growing global trend indicates a decline in semen quality, with a lack of physical activity identified as one of the contributing factors. Exercise is medication, and numerous studies have explored its effects on semen quality. However, there is no consensus on the most effective type and intensity of exercise for improving semen quality, owing to inconsistent findings across studies. These discrepancies may be attributable to variations in study populations ( e.g. , healthy versus infertile individuals) and research methodologies ( e.g., observational versus interventional studies). This paper reviews the existing literature from the databases PubMed, Web of Science, and Google Scholar, reclassifying articles on their subject and research designs to delineate the relationship between exercise and semen quality. It also summarizes the mechanisms through which exercise influences semen quality, including hormonal regulation, oxidative stress, and inflammatory factors.
Humans ; Semen Analysis ; Male ; Exercise/physiology* ; Oxidative Stress/physiology* ; Infertility, Male/physiopathology* ; Sperm Motility/physiology*