Chemico-Biological Interactions最新文献

{"title":"Hesperidin alleviates endothelial cell inflammation and apoptosis of Kawasaki disease through inhibiting the TLR4/IĸBα/NF-ĸB pathway","authors":"Yuting Guan ,&nbsp;Jinghua Ruan ,&nbsp;Pingping Tan ,&nbsp;Songwei Qian ,&nbsp;Size Zhou ,&nbsp;Ao Zhang ,&nbsp;Yuchong Fu ,&nbsp;Shuhui Zhao ,&nbsp;Yuqing Ran ,&nbsp;Xing Feng ,&nbsp;Yijia Wang ,&nbsp;Xinlei Wu ,&nbsp;Bing Zhang ,&nbsp;Weiping Ji ,&nbsp;Lianpin Wu ,&nbsp;Xiaoling Guo","doi":"10.1016/j.cbi.2025.111445","DOIUrl":"10.1016/j.cbi.2025.111445","url":null,"abstract":"<div><div>Kawasaki Disease (KD) is an acute and self-limiting vasculitis of unknown etiology that mainly occurs in infancy and can lead to vascular endothelial injury. Hesperidin (HES) is an economical dietary biological flavonoid with anti-oxidant, anti-inflammatory, and anti-apoptotic pharmacological effects. The main objective of this study was to investigate the protective effects of HES on KD, and try to elucidate the underlying mechanism. The Candida albicans water-soluble fraction (CAWS) was used to induce coronary arteritis of KD mouse model <em>in vivo</em>, and tumor necrosis factor α (TNF-α) was employed to induce human umbilical vein endothelial cell (HUVEC) injury of KD cell model <em>in vitro</em> to investigate the anti-inflammatory and anti-apoptotic effects of HES on KD. Our <em>in vivo</em> results showed that HES significantly reduced coronary artery injury in KD mice by alleviating pericoronary inflammatory infiltration and tissue fibrosis, inhibiting inflammatory cytokines and chemokine expressions, and decreasing vascular endothelial cell apoptosis. Our <em>in vitro</em> study confirmed that HES had the opposite ability of the NF-κB agonist NF-ĸB activator 1 (ACT1) to significantly alleviate the inflammatory response, CellROX level, and apoptosis by decreasing BAX/BCL-2 and Cleaved Caspase-3 levels as well as reducing TUNEL positive cells and the ratio of flow cytometric apoptotic cells in TNF-α induced HUVECs. The further mechanism study based on bioinformatics analysis and western blotting demonstrated that HES could protect against vascular inflammation and cell apoptosis of KD through inhibiting the TLR4/IĸBα/NF-ĸB pathway, suggesting that HES may be a promising therapeutic candidate for KD.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"411 ","pages":"Article 111445"},"PeriodicalIF":4.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485052","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":"Urolithin D: A promising metabolite of ellagitannin in combatting oxidative stress","authors":"Žiko Milanović","doi":"10.1016/j.cbi.2025.111444","DOIUrl":"10.1016/j.cbi.2025.111444","url":null,"abstract":"<div><div>The objective of this research is to examine the function of urolithin D (<strong>UroD,</strong> 3,4,8,9-tetrahydroxy-6H-benzo[<em>c</em>]chromen-6-one), a metabolite obtained from ellagitannins, in the mitigation of oxidative stress. The research is based on estimating the mechanisms through which <strong>UroD</strong> acts as an antioxidant under physiological conditions, emphasizing standard antioxidant mechanisms such as formal Hydrogen Aatom Transfer (<em>f</em>-HAT), Radical Adduct Formation (RAF)/Radical Coupling Formation (RCF), and Single Electron Transfer followed by Proton Transfer (SET-PT). This study utilised advanced quantum mechanical techniques, specifically density functional theory (DFT) and the Quantum Mechanics-based test for Overall free Radical Scavenging activity (QM-ORSA) methodology, to assess the thermodynamic and kinetic parameters of <strong>UroD</strong> in the presence of reactive radical species HOO^•, CH₃OO^• and CCl₃OO^•. The estimated overall rate constants (<em>k</em>_overall) indicate a reactivity order of CCl₃OO^• (<em>k</em>_overall = 2.06 × 10¹⁰ M⁻¹s⁻¹) &gt; HOO^• (<em>k</em>_overall = 2.59 × 10⁹ M⁻¹s⁻¹) &gt; CH₃OO^• (<em>k</em>_overall = 1.89 × 10⁹ M⁻¹s⁻¹). The examination of the relative proportions of products (%) indicates that <strong>UroD</strong> exhibits antiradical action primarily through all examined mechanisms, with the predominant involvement of mononion and dianion acid-base species. In addition to its capacity to directly counteract ROS, <strong>UroD</strong> can restore oxidative DNA damage, specifically targeting oxidative byproducts commonly associated with 2-deoxyguanosine (<strong>2 dG</strong>), which are susceptible to oxidative stress. The <strong>UroD</strong> regenerates G-centered radical cations (<strong>2 dG</strong>^•+) through the SET mechanism, C-centered radicals (<strong>2 dG</strong>^•) in the sugar moiety through <em>f</em>-HAT, and repairs <em>i</em>-OH-2dG lesions through sequential hydrogen atom transfer dehydration (SHATD). Additionally, the radical products formed during antioxidant action can be regenerated in the presence of O₂^•− into anionic species, which are subsequently protonated into neutral species that can re-engage in antioxidant activity. These findings underscore the efficiency of <strong>UroD</strong> in scavenging free radicals and suggest its potential role in preserving cellular integrity and protecting against oxidative stress-related diseases.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"411 ","pages":"Article 111444"},"PeriodicalIF":4.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474663","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":"Protosappanin B activates the Wnt pathway to protect against glucocorticoid-induced osteoblast inhibition and enhance bone formation","authors":"Jigeng Fan ,&nbsp;Yahui Wang ,&nbsp;Houzhi Yang ,&nbsp;Shaoyuan Huang ,&nbsp;Yuan Ma ,&nbsp;Jie Guo ,&nbsp;YuTao Jia ,&nbsp;Ying Zhang ,&nbsp;Yonggang Fan ,&nbsp;Donglun Xiao ,&nbsp;Jiawei Zhang ,&nbsp;Jianwei Li ,&nbsp;Yu Dong ,&nbsp;Ying Zhao ,&nbsp;Miao Guo ,&nbsp;Qiong Tang ,&nbsp;Shan-shan Li ,&nbsp;Tianwei Sun ,&nbsp;Xin Jin","doi":"10.1016/j.cbi.2025.111436","DOIUrl":"10.1016/j.cbi.2025.111436","url":null,"abstract":"<div><div>Osteoporosis remains a major health challenge due to impaired osteoblast function and reduced bone formation, particularly in glucocorticoid-induced osteoporosis (GIOP). The Wnt/β-catenin signaling pathway plays a critical role in osteogenesis, making it a promising target for protective interventions against osteoporosis-related bone loss. In this study, virtual screening of a natural product library identified Protosappanin B (PB) as a potential Wnt pathway activator with high binding affinity for Wnt receptors. We investigated PB's protective effects on osteoblast function under glucocorticoid exposure using MC3T3-E1 cells treated with dexamethasone (DEX) and an in vivo zebrafish model of GIOP. PB significantly promoted osteoblast proliferation, facilitated cell cycle progression, and attenuated DEX-induced apoptosis in a dose-dependent manner. Additionally, PB enhanced osteoblast differentiation and mineralization, counteracting DEX's inhibitory effects on alkaline phosphatase (ALP) activity and calcium deposition. In zebrafish, PB mitigated DEX-induced skeletal defects, improving bone and craniofacial cartilage formation. Western blot analysis confirmed that PB restored β-catenin levels, activating the Wnt/β-catenin pathway. Notably, the osteogenic effects of PB were abolished by XAV939, a Wnt signaling inhibitor, further supporting its Wnt-dependent mechanism of action. These findings indicate that PB provides protective effects against glucocorticoid-induced osteoblast dysfunction and bone loss by modulating Wnt signaling. This study highlight the potential of PB as a natural agent for preventing GIOP-related bone deterioration and warrants further investigation into its clinical applicability.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"410 ","pages":"Article 111436"},"PeriodicalIF":4.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471563","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":"Modeling diabetic cardiomyopathy using human cardiac organoids: Effects of high glucose and lipid conditions","authors":"Xiangyu Wang ,&nbsp;Xin Tan ,&nbsp;Ting Zhang ,&nbsp;Shuai Xu ,&nbsp;Yiyao Zeng ,&nbsp;Anchen Xu ,&nbsp;Xian Li ,&nbsp;Ge Zhang ,&nbsp;Yufeng Jiang ,&nbsp;Hezi Jiang ,&nbsp;Jili Fan ,&nbsp;Xiaohong Bo ,&nbsp;Huimin Fan ,&nbsp;Yafeng Zhou","doi":"10.1016/j.cbi.2025.111421","DOIUrl":"10.1016/j.cbi.2025.111421","url":null,"abstract":"<div><div>Diabetic cardiomyopathy (DCM) is a complex metabolic disorder resulting from chronic hyperglycemia and lipid toxicity, which leads to cardiac dysfunction, fibrosis, inflammation, and mitochondrial impairment. Traditional two-dimensional (2D) cell cultures and animal models have limitations in replicating human cardiac physiology and pathophysiology. In this study, we successfully developed a three-dimensional (3D) model of DCM using cardiac organoids generated from human induced pluripotent stem cells (hiPSCs). These organoids were treated with varying concentrations of glucose and sodium palmitate to mimic the high-glucose and high-lipid environment associated with diabetes. At lower concentrations, glucose and sodium palmitate enhanced cell viability, while higher concentrations induced significant cardiotoxic effects, including apoptosis, oxidative stress, and mitochondrial dysfunction. The cardiac organoids also exhibited increased expression of cardiac injury markers, fibrosis-related genes, and inflammatory cytokines under high-glucose and high-lipid conditions. Treatment with metformin, a widely used antidiabetic drug, mitigated these adverse effects, indicating the model's potential for drug testing and evaluation. Our findings demonstrate that this human-derived 3D cardiac organoid model provides a more physiologically relevant platform for studying DCM and can effectively complement traditional models. This model holds promise for advancing the understanding of diabetic heart disease and for assessing the efficacy of potential therapeutic interventions.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"411 ","pages":"Article 111421"},"PeriodicalIF":4.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471429","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 novel ginseng Rh2 derivative 2-deoxy-Rh2, exhibits potent anticancer effect via the AMPK/mTOR/autophagy signaling pathway against breast cancer","authors":"Xiaodong Li ,&nbsp;Jianyuan Yin ,&nbsp;Qing Song ,&nbsp;Qi Yang ,&nbsp;Chenchen Li ,&nbsp;Huan Gao","doi":"10.1016/j.cbi.2025.111422","DOIUrl":"10.1016/j.cbi.2025.111422","url":null,"abstract":"<div><div>Breast cancer is the most prevalent cancer and the second leading cause of cancer-related mortality among women globally, resulting in considerable psychological and physical distress for patients. Our previous study synthesized a novel derivative, 2-Deoxy-Rh2, which exhibited anticancer properties by influencing glycolysis and mitochondrial respiration. The objective of the current study was to investigate the anti-proliferative effects and underlying mechanisms of 2-Deoxy-Rh2 on human breast cancer cell lines MCF-7 and MDA-MB-231. In our experiments, we observed that 2-Deoxy-Rh2 reduced cell viability and induced cell cycle arrest, reactive oxygen species accumulation, and mitochondrial dysfunction. Furthermore, treatment with 2-Deoxy-Rh2 affected autophagic flux and induction, leading to increased expression of microtubule-associated protein light chain 3B (LC3B) and decreased expression of sequestosome 1 (P62) expression in both two breast cancer cell lines, which could be reversed by 3-Methyladenine (3-MA). Additionally, the AMPK signaling pathway plays a crucial role in 2-Deoxy-Rh2-induced autophagy. 2-Deoxy-Rh2 modulated the expression levels of mTOR and AMPK in MCF-7 and MDA-MB-231 cells, resulting in the cellular homeostasis disruption, autophagy and apoptosis, which was further corroborated by compound C (CC). Finally, the study validated the antitumor activity and mechanism of 2-Deoxy-Rh2 in vivo using Balb/c mice bearing 4T1 tumor cells. Overall, the results suggest that 2-Deoxy-Rh2 can induce apoptosis and autophagic cell death through the AMPK/mTOR signaling pathway, positioning it as a promising candidate for an antitumor agent against breast cancer.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"409 ","pages":"Article 111422"},"PeriodicalIF":4.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437261","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 and in vivo anti-inflammatory effects of 5-hydroxyconiferaldehyde via NF-κB, MAPK/AP-1, and Nrf2 modulation","authors":"Soo-Yeon Kim ,&nbsp;Jae-Min Kim ,&nbsp;Kyung-Sook Chung ,&nbsp;Dae Sik Jang ,&nbsp;Ja-Yeon Lee ,&nbsp;Choi Kim ,&nbsp;Jae Yeol Lee ,&nbsp;Jong Kil Lee ,&nbsp;Kyung-Tae Lee","doi":"10.1016/j.cbi.2025.111427","DOIUrl":"10.1016/j.cbi.2025.111427","url":null,"abstract":"<div><div>We previously reported that 5-hydroxyconiferaldehyde (5-HCA), a phenolic compound isolated from the <em>Campanula takesimana</em>, potently inhibits prostaglandin E₂ (PGE₂) production triggered by lipopolysaccharide (LPS) in macrophages. As the precise molecular mechanisms underlying the anti-inflammatory effects of 5-HCA remain unclear, we further examined these mechanisms in LPS-stimulated RAW 264.7 macrophages and carrageenan-induced paw edema rats. The results revealed that 5-HCA considerably impeded nitric oxide (NO) and PGE₂ production as well as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β expression by suppressing the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) signaling pathways in LPS-induced RAW 264.7 macrophages. Furthermore, 5-HCA suppressed the generation of reactive oxygen species (ROS) triggered by LPS by enhancing heme oxygenase-1 (HO-1) expression via nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). In rats with carrageenan-induced paw edema, administration of 5-HCA (10 or 30 mg/kg, <em>i.p.</em>) resulted in a significant reduction in the inflammatory response (paw volume and thickness) and inflammatory hyperalgesia by suppressing pro-inflammatory mediators through NF-κB, MAPK/AP-1, and Nrf2 regulation. These findings highlight the anti-inflammatory properties of 5-HCA in the acute inflammation model and suggest its potential for further investigation of broader inflammatory disorders.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"409 ","pages":"Article 111427"},"PeriodicalIF":4.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143430043","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 role of mitochondrial dysfunction and calcium dysregulation in 2C-I and 25I-NBOMe-induced neurotoxicity","authors":"Eva Gil-Martins ,&nbsp;Fernando Cagide ,&nbsp;Ana Borer ,&nbsp;Daniel José Barbosa ,&nbsp;Carlos Fernandes ,&nbsp;Daniel Chavarria ,&nbsp;Fernando Remião ,&nbsp;Fernanda Borges ,&nbsp;Renata Silva","doi":"10.1016/j.cbi.2025.111425","DOIUrl":"10.1016/j.cbi.2025.111425","url":null,"abstract":"<div><div>New psychoactive substances (NPS) are designed to evade legal regulation while mimicking the effects of classic illicit drugs such as 3,4-methylenedioxymethamphetamine (MDMA). This category includes phenethylamine derivatives, such as the psychedelic 2C and NBOMe drugs. Given the lack of data regarding the toxicological profile of these substances, the goal of this study was to evaluate the neurotoxicity of 2C-I and 25I-NBOMe and explore their neurotoxic pathways. Lower EC₅₀ values, in both NR uptake and MTT reduction assays in differentiated SH-SY5Y cells and primary rat cortical cultures, revealed that 25I-NBOMe is significantly more cytotoxic than 2C-I, likely due to its higher lipophilicity. Both drugs triggered severe mitochondrial dysfunction, characterized by decreased intracellular ATP levels and mitochondrial membrane depolarization, although no significant changes in intracellular ROS/RNS levels were observed. Additionally, 25I-NBOMe increased the intracellular Ca²⁺ levels. Apoptosis was an observed mechanism of cell death for both drugs, as demonstrated by a significant increase in the number of cells undergoing early apoptosis (AnV⁺/PI⁻) and late apoptosis/necrosis (AnV⁺/PI⁺). However, only 2C-I induced autophagy and strongly triggered caspase-3 activation. This suggests that 2C-I induces caspase-3-dependent apoptosis, whereas 25I-NBOMe may also induce apoptosis through a caspase-3-independent pathway, possibly involving increased intracellular Ca²⁺ levels and direct mitochondrial damage.</div><div>These findings underscore the complex interplay between mitochondrial dysfunction, calcium dysregulation, and cell death pathways, highlighting the central role of mitochondria in the cytotoxicity of 2C-I and 25I-NBOMe.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"411 ","pages":"Article 111425"},"PeriodicalIF":4.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434699","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":"Antimony-induced hippocampal neuronal impairment through ferroptosis activation from NCOA4-mediated ferritinophagy","authors":"Shali Yu ,&nbsp;Ziyu Qin ,&nbsp;Yuqing Chen ,&nbsp;Fengxu Wang ,&nbsp;Zhijie Li ,&nbsp;Ruiyao Huang ,&nbsp;Zhengnan Gao ,&nbsp;Yi Qu ,&nbsp;Peng Xue ,&nbsp;Yonghua Luo ,&nbsp;Xiaoke Wang ,&nbsp;Xinyuan Zhao","doi":"10.1016/j.cbi.2025.111415","DOIUrl":"10.1016/j.cbi.2025.111415","url":null,"abstract":"<div><div>Recently, our group identified antimony (Sb) as a novel nerve pollutant, can lead to neuronal injure. However, Sb-associated neurotoxicological mechanisms yet remain unclear. Herein, we found Sb induced hippocampal neuronal ferroptosis in <em>vivo</em> and in <em>vitro</em>. Moreover, ferroptosis inhibition using ferrostatin-1 effectively attenuated Sb-induced neuronal damage in PC12 cells and mice hippocampal regions. Furthermore, iron chelator deferoxamine (DFO) also effectively attenuated ferroptosis and cytotoxicity in PC12 cells. In vitro, Sb treatment reduced expression of the heavy (H)- and light (L)-chain subunits of ferritin (FTH1 and FTL). Moreover, Sb accelerated FTH1 and FTL protein degradation, while ferritin overexpression by plasmid or hippocampal AAV injections dramatically weaken Sb-induced ferroptosis. Sb exposure accelerated autophagic flux, and autophagy inhibition with beclin1 knockdown effectively reduced Sb-mediated ferroptosis. 3-methyladenine treatment in Sb-exposed mice prevented the decrease of FTH1 and FTL protein, resulting in recovery of Sb-induced hippocampal ferroptosis as well as neuronal loss, suggesting that Sb triggered hippocampal neuronal ferritinophagy. Finally, we found Sb upregulated NCOA4 protein expression, while NCOA4 knockdown significantly attenuated Sb-triggered ferroptosis. Collectively, our results proved that Sb triggers hippocampal neuronal ferroptosis through NCOA4-dependent ferritinophagy.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"409 ","pages":"Article 111415"},"PeriodicalIF":4.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418942","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":"Pulsatilla saponin D inhibited the growth of osteosarcoma by regulating the JNK/ATF3 signaling pathway","authors":"Kaipeng Jin ,&nbsp;Chengchun Shen ,&nbsp;Wei Yu ,&nbsp;Jinti Lin ,&nbsp;Jian Zhu ,&nbsp;Huimin Tao ,&nbsp;Bing Liu","doi":"10.1016/j.cbi.2025.111420","DOIUrl":"10.1016/j.cbi.2025.111420","url":null,"abstract":"<div><div>Osteosarcoma (OS) is a highly malignant and aggressive bone tumor associated with early lung metastasis and high mortality. Traditional chemotherapy does not effectively improve the efficacy and survival rate of patients with OS. Thus, it is vital to search for alternative therapies. Pulsatilla saponin D (PSD) is a potent bioactive compound that has been widely employed in cancer therapy due to its diverse bioactivities and minimal adverse effects. However, any effect on OS remains unclear. We found that PSD induced apoptosis of OS cells and investigated the mechanisms thereof. In vitro, PSD dose-dependently induced apoptosis and inhibited the viability of HOS and K7M2 cells. Furthermore, PSD significantly suppressed cell migration and invasion, and caused cell cycle arrest at the G0/G1 phase. Mechanistically, PSD upregulated ATF3 and JUN transcription by controlling JNK expression. Compared to cells treated with PSD alone, cells pre-treated with SP600125 (a JNK inhibitor), or in which ATF3 had been knocked down ATF3 with siRNA, did not exhibit PSD-mediated cell apoptosis. In a murine OS model, PSD exhibited a powerful anti-cancer effect and an excellent safety profile. Our data imply that PSD could effectively prevent OS occurrence and progression.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"410 ","pages":"Article 111420"},"PeriodicalIF":4.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426811","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":"Knockout of TRPM2 protects against cyclophosphamide-induced premature ovarian failure via inhibiting AMPK/p53 signaling pathway","authors":"Penghui Nie ,&nbsp;Ruiying Zhang ,&nbsp;Tiantian Jia ,&nbsp;Jialyu Huang ,&nbsp;Hengyi Xu","doi":"10.1016/j.cbi.2025.111426","DOIUrl":"10.1016/j.cbi.2025.111426","url":null,"abstract":"<div><div>The global prevalence of premature ovarian failure (POF) is from 3.1 % to 4.3 %, which is a multifactorial disease including genetics, environmental and medical factors. However, the occurrence of POF is not well understood. To further explore the potential mechanism of POF, cyclophosphamide (CTX) was used to construct the model of POF. Additionally, the occurrence of POF was related to oxidative stress, apoptosis, proliferation and others. Ca²⁺ is essential for almost all life processes. Therefore, TRPM2-deficient mice was used to explore the role of Ca²⁺ in POF. The results indicated that the mouse serum E₂ and AMH levels decreased, FSH and LH levels increased, and the activity of antioxidant enzymes including CAT, SOD and GSH decreased with mtROS accumulation in the ovary, thereby causing ovarian DNA damage, promoting ovarian cell apoptosis and inhibiting cell proliferation after wild-type mice exposed to CTX. Notably, these indicators have improved after TRPM2^−/−. Based on these, we have further proved that the activation TRPM2 channel could lead to intracellular Ca²⁺ overload, plentiful Ca²⁺ bind to calmodulin accompanied with mitochondrial ROS accumulation, thereby activating AMPK/p53 signaling pathway, inducing proliferation arrest and excessive apoptosis. We hope to provide therapeutic targets to prevent the occurrence of POF by studying the potential mechanism of POF.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"409 ","pages":"Article 111426"},"PeriodicalIF":4.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418941","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}