Cell. Physiol. Biochem. [JOURNAL]
Sun
200 papers
Mast Cell Response to Parasites: from Recognition and Activation to Host Defense Modulation.
Żelechowska P, Góralczyk-Bińkowska A
Cell Physiol Biochem · 2025 Sep · PMID 41047922 · Publisher ↗
Parasites represent a diverse and widely distributed group of pathogens that cause diseases with significant global health implications. The interaction between parasite and host is characterized by a high degree of comp...
Parasites represent a diverse and widely distributed group of pathogens that cause diseases with significant global health implications. The interaction between parasite and host is characterized by a high degree of complexity, with both parties continuously adapting to changes in the other. The successful host invasion is largely attributable to the evasion strategies employed by parasites to ensure their survival in immunocompetent individuals. In turn, the host's defense mechanisms utilize a variety of structures and processes, ranging from primary barriers to the most sophisticated ones, to counter the parasite attack. Acting as an early line of defense, the immune system includes a variety of cell types that are capable of recognizing, destroying, and eliminating infectious agents. Undoubtedly, the orchestration of first-line innate immune responses but also adaptive immunity processes during infection depends to a large extent on the involvement of tissue-resident mast cells (MCs). MCs are capable of supporting immune reactions to parasites through a broad spectrum of processes, including degranulation, synthesis and release of cytokines/chemokines and other mediators, and the generation of reactive oxygen species (ROS). They may also be involved in immune cell recruitment, phagocytosis, and the provision of extracellular DNA traps. Despite the well documented association of MCs with antibacterial and antiviral defense, their role in host protection against parasites remains incompletely identified. This article provides an overview of the engagement of MCs in host defense mechanisms developed during parasitic infections. Furthermore, it considers the impact of parasites or parasite-derived molecules on the various aspects of MC activity.
Characterization and Industrial Application of the Enzyme Papain Through the Use of a Biosensor.
Vergara Velez G, Domínguez Brito LD, Cerón Erazo ML … +8 more , Rivadeneira Z RA, Intriago Flor FG, Anchundia Loor AM, Alfonso YR, Álvarez Ojeda V, Díaz Izurieta JF, Tumbaco J, Jadán Piedra F
Cell Physiol Biochem · 2025 Sep · PMID 40955539 · Publisher ↗
BACKGROUND/AIMS: Casein influences coagulation, yield, and product quality. This study aimed to develop and validate a papain (EC 3.4.22.2)-based biosensor to quantify casein in whole milk, evaluating its kinetic behavio...
BACKGROUND/AIMS: Casein influences coagulation, yield, and product quality. This study aimed to develop and validate a papain (EC 3.4.22.2)-based biosensor to quantify casein in whole milk, evaluating its kinetic behavior and comparing it with HPLC. METHODS: Papain was immobilized on nylon membranes and a cassava starch biopolymer. Enzyme kinetics (KM), stability, sensitivity, precision, and linearity of the system were evaluated. A t-test (α = 0.05) was applied to compare the casein concentration obtained by the biosensor versus HPLC (n = 20). Interference from milk proteins and calcium was also analyzed. RESULTS: The biosensor showed high affinity for casein (KM = 0.037 mM), with a linear range of 0.001-0.03 mM (R² = 0.9974) and a response time <5 s. No significant differences were found with HPLC (p = 0.0665). Stability reached 70 days at 4°C and was reusable up to 15 times. CONCLUSION: The developed biosensor proved to be an accurate, fast, and sustainable analytical alternative for the determination of casein in complex milk matrices.
Association Between DRD4 rs747302 and VNTR Polymorphisms and Drug Addiction in An Iraqi Population.
Kadhim SAH, Neamaa AF, Mahmoud YI … +1 more , Al-Ganzuri MA
Cell Physiol Biochem · 2025 Sep · PMID 40926693 · Publisher ↗
BACKGROUND/AIMS: Drug addiction is a neuropsychiatric disorder characterised by compulsive drug-seeking behaviour notwithstanding adverse consequences. This work seeks to address a deficiency in the literature by compari...
BACKGROUND/AIMS: Drug addiction is a neuropsychiatric disorder characterised by compulsive drug-seeking behaviour notwithstanding adverse consequences. This work seeks to address a deficiency in the literature by comparing drug-addicted and non-addicted individuals within an Iraqi population through the analysis of a 1000-base pair variable number of tandem repeats (VNTRs) polymorphism of the dopamine receptor gene DRD4. The association of this novel polymorphism with drug addiction has not yet been examined. METHODS: A total of 270 people were registered between May 2022 and June 2023. Of these, 180 had drug addictions and 90 were healthy controls. DNA was extracted from the participants' blood samples. Restriction Fragment Length Polymorphism was used to investigate genetic polymorphisms in the DRD4 and VNTR genes to identify differences. RESULTS: The genotype frequencies differed markedly between the control group (GC, 3% frequency) and the patient group (GC, 37% frequency). The control group had more of the genotype that was more common among addicts. The C allele was present in 60% of the patients but in only 1% of the controls. The results showed that the CC genotype is more common in the patient group than in the control group. A comparison of repetitions between the control and patient groups was made based on the distribution of genotypes of SNP rs747302. Patients with the GG genotype had an average of 17 repetitions, whereas those with the GC genotype had 18, and those with the CC genotype had 18.3. The results showed that people in the CC genotype group had a lot more repetitions. CONCLUSION: The results of our study indicated that the CC, GC, and VNTR genotypes significantly contribute to heroin addiction risk in Iraqis.
Enhanced ISGylation via USP18 Isopeptidase Inactivation Fails to Mitigate the Inflammatory or Functional Course of Coxsackievirus B3-Induced Myocarditis.
Kelm N, Kespohl M, Borowski S … +5 more , Ochs S, Knobeloch KP, Huis In 't Veld LGM, Klingel K, Beling A
Cell Physiol Biochem · 2025 Sep · PMID 40926642 · Publisher ↗
BACKGROUND/AIMS: The ubiquitin-like protein ISG15 and its covalent conjugation to substrates (ISGylation) represent a critical interferon (IFN)-induced antiviral mechanism. USP18 is an ISG15-specific isopeptidase and a k...
BACKGROUND/AIMS: The ubiquitin-like protein ISG15 and its covalent conjugation to substrates (ISGylation) represent a critical interferon (IFN)-induced antiviral mechanism. USP18 is an ISG15-specific isopeptidase and a key negative regulator of type I IFN signaling. While inactivation of USP18's catalytic activity enhances ISGylation and promotes viral resistance, its role in modulating inflammation and cardiac function during CVB3-induced myocarditis remains unclear. This study aimed to determine whether selective inactivation of USP18 isopeptidase activity influences the inflammatory and functional course of viral myocarditis. METHODS: Usp18 C61A/C61A knock-in mice, which lack USP18 isopeptidase activity but retain IFN regulatory function, were used on both C57BL/6 and A/J backgrounds. Mice were infected with the cardiotropic CVB3-Nancy strain, and disease progression was assessed through virological, histological, immunological, and echocardiographic analyses. Immune cell infiltration was quantified by flow cytometry, and ISGylation was assessed by immunoblotting. RESULTS: Despite enhanced ISGylation, Usp18 C61A/C61A mice did not exhibit altered cardiac viral titers or inflammation compared to wild-type controls. Histological scores and immune cell composition in the heart were similar between genotypes in both C57BL/6 and A/J backgrounds. Echocardiography confirmed functional impairment following CVB3 infection but revealed no significant genotype-dependent differences in cardiac performance. Inflammatory cytokine expression was largely unaffected by enhanced ISGylation, with only minor differences observed. CONCLUSION: While ISGylation is critical for antiviral protection in CVB3 infection, selective inactivation of USP18 isopeptidase activity does not mitigate myocardial inflammation or dysfunction during established CVB3 myocarditis. These findings suggest that therapeutic enhancement of ISGylation alone may be insufficient to control inflammation-driven cardiac damage in this model.
Migrasomes in Health and Disease: Insights into Mechanisms, Pathogenesis, and Therapeutic Opportunities.
Akeme L, Sibanda P, Fitzgerald A … +4 more , Bossowska A, Bonowicz K, Jerka D, Gagat M
Cell Physiol Biochem · 2025 Sep · PMID 40916870 · Publisher ↗
Migrasomes are newly discovered, migration-dependent organelles that mediate the release of cellular contents into the extracellular environment through a process known as migracytosis. Since their identification in 2014...
Migrasomes are newly discovered, migration-dependent organelles that mediate the release of cellular contents into the extracellular environment through a process known as migracytosis. Since their identification in 2014, growing evidence has highlighted their critical roles in intercellular communication, organ development, mitochondrial quality control, and disease pathogenesis. Migrasome biogenesis is a complex, multi-step process tightly regulated by lipid composition, tetraspanin-enriched microdomains, and molecular pathways involving sphingomyelin synthase 2, Rab35, and integrins. Unlike exosomes, migrasomes possess distinct structural and functional characteristics, which position them as novel organelles rather than classic extracellular vesicles. Recent studies have revealed their involvement in diverse pathological contexts, including kidney disease, cancer progression, proliferative vitreoretinopathy, viral infections, and myocardial infarction. Notably, migrasomes hold promise as diagnostic biomarkers, especially in early podocyte injury, and as therapeutic targets in oncology and regenerative medicine. This review summarizes the current understanding of migrasome biology, and their implications in health and disease, and explores emerging perspectives on harnessing migrasomes for diagnostic and therapeutic applications.
Macrophage Migration Inhibitory Factor: Its Multifaceted Role in Inflammation and Immune Regulation Across Organ Systems.
Aliyarbayova A, Sultanova T, Yaqubova S … +3 more , Najafova T, Sadiqova G, Salimova A
Cell Physiol Biochem · 2025 Sep · PMID 40916855 · Publisher ↗
Macrophage Migration Inhibitory Factor (MIF) is a pleiotropic cytokine that acts as a central regulator of inflammation and immune responses across diverse organ systems. Functioning upstream in immune activation cascade...
Macrophage Migration Inhibitory Factor (MIF) is a pleiotropic cytokine that acts as a central regulator of inflammation and immune responses across diverse organ systems. Functioning upstream in immune activation cascades, MIF influences macrophage polarization, T and B cell differentiation, and cytokine expression through CD74, CXCR2/4/7, and downstream signaling via NF-κB, ERK1/2, and PI3K/AKT pathways. This review provides a comprehensive analysis of MIF's mechanistic functions under both physiological and pathological conditions, highlighting its dual role as a protective mediator during acute stress and as a pro-inflammatory amplifier in chronic disease. MIF's involvement in autoimmune disorders, neurodegeneration, metabolic syndromes, infectious diseases, and oncogenesis is examined, with particular attention to its contribution to immune dysregulation, immune escape, and the shaping of inflammatory microenvironments. Its clinical relevance as a biomarker is underscored by associations between elevated serum levels, polymorphic variants such as the -173 G>C SNP, and disease susceptibility, progression, and therapeutic response. Advances in therapeutic strategies are also discussed, including the development of small-molecule inhibitors, MIF-2-specific antagonists, CD74-targeted therapies, and gene-based interventions. Taken together, emerging evidence positions MIF as both a diagnostic indicator and a therapeutic target, with its broad regulatory functions across immune, vascular, and metabolic pathways emphasizing its relevance in precision immunotherapy and its potential to serve as a strategic axis in the future of translational medicine.
Knockdown of UBD Ameliorates Experimental Rheumatoid Arthritis by Suppressing TLR4/Myd88/NF-κB and P38/MAPK Pathway.
Chen H, Liu S, Zhang Y … +2 more , Jun O, Wei H
Cell Physiol Biochem · 2025 Sep · PMID 40916849 · Publisher ↗
BACKGROUND/AIMS: Ubiquitin D (UBD), a member of the ubiquitin-like modifier (UBL) family, is significantly overexpressed in various cancers and is positively correlated with tumor progression. However, the role and under...
BACKGROUND/AIMS: Ubiquitin D (UBD), a member of the ubiquitin-like modifier (UBL) family, is significantly overexpressed in various cancers and is positively correlated with tumor progression. However, the role and underlying mechanisms of UBD in rheumatoid arthritis (RA) remain poorly understood. This study aimed to investigate the effects of UBD knockdown on the progression of RA. MATERIALS: We employed the type II collagen and incomplete Freund's adjuvant (CIA) rat model. A variety of analytical techniques were employed, including hematoxylin and eosin (H&E) staining, Safranin O and Fast Green staining, tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis, to elucidate the mechanisms involved. RESULTS: UBD knockdown correlated with diminished cartilage and bone erosion, reduced counts of TRAP-positive osteoclasts, and enhanced Safranin O staining of the cartilage. Additionally, the knockdown significantly reduced serum levels of PGE2, TNF-α, TIMP-1, IL-1β, MMP-9, and IL-6 in CIA rats. Furthermore, UBD knockdown markedly suppressed the expression levels of phosphorylated p38, TLR4, MyD88, and phosphorylated p65, suggesting a critical role in modulating inflammatory signaling pathways in RA. CONCLUSION: Collectively, these results suggested that knockdown of UBD significantly alleviated arthritis progression in the CIA rat model, highlighting UBD as a potential therapeutic target and a promising prognostic biomarker for RA.
Co-Immobilization of Trypsin and Lysine -α- Oxidase For the Quantification of Lysine in Casein Hydrolysate. Evaluation with a Biosensor.
Villavicencio Yanos CM, Cedeño Vivas MJ, Real Pérez GL … +7 more , Muñoz Murillo JP, Guamán SB, Santana Moreira GJ, Cantos SM, Bolaños de la Torre VF, Litardo Velásquez RM, Jadán Piedra F
Cell Physiol Biochem · 2025 Aug · PMID 40916799 · Publisher ↗
BACKGROUND/AIMS: The quantification of amino acids in the dairy industry is necessary for quality control and for the formulation of functional foods. Thus, the development of enzymatic biosensors requires a detailed stu...
BACKGROUND/AIMS: The quantification of amino acids in the dairy industry is necessary for quality control and for the formulation of functional foods. Thus, the development of enzymatic biosensors requires a detailed study of enzyme kinetics. Parameters such as KM and Vmax are necessary to optimize the sensitivity and specificity of the biosensor. METHODS: The enzyme immobilized on nylon and yucca bipolymer membranes was studied to evaluate possible interferences in the amperometric sensor. RESULTS: The sensor developed based on enzyme kinetics proved to be a reliable, sensitive, and low-cost alternative for determining lysine in dairy products. Its performance, comparable to HPLC, together with its low environmental impact, positions it as a useful tool for quality control in the food industry. CONCLUSION: An enzymatic biosensor capable of quickly, accurately, and economically quantifying lysine in casein hydrolysates was developed. Its high sensitivity, enzymatic stability, and low environmental impact make it a viable and comparable alternative to HPLC for quality control in dairy products.
Non-Enzymatic Antioxidant Defense and Polymorphic Changes in Male Infertility.
Baszyński J, Kamiński P, Szymański M … +9 more , Wasilow K, Stanek E, Brodzka S, Grochowalska R, Stuczyński T, Bilski R, Hromada M, Kurhaluk N, Tkaczenko H
Cell Physiol Biochem · 2025 Aug · PMID 40851487 · Publisher ↗
BACKGROUND/AIMS: Male infertility is conditioned in up to 25% genetically, but environmental factors are equally important. Dependencies analyzed here in this area have not been studied using such an approach so far. The...
BACKGROUND/AIMS: Male infertility is conditioned in up to 25% genetically, but environmental factors are equally important. Dependencies analyzed here in this area have not been studied using such an approach so far. Therefore, they are innovative and constitute an important aspect of multi-range interdependencies. That is why we analyzed factors shaping male reproductive condition: glutathione, bilirubin, uric acid, chemical elements (Ca, Na, Mn, Fe, Mo, Li, V, Co, Ag, Ba, Tl, Al, Ni, Sn, B, Pb, Be), and genetic polymorphism (genotypes CC and TT of IL-4v.C589T(rs2243250). We studied infertile men from polluted Poland region with semen perturbations and healthy with normozoospermia. METHODS: We described semen abnormalities according to standard criteria. The population of patients with infertility consisted of 76 men with different fertility disorders. The control group consisted of 87 men with normozoospermia. The majority of infertile men came from Central Poland. The collection of biological samples and seminological tests were conducted by qualified medicians from the andrology clinic and by the authors of this paper (semen morphological parameters). Seminological analyses were based on macro- and microscopic analysis of ejaculate to verify semen volume, time of liquefaction, sperm density, motility, presence of agglutination, presence of leukocytes, and percentage of pathological forms. Concentrations of chemical elements in the blood were analyzed (ICP-MS). In serum, non-enzymatic antioxidants (glutathione GSH, bilirubin, uric acid) and lipid peroxidation intensity were qualified (Cayman Chemicals Co.). In researching gene polymorphisms connected with male infertility, molecular analysis was conducted (PCR-RFLP) and applied to chromosome 5: gene IL-4v.C589T. RESULTS: We found poorer antioxidative defense in infertile men, whilst the higher levels of uric acid, compared to healthy, may act as a deteriorating factor. High correlations between glutathione and uric acid in the infertile and healthy implicated that non-enzymatic antioxidants undergo mutual regulation. It also applies to patients with IL-4v.C589T polymorphism. Interactions between non-enzymatic antioxidants and chemical elements were particularly noticeable in men with CC genotype. The most important modulator appeared to be sodium, while boron was the most meaningful in the interactions. Higher concentration of bilirubin, uric acid, and GSH in men with TT (0.687 mg·dL-1, 6.097 mg·dL-1, 6.345 µM), compared to CC genotype (0.652 mg·dL-1, 4.980 mg·dL-1, 4.630 µM) suggest a better functionality of antioxidative barrier. Estimating the importance of unfavorable changes arising from oxidative stress about the functionality of non-enzymatic antioxidants and correlations with MDA in men's serum allows a complete look at the determinants of male infertility. Among genetic polymorphisms, genotypes TT and CC of IL-4v.C589T gene show their influence on generating fertility perturbations. They had an indirect but differentiated effect on antioxidant mechanisms involving bilirubin, uric acid, and glutathione. Therefore, we conclude that IL-4v.C589T polymorphism differentiated the body's response to environmental stressors. The results presented in our paper on IL-4v.C589T polymorphism and conclusions formulated on their basis are consistent with literature data, indicating the lack of a direct relationship between polymorphism studied and male infertility. However, the primary intention of this paper was, to a lesser extent, to exclude or confirm a direct relationship between studied polymorphism and male infertility. We wanted a broader approach to the subject and to establish relationships between genetic aspects and antioxidant parameters of defense mechanisms. Therefore, we were more interested in the status of antioxidant defense and its relationships to the genetic factor in groups of people with a fixed genotype. We obtained a more detailed picture of the sum of genetic aspects and parameters related to antioxidant defense. CONCLUSION: Non-enzymatic defense, chemical elements, and genetic polymorphisms are related to and shape male reproductive potential. Our results may be helpful in the diagnosis of male infertility; they will enable the reduction of idiopathic cases and the implementation of targeted and more effective treatment. Identification of environmental stressors and their correlations with fertility disorders can help eliminate or reduce the impact of factors unfavorable to fertility. This shows the new importance of environmental and immunogenetic factors, oxidative stress, and genetic polymorphisms in male fertility.
Editorial: Therapeutic Frontiers and Physiological Impacts of Oxidative Stress Across Biological Systems.
Kurhaluk N
Cell Physiol Biochem · 2025 Aug · PMID 40851485 · Publisher ↗
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Role of Gut Microbiota in Modulating Oxidative Stress Induced by Environmental Factors.
Kurhaluk N, Kamiński P, Tkaczenko H
Cell Physiol Biochem · 2025 Aug · PMID 40851483 · Publisher ↗
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 stre...
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.
Oxidative Stress, Antioxidants, Gut Microbiota and Male Fertility.
Kurhaluk N, Kamiński P, Tkaczenko H
Cell Physiol Biochem · 2025 Aug · PMID 40851482 · Publisher ↗
It is imperative to comprehend the multifactorial causes of male infertility and to identify effective treatment methods, to enhance male reproductive health, and to develop more personalised and effective therapeutic in...
It is imperative to comprehend the multifactorial causes of male infertility and to identify effective treatment methods, to enhance male reproductive health, and to develop more personalised and effective therapeutic interventions. This review discusses the multifactorial aspects contributing to male infertility, focusing on oxidative stress (OS), sperm quality, gut microbiota, and the potential role of adaptogens. A comprehensive literature search was conducted across several major databases, including the Cochrane Library, Medline, Embase, SciSearch, PubMed, Web of Science, Scopus, and Google Scholar. The findings from the studies included in the databases highlight the significant role of oxidative stress in male infertility, with reactive oxygen species (ROS) contributing to sperm DNA fragmentation and impairment of spermatogenesis. The review further elucidates the influence of both endogenous and exogenous sources of ROS, including lifestyle factors and environmental exposures, on male reproductive health. Emerging research also highlights the involvement of key molecular pathways, such as Nrf2, AMPK/PGC-1α, and NF-κB, in regulating OS within the male reproductive system. Additionally, the review outlines the relationship between endothelial dysfunction, cardiovascular health, and male infertility, identifying OS as a common underlying factor. In addition to the OS, the gut microbiota has been identified as a pivotal factor in male fertility, influencing inflammation and hormonal regulation. This review underscores the potential merits of a synergistic strategy that integrates dietary interventions, antioxidants, gut microbiota modulation, and adaptogens to enhance fertility outcomes. Adaptogens, recognised for their capacity to assist the body in coping with stress and re-establishing equilibrium, may confer protective effects against OS and improve reproductive health. The review under discussion emphasises the importance of a holistic approach to male infertility, integrating molecular, clinical, and lifestyle factors to optimise reproductive health.
Regulation of αKlotho.
Vogt J, Föller M
Cell Physiol Biochem · 2025 Aug · PMID 40784026 · Publisher ↗
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 a...
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.
Role of NR4A1-Caveolin-1 Axis in the Orchestration of Mitophagy During Macrophage Senescence.
Li P, Tian T, Huang X
Cell Physiol Biochem · 2025 Aug · PMID 40784024 · Publisher ↗
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 infla...
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.
Post-Acute COVID-19 Pathophysiology: Cellular Stress Responses, Immune Dysregulation, and Biochemical Signatures in Recovery Phase.
Alhudiri IM, Gaballa MF, Ebrahim FO … +4 more , Ahire KD, Eltaib FI, Attitalla IH, Elzagheid AI
Cell Physiol Biochem · 2025 Jul · PMID 40755239 · Publisher ↗
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 b...
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 in Abu Dhabi: Advancing Innovation Through Government Support and a Thriving Ecosystem.
Shaabani N, Saleh AI, Alameri MS … +2 more , Hashmi S, Nadi TA
Cell Physiol Biochem · 2025 Jul · PMID 40692424 · Publisher ↗
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 biot...
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.
Magnesium and Zinc Dose-Dependently Stabilize Rat Peritoneal Mast Cells and Enhance the Effects of Adrenaline.
Kazama I, Sonobe H, Shida J
Cell Physiol Biochem · 2025 Jul · PMID 40692390 · Publisher ↗
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...
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.
Protein Tyrosine Kinase 2 Circular RNA Promotes Proliferation and Invasion of Bladder Cancer.
Cao J, Wang G, Zhao Y … +10 more , Zhang G, Wang Q, Peng H, Liang J, Zhou J, Dong Y, Li S, Jiang K, Pei C, Wang Q
Cell Physiol Biochem · 2025 Jul · PMID 40654029 · Publisher ↗
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...
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.
High-Fat Diet Induces MASLD and Adipose Tissue Changes in Obesity-Resistant Rats.
Madureira AR, Martins VVP, Cardoso JC … +7 more , Torezani-Sales S, Miranda KO, Salgado BS, Monteiro LN, Nogueira BV, Leopoldo AS, Lima-Leopoldo AP
Cell Physiol Biochem · 2025 Jul · PMID 40654026 · Publisher ↗
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-Associat...
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.
Novel Roles for Geranylgeranyl Transferase-III (GGTase-III) in Insulin Secretion.
Gleason NF, Hali M, Kowluru A
Cell Physiol Biochem · 2025 Jun · PMID 40598917 · Full text
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 synaptobr...
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, 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 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.
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