Journal of Steroid Biochemistry and Molecular Biology最新文献_第2页

COVID-19 and our understanding of vitamin D and immune function

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-02-20 DOI: 10.1016/j.jsbmb.2025.106710

Martin Hewison

The interaction between vitamin D and the immune system is perhaps the most well recognised extraskeletal facet of vitamin D, encompassing early studies of therapy for TB and leprosy through to more recent links with autoimmune disease. However, the spotlight on vitamin D and immune function has been particularly intense in the last five years following the COVID-19 pandemic. This was due, in part, to the many association studies of vitamin D status and COVID-19 infection and disease prognosis, as well as the smaller number of clinical trials of vitamin D supplementation. However, a potential role for vitamin D in COVID-19 also stemmed from the basic biology of vitamin D that provides a plausible mechanistic rationale for beneficial effects of vitamin D for improved immune health in the setting of respiratory infection. The aim of this review is to summarise the different strands of mechanistic evidence supporting a beneficial effect of vitamin D in COVID-19, how this was modified during the pandemic itself, and the potential new aspects of vitamin D and immune function that are likely to arise in the near future. Key topics that feature in this review are: antibacterial versus antiviral innate immune responses to 1,25-dihydroxyvitamin D (1,25(OH)₂D); the function of immune 1α-hydroxylase (CYP27B1) activity and metabolism of 25-hydroxyvitamin D (25(OH)D) beyond antigen-presenting cells; advances in immune cell target gene responses to 1,25-dihydroxyvitamin D (notably changes in metabolic profile). Whilst much of the interest during the COVID-19 era has focused on vitamin D and public health, the continued evolution of our understanding of how vitamin D interacts with different components of the immune system continues to support a beneficial role for vitamin D in immune health.

{"title":"COVID-19 and our understanding of vitamin D and immune function","authors":"Martin Hewison","doi":"10.1016/j.jsbmb.2025.106710","DOIUrl":"10.1016/j.jsbmb.2025.106710","url":null,"abstract":"<div><div>The interaction between vitamin D and the immune system is perhaps the most well recognised extraskeletal facet of vitamin D, encompassing early studies of therapy for TB and leprosy through to more recent links with autoimmune disease. However, the spotlight on vitamin D and immune function has been particularly intense in the last five years following the COVID-19 pandemic. This was due, in part, to the many association studies of vitamin D status and COVID-19 infection and disease prognosis, as well as the smaller number of clinical trials of vitamin D supplementation. However, a potential role for vitamin D in COVID-19 also stemmed from the basic biology of vitamin D that provides a plausible mechanistic rationale for beneficial effects of vitamin D for improved immune health in the setting of respiratory infection. The aim of this review is to summarise the different strands of mechanistic evidence supporting a beneficial effect of vitamin D in COVID-19, how this was modified during the pandemic itself, and the potential new aspects of vitamin D and immune function that are likely to arise in the near future. Key topics that feature in this review are: antibacterial versus antiviral innate immune responses to 1,25-dihydroxyvitamin D (1,25(OH)<sub>2</sub>D); the function of immune 1α-hydroxylase (CYP27B1) activity and metabolism of 25-hydroxyvitamin D (25(OH)D) beyond antigen-presenting cells; advances in immune cell target gene responses to 1,25-dihydroxyvitamin D (notably changes in metabolic profile). Whilst much of the interest during the COVID-19 era has focused on vitamin D and public health, the continued evolution of our understanding of how vitamin D interacts with different components of the immune system continues to support a beneficial role for vitamin D in immune health.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"249 ","pages":"Article 106710"},"PeriodicalIF":2.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454764","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}

引用次数: 0

Unveiling 2-isopropyl-5-methylphenol’s immunomodulatory potential in breast cancer: A synergistic computational and laboratory investigation

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-02-13 DOI: 10.1016/j.jsbmb.2025.106702

Mehr Un Nissa Bashir , Muhammad Usman Rashid , Naila Malkani

Tumor cells evade immune surveillance and promote their growth by modulating immune checkpoint molecules (ICMs). Various breast cancer subtypes have demonstrated the involvement of these molecules, promoting the investigation of natural compounds for immunomodulatory potential. 2-Isopropyl-5-methylphenol, a bioactive monoterpenoid found in several plant species, was evaluated for its impact on breast cancer immunomodulation. Computational and in-vitro studies were conducted to evaluate 2-Isopropyl-5-methylphenol’s immunomodulatory potential. Molecular docking of ICMs (CTLA-4, PD-1, and PD-L1) with 2-Isopropyl-5-methylphenol was performed using AutoDock Vina. Additional tools utilized were BIOVIA Discovery Studio 2021, PyMOL, and LigPlot⁺. The mRNA expression of ICMs upon treatment of breast cancer cells (MDA-MB-231) with varying concentrations (50, 100, and 200 µg) of 2-Isopropyl-5-methylphenol was measured by qPCR. Docking complexes of CTLA-4, PD-1, and PD-L1 with 2-Isopropyl-5-methylphenol showed binding free energies of −4.3 kcal/mol, −5.2 kcal/mol and −4.4 kcal/mol, respectively. Involvement of different key amino acid residues strengthened 2-Isopropyl-5-methylphenol’s binding with ICMs. Expression analysis revealed 2-Isopropyl-5-methylphenol downregulated CTLA-4 expression while upregulated PD-1 and PD-L1 expression. This study highlights the immunomodulatory potential of the bioactive monoterpene 2-Isopropyl-5-methylphenol. Supported by computational and in-vitro findings, 2-Isopropyl-5-methylphenol could be considered as a potential target for anti-tumor drug development.

{"title":"Unveiling 2-isopropyl-5-methylphenol’s immunomodulatory potential in breast cancer: A synergistic computational and laboratory investigation","authors":"Mehr Un Nissa Bashir , Muhammad Usman Rashid , Naila Malkani","doi":"10.1016/j.jsbmb.2025.106702","DOIUrl":"10.1016/j.jsbmb.2025.106702","url":null,"abstract":"<div><div>Tumor cells evade immune surveillance and promote their growth by modulating immune checkpoint molecules (ICMs). Various breast cancer subtypes have demonstrated the involvement of these molecules, promoting the investigation of natural compounds for immunomodulatory potential. 2-Isopropyl-5-methylphenol, a bioactive monoterpenoid found in several plant species, was evaluated for its impact on breast cancer immunomodulation. Computational and <em>in-vitro</em> studies were conducted to evaluate 2-Isopropyl-5-methylphenol’s immunomodulatory potential. Molecular docking of ICMs (CTLA-4, PD-1, and PD-L1) with 2-Isopropyl-5-methylphenol was performed using AutoDock Vina. Additional tools utilized were BIOVIA Discovery Studio 2021, PyMOL, and LigPlot<sup>+</sup>. The mRNA expression of ICMs upon treatment of breast cancer cells (MDA-MB-231) with varying concentrations (50, 100, and 200 µg) of 2-Isopropyl-5-methylphenol was measured by qPCR. Docking complexes of CTLA-4, PD-1, and PD-L1 with 2-Isopropyl-5-methylphenol showed binding free energies of −4.3 kcal/mol, −5.2 kcal/mol and −4.4 kcal/mol, respectively. Involvement of different key amino acid residues strengthened 2-Isopropyl-5-methylphenol’s binding with ICMs. Expression analysis revealed 2-Isopropyl-5-methylphenol downregulated <em>CTLA-4</em> expression while upregulated <em>PD-1</em> and <em>PD-L1</em> expression. This study highlights the immunomodulatory potential of the bioactive monoterpene 2-Isopropyl-5-methylphenol. Supported by computational and <em>in-vitro</em> findings, 2-Isopropyl-5-methylphenol could be considered as a potential target for anti-tumor drug development.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"248 ","pages":"Article 106702"},"PeriodicalIF":2.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419622","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

Impact of copper nanoparticles (CuNPs) on hypothalamic GnRH and pituitary gonadotropins secretions in a male mouse: An immunohistochemical study

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-02-13 DOI: 10.1016/j.jsbmb.2025.106700

Vanrohlu Nicy, Guruswami Gurusubramanian, Vikas Kumar Roy

The copper nanoparticles (CuNPs) have widely been used for human welfare in the various applications. Despite its uses for beneficial purposes, CuNPs has been known to cause toxicity in the various organ based on the size, dose and duration. Both male and female reproductive functions have been to be compromised under CuNPs toxicity. The aim of this study is to investigate the effects of CuNPs after prolonged duration on the hypothalamus and pituitary in relation to the neuroendocrine regulation of reproduction in male mice since it has not been done before. Due to which the mice were orally treated with three doses of CuNPs viz. 10,100 and 200 mg/kg for 70 consecutive days to examines its adverse effects. The circulating GnRH levels and its abundance in the median eminence did not change in the CuNPs treated groups. However, circulating FSH showed significant decline in all the CuNPs treated groups, while LH was decline only in higher doses of CuNPs. The immunolocalization of LH and FSH also showed decreased abundance in the pituitary. Thus, pituitary function showed severely affected by CuNPs; the architecture of anterior pituitary also showed sign of degeneration such a presence of vacuoles and it was also shown that CuNPs treated groups have higher level of MDA which is an oxidative stress marker as indicated by the MDA staining. Moreover, the abundance of GnRHR and AR exhibited less abundance in the pituitary of higher dose of CuNPs treated groups. Thus, it can be concluded that pituitary becomes less responsive for hypothalamic GnRH and gonadal steroid, which could be reason of suppressed gonadotropin in the CuNPs treated mice.

{"title":"Impact of copper nanoparticles (CuNPs) on hypothalamic GnRH and pituitary gonadotropins secretions in a male mouse: An immunohistochemical study","authors":"Vanrohlu Nicy, Guruswami Gurusubramanian, Vikas Kumar Roy","doi":"10.1016/j.jsbmb.2025.106700","DOIUrl":"10.1016/j.jsbmb.2025.106700","url":null,"abstract":"<div><div>The copper nanoparticles (CuNPs) have widely been used for human welfare in the various applications. Despite its uses for beneficial purposes, CuNPs has been known to cause toxicity in the various organ based on the size, dose and duration. Both male and female reproductive functions have been to be compromised under CuNPs toxicity. The aim of this study is to investigate the effects of CuNPs after prolonged duration on the hypothalamus and pituitary in relation to the neuroendocrine regulation of reproduction in male mice since it has not been done before. Due to which the mice were orally treated with three doses of CuNPs viz. 10,100 and 200 mg/kg for 70 consecutive days to examines its adverse effects. The circulating GnRH levels and its abundance in the median eminence did not change in the CuNPs treated groups. However, circulating FSH showed significant decline in all the CuNPs treated groups, while LH was decline only in higher doses of CuNPs. The immunolocalization of LH and FSH also showed decreased abundance in the pituitary. Thus, pituitary function showed severely affected by CuNPs; the architecture of anterior pituitary also showed sign of degeneration such a presence of vacuoles and it was also shown that CuNPs treated groups have higher level of MDA which is an oxidative stress marker as indicated by the MDA staining. Moreover, the abundance of GnRHR and AR exhibited less abundance in the pituitary of higher dose of CuNPs treated groups. Thus, it can be concluded that pituitary becomes less responsive for hypothalamic GnRH and gonadal steroid, which could be reason of suppressed gonadotropin in the CuNPs treated mice.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"248 ","pages":"Article 106700"},"PeriodicalIF":2.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419624","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

Antiepileptic drugs carbamazepine and valproic acid mediate transcriptional activation of CYP1A1 via aryl hydrocarbon receptor and regulation of estrogen metabolism

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-02-12 DOI: 10.1016/j.jsbmb.2025.106699

Neha Kanojia , Samiksha Kukal , Nitin Machahary , Shivangi Bora , Ankit Srivastava , Priyanka Rani Paul , Shakti Sagar , Reema Kumar , Gurpreet Kaur Grewal , Srishti Sharma , Binukumar B.K. , Ritushree Kukreti

Cytochrome P450 1A1 (CYP1A1) actively catalyzes estrogen hydroxylation reactions and maintains the levels of neuroactive steroid estradiol. The widely prescribed first-line anti-epileptic drugs (AEDs) are considered to be a potent inducer of CYP1A1 and have also been observed to affect serum estradiol and calcium levels in patients with epilepsy. However, the ability of AEDs to interfere with CYP enzyme function and estrogen disposition is a relatively unexplored area. Here we investigate the effect of widely prescribed AEDs (carbamazepine and valproic acid) on CYP1A1 regulation and the levels of estradiol and calcium in cell supernatants of hepatocellular, HepG2, and neuronal, SH-SY5Y cells. We observed that both the AEDs significantly increased CYP1A1 expression and enzyme activity, which was accompanied by a decrease in estradiol and calcium levels in HepG2 cells. This induction of CYP1A1 mRNA and protein was fully prevented by aryl hydrocarbon receptor (AHR) knockdown and StemRegenin 1 (SR1) antagonism. Notably, the AEDs did not affect the AHR expression but regulated its nuclear translocation, potentially driving the transcriptional upregulation of CYP1A1. Furthermore, the knockdown of CYP1A1 in HepG2 cells elucidated a marked increase in estradiol and calcium levels. Later, this increase subsided upon AED exposure. Lastly, we observed a similar trend in estradiol and calcium alterations in SH-SY5Y cells on AED exposure, speculating the involvement of CYP1A1 induction via AEDs at neuronal sites. This work demonstrates that AEDs mediate the upregulation of CYP1A1 via an AHR-dependent mechanism and influence estrogen and calcium homeostasis.

{"title":"Antiepileptic drugs carbamazepine and valproic acid mediate transcriptional activation of CYP1A1 via aryl hydrocarbon receptor and regulation of estrogen metabolism","authors":"Neha Kanojia , Samiksha Kukal , Nitin Machahary , Shivangi Bora , Ankit Srivastava , Priyanka Rani Paul , Shakti Sagar , Reema Kumar , Gurpreet Kaur Grewal , Srishti Sharma , Binukumar B.K. , Ritushree Kukreti","doi":"10.1016/j.jsbmb.2025.106699","DOIUrl":"10.1016/j.jsbmb.2025.106699","url":null,"abstract":"<div><div>Cytochrome P450 1A1 (<em>CYP1A1</em>) actively catalyzes estrogen hydroxylation reactions and maintains the levels of neuroactive steroid estradiol. The widely prescribed first-line anti-epileptic drugs (AEDs) are considered to be a potent inducer of <em>CYP1A1</em> and have also been observed to affect serum estradiol and calcium levels in patients with epilepsy. However, the ability of AEDs to interfere with CYP enzyme function and estrogen disposition is a relatively unexplored area. Here we investigate the effect of widely prescribed AEDs (carbamazepine and valproic acid) on <em>CYP1A1</em> regulation and the levels of estradiol and calcium in cell supernatants of hepatocellular, HepG2, and neuronal, SH-SY5Y cells. We observed that both the AEDs significantly increased <em>CYP1A1</em> expression and enzyme activity, which was accompanied by a decrease in estradiol and calcium levels in HepG2 cells. This induction of <em>CYP1A1</em> mRNA and protein was fully prevented by aryl hydrocarbon receptor (<em>AHR</em>) knockdown and StemRegenin 1 (SR1) antagonism. Notably, the AEDs did not affect the <em>AHR</em> expression but regulated its nuclear translocation, potentially driving the transcriptional upregulation of <em>CYP1A1</em>. Furthermore, the knockdown of <em>CYP1A1</em> in HepG2 cells elucidated a marked increase in estradiol and calcium levels. Later, this increase subsided upon AED exposure. Lastly, we observed a similar trend in estradiol and calcium alterations in SH-SY5Y cells on AED exposure, speculating the involvement of <em>CYP1A1</em> induction via AEDs at neuronal sites. This work demonstrates that AEDs mediate the upregulation of <em>CYP1A1</em> via an AHR-dependent mechanism and influence estrogen and calcium homeostasis.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"248 ","pages":"Article 106699"},"PeriodicalIF":2.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426572","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 effect of vitamin D supplementation on mental and functional health outcomes in African Americans with type 2 diabetes

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-02-12 DOI: 10.1016/j.jsbmb.2025.106698

Kai E. Jones , Amy E. Riek , Esmeralda Castelblanco , Jisu Oh , Daniela Porta , Claudia Villatoro , Robert M. Carney , Adriana S. Dusso , Carlos Bernal-Mizrachi

In patients with type 2 diabetes (T2DM), depression increases the risk of poor glycemic control and decreases adherence to medications, exercise, and diet. Studies have shown an inverse relationship between plasma vitamin D (VD) level and depression risk. However, there are few interventional trials of African Americans (AAs), a demographic with higher prevalence of diabetes, depression, and VD deficiency. This randomized controlled trial evaluated the efficacy of vitamin D₃ supplementation [4000 vs. 600 international units (IU)/day] for one year on mental and functional health outcomes in 75 adult AAs with T2DM with serum 25-hydroxy vitamin D (25(OH)D) level < 25 ng/mL. PHQ-9 and PROMIS questionnaires evaluated mental health outcomes, and 6-minute walk test estimated the ability to perform daily activities. At baseline, groups had similar levels of 25(OH)D, calcium, parathyroid hormone, hemoglobin A1c, and body mass index, and 25(OH)D levels correlated positively with a 6-minute walk distance. Surprisingly, both supplementation strategies increased 25(OH)D to > 30 ng/mL by 6 months with a plateau thereafter. Vitamin D₃ 4000 IU/day in AAs with T2DM did not produce significant difference in mental and functional health scores compared to 600 IU/day. Post-hoc analysis of those with baseline VD deficiency [25(OH)D < 20 ng/mL] demonstrated trends towards worsening pain interference and higher depression and fatigue scores throughout the study, plus consistently shorter 6-minute walk distances, most of which were independent of vitamin D supplementation group. These results suggest that VD deficient AAs with T2DM may be refractory to supplementation for improvement in mental and functional health outcomes.

{"title":"The effect of vitamin D supplementation on mental and functional health outcomes in African Americans with type 2 diabetes","authors":"Kai E. Jones , Amy E. Riek , Esmeralda Castelblanco , Jisu Oh , Daniela Porta , Claudia Villatoro , Robert M. Carney , Adriana S. Dusso , Carlos Bernal-Mizrachi","doi":"10.1016/j.jsbmb.2025.106698","DOIUrl":"10.1016/j.jsbmb.2025.106698","url":null,"abstract":"<div><div>In patients with type 2 diabetes (T2DM), depression increases the risk of poor glycemic control and decreases adherence to medications, exercise, and diet. Studies have shown an inverse relationship between plasma vitamin D (VD) level and depression risk. However, there are few interventional trials of African Americans (AAs), a demographic with higher prevalence of diabetes, depression, and VD deficiency. This randomized controlled trial evaluated the efficacy of vitamin D<sub>3</sub> supplementation [4000 vs. 600 international units (IU)/day] for one year on mental and functional health outcomes in 75 adult AAs with T2DM with serum 25-hydroxy vitamin D (25(OH)D) level < 25 ng/mL. PHQ-9 and PROMIS questionnaires evaluated mental health outcomes, and 6-minute walk test estimated the ability to perform daily activities. At baseline, groups had similar levels of 25(OH)D, calcium, parathyroid hormone, hemoglobin A1c, and body mass index, and 25(OH)D levels correlated positively with a 6-minute walk distance. Surprisingly, both supplementation strategies increased 25(OH)D to > 30 ng/mL by 6 months with a plateau thereafter. Vitamin D<sub>3</sub> 4000 IU/day in AAs with T2DM did not produce significant difference in mental and functional health scores compared to 600 IU/day. Post-hoc analysis of those with baseline VD deficiency [25(OH)D < 20 ng/mL] demonstrated trends towards worsening pain interference and higher depression and fatigue scores throughout the study, plus consistently shorter 6-minute walk distances, most of which were independent of vitamin D supplementation group. These results suggest that VD deficient AAs with T2DM may be refractory to supplementation for improvement in mental and functional health outcomes.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"248 ","pages":"Article 106698"},"PeriodicalIF":2.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419623","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

Mechanistic insights into the anti-fibrotic effects of estrogen via the PI3K-Akt pathway in frozen shoulder

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-02-11 DOI: 10.1016/j.jsbmb.2025.106701

Zhuo Wang , Xinhao Li , Xiaoshan Liu , Yitao Yang , Yan Yan , Dedong Cui , Chenyang Meng , Maslah Idiris Ali , Jinming Zhang , Zeyu Yao , Yi Long , Rui Yang

The development of frozen shoulder (FS) is primarily characterized by pathological fibrosis, yet clinical treatment options remain limited. Recent studies have identified estrogen depletion during perimenopause as a significant contributor to the onset of FS and fibrosis. This study investigates the role of estradiol (E2) and the estrogen-related receptor (GPER) in fibrotic processes associated with FS to elucidate the underlying mechanisms. The functional relationship between E2, GPER, and FS progression was examined using a rat immobilization model and synovial-derived fibroblasts (SFs) from FS patients. E2’s effects on GPER expression, fibroblast activation, and tissue fibrosis were evaluated through Western blotting, immunofluorescence staining, collagen contraction assays, wound healing assays, and histological staining. RNA sequencing identified signaling pathways and key regulators involved in E2 treatment. Both E2 and the GPER activator G1 exhibited antifibrotic effects, improving shoulder mobility, reducing extracellular matrix (ECM) deposition in the periarticular capsule, and decreasing the expression of fibrosis-related genes, including fibronectin, α-SMA, and COL3. In contrast, the GPER inhibitor G15 reversed these effects, suggesting that E2 mediates its antifibrotic action through GPER activation. Mechanistically, KEGG pathway analysis revealed that E2 suppresses the PI3K/AKT signaling pathway by inhibiting PI3K and AKT phosphorylation, thereby preventing fibroblast activation and reversing FS-associated fibrosis. These findings provide mechanistic insights into the previously unrecognized role of GPER in FS progression and may open new avenues for research to optimize future clinical therapies.

{"title":"Mechanistic insights into the anti-fibrotic effects of estrogen via the PI3K-Akt pathway in frozen shoulder","authors":"Zhuo Wang , Xinhao Li , Xiaoshan Liu , Yitao Yang , Yan Yan , Dedong Cui , Chenyang Meng , Maslah Idiris Ali , Jinming Zhang , Zeyu Yao , Yi Long , Rui Yang","doi":"10.1016/j.jsbmb.2025.106701","DOIUrl":"10.1016/j.jsbmb.2025.106701","url":null,"abstract":"<div><div>The development of frozen shoulder (FS) is primarily characterized by pathological fibrosis, yet clinical treatment options remain limited. Recent studies have identified estrogen depletion during perimenopause as a significant contributor to the onset of FS and fibrosis. This study investigates the role of estradiol (E2) and the estrogen-related receptor (GPER) in fibrotic processes associated with FS to elucidate the underlying mechanisms. The functional relationship between E2, GPER, and FS progression was examined using a rat immobilization model and synovial-derived fibroblasts (SFs) from FS patients. E2’s effects on GPER expression, fibroblast activation, and tissue fibrosis were evaluated through Western blotting, immunofluorescence staining, collagen contraction assays, wound healing assays, and histological staining. RNA sequencing identified signaling pathways and key regulators involved in E2 treatment. Both E2 and the GPER activator G1 exhibited antifibrotic effects, improving shoulder mobility, reducing extracellular matrix (ECM) deposition in the periarticular capsule, and decreasing the expression of fibrosis-related genes, including fibronectin, α-SMA, and COL3. In contrast, the GPER inhibitor G15 reversed these effects, suggesting that E2 mediates its antifibrotic action through GPER activation. Mechanistically, KEGG pathway analysis revealed that E2 suppresses the PI3K/AKT signaling pathway by inhibiting PI3K and AKT phosphorylation, thereby preventing fibroblast activation and reversing FS-associated fibrosis. These findings provide mechanistic insights into the previously unrecognized role of GPER in FS progression and may open new avenues for research to optimize future clinical therapies.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"249 ","pages":"Article 106701"},"PeriodicalIF":2.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416249","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

Determination of steroid reference intervals in a pregnancy population

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-02-06 DOI: 10.1016/j.jsbmb.2025.106691

Marius Lahti-Pulkkinen , Katri Räikkönen , Agnieszka Basiukajc , Patricia Lee , Scott G. Denham , Joanna P. Simpson , Pia Villa , Esa Hämäläinen , Hannele Laivuori , Eero Kajantie , Kati Heinonen , Polina Girchenko , Rebecca M. Reynolds , Natalie ZM Homer

Steroids, including mineralocorticoids, glucocorticoids, and sex hormones play a critical role in pregnancy. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis offers an opportunity to conduct simultaneous multiplex steroid analysis within a given sample. This paper describes the LC-MS/MS steroid analysis method developed for assessing plasma specific reference ranges of 18 steroids from plasma samples (200 µL) of pregnant women participating in the PREDO study. Samples were prepared using supported liquid extraction and analyzed on an Acquity I-Class UPLC and a QTrap6500 + mass spectrometer. Mass spectrometry parameters were optimized for each steroid and chromatographic separation of 18 steroids was developed. Changes in steroid levels across pregnancy were assessed. Samples were collected after an overnight fast between 07:00 and 09:00. Data from 257 samples from 96 women with uncomplicated pregnancy (women with pre-pregnancy normal weight and no diabetes or hypertensive disorders before or during pregnancy, who delivered a live child at ≥ 37 weeks of gestation with appropriate for gestational age birth weight) were analyzed to calculate steroid reference ranges over three time points, between 11.6 and 14.3, 17.7–22.9, and 25.6–29.0 pregnancy weeks. Levels of progestogens, glucocorticoids, mineralocorticoids, estrogens, their precursors, and metabolites increased significantly across pregnancy. Androgen levels remained stable, except for a decrease in 5α-dihydrotestosterone. The LC-MS/MS method also showed validity in analyses of 917 samples of 328 women with complicated pregnancies. The method is suitable for the analysis of 18 steroids in plasma during pregnancy and the investigation of pregnancy complications, fetal growth, and development after birth.

{"title":"Determination of steroid reference intervals in a pregnancy population","authors":"Marius Lahti-Pulkkinen , Katri Räikkönen , Agnieszka Basiukajc , Patricia Lee , Scott G. Denham , Joanna P. Simpson , Pia Villa , Esa Hämäläinen , Hannele Laivuori , Eero Kajantie , Kati Heinonen , Polina Girchenko , Rebecca M. Reynolds , Natalie ZM Homer","doi":"10.1016/j.jsbmb.2025.106691","DOIUrl":"10.1016/j.jsbmb.2025.106691","url":null,"abstract":"<div><div>Steroids, including mineralocorticoids, glucocorticoids, and sex hormones play a critical role in pregnancy. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis offers an opportunity to conduct simultaneous multiplex steroid analysis within a given sample. This paper describes the LC-MS/MS steroid analysis method developed for assessing plasma specific reference ranges of 18 steroids from plasma samples (200 µL) of pregnant women participating in the PREDO study. Samples were prepared using supported liquid extraction and analyzed on an Acquity I-Class UPLC and a QTrap6500 + mass spectrometer. Mass spectrometry parameters were optimized for each steroid and chromatographic separation of 18 steroids was developed. Changes in steroid levels across pregnancy were assessed. Samples were collected after an overnight fast between 07:00 and 09:00. Data from 257 samples from 96 women with uncomplicated pregnancy (women with pre-pregnancy normal weight and no diabetes or hypertensive disorders before or during pregnancy, who delivered a live child at ≥ 37 weeks of gestation with appropriate for gestational age birth weight) were analyzed to calculate steroid reference ranges over three time points, between 11.6 and 14.3, 17.7–22.9, and 25.6–29.0 pregnancy weeks. Levels of progestogens, glucocorticoids, mineralocorticoids, estrogens, their precursors, and metabolites increased significantly across pregnancy. Androgen levels remained stable, except for a decrease in 5α-dihydrotestosterone. The LC-MS/MS method also showed validity in analyses of 917 samples of 328 women with complicated pregnancies. The method is suitable for the analysis of 18 steroids in plasma during pregnancy and the investigation of pregnancy complications, fetal growth, and development after birth.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"248 ","pages":"Article 106691"},"PeriodicalIF":2.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374932","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}

引用次数: 0

Supportive effect of corticosteroid on bone marrow recovery in FLT3/ITD positive acute myeloid leukemia with trisomy 13

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-02-06 DOI: 10.1016/j.jsbmb.2025.106697

Rie Tabata , Naoki Yamamoto , Chiharu Tabata

Trisomy 13 is a rare chromosomal abnormality mainly observed in patients with FAB M0, and is associated with increased FLT3 expression, characterized by aggressive and inferior outcomes. Herein, we describe a case of FLT3/ITD-positive acute myeloid leukemia with trisomy 13, whose neutropenia and thrombocytopenia were improved by corticosteroids with a decrease in blasts in the peripheral blood without chemotherapy. Only short-term chemotherapy could be administered because of the patient’s poor general condition. In contrast, repeated administration of methylprednisolone pulse therapy followed by high-dose prednisolone was required to control the interstitial pneumonitis. Although appropriate chemotherapy, such as oral administration of FLT inhibitors, could not be administered, a dramatic decrease in blasts and an increase in both neutrophils and platelets were observed. The addition of corticosteroids to chemotherapy is associated with a better clinical course in patients with hyperleukocytic and pediatric acute myeloid leukemia. In the present patient, the peripheral WBC count was not high, the steroids allowed for the recovery of normal hematopoiesis with diminishing blasts. Although stem cell transplantation is necessary to improve overall survival for aggressive acute myeloid leukemia, intensive chemotherapy cannot often be administered in frail older patients. Lower dose of steroids might be able to effectively control acute myeloid leukemia without serious adverse effects, resulting in a better clinical course in frail older patients with acute myeloid leukemia.

{"title":"Supportive effect of corticosteroid on bone marrow recovery in FLT3/ITD positive acute myeloid leukemia with trisomy 13","authors":"Rie Tabata , Naoki Yamamoto , Chiharu Tabata","doi":"10.1016/j.jsbmb.2025.106697","DOIUrl":"10.1016/j.jsbmb.2025.106697","url":null,"abstract":"<div><div>Trisomy 13 is a rare chromosomal abnormality mainly observed in patients with FAB M0, and is associated with increased <em>FLT3</em> expression, characterized by aggressive and inferior outcomes. Herein, we describe a case of <em>FLT3/</em>ITD-positive acute myeloid leukemia with trisomy 13, whose neutropenia and thrombocytopenia were improved by corticosteroids with a decrease in blasts in the peripheral blood without chemotherapy. Only short-term chemotherapy could be administered because of the patient’s poor general condition. In contrast, repeated administration of methylprednisolone pulse therapy followed by high-dose prednisolone was required to control the interstitial pneumonitis. Although appropriate chemotherapy, such as oral administration of FLT inhibitors, could not be administered, a dramatic decrease in blasts and an increase in both neutrophils and platelets were observed. The addition of corticosteroids to chemotherapy is associated with a better clinical course in patients with hyperleukocytic and pediatric acute myeloid leukemia. In the present patient, the peripheral WBC count was not high, the steroids allowed for the recovery of normal hematopoiesis with diminishing blasts. Although stem cell transplantation is necessary to improve overall survival for aggressive acute myeloid leukemia, intensive chemotherapy cannot often be administered in frail older patients. Lower dose of steroids might be able to effectively control acute myeloid leukemia without serious adverse effects, resulting in a better clinical course in frail older patients with acute myeloid leukemia.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"248 ","pages":"Article 106697"},"PeriodicalIF":2.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350481","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

Comparison of 7-dehydrocholesterol and cholesterol in whole blood vs. plasma samples for diagnosis of SLOS

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-02-06 DOI: 10.1016/j.jsbmb.2025.106682

Zhibin Huang , Yitao Luo , Chao Zhang , Wei Wu , Yangxi Li , Li Ma , Qingxia Zhang , Yulan Rao , Chengqiang Zhang

Background

Smith-Lemli-Opitz Syndrome (SLOS) is an autosomal recessive disorder characterized by specific clinical features. This study investigated the correlation and transference ratio of 7-dehydrocholesterol (7-DHC) and cholesterol (CHOL) as screening/diagnostic markers for SLOS in whole blood and plasma samples.

Methods

The gas chromatography-mass spectrometry (GC-MS) method was employed to analyze whole blood and plasma samples collected from 28 healthy volunteers and one patient with SLOS. Before analysis, an optimized and validated assay for 7-DHC and CHOL in whole blood was developed. Pearson’s correlation analysis was then performed to assess the correlation between the levels of 7-DHC and CHOL in whole blood and plasma.

Results

The correlation analysis revealed a significant correlation between the levels of 7-DHC and CHOL in whole blood and plasma, with correlation coefficients (r) greater than 0.5 (0.565 for 7-DHC and 0.692 for CHOL). These findings suggest the feasibility of transference between whole blood and plasma samples.

Conclusions

Whole blood can be considered an optimal alternative diagnostic tool for predicting SLOS in carriers, surpassing the reliance on plasma alone. This study introduces a new diagnostic matrix for determining 7-DHC and CHOL, expanding the scope of SLOS diagnosis and research.

{"title":"Comparison of 7-dehydrocholesterol and cholesterol in whole blood vs. plasma samples for diagnosis of SLOS","authors":"Zhibin Huang , Yitao Luo , Chao Zhang , Wei Wu , Yangxi Li , Li Ma , Qingxia Zhang , Yulan Rao , Chengqiang Zhang","doi":"10.1016/j.jsbmb.2025.106682","DOIUrl":"10.1016/j.jsbmb.2025.106682","url":null,"abstract":"<div><h3>Background</h3><div>Smith-Lemli-Opitz Syndrome (SLOS) is an autosomal recessive disorder characterized by specific clinical features. This study investigated the correlation and transference ratio of 7-dehydrocholesterol (7-DHC) and cholesterol (CHOL) as screening/diagnostic markers for SLOS in whole blood and plasma samples.</div></div><div><h3>Methods</h3><div>The gas chromatography-mass spectrometry (GC-MS) method was employed to analyze whole blood and plasma samples collected from 28 healthy volunteers and one patient with SLOS. Before analysis, an optimized and validated assay for 7-DHC and CHOL in whole blood was developed. Pearson’s correlation analysis was then performed to assess the correlation between the levels of 7-DHC and CHOL in whole blood and plasma.</div></div><div><h3>Results</h3><div>The correlation analysis revealed a significant correlation between the levels of 7-DHC and CHOL in whole blood and plasma, with correlation coefficients (r) greater than 0.5 (0.565 for 7-DHC and 0.692 for CHOL). These findings suggest the feasibility of transference between whole blood and plasma samples.</div></div><div><h3>Conclusions</h3><div>Whole blood can be considered an optimal alternative diagnostic tool for predicting SLOS in carriers, surpassing the reliance on plasma alone. This study introduces a new diagnostic matrix for determining 7-DHC and CHOL, expanding the scope of SLOS diagnosis and research.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"248 ","pages":"Article 106682"},"PeriodicalIF":2.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374919","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

Role of NR5A2 in regulating sex differentiation, steroidogenesis, and gonadal development in Chlamys farreri

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-02-04 DOI: 10.1016/j.jsbmb.2025.106690

Lianxue Han , Jingjing Miao , Min Ding , Qichao Fan , Xuening Wang , Luqing Pan

Chlamys farreri is a commercially important bivalve species in global aquaculture. However, research on the mechanisms regulating its sex differentiation and reproduction remains relatively sparse. In this study, the role of nuclear receptor subfamily 5 group A member 2 (NR5A2) in sex differentiation, steroidogenesis, and gonadal development in C. farreri was investigated using a 28-day RNA interference experiment. RNA-seq data analysis revealed differentially expressed genes between males and females following NR5A2 knockdown. Weighted gene co-expression network analysis (WGCNA) further identified gene modules closely associated with reproductive development, with the yellow module demonstrating a significant correlation with the sex phenotype. Gene set enrichment analysis (GSEA) identified several signaling pathways related to reproduction that were suppressed, including ovarian follicle development, cholesterol metabolism, and ovarian steroidogenesis. Based on the above analysis, we identified 25 differentially expressed genes linked to these processes. Histological observations revealed that NR5A2 knockdown significantly delayed gonadal development in both sexes of scallops, as indicated by a notable decrease in follicular cell number and size. Taken together, NR5A2 knockdown significantly affected signaling pathways related to cholesterol metabolism, ovarian steroidogenesis, sex differentiation and gonadal development, providing a novel theoretical basis for understanding sex differentiation and reproductive development in invertebrates.

{"title":"Role of NR5A2 in regulating sex differentiation, steroidogenesis, and gonadal development in Chlamys farreri","authors":"Lianxue Han , Jingjing Miao , Min Ding , Qichao Fan , Xuening Wang , Luqing Pan","doi":"10.1016/j.jsbmb.2025.106690","DOIUrl":"10.1016/j.jsbmb.2025.106690","url":null,"abstract":"<div><div><em>Chlamys farreri</em> is a commercially important bivalve species in global aquaculture. However, research on the mechanisms regulating its sex differentiation and reproduction remains relatively sparse. In this study, the role of nuclear receptor subfamily 5 group A member 2 (<em>NR5A2</em>) in sex differentiation, steroidogenesis, and gonadal development in <em>C. farreri</em> was investigated using a 28-day RNA interference experiment. RNA-seq data analysis revealed differentially expressed genes between males and females following <em>NR5A2</em> knockdown. Weighted gene co-expression network analysis (WGCNA) further identified gene modules closely associated with reproductive development, with the yellow module demonstrating a significant correlation with the sex phenotype. Gene set enrichment analysis (GSEA) identified several signaling pathways related to reproduction that were suppressed, including ovarian follicle development, cholesterol metabolism, and ovarian steroidogenesis. Based on the above analysis, we identified 25 differentially expressed genes linked to these processes. Histological observations revealed that <em>NR5A2</em> knockdown significantly delayed gonadal development in both sexes of scallops, as indicated by a notable decrease in follicular cell number and size. Taken together, <em>NR5A2</em> knockdown significantly affected signaling pathways related to cholesterol metabolism, ovarian steroidogenesis, sex differentiation and gonadal development, providing a novel theoretical basis for understanding sex differentiation and reproductive development in invertebrates.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"248 ","pages":"Article 106690"},"PeriodicalIF":2.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350478","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