Journal of Steroid Biochemistry and Molecular Biology最新文献

{"title":"Secosteroid - 1,3,4-Oxadiazole Hybrids: Synthesis and Evaluation of Their Activity Against Hormone-Dependent Breast Cancer Cells.","authors":"Alexey I Ilovaisky, Alexander M Scherbakov, Dumitru Miciurov, Elena I Chernoburova, Valentina M Merkulova, Fedor B Bogdanov, Diana I Salnikova, Danila V Sorokin, Mikhail A Krasil'nikov, Eugene I Bozhenko, Igor V Zavarzin, Alexander O Terent'ev","doi":"10.1016/j.jsbmb.2025.106745","DOIUrl":"https://doi.org/10.1016/j.jsbmb.2025.106745","url":null,"abstract":"<p><p>This study focused on the synthesis of secosteroids with good antiproliferative properties against hormone-dependent breast cancer. A straightforward and efficient method for synthesizing secosteroid - 1,3,4-oxadiazole hybrids was developed starting from 13α-hydroxy-3-methoxy-13,17-secoestra-1,3,5(10)-trien-17-oic acid hydrazide. The cyclization of hydrazide moiety with CS₂ into 1,3,4-oxadiazole-2(3H)-thione fragment followed by sulfur alkylation resulted in the formation of various secosteroid - 2-mercapto-1,3,4-oxadiazole hybrids. These novel compounds were evaluated for their antiproliferative activity against the hormone-dependent human breast cancer cell line MCF-7. Among the synthesized hybrids, compounds 3i, 3o, and 3q displayed notable antiproliferative effects, with IC₅₀ values ranging from 6.5 to 8.9µM, comparable to the reference drug cisplatin. Furthermore, compound 3i showed minimal toxicity toward non-cancerous hFB-hTERT fibroblasts, indicating high selectivity. Compounds 3o and 3q exhibited antiestrogenic activity. Additionally, their effects on PARP and Bcl-2 suggest a pro-apoptotic mechanism of action. These findings highlight the potential of secosteroidal hybrids as promising candidates for the development of new anti-breast cancer agents targeting ERα and apoptosis pathways.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106745"},"PeriodicalIF":2.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755636","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":"From lipids to glucose: Investigating the role of dyslipidemia in the risk of insulin resistance","authors":"Mahtab Jahdkaran ,&nbsp;Mohammad Sistanizad","doi":"10.1016/j.jsbmb.2025.106744","DOIUrl":"10.1016/j.jsbmb.2025.106744","url":null,"abstract":"<div><div>Dyslipidemia is recognized as one of the most prevalent metabolic disorders and is frequently associated with other prevalent conditions, particularly diabetes mellitus. There appears to be a bidirectional connection between these two metabolic disorders. While considerable research has focused on how insulin resistance can lead to lipid abnormalities, the reverse relationship specifically, how dyslipidemia could assist in developing insulin resistance and diabetes mellitus has received relatively less attention. This review aims to comprehensively evaluate the mechanisms through which dyslipidemia can induce insulin resistance. Dyslipidemia is primarily classified into three main categories: hypercholesterolemia, hypertriglyceridemia, and low levels of HDL. These conditions may promote insulin resistance across multiple pathways, including the accumulation of lipid metabolites, dysfunction of pancreatic β-cells, increased reactive oxygen species, endoplasmic reticulum stress and inflammation, endothelial dysfunction, alterations in adiponectin levels, changes in bile acid composition and concentration, and dysbiosis of gut microbiota. However, further investigation is required to fully elucidate the cellular and molecular mechanisms underlying the relationship between lipid disorders and insulin resistance. Emphasizing such research could facilitate the development of therapeutic strategies targeting both conditions simultaneously.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106744"},"PeriodicalIF":2.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739838","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":"High-dose vitamin D supplementation in pregnancy ameliorates obesity-induced increase in maternal IL-1β level without affecting obesity-induced increase in IL-6 and MCP","authors":"Helena H. Andersen ,&nbsp;Matilde K. Andersen ,&nbsp;Krista Agathe Bossow ,&nbsp;Anna Louise Vestergaard ,&nbsp;Pinar Bor ,&nbsp;Agnete Larsen","doi":"10.1016/j.jsbmb.2025.106742","DOIUrl":"10.1016/j.jsbmb.2025.106742","url":null,"abstract":"<div><h3>Background</h3><div>Maternal and placental inflammatory activity is carefully regulated during pregnancy and changes in inflammatory status are associated with pregnancy complications and health deficits in the offspring including adverse effects on neurodevelopment. Overweight/obesity is associated with chronic inflammation, thereby contributing to adverse effects. Disturbingly, overweight and obesity are highly prevalent among pregnant women worldwide. Vitamin D (vitD) possess immunomodulatory effects and is believed to support healthy pregnancy. Endocrinological societies recommend empiric vitD supplementation in pregnancy but there is no consensus on the minimal supplementation dose</div></div><div><h3>Methods</h3><div>An adjacent study to GRAVIT-D (no. NCT04291313, ClinicalTrial.gov), a double-blinded randomized trial investigating the clinical benefits of increasing vitD supplementation in pregnancy from 400IU to 3600IU/day from gestational week 11–16 onwards. In a subgroup, (n = 156), multiplex ELISA targeting third-semester serum levels of IL-1β, IL-6, IL-10, TNFα, MCP-1, and IL-17A was performed. Inflammation signals were correlated with the vitD dose given, subsequently analysing the effect of vitD in relation to the pre-pregnancy body mass index (BMI) within each treatment arm comparing the inflammatory response in WHO-defined BMI groups, &lt; 25, 25–30 and &gt; 30 kg/m².</div></div><div><h3>Main Results</h3><div>High pre-pregnancy BMI was associated with increased IL6 and MCP1 in both the 400IU and the 3600 IU exposed group. IL1β levels increased with BMI if using a 400IU/day supplement. High dose vitD supplementation ameliorated BMI effects on IL1β.</div></div><div><h3>Conclusion and Perspectives</h3><div>Increased vitD supplementation during pregnancy may ameliorate some overweight/obesity-induced inflammatory activity. Further studies are needed to determine the vitD need in pregnancies complicated by obesity and overweight.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106742"},"PeriodicalIF":2.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytoestrogens as Potential Anti-Osteoporosis Nutraceuticals: Major Sources and Mechanism(s) of Action.","authors":"Mohammad Amir Khan, Mohsin Ali Khan, Sahabjada Siddiqui, Aparna Misra, Kusum Yadav, Aditi Srivastava, Anchal Trivedi, Ishrat Husain, Rumana Ahmad","doi":"10.1016/j.jsbmb.2025.106740","DOIUrl":"https://doi.org/10.1016/j.jsbmb.2025.106740","url":null,"abstract":"<p><p>By 2050, the global aging population is predicted to reach 1.5 billion, highlighting the need to enhance elderly quality of life. Osteoporotic fractures are projected to affect one in three women and one in five men over aged 50. Initial treatments for osteoporosis in postmenopausal women include antiresorptive agents such as bisphosphonates, strontium ranelate, estrogen replacement therapy (ERT) and selective estrogen receptor modulators (SERMs). However, these do not rebuild bone, limiting their effectiveness. Denosumab, an FDA-approved antiresorptive monoclonal antibody, also has drawbacks including high costs, biannual subcutaneous injections, slow healing, impaired bone growth, and side effects like eczema, flatulence, cellulitis, osteonecrosis of the jaw (ONJ), and an increased risk of spinal fractures after treatment discontinuation. Nutraceuticals, particularly phytoestrogens, are gaining attention for their health benefits and safety in osteoporosis prevention. Phytoestrogens, plant metabolites similar to mammalian estrogens, include isoflavones, coumestans, lignans, stilbenes, and flavonoids. They interact with estrogen receptor isoforms ERα and ERβ, acting as agonists or antagonists based on concentration and bioavailability. Their tissue-selective activities are particularly significant: anti-estrogenic effects in reproductive tissues may lower the risk of hormone-related cancers (such as ovarian, uterine, breast, and prostate cancers), while estrogenic effects on bone could contribute to the preservation of bone mineral density.Phytoestrogens are, thus, used in managing breast and prostate cancers, cardiovascular diseases, menopause, and osteoporosis. The presentreview focuses on the botanical origin,classification, sources and mechanism(s) of action of major phytoestrogens, their potential in prevention and management of osteoporosis and the requirement for additional clinical trials to achieve more definitive outcomes in order to confirm their efficacy and dosage safety.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106740"},"PeriodicalIF":2.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732969","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":"A comprehensive perspective on the role of vitamin D signaling in maintaining bone homeostasis: Lessons from animal models","authors":"Kayleigh Rillaerts,&nbsp;Lieve Verlinden,&nbsp;Stefanie Doms,&nbsp;Geert Carmeliet,&nbsp;Annemieke Verstuyf","doi":"10.1016/j.jsbmb.2025.106732","DOIUrl":"10.1016/j.jsbmb.2025.106732","url":null,"abstract":"<div><div>1,25(OH)₂D₃ is well known for its role in maintaining normal serum calcium levels. Through its receptor, 1,25(OH)₂D₃ enhances intestinal calcium absorption and renal calcium reabsorption, thereby ensuring serum calcium levels are within physiological range, which is in turn important for normal bone development and mineralization. The vitamin D receptor (VDR) achieves this via transcriptional induction of genes important in calcium transport. When intestinal and renal calcium (re)absorption is impaired, VDR-mediated signaling will stimulate bone resorption and inhibit mineralization in order to maintain normal serum calcium levels, as evidenced in mice with a systemic or intestine-specific deletion of the VDR. However, VDR signaling in bone is also reported to have anabolic effects. In this review we will discuss the effects of 1,25(OH)₂D₃-mediated VDR signaling on bone homeostasis and provide an overview of the <em>in vitro</em> experiments and various transgenic mice models that have been generated to unravel the role of VDR signaling in different bone cell types such as chondrocytes, (pre)osteoblasts, osteocytes, and (pre)osteoclasts.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106732"},"PeriodicalIF":2.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694475","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":"Benzophenone UV-filters: Inhibition on human and rat 17β-hydroxysteroid dehydrogenase 1 - insights from 3D-QSAR and docking studies","authors":"Zhuoqi Chen ,&nbsp;Chaochao Gong ,&nbsp;Shaowei Wang ,&nbsp;Han Lu ,&nbsp;Yang Zhu ,&nbsp;Ren-shan Ge ,&nbsp;Yunbing Tang ,&nbsp;Yingfen Ying","doi":"10.1016/j.jsbmb.2025.106739","DOIUrl":"10.1016/j.jsbmb.2025.106739","url":null,"abstract":"<div><div>Benzophenone (BP) UV-filters have been extensively used for the prevention of UV-induced adverse effects in personal care products. Their potential to interfere with steroidogenesis in the female reproductive system remains uncertain. 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) facilitates the conversion of estrone to estradiol, playing a key role in estrogen activation. This study delves into the effects of eleven BPs on human and rat 17β-HSD1, while also analysing the 3D-quntitative structure-activity relationship (3D-QSAR) and the underlying mechanisms. The inhibitory potency of inhibiting human placental 17β-HSD1 was found to be in the order of BP-2 (IC₅₀, 11.42 μM) &gt; BP-1 (14.17 μM) &gt; BP-4 (49.05 μM) &gt; BP-6 (63.49 μM) = BP-8 (63.46 μM) &gt; others. BP-1 and BP-2 markedly inhibited estradiol secretion by human placental BeWo cells at ≥ 1 μM. In contrast, the inhibitory strength of suppressing rat ovarian 17β-HSD1 activity was found to be in the order of BP-2 (IC₅₀, 13.33 μM) &gt; BP-1 (15.09 μM) &gt; BP-4 (22.68 μM) &gt; BP-12 (31.12 μM) &gt; BP-3 (97.11 μM) &gt; BP (119.99 μM) &gt; others. Mode action analysis revealed that these BP compounds acted as mixed inhibitors of both human and rat 17β-HSD1. The introduction of a 4-hydroxyl substitution in the benzene ring was found to markedly increase the inhibitory potency against human and rat 17β-HSD1. BP-1 and BP-2 demonstrated the ability to penetrate human BeWo cells and inhibit estradiol secretion at ≥ 1 μM. Docking analysis revealed that the 2-hydroxyl group of BP-1 and BP-2 forms a hydrogen bond with catalytic residue Ser142 of human 17β-HSD1. 3D-QSAR pharmacophore analysis showed that there are hydrophobic regions and hydrogen bond donor can interact with BPs. In conclusion, this study establishes that BP-2 is the most potent inhibitors of human 17β-HSD1 among the BPs under investigation, highlighting a significant difference in the structure-activity relationship.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106739"},"PeriodicalIF":2.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687968","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":"Prevalence and determinants of profound vitamin D deficiency (25-hydroxyvitamin D <10 nmol/L) in the UK Biobank and potential implications for disease association studies","authors":"Rasha Shraim ,&nbsp;Margaret M. Brennan ,&nbsp;Jos van Geffen ,&nbsp;Lina Zgaga","doi":"10.1016/j.jsbmb.2025.106737","DOIUrl":"10.1016/j.jsbmb.2025.106737","url":null,"abstract":"<div><h3>Background</h3><div>25-hydroxyvitamin D (25OHD) is the principal biomarker of vitamin D status. Values below the assay detection limit (&lt;10 nmol/L) are often reported as missing. Thus the most severely deficient participants are excluded from research which can lead to inaccurate findings such as underestimated prevalence of deficiency, overlooked risk factors, and biased evaluation of disease associations.</div></div><div><h3>Methods</h3><div>In total 369,626 individuals from the UK Biobank cohort were included in this study. Data on 25OHD concentration and relevant demographic and lifestyle factors such as age, supplement intake, diet, and time spent outdoors were used in the analyses. Ambient UVB radiation was approximated for each participant. 25OHD was evaluated as a categorical outcome and we reintroduced participants with 25OHD values &lt; 10 nmol/L (conventionally reported as missing values) back to the dataset. Adjusted regression models were used to investigate the determinants of profound (25OHD &lt;10 nmol/L) and severe (10–25 nmol/L) vitamin D deficiency and to assess disease associations (with 25–50 nmol/L as the reference category).</div></div><div><h3>Results</h3><div>1,784 (0.48 %) individuals were profoundly deficient and a further 47,226 (12.78 %) individuals were severely vitamin D deficient. The proportions of profoundly and severely deficient were highest among Asians, 9 % and 47 %, respectively. Ambient UVB radiation was the second strongest predictor: comparing the lowest vs. highest quartile, the risk of profound deficiency was 17-fold increased and that of severe deficiency 7.5-fold increased. Use of vitamin D supplements substantially reduced risk of profound (4.4-fold) and severe (2.5-fold) deficiency, as did fish intake (5- and 1.9-fold, respectively). Profound deficiency was more strongly associated with chronic illness, diabetes, and emphysema compared to severe deficiency.</div></div><div><h3>Conclusion</h3><div>The prevalence of profound and severe vitamin D deficiency among Asian and Black ethnicities in the UK is high and requires targeted action. Solar radiation is potent in protecting against profound and severe vitamin D deficiency. Studies evaluating the relationship between vitamin D status and other health outcomes may be biased if profoundly deficient participants are excluded.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106737"},"PeriodicalIF":2.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modifying-antibiotic action of Hecogenin Acetate as an alternative to combat bacterial infections","authors":"Nara Juliana Santos Araújo ,&nbsp;Maria Do Socorro Costa ,&nbsp;Ana Raquel Pereira Da Silva ,&nbsp;Cícera Laura Roque Paulo ,&nbsp;Camila Aparecida Pereira Silva ,&nbsp;Franceildo Jorge Felix ,&nbsp;José Maria Barbosa Filho ,&nbsp;Henrique Douglas Melo Coutinho ,&nbsp;Jacqueline Cosmo Andrade-Pinheiro","doi":"10.1016/j.jsbmb.2025.106721","DOIUrl":"10.1016/j.jsbmb.2025.106721","url":null,"abstract":"<div><div>Bacterial infections are pathologies with specific morbidity and mortality that disrupt a high level of care in health systems. These diseases are treated using antibacterial drugs. Antibiotics are drugs that act by inhibiting bacterial growth or promoting the death of microorganisms. Their indiscriminate use is considered one of the main factors in the emergence of bacterial resistance, which is currently a major public health problem. Among the alternatives for controlling resistance is the search for new drugs, which are mainly based on the use of natural products with known bioactivity. These include Hecogenin Acetate, a sapogenin with significant anti-inflammatory, antifungal and antimicrobial activity. In order to evaluate HA's ability to modulate the antimicrobial activity of commonly used antibiotics, tests were carried out using the microdilution technique with bacterial strains of clinical interest. Hecogenin Acetate was found to be predominantly potentiating the antibiotic action, demonstrating that the association of Hecogenin Acetate with antibiotics presents a potential for innovative treatment, requiring further evaluation for the probable development of new antibacterial drugs. This action could classify the natural product as an important alternative for the pharmaceutical industry in the treatment of bacterial infections, reducing bacterial resistance and increasing the range of therapeutic possibilities, indirectly contributing to improvements in the public health scenario.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106721"},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665365","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":"Continuous flow-through steady state system for in vitro characterization of CYP11B2 inhibitors–Impact on enzyme kinetics of steroidogenesis","authors":"Dennis Fröbel ,&nbsp;Stefanie Hahner ,&nbsp;Britta Heinze ,&nbsp;Peter Dieterich ,&nbsp;Georgiana Constantinescu ,&nbsp;Sanas Mir-Bashiri ,&nbsp;Tracy Ann Williams ,&nbsp;Mirko Peitzsch ,&nbsp;Graeme Eisenhofer ,&nbsp;Andreas Schirbel ,&nbsp;Nicole Bechmann","doi":"10.1016/j.jsbmb.2025.106736","DOIUrl":"10.1016/j.jsbmb.2025.106736","url":null,"abstract":"<div><h3>Background</h3><div>The homology of aldosterone- and cortisol-producing enzymes, aldosterone synthase (CYP11B2) and 11β-hydroxylase, complicates identification of selective CYP11B2 inhibitors required for antihypertensive treatment or for imaging approaches in patients with primary aldosteronism. To improve preclinical evaluation of novel CYP11B2-targeting compounds, we developed a flow-through cell culture system that provides insights into kinetics of steroidogenesis and inhibitory responses at CYP11B2 active sites.</div></div><div><h3>Methods</h3><div>NCI-H295RA and HAC-15 cells were cultured in ibidi flow chambers under constant culture medium flow. Supernatants were collected hourly before and after treatment with (<em>R</em>)-1-[1-(4-iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinylamide (IMAZA), a non-selective CYP11B1/B2 inhibitor, or the potential CYP11B2 inhibitors ID-69 and ID-191. Steroid profiles were analyzed by liquid chromatography-tandem mass spectrometry. Steady state approximation in steroidogenesis allowed mathematical modeling-based calculation of metabolic fluxes and relative rate constants of biocatalytic steps.</div></div><div><h3>Results</h3><div>An optimized flow-through system is now available to characterize inhibitory responses at the three catalytic sites of CYP11B2 in two steroid-producing cell lines. IMAZA non-selectively inhibited CYP11B 11β-hydroxylase function, while ID-69 and ID-191 affected the CYP11B2-specific 18-hydroxylase active site with minor effects on catalytic activity of 11β-hydroxylase. ID-191 simultaneously impaired catalytic activity of cortisol production, whereas ID-69 was highly selective for CYP11B2 inhibition.</div></div><div><h3>Conclusion</h3><div>Our flow-through system provides insights into inhibitor-induced alterations of metabolic fluxes and enzymatic rate constants, and thus represents an improved preclinical model sytem for complex characterization of CYP11B2 inhibitors.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106736"},"PeriodicalIF":2.7,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical trials of vitamin D supplementation and cardiovascular disease: A synthesis of the evidence","authors":"Robert Scragg","doi":"10.1016/j.jsbmb.2025.106733","DOIUrl":"10.1016/j.jsbmb.2025.106733","url":null,"abstract":"<div><div>The evidence linking vitamin D deficiency with increased risk of cardiovascular disease (CVD) extends back to 1970s when case control studies showed lower circulating concentrations of 25-hydroxyvitamin D [25(OH)D] in myocardial infarction cases compared with controls, which was strengthened by the identification of a vitamin D receptor in cardiac muscle in 1980s. Cohort studies published in the 2000s provided stronger evidence (by measuring 25(OH)D concentrations before the onset of CVD) and confirmed the inverse association between circulating 25(OH)D concentrations and CVD risk. However, concerns remained about possible residual confounding as the reason for the inverse association. This stimulated the initiation of several large scale randomized controlled trials (RCTs) of vitamin D supplementation with CVD as a pre-specified outcome. Results from these studies have been combined with findings from earlier RCTs in a recent meta-analysis undertaken on behalf of the US Endocrine Society. In 14 RCTs with 80,547 participants aged 50–74 years, vitamin D supplementation did not protect against CVD when compared to placebo: risk ratio 1.00 (95 % confidence interval 0.93–1.08). This result did not vary by study quality (risk of bias), gender, calcium co-administration, vitamin D dose or trial setting (community or residential care). This finding is consistent with recent mendelian randomization studies which have not detected a beneficial effect associated with genetically predicted 25(OH)D in people with vitamin D deficiency. Overall, the current evidence indicates that vitamin D does not prevent CVD.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106733"},"PeriodicalIF":2.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}