Journal of Steroid Biochemistry and Molecular Biology最新文献

{"title":"Vitamin D pathway as a multi-level predictor of COVID-19 severity and mortality: Integrating serum levels, FokI (rs2228570) VDR polymorphism, and lung tissue expression","authors":"Harem Khdir Awla ,&nbsp;Baghawan Ahmed Othman ,&nbsp;Dawan dlshad rafeeq ,&nbsp;Shukur Wasman Smail ,&nbsp;Raya Kh. Yashooa ,&nbsp;Asmaa Ameen Ghareeb ,&nbsp;Rebaz Hamza Salih ,&nbsp;Shwan Ali Omar ,&nbsp;Christer Janson","doi":"10.1016/j.jsbmb.2025.106879","DOIUrl":"10.1016/j.jsbmb.2025.106879","url":null,"abstract":"<div><h3>Background</h3><div>Vitamin D is a known immunomodulator, but its predictive value in COVID-19 remains incompletely understood. This study investigates the role of vitamin D across molecular, biochemical, and histopathological levels to evaluate its association with COVID-19 severity and mortality.</div></div><div><h3>Methods</h3><div>A prospective case-control study was conducted in the Kurdistan Region of Iraq from May to October 2021. Ninety-five confirmed COVID-19 patients (75 survivors, 20 non-survivors) and 75 healthy controls were enrolled. Serum 25(OH)D levels were quantified by ELISA. Clinical severity was assessed using CURB-65, NEWS, and SOFA scores. Genotyping for the <em>Fok</em>I (rs2228570) polymorphism in the VDR gene was performed via allele-specific PCR. Lung tissue from five survivors (biopsy) and five non-survivors (autopsy) underwent immunohistochemical staining to evaluate VDR expression.</div></div><div><h3>Results</h3><div>Serum vitamin D concentrations were markedly reduced in non-survivors (20.34 ± 0.46 ng/mL) relative to survivors (40.11 ± 0.28 ng/mL, p &lt; 0.001). Vitamin D exhibited a negative correlation with CURB-65 (r = –0.828), NEWS (r = –0.794), and SOFA (r = –0.762) scores. Regression analysis established that vitamin D was independently associated with disease severity in our population. The TT genotype of the <em>Fok</em>I VDR polymorphism correlated with markedly reduced vitamin D levels and elevated severity scores. Mortality exhibited a strong association with the TT genotype (OR = 10.29, 95 % CI: 2.204–49.19, p = 0.003) and the T allele (OR = 3.923, p = 0.0006). ROC analysis determined a vitamin D threshold of ≤ 20.56 ng/mL as indicative of mortality (AUC = 0.784, p &lt; 0.0001). Immunohistochemistry demonstrated elevated VDR expression in lung tissues of deceased COVID-19 patients relative to VDR-negative controls.</div></div><div><h3>Conclusion</h3><div>This study indicates that serum vitamin D levels, VDR gene polymorphism (rs2228570), and lung tissue VDR expression are strongly correlated with the severity and mortality of COVID-19. These findings validate the clinical use of vitamin D and VDR profiling may have associative markers and prospective treatment targets in the management of COVID-19.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"255 ","pages":"Article 106879"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145362994","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":"2025-11-01","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":"Nano-curcumin attenuates tamoxifen resistance and malignant progression in ER-positive breast cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway","authors":"Chenguang Zhang,&nbsp;Hu Wang,&nbsp;Hao Lei,&nbsp;Jianghua Ou","doi":"10.1016/j.jsbmb.2025.106825","DOIUrl":"10.1016/j.jsbmb.2025.106825","url":null,"abstract":"<div><div>Breast cancer (BC) is one of the most prevalent malignant tumors among women, with estrogen receptor (ER)-positive patients constituting approximately 70 % of all cases. Endocrine therapy is currently a treatment option for patients with ER-positive BC; however, the development of resistance significantly limits the effectiveness of this treatment. Nano-curcumin (Nano-CUR) possesses anticancer properties and enhances bioavailability by improving the hydrophobic character of curcumin (CUR). However, the underlying mechanism by which Nano-CUR affects tamoxifen (TAM) resistance in ER-positive BC remains unknown. Here, we found that Nano-CUR promoted apoptosis and cell cycle arrest, inhibited cell proliferation and reduced the levels of cancer stem cells (CSCs)-related markers, including octamer-binding protein (OCT4), Nanog homeobox (NANOG) and sex-determining region Y-box 2 (SOX2) in TAM-resistant BC cells. Additionally, Nano-CUR demonstrated the ability to inhibit tumor malignant progression in TAM-treated BC mice. Mechanistically, Nano-CUR blocked the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in MCF-7/TAM and T47D/TAM cells. The activation of this pathway by its activators (PI3K activator 740Y-P, AKT activator SC-79, and mTOR activator MHY1485) effectively alleviated the anti-tumor effect induced by Nano-CUR in TAM-resistant BC cells. Collectively, these findings reveal that Nano-CUR contributes to the reduction of tumorigenesis and TAM resistance in ER-positive BC cells by inhibiting the PI3K/AKT/mTOR signaling pathway.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106825"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568068","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":"2025-11-01","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":"Mogroside V restores glycolytic function via LDHA promoter demethylation independent of alternative splicing in PCOS granulosa cells","authors":"Shuai Li ,&nbsp;Jiaxin Wu ,&nbsp;Renhong Lu ,&nbsp;Benliang Zhou ,&nbsp;Hongpeng Dai ,&nbsp;Zhen Zhang ,&nbsp;Xiaogan Yang ,&nbsp;Xingwei Liang","doi":"10.1016/j.jsbmb.2025.106839","DOIUrl":"10.1016/j.jsbmb.2025.106839","url":null,"abstract":"<div><div>Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by metabolic dysfunction. This study investigated whether Mogroside V (MV) ameliorates hyperandrogenism-induced glycolytic dysfunction in testosterone (TES)-treated KGN cells. KGN cells treated with 150 µM TES exhibited significantly reduced viability, decreased lactate production, and increased pyruvate levels, which were reversed by 60 µM MV. Transcriptomic analysis revealed that TES dysregulated gene expression associated with alternative splicing (AS) and glycolytic pathways, while MV normalized glycolysis-related genes (<em>LDHA</em>, <em>PKM</em>) without affecting AS events. Although TES upregulated splicing factors <em>HNRNPH3</em> and <em>SRSF1</em>, MV restored the expression of <em>HNRNPH3</em> and <em>SRSF1</em> without inducing aberrant splicing. Mechanistically, MV significantly reduced TES-induced hypermethylation of the <em>LDHA</em> promoter, thereby restoring <em>LDHA</em> mRNA and protein expression. MV mitigates PCOS-associated metabolic dysfunction primarily through <em>LDHA</em> promoter demethylation, independent of alternative splicing regulation. This study highlights MV as a natural compound with epigenetic regulatory potential for PCOS therapy.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106839"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739681","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":"2025-11-01","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":"Vitamin D3 (cholecalciferol) is more efficacious than Vitamin D2 (ergocalciferol) at regulating calcium absorption and bone quality in rats","authors":"Soumam Dutta ,&nbsp;Athira Anilkumar Sudharma ,&nbsp;Shabna Aboo ,&nbsp;Surendar Jatavath ,&nbsp;Sivaramakrishna Siginam ,&nbsp;Pradeep B. Patil ,&nbsp;Sai Santhosh Vadakattu ,&nbsp;Mullapudi Venkata Surekha ,&nbsp;G. Bhanuprakash Reddy ,&nbsp;Ayesha Ismail","doi":"10.1016/j.jsbmb.2025.106837","DOIUrl":"10.1016/j.jsbmb.2025.106837","url":null,"abstract":"<div><div>Differential efficacy of vitamin D2 (D2) versus vitamin D3 (D3) in improving classical functions in target organs remain incompletely understood. Previous studies show contradictory results, with limited comprehensive assessment of functional and molecular outcomes across classical target organs namely intestine, bone and kidney. This study investigated the comparative effects of D2 and D3, administered independently or in combination at different dosages, on these organs using a rat model. Weanling male Sprague-Dawley rats were subjected to a depletion-repletion study design with diets containing D2, D3, combination (D2 +D3), or vitamin D deficient (VDD) diet. Our results demonstrated that vitamin D3 supplementation elevated serum 25(OH)D levels more efficiently compared to vitamin D2, while concurrent D2 administration reduced the potential of D3 to increase 25(OH)D3 levels. Both D2 and D3 maintained serum Ca and PTH in the normal range. Intestinal ⁴⁵Ca absorption was higher in groups receiving D3-based diets in a dose-dependent manner. Furthermore, D3 supplementation had superior effects on bone length, width and strength compared to D2. Vitamin D3 more effectively reduced trabecular bone area in the rehabilitation phase. Additionally, the expression of genes involved in renal calcium reabsorption (<em>Trpv5</em>, <em>Calbindin-D28k</em>, <em>Pmca1b</em>) and vitamin D metabolism/function (<em>Cubilin</em>, <em>Vdr</em>) were significantly altered in VDD group and better corrected with D3 than D2 during rehabilitation. These findings suggest that vitamin D3 is more efficacious than vitamin D2 in improving blood levels of 25(OH)D and majority of the classical functions. Hence vitamin D3 appears to be the superior choice for both prevention and rehabilitation purposes.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106837"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711405","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":"Inducing agents and PCOS - A comprehensive analysis.","authors":"Dhanyaa Muthukumaran, Jayalakshmi Kumar, Rajeshkumar Shanmugam","doi":"10.1016/j.jsbmb.2025.106840","DOIUrl":"10.1016/j.jsbmb.2025.106840","url":null,"abstract":"<p><p>Polycystic Ovary Syndrome (PCOS) is a severe and heterogeneous endocrine disorder affecting 6-20 % of women of reproductive age globally. Despite its high prevalence, the underlying etiology and pathophysiology remain unclear, necessitating the use of animal models to study disease mechanisms and therapeutic targets. This review critically evaluates various induction agents used in PCOS animal models and their ability to mimic the clinical, metabolic, and reproductive manifestations of the human condition. Induction agents explored include androgens [Testosterone, Dihydrotestosterone (DHT), Dehydroepiandrosterone (DHEA)], estrogen (estradiol valerate), aromatase inhibitors (letrozole), endocrine disruptors (bisphenol A), and dietary modifications (high-fat or high-sugar diets). These agents, administered in species such as rats, mice, zebrafish, reproduce hallmark PCOS features, including hyperandrogenism, anovulation, polycystic ovaries, and insulin resistance. The review highlights the mechanisms, symptom profiles, and translational relevance of each model. Comparative analysis is provided to assess the strengths and limitations associated with each agent, considering factors such as hormonal balance, metabolic function, and reproductive outcomes. Animal models serve as essential tools for understanding PCOS and testing therapeutic interventions. Each inducing agent offers unique insights into specific aspects of the disorder, although none fully replicates the human syndrome. The selection of the agent and animal species based on research goals is vital for clinical relevance. Future work should focus on integrating models that reflect both reproductive and metabolic features of PCOS to improve translational value.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106840"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800807","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":"2025-11-01","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}

{"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":"2025-11-01","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}