Chemico-biological interactions最新文献

{"title":"Correspondence Comments on \"Differential effects of alcohol-derived serum metabolites and direct ethanol exposure on mouse preantral follicle development\".","authors":"Mingqi Zheng, Jiehua Han","doi":"10.1016/j.cbi.2026.112390","DOIUrl":"https://doi.org/10.1016/j.cbi.2026.112390","url":null,"abstract":"","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"112390"},"PeriodicalIF":5.4,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triphenyl phosphate may reduced oxidative muscle-fiber phenotype involving IL-17A-p38 MAPK -PGC1- α signaling pathway.","authors":"Yuting Huang, Lei Shi, Yang Li, Zhijin Ma, Keshu Liu, Shuhao Fang, Guangning Kou","doi":"10.1016/j.cbi.2026.112391","DOIUrl":"https://doi.org/10.1016/j.cbi.2026.112391","url":null,"abstract":"<p><strong>Background: </strong>TPHP is widely used in various fields. In recent years, the potential health hazards of this pollutant have attracted great attention from people. However, the impact and potential mechanisms of TPHP on skeletal muscle function still need to be studied.</p><p><strong>Methods: </strong>This study combined in vivo animal and in vitro cell experiments. Thirty C57BL/6J mice were randomly assigned to CON, T25, and T50 groups and received 8-week TPHP gavage treatment. Gastrocnemius tissues were collected for transcriptome sequencing, qPCR, Western blotting (WB), and immunofluorescence (IF) analyses. In vitro, C2C12 myoblasts were exposed to gradient TPHP concentrations for 24 h and subjected to identical molecular detections.</p><p><strong>Results: </strong>This study showed that after intervention with TPHP, muscle atrophy markers increased in the gastrocnemius muscle of mice( p < 0.05 for T25; p < 0.01 for T50), while the expression of genes and proteins related to oxidative muscle fibers decreased( p < 0.05 for T25; p < 0.01 for T50). Gene sequencing results showed an increase in IL-17A pathway expression. Cell experiments also showed that after TPHP intervention, the expression of genes and proteins related to muscle atrophy increased in cells ( p < 0.05 for T25; p < 0.01 for T50), while the expression of genes and proteins related to oxidative muscle fibers decreased( p < 0.05 for T25; p < 0.01 for T50). By using relevant inhibitors, provides validation that the IL-17A -p38 MAPK-PGC1-α pathway can reduce oxidative muscle -fiber phenotype.</p><p><strong>Conclusions: </strong>Our research findings indicate that TPHP may reduced oxidative muscle-fiber phenotype involving IL-17A-p38 MAPK-PGC1-α signaling pathway.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"112391"},"PeriodicalIF":5.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The unfolded protein response as a proteotoxic stress-resolution circuit: branch-selective signaling and failed resolution in environmental immunotoxicity.","authors":"Ardie Barry Sailis","doi":"10.1016/j.cbi.2026.112392","DOIUrl":"https://doi.org/10.1016/j.cbi.2026.112392","url":null,"abstract":"<p><p>Environmental immunotoxicity is commonly framed through oxidative stress, cytotoxicity, inflammation, receptor-mediated signaling and cell- or tissue-specific mechanisms. This review proposes that proteotoxic stress resolution represents an additional layer linking environmental exposure to immune dysfunction. Specifically, the unfolded protein response (UPR) is considered as a branch-selective proteotoxic stress-resolution circuit that can shape immune outcomes when endoplasmic reticulum (ER) homeostasis is perturbed. The framework is offered as a hypothesis-generating conceptual structure rather than an established mechanistic paradigm, and the causal step linking failed resolution to immune dysfunction remains largely extrapolated from non-toxicological ER-stress models. Evidence from ER proteostasis biology, immune-cell function and toxicology indicates that environmental toxicants can disrupt protein folding, ER calcium balance, redox homeostasis, lipid composition, degradation pathways and secretory load, thereby engaging distinct combinations of IRE1α, PERK and ATF6 signaling. These branches generate immune-relevant outputs: IRE1α links ER stress to RNA processing and inflammatory signaling, PERK controls translational suppression and fate selection, and ATF6 supports restoration of folding capacity and secretory competence. Across macrophages, dendritic cells, T cells, plasma cells and barrier epithelial cells, immune outcomes depend on branch bias, signaling duration, cell-type context and resolution through ER-associated degradation, autophagy, ER-phagy, translational recovery and restoration of calcium and redox balance. This framework predicts that repeated low-dose exposures, mixed toxicant inputs and incomplete post-exposure recovery can shift immune or barrier cells into inflammatory, suppressive or barrier-disruptive states without overt cytotoxicity. It also supports time-resolved, branch-specific and cell-specific profiling for immunotoxic risk assessment.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"112392"},"PeriodicalIF":5.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiota Remodeling Correlates with Pentose Phosphate Pathway Activation and Steroid Hormone Biosynthesis Dysregulation in Polystyrene Nanoplastic-Induced Hepatic Lipotoxicity.","authors":"Zelong Yang, Xin Zhang, Sida Zheng, Yidan Huang, Xin Wei, Yunbo Zhang","doi":"10.1016/j.cbi.2026.112378","DOIUrl":"https://doi.org/10.1016/j.cbi.2026.112378","url":null,"abstract":"<p><p>Polystyrene nanoplastics (PS-NPs) have been detected in human tissues, but the systemic consequences of chronic oral exposure remain unclear. Female Sprague-Dawley rats received environmentally relevant PS-NP concentrations of 5 or 50 mg/L in drinking water for 42 days. Gut-liver-endocrine interactions were assessed by 16S rRNA sequencing, shotgun metagenomics, fecal metabolomics, hepatic transcriptomics, and biochemical validation of selected nodes. PS-NP exposure caused notable dysregulation of serum and hepatic lipids and produced histopathological damage in the liver. The exposure was also associated with gut dysbiosis dominated by Bacteroidia, along with hepatic glucose-6-phosphate dehydrogenase (G6PD) upregulation and pentose phosphate pathway (PPP) activation, as well as NADPH accumulation. Low-dose exposure was associated with adaptive redox responses (elevated hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX)) and lipid clearance signatures, whereas high-dose exposure correlated with GSH-PX depletion, elevated 8-iso-prostaglandin (8-iso-PG), and transcriptomic evidence of mitochondrial impairment and ferroptosis vulnerability. Steroid hormone biosynthesis (SHB) disruption-declining estradiol and rising cortisol-was observed across both doses, with ovarian Cyp19a1/Cyp11a1 downregulation at low dose and additional adrenal Cyp21a2 upregulation at high dose. Multi-omics integration linked Bacteroidia enrichment to the PPP intermediate deoxyribose 5-phosphate and to reduced estrogen metabolites. Collectively, these findings outline a Gut Microbiota-PPP-SHB (GMPS) axis as a candidate integrative framework for understanding PS-NP-associated hepatic lipotoxicity. This work offers an integrative resource that identifies candidate pathways and testable hypotheses for future investigation of metabolic risks from chronic nanoplastic exposure.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"112378"},"PeriodicalIF":5.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polylactic acid nanoplastics induce kidney injury by activating the TRPM2-mediated mitophagy pathway.","authors":"Ziwen Yan, Tiantian Jia, Yuankun Zhou, Hengyi Xu","doi":"10.1016/j.cbi.2026.112385","DOIUrl":"10.1016/j.cbi.2026.112385","url":null,"abstract":"<p><p>Polylactic acid nanoparticles (PLA NPs) are widely used biodegradable plastics, but their potential health risks remain unclear. This study explores whether PLA NPs induce renal cell apoptosis through a mitochondrial pathway involving transient receptor potential melastatin 2 (TRPM2) and mitophagy. Adult male C57BL/6 mice were orally exposed to 0.1, 1, and 10 mg/kg/day PLA NPs for 28 consecutive days. PLA NPs caused dose-dependent kidney injury, with the high-dose group (group H, 10 mg/kg/day) showing the most severe renal apoptosis and functional impairment. In group H, renal calcium ion (Ca²⁺) levels, mitophagy, and TRPM2 expression were significantly elevated. To investigate the mechanism, TRPM2-KO mice (group KH) and mitophagy inhibitor Mdivi-1-treated mice (group Md) were orally administered 10 mg/kg/day PLA NPs daily. Compared with group H, both group KH and group Md showed reduced renal injury, as evidenced by decreased apoptosis and restored mitochondrial function. These results indicate that PLA NPs induce oxidative stress, activate the TRPM2 channel, cause calcium overload and excessive mitophagy, and ultimately trigger renal cell apoptosis. This study provides a theoretical basis for targeted treatment of kidney diseases caused by PLA NPs.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"112385"},"PeriodicalIF":5.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Multifunctional roles and pharmacological potential of β-sitosterol: Emerging evidence toward clinical applications\" [Chem. Biol. Interact. 365, (2022), 110117].","authors":"Zidan Khan, Nikhil Nath, Abdur Rauf, Talha Bin Emran, Saikat Mitra, Fahadul Islam, Deepak Chandran, Jackie Barua, Mayeen Uddin Khandaker, Abubakr M Idris, Polrat Wilairatana, Muthu Thiruvengadam","doi":"10.1016/j.cbi.2026.112384","DOIUrl":"https://doi.org/10.1016/j.cbi.2026.112384","url":null,"abstract":"","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"112384"},"PeriodicalIF":5.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exemestane induces a reduction in hematopoietic stem cells and immunotoxicity in zebrafish larvae by downregulating Wnt signaling pathway.","authors":"Weirong Li, Wenjia Peng, Wanqing Chen, Jingrong Tang, Xiying Zhou, Zhonghao Xiao, Ziang Wang, Junquan Zeng, Sizhou Huang, Milen I Georgiev, Juhua Xiao, Zigang Cao, Shouhua Zhang","doi":"10.1016/j.cbi.2026.112382","DOIUrl":"https://doi.org/10.1016/j.cbi.2026.112382","url":null,"abstract":"<p><p>Exemestane is a third-generation aromatase inhibitor commonly prescribed for estrogen-dependent breast cancer. Given the widespread clinical use of exemestane, various adverse reactions have been reported. However, there are only a limited number of reports on the effects on the immune system. Therefore, it is essential to examine its potential toxicity and mechanism of action. In this research, zebrafish were employed as a model organism to examine the impact of exemestane on embryonic development and immune function. The larvae that were fertilized 8 hours post-fertilization (hpf) were respectively exposed to exemestane solutions of different concentrations (0.9, 1.8 and 2.7 mg/L).The results demonstrated that exemestane exposure induced a concentration-dependent reduction in larval body length and an increase in yolk sac area, indicative of developmental toxicity. Subsequently, exemestane was administered to the corresponding transgenic fish lines, and it was observed that the numbers of hematopoietic stem cells (HSCs), neutrophils, macrophages, and thymic T cells exhibited dose dependent decreases during exposure. Concurrently, exemestane-exposed zebrafish exhibited significantly elevated oxidative stress levels and an increased incidence of apoptotic cells. Gene expression analysis demonstrated that the immune-related gene NF-kB was downregulated, whereas tlr2 and tlr3 were upregulated in response to treatment. Notably, no significant alterations were observed in the expression levels of il-1b, prl, or lakros. . The use of astaxanthin (AS) and the wnt signaling pathway activator BML-284 can alleviate the embryonic immunotoxicity caused by exemestane. In conclusion, our study represents the first comprehensive evaluation of the immunomodulatory effects of exemestane on zebrafish larvae. These effects are likely associated with exemestane-induced elevation of oxidative stress and suppression of the Wnt signaling pathway.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"112382"},"PeriodicalIF":5.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Sind krait (Bungarus sindanus): Insights into natural history, venom toxicology, neurotoxic mechanisms, and future directions.","authors":"Amit Talukdar, Arpita Devi, Mandira Basumatary","doi":"10.1016/j.cbi.2026.112292","DOIUrl":"10.1016/j.cbi.2026.112292","url":null,"abstract":"<p><p>Kraits are a group of medically important venomous snakes responsible for numerous snakebite cases annually, leading to thousands of mortalities and associated co-morbidities in patients. The Sind krait (Bungarus sindanus) is an underexplored venomous elapid of South Asia distributed towards the North-western region of the Indian subcontinent. The cryptic natural history of the snake, geographically variable venom composition, and venom induced neurotoxicity pose a significant challenge for researchers and clinicians. This review integrates current knowledge on the distribution, ecology, and behaviour of the species across Pakistan and north-western India. We critically evaluated venom composition studies that suggest plausible mechanisms of neurotoxicity with predominance of β-bungarotoxins or phospholipase A₂s (PLA₂s), and ancillary role of three-finger toxins (3FTxs), like κ- and α-neurotoxins depending on the region. Neutralization assays and limited clinical reports indicate reduced effectiveness of polyvalent \"Big Four\" antivenom against B. sindanus envenoming. We explored relevant strategies for the development of effective therapeutics against B. sindanus venom, including conventional, region-specific, and next-generation antivenom along with combination or adjunct therapies. In this context, we explored the potential of recently developed broadly-neutralizing recombinant monoclonal antibodies to bind B. sindanus venom toxins across different populations and geographies using a hypothesis-driven in silico molecular docking and residue-interaction approach. Prioritized research agenda should explore the natural history and venom dynamics of this species to better understand the venom evolution, venom variation, clinical relevance, and antivenom neutralization, and utilize the learning for the development of safer and effective therapeutic approaches.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"112292"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of a new function of human butyrylcholinesterase and the catalytic activity of its natural variants toward homocysteine thiolactone hydrolysis.","authors":"Xiabin Chen, Xiaoxuan Li, Huan Liu, Jianzhuang Yao, Yishuang Li, Hualing Li, Zelin Wu, Yun Zhang, Tingjun Hou, Jiye Wang, Shurong Hou","doi":"10.1016/j.cbi.2025.111683","DOIUrl":"10.1016/j.cbi.2025.111683","url":null,"abstract":"<p><p>Abnormal activity level of human butyrylcholinesterase (BChE) was detected in patients with cardiovascular disease and neurodegenerative disorders, however, the specific role of BChE in the pathology of these diseases are not known yet. Homocysteine thiolactone (HTL) is a toxic thioester metabolite of homocysteine in conditions of hyperhomocysteinemia (HHcy). Experimental evidences suggest that HTL and resultant N-Hcy proteins that disrupt normal protein function, are associated with the pathology of HHcy-related complications such as cardiovascular diseases. Given the abundance of BChE in the blood and its esterase capacity, it is worthy to investigate the hydrolytic ability of BChE and its genetic polymorphism effects towards the endogenous toxic HTL in order to delineate its function in the complex disease network. In this study, human BChE and acetylcholinesterase were examined for their ability in HTL hydrolysis, and BChE demonstrates higher catalytic efficiency than reported serum paraoxonase 1. Furthermore, the catalytic mechanism uncovered by Quantum mechanics/Molecular mechanics molecular dynamics method helps to understand and substantiate the function of BChE in HTL metabolism. Six frequent BChE nonsynonymous coding single nucleotide polymorphisms (SNPs) variants were recombinantly produced and their catalytic activity was assessed. Differential catalytic efficiency toward HTL was observed among these variants, suggesting their distinct metabolic capability in vivo. These findings highlight the potential protection role of BChE against HTL-induced toxicity, and pave a way for future investigation into BChE's contribution in HTL metabolism and the possible correlation between specific BChE SNPs and susceptibility for developing HTL-associated diseases.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111683"},"PeriodicalIF":5.4,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cigarette smoke-induced glycerophospholipid DLPC promotes macrophage ferroptosis through the USP7/GPX4 regulatory axis in chronic obstructive pulmonary disease.","authors":"Weibin Ruan, Zhimin Peng, Mingsi Huang, Hui Zhang, Xiaohua Li, Tingting Ma, Jiehua Deng, Mianluan Pan, Ziqing Mai, Xia Meng, Jianquan Zhang","doi":"10.1016/j.cbi.2025.111697","DOIUrl":"10.1016/j.cbi.2025.111697","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD), a smoking-associated chronic inflammatory disorder, involves macrophage-mediated inflammation and cell death, yet the mechanisms linking cigarette smoke (CS) to macrophage ferroptosis remain unclear. Through integrated transcriptomic and metabolomic analyses of CS-exposed macrophages, we identified activation of the ferroptosis pathway accompanied by dysregulated glycerophospholipid metabolism. Notably, phosphatidylcholine species enriched in polyunsaturated fatty acids (PUFA-PC), particularly 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), were markedly elevated. Functional studies revealed that DLPC exacerbated lipid peroxidation and triggered ferroptosis in macrophages. Mechanistically, DLPC downregulated the deubiquitinase ubiquitin-specific peptidase 7 (USP7), which normally stabilizes glutathione peroxidase 4 (GPX4) through TRAF/CAT domain-mediated binding and deubiquitination activity. This suppression accelerated GPX4 ubiquitination and subsequent proteasomal degradation. Furthermore, CS upregulated glycerol-3-phosphate acyltransferase 3 (GPAT3), whose genetic ablation diminished PUFA-PC (including DLPC) synthesis, attenuated lipid reactive oxygen species (ROS) accumulation, and inhibited ferroptosis in CS-stimulated macrophages. In vivo, adeno-associated virus-mediated GPAT3 knockdown in murine lung tissues mitigated ROS production, ferroptosis, and emphysema in an experimental emphysema murine model. Collectively, our findings delineate a CS-GPAT3-DLPC axis that drives macrophage ferroptosis via USP7/GPX4 dysregulation, offering novel mechanistic insights into COPD pathogenesis and identifying DLPC and GPAT3 as potential therapeutic targets.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111697"},"PeriodicalIF":5.4,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}