Mucosa‑associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a key paracaspase enzyme regulating immune responses, inflammation and oxidative stress. The present study aimed to investigate the effect of MALT1 inhibition on neuroinflammation, neuronal loss and oxidative stress in Alzheimer's disease (AD). A co‑culture system involving microglia and neuron cells under β‑amyloid (Aβ) intervention was used to establish AD cellular models using human microglia HMC3 cells and neuroblastoma SH‑SY5Y cells and mouse microglia BV‑2 and hippocampal neuron HT‑22 cells. The inhibition of MALT1 proteolytic activity was achieved by MALT1 inhibitor 2 (MI‑2) treatment, and the NF‑κB pathway was activated by phorbol 12‑myristate 13‑acetate (PMA) treatment in HMC3 and BV‑2 cells. Western blotting, ELISA, Cell Counting Kit‑8, EdU staining, reactive oxygen species (ROS) detection and reduced glutathione (GSH) assays were performed to evaluate molecular changes, inflammatory responses, neuronal viability and oxidative stress. MALT1 expression was upregulated following Aβ treatment in HMC3 and BV‑2 cells. MALT1 inhibition by MI‑2 suppressed the microglial M1 phenotype but enhanced the M2 phenotype, reduced the levels of the proinflammatory cytokines TNF‑α and IL‑1β and inactivated the NF‑κB pathway in HMC3 and BV‑2 cells. Moreover, microglial MALT1 inhibition elevated cell viability (verified by Cell Counting Kit‑8 and EdU assays), increased the level of reduced glutathione and decreased the levels of reactive oxygen species in SH‑SY5Y and HT‑22 cells. NF‑κB activation by PMA attenuated the effects of MALT1 inhibition on the microglial phenotype switch and proinflammatory cytokine secretion in HMC3 and BV‑2 cells, as well as cell viability and oxidative stress in SH‑SY5Y and HT‑22 cells. The present study reveals that MALT1 inhibition may suppress microglial M1 phenotype, neuroinflammation, neuronal loss and oxidative stress by inactivating the NF‑κB pathway in AD.
Osteoarthritis (OA) is a heterogeneous joint disorder lacking disease‑modifying therapies. Recent advances in single‑cell transcriptomics, metabolomics, lipidomics, and spatial omics have enabled the reconstruction of cell‑type‑specific gene‑metabolite networks and revealed that metabolic reprogramming differs markedly across chondrocyte subsets, synovial fibroblasts and immune cells. Lipid metabolism disturbances, particularly those involving glycerophospholipids, sphingolipids and cholesterol, are consistently linked to OA severity and pain generation. Integrative multi‑omics approaches further facilitate molecular endotyping, informing patient stratification and endotype‑driven clinical trial design. However, a systematic synthesis of these emerging findings is still lacking. This review critically synthesizes current multi‑omics integration strategies, delineates cell‑type‑specific metabolic networks derived from transcriptomic and metabolomic data and discusses their implications for precision medicine in OA, while also considering the emerging contributions of spatial omics technologies.
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the Transwell assay data shown in Fig. 2C and 4D, two pairs of overlapping sections of data were identified comparing the panels in these figures, where the results from differently performed experiments were intended to have been portrayed. An Expression of Concern statement was published to account for these concerns (doi: 10.3892/or.2025.9001), after which the authors have responded to the Editorial Office to offer an explanation for this apparent duplication of data within the two figures. To address the issue of the scientific rigor and integrity of this paper, the affected experiments in Figs. 2C and 4D have been performed again in triplicate by the authors. The results obtained were broadly similar to those obtained in the original experiments, and the revised versions of Figs. 2 and 4 are shown on the next page. Also note that the following changes are required to the text in the paper describing the results of these experiments: In the Results section, the corrected data values and text for these experiments should now read as follows: For Fig. 2: 'The cells that invaded through the pores to the lower surface of the filter were 29±16 and 95±36 (P<0.05), respectively (Fig. 2C and D)'; and for Fig. 4: 'Smad2 RNAi abrogated the TGF‑β1‑induced suppression of E‑cadherin expression (Fig. 4C) and suppressed the invasion capacity of Tu686 cells (P<0.05, 70±22 vs. 23±8; Fig. 4D and E)'. The data values have also been amended in the respective figure legends for Figs. 2 and 4, as shown on the next page. Note that these errors did not have a significant impact on the conclusions reached in this study. The authors regret the errors that were made during the compilation of the original figures, and are grateful to the editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they apologize to the readership for any incon-venience caused. [Oncology Reports 25: 1581‑1587, 2011; DOI: 10.3892/or.2011.1251].
Sepsis‑associated acute kidney injury (SA‑AKI) presents a significant challenge in critical care, largely due to the multifaceted nature of renal injury stemming from interconnected disturbances in inflammation, metabolism, microcirculation, mitochondrial function and programmed cell death, rather than arising from a singular dominant pathway. Increasing evidence indicates that apoptosis, pyroptosis, ferroptosis, necroptosis and autophagy‑related responses function as an integrated yet heterogeneous cell death network, characterized by extensive crosstalk, compensatory signaling and disease stage‑dependent regulation. The present review uses an integrated cell death network framework for SA‑AKI, rather than simply summarizing individual cell death pathways or sequentially cataloguing diet‑related small molecules. Current evidence was synthesized by organizing shared regulatory nodes according to their mechanistic roles, including upstream drivers, amplifiers or permissive states, context‑dependent modifiers, and terminal execution mechanisms. Focus is placed on mitochondrial dysfunction, redox‑iron imbalance, NF‑κB‑dependent inflammatory activation, inflammasome priming, failures in autophagy/mitophagy and immunometabolic stress. Furthermore, the present review explores how diet‑related small molecules may influence these shared injury conditions, differentiating between food‑derived phytochemicals, nutritional compounds, microbiota‑derived metabolites and intensive care unit‑based antioxidant or vitamin regimens. The potential efficacy of these compounds may derive less from their ability to selectively inhibit isolated death programs and more from their capacity to reshape common upstream environments that allow multiple death pathways to manifest. Finally, major translational barriers are discussed, including limited bioavailability, uncertainty surrounding active metabolites, altered pharmacokinetics during sepsis, disease‑stage specificity, renal target exposure and inter‑patient heterogeneity. An exposure‑aware and endotype‑guided framework is proposed for the future evaluation of diet‑related small molecules in the context of SA‑AKI.
Autophagy, as a core mechanism for maintaining cellular homeostasis, influences differentiation and functional activation of immune cells by regulating metabolic reprogramming. Crucially, autophagy serves as a molecular switch that precisely modulates differentiation and subsequent cell fate decisions. It achieves this by eliminating intracellular danger signals or key complexes, thereby determining whether immune cells undergo PANoptosis, an inflammatory death mode that integrates features of pyroptosis, apoptosis and necroptosis. The present review systematically discusses the regulatory role of autophagy in the developmental, differentiation and metabolic pathways of various immune cells. Furthermore, it elucidates the mechanistic details by which autophagy, and particularly mitophagy, dampens excessive PANoptosis activation through the elimination of danger signals (such as mitochondrial DNA and reactive oxygen species) or the degradation of PANoptosome components. Additionally, it clarifies the molecular mechanism by which autophagy dysregulation, induced by specific pathological conditions, leads to inflammatory responses and immunopathological damage. Overall, this review establishes the significance of the autophagy‑PANoptosis axis in the development and progression of autoimmune diseases and tumors, providing a solid theoretical foundation for the optimization and innovation of therapeutic strategies for these diseases.
Following the publication of the above article, a concerned reader drew the Editor's attention to the fact that, regarding the EdU assay experiments shown in Fig. 6 on p. 657, discrete areas of the cells appeared to overlap in different data panels, which were intended to show differently performed experiments in two distinct cell lines (the SW1990 and Panc‑1 cell lines), albeit the areas were inverted in the case of the 'LV‑RNAi' data panels. Moreover, within these areas of overlapping cells, certain of the cells were uniquely found to be coloured differently in the associated data panels. In addition, in Fig. 9 on p. 658, the bands shown for the caspase‑3 and caspase‑3 experiments with the SW1990 cell line looked remarkably similar, suggesting that the data in this figure may also have been assembled incorrectly. After having conducted an internal investigation of the data in this paper, the Editor of International Journal of Molecular Medicine has decided that this article should be retracted from the publication on the grounds of an overall lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor sincerely apologizes to the readership for any incovenience caused, and we thank the reader for drawing this matter to our attention. [International Journal of Molecular Medicine 32: 653‑660, 2013; DOI: 10.3892/ijmm.2013.1437].
Salvianolic acids (SAs), a water‑soluble active component extracted from the traditional Chinese herb Salvia miltiorrhiza, have attracted considerable attention as an anti‑tumor agent. Accumulating evidence demonstrates that SAs potently inhibit tumor‑cell migration, invasion and metastasis through multiple signaling pathways and molecular targets. First, SAs remodel the extracellular matrix and suppress matrix metalloproteinase activities, thereby attenuating the epithelial‑mesenchymal transition and the associated stem‑like properties of cancer cells. Second, SAs block tumor angiogenesis, depriving tumors of essential nutrients and routes for metastasis. Third, SAs reprogram the tumor microenvironment by modulating immune cells, enhancing immune cell infiltration and relieving immunosuppression, ultimately curbing tumor progression. Fourth, SAs target metastatic cellular plasticity and therapy resistance by disrupting cytoskeletal reorganization, impairing cell motility and reversing drug‑resistant phenotypes, thereby enhancing cancer treatment efficacy with reduced toxicity. At the molecular level, SAs suppress the PI3K/AKT, MAPK and TGF‑β1/Smad signaling cascades, thereby diminishing the invasive and migratory capacity of tumor cells. In this review, recent advances in understanding the anti‑metastatic effects and underlying mechanisms of SAs were systematically summarized, the challenges hindering their clinical translation were discussed and future directions that may facilitate their development as a promising anti‑metastatic therapeutic agent were outlined.
Metabolic syndrome (MetS) is a clinical syndrome primarily characterized by insulin resistance, integrating central obesity, hyperglycemia, hypertension and dyslipidemia. It is associated with increased risks of type 2 diabetes mellitus, non‑alcoholic fatty liver disease and atherosclerosis. Due to its high prevalence, complex pathogenesis and lack of effective treatments, MetS has become a notable global health issue. Current therapeutic approaches mainly emphasize weight reduction through caloric restriction and increased physical activity, or pharmacological interventions to improve lipid profiles, blood pressure and blood glucose; however, their efficacy remains suboptimal. Growing evidence indicates that programmed cell death (PCD), as a key driver of inflammation, serves a crucial role in the development and progression of MetS. The present review provides a comprehensive overview of recent advances in the understanding of how established and emerging forms of PCD contribute to MetS pathogenesis, including apoptosis, pyroptosis, autophagy, ferroptosis, necroptosis, PANoptosis and disulfidptosis. Particular emphasis is placed on their molecular mechanisms, tissue‑specific functions, regulatory crosstalk and therapeutic potential. Additionally, the present review discusses novel regulatory approaches and potential therapeutic strategies based on PCD network intervention, offering theoretical foundations and directions for developing innovative therapies to prevent and treat MetS and its complications.
Knee osteoarthritis (KOA) is a chronic, disabling disease with multiple etiologies and a complex pathophysiology. Conservative treatment is the cornerstone of KOA management, and when it proves insufficient, extracorporeal shock wave therapy (ESWT) has emerged as a practical non‑invasive alternative. The present narrative review systematically summarizes current preclinical and clinical evidence on ESWT for KOA through a structured literature search, aiming to integrate its therapeutic effects and identify knowledge gaps. Accumulating evidence indicates that ESWT can slow KOA progression through multiple biological pathways, encompassing anti‑inflammatory, anti‑apoptotic, pro‑proliferative and cartilage‑protective effects, while also relieving pain and improving function clinically. Summarizing the available data, this review finds that ESWT exhibits a favorable safety profile for articular tissues and disease‑modifying potential in preclinical models, although treatment outcomes depend critically on energy flux density and protocol selection. In human studies, the current evidence primarily supports symptomatic relief, including pain reduction and functional improvement; high‑quality trials with structural endpoints to verify cartilage regeneration or joint space preservation remain scarce. Given its non‑invasive nature, safety and growing clinical support, ESWT merits consideration as an adjunctive therapy. However, heterogeneity in treatment parameters and limited long‑term data preclude standardized guidelines. Despite these limitations, ESWT remains a promising adjunctive therapy for patients who are unresponsive to conventional conservative treatments. Future research should prioritize parameter optimization, extended follow‑up and translational studies to bridge the gap between preclinical structural findings and clinical application. Addressing these gaps will strengthen the therapeutic role and scientific foundation of ESWT.
Lysine acetylation is recognized as a critical and reversible post‑translational modification that is essential for numerous cellular functions and biological processes. The dynamic interplay between lysine acetylation and deacetylation to regulates a wide spectrum of processes, including histone modification, gene expression, cell cycle progression, DNA repair and signal transduction. Emerging evidence has demonstrated that the dysregulation of lysine acetylation is strongly associated with multiple diseases, including cancer, cardiovascular diseases, chronic inflammatory diseases and neurological diseases. These alterations can modify gene expression and disrupt cellular homeostasis. The present review aimed to highlight the biological functions of lysine acetyltransferases and lysine deacetylases, their contributions to disease pathogenesis, and the interplay the crosstalk of lysine acetylation with other post‑translational modifications. Drawing on the latest research findings, the therapeutic potential of targeting acetylation pathways is discussed, with the aim of providing new insight into the development of innovative treatment strategies and clinical applications.
Following the publication of the above paper, it has been drawn to the Editor's attention by an interested reader that, regarding the Hoechst‑stained images shown in Fig. 4 on p. 1258, the 'WT‑hERG+L539fs/47‑hERG' panel (top row, on the right) and the 'L539fs/47‑hERG+4‑PBA' panel (bottom row, middle panel) shared an overlapping section, such that data which were intended to show the results of differently performed experiments had apparently been derived from the same original source. Furthermore, upon performing an independent analysis of the data in this paper in the Editorial Office, it came to light that the western blot data featured in Fig. 5A contained a number of potential anomalies: there appeared to be possible breaks in continuity in the gel showing the blots for cleaved caspase‑3 in this figure, and the backgrounds for the western blots in this figure also appeared to be rather heterogenous. Although the authors responded to this initial query concerning the incorrect assembly of data in Fig. 4, up to this time no response from them has been forthcoming concerning the western blots shown in Fig. 5. Owing to the time that has now elapsed, and given the fact that the Editorial Office has been made aware of potential problems associated with the scientific integrity of this study, we are issuing an Expression of Concern to notify readers of these issues while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine, 43:1253‑1262, 2019; DOI: 10.3892/ijmm.2019.4049].
The emergence of molecular classifications for gastric cancer (GC), The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG), has advanced targeted and immunotherapies, but their clinical translation faces real‑world obstacles including high cost, tissue availability, standardization, and intratumoral heterogeneity. The present review critically compares the two classification systems regarding prognostic utility across geographic populations and boundary conflicts, noting that ACRG is more operable in East Asian populations whereas TCGA is better suited for mechanistic exploration. Focusing on acquired resistance as a core bottleneck in precision therapy, mechanisms underlying anti‑Human Epidermal Growth Factor Receptor 2 (HER2) resistance and primary/secondary resistance to immune checkpoint inhibitors (ICIs) were systematically dissected, while also addressing immune‑related adverse events and pseudo‑/hyperprogression. Moreover, non‑immune elements of the tumor microenvironment deserve attention: Cancer‑associated fibroblasts limit drug penetration and promote epithelial‑mesenchymal transition through physical barriers and paracrine signaling; metabolic reprogramming (high glycolysis and glutamine addiction) impairs chemotherapy and ICI efficacy via an acidic microenvironment and metabolic competition. Finally, multi‑target combination strategies are envisioned based on pathway redundancy, along with liquid biopsy‑driven dynamic adaptive therapy and single‑cell/spatial multi‑omics integration for precise microenvironment intervention. The present review aims to offer a systematic reference for moving GC precision therapy from static subtyping toward dynamic, multi‑dimensional integration.
Following the publication of the above article, an interested reader drew the authors' attention to the fact that, in Fig. 4B on p. 987, the 'Mon' and 'EBM84‑M' data panels showed apparently the same data, albeit the images were rotated through 180° relative to each other, suggesting that this figure part had been assembled incorrectly. The authors were able to consult their original data, and acknowledged that errors had been made in compiling Fig. 4B; specifically, the panel labeled as 'Mon' was inadvertently published using the image corresponding to the 'EBM84‑H' group; secondly, the panel labeled as 'EBM84‑M' incorrectly duplicated the published 'Mon' panel (which, as noted above, was the 'EBM84‑H' image); and finally, the panel labeled as 'EBM84‑H' mistakenly displayed the image corresponding to the 'EBM84‑M' group. The revised version of Fig. 4, now showing the correct data for the 'Mon', 'EBM84‑M' and 'EBM84‑H' data panels in Fig. 4B, is shown on the next page. The authors confirm that the errors made during the assembly of this figure did not have a significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 31: 982‑988, 2013; DOI: 10.3892/ijmm.2013.1273].
The growing burden of liver diseases underscores the urgent need to elucidate the adipose‑liver axis. Although adipocyte dysfunction, dysregulated adipokine secretion and adipocyte‑derived extracellular vesicles (Ad‑EVs) have been implicated in hepatic steatosis, inflammation and fibrogenesis, their precise pathogenic roles and translational potential remain incompletely defined. The present review uniquely centers on adipocytes as a specific cellular source, systematically examining their biological functions and those of Ad‑EVs, delineating their differential roles across the stages of liver disease, and evaluating adipocyte‑targeted therapeutic strategies together with their clinical prospects. However, the clinical translation of adipocyte‑targeted interventions and Ad‑EV‑based applications is constrained by several limitations: Current mechanistic evidence derives largely from preclinical models and awaits validation in human adipose tissue and liver biopsy specimens; moreover, methods for the isolation and characterization of Ad‑EVs have yet to be standardized. The present review aimed to identify the translational connections and unresolved challenges within the adipose‑liver axis, thereby informing basic research and the clinical diagnosis and treatment of liver diseases.
Disrupting energy metabolic pathways has emerged as a promising strategy for cancer therapy including non‑small cell lung cancer (NSCLC). However, the ultimate anticancer effects have not been satisfactory. This is likely because cellular energy metabolism encompasses multiple processes and pathways, and tumor cells can flexibly regulate these processes and pathways to adapt to external disturbances and changes in the microenvironment in order to maintain their growth and proliferation. As a result, current strategies which only target certain aspects of energy metabolism have not achieved commendable results. In the present study, two inhibitors lonidamine and devimistat, each with their own limitations, were combined to treat A549 NSCLC by synergistically interfering with the main aspects of cellular energy metabolism including glycolysis, the tricarboxylic acid cycle and oxidative phosphorylation. The synergistic potency was examined in vitro and in vivo including cytotoxicity, optimal combination doses, colony formation, mitochondrial function, adenosine triphosphate (ATP) and reactive oxygen species (ROS) production, apoptosis and pharmacodynamics in a xenograft mouse model. Moreover, characteristic metabolite levels were measured to elucidate the effects of combination treatment on cellular energy metabolism. The results showed that this combination therapy could synergistically inhibit tumor growth in vitro and in vivo. Furthermore, combining these two metabolic inhibitors could induce the production of ROS, reduce the generation of ATP, impair mitochondrial morphology and function, and ultimately activate apoptosis in tumor cells through metabolic regulation, facilitating antitumor treatment. The findings underscore the necessity and effectiveness of targeting tumor energy metabolism for lung cancer therapy, providing reliable evidence that metabolic therapies can effectively participate in cancer treatment.
Subsequently to the publication of the above article, an interested reader drew to the Editor's attention that apparently the same set of GADPH data panels had been featured in a number of research articles by this group, even though it appeared as if these were intended to have shown the same experimental conditions in most cases. The authors have realized that the GAPDH loading control panel in question, shown in Fig. 1C on p. 2581, had been inappropriately used to represent the same batch of tissue samples in several articles. Although the tissue samples were from the same batch, the authors recognize that using the same GAPDH panel as the loading control across a number of different publications was inappropriate. To address this issue, the authors have replaced both the RRM2 and the GAPDH data in Fig. 1C of the above paper, and the revised version of Fig. 1 is shown on the next page. In addition, upon re‑examining their original data, the authors also realized that certain images captured for the invasion assay in Fig. 3C on p. 2584 contained overlapping sections (for example, the 'Scramble siRNA' and 'RPM2 siRNA' data panels for the AGS cell line). Therefore, the invasion assay experiments were also repeated, and the corresponding panels in Fig. 3C have been replaced. The revised version of Fig. 3 is shown on the second subsequent page. The authors wish to emphasize that the errors made in assembling the data in these figures did not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for granting them this opportunity to publish a Corrigendum, and apologize to both the Editor and the readership for any inconvenience caused. [Oncology Reports 31: 2579‑2586, 2014; DOI: 10.3892/or.2014.3148].
Fibrosis is a progressive pathological process characterized by excessive extracellular matrix (ECM) deposition and structural remodeling that ultimately leads to organ dysfunction. In organs such as the liver, lung, heart and kidney, sustained activation of fibroblasts and their differentiation into myofibroblasts are key drivers of fibrotic progression. Growing evidence suggests that these cellular transitions are regulated by intricate transcriptional networks that integrate inflammatory, metabolic and mechanical signals. Liver fibrosis provides a well‑established framework for studying the transcriptional regulation of fibroblast activation, largely driven by the differentiation of hepatic stellate cells (HSCs) into collagen‑secreting myofibroblasts. Various transcription factors coordinate major signaling pathways to regulate fibroblast proliferation, ECM production and cell survival. These transcriptional programs not only sustain fibrogenesis but also influence whether fibrotic responses resolve or progress to chronic tissue scarring. In the present review, current advances in understanding transcriptional regulatory networks governing fibroblast activation were summarized, with a primary focus on HSCs while highlighting shared mechanisms across multiple fibrotic organs. Emerging therapeutic strategies targeting transcription factors and their upstream regulatory pathways were further discussed. A deeper understanding of these transcriptional circuits may facilitate the development of novel antifibrotic therapies and enhance strategies for resolving fibrosis in various organs.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide, characterized by late diagnosis, rapid progression and resistance to conventional therapies. Cancer‑associated fibroblast (CAF)‑derived extracellular vesicles (EVs) contribute to PDAC progression, but their downstream molecular effectors remain unclear. In the present study, it was demonstrated that CAF‑derived EVs enhanced the proliferative, migratory and invasive capacity of PDAC cells across two independent cell lines, as assessed by Cell Counting Kit‑8 assays and Transwell migration and Matrigel invasion assays. RAP1B was identified as a prominently upregulated protein by label‑free proteomic profiling following EV exposure. High RAP1B expression, evaluated by immunohistochemistry, in a cohort of 77 resected PDAC specimens tended to be more frequent with advancing pathological stage and was associated with poorer overall survival. RAP1B knockdown using small interfering RNA suppressed proliferation and motility in PDAC cells and induced cytokinesis failure characterized by multinucleation and cytoskeletal abnormalities, as demonstrated by time‑lapse imaging and immunofluorescence staining. Proteomic profiling of RAP1B‑knockdown cells identified anillin (ANLN) as a downstream mediator; ANLN knockdown recapitulated these cytokinetic defects, whereas ANLN knockdown did not reciprocally affect RAP1B levels, establishing a unidirectional RAP1B/ANLN axis. Furthermore, RAP1B depletion sensitized PDAC cells to gemcitabine, showing additive growth inhibition. In conclusion, CAF‑derived EVs mediate PDAC progression via the RAP1B/ANLN axis, representing a novel and promising therapeutic target in PDAC.
Polycystic ovary syndrome (PCOS) is a lifelong endocrine‑metabolic disorder affecting 11‑13% of women worldwide. Beyond ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology, PCOS is tightly linked to insulin resistance, dyslipidemia, hypertension, and increased cardiometabolic risk. Converging evidence places oxidative stress at the core of PCOS pathophysiology, but current evidence should be interpreted in a phenotype‑aware manner. Obese, hyperandrogenic, and Rotterdam phenotype A/B presentations generally carry a heavier systemic oxidant‑inflammatory burden than phenotype D, whereas lean PCOS may still exhibit clinically relevant local ovarian redox abnormalities despite a milder metabolic background. Mitochondrial dysfunction, insulin resistance, and androgen excess amplify reactive oxygen species generation, while granulosa‑cell mitochondrial depolarization, apoptotic signaling, and NF‑κB‑driven inflammation degrade follicular fluid quality, oocyte competence, and embryo development. However, the literature remains heterogeneous because assay platform, specimen type, cycle phase, adiposity, and treatment exposure all influence biomarker reproducibility and comparability. In addition, most human research supports association, whereas stronger causal support comes from interventional or mechanistic research showing that modulation of NADPH oxidase 4, antioxidant pathways, mitochondrial function, or sex hormone‑binding globulin‑related oxidative signaling can alter key reproductive and metabolic phenotypes. To improve translational value, the present review prioritizes a core biomarker panel spanning serum/plasma and follicular fluid, distinguishes systemic oxidative markers from local ovarian microenvironmental markers, and critically compares antioxidant and metabolic interventions by evidence level, sample size, endpoint type, and major limitations. Recent phenotype‑oriented and multi‑omics reearch is further integrated to propose a biomarker‑guided framework for phenotype‑stratified trials and precision management of PCOS.
Inflammatory bowel disease (IBD) is a group of chronic, relapsing and systemic inflammatory disorders primarily affecting the gastrointestinal tract, including Crohn's disease, ulcerative colitis and rarer distinct subtypes such as indeterminate colitis. IBD has shown a marked shift in global epidemiology, with increasing incidence in newly industrialized regions across Africa, Asia and Latin America. The pathogenesis of IBD reflects a complex interplay between genetic susceptibility, mucosal immune dysregulation, intestinal barrier dysfunction, microbial dysbiosis and environmental exposures. Clinically, conventional therapy, including 5‑aminosalicylic acid, corticosteroids and conventional immunosuppressants, is limited by incomplete efficacy and safety concerns. Alternative therapeutic strategies included biological agents (anti‑tumor necrosis factor α, anti‑integrin, anti‑IL‑12/23 and anti‑tumor necrosis factor‑like ligand 1A), small‑molecule inhibitors (JAK inhibitors, tyrosine kinase 2 inhibitors, sphingosine‑1‑phosphate receptor modulators and NLRP3 inhibitors), microbiome‑based interventions (fecal microbiota transplantation, probiotics and engineered microbes) and regenerative approaches (mesenchymal stem cells and intestinal organoids). The present review aimed to summarize mechanistic insights and clinical evidence for established and emerging therapies and discusses current challenges and future directions for individualized, disease‑modifying treatment of IBD.
