Archives of Physiology and Biochemistry最新文献

Introduction: Renal fibrosis is a significant factor in the progression of chronic kidney disease. This study examined how menthol affects thioacetamide (TA)-induced biochemical, molecular, and histopathological damage that leads to renal fibrosis and dysfunction.

Methods: Male Wistar rats were treated with TA (200 mg/kg, intraperitoneally) twice a week for four consecutive weeks, along with menthol (10 mg/kg, intraperitoneally) for the same duration.

Results: Menthol effectively reduced oxidative stress and inflammation in the kidneys of rats treated with TA. It also lowered the expression of TGF-β1, SMAD3, α-SMA, and KIM-1. Furthermore, menthol prevented the decline in SIRT1 mRNA expression and protein levels while increasing the expression of Nrf2. It inhibited collagen deposition and histological damage in the kidneys and prevented the rise in serum creatinine and BUN levels.

Conclusion: Menthol provides protective effects against renal fibrosis induced by thioacetamide. Its antifibrotic effects are mediated by upregulating SIRT1/Nrf2 and downregulating TGF-β1/Smad3 pathways.

Context: Diabetic cardiomyopathy (DCM) is a chronic cardiac disorder that develops independently of coronary artery disease or hypertension in individuals with diabetes. Despite being identified over fifty years ago, it remains poorly recognized, and its management lacks standardization. The rising global prevalence of diabetes has amplified the incidence of DCM, underscoring the urgent need to clarify its molecular underpinnings and clinical progression.

Objective: To provide a comprehensive review of the molecular and physiological mechanisms underlying diabetic cardiomyopathy, elucidating how metabolic dysregulation contributes to cardiac structural and functional alterations. This study also aims to highlight the potential therapeutic targets involved in the key signaling pathways of DCM pathogenesis.

Methods: A systematic literature review was conducted using major scientific databases, including PubMed, Scopus, and Web of Science, covering studies published between 2000 and 2025. Keywords used included "diabetic cardiomyopathy," "hyperglycemia," "insulin resistance," "oxidative stress," "inflammation," "mitochondrial dysfunction," and "therapeutic targets."

Data sources, study selection, and data extraction: Peer-reviewed articles, original research papers, and review articles focusing on molecular mechanisms, signaling pathways, and therapeutic interventions related to DCM were included. Studies involving both experimental models and human subjects were considered. Data were extracted regarding metabolic alterations, key signaling cascades (NF-κB, PARP1, GLUT4, AT1R), and their association with cardiac remodeling, fibrosis, and functional impairment. The information was synthesized to illustrate the progression from metabolic imbalance to clinical manifestations and to identify promising molecular targets for therapy.

Background: Ulcerative colitis is a chronic inflammatory bowel disease characterised by disrupted anti-inflammatory cell mechanisms in the intestinal mucosa.

Purpose: This study explores quercetin's protective role by restoring anti-inflammatory mechanisms and regulating this pathway.

Methods: Experimental models included DSS-induced mice and LPS-stimulated RAW264.7 cells, assessed via disease activity scoring, histopathology, qPCR, ELISA, and Western blot.

Results: Quercetin intervention could effectively repair the anti-inflammatory cell function, reverse the imbalance of inflammatory factors, inhibit the phosphorylation of p38 MAPK and the expression of MK2 and MK3, improve the intestinal mucosal damage and disease activity in mice, and reverse the pro-inflammatory polarisation of macrophages in vitro. Quercetin could further enhance the anti-inflammatory effect when combined with p38 MAPK inhibitor.

Conlusion: Therefore, quercetin can repair the anti-inflammatory cell action mechanism, inhibit the activation of p38 MAPK-MK2/MK3 signalling pathway, alleviate the inflammatory damage of intestinal mucosa in ulcerative colitis, and provide experimental basis for anti-inflammatory cell-targeted treatment of ulcerative colitis.

Aflatoxin B1 (AFB1) is a prominent mycotoxin known to cause significant toxic effects in numerous organs and tissues. Experimental studies on intestinal tissue demonstrate that AFB1-induced damage is primarily driven by free radical generation, oxidative stress, inflammatory responses, cytochrome P450 upregulation, lipid peroxidation, and apoptosis. In recent years, phytochemicals have attracted considerable interest due to their antioxidant, anti-inflammatory, and anti-apoptotic properties, which suggest a promising strategy for alleviating AFB1-related intestinal toxicity. Nevertheless, research on their therapeutic efficacy remains relatively limited. This review aims to assess the protective roles of phytochemicals in mitigating oxidative stress and inflammation associated with AFB1 exposure. Evidence indicates that well-studied phytochemicals such as curcumin, resveratrol, lycopene, melatonin, and polydatin reduce intestinal injury by modulating critical signalling pathways, including Nrf2/ARE, TLR4, NF-κB, and NLRP3, as well as by influencing the intestinal microbiota composition. Overall, this review highlights their potential therapeutic value and underlying molecular mechanisms.

Background: Osteoporosis is a global health problem characterised by decreased bone density and degeneration of bone microstructure, leading to an increased risk of fractures.

Purpose: The aim of this study is to explore the role of SOST protein regulation mechanism in enhancing bone strength during endurance training.

Methods: An animal model was constructed using 8-week-old male C57BL/6 mice and divided into five groups: blank control group, sham operation control group, endurance training group, SOST gene knockout (KO) control group, and SOST KO+endurance training group.

Results: The results showed that the levels of bone formation markers PINP and BALP in serum were significantly increased (P < 0.05), while the levels of bone resorption markers CTX and TRACP-5b did not show significant changes.

Conclusion: Therefore, endurance training activates the Wnt/β-catenin signalling pathway by downregulating SOST protein expression. SOST protein is a core molecular target for endurance training to enhance bone strength.

Introduction: The conditions associated with pregnancy, such as preeclampsia, gestational diabetes, and disruptions of Placental lipid transport, are increasingly becoming known to be the cause of intrauterine growth restriction. Recent data indicate that compensatory efforts can initiate neuroinflammatory and systemic reactions in the mother, which can influence foetal development. Methods: This study aims to learn how maternal brain inflammation and neuroimmune activation during complicated pregnancies can be triggered by abnormal placental lipid carriage. Results: PBIC-SM and NLIP-IM models are employed to examine lipid-induced CNS inflammation and neuroimmune lipidomic changes, focusing on how altered placental lipid transport affects maternal lipid profiles, oxidative stress, and inflammation. Conclusion: Disrupted lipid balance alters microglial activity and increases IL-6 and TNF-α levels, showing that impaired placental transport can trigger neuroinflammation during pregnancy. In high-risk cases, early intervention and targeted therapies may help preserve maternal mental health by addressing placenta-brain immune dysregulation.

Backgound: Breast cancer exhibits high heterogeneity and drug resistance, presenting severe challenges in clinical treatment.

Purpose and method: This study takes cellular lipid metabolism regulation as the core entry point, integrates network pharmacology and computational biology techniques to mine the breast cancer transcriptome data from the GEO database GSE45827, GSE33447, and TCGA-BRCA database. Combined with molecular docking technology, it verifies the binding characteristics and action mode of lidocaine with the core target proteins.

Result: The study identified 6 core genes regulated by lidocaine in breast cancer, G6PD, ALB, EDN3, FGF2, MAOB, and DMD, all of which are directly or indirectly related to cellular lipid metabolism regulation.

Conclusion: This study clarified the core mechanism by which lidocaine regulates the lipid metabolism reprogramming of breast cancer cells through multiple targets, revealed that cellular lipid metabolism regulation is the key pathway for its anti-tumour effect, and provided a metabolic-level theoretical basis for repurposing of lidocaine as an old drug.

Background:​ Delayed healing of diabetic wounds is driven by insufficient angiogenesis and maladaptive immunity. An unbiased screen of wound transcriptomes identified prolactin-induced protein (GCDFP-15) as consistently upregulated. Methods:​ Utilizing murine diabetic wound models, we investigated the functional role of GCDFP-15 through genetic deletion and topical recombinant protein administration. Results:​ Genetic deletion of GCDFP-15 accelerated wound closure, enhanced angiogenesis, and promoted a pro-reparative macrophage phenotype. This was mediated by activation of the PI3K/AKT/mTOR/STAT3 signalling axis. Conversely, topical GCDFP-15 impaired repair and inhibited this pathway in knockout mice. Conclusion:​ GCDFP-15 acts as an endogenous inhibitor of diabetic wound healing by suppressing pro-reparative signalling. Targeting GCDFP-15 may represent a novel therapeutic strategy.

Background: Urotensin II (U-II) is one of the most potent endogenous vasoconstrictors, with its vascular effects tightly regulated by endothelial function and ion channel activity. The impact of diabetes mellitus on the signalling mechanisms underlying U-II-induced vascular reactivity remains insufficiently understood.

Objective: This study systematically investigated how diabetes alters U-II-induced vasoconstriction by dissecting the contributions of endothelial integrity, potassium channel subtypes, calcium influx, and gap junction communication in the thoracic aorta of normoglycemic and streptozotocin-induced diabetic rats.

Methods: Isolated aortic rings with intact or denuded endothelium were exposed to cumulative concentrations of U-II (1 0 ^-11-1 0 -8 M). Pharmacological inhibitors-including L-NAME (NOS inhibitor), indomethacin (COX inhibitor), TEA (Kv channel blocker), BaCl₂ (Kir channel blocker), clotrimazole (IKCa channel blocker), nifedipine (L-type Ca²⁺ channel blocker), and GAP27 (gap junction inhibitor) were employed to delineate mechanistic pathways.

Results: Endothelial removal significantly potentiated U-II-induced contractions in both non-diabetic and diabetic vessels, affirming the critical modulatory role of endothelium-derived vasodilators. Diabetic vessels exhibited marked reductions in maximal contraction (Emax) and sensitivity (pD₂) to U-II. In non-diabetic aorta, Kir and IKCa channel blockade robustly suppressed U-II-induced contraction, whereas these effects were diminished or reversed in diabetic tissue, indicating functional channel dysregulation. L-NAME potentiated U-II responses selectively in diabetes, implicating impaired nitric oxide bioavailability. Strikingly, nifedipine enhanced U-II-mediated contraction in diabetic rats, suggesting maladaptive remodelling of calcium influx. GAP27 reduced U-II responses, with a more pronounced inhibitory effect in diabetic vessels, highlighting disease-specific alterations in gap junction signalling.

Conclusion: Diabetes markedly impairs urotensin II-induced vascular contractility by disrupting Kir and IKCa potassium channel function, alongside distinct changes in calcium channels, gap junctions, and prostanoids. Restoring Kir and IKCa  may offer an effective therapeutic strategy to reverse vascular dysfunction in diabetic vascular myopathy.