Journal of Steroid Biochemistry and Molecular Biology最新文献

{"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}

{"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}

{"title":"Corrigendum to “Analysis of star promoter in common carp and catfish testis: Role of c-jun and its association with testicular function as a transcription factor” [J. Steroid Biochem. Mol. Biol. 253 (2025) 106817]","authors":"Swathi Tenugu,&nbsp;Balasubramanian Senthilkumaran","doi":"10.1016/j.jsbmb.2025.106847","DOIUrl":"10.1016/j.jsbmb.2025.106847","url":null,"abstract":"","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106847"},"PeriodicalIF":2.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001894","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}

{"title":"Guggulsterone as a dual-function steroidal scaffold: Cholesterol modulation and bioenhancement potential against 7-Ketocholesterol-Linked pathologies","authors":"Sarvesh Sabarathinam ,&nbsp;Nila Ganamurali","doi":"10.1016/j.jsbmb.2025.106848","DOIUrl":"10.1016/j.jsbmb.2025.106848","url":null,"abstract":"<div><div>7-Ketocholesterol (7-KC), a cytotoxic cholesterol oxidation product, drives oxidative stress, inflammation, and apoptosis in cardiovascular, neurodegenerative, and metabolic disorders. Current lipid-lowering agents, such as statins, do not eliminate pre-formed oxysterols, highlighting an unmet therapeutic need. Guggulsterone(GGS), a steroidal phytoconstituent from <em>Commiphora mukul</em>, exhibits dual-function potential by reducing 7-KC formation through antioxidant, anti-inflammatory, and Nrf2-activating effects, while enhancing cholesterol efflux via LDLR and ABC transporters. Additionally, it improves endothelial and neuronal resilience to oxysterol-induced apoptosis. Guggulsterone’s amphiphilic nature supports its integration into nanocarriers, enabling co-delivery with therapeutics for synergistic effects. Advanced formulations such as SEDDS, nanoparticle co-encapsulation, and solid lipid nanoparticles enhance its bioavailability, stability, and tissue targeting, including brain delivery. These properties position guggulsterone as both a therapeutic agent and bioenhancer, offering a promising strategy to mitigate oxysterol burden and improve clinical outcomes in 7-KC–related disorders.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106848"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144931898","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}

{"title":"Targeting 7-ketocholesterol-induced oxidative stress and inflammation: Guggulsterone as a novel vascular protectant","authors":"Sarvesh Sabarathinam ,&nbsp;Nila Ganamurali","doi":"10.1016/j.jsbmb.2025.106846","DOIUrl":"10.1016/j.jsbmb.2025.106846","url":null,"abstract":"<div><div>7-Ketocholesterol (7-KC), a prominent oxysterol found in oxidized LDL, plays a central role in atherosclerosis through mechanisms involving oxidative stress, NF-κB activation, and mitochondrial dysfunction. Guggulsterone (GGS), a bioactive steroid from <em>Commiphora mukul</em>, exhibits antioxidant, anti-inflammatory, and FXR-antagonistic properties. This work highlights guggulsterone’s ability to counteract 7-KC-induced endothelial injury by inhibiting NF-κB translocation, reducing reactive oxygen species (ROS), and modulating apoptosis. These multimodal effects suggest guggulsterone as a promising natural agent for vascular protection. A systems-based pharmacological approach may further define its therapeutic utility in oxysterol-driven cardiovascular diseases.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106846"},"PeriodicalIF":2.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895523","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}

{"title":"In silico multitargeted molecular docking study of interacting partners of epibrassinolide in cancer cells and in vitro evaluation of cell death mechanisms associated with these partners","authors":"Leila Mehdizadehtapeh ,&nbsp;Zeynep Demirel ,&nbsp;Esranur Kopal ,&nbsp;Elif Damla Arısan ,&nbsp;Tugba Taşkın Tok ,&nbsp;Pınar Obakan Yerlikaya","doi":"10.1016/j.jsbmb.2025.106845","DOIUrl":"10.1016/j.jsbmb.2025.106845","url":null,"abstract":"<div><div>Elucidating the mechanisms of action of natural metabolites may be promising in the emergence of alternative candidate therapeutics. In the present study, the combined approaches of <em>in silico</em> molecular docking (MD) and <em>in vitro</em> analyses were conducted to investigate the interacting partners of 24-epibrassinolide (EBR) as a steroid-derived phytohormone in cancer cells and evaluate the cell death mechanisms associated with these partners. EBR scoring functions were initially calculated against the selected 35 functional target proteins, which may interact with steroids, for tumor biology using AutoDock Tools-1.5.7 receptor-ligand MD software. Molecular analyses were carried out in breast, pancreatic, and hepatocellular carcinoma cell lines. Our results showed that the retinoic acid nuclear receptor γ (RARγ) was the most stable interacting partner with a binding energy (BE). Furthermore, the secondary simulation analyses obtained the lowest BE score for EBR among RARγ selective agonistic compounds. According to our data, EBR was significantly inhibited the cell viability of MDA-MB-231, MIA-PaCa-2, and Hep-G2 cells, and diminished the colony formation potential. We showed that RARγ was inhibited after increasing concentration of EBR, by affecting the downstream target’s expressions including p21, p16, p27, p57 and cyclin D1 detected by qRT-PCR. We also investigated the effect of EBR treatment on the expression levels of the proteins linked to nuclear hormone receptor (NHR) expressions, apoptosis, endoplasmic reticulum stress, and Hippo-Yes-associated protein (YAP)/ Transcriptional coactivator with PDZ-binding motif (TAZ) signaling pathways. Our findings indicated that EBR is a strong ER stress modulator, apoptosis inducer in a caspase-dependent manner, and effector for the modulation of Hippo-YAP-TAZ signaling pathways through the interaction with retinoic acid receptor.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106845"},"PeriodicalIF":2.5,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922751","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}

{"title":"The benefit of mineralocorticoid receptor blockade in the treatment of experimental autoimmune encephalomyelitis mice","authors":"Franco Veloso ,&nbsp;Sofía D'Alessandro ,&nbsp;Analia Lima ,&nbsp;Paulina Roig ,&nbsp;Alejandro F. De Nicola ,&nbsp;Laura I. Garay","doi":"10.1016/j.jsbmb.2025.106844","DOIUrl":"10.1016/j.jsbmb.2025.106844","url":null,"abstract":"<div><div>Research on the effects of the mineralocorticoid receptor (MR) suggested a role in innate and adaptive immune responses. The inflammatory profile is directly linked to MR activation in several pathologies such as cardiovascular diseases, autoimmunity, chronic renal disease and obesity. MR is a high-affinity receptor binding both mineralocorticoids and glucocorticoids. In this study, we explored the pharmacological modulation of MR with the mineralocorticoid agonist deoxycorticosterone (DOCA) and the antagonist spironolactone (SPIRO) on corticosterone levels in plasma, neuroinflammation, myelin status and neurodegeneration in the spinal cord of mice with experimental autoimmune encephalomyelitis (EAE) model of Multiple Sclerosis. Animals were treated from day 1 until sacrificed on day 17 post-induction, and experimental groups were divided into: EAE+DOCA (0.75 mg/kg s.c every 3 days), EAE+DOCA+SPIRO (Spironolactone: 25 mg/kg i.p daily), vehicle-treated EAE (EAE+VEH) and Control (CTRL). Administration of DOCA or vehicle to EAE conducted to similar neuropathological alterations. The MR antagonist (a) significantly decreased inflammatory parameters TLR4, IL-1β and microglial CD11b mRNAs and showed a tendency to reduced osteopontin, b) reduced the % of infiltrated cellular and demyelinated area, as well as the reactive gliosis (GFAP+ area and number of IBA1 + cells) vs EAE+DOCA (c) increased the area of the neuronal marker NeuN vs EAE+DOCA and EAE+VEH groups (d) improved functional performance in the rotarod test and clinical signs vs EAE+DOCA. Interestingly, plasma corticosterone was increased in EAE+VEH and EAE+DOCA vs CTRL, while SPIRO administration raised even more corticosterone levels. This hypercorticosteronemia had functional consequences, because the glucocorticoid receptor (GR) and the target gene serum glucocorticoid regulated kinase 1 (SGK1) mRNAs expression were also increased vs DOCA alone. We hypothesized that MR blockage with SPIRO downregulated inflammation-related spinal cord pathology whereas excess glucocorticoids circulating in the EAE+DOCA+SPIRO group may contribute to anti-inflammatory effects.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106844"},"PeriodicalIF":2.5,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895522","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}

{"title":"Sexual dimorphism and susceptibility to Alzheimer’s disease: Understanding genetic involvement and other risk factors","authors":"Abayomi Oyeyemi Ajagbe ,&nbsp;Abdulateef Ayoola Mobolaji ,&nbsp;Oluwanisola Akanji Onigbinde ,&nbsp;Tolulope Josiah Mosaku ,&nbsp;Blessing Simon Oyeleye ,&nbsp;Elizabeth Fisayo Ajenikoko-Ugbor ,&nbsp;Al-Hassan Soliman Wadan ,&nbsp;Abdulrahman Adesola Bello ,&nbsp;Michael Kunle Ajenikoko ,&nbsp;Ayodeji Zabdiel Abijo","doi":"10.1016/j.jsbmb.2025.106843","DOIUrl":"10.1016/j.jsbmb.2025.106843","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by persistent cognitive decli ne, tau-containing intracellular neurofibrillary tangles, and β-amyloid (Aβ)-containing extracellular plaques. Early symptoms include patchy memory loss and some behavioural abnormalities. There is a plethora of studies that have reported sexual dimorphism and a higher prevalence of Alzheimer's disease in women. However, the molecular mechanisms responsible for these differences remain an enigma. The increasing aging population, as well as the decline in estrogen levels, have been attributed to increased risk in the development of AD in women. Hormone replacement therapy (HRT) has been proposed as an approach for tackling the increased AD susceptibility in women; increased AD vulnerability in men is also linked to testosterone levels. In addition to the hormonal influence as one of the causative factors for increased risk of AD, there is the involvement of genetic factors, with APOE ε4 gene documented as a risk gene leading to tau pathological changes in the brain of female AD patients. Here, we aim to systematically examine literature on the factors and molecular mechanisms responsible for sexual dimorphism in increased vulnerability and pathological features of AD, with the hope that it may provide information on the diagnosis and therapeutic interventions in AD.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106843"},"PeriodicalIF":2.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829991","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}

{"title":"Neurosteroids for the treatment of neurodegenerative disorders: We still have a long way to go","authors":"Yongjiu Ji ,&nbsp;Mengyu Wang ,&nbsp;Chun Yang","doi":"10.1016/j.jsbmb.2025.106841","DOIUrl":"10.1016/j.jsbmb.2025.106841","url":null,"abstract":"","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106841"},"PeriodicalIF":2.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829992","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}

{"title":"Function of ceramides in the skin and its relationship with skin disease","authors":"Weihao Huang ,&nbsp;Jiahui Liu ,&nbsp;Lunxuan Zhao ,&nbsp;Huaming He","doi":"10.1016/j.jsbmb.2025.106842","DOIUrl":"10.1016/j.jsbmb.2025.106842","url":null,"abstract":"<div><div>The skin is a vital organ that protects the body from external insults. Ceramides, the major lipid components of the skin, are synthesized through three main pathways: <em>de novo</em> synthesis, sphingomyelin hydrolysis, and the salvage pathway. Ceramides are crucial for maintaining the skin barrier and hydration, and their deficiencies are associated with various skin diseases such as atopic dermatitis, psoriasis, and Netherton's syndrome. In the cosmetic industry, ceramides are used for skin barrier repair and moisturization. However, their poor water solubility necessitates the development of effective delivery systems. Alternatively, exogenous substances can be utilized to promote ceramide synthesis in skin. Therefore, elucidating the mechanisms by which ceramides influence the skin barrier and hydration, and developing ceramide-containing cosmetic products based on these mechanisms, represent promising research directions for improving skin health.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106842"},"PeriodicalIF":2.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849568","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}