Cellular Physiology and Biochemistry最新文献

The widespread presence of environmental pollutants, including toxic metals, microplastics, and antibiotics, has significantly altered gut microbiota composition and functionality, leading to dysbiosis and oxidative stress. These changes contribute to various adverse physiological effects, including systemic inflammation, mitochondrial dysfunction, and intestinal barrier dysfunction. This review provides a comprehensive analysis of the molecular mechanisms by which these environmental factors induce oxidative damage, emphasising the importance of redox imbalance, the overproduction of reactive oxygen species, and inflammatory signalling pathways. Key pathways involved include NF-κB, Nrf2/Keap1, PI3K/AKT, p38-MAPK, JAK/STAT and TLR4/MyD88. These pathways collectively contribute to the progression of chronic inflammatory conditions. Furthermore, this article synthesises findings from 354 studies published between 2016 and 2024, integrating human and animal research evidence. Existing literature suggests that gut dysbiosis exacerbates oxidative stress through impaired short-chain fatty acid production, downregulation of peroxisome proliferator-activated receptor gamma, and disruption of antioxidant enzyme activity. This review explores these mechanisms in more detail. Additionally, the review evaluates studies investigating microbiota-targeted therapeutic interventions to mitigate oxidative stress. These interventions include probiotics, prebiotics, polyphenols, and postbiotics, focusing on their reported modulation of Nrf2 and AMPK signalling pathways. The potential of faecal microbiota transplantation as an innovative approach to restoring a healthy gut ecosystem and counteracting pollutant-induced oxidative damage is also discussed. In light of the growing global exposure to environmental pollutants and their associated long-term health implications, it is imperative to gain a deeper understanding of their impact on gut microbiota and oxidative stress. This topic remains at the forefront of biomedical research due to its implications for public health, disease prevention, and developing novel therapeutic strategies.

Since its discovery in 1997, αKlotho has gained a lot of attention due to its powerful anti-aging and health-promoting properties. It exists as a membrane-bound protein or as a soluble factor. Membrane-bound αKlotho is an essential cofactor for fibroblast growth factor 23 (FGF23), thereby being involved in the regulation of renal phosphate and vitamin D metabolism. Soluble αKlotho (sKL) is present in different body fluids and exerts hormone-like effects. Through the αKlotho-FGF23 signaling axis, FGF23 regulates phosphate excretion by downregulating Na+-dependent phosphate transporter (NaPi-2a). In addition, this axis suppresses expression of 1α-hydroxylase, thereby reducing active vitamin D (calcitriol) serum concentration. Disruptions of this axis lead to deranged mineral metabolism. Low levels of αKlotho and elevated FGF23 are early biomarkers for different diseases, including chronic kidney disease (CKD) and cardiovascular diseases (CVD). In CKD, decreased renal αKlotho expression and enhanced FGF23 production contribute to worsening kidney function. Activated transforming growth factor b1 (TGF-b1) signaling, promoting renal fibrosis, contributes to the pathophysiology. Moreover, FGF23 directly induces left ventricular hypertrophy (LVH) through FGF receptor-induced calcineurin/nuclear factor of activated T cells (NFAT) signaling in CKD. Our review aims to comprehensively summarize the regulation and function of αKlotho, highlighting its central role in maintaining mineral metabolism and its therapeutic potential in age-related and chronic diseases.

Background/aims: Arteriosclerosis (AS) remains a leading cause of global mortality, with macrophage senescence playing a crucial role in its progression. Senescent macrophages, characterized by oxidative stress and inflammation, exhibit dysregulated mitophagy. However, the underlying mechanisms remain unclear.

Methods: This study explores the role of caveolin-1, a structural protein of caveolae, in NR4A1-mediated mitophagy during oxLDL-induced macrophage senescence. Using gene knockdown and overexpression models, we assessed mitochondrial dysfunction, ROS production, cytokine secretion, and mitophagy activity in murine macrophages.

Results: It revealed that NR4A1 promoted mitochondrial dysfunction and senescence through enhanced ROS production and disrupted mitochondrial potential. Caveolin-1 mediated this effect by facilitating NR4A1-induced mitophagy, as evidenced by colocalization of mitochondria and lysosomes and the activation of Parkin-related pathways. NR4A1 upregulated caveolin-1 expression, forming a signaling axis critical for senescence-associated pro-inflammatory cytokine production.

Conclusion: Overall, our study unraveled The NR4A1-caveolin-1 axis orchestrates mitophagy and inflammation in senescent macrophages, shedding light on AS pathogenesis and suggesting potential therapeutic targets to mitigate macrophage-driven inflammation and oxidative stress.

Background/aims: Post-acute COVID-19 syndrome (PACS) presents with persistent symptoms such as fatigue, dyspnea, and cognitive impairment, even after apparent clinical recovery. Although widely reported, the biological basis of these symptoms remains unclear. This study aimed to investigate the underlying cellular, immunological, oxidative, and biochemical disturbances during the recovery phase of COVID-19 and evaluate their association with clinical symptomatology.

Methods: A cross-sectional observational study was conducted involving 120 participants who were previously SARS-CoV-2 positive, recruited ≥30 days post-recovery. Peripheral blood samples were analyzed for ER stress markers (HSP70, CHOP, GRP78), Pro- and anti-inflammatory cytokines (IL-6, TNF-α, IFN-γ, IL-10), oxidative biomarkers (MDA, SOD, GSH), and biochemical parameters (ALT, AST, CRP, ferritin). T cell subsets were evaluated via flow cytometry. Statistical comparisons and correlation analyses were performed using SPSS v22.0.

Results: Significant elevations were observed in all stress and inflammatory markers (p < 0.05). IL-6, CRP, and MDA showed strong positive correlations with fatigue and dyspnea scores. Treg percentages were reduced, and males exhibited higher biomarker levels than females. Persistent immune and oxidative activation was evident in the recovery phase.

Conclusion: Post-acute COVID-19 is associated with quantifiable cellular and molecular disturbances. This integrated analysis of ER stress, immune dysregulation, and oxidative imbalance provides a novel and comprehensive view of long COVID pathophysiology.

Drug development is a complex, high-risk, and resource-intensive process, with global challenges such as high costs, regulatory hurdles, and low clinical trial success rates. These obstacles are especially acute for biotech startups and companies in emerging markets, where access to infrastructure, patient populations, and capital can be limited. This Perspective advocates for Abu Dhabi's emerging life sciences ecosystem as a potential framework for other regions seeking to accelerate pharmaceutical innovation. By offering government-backed incentives, advanced research infrastructure, regulatory support, and access to regional genomic data, Abu Dhabi provides a model for addressing industry bottlenecks and fostering sustainable drug development growth in new markets.

Background/aims: Magnesium and zinc are vital trace elements found in numerous foods and dietary supplements. In addition to their antioxidant, anticancer, antibacterial, and anti-inflammatory effects, clinical research has suggested that they possess anti-allergic properties.

Methods: Using differential-interference contrast (DIC) microscopy, we examined the effects of magnesium chloride (MgCl2) and zinc chloride (ZnCl2) on rat peritoneal mast cell degranulation. We also examined their effects in conjunction with adrenaline, the first-choice drug for anaphylaxis treatment.

Results: Both MgCl2 and ZnCl2 reduced the number of degranulating mast cells in a dose-dependent manner. MgCl2 significantly decreased the number of degranulating mast cells at concentrations of 50 mM or higher, whereas ZnCl2 achieved similar effects at much lower concentrations of 25 µM or more. These levels of MgCl2 or ZnCl2 enhanced the inhibitory effects of 1 mM adrenaline on mast cell degranulation. Additionally, pharmacological inhibition of the transient receptor potential cation channel subfamily M member 7 (TRPM7) by NS8593 reduced the number of degranulating mast cells in a dose-dependent manner.

Conclusion: This study is the first to provide in vitro evidence that magnesium and zinc stabilize mast cells in a dose-dependent manner and also enhance the effects of adrenaline. TRPM7, which has higher permeability to zinc ions than to magnesium ions, may contribute to the stronger mast cell-stabilizing properties of zinc.

Background/aims: Bladder cancer is a type of malignant tumor that disrupts normal urinary function in patients, thereby significantly impacting their quality of life. This disease also imposes a heavy economic burden on both patients and public health agencies due to high medical costs. Current common therapies, such as surgical intervention, chemical treatment, and radiotherapy, are associated with serious adverse reactions and risks of metastasis recurrence. Effective attenuation of bladder cancer proliferation and invasion remains a significant challenge. Circular RNAs have shown promise in regulating proliferation and migration of cancer cells, thus making it a potential therapeutic target for bladder cancer treatment and prognosis. This study aims to evaluate the impact of regulating circPTK2 expression on progression of bladder cancer.

Methods: This research established overexpression and knock down circPTK2 models of bladder cancer cells (SW780 and UM-UC-3) primarily. Then evaluate the effect by a series of cell function test (including RT-qPCR, MTT, EdU assay, cell clone, transwell, cell cycle and cell apoptosis).

Results: The findings suggest that regulated expression of circPTK2 in bladder cancer cells correlated with the abundance of mir129-5p. Meanwhile, knock down circPTK2 expression in bladder cancer cells reduced their ability to proliferate and invade; but these processes were reversed when circPTK2 expression was increased.

Conclusion: In conclusion, circPTK2 may play a vital role in regulating bladder cancer progression, thereby showing potential for treatment of bladder cancer and improvement of prognosis by modulating circPTK2.

Background/aims: Obesity Resistance (OR) is characterized by limited weight gain and reduced fat accumulation despite an obesogenic diet. However, the metabolic risk, particularly regarding Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), remains unclear. The current study aims to investigate the presence of MASLD, as well as metabolic parameters and morphological aspects of adipose tissues in obesity-resistant (OR) R rats fed a high-fat diet (HFD).

Methods: ale Wistar rats (n=71) were initially randomized into two groups: a) standard diet (SD, n=35) and b) high-fat diet (HFD, n=36). The protocol was performed for 14 weeks, including 4 weeks of induction and 10 weeks of exposure to obesity. Subsequently, after applying the tertile classification criterion, the animals were redistributed into three groups: a) control (C, n=12), fed a standard diet; b) obesity-prone (OP, n=12); and c) OR (n=12). Body weight evolution, adiposity, nutritional behavior, metabolic markers, and liver morphology were assessed, along with the staging of MASLD.

Results: OR rats exhibited lower body weight, total fat pads, and leptin compared to OP but higher values than C. MASLD was observed in 50% of OR animals, while 37.5% progressed to metabolic dysfunction-associated steatohepatitis (MASH). OP rats had a higher incidence of MASH (87.5%).

Conclusion: Chronic HFD exposure in OR rats lead to metabolic changes and MASLD development, including MASH, demonstrating that OR does not protect against HFD-induced hepatic alterations.

Background/aims: Post-translational prenylation of G proteins is implicated in physiological insulin secretion. It has been reported recently that GGTase-III participates in the functional regulation of Ykt6, a synaptobrevin homolog, via geranylgeranylation. However, potential localization and putative regulatory roles of GGTase-III in insulin secretion remains unknown. The current study is aimed at determining the expression and contributory roles of GGTase-III in glucose- and KCl-induced insulin secretion from pancreatic β-cells.

Methods: Mouse islets were isolated by the collagenase digestion method. Human islets were from Prodo Laboratories. INS-1 832/13 cells were transfected with either control (scrambled) or siRNA-PTAR1 (the α-subunit of GGTase-III) using lipofectamine RNAiMax. Insulin released into the medium was quantified using a commercially available Insulin ELISA kit. Expression of GGTase-III subunits and ykt6 was determined by Western blotting and quantified by densitometry.

Results: Western blotting revealed that both subunits of GGTase-III (PTAR1 and RabGGTB) are expressed in human islets, mouse islets and INS-1 832/13 cells. Transfection of INS-1 832/13 cells with siRNA-PTAR1 resulted in significant reduction (~50%) in the expression of PTAR1. siRNA-mediated knockdown of PTAR1 significantly attenuated (~60%) glucose-stimulated insulin secretion (GSIS) in INS-1 832/13 cells. Furthermore, insulin secretion elicited via KCl-induced membrane depolarization was markedly reduced (~69%) in INS-1 832/13 cells following PTAR1 depletion. Lastly, immunoblotting data suggested expression of Ykt6, a known substrate for GGTase-III, in human islets, rodent islets, and INS-1 832/13 cells.

Conclusion: GGTase-III-dependent signaling step is necessary for glucose- and KCl-induced insulin secretion.