Chemico-Biological Interactions最新文献

{"title":"Bucidarasin A suppresses the proliferation and metastasis of HCC by targeting the FAK and STAT3 pathways","authors":"Jiantong Hou ,&nbsp;Ruyu Cao ,&nbsp;Sibei Wang ,&nbsp;Jun Ma ,&nbsp;Jing Xu ,&nbsp;Yuanqiang Guo","doi":"10.1016/j.cbi.2024.111191","DOIUrl":"10.1016/j.cbi.2024.111191","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) is a significant global health concern, with high rates of morbidity and mortality. Bucidarasin A, a natural diterpenoid, has been shown to exert notable cytotoxic effects across a range of tumor cell lines. However, the underlying mechanisms responsible for this cytotoxicity remain unclear. In this study, we sought to elucidate the antitumor mechanisms of bucidarasin A, a natural diterpenoid derived from <em>Casearia graveolens</em>, with a particular focus on its effects on HCC. Furthermore, we employed surface plasmon resonance (SPR), molecular docking, and cellular thermal shift assay (CETSA) to gain further insight into the target protein of bucidarasin A. Our findings revealed that bucidarasin A exhibited pronounced cytotoxicity towards HepG2 cells. <em>In vitro</em> analysis indicated that bucidarasin A interrupted the cell cycle at the S phase and inhibited the proliferation and metastasis of HepG2 cells by modulating the FAK and STAT3 signaling pathways. Moreover, <em>in vivo</em> studies demonstrated that bucidarasin A not only exhibited antitumor effects but also impeded neovascularization, a finding that was corroborated by SPR interactions between vascular endothelial growth factor (VEGF) and bucidarasin A. This research substantiated that bucidarasin A, a clerodane diterpenoid, held promise as a therapeutic candidate against HCC, showcasing substantial antitumor efficacy both <em>in vitro</em> and in <em>vivo</em> through direct targeting of the STAT3 and FAK signaling pathways.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"402 ","pages":"Article 111191"},"PeriodicalIF":4.7,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914808","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":"Metformin promotes the survival of random skin flaps via the activation of Nrf2/HO-1 signaling","authors":"Yan Chen ,&nbsp;Ruxin Cheng ,&nbsp;Wenyan Lu ,&nbsp;Yonghao Fan ,&nbsp;Ye Yu ,&nbsp;Ling Huang ,&nbsp;Zhenling Wan ,&nbsp;Shaojiang Zheng","doi":"10.1016/j.cbi.2024.111188","DOIUrl":"10.1016/j.cbi.2024.111188","url":null,"abstract":"<div><p>The random flap is one of the commonly used techniques for tissue defect repair in surgery and orthopaedics, however the risk of ischaemic necrosis at the distal end of the flap limits its size and clinical application. Metformin (Met) is a first-line medication in the treatment of type 2 diabetes, with additional effects such as anti-tumor, anti-aging, and neuroprotective properties. In this study, we aimed to investigate the biological effects and potential mechanisms of Met in improving the survival of random skin flaps. Twenty-four male Sprague-Dawley rats and 12 male C57BL/6J mice underwent McFarlane flap surgery and divided into control (Ctrl) and Met groups (100 mg/kg). The survival rate of the flap were evaluated on day 7. Angiography, Laser doppler blood flow imaging, and H&amp;E staining were used to assess blood flow supply and the levels of microvascular density. Then, reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured by test kits. Immunohistochemistry analysis was conducted to evaluate the expression of Vascular Endothelial Growth Factor A (VEGFA), Vascular endothelial cadherin (VE-cadherin) and CD31. Rats and mice in the Met group exhibited higher flap survival rate, microcirculatory flow, and higher expression levels of VEGFA and VE-cadherin compared with the Ctrl group. In addition, the level of oxidative stress was significantly lower in the met group. And then we demonstrated that the human umbilical vein endothelial cells (HUVECs) treated with Met can alleviate <em>tert</em>-butyl hydroperoxide (TBHP)-stimulated cellular dysfunction and oxidative stress injury. Mechanistically, Met markedly stimulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and promoted Nrf2 nuclear translocation. Silencing of Nrf2 partially abolished the antioxidant and therapeutic effects of Met. In summary, our data have confirmed that Met has a positive effect on flap survival and reduces necrosis. The mechanism of action involves the regulation of the Nrf2/HO-1 signaling pathway to combat oxidative stress and reduce damage.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"401 ","pages":"Article 111188"},"PeriodicalIF":4.7,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914809","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":"Neuroprotective thiourea derivative uncouples mitochondria and exerts weak protonophoric action on lipid membranes","authors":"Yuri N. Antonenko ,&nbsp;Ivan M. Veselov ,&nbsp;Tatyana I. Rokitskaya ,&nbsp;Daria V. Vinogradova ,&nbsp;Lyudmila S. Khailova ,&nbsp;Elena A. Kotova ,&nbsp;Andrey V. Maltsev ,&nbsp;Sergey O. Bachurin ,&nbsp;Elena F. Shevtsova","doi":"10.1016/j.cbi.2024.111190","DOIUrl":"10.1016/j.cbi.2024.111190","url":null,"abstract":"<div><p>The isothiourea derivative NT-1505 is known as a neuroprotector and cognition enhancer in animal models of neurodegenerative diseases. Bearing in mind possible relation of the NT-1505-mediated neuroprotection to mitochondrial uncoupling activity, here, we examine NT-1505 effects on mitochondria functioning. At concentrations starting from 10 μM, NT-1505 prevented Ca²⁺-induced mitochondrial swelling, similar to common uncouplers. Alongside the inhibition of the mitochondrial permeability transition, NT-1505 caused a decrease in mitochondrial membrane potential and an increase in respiration rate in both isolated mammalian mitochondria and cell cultures, which resulted in the reduction of energy-dependent Ca²⁺ uptake by mitochondria. Based on the oppositely directed effects of bovine serum albumin and palmitate, we suggest the involvement of fatty acids in the NT-1505–mediated mitochondrial uncoupling. In addition, we measured the induction of electrical current across planar bilayer lipid membrane upon the addition of NT-1505 to the bathing solution. Importantly, introduction of the palmitic acid into the lipid bilayer composition led to weak proton selectivity of the NT-1505-mediated BLM current. Thus, the present study revealed an ability of NT-1505 to cause moderate protonophoric uncoupling of mitochondria, which could contribute to the neuroprotective effect of this compound.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"402 ","pages":"Article 111190"},"PeriodicalIF":4.7,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914810","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":"Molecular and toxicological mechanisms behind the effects of chromium (VI) on the male reproductive system of Mytilus galloprovincialis: First evidence for poly-ADP-ribosylation of protamine-like II","authors":"Carmela Marinaro ,&nbsp;Alberto Marino ,&nbsp;Anna Rita Bianchi ,&nbsp;Bruno Berman ,&nbsp;Marco Trifuoggi ,&nbsp;Alessandra Marano ,&nbsp;Giancarlo Palumbo ,&nbsp;Teresa Chianese ,&nbsp;Rosaria Scudiero ,&nbsp;Luigi Rosati ,&nbsp;Anna De Maio ,&nbsp;Gennaro Lettieri ,&nbsp;Marina Piscopo","doi":"10.1016/j.cbi.2024.111186","DOIUrl":"10.1016/j.cbi.2024.111186","url":null,"abstract":"<div><p>Studies on the molecular mechanisms of heavy metal toxicity in invertebrate reproduction are limited. Given that PARP-catalysed ADP-ribosylation is also involved in counteracting heavy metal toxicity and maintaining genomic integrity, and that PARylation is implicated in chromatin remodelling but its role in sperm chromatin remains to be elucidated, we investigated the effects of chromium(VI) at 1, 10 and 100 nM on the reproductive health of <em>Mytilus galloprovincialis</em>. The damage to the gonads was assessed by morphological analyses and the damage indices PARP and ɣH2A.X were measured. Changes in the binding of protamine-like (PL) to DNA and the possibility of poly(ADP-ribosyl)ation of PL proteins were also investigated. Gonadal chromium accumulation and morphological damage were found, especially when the mussels were exposed to the highest dose of chromium(VI). In addition, the maximum expression of gonadal ɣH2A.X and PARP were obtained at 100 and 10 nM Cr(VI), respectively. Interestingly, for the first time in all exposed conditions, poly(ADP)-ribosylation was detected on PL-II, which, together with PL-III and PL-IV, are the major nuclear basic proteins of <em>Mytilus galloprovincialis</em> sperm chromatin. Since PL-II is involved in the final high level of sperm chromatin compaction, this post-translational modification altered the binding of the PL protein to DNA, favouring the action of micrococcal nuclease on sperm chromatin. This study provides new insights into the effects of chromium(VI) on <em>Mytilus galloprovincialis</em> reproductive system and proposes a molecular mechanism hypothesis describing the toxic effects of this metal on PL-DNA binding, sperm chromatin and gonads.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"401 ","pages":"Article 111186"},"PeriodicalIF":4.7,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009279724003326/pdfft?md5=c8715ca233b5437db3ab6266c1797e50&pid=1-s2.0-S0009279724003326-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “2′-O-galloylhyperin attenuates LPS-induced acute lung injury via upregulation antioxidation and inhibition of inflammatory responses in vivo” [Chem. Biol. Interact. 304 (1 May 2019) 20–27]","authors":"Sun-Dong Zhang ,&nbsp;Peng Wang ,&nbsp;Jing Zhang ,&nbsp;Wei Wang ,&nbsp;Li-Ping Yao ,&nbsp;Cheng-Bo Gu ,&nbsp;Thomas Efferth ,&nbsp;Yu-Jie Fu","doi":"10.1016/j.cbi.2024.111185","DOIUrl":"10.1016/j.cbi.2024.111185","url":null,"abstract":"","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"400 ","pages":"Article 111185"},"PeriodicalIF":4.7,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009279724003314/pdfft?md5=2eee6e92fc929de9fbe49da203d2e26d&pid=1-s2.0-S0009279724003314-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ganoderic Acid A prevents bone loss in lipopolysaccharide-treated male rats by reducing oxidative stress and inflammatory","authors":"Zhou-Shan Tao ,&nbsp;Xu-Feng Hu ,&nbsp;Xing-Jing Wu ,&nbsp;Zheng-Yu Wang ,&nbsp;Min Yang ,&nbsp;Cai-Liang Shen","doi":"10.1016/j.cbi.2024.111164","DOIUrl":"10.1016/j.cbi.2024.111164","url":null,"abstract":"<div><p>Ganoderic Acid A (GAA) has demonstrated beneficial effects in anti-inflammatory and anti-oxidative stress studies. However, it remains unknown whether GAA exerts positive impacts on bone loss induced by lipopolysaccharide (LPS). This study aims to investigate the influence of GAA on bone loss in LPS-treated rats. The study assesses changes in the viability and osteogenic potential of MC3T3-E1 cells, as well as osteoclast differentiation in RAW264.7 cells in the presence of LPS using CCK-8, ALP staining, AR staining, and Tartrate-resistant acid phosphatase (TRAP) staining. In vitro experiments indicate that LPS-induced inhibition of osteoclasts (OC) and Superoxide Dismutase 2 (SOD2) correlates with heightened levels of inflammation and oxidative stress. Furthermore, GAA has displayed the ability to alleviate oxidative stress and inflammation, enhance osteogenic differentiation, and suppress osteoclast differentiation. Animal experiment also proves that GAA notably upregulates SOD2 expression and downregulates TNF-α expression, leading to the restoration of impaired bone metabolism, improved bone strength, and increased bone mineral density. The collective experimental findings strongly suggest that GAA can enhance osteogenic activity in the presence of LPS by reducing inflammation and oxidative stress, hindering osteoclast differentiation, and mitigating bone loss in LPS-treated rat models.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"401 ","pages":"Article 111164"},"PeriodicalIF":4.7,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903973","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":"Developmental exposure to nonylphenol leads to depletion of the neural precursor cell pool in the hippocampal dentate gyrus","authors":"Dianqi Yao ,&nbsp;Siyao Li ,&nbsp;Mingdan You ,&nbsp;Yin Chen ,&nbsp;Siyu Yan ,&nbsp;Bing Li ,&nbsp;Yi Wang","doi":"10.1016/j.cbi.2024.111187","DOIUrl":"10.1016/j.cbi.2024.111187","url":null,"abstract":"<div><p>Developmental exposure to nonylphenol (NP) results in irreversible impairments of the central nervous system (CNS). The neural precursor cell (NPC) pool located in the subgranular zone (SGZ), a substructure of the hippocampal dentate gyrus, is critical for the development of hippocampal circuits and some hippocampal functions such as learning and memory. However, the effects of developmental exposure to NP on this pool remain unclear. Thus, our aim was to clarify the impacts of developmental exposure to NP on this pool and to explore the potential mechanisms. Animal models of developmental exposure to NP were created by treating Wistar rats with NP during pregnancy and lactation. Our data showed that developmental exposure to NP decreased Sox2-and Ki67-positive cells in the SGZ of offspring. Inhibited activation of Shh signaling and decreased levels of its downstream mediators, E2F1 and cyclins, were also observed in pups developmentally exposed to NP. Moreover, we established the <em>in vitro</em> model in the NE-4C cells, a neural precursor cell line, to further investigate the effect of NP exposure on NPCs and the underlying mechanisms. Purmorphamine, a small purine-derived hedgehog agonist, was used to specifically modulate the Shh signaling. Consistent with the <em>in vivo</em> results, exposure to NP reduced cell proliferation by inhibiting the Shh signaling in NE-4C cells, and purmorphamine alleviated this reduction in cell proliferation by restoring this signaling. Altogether, our findings support the idea that developmental exposure to NP leads to inhibition of the NPC proliferation and the NPC pool depletion in the SGZ located in the dentate gyrus. Furthermore, we also provided the evidence that suppressed activation of Shh signaling may contribute to the effects of developmental exposure to NP on the NPC pool.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"401 ","pages":"Article 111187"},"PeriodicalIF":4.7,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903972","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":"Synthesis of glucosamine-selenium compound and evaluation of its oral toxicity and in vitro anti-hepatitis B virus activity","authors":"Hong Ding ,&nbsp;XiaoXuan Lu ,&nbsp;Xiaoguo Ji ,&nbsp;Shijie Wang ,&nbsp;Jiayang Jin ,&nbsp;Mengyao Zhao ,&nbsp;Xiaofeng Hang ,&nbsp;Liming Zhao","doi":"10.1016/j.cbi.2024.111184","DOIUrl":"10.1016/j.cbi.2024.111184","url":null,"abstract":"<div><p>Selenium supplements are beneficial to human health, however, concerns regarding the toxicity of inorganic selenium have stimulated research on safer organic compounds. The main objective of this study was to develop a novel glucosamine-selenium compound (Se-GlcN), clarify its structure, and subsequently investigate its oral toxicity and <em>in vitro</em> anti-hepatitis B virus (HBV) activity. Electron microscopy, infrared, ultraviolet spectroscopy, nuclear magnetic resonance and thermogravimetric analyses revealed a unique binding mode of Se-GlcN, with the introduction of the Se-O bond at the C6 position, resulting in the formation of two carboxyl groups. In acute toxicity studies, the median lethal dose (LD₅₀) of Se-GlcN in ICR mice was 92.31 mg/kg body weight (BW), with a 95 % confidence interval of 81.88–104.07 mg/kg BW. A 30-day subchronic toxicity study showed that 46.16 mg/kg BW Se-GlcN caused livers and kidneys damage in mice, whereas doses of 9.23 mg/kg BW and lower were safe for the livers and kidneys. <em>In vitro</em> studies, Se-GlcN at 1.25 μg/mL exhibited good <em>anti</em>-HBV activity, significantly reducing HBsAg, HBeAg, 3.5 kb HBV RNA and total HBV RNA by 45 %, 54 %, 84 %, 87 %, respectively. In conclusion, the Se-GlcN synthesized in this study provides potential possibilities and theoretical references for its use as an organic selenium supplement.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"402 ","pages":"Article 111184"},"PeriodicalIF":4.7,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895090","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":"Geniposide exerts the antidepressant effect by affecting inflammation and glucose metabolism in a mouse model of depression","authors":"Guanghui Chen ,&nbsp;Wenbin Zhang ,&nbsp;Qiang Chen ,&nbsp;Meixue Dong ,&nbsp;Miao Liu ,&nbsp;Gang Liu","doi":"10.1016/j.cbi.2024.111182","DOIUrl":"10.1016/j.cbi.2024.111182","url":null,"abstract":"<div><p>Depression is a severe mental illness affecting patient's physical and mental health. However, long-term effects of existing therapeutic modalities for depression are not satisfactory. Geniposide is an iridoid compound highly expressed in gardenia jasminoides for removing annoyance. The activity of geniposide against depression has been widely studied while most studies concentrated on the expression levels of gene and protein. Herein, the aim of the present study was to employ non-target metabolomic platform of serum to investigate metabolic changes of depression mice and further verify in hippocampus for analyzing the antidepressant mechanism of geniposide. Then we discovered that 9 metabolites of serum were significantly increased in depressive group (prostaglandin E2, leukotriene C4, arachidonic acid, phosphatidylcholine (PC, 16:0/16:0), LysoPC (18:1 (9Z)/0:0), phosphatidylethanolamine (14:0/16:0), creatine, oleamide and aminomalonic acid) and 6 metabolites were decreased (indoxylsulfuric acid, testosterone, lactic acid, glucose 6-phosphate, leucine and valine). The levels of arachidonic acid, LysoPC, lactic acid and glucose 6-phosphate in hippocampus were consistent change with serum in depression mice. Most of them showed significant tendencies to be normal by geniposide treatment. Metabolic pathway analysis indicated that arachidonic acid metabolism and glucose metabolism were the main pathogenesis for the antidepressant effect of geniposide. In addition, the levels of serum tumor necrosis factor-α and interleukin-1 were increased in depressive mice and reversed after geniposide treatment. This study revealed that abnormal metabolism of inflammatory response and glucose metabolism of the serum and hippocampus involved in the occurrence of depressive disorder and antidepressant effect of geniposide.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"400 ","pages":"Article 111182"},"PeriodicalIF":4.7,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891260","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":"α7-nAChR/P300/NLRP3-regulated pyroptosis mediated poor articular cartilage quality induced by prenatal nicotine exposure in female offspring rats","authors":"Hangyuan He ,&nbsp;Jun Chen ,&nbsp;Yi Hua ,&nbsp;Zhe Xie ,&nbsp;Ming Tu ,&nbsp;Liang Liu ,&nbsp;Hui Wang ,&nbsp;Xu Yang ,&nbsp;Liaobin Chen","doi":"10.1016/j.cbi.2024.111183","DOIUrl":"10.1016/j.cbi.2024.111183","url":null,"abstract":"<div><p>Nicotine is developmentally toxic. Prenatal nicotine exposure (PNE) affects the development of multiple fetal organs and causes susceptibility to a variety of diseases in offspring. In this study, we aimed to investigate the effect of PNE on cartilage development and osteoarthritis susceptibility in female offspring rats. Wistar rats were orally gavaged with nicotine on days 9–20 of pregnancy. The articular cartilage was obtained at gestational day (<em>GD</em>) 20 and postnatal week (<em>PW</em>) 24, respectively. Further, the effect of nicotine on chondrogenic differentiation was explored by the chondrogenic differentiation model in human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs). The PNE group showed significantly shallower Safranin O staining and lower Collagen 2a1 content of articular cartilage in female offspring rats. Further, we found that PNE activated pyroptosis in the articular cartilage at <em>GD20</em> and <em>PW24</em>. <em>In vitro</em> experiments revealed that nicotine inhibited chondrogenic differentiation and activated pyroptosis. After interfering with nod-like receptors3 (NLRP3) expression by SiRNA, it was found that pyroptosis mediated the chondrogenic differentiation inhibition of WJ-MSCs induced by nicotine. In addition, we found that α7-nAChR antagonist α-BTX reversed nicotine-induced NLRP3 and P300 high expression. And, P300 SiRNA reversed the increase of NLRP3 mRNA expression and histone acetylation level in its promoter region induced by nicotine. In conclusion, PNE caused chondrodysplasia and poor articular cartilage quality in female offspring rats. PNE increased the histone acetylation level of NLRP3 promoter region by α7-nAChR/P300, which resulting in the high expression of NLRP3. Further, NLRP3 mediated the inhibition of chondrogenic differentiation by activating pyroptosis.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"400 ","pages":"Article 111183"},"PeriodicalIF":4.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891261","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}