Chemico-Biological Interactions最新文献

{"title":"Immunomodulatory evaluation of caffeic acid and its quinic acid derivatives using Th1/Th2 cytokine secretion profiles and principal component analysis","authors":"Kai-Chi Chang,&nbsp;Jin-Yuarn Lin","doi":"10.1016/j.cbi.2025.111865","DOIUrl":"10.1016/j.cbi.2025.111865","url":null,"abstract":"<div><div>Eleven Caffeic acid and its Quinic acid derivatives, including Caffeic acid, 1-<em>O</em>-Caffeoylquinic acid, 3-<em>O</em>-Caffeoylquinic acid, 4-<em>O</em>-Caffeoylquinic acid, 5-<em>O</em>-Caffeoylquinic acid, 1,3-Dicaffeoylquinic acid, 1,4-Dicaffeoylquinic acid, 1,5-Dicaffeoylquinic acid, 3,4-Dicaffeoylquinic acid, 3,5-Dicaffeoylquinic acid, and 4,5-Dicaffeoylquinic acid, were selected to evaluate their Th1/Th2 immune balance using mouse primary splenocytes. The optimal non-cytotoxic concentrations of each test compound were determined using the 3-(4,5-dimethylthiazol-2-diphenyl)-2,5-tetrazolium bromide assay. Th1 (IL-2, TNF-α) and Th2 (IL-4, IL-10) cytokine secretion levels by treated splenocytes were measured using an enzyme-linked immunosorbent assay. The tendency of each test sample towards the Th1/Th2 immune balance was further analyzed by Principal Component Analysis. The results showed that the half-maximal inhibitory concentration of Dicaffeoylquinic acids (18.0–37.8 μM) had higher cytotoxicity to splenocytes than that of Caffeic acid (49.4 μM) and Caffeoylquinic acids (45.6–52.3 μM). Caffeic acid, 3-<em>O</em>-Caffeoylquinic acid, and 5-<em>O</em>-Caffeoylquinic acid among eleven selected compounds exhibited a much higher Th1-inclined immune response, suggesting their potent Th1-inclined immunomodulatory and anti-allergic potential, but they might slightly enhance inflammation. In contrast, 1,4-Dicaffeoylquinic acid, 1,5-Dicaffeoylquinic acid, and 3,4-Dicaffeoylquinic acid tended to have a relative Th2-inclined immunomodulatory property but were speculated to have anti-inflammatory potential.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"424 ","pages":"Article 111865"},"PeriodicalIF":5.4,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights into antibody recognition of tetrodotoxin analogues: Implications for neurotoxicological assessment","authors":"Jaume Reverté ,&nbsp;Mounira Alkassar ,&nbsp;Maria Rambla-Alegre ,&nbsp;Andres Sanchez-Henao ,&nbsp;Manolis Mandalakis ,&nbsp;Panagiota Peristeraki ,&nbsp;Francesc X. Sureda ,&nbsp;Jorge Diogène ,&nbsp;Mònica Campàs","doi":"10.1016/j.cbi.2025.111871","DOIUrl":"10.1016/j.cbi.2025.111871","url":null,"abstract":"<div><div>Tetrodotoxins (TTXs) pose significant food safety risks due to their potent neurotoxicity. Growing concerns about the impact of these toxins on public health have driven the development of new detection methods, with immunoassays showing strong potential. However, limited knowledge of the cross-reactivity of anti-TTX antibodies with analogues may compromise the reliability of these assays in food safety applications. To address this, cross-reactivity factors (CRFs) for five TTX analogues (i.e., 11-norTTX-6(<em>S</em>)-ol, 11-deoxyTTX, 6,11-dideoxyTTX, 5,11-dideoxyTTX, and 5,6,11-trideoxyTTX) were assessed using a magnetic bead-based immunoassay. In parallel, the antibody's ability to neutralise the toxicity of TTX analogues was evaluated in Neuro-2a cells using automated patch clamp, a single-cell biosensing platform specifically designed for <em>in vitro</em> toxicity assessment and characterisation. Antibody cross-reactivity towards the tested analogues correlated with their relative toxicity, enabling a selective detection of the most hazardous compounds. These findings highlight the dual role of molecular structure in dictating both toxicological potency and immunological recognition, and support the use of immunoassays as effective tools for TTX monitoring in food safety applications.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"424 ","pages":"Article 111871"},"PeriodicalIF":5.4,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-activity relationships reveal a 4-(2-pyridyl)chalcone as a potent cell death inducer","authors":"Juan Perdomo ,&nbsp;Henoc del Rosario ,&nbsp;Ester Saavedra ,&nbsp;Mercedes Said ,&nbsp;Celina García ,&nbsp;Lía Cruces ,&nbsp;Susana Abdala ,&nbsp;Ignacio Brouard ,&nbsp;José Quintana ,&nbsp;Francisco Estévez","doi":"10.1016/j.cbi.2025.111877","DOIUrl":"10.1016/j.cbi.2025.111877","url":null,"abstract":"<div><div>Chalcones are biosynthetic precursors of flavonoids and are considered potential anticancer drugs. Here, twenty-two chalcones were synthesized and evaluated for their effects on the viability of eight human leukaemia cells. This series of chalcones was characterized by the presence or absence of a benzyloxy group on the A ring and one or two substituents on the B ring including halogen, methoxy, trifluoromethyl, benzyloxy, morpholine and pyridine in the chalcone skeleton. Chalcones with the lowest IC₅₀ values against leukaemia cells contained a benzyloxy group at position 2′ on the A ring and one or two halogens, or a 2-pyridyl group at position 4 on the B ring. The chalcone 6′-benzyloxy-2′-hydroxy-4-(2-pyridyl)chalcone (BHP) exhibited potency comparable to the antitumor agent etoposide against U-937 cells while showing lower toxicity against human peripheral blood mononuclear cells. BHP-induced viability inhibition was not linked to cell cycle arrest but was associated with apoptosis. Overexpression of the antiapoptotic protein Bcl-2 and the P-glycoprotein did not prevent its activity. In U-937 and HL-60 cells, BHP triggered mitochondrial cytochrome <em>c</em> release, activation of caspases and poly(ADP-ribose) polymerase cleavage and increased annexin-V positive cells. Cell death triggered by BHP was (<em>i</em>) blocked by a pan-caspase inhibitor and by a specific caspase-9 inhibitor, (<em>ii</em>) associated with the phosphorylation of the mitogen-activated protein kinases and (<em>iii</em>) dependent of the generation of reactive oxygen species.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"424 ","pages":"Article 111877"},"PeriodicalIF":5.4,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to polyhexamethylene guanidine, a humidifier disinfectant, disrupts protective immunity and accelerates tuberculosis progression via type I IFN signaling and neutrophil influx in mice","authors":"Hagyu Kim ,&nbsp;YuJin Shin ,&nbsp;Hong-Hee Choi ,&nbsp;Kyungmin Kim ,&nbsp;Hye-Jin Kim ,&nbsp;Haewon Kim ,&nbsp;Wonsik Lee ,&nbsp;Sung Jae Shin","doi":"10.1016/j.cbi.2025.111884","DOIUrl":"10.1016/j.cbi.2025.111884","url":null,"abstract":"<div><div>Tuberculosis (TB), caused by <em>Mycobacterium tuberculosis</em> (Mtb), remains a major infectious disease with high mortality globally. Polyhexamethylene guanidine (PHMG), a cationic polymer and major ingredient of humidifier disinfectants, was implicated in an outbreak of severe pulmonary diseases including TB in the Republic of Korea. During the period when humidifier disinfectants were widely used, the incidence of TB exhibited a rising trend. In this study, we aimed to investigate whether PHMG aggravates TB pathogenesis and elucidate the underlying mechanisms by which PHMG exposure modulates TB progression. In a murine model of Mtb infection, PHMG exposure accelerated TB progression, characterized by increased Mtb burden, alveolar macrophage (AM) depletion, excessive neutrophil accumulation-mediated severe pulmonary inflammation, and impaired Th1 immunity. Transcriptomic profiling of PHMG-exposed Mtb-infected AMs revealed induction of type I interferon (IFN) signatures, inflammatory cytokines including <em>Il1a</em>, <em>Tnf</em>, and <em>Il6</em>, and chemokines for neutrophil recruitment such as <em>Cxcl2</em> and <em>Cxcl3</em>, indicating a pathway associated with aggravated TB outcomes. Consistently, blockade of type I IFN receptor signaling or depletion of neutrophils by relevant antibodies significantly reduced inflammation and Mtb burden in the lungs. Our study demonstrated that PHMG exacerbated TB via the elevated type I IFN signaling and neutrophilic inflammation and uncovered how environmental toxicants such as PHMG would influence host defense system and act as risk factors for TB progression.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"424 ","pages":"Article 111884"},"PeriodicalIF":5.4,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Midazolam-induced developmental toxicity and neurotoxicity in zebrafish embryos: Insights from phenotypic, behavioural, and transcriptomic analyses","authors":"Daohua Cao ,&nbsp;Xiaoyang Zhou ,&nbsp;Jiaolong Huang ,&nbsp;Peng Duan ,&nbsp;Zhen Zhang ,&nbsp;Ying Liu ,&nbsp;Huiyu Luo","doi":"10.1016/j.cbi.2025.111878","DOIUrl":"10.1016/j.cbi.2025.111878","url":null,"abstract":"<div><div>Midazolam (MDZ), a widely used short-acting benzodiazepine, has been linked to developmental and neurotoxic effects, yet its underlying molecular mechanisms during early development remain unclear. This study examined the impact of MDZ on zebrafish embryos and larvae through phenotypic, behavioural, and transcriptomic analyses. Embryos were exposed to MDZ at 2 and 4 mg/L from 6 to 96 h post-fertilisation (hpf). MDZ exposure significantly increased mortality, delayed hatching, and induced morphological abnormalities, indicating developmental toxicity. Neurotoxic effects included elevated apoptosis in both brain and heart regions, reduced spontaneous movement, and altered motor responses to light–dark stimulation. MDZ also decreased heart rate and body size, highlighting its detrimental impact on growth and cardiac function. Transcriptomic profiling identified 1496 DEGs (380 up-regulated and 1116 down-regulated) and revealed altered expression of genes involved in GABAergic synapse, PPAR signalling, cardiac muscle contraction, oestrogen and MAPK signalling, apoptosis, phototransduction, and osteoclast differentiation. These molecular changes likely underpin the observed developmental and neurotoxic outcomes. Notably, locomotor impairments persisted up to 5 days post-fertilisation (dpf), partially recovered by 7 dpf, and approached normalization by 10 dpf. Collectively, these findings underscore the developmental risks of MDZ exposure and provide molecular insights that may inform safer clinical practice.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"424 ","pages":"Article 111878"},"PeriodicalIF":5.4,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stereochemical insight for MexXY-OprM efflux system inhibition in Pseudomonas aeruginosa from a pool of dihydro and tetrahydro berberine derivatives","authors":"Venanzio Daniele Tosiani ,&nbsp;Alessandra Di Gregorio ,&nbsp;Giorgia Giorgini ,&nbsp;Carla Vignaroli ,&nbsp;Giacomo Mari ,&nbsp;Fabio Mantellini ,&nbsp;Gianfranco Favi ,&nbsp;Cristina Minnelli ,&nbsp;Giovanna Mobbili ,&nbsp;Serena Simoni ,&nbsp;Roberta Galeazzi","doi":"10.1016/j.cbi.2025.111850","DOIUrl":"10.1016/j.cbi.2025.111850","url":null,"abstract":"<div><div><em>Pseudomonas aeruginosa</em> is a Gram-negative pathogen responsible for severe infections, particularly in immunocompromised patients. Its widespread antibiotic resistance is a growing concern, primarily due to the overexpression of efflux pumps (EPs) such as the MexXY-OprM system, which plays a major role in aminoglycoside resistance. Targeting EPs with specific inhibitors (EPIs) represents a promising strategy to restore antibiotic efficacy. In this study, we performed High-Throughput Virtual Screening (HTVS) of a library of synthetic berberine derivatives (tetrahydro and dihydro) targeting MexY, the inner membrane protein of the MexXY-OprM system. Based on affinity data, four racemic compounds were selected for further investigation, but only two exhibited <em>in vitro</em> activity against <em>P. aeruginosa</em> laboratory and clinical strains. Subsequent experimental and computational analyses identified compound <strong>2f</strong> as the most effective inhibitor, selectively binding to the allosteric pocket ALP. Notably, the differences in activity between its enantiomers highlighted the importance of the chiral environment at the binding cleft, with the (S)-enantiomer showing significantly higher efficacy than the (R)-enantiomer, particularly against PA7 and CF48 clinical strain. Structural investigations comparing all previously identified berberine derivatives revealed key interactions at the ALP site, mainly involving apolar and aromatic residues, providing a valuable framework for rational drug design. These findings led to the rationalization of a 3D-pharmacophoric model for berberine-derived EPIs, offering a foundation for further optimization.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"424 ","pages":"Article 111850"},"PeriodicalIF":5.4,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical interplay between PAF receptor and PKCδ is involved in dopaminergic insult evoked by methamphetamine in mice","authors":"Quynh Dieu Trinh ,&nbsp;Ji Hoon Jeong ,&nbsp;Naveen Sharma ,&nbsp;Yen Nhi Doan Nguyen ,&nbsp;Jung Hoon Park ,&nbsp;Duc Toan Pham ,&nbsp;Hoang-Yen Phi Tran ,&nbsp;Duy-Khanh Dang ,&nbsp;Dae-Joong Kim ,&nbsp;Dae-Hun Park ,&nbsp;Toshitaka Nabeshima ,&nbsp;Hyoung-Chun Kim ,&nbsp;Eun-Joo Shin","doi":"10.1016/j.cbi.2025.111847","DOIUrl":"10.1016/j.cbi.2025.111847","url":null,"abstract":"<div><div>Methamphetamine (MA)-induced neurodegeneration has been reported to resemble behavioral and neurochemical changes in patients with Parkinson's disease. Although it is recognized that platelet-activating factor receptor (PAFR) is involved in the neurodegenerative change, little is known about the role of PAFR in the MA-induced neurodegeneration. Thus, we investigated the mechanistic role of PAFR in MA-induced neurodegeneration. Simultaneously, we asked whether PAFR can interplay with another inflammatory/proapoptotic factor protein kinase Cδ (PKCδ). A single dose of MA (35 mg/kg, i.p.) caused significant increases in PAFR and phospho-protein kinase Cδ (p-PKCδ) expression in the striatum of wild-type mice. MA also increased the interaction between PAFR and p-PKCδ, as assessed by co-immunoprecipitation. Furthermore, triple labelling immunocytochemical analysis showed that PAFR-immunoreactivity (IR) and p-PKCδ-IR were localized in the same Iba-1-labeled microglial cells, suggesting that they express PAFR and PKCδ. Consistently, rottlerin, a PKCδ inhibitor or ginkgolide B, a PAFR inhibitor significantly attenuated MA-induced pro-apoptotic changes (i.e., TUNEL-positive cells and cleaved caspase-3/Bax expression) in Taconic ICR mice. Genetic and pharmacological inhibition of PAFR or PKCδ reduced the MA-caused dopaminergic degenerative effects (i.e., a decrease in tyrosine hydroxylase expression, an increase in dopamine turnover rate, microgliosis, and behavioral impairments), suggesting that PAFR and PKCδ mediate dopaminergic neurodegeneration. MA-induced increases in PAFR and p-PKCδ were attenuated by rottlerin or PKCδ gene knockout. However, ginkgolide B or PAFR gene knockout failed to affect the increase in p-PKCδ expression after MA treatment. Therefore, we suggest that PKCδ is an upstream molecule that increases PAFR for activating the morbid signaling cascade induced by MA.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"424 ","pages":"Article 111847"},"PeriodicalIF":5.4,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From sweetener to risk factor: Network toxicology, molecular docking and molecular dynamics reveal the mechanism of aspartame in promoting coronary heart disease","authors":"Ming Xia ,&nbsp;Xiaoli Liu ,&nbsp;Kun Wang ,&nbsp;Boping Liang ,&nbsp;Peilin Xiao","doi":"10.1016/j.cbi.2025.111876","DOIUrl":"10.1016/j.cbi.2025.111876","url":null,"abstract":"<div><div>Aspartame, a widely used non-nutritive sweetener, has been epidemiologically linked to coronary heart disease (CHD), although the underlying mechanisms remain unclear. This study employed an integrative computational strategy combining network toxicology, molecular docking, and molecular dynamics to decode aspartame's CHD-promoting mechanisms. Initially, the toxicity profile of aspartame was predicted using ProTox 3.0 and ADMETlab 3.0, which highlighted significant cardiotoxicity. Through multi-source target screening of aspartame (PharmMapper, SEA, etc.) and CHD (GeneCards, OMIM), 216 shared targets were identified. Protein-protein interaction network analysis revealed 10 hub targets (INS, PPARGC1A, TNF, AKT1, IL6, MMP9, IGF1, PTGS2, SIRT1, PPARG). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed significant enrichment in lipid metabolism, inflammatory responses, insulin resistance, and atherosclerosis-related pathways. Molecular docking and molecular dynamics simulations (MDS) demonstrated high-affinity binding of aspartame to three core targets (PTGS2, TNF, and PPARGC1A), with a binding energy ≤ −7.0 kcal/mol, and confirmed high binding stability. This study reveals that aspartame may promote the pathogenesis of CHD by disrupting cardiovascular homeostasis through multi-target interactions, including inflammatory response, metabolic dysregulation, and vascular remodeling. These findings provide molecular evidence for re-evaluating the safety profile of aspartame and establish a computational framework to guide experimental validation and preventive strategies.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"424 ","pages":"Article 111876"},"PeriodicalIF":5.4,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The p -JNKThr183/Tyr185 / p -Keap1Thr43 /Keap1 axis mediates arsenic-induced endothelial dysfunction by coordinating Chaperone-mediated autophagy with macroautophagy","authors":"Jinyu Li ,&nbsp;Jin Cheng ,&nbsp;Zhihan Yang ,&nbsp;Lin Gao ,&nbsp;Qiaoling Liu ,&nbsp;Jing He ,&nbsp;Yishan Dong ,&nbsp;Shuo Wang ,&nbsp;Jing Cui ,&nbsp;Ziqi Xu ,&nbsp;Dianjun Sun ,&nbsp;Wei Zhang","doi":"10.1016/j.cbi.2025.111874","DOIUrl":"10.1016/j.cbi.2025.111874","url":null,"abstract":"<div><div>Arsenic exposure leads to vascular endothelial dysfunction (VED), which plays a driving role in the development of cardiovascular disease. Macroautophagy and chaperone-mediated autophagy (CMA), two major forms of autophagy in mammals, jointly maintain intracellular homeostasis. Our group has revealed that excessive macroautophagy induces VED. However, the function of CMA in arsenic-induced endothelial dysfunction as well as the regulatory relationship between macroautophagy and CMA have not been unveiled. Here, we demonstrate that the co-activation of macroautophagy and CMA promotes VED <em>in vivo</em> and <em>in vitro</em>. We also identify a damaging role of CMA in arsenic-induced vascular endothelial dysfunction, which contrasts with its previously reported protective effects. In addition, our results showed that macroautophagy and CMA were activated successively, and macroautophagy played a dominant regulatory role in VED induced by arsenic. Mechanistically, phosphorylation proteomics suggested that KEAP1 may play a pivotal role in arsenic-induced macroautophagy and CMA in mouse aortic endothelial cells. Moreover, a novel Keap1 phosphorylation site, Thr43, was significantly activated by the JNK pathway. Furthermore, when Keap1 levels decrease to a considerable lower level, macroautophagy and CMA decrease remarkably, endothelial dysfunction was accordingly alleviated. Collectively, our study demonstrates that the <em>p</em>-JNK^{Thr183/Tyr185}/<em>p</em>-Keap1^Thr43/Keap1 axis mediates arsenic-induced VED by coordinately activating both CMA and macroautophagy, which revealing a new regulation mechanism of Keap1 in autophagy. Additionally, the genetic polymorphism of Keap1 was found have a significant correlation with the susceptibility to hypertension in arsenicosis areas. Collectively, these findings provide promising new ideas for the prevention and treatment of arsenic-induced CVD through regulating autophagy.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"424 ","pages":"Article 111874"},"PeriodicalIF":5.4,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro methods for evaluation of sulfur mustard on cell senescence","authors":"S. Emma Sarles ,&nbsp;Adrian Neu ,&nbsp;Linda N. Pettersson ,&nbsp;Tobias Demel ,&nbsp;Priscilla Lee ,&nbsp;Daniel Angelini ,&nbsp;Simone Rothmiller ,&nbsp;Dirk Steinritz","doi":"10.1016/j.cbi.2025.111875","DOIUrl":"10.1016/j.cbi.2025.111875","url":null,"abstract":"<div><div>Even though the Chemical Weapons Convention forbids the use of chemical weapons, there have been cases of chemical warfare agents used in prior conflicts and terror attacks. Sulfur Mustard (SM), an alkylating and blistering agent, has been reported to seriously harm the skin, mucous membranes, eyes, and lungs. Prolonged wound healing issues or pulmonary oedema may arise. The exact process by which SM results in long-term injury is yet unclear. Senescent cells in wounds, which have been shown to impede the healing process, may be one possible contributing reason. This review summarizes the current state of knowledge in the field of <em>in vitro</em> methods for studying cell senescence after SM exposure. A multitude of studies have demonstrated that several cell types show a higher tendency for senescence induction following SM. This review of the literature not only comprises these cell types and different model types, but also various <em>in vitro</em> methods for SM exposure. In addition, we review the most common endpoints associated with senescence. This overview aims to give scientists a complete summary of the present status of <em>in vitro</em> research on SM and senescence as well as recommendations for new experimental setups and future studies. These recommendations aim to close research gaps and may facilitate the identification of additional druggable targets and the development of novel drug candidates for innovative therapeutic options.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"424 ","pages":"Article 111875"},"PeriodicalIF":5.4,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}