Mengxin Li , Wanqi Wu , Boran Hu , Huizhen Chen , Jun Wang , Shasha Zhang , Tianyue Guan , Hujing Lu , Jiawen Zhou , Panpan Zhao , Yong Sun
{"title":"Atraric acid activates the FoxO3a/PINK1/Parkin signaling pathway to suppress chronic intermittent hypoxia-induced cardiac oxidative stress, inflammatory responses, and NLRP3 inflammasome activation","authors":"Mengxin Li , Wanqi Wu , Boran Hu , Huizhen Chen , Jun Wang , Shasha Zhang , Tianyue Guan , Hujing Lu , Jiawen Zhou , Panpan Zhao , Yong Sun","doi":"10.1016/j.cbi.2025.111773","DOIUrl":"10.1016/j.cbi.2025.111773","url":null,"abstract":"<div><div>Obstructive sleep apnea syndrome (OSAS)-induced cardiac injury is closely associated with chronic intermittent hypoxia (CIH), but its molecular mechanisms and potential intervention strategies require further exploration. Atraric acid (AA), a compound extracted from oakmoss, has garnered attention due to its anti-inflammatory and antioxidant properties. However, its protective effects on the cardioprotective effects in the context of CIH have not been systematically investigated. Through the establishment of CIH mouse models and H9C2 cell IH injury models, combined with histopathological analysis, mitochondrial function assessment, qPCR, immunofluorescence, and Western blot, the protective effects and molecular mechanisms of AA against CIH-induced myocardial injury were evaluated. Experimental groups included a control group, CIH group, and AA intervention groups with varying doses. AA treatment significantly alleviated CIH-induced cardiac damage, suppressed ROS accumulation, mitochondrial dysfunction, and oxidative stress, and activated Pink1/Parkin pathway-mediated mitophagy by promoting FoxO3a nuclear translocation. Meanwhile, AA inhibited NLRP3 inflammasome activation and inflammatory responses. The protective effects of AA were reversed by autophagy inhibition or ROS enhancement, suggesting an interaction mechanism between mitophagy and inflammation regulation. This study is the first to demonstrate that AA mitigates CIH-related myocardial injury by enhancing mitophagy via the FoxO3a-PINK1/Parkin pathway while synergistically suppressing oxidative stress and NLRP3 inflammasome activation. These findings provide novel therapeutic targets for OSAS-associated cardiac complications and establish a theoretical foundation for the clinical translation of AA, though further clinical validation is warranted.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111773"},"PeriodicalIF":5.4,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305005","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":"Targeting neuroblastoma with 3β,5α-tetrahydrocorticosterone: Activation of aryl hydrocarbon receptor inhibits tumor growth, metastasis, and stemness while promoting neural differentiation","authors":"Zhu-Qian Wen , Wen-Ming Hsu , Chien-Chun Chiou , Farhan Azhwin Maulana , Chia-Hwa Chang , Jie-Ming Huang , Zhi-Kai Yu , Chien-Chin Chen , Neng-Yu Lin , Chun-FA. Tsai , Jheng-Siou Lai , Yue-Ling Chen , Pei-Yi Wu","doi":"10.1016/j.cbi.2025.111780","DOIUrl":"10.1016/j.cbi.2025.111780","url":null,"abstract":"<div><div>Neuroblastoma (NB) is a highly malignant pediatric cancer that originates from the sympathoadrenal lineage of the neural crest. Recent studies have suggested the aryl hydrocarbon receptor (AHR) pathway as a promising therapeutic target for NB. In this study, we investigated the therapeutic potential of 3β,5α-Tetrahydrocorticosterone (3β-THB) for NB by activating AHR signaling. By means of homology modeling and docking simulations, we demonstrated that 3β-THB binds strongly to the PAS-B domain of human AHR. Experimental validation further confirmed that 3β-THB promotes the nuclear translocation of AHR and upregulates AHR downstream gene <em>CYP1A1</em> in NB cells, suggesting the AHR agonist role of 3β-THB. <em>In vitro</em> evaluation of its efficacy demonstrated that 3β-THB significantly inhibited NB cell proliferation, promoted neural differentiation, and induced cell cycle arrest at the G0/G1 phase. Additionally, 3β-THB treatment increased apoptosis, reduced metastatic potential, and suppressed tumorsphere growth in NB cells. The expression of the NB oncogenic driver MYCN and markers associated with stemness was also inhibited by 3β-THB. <em>In vivo</em>, 3β-THB significantly suppressed tumor growth in both xenograft and TH-MYCN transgenic mouse models, with improved survival rates and minimal liver or kidney toxicity. These findings underscore the potential of 3β-THB as a powerful AHR agonist for treating neuroblastoma.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111780"},"PeriodicalIF":5.4,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305025","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}
Sergio M. Borghi , Thacyana T. Carvalho , Mariana M. Bertozzi , Cátia C.F. Bernardy , Ana C. Zarpelon , Felipe A. Pinho-Ribeiro , Cássia Calixto-Campos , Victor Fattori , José C. Alves-Filho , Thiago M. Cunha , Fernando Q. Cunha , Rubia Casagrande , Waldiceu A. Verri Jr.
{"title":"Reply to the Correspondence “Comments on Role of the interleukin-33 (IL-33)/suppressor of tumorigenicity 2 (ST2) signaling in superoxide anion-triggered inflammation and pain behavior in mice”","authors":"Sergio M. Borghi , Thacyana T. Carvalho , Mariana M. Bertozzi , Cátia C.F. Bernardy , Ana C. Zarpelon , Felipe A. Pinho-Ribeiro , Cássia Calixto-Campos , Victor Fattori , José C. Alves-Filho , Thiago M. Cunha , Fernando Q. Cunha , Rubia Casagrande , Waldiceu A. Verri Jr.","doi":"10.1016/j.cbi.2025.111774","DOIUrl":"10.1016/j.cbi.2025.111774","url":null,"abstract":"","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111774"},"PeriodicalIF":5.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282107","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":"Sublethal effects of L-tryptophan and caffeine on planarian physiology: Insights into serotonergic and purinergic disruption in freshwater ecosystems","authors":"Elisa Martins Castro, Welligton Luciano Braguini","doi":"10.1016/j.cbi.2025.111776","DOIUrl":"10.1016/j.cbi.2025.111776","url":null,"abstract":"<div><div>L-tryptophan (Trp) and caffeine (Caf) are persistent neuroactive contaminants in aquatic systems. We investigated the sublethal toxicity of Trp and Caf to the freshwater planarian <em>Girardia tigrina</em> by assessing reproduction, regeneration, energy metabolism, and oxidative stress. Trp exposure (10–100 μM) significantly reduced fecundity in a concentration-dependent manner (number of cocoons) and fertility (hatching success) by up to 67 % and 100 %, respectively, and delayed hatching. Caf showed a biphasic effect on fertility (stimulation at 10 μM, inhibition at higher doses) while reducing fecundity by 22–59 %. Head regeneration was differentially impaired: Trp caused transient stimulation followed by inhibition, whereas Caf induced early and persistent suppression (up to 72 % inhibition). Both compounds depleted glycogen reserves, indicating disrupted energy metabolism. The antioxidant responses differed markedly between the two compounds: Trp caused an initial increase in catalase (CAT) activity followed by a suppression of superoxide dismutase (SOD) and CAT, suggesting a collapse of redox defenses. In contrast, Caf prompted a sustained increase in both enzymes, but an imbalanced SOD/CAT ratio at high doses indicated potential dysregulation. These results reveal distinct, temporally dynamic toxicity profiles for Trp and Caf, disrupting key physiological processes at environmentally relevant concentrations. The findings suggest Trp's effects may progress from serotonergic modulation to metabolic oxidative stress, while Caf acts via sustained purinergic signaling disruption. This study underscores the sensitivity of freshwater invertebrates to neuroactive pollutants and validates <em>G. tigrina</em> as a model for elucidating complex toxicological mechanisms.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111776"},"PeriodicalIF":5.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282080","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}
Yizhong Bao , Jitao Li , Aokang zhang , Yixiu Ni , Mingjing Bi , Jun Chen
{"title":"The novel selective HDAC1 inhibitor ZJH-1 exhibits potent antitumor activity in castration-resistant prostate cancer, potentially involving HSP90AA1","authors":"Yizhong Bao , Jitao Li , Aokang zhang , Yixiu Ni , Mingjing Bi , Jun Chen","doi":"10.1016/j.cbi.2025.111777","DOIUrl":"10.1016/j.cbi.2025.111777","url":null,"abstract":"<div><div>Histone deacetylase (HDAC) inhibitors are being explored as a therapeutic approach for prostate cancer (PCa), particularly castration-resistant variants with limited treatment options. In this study, we designed and synthesized ZJH-1, a novel hydroxamate-based HDAC1-selective inhibitor, and systematically evaluated its anti-tumor efficacy and molecular mechanisms. Biochemical and affinity analyses showed ZJH-1 possesses the highest HDAC1 selectivity among isoforms, associated with H3 hyperacetylation at Lys9/27 in PCa cells. ZJH-1 demonstrated cytotoxic effects (IC<sub>50</sub> = 65 nM in PC3 cells and 345 nM in patient-derived xenograft organoids (PDXOs)) via dual mechanisms: 1) cell cycle modulation, inducing G1 arrest through Cyclin D1 downregulation; and 2) intrinsic apoptosis induction, evidenced by caspase-3 cleavage and an elevated Bax/Bcl-2 ratio. ZJH-1 also showed potential to affect metastasis-related processes, as suggested by reduced activity of MMP-2/MMP-9 and reversed markers of epithelial-mesenchymal transition (EMT). Network pharmacology analysis predicted HSP90AA1 as a potential docking target of ZJH-1. Furthermore, protein expression analysis demonstrated that ZJH-1 upregulates disabled homolog 2 interacting protein (DAB2IP) and downregulates heat shock protein 90AA1 (HSP90AA1). In vivo, ZJH-1 (20 mg/kg, i.p.) significantly attenuated tumor growth in PC3 xenograft models (75 % volume reduction vs. controls) with no obvious weight loss or overt toxic side effects observed. These findings suggest that ZJH-1, a selective HDAC1 inhibitor, merits further investigation as a potential treatment for PCa.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111777"},"PeriodicalIF":5.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282063","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}
Jiabing Wang , Kaiwen Jin , Nan Jin , Guran Lu , Ye Zhang , Yajie Wu , Zhiyi Zhou , Ruining Wang , Xueqiang Ma , Binhui Wang , Xi Chen
{"title":"Targeting thioredoxin reductase 1 by Andrographolide contributes to inducing ROS-mediated apoptosis in human NSCLC cells","authors":"Jiabing Wang , Kaiwen Jin , Nan Jin , Guran Lu , Ye Zhang , Yajie Wu , Zhiyi Zhou , Ruining Wang , Xueqiang Ma , Binhui Wang , Xi Chen","doi":"10.1016/j.cbi.2025.111778","DOIUrl":"10.1016/j.cbi.2025.111778","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) is the most commonly diagnosed malignancy, causing a large number of deaths annually. Finding new drug candidates for treating advanced lung cancer is an urgent need. Andrographolide (Andro), a diterpenoid lactone, derived from <em>Andrographis paniculata</em> Nees and used in traditional Chinese medicine. Andro exhibits potential anticancer activity in multiple types of human cancers. In the present study, we focused on exploring the underlying mechanisms of Andro treatment in NSCLC. The results showed that Andro targets and inhibits the thioredoxin reductase 1 (TrxR1), which caused reactive oxygen species (ROS) production and induce ROS-dependent endoplasmic reticulum (ER) stress and apoptosis in human NSCLC cells. Blockage of ROS generation totally reversed Andro-induced ER stress and apoptosis effects. Critically, TrxR1 knockdown sensitized H460 cancer cells to Andro treatment, whereas TrxR1 overexpression conferred resistance to Andro-induced cytotoxicity in these cells. Treatment with Andro in mice bearing NSCLC xenografts significantly suppressed tumor progression, which was closely linked to TrxR1 activity inhibition and subsequent ROS accumulation. Notably, clinical data revealed that elevated TrxR1 expression levels in lung cancer patients were positively associated with poor prognosis. Our study reveals the molecular mechanism underlying Andro's antitumor effects in NSCLC and highlights TrxR1 as a promising therapeutic target for NSCLC treatment.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111778"},"PeriodicalIF":5.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282049","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}
Syed Shams ul Hassan , Wei Luo , Yan Ji , Jiajia Wu , Xue Xiao , Shikai Yan , Huizi Jin
{"title":"Alsospinones A and B: Novel flavonoid modulators of CAT/GPX/TrxR with integrated ADMET and molecular modeling","authors":"Syed Shams ul Hassan , Wei Luo , Yan Ji , Jiajia Wu , Xue Xiao , Shikai Yan , Huizi Jin","doi":"10.1016/j.cbi.2025.111772","DOIUrl":"10.1016/j.cbi.2025.111772","url":null,"abstract":"<div><div>In the relentless pursuit of next-generation antioxidants, we have unveiled two unprecedented flavonoids—alsospinones A (<strong>1</strong>) and B (<strong>2</strong>) from the ancient fern <em>Alsophila spinulosa,</em> among which carbon skeleton of compound <strong>2</strong> was reported for the first time. Both compounds demonstrate potent, dose-dependent scavenging of DPPH• radicals (IC<sub>50</sub> = 38.13 ± 3.79 and 22.81 ± 1.54 μmol/L). Both new compounds have shown potent antioxidant activity in dose dependent manner against biomarkers including CAT, GSH and MDA. Furthermore, molecular docking and 100-ns dynamics simulations reveal that these scaffolds engage CAT, glutathione peroxidase (GPX), and thioredoxin reductase (TrxR) with exceptional affinities (−13.9 to −18.2 kcal/mol), stabilized by key hydrogen bonds and π–anion contacts to active-site residues (Asp202, Arg203, Asn92, Glu104, Cys–Sec). ADMET profiling confirms their drug-like properties−optimal permeability, minimal cytochrome P450 inhibition, and negligible toxicity risk−especially for <strong>2</strong>, which combines high solubility with superior metabolic clearance. Furthermore, this is the first study to describe detailed mechanism and structural insights of both compounds simultaneously: (i) modulate three major antioxidant enzymes (CAT, GPX, TrxR); (ii) reveal a ligand-mediated allosteric relay stabilizing both Cys clusters in TrxR; and (iii) link specific methoxy vs. hydroxyl substitutions to divergent Nrf2 activation and radical-scavenging efficiencies, providing new structure-guided cues for antioxidant drug design.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111772"},"PeriodicalIF":5.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282079","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}
Yan Wu , Xinlan Hu , Songkai Wang , Hanyi Ouyang , Mengmeng Yao , Zhuo Chen , Qianbin Li
{"title":"Fragment-based discovery, dynamics simulation and pharmacological study of 2-amino-pyrimidine derivative as HIPK2 inhibitor","authors":"Yan Wu , Xinlan Hu , Songkai Wang , Hanyi Ouyang , Mengmeng Yao , Zhuo Chen , Qianbin Li","doi":"10.1016/j.cbi.2025.111771","DOIUrl":"10.1016/j.cbi.2025.111771","url":null,"abstract":"<div><div>Chronic kidney disease (CKD) represents a major global public health challenge, pathologically characterized by renal fibrosis and frequently accompanied by inflammatory responses. Recent study indicates that homeodomain-interacting protein kinase 2 (HIPK2) is a key regulator of these fibrotic and inflammatory pathways. However, highly effective inhibitors targeting HIPK2 are currently lacking. In this study, we employed a fragment-based drug discovery (FBDD) strategy to develop a novel HIPK2 inhibitor, <strong>Hit 2c</strong>. <strong>Hit 2c</strong> demonstrated potent kinase inhibitory activity (IC<sub>50</sub> = 0.20 μM) and significant antiproliferative effects (NRK-49F IC<sub>50</sub> = 0.29 μM, induced by 10 ng/mL TGF-β). Molecular docking, molecular dynamics simulations, and free energy landscape analysis—revealed a stable binding mode between <strong>Hit 2c</strong> and HIPK2, in which a hydrogen bond formed with the key residue Lys288 serves as the central factor sustaining high binding affinity. Umbrella sampling further indicated that breaking this hydrogen bond requires a high dissociation energy barrier (3.22 kcal/mol). <em>In vitro</em>, <strong>Hit 2c</strong> inhibited HIPK2 downstream pathways (p53, TGF-β/Smad3, and NF-κB) and significantly downregulated fibrosis markers (Fn Ⅰ, Collagen Ⅰ, α-SMA) in NRK-49F cells induced by 10 ng/mL TGF-β and inflammatory cytokine IL-6 in HK-2 cells induced by 10 ng/mL TNF-α. In vivo, pharmacodynamic studies showed that oral administration of <strong>Hit 2c</strong> at 10 mg/kg attenuated renal injury and fibrosis in an adenine-induced mouse CKD model, comparable to the positive control dapagliflozin. Pharmacokinetic analysis revealed a half-life of 4.74 h, C<sub>max</sub> of 426.35 ng/mL, AUC<sub>0-∞</sub> of 689.05 h ng/mL, suggesting relatively high clearance and low oral bioavailability (3.92 %). Liver microsome experiments suggested potential first-pass metabolism of <strong>Hit 2c</strong>. Collectively, <strong>Hit 2c</strong> represents a novel HIPK2 inhibitor scaffold with effective anti-fibrotic activity in vitro and in vivo, providing a lead compound for the development of HIPK2-targeted therapeutics.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111771"},"PeriodicalIF":5.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276985","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}
Mariana Barbosa Detoni , Luryan Silvério Fidélis Ortiz , Amanda Caroliny Gomilde , Bruna Taciane da Silva Bortoleti , Fernanda Tomiotto-Pellissier , Virgínia Marcia Concato-Lopes , Manoela Daiele Gonçalves-Lens , Taylon Felipe Silva , Ana Carolina Jacob Rodrigues , Amanda Cristina Machado Carloto , Ellen Mayara Souza Cruz , Danielle Lazarin-Bidóia , Waldiceu Aparecido Verri , Francisco José de Abreu Oliveira , Milena Menegazzo Miranda-Sapla , Ivete Conchon-Costa , Wander Rogério Pavanelli
{"title":"Trans-chalcone affects schistosomula and adult worms by impairing membrane integrity and attenuates the effects of Schistosoma mansoni-induced liver fibrosis","authors":"Mariana Barbosa Detoni , Luryan Silvério Fidélis Ortiz , Amanda Caroliny Gomilde , Bruna Taciane da Silva Bortoleti , Fernanda Tomiotto-Pellissier , Virgínia Marcia Concato-Lopes , Manoela Daiele Gonçalves-Lens , Taylon Felipe Silva , Ana Carolina Jacob Rodrigues , Amanda Cristina Machado Carloto , Ellen Mayara Souza Cruz , Danielle Lazarin-Bidóia , Waldiceu Aparecido Verri , Francisco José de Abreu Oliveira , Milena Menegazzo Miranda-Sapla , Ivete Conchon-Costa , Wander Rogério Pavanelli","doi":"10.1016/j.cbi.2025.111770","DOIUrl":"10.1016/j.cbi.2025.111770","url":null,"abstract":"<div><div>Schistosomiasis is an acute and chronic parasitic disease caused by helminths of the genus <em>Schistosoma</em>. The current treatment, praziquantel, is ineffective against immature forms and during granuloma formation in chronic phase. Chalcones belong to the flavonoid family and are known for their wide biological activities. <em>Trans</em>-Chalcone (TC), the thermodynamically stable isomeric form, exhibits anti-fibrotic and hepatoprotective effects in liver injury models. This study evaluates the <em>in vitro</em> and <em>in vivo</em> effects of TC on <em>S. mansoni</em>. <em>In vitro</em>, TC cytotoxicity was tested on LLC-MK2 cells, while schistosomula and adult worms were assessed for viability, oxidative stress, mitochondrial membrane potential, tegument integrity, morphological changes, and egg production. <em>In vivo</em>, <em>S. mansoni</em>-infected BALB/c mice received oral doses of TC (5, 10, and 20 mg/kg) for 15 days. Parasite burden, liver function (measuring NO, NAG, MPO, IL-12, IL-4, IL-13, and TGF-β), and hepatic histology (granuloma size, stage, and collagen deposition) were analyzed. TC reduced viability in normal cells only at high concentrations (175.60 and 264.90 μM). It was selective for juvenile (17.74 μM) and adult worms (50.00 μM), especially males. TC increased nitric oxide levels, altered mitochondrial and membrane integrity, and reduced egg laying in paired worms. In mice, TC improved liver function, reduced worm and egg counts, and altered granuloma area and profile, with lower levels of pro-inflammatory and pro-fibrotic cytokines, suggesting a modulatory effect on granuloma formation.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111770"},"PeriodicalIF":5.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276933","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}
Yudeng Wang , Xinrong Wang , Bei Gan , Tiantian Jia , Te Xu , Hengyi Xu
{"title":"The “Butterfly Effect” of heart failure: Induced by the combination of polylactic acid nanoplastics and copper from the perspective of gut microbiome","authors":"Yudeng Wang , Xinrong Wang , Bei Gan , Tiantian Jia , Te Xu , Hengyi Xu","doi":"10.1016/j.cbi.2025.111769","DOIUrl":"10.1016/j.cbi.2025.111769","url":null,"abstract":"<div><div>Plastic and heavy metal pollution have received extensive attention, but there is relatively little research on the damage to the gut-heart axis induced by the co-exposure to plastics and heavy metals. This study investigated the impact of the co-exposure of Polylactic acid nanoplastics (PLA-NPs) and copper (Cu) on heart failure (HF) in mice and explored the role of the gut microbiota in mediating this adverse outcome. Male C57BL/6J mice were divided into four groups: the Control group, the PLA-NPs group, the Cu group, and the Co-exposure group (PLA-NPs + Cu group). A 28-day exposure experiment was conducted. The research results indicate that, compared with the Single-exposure groups (PLA-NPs and Cu groups), the mice of Co-exposure group exhibited more severe toxic effects, including more pronounced myocardial hypertrophy and more severe myocardial fibrosis. These damages might be caused by increasing the heart's sensitivity to ferroptosis. Additionally, the co-exposure caused significant damage to the gut barrier and remarkable dysbiosis in the gut microbiota, such as a reduction in the abundances of beneficial bacteria like <em>Lactobacillus</em>. The fecal Microbiota Transplantation experiment confirmed that the alterations in gut microbiota play a pivotal role in the synergistic toxicity induced by PLA-NPs and Cu. This study for the first time reveals the mechanism of the combined effect of PLA-NPs and Cu on cardiac damage and emphasizes the crucial role of gut microbiota in this process.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111769"},"PeriodicalIF":5.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276906","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}