Xiangyu Wang , Xin Tan , Ting Zhang , Shuai Xu , Yiyao Zeng , Anchen Xu , Xian Li , Ge Zhang , Yufeng Jiang , Hezi Jiang , Jili Fan , Xiaohong Bo , Huimin Fan , Yafeng Zhou
{"title":"Modeling diabetic cardiomyopathy using human cardiac organoids: Effects of high glucose and lipid conditions","authors":"Xiangyu Wang , Xin Tan , Ting Zhang , Shuai Xu , Yiyao Zeng , Anchen Xu , Xian Li , Ge Zhang , Yufeng Jiang , Hezi Jiang , Jili Fan , Xiaohong Bo , Huimin Fan , 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}
Xiaodong Li , Jianyuan Yin , Qing Song , Qi Yang , Chenchen Li , Huan Gao
{"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 , Jianyuan Yin , Qing Song , Qi Yang , Chenchen Li , 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}
Kai-Ting Fu , Deng-Chyang Wu , Hauh-Jyun Candy Chen
{"title":"Elevated hemoglobin adducts derived from crotonaldehyde in healthy smokers and oral cancer patients by nanoflow liquid chromatography tandem mass spectrometry☆","authors":"Kai-Ting Fu , Deng-Chyang Wu , Hauh-Jyun Candy Chen","doi":"10.1016/j.cbi.2025.111435","DOIUrl":"10.1016/j.cbi.2025.111435","url":null,"abstract":"<div><div>Hemoglobin adducts derived from reactive chemicals have been used as exposure biomarkers in vivo. We previously identified and quantified adducted peptides derived from acrolein in human hemoglobin after trypsin digestion. In this study, we characterized the Schiff base and Michael adducts of crotonaldehyde in human hemoglobin after NaBH<sub>4</sub> reduction to the stable adducts with a respective mass increase of 54.0470 and 72.0575 Da, determined by high-resolution mass spectrometry. We developed a workflow based on nanoflow liquid chromatography nanoelectrospray ionization tandem mass spectrometry to simultaneously quantify 29 adducted peptides derived from acrolein and crotonaldehyde in one drop of blood from smoking oral cavity cancer patients, healthy smokers, and healthy nonsmokers. Levels of ten adducted peptides were significantly elevated in smokers, despite their cancer status, and the adduct levels correlate with the extent of cigarette smoking. Comparing the adduct levels at the same site, the Michael adduct of acrolein is much higher than that of crotonaldehyde. Multivariate analysis by orthogonal partial least squares discriminant analysis suggests that the Michel adducts of acrolein at α-Lys-7, α-His-50, β-Lys-17, and the Schiff base adduct of crotonaldehyde at β-Lys-59 are the predominate contributors. This is the first report on the structural characterization of human hemoglobin adducts of crotonaldehyde and the detection and quantification of these adducts in human subjects. Our results reveal that cigarette smoking plays a major role in forming these adducted peptides which might serve as potential biomarkers for exposure to acrolein and crotonaldehyde.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"410 ","pages":"Article 111435"},"PeriodicalIF":4.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434697","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}
Soo-Yeon Kim , Jae-Min Kim , Kyung-Sook Chung , Dae Sik Jang , Ja-Yeon Lee , Choi Kim , Jae Yeol Lee , Jong Kil Lee , Kyung-Tae Lee
{"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 , Jae-Min Kim , Kyung-Sook Chung , Dae Sik Jang , Ja-Yeon Lee , Choi Kim , Jae Yeol Lee , Jong Kil Lee , 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 E<sub>2</sub> (PGE<sub>2</sub>) 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 PGE<sub>2</sub> 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}
Eva Gil-Martins , Fernando Cagide , Ana Borer , Daniel José Barbosa , Carlos Fernandes , Daniel Chavarria , Fernando Remião , Fernanda Borges , Renata Silva
{"title":"The role of mitochondrial dysfunction and calcium dysregulation in 2C-I and 25I-NBOMe-induced neurotoxicity","authors":"Eva Gil-Martins , Fernando Cagide , Ana Borer , Daniel José Barbosa , Carlos Fernandes , Daniel Chavarria , Fernando Remião , Fernanda Borges , 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 EC<sub>50</sub> 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 Ca<sup>2</sup>⁺ 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<sup>+</sup>/PI<sup>−</sup>) and late apoptosis/necrosis (AnV<sup>+</sup>/PI<sup>+</sup>). 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 Ca<sup>2</sup>⁺ 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}
Shali Yu , Ziyu Qin , Yuqing Chen , Fengxu Wang , Zhijie Li , Ruiyao Huang , Zhengnan Gao , Yi Qu , Peng Xue , Yonghua Luo , Xiaoke Wang , Xinyuan Zhao
{"title":"Antimony-induced hippocampal neuronal impairment through ferroptosis activation from NCOA4-mediated ferritinophagy","authors":"Shali Yu , Ziyu Qin , Yuqing Chen , Fengxu Wang , Zhijie Li , Ruiyao Huang , Zhengnan Gao , Yi Qu , Peng Xue , Yonghua Luo , Xiaoke Wang , 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}
Kaipeng Jin , Chengchun Shen , Wei Yu , Jinti Lin , Jian Zhu , Huimin Tao , Bing Liu
{"title":"Pulsatilla saponin D inhibited the growth of osteosarcoma by regulating the JNK/ATF3 signaling pathway","authors":"Kaipeng Jin , Chengchun Shen , Wei Yu , Jinti Lin , Jian Zhu , Huimin Tao , 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 , Ruiying Zhang , Tiantian Jia , Jialyu Huang , 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. Ca<sup>2+</sup> is essential for almost all life processes. Therefore, TRPM2-deficient mice was used to explore the role of Ca<sup>2+</sup> in POF. The results indicated that the mouse serum E<sub>2</sub> 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<sup>−/−</sup>. Based on these, we have further proved that the activation TRPM2 channel could lead to intracellular Ca<sup>2+</sup> overload, plentiful Ca<sup>2+</sup> 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}
Yaxuan Zhu , Xiuxiang Liu , Xiuying Liu , Yijiao Shi , Huaxin Li , Shaoguo Ru , Hua Tian
{"title":"Toxicokinetics and reproductive toxicity of maternal bisphenol AF exposure during gestation in offspring of Sprague Dawley rats","authors":"Yaxuan Zhu , Xiuxiang Liu , Xiuying Liu , Yijiao Shi , Huaxin Li , Shaoguo Ru , Hua Tian","doi":"10.1016/j.cbi.2025.111424","DOIUrl":"10.1016/j.cbi.2025.111424","url":null,"abstract":"<div><div>Bisphenol AF (BPAF) has been widely used as a main alternative to bisphenol A (BPA), and previous <em>in vitro</em> studies have shown that BPAF has higher reproductive toxicity potentials than BPA. However, data on <em>in vivo</em> toxicity of BPAF is still limited. In this study, Sprague Dawley rats were exposed to BPAF (0, 50, and 100 mg/kg/day) during gestation to study toxicokinetics and reproductive toxicity in offspring. The results showed that plasma concentrations BPAF peaked within 6 h after birth, followed by a two-phase decay, with clearance rates of approximately 3.0 l/h and terminal half-life values ranging from 77 h to 114 h, suggesting fast absorption and high persistence of BPAF. At postnatal day 21 (PND21), BPAF was found to be bioaccumulated in reproductive organs (testes and ovaries) of the offspring, resulting in adverse effects on reproduction in both sexes. Lower anogenital distance, reduced relative testicular weight, dissolved interstitial cells, fewer primary spermatocytes, decreased testosterone levels, and increased luteinizing hormone levels were detected in male offspring. In female offspring, vacuolization in follicular antrum, fewer follicles, increased 17<em>β</em>-estradiol levels, and increased luteinizing hormone levels in female offspring were found. Gene expression of <em>scavenger receptor class B type I</em> (<em>SR-B1</em>), <em>3-hydroxy-3-methylglutaryl-CoA reductase</em> (<em>HMGR</em>), <em>sterol regulatory element-binding protein-1c</em> (<em>SREBP-1c</em>), and several steroidogenic enzymes was significantly decreased in male offspring following maternal exposure to BPAF, suggesting that the decreases in testosterone levels is a result of inhibited cholesterol uptake, cholesterol <em>de novo</em> synthesis, and steroidogenesis. In addition, inhibition of pathways of phagosome and cell adhesion molecules might be the underlying molecular mechanism involved in BPAF-induced reproductive disorders in male offspring. This study provides the scientific basis for a comprehensive assessment of the safety of BPAF.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"409 ","pages":"Article 111424"},"PeriodicalIF":4.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403633","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}
Hailin Xu , Yurou Zhu , Lingnan Zhu , Donglei Wang , Songqing Lv , Xueyan Li , Caixia Guo , Yanbo Li
{"title":"Warning on the inhalation of silica nanoparticles: Experimental evidence for its easy passage through the air-blood barrier, resulting in systemic distribution and pathological injuries","authors":"Hailin Xu , Yurou Zhu , Lingnan Zhu , Donglei Wang , Songqing Lv , Xueyan Li , Caixia Guo , Yanbo Li","doi":"10.1016/j.cbi.2025.111423","DOIUrl":"10.1016/j.cbi.2025.111423","url":null,"abstract":"<div><div>As a result of accumulating data, silica nanoparticles (SiNPs) are known to be harmful when inhaled. Nevertheless, the systemic research on its biological processes remains incompletely understood. In our work, we investigated the systemic effects in rats in response to the respiratory exposure of SiNPs, and in-depth clarified the particle distribution <em>in vivo</em>. Moreover, a model of the air-blood barrier was developed to assess the interplay of SiNPs with the epithelium/endothelium interface <em>in vitro</em>. The model was established <em>via</em> a transwell co-culturing of the alveolar epithelium (MLE-12) and the pulmonary microvascular epithelium (MPVECs). Consequently, our data revealed a systemic particle distribution and ensuing multi-tissue pathological injuries in SiNPs-instilled rats, including the heart, spleen, and kidneys. Simultaneously, the translocation of SiNPs passing through the air-blood barrier was verified <em>in vitro</em>. Also, a dose-dependent interruption to the air-blood barrier integrity by SiNPs was noticed <em>in vitro</em>, accompanied by the damage of tight junctions. SiNPs translocation across the air-blood barrier can inevitably facilitate the extra-pulmonary distribution of SiNPs and ensuing systemic effects. Overall, this study provides evidence on the systemic toxicity potential of SiNPs, while highlighting the significance of comprehending SiNPs toxicity and ultimately controlling the health hazards.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"409 ","pages":"Article 111423"},"PeriodicalIF":4.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416394","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}