Journal of physiology and biochemistry最新文献

{"title":"The anti-obesity and hepatoprotective effects of bacterial cyclodipeptides in a rat obesity model involve aquaporins, inflammatory factors, and GAB1 modulation.","authors":"Citlali Figueroa-Guzmán, Roxana Y Gaona-García, Marlene E Campos-Morales, Lorena Martínez-Alcantar, Jesús Campos-García","doi":"10.1007/s13105-026-01223-w","DOIUrl":"10.1007/s13105-026-01223-w","url":null,"abstract":"<p><p>Obesity is a major risk factor for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and its progressive form, Metabolic Dysfunction-Associated Steatohepatitis (MASH). Bacterial cyclodipeptides (CDPs) have previously been shown to modulate PI3K/Akt/mTOR signaling and transcriptional programs involved in lipid and cholesterol metabolism, highlighting their potential to regulate metabolic homeostasis. Given the central role of the PI3K/Akt/FoxO1 pathway in regulating aquaporins, inflammatory cytokines, and metabolic homeostasis during obesity and MASLD, the therapeutic potential of CDPs was evaluated in a rat model of MASLD. Treatment of obese animals with CDPs decreased body weight and abdominal and thoracic circumferences. The obesogenic diet induced liver damage after the 34th week, which was alleviated by ten weeks of CDP treatment administered three times a week. This reduced the number and size of lipid droplets and inflammatory infiltrates. Additionally, CDPs improved parameters associated with atherogenic dyslipidemia and metabolic dysfunction, including triglycerides and cholesterol, as well as hepatic injury markers. These changes were accompanied by restoration of mitochondrial membrane potential and a significant reduction in mitochondrial ROS generation. CDP treatment in obese animals restored protein expression levels of aquaporins AQP1, AQP5, AQP8, and AQP9 and downregulated the expression of the inflammatory markers NF-κB and IL-1β. Interestingly, the downstream cellular mediator GAB1 from the PI3K/Akt/FoxO1 pathway was also downregulated. These findings demonstrate that CDP treatment restored the expression of glycerol/water transporting aquaporins altered during obesity and MASLD. Overall, CDPs ameliorated MASLD in obese animals through coordinated modulation of lipid metabolism, mitochondrial function, aquaporin expression, and PI3K/Akt/FoxO1 signaling associated with inflammation, supporting their potential as therapeutic candidates for metabolic liver disease.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathological mutation L241P in Kir7.1 channel inhibits its activity in the choroid plexus epithelium and decreases cerebrospinal fluid K⁺ concentration in the mouse.","authors":"Juan Carlos Henao, Erwin Vera, Sandra Villanueva, Iván Ruminot, L Pablo Cid, Francisco V Sepúlveda, Isabel Cornejo","doi":"10.1007/s13105-026-01220-z","DOIUrl":"10.1007/s13105-026-01220-z","url":null,"abstract":"<p><p>The inwardly rectifying K⁺ channel Kir7.1 is prominently expressed at the apical membrane of the choroid plexus epithelium (CPE) and defines the membrane potential of these cells. The unusual independence of its conductance of extracellular K⁺ ([K⁺]_o) underpins an important role in the regulation of the concentration of this ion in the cerebrospinal fluid [K⁺]_CSF. A similar function for retinal pigment epithelium (RPE) Kir7.1 has been proposed with respect to subretinal K⁺ ([K⁺]_SRS) buffering. We have now studied the effect of expressing in mice the mutant Kir7.1-L241P, a blindness-associated Leber's congenital amaurosis mutation, on channel expression and function in the CPE and on [K⁺]_CSF, taken as a proxy for less accessible [K⁺]_SRS. We used genome-edited knockin mice carrying the L241P mutation of Kir7.1 and studied the electrical properties and NKCC1 cotransporter activity of CPE cells in vitro, as well as CSF secretion rate and [K⁺]_CSF in vivo. CPE cells from Kir7.1-L241P knockin mice had a two-third reduction in K⁺ conductance with respect to that of cells from control animals. While CSF secretion rates and NKCC1 cotransporter activity were unaltered in mutant animals, [K⁺]_CSF was significantly decreased while [Na⁺]_CSF is increased. These results reaffirm the importance of choroid plexus Kir7.1 in the regulation of [K⁺]_CSF. We speculate that the alteration in [K⁺]_CSF regulation by mutation Kir7.1-L241P might be paralleled by a disease-related impairment of retinal [K⁺]_SRS buffering.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating succinate changes during acute cold exposure are not related with brown adipose tissue in humans.","authors":"Francisco J Osuna-Prieto, Borja Martinez-Tellez, Guillermo Sánchez-Delgado, Francisco M Acosta, Lucas Jurado-Fasoli, Joan Vendrell, Jonatan R Ruiz, Sonia Fernández-Veledo","doi":"10.1007/s13105-026-01212-z","DOIUrl":"10.1007/s13105-026-01212-z","url":null,"abstract":"<p><p>Brown adipose tissue (BAT) activity in humans is linked to better glucose metabolism and cardiometabolic health. In mice, cold exposure increases circulating succinate and enhances BAT thermogenesis, but whether similar succinate responses occur in humans remains undetermined. We analysed data from 33 young (18-25 years), sedentary adults (20 women) from the ACTIBATE cohort (NCT02365129). Plasma succinate was measured enzymatically at baseline and 60 and 120 min during a personalized cooling protocol. BAT volume, activity, and radiodensity were assessed via static ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (¹⁸F-FDG PET-CT) at the end of the cold exposure. Circulating succinate changed over time during cold exposure, with no significant change at 60 min and a significant increase at 120 min versus baseline (+ 23.8%, P = 0.017), with substantial interindividual variability. Exploratory stratification by median baseline succinate revealed divergent temporal patterns: the low-baseline group showed increases at 60 min (+ 46%) and 120 min (+ 80.5%; both P ≤ 0.021), while the high-baseline group showed reductions at both timepoints (-31.4% and - 2.4%; both P ≤ 0.003). These profiles were not explained by phenotypic or BAT-related parameters. In the full cohort, changes in circulating succinate were not associated with BAT outcomes. Overall, our findings indicate that circulating succinate responses during acute cold exposure are highly heterogeneous and no associated with BAT PET/CT-derived parameters in humans.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dieckol suppresses lipid accumulation and promotes thermogenic markers in 3T3-L1 adipocytes via ERK/p38 MAPK signaling.","authors":"Indyaswan T Suryaningtyas, Won-Kyo Jung, Jae-Young Je","doi":"10.1007/s13105-026-01216-9","DOIUrl":"10.1007/s13105-026-01216-9","url":null,"abstract":"<p><p>Thermogenic programming of adipocytes represents a promising strategy to enhance energy expenditure; however, most pharmacological browning agents activate PPARγ, which simultaneously promotes lipid accumulation and adipocyte hypertrophy. This study aimed to investigate whether dieckol induces thermogenic markers during adipocyte differentiation under conditions of restrained adipogenic commitment and to elucidate the involvement of MAPK and Nrf2 signaling pathways. 3T3-L1 preadipocytes were differentiated in the presence of dieckol (5-25 µM). Lipid accumulation, lipolytic activity, and intracellular reactive oxygen species were assessed using Oil Red O staining, enzymatic assays, and fluorescence analysis. Protein expression and signaling pathway activation were evaluated by Western blotting using pharmacological inhibitors of ERK1/2 (PD98059) and p38 MAPK (SB203580). Dieckol increased the expression of PRDM16, PGC-1α, and UCP1 while concurrently suppressing PPARγ, C/EBPα, and lipogenic marker expression, resulting in reduced intracellular triglyceride and cholesterol accumulation. Dieckol also enhanced lipolytic signaling and glycerol release, activated ERK1/2- and p38-dependent MAPK signaling, and promoted nuclear translocation of Nrf2 with increased activities of SOD, GPx, and CAT. Inhibition of MAPK signaling, particularly ERK1/2, attenuated dieckol-induced thermogenesis-associated modulation and lipid metabolic regulation. In conclusion, dieckol promotes thermogenic markers in differentiating 3T3-L1 adipocytes through coordinated ERK/p38 MAPK and Nrf2 signaling, enhancing UCP1 expression and lipolysis while suppressing lipid accumulation and adipogenic markers.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox-regulated cell death in gastric cancer: Molecular insights and therapeutic opportunities.","authors":"He Qi, Chenbin Cao, Wenyan Li, Wenshuai Zhu, Yuanxin Xing, Xiaoli Ma, Yunshan Wang, Yanfei Jia","doi":"10.1007/s13105-026-01214-x","DOIUrl":"10.1007/s13105-026-01214-x","url":null,"abstract":"<p><p>Oxidative stress, resulting from the disruption of redox homeostasis, is increasingly recognized as a central driver of gastric cancer pathogenesis and a critical determinant of cell fate. An imbalance between reactive oxygen species (ROS) production and cellular antioxidant defenses leads to oxidative stress, which may ultimately result in cellular oxidative death. Helicobacter pylori (H. pylori), through its virulence factors, induces a vicious cycle of oxidative stress and inflammation that collectively remodels the tumor microenvironment. Gastric cancer is molecularly heterogeneous, and ROS demonstrate profound context dependency across these different subtypes, with distinct mechanisms governing ROS generation, antioxidant defense, and redox-regulated cell death. Importantly, ROS orchestrate a diverse repertoire of cell death modalities in gastric cancer, including ferroptosis, apoptosis, necroptosis, cuproptosis, paraptosis, pyroptosis, and oxeiptosis via a regulatory network involving key molecules such as GPX4, SLC7A11, NRF2, and caspases. In-depth research into the mechanisms of cell death holds promise for developing preventive and therapeutic agents. This review summarizes the mechanisms of ROS‑regulated cell death and explores various therapeutic strategies, including the combined use of small‑molecule compounds and emerging nanomaterial‑based approaches, alongside conventional chemotherapy, immunotherapy, and radiotherapy, to target oxidative stress. It also highlights recent advances, opportunities, and challenges in translating these strategies into gastric cancer therapy. In conclusion, this review offers a mechanistically grounded framework for developing redox-targeted precision therapies in gastric cancer.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of acute severe hypobaric hypoxia on gut-muscle axis in rats.","authors":"Garoa Santocildes, Karenia Lorenzo, José Magalhães, Susana Amézqueta, Teresa Pagès, Josep Lluís Torres, Ginés Viscor, Sara Ramos-Romero, Joan Ramon Torrella","doi":"10.1007/s13105-026-01213-y","DOIUrl":"10.1007/s13105-026-01213-y","url":null,"abstract":"<p><p>Acute exposure to high-altitude hypobaric hypoxia (HH) disrupts physiological homeostasis. While gastrointestinal and neurological disturbances are its main manifestations, muscle function is also affected. However, its short-term effects on the gut-muscle axis remain poorly understood. The present study investigated the impact of a 4-hour exposure to simulated altitude (5,000 m) on intestinal morphology, gut microbiota composition, short-chain fatty acid (SCFA) levels, and skeletal muscle mitochondrial function in male Sprague-Dawley rats. Despite the severity of the hypoxic stimulus, biometric and hematological parameters remained largely unchanged, suggesting preserved systemic stability. Histological analysis revealed a significant reduction in intestinal crypt depth, indicating early structural alterations, while villus morphology and goblet cell counts remained unchanged. Microbiota profiling showed a decrease in Enterobacteriales abundance, while other bacterial groups and SCFA concentrations remained stable, pointing to limited microbial shifts under acute conditions. In skeletal muscle, reactive oxygen species (ROS) production increased under complex I-supported respiration while mitochondrial respiration was maintained across all respiratory states. This suggests a qualitative shift in redox balance. Collectively, these findings indicate that acute HH triggers early localized responses in intestinal and muscular tissues without inducing widespread systemic disruption, highlighting the resilience of the gut-muscle axis to short-term hypoxic stress. Longer or repeated exposures may be required to elicit broader physiological adaptations. This study contributes to understanding the early effects of altitude-related hypoxia and underscore the importance of exposure duration in shaping host responses.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stabilization of HSP70 by deubiquitinase OTUB1 attenuates sleep deprivation-induced cognitive impairment in mice.","authors":"Changsheng Su, Guoshao Zhu, Zhenming Kang, Yangyi Li, Yiqin Lin","doi":"10.1007/s13105-026-01209-8","DOIUrl":"10.1007/s13105-026-01209-8","url":null,"abstract":"<p><p>This study aims to investigate the role of the deubiquitinase OTUB1 in regulating sleep deprivation-induced cognitive impairment in mice and to elucidate the underlying molecular pathways. A mouse model of sleep deprivation was established, and mice were pretreated with OTUB1 protein. Cognitive function was assessed using the Y-maze test, the novel object recognition test (NORT), and the open field test. In vitro experiments involved the generation of OTUB1-overexpressing cell lines. Target gene expression was analyzed by western blot, qRT-PCR, and ELISA assays. Protein-protein interactions were assessed via co-immunoprecipitation. Our findings revealed a decrease in heat shock protein 70 (HSP70) protein levels in the hippocampus of sleep-deprived mice, along with an interaction between OTUB1 and HSP70 in mouse microglial cells. OTUB1 stabilized HSP70 by reducing its polyubiquitination. Furthermore, OTUB1 ameliorated sleep deprivation-induced cognitive deficits and reduced neuroinflammation in the hippocampus, as evidenced by changes in cytokine levels. OTUB1 mitigates sleep deprivation-induced cognitive impairment and neuroinflammation in the hippocampus by stabilizing HSP70 and attenuating inflammatory responses.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute mitochondrial dysfunction impairs neuromuscular transmission and contractility in mouse diaphragm: the protective potential of 25-hydroxycholesterol.","authors":"Eva A Kapliukhina, Nikita S Fedorov, Andrei N Tsentsevitsky, Vadim V Salnikov, Anastasia A Ponomareva, Guzel F Zakyrjanova, Artem I Malomouzh, Alexey M Petrov","doi":"10.1007/s13105-026-01211-0","DOIUrl":"10.1007/s13105-026-01211-0","url":null,"abstract":"<p><p>Mitochondrial impairment, accompanied by excessive reactive oxygen species (ROS) production, is a key contributor to muscle atrophy and neuromuscular disorders, leading to locomotor and respiratory failure. Antimycin A (AA), an inhibitor of the electron transport chain complex III, is an effective tool to mimic mitochondrial dysfunction, whereas 25-hydroxycholesterol (25-HC) is an immune-related oxysterol that can modulate neuromuscular activity via the membrane estrogen receptor α (ERα)/inositol triphosphate receptor/cytoplasmic Ca²⁺ axis. Herein, we investigated the effects of AA treatment in mouse diaphragm nerve-muscle preparations and tested the hypothesis that 25-HC can mitigate AA-induced mitochondrial damage. AA increased mitochondrial ROS production and reduced mitochondrial Ca²⁺ levels and membrane potential. This was accompanied by an elevation of extracellular H₂O₂ levels and lipid peroxidation, as well as a decline in both muscle fiber contractility and evoked exocytosis at the neuromuscular junction (NMJ). Furthermore, alterations were observed in the shape of miniature end-plate responses to the release of single neurotransmitter quanta. 25-HC, at a submicromolar concentration, inhibited AA-induced mitochondrial dysfunction and oxidative stress. Additionally, 25-HC alleviated AA-dependent functional NMJ disturbances but did not reverse the muscle fiber contraction deficit. The ability of 25-HC to decrease AA-driven mitochondrial ROS generation was blocked by a selective ERα antagonist and by chelation of cytoplasmic Ca²⁺. Thus, AA induces mitochondrial damage accompanied by oxidative stress, contractile and NMJ impairments. 25-HC can counteract AA-mediated mitochondrial dysfunction and partially restore NMJ function.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting canonical TGFβ/SMAD3 and ERK1/2 signaling in human valve interstitial cells to modulate immune-fibrotic responses in rheumatic heart disease.","authors":"Charan Sai Ramireddi, Mohit K Rai, Anjali Singh, Vikas Agarwal, Surendra K Agarwal, Alok Kumar, Shantanu Pande","doi":"10.1007/s13105-026-01204-z","DOIUrl":"10.1007/s13105-026-01204-z","url":null,"abstract":"<p><p>Rheumatic heart disease (RHD) is a chronic sequel of acute rheumatic fever characterized by sustained inflammation, fibrosis, and valve degeneration; however, the underlying processes remain unclear. To identify dysregulated molecular pathways, we conducted LC-MS/MS-based proteomic profiling of RHD mitral valve tissue compared with ischemic controls and validated systemic inflammation in RHD patients through peripheral blood analysis. Proteomic analysis revealed upregulation of immune response proteins, TGFβ signaling, and extracellular matrix (ECM) regulators. Notably, proteins associated with innate immune activation and macrophage-related pro- and anti-inflammatory responses were found to be enriched. Peripheral blood analysis further confirmed elevated levels of IL6, TNFα, and TIMP1, indicating systemic inflammation. To investigate the underlying mechanisms, we isolated human valve interstitial cells (hVICs) and treated them with proinflammatory stimuli (TNFα, IFNγ) and profibrotic/ anti-inflammatory (TGFβ) stimulation. TGFβ induced morphological changes within 24 h, consistent with fibrotic transformation, and upregulated fibrotic markers (ACTA2, COL1A1, COL1A2, TIMP1, CTGF, MMP2, and TGFβ) along with increased collagen deposition. In contrast, TNFα and IFNγ suppressed fibrotic gene expression while upregulating TIMP1. Notably, TGFβ induced canonical Smad3 phosphorylation, whereas TNFα and IFNγ did not find, any change. Further, macrophage-hVIC interactions were evaluated using conditioned media from M1 [LPS (100 ng/ml) + TNFα (10 ng/ml)] and M2c [TGFβ (10 ng/ml)] polarized macrophages. M2c macrophage-conditioned media enhanced profibrotic gene expression, whereas M1-conditioned media suppressed it, highlighting the role of immune-fibrotic crosstalk in valvular fibrosis. Notably, the 5-HT₂B receptor antagonist SB204741 and tadalafil effectively inhibited TGFβ-induced Smad3 phosphorylation in hVICs, thereby reducing fibrotic signaling. In addition, tadalafil selectively suppressed ERK1/2-mediated non-canonical signaling, while no significant changes were observed in the STAT3, p38 MAPK and JNK pathways. Collectively, these findings identify immune-fibrotic crosstalk and selective activation of canonical TGFβ/Smad3 and ERK1/2-mediated non-canonical signaling pathways as important contributors to valvular fibrosis in rheumatic heart disease and suggest that targeting these pathways may provide potential therapeutic approaches to limit disease progression.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyroptosis: Molecular mechanisms and function.","authors":"Amir Ajoolabady, Altaf A Abdulkhaliq, Johra Khan, Domenico Pratico, Suhad Bahijri, Jaakko Tuomilehto, Anwar Borai, Bonglee Kim, Jun Ren","doi":"10.1007/s13105-026-01210-1","DOIUrl":"10.1007/s13105-026-01210-1","url":null,"abstract":"<p><p>Pyroptosis is a lytic form of cell death that is highly regulated and executed by certain members of the Gasdermin protein family. The lytic process occurs because the N-terminal domains of gasdermins possess pore-forming capabilities, thereby leading to cellular swelling and plasma membrane rupture. This process is characterized by membrane pore formation - mediated by caspase-cleaved gasdermins-followed by cell lysis and the release of pro-inflammatory mediators. Depending on the nature of stimuli, different inflammasomes and caspases are activated, leading to pyroptosis via two main mechanisms: the caspase-1-dependent canonical pathway and caspase-1-independent non-canonical pathway. In this review, we first summarize the current understanding of pyroptosis, including its underlying mechanisms and the diverse stimuli that trigger it. We then highlight recent findings related to altered signaling pathways and regulatory mechanisms. Finally, we discuss emerging perspectives and its implications, aiming to deepen insight into this form of cell death and stimulate new avenues for research.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}