Pub Date : 2025-02-04DOI: 10.1016/j.jsbmb.2025.106692
Romina P. Martinelli , Candela Petroni , Josefina Martinez , Cristina Cuesta , Luis Esteban , Alejandra M. Pacchioni , Pablo Arias
There is mounting evidence that suggests vitamin D insufficiency may have a role in the emergence of type 2 diabetes. Additionally, as VDR mediates the actions of vitamin D, variants in its sequence could have implications in this disease. One of these polymorphisms, Fok1 (rs2228570), has been demonstrated to generate changes in the receptor’s structure, causing a shorter protein. The purpose of this research is to establish a potential association between the Fok1 polymorphism and DM2. To achieve such goal, a comprehensive study of this SNP was conducted using functional in-silico analysis and a systematic review with meta-analysis. Additionally, an examination of VDR gene expression in patients with diabetes compared to controls was performed in order to investigate possible differences in expression levels. Our expression analysis showed that VDR has no differential expression between these two groups. To study its functional consequences and stability, different tools were combined, without consistent results. Finally, our systematic review and meta-analysis showed that theFok1 variant was not significantly associated with the DM2 prevalence. This extensive analysis did not provide support for an association between the presence of Fok1 polymorphism and DM2. This result aligns with some previous studies but contrasts others that have reported both protective and risk factors.
{"title":"Investigating the association between FOK1 polymorphism in the vitamin D receptor (VDR) gene and type 2 diabetes prevalence: A comprehensive analysis","authors":"Romina P. Martinelli , Candela Petroni , Josefina Martinez , Cristina Cuesta , Luis Esteban , Alejandra M. Pacchioni , Pablo Arias","doi":"10.1016/j.jsbmb.2025.106692","DOIUrl":"10.1016/j.jsbmb.2025.106692","url":null,"abstract":"<div><div>There is mounting evidence that suggests vitamin D insufficiency may have a role in the emergence of type 2 diabetes. Additionally, as VDR mediates the actions of vitamin D, variants in its sequence could have implications in this disease. One of these polymorphisms, Fok1 (rs2228570), has been demonstrated to generate changes in the receptor’s structure, causing a shorter protein. The purpose of this research is to establish a potential association between the Fok1 polymorphism and DM2. To achieve such goal, a comprehensive study of this SNP was conducted using functional in-silico analysis and a systematic review with meta-analysis. Additionally, an examination of VDR gene expression in patients with diabetes compared to controls was performed in order to investigate possible differences in expression levels. Our expression analysis showed that VDR has no differential expression between these two groups. To study its functional consequences and stability, different tools were combined, without consistent results. Finally, our systematic review and meta-analysis showed that theFok1 variant was not significantly associated with the DM2 prevalence. This extensive analysis did not provide support for an association between the presence of Fok1 polymorphism and DM2. This result aligns with some previous studies but contrasts others that have reported both protective and risk factors.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"248 ","pages":"Article 106692"},"PeriodicalIF":2.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143331772","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}
Pub Date : 2025-02-04DOI: 10.1016/j.jsbmb.2025.106693
Ze Fu , Xin Xin , Yongtong Zhan , Xuhong Fan , Xin Li , Tongsheng Chen , Xiaoping Wang
G-1, a G protein-coupled estrogen receptor (GPER)-specific agonist, exhibits anticancer potential in breast cancer cells. This study aims to explore the molecular basis of apoptosis induced by G-1 in MCF-7 and MDA-MB-231 breast cancer cells. Here, we found that G-1 induced cytotoxicity and GPER-dependent apoptosis with PARP cleavage and mitochondrial membrane potential (MMP) loss, as well as nuclear condensation. Fluorescence resonance energy transfer (FRET) analysis in living cells indicated that G-1 effectively disrupted the interaction between large tumor suppressor 1/2 (LATS1/2) and Yes-associated protein (YAP). Furthermore, G-1 reduced YAP phosphorylation levels and promoted its nuclear accumulation. Notably, knockdown of YAP attenuated G-1-induced apoptosis, highlighting the crucial role of YAP in this process. Additionally, FRET analysis revealed that G-1 enhanced the binding of YAP to p73, leading to an increase in Bcl-2-associated X protein (Bax) expression and an induction of apoptosis. In summary, our findings demonstrate that G-1 induces apoptosis through the GPER/YAP/p73-mediated pathway.
{"title":"GPER agonist G-1 activates YAP to induce apoptosis in breast cancer cells","authors":"Ze Fu , Xin Xin , Yongtong Zhan , Xuhong Fan , Xin Li , Tongsheng Chen , Xiaoping Wang","doi":"10.1016/j.jsbmb.2025.106693","DOIUrl":"10.1016/j.jsbmb.2025.106693","url":null,"abstract":"<div><div>G-1, a G protein-coupled estrogen receptor (GPER)-specific agonist, exhibits anticancer potential in breast cancer cells. This study aims to explore the molecular basis of apoptosis induced by G-1 in MCF-7 and MDA-MB-231 breast cancer cells. Here, we found that G-1 induced cytotoxicity and GPER-dependent apoptosis with PARP cleavage and mitochondrial membrane potential (MMP) loss, as well as nuclear condensation. Fluorescence resonance energy transfer (FRET) analysis in living cells indicated that G-1 effectively disrupted the interaction between large tumor suppressor 1/2 (LATS1/2) and Yes-associated protein (YAP). Furthermore, G-1 reduced YAP phosphorylation levels and promoted its nuclear accumulation. Notably, knockdown of YAP attenuated G-1-induced apoptosis, highlighting the crucial role of YAP in this process. Additionally, FRET analysis revealed that G-1 enhanced the binding of YAP to p73, leading to an increase in Bcl-2-associated X protein (Bax) expression and an induction of apoptosis. In summary, our findings demonstrate that G-1 induces apoptosis through the GPER/YAP/p73-mediated pathway.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"248 ","pages":"Article 106693"},"PeriodicalIF":2.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366622","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}
Perimenopausal depression is a psychiatric disorder that occurs around the time of menopause and seriously affects women's health. The pathogenesis of perimenopausal depression is unclear which affects its prevention and treatment. Quercetin is a flavonoid compound with antidepressant and estrogen-like effects. The aim of this research was to investigate the role of quercetin on adrenal gland metabolic disorders in perimenopausal depressed rats based on untargeted metabolomics. Female Wistar rats with no difference in sucrose preference were randomly separated into four groups (n = 12): sham-operated group; perimenopausal depression model group; model + 50 mg/kg.bw quercetin group; model + 0.27 mg/kg.bw 17β-estradiol group. After successful modeling, adrenal gland and hypothalamic samples were collected for metabolomics experiments and detection of related indicators. A total of 22 differential metabolites were identified in the model group, and pathway analysis revealed adrenal gland metabolism abnormalities including steroid hormone biosynthesis, arachidonic acid metabolism, and linoleic acid metabolism. Notably, Spearman’s rank correlation analysis between differential metabolites and rat behavioral results showed strong positive or negative correlations (P < 0.01). Meanwhile, the hypothalamus of the model group showed TrkB-BDNF signaling pathway abnormality, and the HPA axis was found to play an important role in perimenopausal depression. Treatment with quercetin or 17β-estradiol restored these abnormal changes. It suggested that quercetin can regulate adrenal metabolic disorders through multiple pathways, thereby ameliorating perimenopausal depression.Further more, quercetin can modulate HPA axis through the TrkB-BDNF signaling pathway. This research provides new ideas for the application of quercetin in the precaution and treatment of perimenopausal depression.
{"title":"Untargeted metabolomics revealed that quercetin improved adrenal gland metabolism disorders and modulated the HPA axis in perimenopausal depression model rats","authors":"Ziran Yu, Chenlu Feng, Ying Chen, Weidi Wang, Xiujuan Zhao","doi":"10.1016/j.jsbmb.2025.106696","DOIUrl":"10.1016/j.jsbmb.2025.106696","url":null,"abstract":"<div><div>Perimenopausal depression is a psychiatric disorder that occurs around the time of menopause and seriously affects women's health. The pathogenesis of perimenopausal depression is unclear which affects its prevention and treatment. Quercetin is a flavonoid compound with antidepressant and estrogen-like effects. The aim of this research was to investigate the role of quercetin on adrenal gland metabolic disorders in perimenopausal depressed rats based on untargeted metabolomics. Female Wistar rats with no difference in sucrose preference were randomly separated into four groups (n = 12): sham-operated group; perimenopausal depression model group; model + 50 mg/kg.bw quercetin group; model + 0.27 mg/kg.bw 17β-estradiol group. After successful modeling, adrenal gland and hypothalamic samples were collected for metabolomics experiments and detection of related indicators. A total of 22 differential metabolites were identified in the model group, and pathway analysis revealed adrenal gland metabolism abnormalities including steroid hormone biosynthesis, arachidonic acid metabolism, and linoleic acid metabolism. Notably, Spearman’s rank correlation analysis between differential metabolites and rat behavioral results showed strong positive or negative correlations (<em>P</em> < 0.01). Meanwhile, the hypothalamus of the model group showed TrkB-BDNF signaling pathway abnormality, and the HPA axis was found to play an important role in perimenopausal depression. Treatment with quercetin or 17β-estradiol restored these abnormal changes. It suggested that quercetin can regulate adrenal metabolic disorders through multiple pathways, thereby ameliorating perimenopausal depression.Further more, quercetin can modulate HPA axis through the TrkB-BDNF signaling pathway. This research provides new ideas for the application of quercetin in the precaution and treatment of perimenopausal depression.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"248 ","pages":"Article 106696"},"PeriodicalIF":2.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143331762","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}
Pub Date : 2025-02-01DOI: 10.1016/j.jsbmb.2024.106652
Yilong Lin , Songsong Wang , Yun Zhang , Jing She , Yue Zhang , Ruidan Zhao , Zhongquan Qi , Ruiqin Yang , Liyi Zhang , Qingmo Yang
Breast cancer is a substantial global health problem, and drug repurposing provides novel opportunities to address the urgent need for therapeutics. According to significant Mendelian randomization (MR) results, we identified 26 genes for overall breast cancer, 25 genes for ER+ breast cancer and 4 genes (CASP8, KCNN4, MYLK4, TNNT3) for ER- breast cancer. In order to explore the differences between 5 intrinsic subtypes, we found 29 actionable druggable genes for Luminal A breast cancer, 2 genes (IGF2 and TNNT3) for Luminal B breast cancer, 1 gene (FAAH) for Luminal B HER2 negative breast cancer, and 3 genes (CASP8, KCNN4, and TP53) for triple-negative breast cancer. After colocalization analysis, we determined OPRL1 as a prioritized target in both overall and Luminal A breast cancer. Additionally, FES and FAAH were considered prioritized targets for ER+ breast cancer. Through molecular docking, crizotinib stand out as a prioritized FES target drug repurposing opportunity with the lowest binding energy (-10.13 kJ·mol−1) and CCK-8 assay showed ER+ cell groups were more sensitive to crizotinib than ER- cell groups. In conclusion, OPRL1 was identified as a prioritized target for both overall and Luminal A breast cancer. Moreover, FES and FAAH were recognized as prioritized targets for ER+ breast cancer.
乳腺癌是一个重大的全球健康问题，药物再利用为解决治疗方法的迫切需求提供了新的机会。根据显著的孟德尔随机化（MR）结果，我们鉴定出26个与整体乳腺癌相关的基因，25个与ER+乳腺癌相关的基因，以及4个与ER-乳腺癌相关的基因（CASP8、KCNN4、MYLK4、TNNT3）。为了探讨5种内在亚型之间的差异，我们发现了29个Luminal A乳腺癌的可操作药物基因，2个Luminal B乳腺癌的可操作基因（IGF2和TNNT3）， 1个Luminal B HER2阴性乳腺癌的可操作基因（FAAH）， 3个三阴性乳腺癌的可操作基因（CASP8、KCNN4和TP53）。经过共定位分析，我们确定OPRL1是整体和腔内a型乳腺癌的优先靶点。此外，FES和FAAH被认为是ER+乳腺癌的优先靶点。通过分子对接，克唑替尼以最低结合能（-10.13 kj·mol-1）成为FES优先靶向药物再利用机会，CCK-8实验显示ER+细胞组对克唑替尼的敏感性高于ER-细胞组。总之，OPRL1被确定为整体和腔a乳腺癌的优先靶点。此外，FES和FAAH被认为是ER+乳腺癌的优先靶点。
{"title":"Drug repurposing opportunities for breast cancer and seven common subtypes","authors":"Yilong Lin , Songsong Wang , Yun Zhang , Jing She , Yue Zhang , Ruidan Zhao , Zhongquan Qi , Ruiqin Yang , Liyi Zhang , Qingmo Yang","doi":"10.1016/j.jsbmb.2024.106652","DOIUrl":"10.1016/j.jsbmb.2024.106652","url":null,"abstract":"<div><div>Breast cancer is a substantial global health problem, and drug repurposing provides novel opportunities to address the urgent need for therapeutics. According to significant Mendelian randomization (MR) results, we identified 26 genes for overall breast cancer, 25 genes for ER+ breast cancer and 4 genes (CASP8, KCNN4, MYLK4, TNNT3) for ER- breast cancer. In order to explore the differences between 5 intrinsic subtypes, we found 29 actionable druggable genes for Luminal A breast cancer, 2 genes (IGF2 and TNNT3) for Luminal B breast cancer, 1 gene (FAAH) for Luminal B HER2 negative breast cancer, and 3 genes (CASP8, KCNN4, and TP53) for triple-negative breast cancer. After colocalization analysis, we determined OPRL1 as a prioritized target in both overall and Luminal A breast cancer. Additionally, FES and FAAH were considered prioritized targets for ER+ breast cancer. Through molecular docking, crizotinib stand out as a prioritized FES target drug repurposing opportunity with the lowest binding energy (-10.13 kJ·mol<sup>−1</sup>) and CCK-8 assay showed ER+ cell groups were more sensitive to crizotinib than ER- cell groups. In conclusion, OPRL1 was identified as a prioritized target for both overall and Luminal A breast cancer. Moreover, FES and FAAH were recognized as prioritized targets for ER+ breast cancer.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"246 ","pages":"Article 106652"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774642","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}
Pub Date : 2025-02-01DOI: 10.1016/j.jsbmb.2025.106683
Yong-Zi Chen , Shilei Xu , Hailing Ren , Jun Zhang , Yongsheng Jia , Haiyan Sun
Sialylation, a key post-translational modification essential for protein function, is regulated by steroid hormones, along with other glycosylations like fucosylation. These modifications influence tumor growth and metastasis by modulating immune activation. MicroRNAs (miRNAs), crucial in gene expression, affect sialylation and are emerging as promising biomarkers in breast cancer, though their prognostic value remains unclear. Sialylation-related miRNAs were identified through Pearson correlation analysis, and an eight-miRNA risk signature was developed using univariate and Least Absolute Shrinkage and Selection Operator (LASSO) regression in the TCGA dataset. The prognostic value was validated in two independent GEO datasets. Multivariate analysis confirmed that the miRNA risk score is an independent predictor of overall survival (OS). A nomogram integrating clinical characteristics and the risk score was created to predict 1-, 3-, and 5-year OS, assessed through calibration curves, ROC curves, and area under the ROC curve (AUC). Biological pathways were explored using GSEA and GSVA, while immune infiltrates were identified through CIBERSORT and TIMER.
The eight-miRNA signature effectively predicted OS, recurrence-free survival, and disease-free survival. High-risk patients exhibited increased macrophage and neutrophil levels, indicative of a poor prognosis. High-risk patients, especially those with triple-negative breast cancer, had significantly worse outcomes. This risk score could inform personalized treatment strategies in breast cancer management.
{"title":"Characterization of novel sialylation-associated microRNA signature for prognostic assessment in breast cancer and its implications for the tumor microenvironment","authors":"Yong-Zi Chen , Shilei Xu , Hailing Ren , Jun Zhang , Yongsheng Jia , Haiyan Sun","doi":"10.1016/j.jsbmb.2025.106683","DOIUrl":"10.1016/j.jsbmb.2025.106683","url":null,"abstract":"<div><div>Sialylation, a key post-translational modification essential for protein function, is regulated by steroid hormones, along with other glycosylations like fucosylation. These modifications influence tumor growth and metastasis by modulating immune activation. MicroRNAs (miRNAs), crucial in gene expression, affect sialylation and are emerging as promising biomarkers in breast cancer, though their prognostic value remains unclear. Sialylation-related miRNAs were identified through Pearson correlation analysis, and an eight-miRNA risk signature was developed using univariate and Least Absolute Shrinkage and Selection Operator (LASSO) regression in the TCGA dataset. The prognostic value was validated in two independent GEO datasets. Multivariate analysis confirmed that the miRNA risk score is an independent predictor of overall survival (OS). A nomogram integrating clinical characteristics and the risk score was created to predict 1-, 3-, and 5-year OS, assessed through calibration curves, ROC curves, and area under the ROC curve (AUC). Biological pathways were explored using GSEA and GSVA, while immune infiltrates were identified through CIBERSORT and TIMER.</div><div>The eight-miRNA signature effectively predicted OS, recurrence-free survival, and disease-free survival. High-risk patients exhibited increased macrophage and neutrophil levels, indicative of a poor prognosis. High-risk patients, especially those with triple-negative breast cancer, had significantly worse outcomes. This risk score could inform personalized treatment strategies in breast cancer management.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"248 ","pages":"Article 106683"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124083","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}
Pub Date : 2025-02-01DOI: 10.1016/j.jsbmb.2024.106648
Noemi Iaia , Federico Canzoneri , Fiorella Biasi , Giuseppe Poli , Roberto Menta , Gabriella Testa , Paola Gamba
The selective permeability of the gut epithelial barrier is heavily reliant on the stability of cell junctions, often challenged by a variety of dietary stressors, including non-enzymatic cholesterol oxidation products (COPs). A marked decrease of the tight junctions claudin-1 and occludin, and of the adherens junction E-cadherin was previously detected in differentiated CaCo-2 monolayers challenged by a single addition of 7β-hydroxycholesterol (7βOHC) or 7-ketocholesterol (7KC) in the lowest micromolar range. However, in the diet, oxysterols are occurring in a mixture. Hence, the aim of the present study was to evaluate whether cell incubation with all the main dietary COPs together quench the intercellular junction derangement previously observed as exerted by 7βOHC and 7KC singularly added. Two chocolate prototypes, respectively made with fresh (oxy-Mix1) or six-months stored whole milk powder (oxy-Mix2), were compared. The second prototype showed an almost double content of total COPs (3.34 µM, approximately 1337 ng /g of chocolate) than the first one (1.69 µM, approximately 675 ng /g of chocolate). Importantly, even in the CaCo-2 cell monolayers treated with six-months stored mixture of COPs oxy-Mix2, no alterations were observed of those cell junctions markedly affected by identical concentration of 7βOHC or 7KC used alone. The junctions’ derangement started to be significantly evident when oxy-Mix2 was used at higher concentration (5 µM, approximately 2 µg oxysterols/g of product) or when treatments were carried out with repeated doses of oxy-Mix2 every 24 hours. Although achieved in a still widely adopted in vitro model system, these findings could orientate the definition of a safe shelf-life for dairy products, certainly for milk chocolate.
{"title":"The CaCo-2 cell junction derangement exerted by the single addition of oxysterols commonly detected in foods is markedly quenched when they are in mixture","authors":"Noemi Iaia , Federico Canzoneri , Fiorella Biasi , Giuseppe Poli , Roberto Menta , Gabriella Testa , Paola Gamba","doi":"10.1016/j.jsbmb.2024.106648","DOIUrl":"10.1016/j.jsbmb.2024.106648","url":null,"abstract":"<div><div>The selective permeability of the gut epithelial barrier is heavily reliant on the stability of cell junctions, often challenged by a variety of dietary stressors, including non-enzymatic cholesterol oxidation products (COPs). A marked decrease of the tight junctions claudin-1 and occludin, and of the adherens junction E-cadherin was previously detected in differentiated CaCo-2 monolayers challenged by a single addition of 7β-hydroxycholesterol (7βOHC) or 7-ketocholesterol (7KC) in the lowest micromolar range. However, in the diet, oxysterols are occurring in a mixture. Hence, the aim of the present study was to evaluate whether cell incubation with all the main dietary COPs together quench the intercellular junction derangement previously observed as exerted by 7βOHC and 7KC singularly added. Two chocolate prototypes, respectively made with fresh (oxy-Mix1) or six-months stored whole milk powder (oxy-Mix2), were compared. The second prototype showed an almost double content of total COPs (3.34 µM, approximately 1337 ng /g of chocolate) than the first one (1.69 µM, approximately 675 ng /g of chocolate). Importantly, even in the CaCo-2 cell monolayers treated with six-months stored mixture of COPs oxy-Mix2, no alterations were observed of those cell junctions markedly affected by identical concentration of 7βOHC or 7KC used alone. The junctions’ derangement started to be significantly evident when oxy-Mix2 was used at higher concentration (5 µM, approximately 2 µg oxysterols/g of product) or when treatments were carried out with repeated doses of oxy-Mix2 every 24 hours. Although achieved in a still widely adopted <em>in vitro</em> model system, these findings could orientate the definition of a safe shelf-life for dairy products, certainly for milk chocolate.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"246 ","pages":"Article 106648"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755806","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}
Pub Date : 2025-02-01DOI: 10.1016/j.jsbmb.2024.106649
Padraig Maher , Martin Healy , Eamon Laird , Jelena Marunica Karšaj , Wei Gao , Lina Zgaga
Background
Endogenous steroid hormone assessment is essential for clinical practice. These hormones are typically measured in blood. More recently, measurement of steroids in hair samples has been gaining in popularity, so we have reviewed the methodologies used for this to-date.
Methods
Ovid Medline, CINAHL, Psychinfo, and EMBASE were searched to identify manuscripts that analysed cortisol, testosterone, androstenedione, 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone sulphate (DHEAS), and/or 25-hydroxyvitamin D (25(OH)D), in hair or fur. Data related to sampling and measurement procedures were extracted and analysed.
Results
The systematic review included a total of 180 papers, with 82 % published in the past 8 years; 67 % were human and 33 % animal studies. Cortisol was by far the most common analyte. Incomplete reporting on sample harvest, preparation, and measurement procedures was common. Typically, samples were collected from posterior vertex of humans or back/neck of animals, weighing between 11 and 50 mg (with a range of 1.25–1000 mg). Samples were usually stored at room temperature, often using aluminium foil. Isopropanol was the most common cleaning solution. Hair was normally powdered or segmented prior to extraction. Extraction was typically carried out over 18–24 hours using methanol. Validation and precision information was provided in 47 % of studies.
Conclusions
This systematic review highlights the lack of standardisation in the analysis of endogenous steroids in hair. Reporting was typically incomplete, and assay validations were partial or absent. Together, these limit the value of these exciting new methods and hold back transition to clinical use.
{"title":"The determination of endogenous steroids in hair and fur: A systematic review of methodologies","authors":"Padraig Maher , Martin Healy , Eamon Laird , Jelena Marunica Karšaj , Wei Gao , Lina Zgaga","doi":"10.1016/j.jsbmb.2024.106649","DOIUrl":"10.1016/j.jsbmb.2024.106649","url":null,"abstract":"<div><h3>Background</h3><div>Endogenous steroid hormone assessment is essential for clinical practice. These hormones are typically measured in blood. More recently, measurement of steroids in hair samples has been gaining in popularity, so we have reviewed the methodologies used for this to-date.</div></div><div><h3>Methods</h3><div>Ovid Medline, CINAHL, Psychinfo, and EMBASE were searched to identify manuscripts that analysed cortisol, testosterone, androstenedione, 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone sulphate (DHEAS), and/or 25-hydroxyvitamin D (25(OH)D), in hair or fur. Data related to sampling and measurement procedures were extracted and analysed.</div></div><div><h3>Results</h3><div>The systematic review included a total of 180 papers, with 82 % published in the past 8 years; 67 % were human and 33 % animal studies. Cortisol was by far the most common analyte. Incomplete reporting on sample harvest, preparation, and measurement procedures was common. Typically, samples were collected from posterior vertex of humans or back/neck of animals, weighing between 11 and 50 mg (with a range of 1.25–1000 mg). Samples were usually stored at room temperature, often using aluminium foil. Isopropanol was the most common cleaning solution. Hair was normally powdered or segmented prior to extraction. Extraction was typically carried out over 18–24 hours using methanol. Validation and precision information was provided in 47 % of studies.</div></div><div><h3>Conclusions</h3><div>This systematic review highlights the lack of standardisation in the analysis of endogenous steroids in hair. Reporting was typically incomplete, and assay validations were partial or absent. Together, these limit the value of these exciting new methods and hold back transition to clinical use.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"246 ","pages":"Article 106649"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755808","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}
Epidemiological studies often link circulatory levels of 25 hydroxy vitamin D with an overwhelming variety of disorders. Of such studies, an increasing number are now linking blood 25 hydroxy vitamin D levels with certain brain disorders. Prominent amongst such disorders are schizophrenia and Parkinson’s disease. The neurotransmitter dopamine is central to understanding the eitiology of both disorders with schizophrenia representing increased subcortical dopamine function and Parkinson’s disease a disorder with the pathological hallmark of dopamine cellular pathology. Our group have established the epidemiology linking vitamin D deficiency in utero and later onset of schizophrenia. We have clarified many of the mechanisms behind how vitamin D effects dopamine neuron positioning, differentiation and survival. In this study we confirm vitamin D differentiates the dendritic architecture of dopamine neurons, that vitamin D may represent a requirement for drug-mediated dopamine release and that vitamin D may sculpt presynaptic proteins related to fast or phasic dopamine release.
{"title":"Vitamin D differentiates dopamine neurons in vitro, increasing neurite architecture, dopamine release and expression of relevant synaptic proteins","authors":"Xiaoying Cui , Renata Aparecida Nedel Pertile , Vanshika Raman , Darryl Eyles","doi":"10.1016/j.jsbmb.2025.106681","DOIUrl":"10.1016/j.jsbmb.2025.106681","url":null,"abstract":"<div><div>Epidemiological studies often link circulatory levels of 25 hydroxy vitamin D with an overwhelming variety of disorders. Of such studies, an increasing number are now linking blood 25 hydroxy vitamin D levels with certain brain disorders. Prominent amongst such disorders are schizophrenia and Parkinson’s disease. The neurotransmitter dopamine is central to understanding the eitiology of both disorders with schizophrenia representing increased subcortical dopamine function and Parkinson’s disease a disorder with the pathological hallmark of dopamine cellular pathology. Our group have established the epidemiology linking vitamin D deficiency <em>in utero</em> and later onset of schizophrenia. We have clarified many of the mechanisms behind how vitamin D effects dopamine neuron positioning, differentiation and survival. In this study we confirm vitamin D differentiates the dendritic architecture of dopamine neurons, that vitamin D may represent a requirement for drug-mediated dopamine release and that vitamin D may sculpt presynaptic proteins related to fast or phasic dopamine release.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"247 ","pages":"Article 106681"},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069343","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}
Pub Date : 2025-01-25DOI: 10.1016/j.jsbmb.2025.106680
Mohammed Mahdi Sami , Mataz J. Jamai , Tamara Ahmed Abd Alkareem , Nabeel Bunyan Ayram
Polycystic ovarian syndrome (PCOS) is a low-grade and chronic inflammation defined by irregular hormonal status that primarily triggers females in their reproductive age. Multi cysts are a primary manifestation of PCOS; a high level of androgen production characterizes the condition via ovaries. Rheumatoid arthritis (RA) is a chronic, systemic, and symmetrical inflammatory autoimmune disease that affects 1–2 % of adults. Females are more likely to generate RA. During the inflammatory activity, immune cells attack the synovium and the synovial space. This invasion is essential in releasing many cytokines in the synovial and joint spaces, leading to joint damage and pain, stiffens, heat, and tenderness in the joint. To evaluate the strength of the link between PCOS and RA, the cross-sectional study examined hormonal, metabolic, and autoantibodies in PCOS, RA as a positive control and the study groups. Statistical analysis Shapiro-Wilk test, student t-test, one-way ANOVA, and multi-linear regression analysis were used to evaluate the results. The data highlights significant values for the BMI, WHR, and hirsutism of PCOS and RA groups in comparison to the negative control. The ANOVA results of these parameters also showed a significant p < 0.05 among the groups. According to the negative control, the levels of insulin, HOMA-IR, testosterone, LH, estradiol, and CRP showed a substantial increase in the PCOS group. Also, the RA group showed a significant p < 0.05 rise in CRP, RF, and Ani-CCP, and the ANOVA results showed significant value among the groups under investigation. Progesterone D as a model showed a correlation with Anti-CCP B, RF C, Anti-CCP C, CRP D, RF D, and Anti-CCP D with the highest level of f2 between other models. In addition, statistical tests show that progesterone D with R2= 0.565 and RMSE equal to 0.996 have heteroscedasticity, which means that low levels of progesterone are associated inversely with high levels of RF and Anit-CCP. There is a relative association between the progesterone D model and corresponding predictions. Regardless of solid f2, only 56 % of the sample shows an association between the model and predictors; this relation may differ if we consider the study's limitations.
{"title":"Low progesterone levels and their role in the co-existence of polycystic ovary syndrome and rheumatoid arthritis: A comprehensive analysis among Iraqi patient","authors":"Mohammed Mahdi Sami , Mataz J. Jamai , Tamara Ahmed Abd Alkareem , Nabeel Bunyan Ayram","doi":"10.1016/j.jsbmb.2025.106680","DOIUrl":"10.1016/j.jsbmb.2025.106680","url":null,"abstract":"<div><div>Polycystic ovarian syndrome (PCOS) is a low-grade and chronic inflammation defined by irregular hormonal status that primarily triggers females in their reproductive age. Multi cysts are a primary manifestation of PCOS; a high level of androgen production characterizes the condition via ovaries. Rheumatoid arthritis (RA) is a chronic, systemic, and symmetrical inflammatory autoimmune disease that affects 1–2 % of adults. Females are more likely to generate RA. During the inflammatory activity, immune cells attack the synovium and the synovial space. This invasion is essential in releasing many cytokines in the synovial and joint spaces, leading to joint damage and pain, stiffens, heat, and tenderness in the joint. To evaluate the strength of the link between PCOS and RA, the cross-sectional study examined hormonal, metabolic, and autoantibodies in PCOS, RA as a positive control and the study groups. Statistical analysis Shapiro-Wilk test, student t-test, one-way ANOVA, and multi-linear regression analysis were used to evaluate the results. The data highlights significant values for the BMI, WHR, and hirsutism of PCOS and RA groups in comparison to the negative control. The ANOVA results of these parameters also showed a significant p < 0.05 among the groups. According to the negative control, the levels of insulin, HOMA-IR, testosterone, LH, estradiol, and CRP showed a substantial increase in the PCOS group. Also, the RA group showed a significant p < 0.05 rise in CRP, RF, and Ani-CCP, and the ANOVA results showed significant value among the groups under investigation. Progesterone D as a model showed a correlation with Anti-CCP B, RF C, Anti-CCP C, CRP D, RF D, and Anti-CCP D with the highest level of f<sup>2</sup> between other models. In addition, statistical tests show that progesterone D with R<sup>2</sup>= 0.565 and RMSE equal to 0.996 have heteroscedasticity, which means that low levels of progesterone are associated inversely with high levels of RF and Anit-CCP. There is a relative association between the progesterone D model and corresponding predictions. Regardless of solid f<sup>2</sup>, only 56 % of the sample shows an association between the model and predictors; this relation may differ if we consider the study's limitations.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"247 ","pages":"Article 106680"},"PeriodicalIF":2.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054226","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}
Pub Date : 2025-01-21DOI: 10.1016/j.jsbmb.2025.106679
Deborah Simão Souza , Carolina Meloni Vicente , Carla Macheroni , Vanessa Leiria Campo , Catarina Segreti Porto
The aims of this study were to investigate the localization of non-phosphorylated β‑catenin and Galectin-3 (GAL-3), the regulation of the expression of both proteins by activation of estrogen receptors (ERs) and their role in tumorigenic characteristics of androgen-independent prostate cancer DU-145 cells. DU-145 cells were cultured in the absence (control), and presence of 17β-estradiol (E2). Cells were also untreated or pre-treated with the inhibitor of GAL‑3, VA03, or with a compound that disrupts the complex β-catenin-TCF/LEF transcription factor, PKF 118–310. Immunofluorescence assay for non-phosphorylated β-catenin and GAL-3, cell proliferation, wound healing and cell invasion assays were performed. 17β-estradiol (E2, 4 h) increased the expression of non-phosphorylated β-catenin and GAL-3. E2 also increased (2-fold) the co-localization of the fluorescence of non-phosphorylated β-catenin and GAL‑3 in the whole cells compared to the control. The up-regulation of non-phosphorylated β-catenin expression was blocked by VA03, suggesting that GAL-3 is upstream protein involved in this process. E2 (24 h) increased the cell number, migration, and invasion of the DU‑145 cells compared to control. Furthermore, PKF 118–310 completely blocked the proliferation, migration, and invasion of the DU-145 cells induced by activation of ERs. The activation of ERs increases the expression, co-localization and signaling of the GAL-3 and non-phosphorylated β-catenin in DU-145 cells. Non-phosphorylated β-catenin is downstream protein involved in proliferation, migration, and invasion of the DU‑145 cells.
{"title":"Signaling crosstalk of Galectin-3, β-catenin, and estrogen receptor in androgen-independent prostate cancer DU-145 cells","authors":"Deborah Simão Souza , Carolina Meloni Vicente , Carla Macheroni , Vanessa Leiria Campo , Catarina Segreti Porto","doi":"10.1016/j.jsbmb.2025.106679","DOIUrl":"10.1016/j.jsbmb.2025.106679","url":null,"abstract":"<div><div>The aims of this study were to investigate the localization of non-phosphorylated β‑catenin and Galectin-3 (GAL-3), the regulation of the expression of both proteins by activation of estrogen receptors (ERs) and their role in tumorigenic characteristics of androgen-independent prostate cancer DU-145 cells. DU-145 cells were cultured in the absence (control), and presence of 17β-estradiol (E2). Cells were also untreated or pre-treated with the inhibitor of GAL‑3, VA03, or with a compound that disrupts the complex β-catenin-TCF/LEF transcription factor, PKF 118–310. Immunofluorescence assay for non-phosphorylated β-catenin and GAL-3, cell proliferation, wound healing and cell invasion assays were performed. 17β-estradiol (E2, 4 h) increased the expression of non-phosphorylated β-catenin and GAL-3. E2 also increased (2-fold) the co-localization of the fluorescence of non-phosphorylated β-catenin and GAL‑3 in the whole cells compared to the control. The up-regulation of non-phosphorylated β-catenin expression was blocked by VA03, suggesting that GAL-3 is upstream protein involved in this process. E2 (24 h) increased the cell number, migration, and invasion of the DU‑145 cells compared to control. Furthermore, PKF 118–310 completely blocked the proliferation, migration, and invasion of the DU-145 cells induced by activation of ERs. The activation of ERs increases the expression, co-localization and signaling of the GAL-3 and non-phosphorylated β-catenin in DU-145 cells. Non-phosphorylated β-catenin is downstream protein involved in proliferation, migration, and invasion of the DU‑145 cells.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"247 ","pages":"Article 106679"},"PeriodicalIF":2.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029695","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}
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