Journal of Steroid Biochemistry and Molecular Biology最新文献_第3页

Exploring the feature prioritization and data sampling of PCOS diagnosis via densely connected attention based squeeze deep learning detection model 基于密集连接注意的挤压深度学习检测模型在PCOS诊断中的特征优先化和数据采样研究。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-12-31 DOI: 10.1016/j.jsbmb.2025.106933

Siji Jose Pulluparambil , Subrahmanya Bhat

Accurate and timely diagnosis remains a challenge due to the complexity of Polycystic Ovary Syndrome (PCOS) symptoms and data imbalance issues in the existing datasets. This research aims to develop a robust PCOS detection model that addresses these challenges by introducing a novel hybrid methodology with effective feature prioritization while handling data balancing issues. The research involves three major phases: pre-processing, feature selection, and PCOS detection. In the pre-processing stage, dataset balancing is emphasized by the combination of Synthetic Minority Oversampling Techniques (SMOTE) and Edited Nearest Neighbor (ENN). Under this stage, replacing null values, balancing the dataset, and dropping unnecessary columns are accomplished to increase PCOS detection accuracy. The second stage is feature selection, where a distinct hybrid bionic strategy named the Gorilla Salp Swarm Troop Model (GS2TM) is proposed to pick the optimal set of dominant features. The GS2TM algorithm reduces the feature set by 51.1 %, retaining only 23 features while achieving a state-of-the-art accuracy of 98.7 %. In addition, the Densely Connected Attention-Based Squeeze Convolutional Detection Model (DASCD) is proposed for the prediction of PCOS, in which multiple layers are adjusted in a feed-forward manner. The novelty of this work lies in the unified pipeline that simultaneously addresses three major challenges in PCOS detection, such as dataset imbalance (SMOTE-ENN), feature redundancy (GS2TM), and overfitting (DASCD with attention), providing both high accuracy and enhanced interpretability. As a result, the proposed detection model greatly improves accuracy compared to other existing ML-based strategies. Specifically, by utilizing 23 characteristics with GS2TM, the proposed model outperforms with an accuracy of 98.7 % in categorizing PCOS and non-PCOS.

由于多囊卵巢综合征（PCOS）症状的复杂性和现有数据集的数据不平衡问题，准确和及时的诊断仍然是一个挑战。本研究旨在开发一个强大的PCOS检测模型，通过在处理数据平衡问题时引入一种具有有效特征优先级的新型混合方法来解决这些挑战。研究包括预处理、特征选择和PCOS检测三个主要阶段。在预处理阶段，通过结合合成少数派过采样技术（SMOTE）和编辑近邻（ENN）来强调数据集平衡。在此阶段，通过替换空值、平衡数据集和删除不必要的列来提高PCOS检测精度。第二阶段是特征选择，提出了一种独特的混合仿生策略，即大猩猩Salp蜂群模型（GS2TM），以选择最优的优势特征集。GS2TM算法将特征集减少了51.1%，仅保留了23个特征，同时达到了98.7%的最先进精度。此外，针对PCOS的预测，提出了一种多层前馈调整的基于密集连接注意力的挤压卷积检测模型（DASCD）。这项工作的新颖之处在于，统一的管道同时解决了PCOS检测中的三大挑战，即数据集不平衡（SMOTE-ENN）、特征冗余（GS2TM）和过拟合（DASCD with attention），提供了高精度和增强的可解释性。因此，与其他现有的基于ml的检测策略相比，所提出的检测模型大大提高了准确性。具体而言，通过利用GS2TM的23个特征，该模型在PCOS和非PCOS分类方面的准确率达到98.7%。

{"title":"Exploring the feature prioritization and data sampling of PCOS diagnosis via densely connected attention based squeeze deep learning detection model","authors":"Siji Jose Pulluparambil , Subrahmanya Bhat","doi":"10.1016/j.jsbmb.2025.106933","DOIUrl":"10.1016/j.jsbmb.2025.106933","url":null,"abstract":"<div><div>Accurate and timely diagnosis remains a challenge due to the complexity of Polycystic Ovary Syndrome (PCOS) symptoms and data imbalance issues in the existing datasets. This research aims to develop a robust PCOS detection model that addresses these challenges by introducing a novel hybrid methodology with effective feature prioritization while handling data balancing issues. The research involves three major phases: pre-processing, feature selection, and PCOS detection. In the pre-processing stage, dataset balancing is emphasized by the combination of Synthetic Minority Oversampling Techniques (SMOTE) and Edited Nearest Neighbor (ENN). Under this stage, replacing null values, balancing the dataset, and dropping unnecessary columns are accomplished to increase PCOS detection accuracy. The second stage is feature selection, where a distinct hybrid bionic strategy named the Gorilla Salp Swarm Troop Model (GS2TM) is proposed to pick the optimal set of dominant features. The GS2TM algorithm reduces the feature set by 51.1 %, retaining only 23 features while achieving a state-of-the-art accuracy of 98.7 %. In addition, the Densely Connected Attention-Based Squeeze Convolutional Detection Model (DASCD) is proposed for the prediction of PCOS, in which multiple layers are adjusted in a feed-forward manner. The novelty of this work lies in the unified pipeline that simultaneously addresses three major challenges in PCOS detection, such as dataset imbalance (SMOTE-ENN), feature redundancy (GS2TM), and overfitting (DASCD with attention), providing both high accuracy and enhanced interpretability. As a result, the proposed detection model greatly improves accuracy compared to other existing ML-based strategies. Specifically, by utilizing 23 characteristics with GS2TM, the proposed model outperforms with an accuracy of 98.7 % in categorizing PCOS and non-PCOS.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"258 ","pages":"Article 106933"},"PeriodicalIF":2.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893463","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

Molecular targets of ergosterol and its derivatives in cancer therapy: Recent trends and strategies to improve its bioavailability 麦角甾醇及其衍生物在癌症治疗中的分子靶点：最近的趋势和提高其生物利用度的策略

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-12-31 DOI: 10.1016/j.jsbmb.2025.106928

Shivali, Hitesh Kumar, Navneet Agnihotri

Cancer poses a major global health concern, with an alarming increase in incidence and associated mortality. Surgical resection of tumor, radiotherapy and chemotherapy remains the mainstay of therapeutic options available. Though these treatments do increase the life span of the patients but severely impact their quality of life due to their short term or long term adverse effects. The current research is therefore focused on exploring the natural compounds as an alternative and indeed many do exhibit anticancer activity. Complex metabolic reprogramming in cancer prompts the need for researchers to explore novel and innovative strategies to target such aberrant pathways by using safer and effective natural products. The present review focusses on Ergosterol, a mycosterol present in mushrooms which not only modulates the aberrant cholesterol homeostasis but also show independent anticancer activity due to its antioxidant, anti-inflammatory and lipid lowering properties. In addition, the challenges and limitations related to its utility as a drug molecule and advancements in improving its pharmacological properties using chemical and physical modifications has also been addressed.

癌症是一个重大的全球健康问题，发病率和相关死亡率以惊人的速度增加。手术切除肿瘤，放疗和化疗仍然是主要的治疗选择。虽然这些治疗确实延长了患者的寿命，但由于其短期或长期的不良反应，严重影响了患者的生活质量。因此，目前的研究重点是探索天然化合物作为一种替代品，事实上，许多天然化合物确实表现出抗癌活性。癌症中复杂的代谢重编程促使研究人员需要探索新的和创新的策略，通过使用更安全有效的天然产物来靶向这种异常途径。麦角甾醇是一种存在于蘑菇中的真菌甾醇，它不仅调节异常的胆固醇稳态，而且由于其抗氧化、抗炎和降脂的特性而显示出独立的抗癌活性。此外，还讨论了与其作为药物分子的效用有关的挑战和限制，以及利用化学和物理修饰改善其药理学特性的进展。

{"title":"Molecular targets of ergosterol and its derivatives in cancer therapy: Recent trends and strategies to improve its bioavailability","authors":"Shivali, Hitesh Kumar, Navneet Agnihotri","doi":"10.1016/j.jsbmb.2025.106928","DOIUrl":"10.1016/j.jsbmb.2025.106928","url":null,"abstract":"<div><div>Cancer poses a major global health concern, with an alarming increase in incidence and associated mortality. Surgical resection of tumor, radiotherapy and chemotherapy remains the mainstay of therapeutic options available. Though these treatments do increase the life span of the patients but severely impact their quality of life due to their short term or long term adverse effects. The current research is therefore focused on exploring the natural compounds as an alternative and indeed many do exhibit anticancer activity. Complex metabolic reprogramming in cancer prompts the need for researchers to explore novel and innovative strategies to target such aberrant pathways by using safer and effective natural products. The present review focusses on Ergosterol, a mycosterol present in mushrooms which not only modulates the aberrant cholesterol homeostasis but also show independent anticancer activity due to its antioxidant, anti-inflammatory and lipid lowering properties. In addition, the challenges and limitations related to its utility as a drug molecule and advancements in improving its pharmacological properties using chemical and physical modifications has also been addressed.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"257 ","pages":"Article 106928"},"PeriodicalIF":2.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884497","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

Vitexin reduced the dihydrotestosterone (DHT)-induced fibrosis in KGN cells by regulating the NR4A1/NLRP3 pathway 牡荆素通过调节NR4A1/NLRP3通路减少双氢睾酮（DHT）诱导的KGN细胞纤维化。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-12-31 DOI: 10.1016/j.jsbmb.2025.106927

Jie-Jing Xu , Chuan-Zhi Yan , Zhi-Qiang Liu , Hao-Ran Sun , Ming-Yu Zhang , Qiu-Ping Huang , Chen-Xi Tong , Cheng-Xue Pan , Jia-Le Song , Yan-Yuan Zhou

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder in women of reproductive age, markedly impairing their health and reducing overall quality of life. Vitexin is a natural flavonoid compound that has demonstrated diverse pharmacological properties, including anti-inflammatory and antioxidant effects. The aim of this study was to investigate the effects of vitexin on dihydrotestosterone (DHT)-induced fibrosis in KGN cells, as well as its regulatory role in the NR4A1/NLRP3 signaling pathway. Experimental findings suggested that DHT treatment resulted in decreased cell viability, disrupted sex hormone balance, increased oxidative stress, and elevated levels of inflammation and fibrosis in KGN cells. However, vitexin intervention significantly reversed these pathological changes. Transcriptomics sequencing analysis and molecular docking further indicated that NR4A1 is a pivotal target of vitexin in modulating the inflammatory response. Vitexin significantly inhibited NLRP3 inflammasome-mediated inflammation by activating NR4A1, conversely NR4A1 knockdown partially attenuated the protective effects of vitexin (P < 0.01). Therefore, vitexin was found to effectively ameliorate DHT-induced alterations in cell viability, sex hormone levels, oxidative stress, inflammation and fibrosis in KGN cells. These protective effects appear to be closely related to the regulation of the NR4A1/NLRP3 signaling pathway.

多囊卵巢综合征（PCOS）是育龄妇女普遍存在的内分泌和代谢紊乱，显著损害她们的健康并降低整体生活质量。牡荆素是一种天然的类黄酮化合物，具有多种药理特性，包括抗炎和抗氧化作用。本研究旨在探讨牡荆素对双氢睾酮（DHT）诱导的KGN细胞纤维化的影响及其在NR4A1/NLRP3信号通路中的调节作用。实验结果表明，DHT治疗导致KGN细胞活力下降，性激素平衡被破坏，氧化应激增加，炎症和纤维化水平升高。然而，牡荆素干预显著逆转了这些病理变化。转录组学测序分析和分子对接进一步表明NR4A1是牡荆素调节炎症反应的关键靶点。牡荆素通过激活NR4A1显著抑制NLRP3炎症小体介导的炎症，反之，NR4A1敲低部分减弱牡荆素的保护作用（P < 0.01）。因此，牡荆素被发现能有效改善dht诱导的KGN细胞活力、性激素水平、氧化应激、炎症和纤维化的改变。这些保护作用似乎与NR4A1/NLRP3信号通路的调控密切相关。

{"title":"Vitexin reduced the dihydrotestosterone (DHT)-induced fibrosis in KGN cells by regulating the NR4A1/NLRP3 pathway","authors":"Jie-Jing Xu , Chuan-Zhi Yan , Zhi-Qiang Liu , Hao-Ran Sun , Ming-Yu Zhang , Qiu-Ping Huang , Chen-Xi Tong , Cheng-Xue Pan , Jia-Le Song , Yan-Yuan Zhou","doi":"10.1016/j.jsbmb.2025.106927","DOIUrl":"10.1016/j.jsbmb.2025.106927","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder in women of reproductive age, markedly impairing their health and reducing overall quality of life. Vitexin is a natural flavonoid compound that has demonstrated diverse pharmacological properties, including anti-inflammatory and antioxidant effects. The aim of this study was to investigate the effects of vitexin on dihydrotestosterone (DHT)-induced fibrosis in KGN cells, as well as its regulatory role in the NR4A1/NLRP3 signaling pathway. Experimental findings suggested that DHT treatment resulted in decreased cell viability, disrupted sex hormone balance, increased oxidative stress, and elevated levels of inflammation and fibrosis in KGN cells. However, vitexin intervention significantly reversed these pathological changes. Transcriptomics sequencing analysis and molecular docking further indicated that NR4A1 is a pivotal target of vitexin in modulating the inflammatory response. Vitexin significantly inhibited NLRP3 inflammasome-mediated inflammation by activating NR4A1, conversely NR4A1 knockdown partially attenuated the protective effects of vitexin (<em>P</em> < 0.01). Therefore, vitexin was found to effectively ameliorate DHT-induced alterations in cell viability, sex hormone levels, oxidative stress, inflammation and fibrosis in KGN cells. These protective effects appear to be closely related to the regulation of the NR4A1/NLRP3 signaling pathway.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"257 ","pages":"Article 106927"},"PeriodicalIF":2.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893515","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

Design, synthesis, and biological evaluation of novel steroidal selenosemicarbazone derivatives as potent antitumor agents 新型甾体硒代氨基脲衍生物的设计、合成和生物学评价。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-12-31 DOI: 10.1016/j.jsbmb.2025.106931

Chunfang Gan , Beijun Gan , Ying Li , Yanmin Huang , Zhiping Liu , Yunqiong Gu , Haifeng Chen , Qifu Lin

The development of novel chemotherapeutic agents with high efficacy and low toxicity remains a critical challenge in oncology. In this study, a novel series of steroidal selenosemicarbazone derivatives were designed and synthesized through the selenium functionalization of diverse steroid scaffolds. Key ketone intermediates derived from cholesterol, dehydroepiandrosterone (DHEA), estrone, and pregnenolone were condensed with various selenosemicarbazides to achieve structural diversification across the steroid nucleus. The antiproliferative activities of the synthesized compounds were evaluated against a panel of human cancer cell lines. Most compounds exhibited broad-spectrum cytotoxicity, among which compound 17c, based on the DHEA scaffold, showed superior potency against MCF-7 breast cancer cells(IC₅₀ = 4.80 ± 0.43 μM)and high selectivity over normal cells. Mechanism-of-action studies revealed that 17c induces mitochondrial-mediated apoptosis, characterized by the loss of mitochondrial membrane potential, activation of caspase-9, and G2/M phase cell cycle arrest. Molecular docking simulations implicated glutathione reductase (GR) as a potential molecular target, suggesting that the binding of 17c to GR may initiate the observed mitochondrial dysfunction. Furthermore, the concentration-dependent suppression of cell proliferation, migration, and clonogenic survival by 17c was confirmed through a suite of functional assays. Collectively, this work identifies 17c as a promising lead compound with a clarified mechanistic profile for the development of efficient and low-toxicity anticancer agents.

开发高效低毒的新型化疗药物仍然是肿瘤学领域面临的重大挑战。在本研究中，通过多种类固醇支架的硒功能化，设计并合成了一系列新的甾体硒糖氨基脲衍生物。源自胆固醇、脱氢表雄酮（DHEA）、雌酮和孕烯醇酮的关键酮中间体与各种硒半氨基脲缩合，以实现类固醇核的结构多样化。合成的化合物对一组人类癌细胞系的抗增殖活性进行了评估。大多数化合物具有广谱细胞毒性，其中基于DHEA支架的化合物17c对MCF-7乳腺癌细胞具有较强的抑制作用（IC50 = 4.80±0.43μM），对正常细胞具有较高的选择性。作用机制研究表明，17c诱导线粒体介导的细胞凋亡，其特征是线粒体膜电位丧失，caspase-9激活，G2/M期细胞周期阻滞。分子对接模拟表明谷胱甘肽还原酶（GR）是一个潜在的分子靶点，这表明17c与GR结合可能引发观察到的线粒体功能障碍。此外，通过一系列功能试验证实了17c对细胞增殖、迁移和克隆存活的浓度依赖性抑制。总的来说，这项工作确定了17c作为一种有前途的先导化合物，具有明确的开发高效低毒抗癌药物的机制。

{"title":"Design, synthesis, and biological evaluation of novel steroidal selenosemicarbazone derivatives as potent antitumor agents","authors":"Chunfang Gan , Beijun Gan , Ying Li , Yanmin Huang , Zhiping Liu , Yunqiong Gu , Haifeng Chen , Qifu Lin","doi":"10.1016/j.jsbmb.2025.106931","DOIUrl":"10.1016/j.jsbmb.2025.106931","url":null,"abstract":"<div><div>The development of novel chemotherapeutic agents with high efficacy and low toxicity remains a critical challenge in oncology. In this study, a novel series of steroidal selenosemicarbazone derivatives were designed and synthesized through the selenium functionalization of diverse steroid scaffolds. Key ketone intermediates derived from cholesterol, dehydroepiandrosterone (DHEA), estrone, and pregnenolone were condensed with various selenosemicarbazides to achieve structural diversification across the steroid nucleus. The antiproliferative activities of the synthesized compounds were evaluated against a panel of human cancer cell lines. Most compounds exhibited broad-spectrum cytotoxicity, among which compound <strong>17c</strong>, based on the DHEA scaffold, showed superior potency against MCF-7 breast cancer cells(IC<sub>50</sub> = 4.80 ± 0.43 μM)and high selectivity over normal cells. Mechanism-of-action studies revealed that <strong>17c</strong> induces mitochondrial-mediated apoptosis, characterized by the loss of mitochondrial membrane potential, activation of caspase-9, and G2/M phase cell cycle arrest. Molecular docking simulations implicated glutathione reductase (GR) as a potential molecular target, suggesting that the binding of <strong>17c</strong> to GR may initiate the observed mitochondrial dysfunction. Furthermore, the concentration-dependent suppression of cell proliferation, migration, and clonogenic survival by <strong>17c</strong> was confirmed through a suite of functional assays. Collectively, this work identifies <strong>17c</strong> as a promising lead compound with a clarified mechanistic profile for the development of efficient and low-toxicity anticancer agents.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"257 ","pages":"Article 106931"},"PeriodicalIF":2.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893523","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

Seasonal variation of prostatic steroid hormone synthesis capacity in wild ground squirrels (Spermophilus dauricus) 野生地松鼠前列腺甾体激素合成能力的季节变化

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-12-31 DOI: 10.1016/j.jsbmb.2025.106930

Pengyu Chen , Qingjing Gao , Wenqian Xie , Huan Yu , Yuning Liu , Haolin Zhang , Qiang Weng

Our previous studies showed that the prostates of the wild ground squirrels were capable of locally synthesizing testosterone (T), dihydrotestosterone (DHT) and estrogen. In this study, we investigated expression levels of luteinizing hormone receptor (LHR), steroidogenic factor 1 (SF-1), steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase (3βHSD) and 17α-hydroxylase cytochrome P450 (P450c17) in the prostates of the wild ground squirrels during the breeding and non-breeding seasons. LHR, SF-1, StAR, P450scc, 3βHSD and P450c17 were identified in the stromal cells or epithelial cells. The mRNA expression levels of LHR, SF-1, StAR, P450scc, P450c17, 3βHSD and Sterol Regulatory Element-Binding Protein 2 (Srebp2) in the prostate were remarkedly higher during the breeding period than those in the non-breeding period. In contrast, the mRNA expression levels of Melatonin Receptor 1a (Mtnr1a) and Melatonin Receptor 1b (Mtnr1b) were elevated during the non-breeding period. Consistently, the circulating LH and T as well as the prostatic T and DHT concentrations were remarkably higher in the breeding season than those of the non-breeding season, which were positively correlated with the seasonal changes of prostatic weight. Additionally, the transcriptomic study in the prostates identified that differentially expressed genes might be related to signal transduction and signaling receptor activity using GO analysis. The KEGG pathway enriched by differentially expressed genes detected to be involved in steroid biosynthesis, estrogen signaling pathway or steroidogenesis. Taken together, these findings suggested that the prostates of the wild ground squirrels potentially owned ability to synthesize steroid hormones de novo, and the steroid hormones might affect the prostatic functions of the wild ground squirrels via an autocrine or paracrine manner.

我们之前的研究表明，野生地松鼠的前列腺能够局部合成睾酮(T)、二氢睾酮（DHT）和雌激素。本研究研究了黄体生成素受体（LHR）、甾体生成因子1 （SF-1）、甾体生成急性调节蛋白（StAR）、细胞色素P450胆固醇侧链切割酶（P450scc）、3β-羟基类固醇脱氢酶（3βHSD）和17α-羟化酶细胞色素P450 （P450c17）在野生地松鼠繁殖期和非繁殖期前列腺中的表达水平。间质细胞和上皮细胞中分别检测到LHR、SF-1、StAR、P450scc、3βHSD和P450c17。繁殖期前列腺组织中LHR、SF-1、StAR、P450scc、P450c17、3βHSD和固醇调节元件结合蛋白2 (Srebp2) mRNA表达水平显著高于非繁殖期。相反，在非繁殖期，褪黑激素受体1a （Mtnr1a）和褪黑激素受体1b （Mtnr1b）的mRNA表达水平升高。繁殖季节循环LH和T以及前列腺T和DHT浓度均显著高于非繁殖季节，且与前列腺体重的季节变化呈正相关。此外，通过氧化石墨烯分析，前列腺的转录组学研究发现，差异表达的基因可能与信号转导和信号受体活性有关。由差异表达基因富集的KEGG通路被检测到参与类固醇生物合成、雌激素信号通路或类固醇发生。综上所述，这些发现表明野生地松鼠的前列腺可能具有重新合成类固醇激素的能力，类固醇激素可能通过自分泌或旁分泌的方式影响野生地松鼠的前列腺功能。

{"title":"Seasonal variation of prostatic steroid hormone synthesis capacity in wild ground squirrels (Spermophilus dauricus)","authors":"Pengyu Chen , Qingjing Gao , Wenqian Xie , Huan Yu , Yuning Liu , Haolin Zhang , Qiang Weng","doi":"10.1016/j.jsbmb.2025.106930","DOIUrl":"10.1016/j.jsbmb.2025.106930","url":null,"abstract":"<div><div>Our previous studies showed that the prostates of the wild ground squirrels were capable of locally synthesizing testosterone (T), dihydrotestosterone (DHT) and estrogen. In this study, we investigated expression levels of luteinizing hormone receptor (LHR), steroidogenic factor 1 (SF-1), steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase (3βHSD) and 17α-hydroxylase cytochrome P450 (P450c17) in the prostates of the wild ground squirrels during the breeding and non-breeding seasons. LHR, SF-1, StAR, P450scc, 3βHSD and P450c17 were identified in the stromal cells or epithelial cells. The mRNA expression levels of LHR, SF-1, StAR, P450scc, P450c17, 3βHSD and Sterol Regulatory Element-Binding Protein 2 (Srebp2) in the prostate were remarkedly higher during the breeding period than those in the non-breeding period. In contrast, the mRNA expression levels of Melatonin Receptor 1a (Mtnr1a) and Melatonin Receptor 1b (Mtnr1b) were elevated during the non-breeding period. Consistently, the circulating LH and T as well as the prostatic T and DHT concentrations were remarkably higher in the breeding season than those of the non-breeding season, which were positively correlated with the seasonal changes of prostatic weight. Additionally, the transcriptomic study in the prostates identified that differentially expressed genes might be related to signal transduction and signaling receptor activity using GO analysis. The KEGG pathway enriched by differentially expressed genes detected to be involved in steroid biosynthesis, estrogen signaling pathway or steroidogenesis. Taken together, these findings suggested that the prostates of the wild ground squirrels potentially owned ability to synthesize steroid hormones <em>de novo</em>, and the steroid hormones might affect the prostatic functions of the wild ground squirrels via an autocrine or paracrine manner.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"257 ","pages":"Article 106930"},"PeriodicalIF":2.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884498","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

The dual carbonyl reductase activities of 17β-HSD12a during ovarian development in Japanese eel (Anguilla japonica) 17β-HSD12a双羰基还原酶在日本鳗鲡卵巢发育过程中的活性。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-12-30 DOI: 10.1016/j.jsbmb.2025.106929

Penghui Huo , Shixi Chen , Jing Huang , Ying Yang , Zhaoren Bai , Yangjie Xie , Xiaojian Lai

17β-hydroxysteroid dehydrogenase subtype 12 (17β-HSD12) is responsible for the reactions between carbonyl and hydroxyl groups at the C17 position of sex steroids. Our previous research revealed that hsd17b12a was expressed at a high level during follicular maturation in Anguilla japonica, peaking at the migrating nucleus stage. This indicated the potential of 17β-HSD12 may convert 17α-hydroxyprogesterone (17OHP) into 17α,20β-dihydroxy-4-pregnen-3-one (DHP), a maturation-inducing steroid. To elucidate the functions of hsd17b12a in A. japonica, the spatiotemporal expression patterns of hsd17b12a were investigated, as well as its role in sex steroid hormone synthesis, and its regulation by upstream gonadotropins. The results showed that hsd17b12a expression was the highest in the ovaries compared to other tissues. Within the ovary, hsd17b12a expression peaked at the migrating nucleus stage, followed by the mid-vitellogenic stage, both significantly higher than other stages. HEK293T cells transfected with a plasmid expressing A. japonica hsd17b12a converted estrone, androstenedione, and 17OHP into 17β-estradiol, testosterone, and DHP, with the conversion rates of 23.70 ± 10.65, 14.95 ± 4.42, and 22.35 ± 0.53 %, respectively. In vitro experiment showed that stimulation with 10 ng/mL 17OHP and 100 µg/mL carp pituitary extract greatly significantly increased hsd17b12a expression of follicles with migrating nucleus stage, although DHP synthesis did not change significantly. The present study demonstrates that the enzyme encoded by eel hsd17b12a possesses both C17 and C20 carbonyl reductase activities. These findings provide new insights into the reproductive endocrine regulatory mechanisms and offer theoretical support for optimizing artificial maturation and spawning in eels.

17β-羟基类固醇脱氢酶亚型12 （17β-HSD12）负责性类固醇C17位羰基和羟基之间的反应。我们之前的研究表明，hsd17b12a在日本鳗鲡卵泡成熟期间高水平表达，在迁移核阶段达到峰值。这表明17β-HSD12可能将17α-羟孕酮（17OHP）转化为17α，20β-二羟基-4-孕酮-3-酮（DHP），这是一种诱导成熟的类固醇。为了阐明hsd17b12a在粳稻中的功能，研究了hsd17b12a在粳稻中的时空表达模式，以及其在性类固醇激素合成中的作用和上游促性腺激素的调控作用。结果显示，卵巢中hsd17b12a的表达量高于其他组织。在卵巢内，hsd17b12a的表达在迁移核期达到高峰，其次是卵黄形成中期，均显著高于其他时期。转染表达粳稻hsd17b12a质粒的HEK293T细胞可将雌二醇、雄烯二酮和17OHP转化为17β-雌二醇、睾酮和DHP，转化率分别为23.70±10.65、14.95±4.42和22.35±0.53%。体外实验表明，10ng/mL 17OHP和100µg/mL鲤鱼垂体提取物刺激可显著提高迁移核期卵泡hsd17b12a表达，但DHP合成无显著变化。本研究表明，鳗hsd17b12a编码的酶具有C17和C20羰基还原酶活性。这些发现为研究鳗鱼生殖内分泌调控机制提供了新的思路，并为优化鳗鱼人工成熟和产卵提供了理论支持。

{"title":"The dual carbonyl reductase activities of 17β-HSD12a during ovarian development in Japanese eel (Anguilla japonica)","authors":"Penghui Huo , Shixi Chen , Jing Huang , Ying Yang , Zhaoren Bai , Yangjie Xie , Xiaojian Lai","doi":"10.1016/j.jsbmb.2025.106929","DOIUrl":"10.1016/j.jsbmb.2025.106929","url":null,"abstract":"<div><div>17β-hydroxysteroid dehydrogenase subtype 12 (17β-HSD12) is responsible for the reactions between carbonyl and hydroxyl groups at the C17 position of sex steroids. Our previous research revealed that <em>hsd17b12a</em> was expressed at a high level during follicular maturation in <em>Anguilla japonica</em>, peaking at the migrating nucleus stage. This indicated the potential of 17β-HSD12 may convert 17α-hydroxyprogesterone (17OHP) into 17α,20β-dihydroxy-4-pregnen-3-one (DHP), a maturation-inducing steroid. To elucidate the functions of <em>hsd17b12a</em> in <em>A. japonica</em>, the spatiotemporal expression patterns of <em>hsd17b12a</em> were investigated, as well as its role in sex steroid hormone synthesis, and its regulation by upstream gonadotropins. The results showed that <em>hsd17b12a</em> expression was the highest in the ovaries compared to other tissues. Within the ovary, <em>hsd17b12a</em> expression peaked at the migrating nucleus stage, followed by the mid-vitellogenic stage, both significantly higher than other stages. HEK293T cells transfected with a plasmid expressing <em>A. japonica hsd17b12a</em> converted estrone, androstenedione, and 17OHP into 17β-estradiol, testosterone, and DHP, with the conversion rates of 23.70 ± 10.65, 14.95 ± 4.42, and 22.35 ± 0.53 %, respectively. <em>In vitro</em> experiment showed that stimulation with 10 ng/mL 17OHP and 100 µg/mL carp pituitary extract greatly significantly increased <em>hsd17b12a</em> expression of follicles with migrating nucleus stage, although DHP synthesis did not change significantly. The present study demonstrates that the enzyme encoded by eel <em>hsd17b12a</em> possesses both C17 and C20 carbonyl reductase activities. These findings provide new insights into the reproductive endocrine regulatory mechanisms and offer theoretical support for optimizing artificial maturation and spawning in eels.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"257 ","pages":"Article 106929"},"PeriodicalIF":2.5,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890606","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

The multi-target mechanisms of β-sitosterol in Alzheimer’s disease: Integrative evidence from network pharmacology, molecular docking, and mendelian randomization β-谷甾醇在阿尔茨海默病中的多靶点机制：来自网络药理学、分子对接和孟德尔随机化的综合证据。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-12-23 DOI: 10.1016/j.jsbmb.2025.106926

Meiling Zhang , Ying Huang , Wenji Du , Ting Lu , Linshuang Ye , Xiao Cheng , Xiang Zeng , Jingbo Sun

β-Sitosterol, a widely distributed phytosterol, has shown therapeutic potential against Alzheimer’s disease (AD); however, its system-level mechanisms remain unclear. This study aimed to generate testable hypotheses regarding β-sitosterol activity in AD using an integrative computational framework. Potential targets were predicted using SwissTargetPrediction and were intersected with AD-related genes. Core targets were identified via protein-protein interaction network analysis, followed by pathway enrichment and validation using Gene Expression Omnibus transcriptomic datasets. Binding interactions were evaluated using molecular docking and 100-ns molecular dynamics (MD) simulations. Mendelian randomization (MR) was used to assess the causal association between circulating estradiol levels (proxy for aromatase activity) and AD risk. Nineteen potential targets were identified, with core genes (e.g., CYP19A1, ESR1, and NR3C1) significantly enriched in steroid hormone biosynthesis pathways. Β-Sitosterol exhibited strong binding affinities to CYP19A1 (−9.7 kcal/mol) and ESR1 (−8.2 kcal/mol), and MD simulations confirmed β-sitosterol–CYP19A1 complex stability. Differential expression analysis validated the dysregulation of key targets in AD. MR analysis further indicated that genetically predicted higher estradiol levels were significantly associated with reduced AD risk (IVW: β = −11.02, SE = 2.77, p = 6.78 × 10⁻⁵). This study provides predictive evidence that β-sitosterol may influence AD pathology by modulating steroidogenic enzymes and hormone signaling. However, as all findings were computationally derived and estradiol serves only as an indirect proxy for aromatase activity, experimental validation is required to confirm these proposed mechanisms. Our results offer a hypothesis-generating framework for further investigation of β-sitosterol as a multitarget candidate for AD.

β-谷甾醇是一种广泛分布的植物甾醇，已显示出治疗阿尔茨海默病（AD）的潜力；然而，其系统级机制尚不清楚。本研究旨在通过综合计算框架生成关于β-谷甾醇在AD中的活性的可测试假设。使用SwissTargetPrediction预测潜在靶标，并与ad相关基因交叉。通过蛋白相互作用网络分析确定核心靶点，然后使用Gene Expression Omnibus转录组数据集进行途径富集和验证。结合相互作用通过分子对接和100-ns分子动力学（MD）模拟进行评估。孟德尔随机化（MR）用于评估循环雌二醇水平（芳香化酶活性的代表）与AD风险之间的因果关系。鉴定出19个潜在靶点，其中核心基因（如CYP19A1、ESR1和NR3C1）在类固醇激素生物合成途径中显著富集。Β-Sitosterol与CYP19A1 （-9.7kcal/mol）和ESR1 （-8.2kcal/mol）具有较强的结合亲和力，MD模拟证实了β-谷甾醇-CYP19A1复合物的稳定性。差异表达分析证实了AD中关键靶点的失调。磁共振分析进一步表明，基因预测的高雌二醇水平与降低AD风险显著相关（IVW: β = -11.02, SE = 2.77, p = 6.78 × 10毒血症）。本研究为β-谷甾醇可能通过调节甾体生成酶和激素信号传导影响AD病理提供了预测性证据。然而，由于所有的研究结果都是通过计算得出的，雌二醇仅作为芳香酶活性的间接代表，因此需要实验验证来证实这些提出的机制。我们的结果为进一步研究β-谷甾醇作为AD的多靶点候选物提供了一个假设生成框架。

{"title":"The multi-target mechanisms of β-sitosterol in Alzheimer’s disease: Integrative evidence from network pharmacology, molecular docking, and mendelian randomization","authors":"Meiling Zhang , Ying Huang , Wenji Du , Ting Lu , Linshuang Ye , Xiao Cheng , Xiang Zeng , Jingbo Sun","doi":"10.1016/j.jsbmb.2025.106926","DOIUrl":"10.1016/j.jsbmb.2025.106926","url":null,"abstract":"<div><div>β-Sitosterol, a widely distributed phytosterol, has shown therapeutic potential against Alzheimer’s disease (AD); however, its system-level mechanisms remain unclear. This study aimed to generate testable hypotheses regarding β-sitosterol activity in AD using an integrative computational framework. Potential targets were predicted using SwissTargetPrediction and were intersected with AD-related genes. Core targets were identified via protein-protein interaction network analysis, followed by pathway enrichment and validation using Gene Expression Omnibus transcriptomic datasets. Binding interactions were evaluated using molecular docking and 100-ns molecular dynamics (MD) simulations. Mendelian randomization (MR) was used to assess the causal association between circulating estradiol levels (proxy for aromatase activity) and AD risk. Nineteen potential targets were identified, with core genes (e.g., CYP19A1, ESR1, and NR3C1) significantly enriched in steroid hormone biosynthesis pathways. Β-Sitosterol exhibited strong binding affinities to CYP19A1 (−9.7 kcal/mol) and ESR1 (−8.2 kcal/mol), and MD simulations confirmed β-sitosterol–CYP19A1 complex stability. Differential expression analysis validated the dysregulation of key targets in AD. MR analysis further indicated that genetically predicted higher estradiol levels were significantly associated with reduced AD risk (IVW: β = −11.02, SE = 2.77, p = 6.78 × 10⁻⁵). This study provides predictive evidence that β-sitosterol may influence AD pathology by modulating steroidogenic enzymes and hormone signaling. However, as all findings were computationally derived and estradiol serves only as an indirect proxy for aromatase activity, experimental validation is required to confirm these proposed mechanisms. Our results offer a hypothesis-generating framework for further investigation of β-sitosterol as a multitarget candidate for AD.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"257 ","pages":"Article 106926"},"PeriodicalIF":2.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835209","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

Cholecystokinin (CCK) mediates CCKBR to regulate androgen secretion via the steroid pathway in Bactrian camel Sertoli cells 胆囊收缩素（CCK）介导CCKBR通过类固醇途径调节双峰驼支持细胞雄激素分泌。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-12-17 DOI: 10.1016/j.jsbmb.2025.106922

Qi Wang, Wenjing Wang, Jinghong Nan, Yong Zhang, Xingxu Zhao

This study aimed to identify differentially expressed genes (DEGs) in the testes of Bactrian camels during estrus and anestrus and investigate the regulatory role of cholecystokinin (CCK) and its receptor (CCKBR) in androgen synthesis. RNA sequencing was performed on six testicular samples (estrus, n = 3; anestrus, n = 3). A total of 291 DEGs were identified, including 27 upregulated and 264 downregulated in estrus. Gene Ontology (GO) enrichment analysis revealed that CCKBR was significantly enriched in reproduction-related pathways, and STRING analysis showed a close association between CCK and CCKBR. Further qRT-PCR, Western blot, and immunofluorescence (IF) analyses demonstrated significantly higher mRNA and protein levels of CCK/CCKBR in estrus testes (P < 0.01), with both localized in Sertoli cells, Leydig cells, primary spermatocytes, and spermatogonia. Primary Sertoli cells, confirmed by WT1 co-localization, were transfected with p-IRES2-EGFP-CCK and siRNA-CCK. Results showed that CCK overexpression significantly reduced testosterone (T) and dihydrotestosterone (DHT) levels (P < 0.05), while upregulating androgen receptor (AR) and key androgen synthesis enzymes (StAR, P450scc, 3β-HSD) (P < 0.05 or P < 0.01). In contrast, siRNA-CCK exerted the opposite effects. In conclusion, our study highlights the CCK/CCKBR axis as a crucial regulator of seasonal testicular function in Bactrian camels, with CCK negatively regulating testicular androgen synthesis by modulating AR and androgen synthesis enzymes. These findings provide valuable insights into the reproductive biology of Bactrian camels and offer a novel pathway for understanding seasonal fertility regulation in male mammals. This has important implications for enhancing camel breeding efficiency and supporting conservation efforts.

本研究旨在鉴定双峰驼发情期和无发情期睾丸中的差异表达基因（DEGs），并探讨胆囊收缩素（CCK）及其受体（CCKBR）在雄激素合成中的调控作用。对6个睾丸样本（发情期，n = 3；不发情期，n = 3）进行RNA测序。共鉴定出291个deg，其中27个在发情期上调，264个在发情期下调。基因本体（Gene Ontology， GO）富集分析显示CCKBR在生殖相关通路中显著富集，STRING分析显示CCK与CCKBR密切相关。进一步的qRT-PCR、Western blot和免疫荧光（IF）分析显示，发情期睾丸中CCK/CCKBR mRNA和蛋白水平显著升高(P

{"title":"Cholecystokinin (CCK) mediates CCKBR to regulate androgen secretion via the steroid pathway in Bactrian camel Sertoli cells","authors":"Qi Wang, Wenjing Wang, Jinghong Nan, Yong Zhang, Xingxu Zhao","doi":"10.1016/j.jsbmb.2025.106922","DOIUrl":"10.1016/j.jsbmb.2025.106922","url":null,"abstract":"<div><div>This study aimed to identify differentially expressed genes (DEGs) in the testes of Bactrian camels during estrus and anestrus and investigate the regulatory role of cholecystokinin (CCK) and its receptor (CCKBR) in androgen synthesis. RNA sequencing was performed on six testicular samples (estrus, n = 3; anestrus, n = 3). A total of 291 DEGs were identified, including 27 upregulated and 264 downregulated in estrus. Gene Ontology (GO) enrichment analysis revealed that CCKBR was significantly enriched in reproduction-related pathways, and STRING analysis showed a close association between CCK and CCKBR. Further qRT-PCR, Western blot, and immunofluorescence (IF) analyses demonstrated significantly higher mRNA and protein levels of CCK/CCKBR in estrus testes (<em>P < 0.01</em>), with both localized in Sertoli cells, Leydig cells, primary spermatocytes, and spermatogonia. Primary Sertoli cells, confirmed by WT1 co-localization, were transfected with p-IRES2-EGFP-CCK and siRNA-CCK. Results showed that CCK overexpression significantly reduced testosterone (T) and dihydrotestosterone (DHT) levels (P < 0.05), while upregulating androgen receptor (AR) and key androgen synthesis enzymes (StAR, P450scc, 3β-HSD) (P < 0.05 or P < 0.01). In contrast, siRNA-CCK exerted the opposite effects. In conclusion, our study highlights the CCK/CCKBR axis as a crucial regulator of seasonal testicular function in Bactrian camels, with CCK negatively regulating testicular androgen synthesis by modulating AR and androgen synthesis enzymes. These findings provide valuable insights into the reproductive biology of Bactrian camels and offer a novel pathway for understanding seasonal fertility regulation in male mammals. This has important implications for enhancing camel breeding efficiency and supporting conservation efforts.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"257 ","pages":"Article 106922"},"PeriodicalIF":2.5,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783580","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

Coffee consumption and its association with vitamin D level, lifestyle factors, and mental health symptoms among adults in Saudi Arabia 沙特阿拉伯成年人中咖啡消费量及其与维生素D水平、生活方式因素和心理健康症状的关系

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-12-17 DOI: 10.1016/j.jsbmb.2025.106923

Noor A. Hakim

Coffee is widely consumed in Saudi Arabia, but its relationship with vitamin D status and related health indicators remains unclear. This cross-sectional study examined associations between coffee consumption, serum 25-hydroxyvitamin D [25(OH)D], lifestyle factors, and mental health symptoms in 387 adults aged 20–60 years recruited in Saudi Arabia (February–March 2024). Participants were classified as normal (≤3 cups/day) or high (>3 cups/day) coffee consumers. Anthropometric measures and serum 25(OH)D and parathyroid hormone were obtained from medical records, and diet, physical activity, sun exposure, and mental health symptoms were assessed by questionnaire. Associations were examined using group comparisons and multivariable regression models. Compared with normal coffee consumers, high coffee consumers had higher BMI (p = 0.043) and lower serum 25(OH)D (p = 0.05). In multivariable linear regression, higher caffeine intake was associated with lower serum 25(OH)D (β = −0.04 nmol/L per mg/day; 95 % CI −0.055 to −0.027; p < 0.001). In logistic regression, higher caffeine intake was associated with lower odds of vitamin D deficiency (<30 nmol/L) (OR = 0.98 per mg/day; 95 % CI 0.97–0.99; p < 0.001). High coffee consumers more frequently reported sleep disturbance/insomnia (49.1 % vs 34.2 %), sweating (20.8 % vs 9.6 %), and raised heart rate (27.7 % vs 17.2 %) (all p < 0.01), whereas headache, irritability, anxiety, and depression did not differ between groups. In this sample of Saudi adults, higher coffee intake was associated with lower 25(OH)D, higher BMI, and more arousal-related symptoms. These observational findings warrant confirmation in longitudinal or interventional studies to clarify temporality and inform public health strategies.

咖啡在沙特阿拉伯被广泛消费，但其与维生素D水平和相关健康指标的关系尚不清楚。本横断面研究在沙特阿拉伯招募了387名年龄在20-60岁的成年人（2024年2月至3月），研究了咖啡摄入量、血清25-羟基维生素D [25(OH)D]、生活方式因素和精神健康症状之间的关系。参与者被分为普通（≤3杯/天）和高（bb0 - 3杯/天）咖啡消费者。从医疗记录中获得人体测量值和血清25(OH)D和甲状旁腺激素，并通过问卷调查评估饮食、身体活动、日晒和心理健康症状。使用组比较和多变量回归模型检验相关性。与正常咖啡饮用者相比，高咖啡饮用者BMI较高（p = 0.043），血清25(OH)D较低（p = 0.05）。在多变量线性回归中，较高的咖啡因摄入量与较低的血清25(OH)D相关（β = -0.04 nmol/L / mg/day； 95% CI为-0.055 ~ -0.027;p < 0.001）。在逻辑回归中，摄入较多的咖啡因与较低的维生素D缺乏症(

{"title":"Coffee consumption and its association with vitamin D level, lifestyle factors, and mental health symptoms among adults in Saudi Arabia","authors":"Noor A. Hakim","doi":"10.1016/j.jsbmb.2025.106923","DOIUrl":"10.1016/j.jsbmb.2025.106923","url":null,"abstract":"<div><div>Coffee is widely consumed in Saudi Arabia, but its relationship with vitamin D status and related health indicators remains unclear. This cross-sectional study examined associations between coffee consumption, serum 25-hydroxyvitamin D [25(OH)D], lifestyle factors, and mental health symptoms in 387 adults aged 20–60 years recruited in Saudi Arabia (February–March 2024). Participants were classified as normal (≤3 cups/day) or high (>3 cups/day) coffee consumers. Anthropometric measures and serum 25(OH)D and parathyroid hormone were obtained from medical records, and diet, physical activity, sun exposure, and mental health symptoms were assessed by questionnaire. Associations were examined using group comparisons and multivariable regression models. Compared with normal coffee consumers, high coffee consumers had higher BMI (p = 0.043) and lower serum 25(OH)D (p = 0.05). In multivariable linear regression, higher caffeine intake was associated with lower serum 25(OH)D (β = −0.04 nmol/L per mg/day; 95 % CI −0.055 to −0.027; p < 0.001). In logistic regression, higher caffeine intake was associated with lower odds of vitamin D deficiency (<30 nmol/L) (OR = 0.98 per mg/day; 95 % CI 0.97–0.99; p < 0.001). High coffee consumers more frequently reported sleep disturbance/insomnia (49.1 % vs 34.2 %), sweating (20.8 % vs 9.6 %), and raised heart rate (27.7 % vs 17.2 %) (all p < 0.01), whereas headache, irritability, anxiety, and depression did not differ between groups. In this sample of Saudi adults, higher coffee intake was associated with lower 25(OH)D, higher BMI, and more arousal-related symptoms. These observational findings warrant confirmation in longitudinal or interventional studies to clarify temporality and inform public health strategies.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"257 ","pages":"Article 106923"},"PeriodicalIF":2.5,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795623","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

Bisphenol A derivatives as potent inhibitors of 11β-hydroxysteroid dehydrogenase 2: A structure-activity study 双酚A衍生物作为11β-羟基类固醇脱氢酶2的有效抑制剂：结构-活性研究。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-12-17 DOI: 10.1016/j.jsbmb.2025.106924

Xiya Ren , Lei Shi , Xinyue Chen , Yunbing Tang , Yingfen Ying , Renshan Ge , Qiqi Zhu

Bisphenol A (BPA) has been restricted for its use due to endocrine-disrupting effects and its benzene-ring-substituted derivatives (BPADs) are increasingly used. However, their effects on 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), a pivotal enzyme in glucocorticoid regulation, remain poorly characterized. Here, we evaluated, for the first time, how BPADs modulate 11β-HSD2 inhibition, providing mechanistic insights into their endocrine-disrupting potential. This study evaluated six BPADs, identifying 4-hydroxyphenyl-naphthalene (BPH) as the most potent inhibitor (human IC₅₀ = 1.26 µM; rat IC₅₀ = 4.17 µM), with structure-activity relationships (SAR) revealing critical roles for hydrophobicity (LogP) and steric bulk. Enzyme kinetic inhibition analyses demonstrated competitive or mixed-type inhibition of BPADs, and surface plasmon resonance (SPR) confirmed direct binding of BPH to 11β-HSD2. Molecular docking further highlighted key interactions with residues (Asn167, Lys236) in the steroid-binding pocket. Cellular assays in BeWo cells confirmed functional inhibition of endogenous 11β-HSD2. Notably, human 11β-HSD2 exhibited greater sensitivity than rat ortholog towards BPADs, attributed to a Ser92→Thr92 substitution of 11β-HSD2 sequences. These findings positioned BPADs as novel chemical probes for 11β-HSD2 studies and warranted investigation into their endocrine-disrupting potential, particularly in prenatal contexts where placental 11β-HSD2 safeguards fetal development.

双酚A （BPA）由于其内分泌干扰作用而受到限制，其苯环取代衍生物（bpad）的使用越来越多。然而，它们对糖皮质激素调节中的关键酶11β-羟基类固醇脱氢酶2 （11β-HSD2）的影响仍然知之甚少。在这里，我们首次评估了bpad如何调节11β-HSD2抑制，为其内分泌干扰潜力提供了机制见解。本研究评估了6种bpad，确定4-羟基苯基萘（BPH）是最有效的抑制剂（人IC50 = 1.26µM，大鼠IC50 = 4.17µM），其构效关系（SAR）揭示了疏水性（LogP）和空间体积的关键作用。酶动力学抑制分析表明bpad具有竞争性或混合型抑制作用，表面等离子体共振（SPR）证实BPH与11β-HSD2直接结合。分子对接进一步突出了与类固醇结合口袋中残基（Asn167, Lys236）的关键相互作用。BeWo细胞的细胞实验证实了内源性11β-HSD2的功能抑制。值得注意的是，人类11β-HSD2对bpad的敏感性高于大鼠，这归因于11β-HSD2序列的Ser92→Thr92替换。这些发现将bpad定位为11β-HSD2研究的新型化学探针，并为其内分泌干扰潜力的研究提供了依据，特别是在胎盘11β-HSD2保护胎儿发育的产前环境中。

{"title":"Bisphenol A derivatives as potent inhibitors of 11β-hydroxysteroid dehydrogenase 2: A structure-activity study","authors":"Xiya Ren , Lei Shi , Xinyue Chen , Yunbing Tang , Yingfen Ying , Renshan Ge , Qiqi Zhu","doi":"10.1016/j.jsbmb.2025.106924","DOIUrl":"10.1016/j.jsbmb.2025.106924","url":null,"abstract":"<div><div>Bisphenol A (BPA) has been restricted for its use due to endocrine-disrupting effects and its benzene-ring-substituted derivatives (BPADs) are increasingly used. However, their effects on 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), a pivotal enzyme in glucocorticoid regulation, remain poorly characterized. Here, we evaluated, for the first time, how BPADs modulate 11β-HSD2 inhibition, providing mechanistic insights into their endocrine-disrupting potential. This study evaluated six BPADs, identifying 4-hydroxyphenyl-naphthalene (BPH) as the most potent inhibitor (human IC<sub>50</sub> = 1.26 µM; rat IC<sub>50</sub> = 4.17 µM), with structure-activity relationships (SAR) revealing critical roles for hydrophobicity (LogP) and steric bulk. Enzyme kinetic inhibition analyses demonstrated competitive or mixed-type inhibition of BPADs, and surface plasmon resonance (SPR) confirmed direct binding of BPH to 11β-HSD2. Molecular docking further highlighted key interactions with residues (Asn167, Lys236) in the steroid-binding pocket. Cellular assays in BeWo cells confirmed functional inhibition of endogenous 11β-HSD2. Notably, human 11β-HSD2 exhibited greater sensitivity than rat ortholog towards BPADs, attributed to a Ser92→Thr92 substitution of 11β-HSD2 sequences. These findings positioned BPADs as novel chemical probes for 11β-HSD2 studies and warranted investigation into their endocrine-disrupting potential, particularly in prenatal contexts where placental 11β-HSD2 safeguards fetal development.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"257 ","pages":"Article 106924"},"PeriodicalIF":2.5,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795599","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