The adenosine monophosphate (AMP)-activated protein kinase (AMPK) signalling pathway regulates cell metabolism, inflammation and the immune response. This signalling pathway is essential for maintaining reproductive homeostasis and influencing steroidogenesis, implantation, and embryonic development. The central sensor, AMPK, regulates cell function in response to metabolic stress. The dysregulation of AMPK signalling has been implicated in several female reproductive disorders, including polycystic ovary syndrome (PCOS), endometriosis, infertility, and reproductive ageing. This review provides an overview of the role of AMPK in reproductive function and disorders, as well as potential therapeutic targets to restore balance in this signalling pathway. It discusses AMPK signalling in folliculogenesis, oocyte maturation, pregnancy maintenance, pre-eclampsia (PE) pathogenesis, PCOS, preterm birth, endometriosis, dysmenorrhoea and other disorders related to female reproduction. A deeper understanding of AMPK signalling in these contexts could provide new insights for the development of therapeutic interventions for reproductive health.

The colonic epithelial barrier is a multilayered defense system comprising the mucus layer, intestinal epithelial cells (IECs), and the underlying lamina propria. These components collectively maintain mucosal homeostasis and restrict microbial translocation. Disruption of this barrier is a hallmark of chronic intestinal inflammation particularly in IBDs, and is primarily driven by pro-inflammatory cytokines, such as TNF-α, IFN-γ, IL-1β, and IL-6. TNF-α and IFN-γ synergistically induce epithelial cell apoptosis and tight junction disassembly through mechanisms involving TNFR2 upregulation, myosin light chain kinase (MLCK) activation, and adherens junction destabilization. IL-1β amplifies paracellular permeability via NF-κB-dependent MLCK induction and OCLN downregulation, while IL-6 promotes barrier leakiness by upregulating CLDN-2 and sustaining self-reinforcing inflammatory loops that maintain chronic inflammation and impede epithelial repair. This leads to persistent immune-cell infiltration, chronic tight junction remodeling, and failure of barrier replenishment. Consequently, leaky colon facilitates microbial and antigen translocation into the lamina propria, further activating immune cells and perpetuating pro-inflammatory signaling. This review synthesizes current evidence and studies on the cooperative and self-reinforcing roles of pro-inflammatory cytokines, providing insight into the mechanisms underlying chronic intestinal barrier dysfunction and highlighting the need for therapeutic strategies that simultaneously target multiple inflammatory axes to restore barrier integrity in inflammatory bowel disorders.

Objective: This study investigated the effects of a supraphysiological dose of testosterone on uterine morphology and the regulation of the leukaemia inhibitory factor (LIF) signalling pathway during endometrial receptivity. Methods: In this study, 30 adult female Sprague–Dawley rats were divided into treatment and control groups. The treatment groups received subcutaneous injections of 1 mg/kg/day of testosterone from gestational day 1 to day 3, either testosterone alone or in combination with inhibitors (anastrozole, finasteride, or both). A control group of six untreated rats was maintained for comparison. Rats were euthanised on the evening of gestational day 4 to examine uterine morphological changes, gene expression and the distribution of proteins associated with the LIF signalling pathway (LIF, LIFR, JAK1 and STAT3) and MUC1 by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC), respectively. Results: The results of this study showed that the thickness of the endometrium and myometrium, as well as the number of glands, markedly decreased in all testosterone-treated rats. In addition, the mRNA levels of LIF, LIFR, JAK1 and STAT3 were significantly downregulated in response to supraphysiological testosterone treatment, while the mRNA of MUC1 was significantly upregulated. The IHC results were consistent with the mRNA data and confirmed the changes in protein distribution in all treatment groups. Conclusions: A supraphysiological dose of testosterone may impair endometrial receptivity through dysregulation of the LIF signalling pathway, potentially affecting fertility.

Offspring of mothers with hypertensive disorders of pregnancy (HDP) are at increased risk of developing endothelial dysfunction and cardiovascular disease (CVD) in adulthood. MicroRNAs (miRNAs), as key regulators of endothelial cells, may contribute to the early onset of endothelial dysfunction. However, there are limited studies characterizing the miRNA profile of endothelial cells in offspring of HDP. Therefore, this study aims to determine the miRNA expression profile of human umbilical vein endothelial cells (HUVECs) isolated from the offspring of HDP. HUVECs were obtained from both normal and hypertensive umbilical cords. RNA sequencing analysis revealed that eight miRNAs were significantly upregulated in HUVECs from HDP (p < 0.05). The target genes of these miRNAs were then predicted using four databases: miRDB, TargetScan, DIANA-microT-CDS, and miRWalk. Gene ontology, pathway enrichment, and protein-protein interaction network analyses revealed that the target genes of these miRNAs are involved in cellular functions and pathways related to angiogenesis and cellular senescence, which may contribute to endothelial dysfunction and CVD. The most significantly upregulated miRNA, hsa-miR-196a-5p expression was then validated through stem-loop RT-qPCR where its expression was significantly upregulated in hypertensive HUVEC by 6-fold as compared to normal HUVEC (p < 0.01). These findings offer insights into the role of miRNAs in the development of CVD in offspring exposed to HDP, highlighting their potential as predictive markers and therapeutic targets in the future.

Ulcerative colitis (UC) is a chronic disease marked by mucosal inflammation of the colon, and its prevalence has progressively increased worldwide. Gut dysbiosis is recognized as a key contributor to its pathogenesis. Although conventional treatments are effective in managing symptoms, they often fail to address the underlying gut microbial imbalance, prompting growing interest in microbiota-based therapies. Probiotic supplementation has demonstrated potential to modulate the disease. However, its clinical application is limited by variability in formulations and strain composition. Debate persists regarding the relative benefits of single-strain probiotics (SSPs), which depend on strain specificity, versus multi-strain probiotics (MSPs), which may provide synergistic effects. The literature remains inconclusive, with some studies indicating that MSPs outperform SSPs, while others emphasize the importance of strain specificity. This review describes the mechanistic basis of both approaches and descriptively synthesizes their clinical efficacy in UC management based on the clinical studies published between 2018 and 2025. Several studies report that both SSPs and MSPs are associated with clinical improvements, including reduced disease activity, symptom alleviation, and enhanced endoscopic outcomes. Given the methodological heterogeneity across included studies, comparative findings should be interpreted with appropriate caution. A direct head-to-head trial could provide a better understanding to determine the optimal approach. Advancing toward personalized probiotic therapy may further enhance the clinical application of probiotics for disease management.

Diabetes mellitus induces endothelial dysfunction and oxidative stress, contributing to the development of vascular complications. Although metformin exerts well-established vasculoprotective and antioxidant effects, the molecular mechanisms underlying these actions remain incompletely understood. Novel miR-1133 was previously identified as a metformin-responsive putative microRNA (miRNA), and bioinformatic analysis identified PIK3CA as a biologically plausible candidate target for further investigation. This study investigated the functional significance of novel miR-1133 in the antioxidant effects of metformin in hyperglycemia-induced human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to normal glucose (5.5 mmol/L), hyperglycemia (33.3 mmol/L), or hyperglycemia supplemented with metformin (10 μM) for 24 h. Metformin-treated hyperglycemic HUVECs were subsequently transfected with a novel miR-1133 mimic during continued hyperglycemic and metformin exposure. PIK3CA expression and oxidative stress markers, including reactive oxygen species (ROS), superoxide dismutase (SOD), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), were evaluated. Hyperglycemia increased novel miR-1133 expression, whereas metformin reduced its expression. Metformin treatment was associated with increased PIK3CA mRNA and protein expression, reduced ROS and 8-OHdG levels, and increased SOD expression and activity. Novel miR-1133 mimic transfection was associated with reduced PIK3CA expression, increased ROS and 8-OHdG levels, and decreased SOD expression and activity compared with the corresponding transfection control. Collectively, these findings demonstrate that metformin attenuates oxidative stress in hyperglycemia-induced endothelial cells and overall provide the first functional characterization of novel miR-1133. The reciprocal changes in PIK3CA expression and oxidative stress observed following novel miR-1133 mimic transfection suggest that novel miR-1133 may represent a candidate mediator of the endothelial antioxidant responses associated with metformin. Further studies are required to validate the direct interaction between novel miR-1133 and PIK3CA and to elucidate the underlying molecular mechanisms.