Journal of Steroid Biochemistry and Molecular Biology最新文献

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Design, synthesis, and biological evaluation of estratriene-based hydroxamic acid derivatives as histone deacetylase inhibitors 以雌二醇为基础的羟肟酸衍生物作为组蛋白去乙酰化酶抑制剂的设计、合成和生物学评价。
IF 2.5 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-09-22 DOI: 10.1016/j.jsbmb.2025.106867
Haifeng Chen , Ying Li , Zhenghui Liang , Zhiwei Zhong , Yanmin Huang , Zhiping Liu , Yunqiong Gu , Lihe Jiang , Beijun Gan , Chunfang Gan
{"title":"Design, synthesis, and biological evaluation of estratriene-based hydroxamic acid derivatives as histone deacetylase inhibitors","authors":"Haifeng Chen ,&nbsp;Ying Li ,&nbsp;Zhenghui Liang ,&nbsp;Zhiwei Zhong ,&nbsp;Yanmin Huang ,&nbsp;Zhiping Liu ,&nbsp;Yunqiong Gu ,&nbsp;Lihe Jiang ,&nbsp;Beijun Gan ,&nbsp;Chunfang Gan","doi":"10.1016/j.jsbmb.2025.106867","DOIUrl":"10.1016/j.jsbmb.2025.106867","url":null,"abstract":"<div><div>A series of estratriene-based hydroxamic acid derivatives were rationally designed as histone deacetylase (HDAC) inhibitors, utilizing estrone and estradiol scaffolds with hydroxamic acid groups attached at the 3-position via alkoxy linkers of varying chain lengths. Structure-activity relationship studies indicated that compounds with n = 4 exhibited optimal activity. The lead compounds <strong>CFT-2b</strong> and <strong>CEC-2b</strong> showed potent antiproliferative effects against HeLa and SKOV-3 cells (IC<sub>50</sub>, 6.09–8.36 μM) and favorable selectivity indices (8.5 to &gt;13.1 versus 293 T cells). Notably, several compounds showed superior HDAC inhibitory activity compared to SAHA. Mechanistic studies showed that <strong>CFT-2b</strong> and <strong>CEC-2b</strong> induced dose-dependent apoptosis, caused G1-phase cell-cycle arrest, and significantly increased acetylated histone H3 levels in HeLa cells, consistent with intracellular HDAC inhibition. Molecular docking supported favorable binding within the HDAC2 and HDAC6 active sites via zinc chelation and proper cap-group positioning. These findings establish estratriene-based hydroxamic acids as promising HDAC inhibitor scaffolds for cancer therapy development.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106867"},"PeriodicalIF":2.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficient whole-cell biocatalytic production of 7α-hydroxy-4-cholesten-3-one via human CYP7A1 expressed in Escherichia coli 通过大肠杆菌表达的人CYP7A1高效全细胞生物催化生产7α-羟基-4-胆固醇-3- 1。
IF 2.5 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-09-18 DOI: 10.1016/j.jsbmb.2025.106866
Qiannan Shang , Jiahui Huang , Shi Qin , Haichao Zhu , Riling Chen , Lina Yin , Qingzhong Hu
{"title":"Efficient whole-cell biocatalytic production of 7α-hydroxy-4-cholesten-3-one via human CYP7A1 expressed in Escherichia coli","authors":"Qiannan Shang ,&nbsp;Jiahui Huang ,&nbsp;Shi Qin ,&nbsp;Haichao Zhu ,&nbsp;Riling Chen ,&nbsp;Lina Yin ,&nbsp;Qingzhong Hu","doi":"10.1016/j.jsbmb.2025.106866","DOIUrl":"10.1016/j.jsbmb.2025.106866","url":null,"abstract":"<div><div>Human cytochrome P450 enzyme CYP7A1 catalyzes the rate-limiting 7α-hydroxylation of cholesterol in bile acid biosynthesis but is difficult to express functionally in microbial hosts. Here, we report a whole-cell <em>Escherichia coli</em> biocatalytic platform co-expressing truncated CYP7A1 and its redox partner cytochrome P450 reductase (CPR) using bicistronic or dual-promoter vector systems. Protein expression was improved via GroES-GroEL co-expression, and Rosetta(DE3)-pET-tCYP7A1-tCPR was identified as the optimal strain. With the aid of hydroxypropyl-β-cyclodextrin and polymyxin B, 7α-hydroxy-4-cholesten-3-one (7α-HCO) was produced at 118.3 mg·L⁻¹ ·d⁻¹ with &gt; 98 % purity. The product was verified by NMR and high-resolution mass spectrometry. This work presents the first microbial system for 7α-HCO biosynthesis via human CYP7A1, offering a scalable strategy for steroid production and potential applications in drug metabolism and inhibitor screening.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106866"},"PeriodicalIF":2.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Why 7-ketocholesterol matters now: A rapid review of its pathogenic and therapeutic relevance 为什么7-酮胆固醇现在很重要:对其致病和治疗相关性的快速回顾
IF 2.5 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-09-18 DOI: 10.1016/j.jsbmb.2025.106865
Evelyn Sharon Sukumaran , Arin Natania S
{"title":"Why 7-ketocholesterol matters now: A rapid review of its pathogenic and therapeutic relevance","authors":"Evelyn Sharon Sukumaran ,&nbsp;Arin Natania S","doi":"10.1016/j.jsbmb.2025.106865","DOIUrl":"10.1016/j.jsbmb.2025.106865","url":null,"abstract":"<div><div>7-Ketocholesterol (7-KC), a major oxysterol formed through cholesterol autoxidation, is increasingly recognized as a pathogenic mediator in ageing and chronic disease. Detected in atherosclerotic plaques, Alzheimer’s cortex, aged retina, and lysosomal storage disorders, 7-KC actively drives oxidative stress, chronic inflammation, organelle dysfunction, and oxiapoptophagy. These mechanisms underpin its role in cardiovascular, neurodegenerative, and metabolic pathologies. Recent advances highlight nutritional antioxidants, pharmacological agents, microbial bioremediation, and nanotechnology as promising therapeutic avenues. Recognizing 7-KC as both a biomarker and therapeutic target offers opportunities for innovation in diagnostics and treatment of age-related and inflammatory disorders.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106865"},"PeriodicalIF":2.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Research progress on the function, expression and enzyme activity regulation of 17β-HSD1 in mammals 哺乳动物17β-HSD1的功能、表达及酶活性调控研究进展
IF 2.5 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-09-17 DOI: 10.1016/j.jsbmb.2025.106864
Shanshan Chen , Haoyi Feng , Tong Yu, Yizhao Li, Xuelei Han, Xinjian Li, Kejun Wang, Feng Yang
{"title":"Research progress on the function, expression and enzyme activity regulation of 17β-HSD1 in mammals","authors":"Shanshan Chen ,&nbsp;Haoyi Feng ,&nbsp;Tong Yu,&nbsp;Yizhao Li,&nbsp;Xuelei Han,&nbsp;Xinjian Li,&nbsp;Kejun Wang,&nbsp;Feng Yang","doi":"10.1016/j.jsbmb.2025.106864","DOIUrl":"10.1016/j.jsbmb.2025.106864","url":null,"abstract":"<div><div>17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) can catalyze the reduction of the less active estrone (E<sub>1</sub>) to the more active estradiol (E<sub>2</sub>). It has a significant impact on the reproduction of female animals, follicular development, the development of the breasts and reproductive organs in reproductive-age women, as well as the physical health, bones and cardiovascular system of postmenopausal women. This review summarizes the research progress on the expression, biological function, and regulatory mechanisms of 17β-HSD1 in estrogen-dependent diseases, including cancer. It also discusses the role of 17β-HSD1 in female reproduction processes, such as follicle development, and the regulation of its enzyme activity by activin A and insulin-like growth factor 1 (IGF-1). Furthermore, the review explores how phosphorylation at key sites influences its enzyme’s activity, aiming to enhance the understanding of its regulatory mechanisms and improve the clarity of related research findings. This review systematically summarizes the research progress of 17β-HSD1 expression and enzyme activity regulation, which can provide theoretical reference for the development of animal breeding technology and the treatment of estrogen dependent diseases.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106864"},"PeriodicalIF":2.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bushen Huoxue formula component β-Estradiol 3-acetate treats osteoarthritis through enhancing the TLR4 ubiquitination 补肾活血方成分β-雌二醇3-醋酸酯通过增强TLR4泛素化治疗骨关节炎。
IF 2.5 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-09-12 DOI: 10.1016/j.jsbmb.2025.106862
Xiaoli Liu , Shan Wang , Chuangfu Kuang , Yuwen Deng , Shuaicai Yuan , Juying Zou
{"title":"Bushen Huoxue formula component β-Estradiol 3-acetate treats osteoarthritis through enhancing the TLR4 ubiquitination","authors":"Xiaoli Liu ,&nbsp;Shan Wang ,&nbsp;Chuangfu Kuang ,&nbsp;Yuwen Deng ,&nbsp;Shuaicai Yuan ,&nbsp;Juying Zou","doi":"10.1016/j.jsbmb.2025.106862","DOIUrl":"10.1016/j.jsbmb.2025.106862","url":null,"abstract":"<div><div>We aim to explore the key metabolic components and underlying mechanisms of the Bushen Huoxue Formula (BH) in treating Osteoarthritis (OA). The mouse knee OA model was constructed using the destabilization of the medial meniscus method. OA mice were orally administered the BH. Mouse cartilage damage was assessed. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS), network pharmacology analysis and molecular docking were employed to analyze the serum metabolite components and target protein of BH. After lipopolysaccharide (LPS) treatment, different concentrations of β-Estradiol 3-acetate were added to primary chondrocytes. Flow cytometry was utilized for detecting cell apoptosis. The Ubiquitin-Specific Protease 13 (USP13)/Toll-like Receptor 4 (TLR4)/Myeloid Differentiation Primary Response Protein 88 (MYD88)/NF-κB pathway and the TLR4 ubiquitination levels were assessed using immunological quantification and biochemical methods. Relative to normal mice, OA mice exhibited decreased knee joint cartilage thickness and increased inflammatory damage. BH treatment reversed these effects. Furthermore, BH enhanced TLR4 ubiquitination. Estradiol acetate was identified as the metabolic component of BH that alleviates OA. Estradiol acetate and its subtype molecule β-Estradiol 3-acetate could bind to the USP13 protein. The β-Estradiol 3-acetate concentration-dependently decreased the elevated levels of USP13, TLR4, MYD88, p-p65/p65 in chondrocytes induced by LPS, while increasing the TLR4 ubiquitination. β-Estradiol 3-acetate reversed LPS-induced chondrocyte apoptosis and elevation of inflammatory factors. Moreover, USP13 overexpression abolished the protective effects of BH and β-Estradiol 3-acetate against LPS-induced chondrocytes. In Conclusion, the BH metabolite β-Estradiol 3-acetate promotes TLR4 ubiquitination to relieve inflammation and apoptosis in OA chondrocytes by inhibiting USP13.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106862"},"PeriodicalIF":2.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
POMC mediates orofacial hyperalgesia under hypoestrogenic conditions POMC介导低雌激素条件下的口面部痛觉过敏。
IF 2.5 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-09-12 DOI: 10.1016/j.jsbmb.2025.106861
Cong Chen , Linqian Zhang , Wenjuan Wang , Yanrong Sun , Yu Bai , Qinhan Yao , Shuo Qin , Lihua Qin , Jing Jia
{"title":"POMC mediates orofacial hyperalgesia under hypoestrogenic conditions","authors":"Cong Chen ,&nbsp;Linqian Zhang ,&nbsp;Wenjuan Wang ,&nbsp;Yanrong Sun ,&nbsp;Yu Bai ,&nbsp;Qinhan Yao ,&nbsp;Shuo Qin ,&nbsp;Lihua Qin ,&nbsp;Jing Jia","doi":"10.1016/j.jsbmb.2025.106861","DOIUrl":"10.1016/j.jsbmb.2025.106861","url":null,"abstract":"<div><div>Estrogen modulates sensory neuron excitability via metabolic pathways, regulating women's pain perception. pro-opiomelanocortin (POMC), an endogenous polypeptide precursor, regulates pain response and is highly expressed in the trigeminal ganglion (TG). In this study, we used ovariectomized female rats to study how trigeminal ganglion POMC links to orofacial allodynia in hypoestrogenic state, and verified at both the gene and protein levels that the expression of POMC in the trigeminal ganglion decreased under the hypoestrogenic state. Subsequently, overexpressing the POMC gene in the TG reversed the pain hyperalgesia in ovariectomized rats. To further explore the regulatory mechanism of estrogen on POMC, we injected a selective estrogen receptor agonist at the trigeminal ganglion. Estradiol (E2) in the TG regulates the expression of POMC through estrogen receptor α (ERα). Subsequently, the Chromatin Cleavage and Tagging technology (CUT&amp;Tag) and the dual-luciferase assay revealed that estrogen receptor α in the trigeminal ganglion has a positive regulatory effect on the promoter of POMC. In conclusion, this study has found that in the trigeminal ganglion, estrogen receptor α may reduce the expression of the POMC gene by inhibiting the activity of the POMC promoter. Meanwhile, this study has also found that in the TG, ERα may further regulate the biological activity of the POMC protein by binding to it. This dual regulation at both the transcriptional level and the protein level collectively mediates a decrease in the orofacial mechanical pain threshold and triggers an orofacial allodynia response.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106861"},"PeriodicalIF":2.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Network pharmacology-guided systems biology reveals β-Sitosterol’s multi-target role in reversing 7-ketocholesterol-induced oxidative and inflammatory stress 网络药理学引导的系统生物学揭示了β-谷甾醇在逆转7-酮胆固醇诱导的氧化和炎症应激中的多靶点作用
IF 2.5 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-09-12 DOI: 10.1016/j.jsbmb.2025.106863
Nila Ganamurali , Sarvesh Sabarathinam
{"title":"Network pharmacology-guided systems biology reveals β-Sitosterol’s multi-target role in reversing 7-ketocholesterol-induced oxidative and inflammatory stress","authors":"Nila Ganamurali ,&nbsp;Sarvesh Sabarathinam","doi":"10.1016/j.jsbmb.2025.106863","DOIUrl":"10.1016/j.jsbmb.2025.106863","url":null,"abstract":"<div><div>7-Ketocholesterol (7-KC), a cytotoxic oxysterol generated through cholesterol oxidation, plays a central role in the progression of atherosclerosis, neurodegeneration, and metabolic syndromes through mitochondrial dysfunction, ROS overproduction, and NLRP3 inflammasome activation. This study presents the first integrative systems pharmacology analysis exploring the molecular mechanisms by which β-sitosterol (BS), a phytosterol with antioxidant and anti-inflammatory properties, mitigates 7KC-induced toxicity. Shared targets between BS and 7KC were identified through target prediction databases and subjected to protein–protein interaction (PPI) network analysis using Cytoscape with bottleneck centrality. Top hub genes were functionally enriched using Gene Ontology and KEGG pathway tools, revealing BS’s modulation of nuclear receptor activity, redox homeostasis, and OXPHOS pathways. BS targets were localized across cytosol, nucleus, and membrane compartments, supporting its multi-compartmental regulatory role. This mechanistic framework highlights BS as a potential nutraceutical intervention for 7KC-driven chronic diseases, including atherosclerosis, NAFLD, and Alzheimer’s disease, warranting further biological validation.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106863"},"PeriodicalIF":2.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145050223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
White kidney bean extract improves letrozole-induced polycystic ovary syndrome in rats by regulating the Wnt signaling pathway 白芸豆提取物通过调节Wnt信号通路改善来曲唑诱导的大鼠多囊卵巢综合征
IF 2.5 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-09-07 DOI: 10.1016/j.jsbmb.2025.106858
Jiani Zhu , Ran Gu , Ya Zhu , Qun Zhou , Zijuan Zhang , Xinyue Qi , Xiaorong Wu , Bo Deng , Lanping Zhong
{"title":"White kidney bean extract improves letrozole-induced polycystic ovary syndrome in rats by regulating the Wnt signaling pathway","authors":"Jiani Zhu ,&nbsp;Ran Gu ,&nbsp;Ya Zhu ,&nbsp;Qun Zhou ,&nbsp;Zijuan Zhang ,&nbsp;Xinyue Qi ,&nbsp;Xiaorong Wu ,&nbsp;Bo Deng ,&nbsp;Lanping Zhong","doi":"10.1016/j.jsbmb.2025.106858","DOIUrl":"10.1016/j.jsbmb.2025.106858","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder characterized by ovarian dysfunction, with limited effective treatments. This study investigates the therapeutic effects and mechanisms of white kidney bean extract (WKBE) in a PCOS rat model. A PCOS model was established using letrozole, followed by intervention with varying doses of WKBE. Serum sex hormone levels, insulin resistance, and metabolic markers were measured. Ovarian histopathology, fibrosis, and apoptosis were assessed. Transcriptomic sequencing was performed on ovarian tissues from control, PCOS, and high-dose WKBE groups. High-dose WKBE significantly ameliorated endocrine-metabolic disturbances in PCOS rats, including reduced testosterone, LH/FSH ratio, insulin resistance, and lipid abnormalities, outperforming low/medium doses. It decreased body weight, ovarian index, and organ fat deposition, repaired ovarian histopathological damage, and reduced fibrosis and apoptosis. Transcriptomic analysis revealed that high-dose WKBE altered the expression of Wnt signaling pathway-related genes, suggesting its therapeutic role may involve modulation of this pathway. High-dose WKBE alleviates endocrine-metabolic dysregulation and ovarian dysfunction in PCOS rats by regulating the Wnt signaling pathway, offering a potential novel therapeutic strategy.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106858"},"PeriodicalIF":2.5,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeted deletion of Cyp24a1 in the intestine reduces mucosal injury and preserves epithelial proliferation after 5-fluorouracil treatment 在5-氟尿嘧啶治疗后,肠道中Cyp24a1的靶向缺失减少了粘膜损伤并保持了上皮细胞的增殖。
IF 2.5 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-09-05 DOI: 10.1016/j.jsbmb.2025.106857
Phir C.K. Thianhlun , Cyan L. Sylvester , Rebecca K. Sawyer , Hannah R. Wardill , Andrea M. Stringer , Paul H. Anderson
{"title":"Targeted deletion of Cyp24a1 in the intestine reduces mucosal injury and preserves epithelial proliferation after 5-fluorouracil treatment","authors":"Phir C.K. Thianhlun ,&nbsp;Cyan L. Sylvester ,&nbsp;Rebecca K. Sawyer ,&nbsp;Hannah R. Wardill ,&nbsp;Andrea M. Stringer ,&nbsp;Paul H. Anderson","doi":"10.1016/j.jsbmb.2025.106857","DOIUrl":"10.1016/j.jsbmb.2025.106857","url":null,"abstract":"<div><div>Vitamin D has been proposed to attenuate chemotherapy-induced gastrointestinal mucositis (GM). In the intestine, local catabolism of active vitamin D [1,25-dihydroxyvitamin D₃] is mediated by the enzyme Cyp24a1. This study assessed whether deletion of Cyp24a1 specifically in intestinal epithelial cells can protect against 5-fluorouracil (5-FU)-induced intestinal injury and microbiome disruption in mice. Using the Cre-loxP system, Cyp24a1 was selectively ablated in the intestinal epithelium (IEC-KO mice). Male IEC-KO and Cyp24a1^fl/fl^ littermate control mice received a single intraperitoneal injection of 5-FU (450 mg/kg) or saline and were euthanised 48 h later. In control mice, 5-FU markedly reduced duodenal villous height and crypt area (p &lt; 0.01), whereas IEC-KO mice retained intestinal architecture. Proliferation, measured by Ki-67 immunostaining, was preserved in both the small and large intestine of IEC-KO mice following 5-FU treatment (p &lt; 0.05). Notably, colonic Tlr4 mRNA was significantly upregulated in IEC-KO mice (p &lt; 0.001), with no corresponding increase in inflammatory cytokines. 16S rRNA sequencing revealed no change in overall microbial diversity; however, there were notable differences in the relative abundance of key taxa, such as Bifidobacteriaceae and Alistipes. These findings suggest that intestinal Cyp24a1 contributes to susceptibility to chemotherapy-induced intestinal injury and microbial dysbiosis, and that its deletion enhances epithelial regeneration, potentially via innate immune pathways.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106857"},"PeriodicalIF":2.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
7-ketocholesterol as a critical oxysterol: Impact on human health and safety in food systems 7-酮胆固醇作为一种重要的氧化固醇:对食品系统中人类健康和安全的影响。
IF 2.5 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-09-05 DOI: 10.1016/j.jsbmb.2025.106856
Sheethal S Kumar, Akash Prakash, P.V. Keerthana, Mathew John
{"title":"7-ketocholesterol as a critical oxysterol: Impact on human health and safety in food systems","authors":"Sheethal S Kumar,&nbsp;Akash Prakash,&nbsp;P.V. Keerthana,&nbsp;Mathew John","doi":"10.1016/j.jsbmb.2025.106856","DOIUrl":"10.1016/j.jsbmb.2025.106856","url":null,"abstract":"<div><div>7-Ketocholesterol (7-KC) is a biologically active oxysterol formed through the oxidation of cholesterol, predominantly under conditions of oxidative stress. It is generated both enzymatically in specific tissues such as the brain and liver, and non-enzymatically <em>via</em> reactive oxygen species (ROS), especially in aging tissues and heat-processed animal-derived foods. 7-KC exerts multifaceted effects on human health, extending beyond lipid metabolism to disrupt glucose and amino acid utilization, impair mitochondrial function, and provoke endoplasmic reticulum (ER) stress. These disturbances contribute to chronic inflammation and oxidative damage, playing pivotal roles in the development of various diseases, including atherosclerosis, neurodegenerative disorders, diabetes, cancer, hepatic steatosis, and ocular and gastrointestinal pathologies. Additionally, 7-KC is a marker of cholesterol oxidation in the food industry, where it signals product degradation and potential toxicity in long-stored or thermally processed animal-based foods. This review explores the biosynthesis, metabolic fate, and pathophysiological role of 7-KC, highlighting its critical role in intermediary metabolism, disease progression, and food safety. Furthermore, it outlines mitigation strategies to reduce 7-KC exposure through dietary modifications, antioxidant interventions, and advanced food processing technologies aimed at enhancing public health.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106856"},"PeriodicalIF":2.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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