Pub Date : 2025-03-06DOI: 10.1016/j.mce.2025.112519
Michelle Maartens , Mare Vlok , Mari van de Vyver
Bone marrow mesenchymal stem cell (BM-MSC) dysfunction and poor viability are prominent in diabetes and limit their therapeutic efficacy. A proteomic investigation was performed to assess disease associated alterations and the efficacy of antioxidants to rescue cellular function. BM-MSCs were isolated from obese diabetic mice (B6.Cg-Lepob/J) cultured in the presence or absence of N-acetylcysteine (NAC) and ascorbic acid-2phosphate (AAP). Label free Liquid Chromatography and Mass Spectrometry (LC-MS) analysis detected 5079 proteins with 251 being differentially expressed between treatment groups. NAC/AAP improved cellular growth/viability post isolation by up-regulating proteins involved in redox status, ATP synthesis, Rho-GTPase signaling and modulated the immunophenotype of BM-MSCs. Despite a single application of the secretome not providing any advantage for wound bed regeneration in full thickness excisional diabetic wounds, the intracellular proteome illustrated the potential mechanisms of action by which NAC/AAP targeted the respiratory chain and modulated the immune phenotype of BM-MSCs. Given these observations, antioxidant supplementation might be more effective as prophylactic strategy to protect MSCs against functional decline instead of using it as a restorative agent and warrants further investigation.
{"title":"Antioxidants improve the viability of diabetic bone marrow MSCs without rescuing their pro-regenerative secretome function","authors":"Michelle Maartens , Mare Vlok , Mari van de Vyver","doi":"10.1016/j.mce.2025.112519","DOIUrl":"10.1016/j.mce.2025.112519","url":null,"abstract":"<div><div>Bone marrow mesenchymal stem cell (BM-MSC) dysfunction and poor viability are prominent in diabetes and limit their therapeutic efficacy. A proteomic investigation was performed to assess disease associated alterations and the efficacy of antioxidants to rescue cellular function. BM-MSCs were isolated from obese diabetic mice (B6.Cg-Lep<sup>ob</sup>/J) cultured in the presence or absence of N-acetylcysteine (NAC) and ascorbic acid-2phosphate (AAP). Label free Liquid Chromatography and Mass Spectrometry (LC-MS) analysis detected 5079 proteins with 251 being differentially expressed between treatment groups. NAC/AAP improved cellular growth/viability post isolation by up-regulating proteins involved in redox status, ATP synthesis, Rho-GTPase signaling and modulated the immunophenotype of BM-MSCs. Despite a single application of the secretome not providing any advantage for wound bed regeneration in full thickness excisional diabetic wounds, the intracellular proteome illustrated the potential mechanisms of action by which NAC/AAP targeted the respiratory chain and modulated the immune phenotype of BM-MSCs. Given these observations, antioxidant supplementation might be more effective as prophylactic strategy to protect MSCs against functional decline instead of using it as a restorative agent and warrants further investigation.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"601 ","pages":"Article 112519"},"PeriodicalIF":3.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-05DOI: 10.1016/j.mce.2025.112518
Christina Brummer , Katrin Singer , Kathrin Renner , Christina Bruss , Claus Hellerbrand , Christoph Dorn , Simone Reichelt-Wurm , Wolfram Gronwald , Tobias Pukrop , Wolfgang Herr , Miriam Banas , Marina Kreutz
Obesity promotes adipose tissue inflammation and leads to impaired local but also systemic immune cell homeostasis. This chronic low-grade inflammation plays a significant role in the development of obesity-associated secondary diseases such as metabolic associated fatty liver disease or cancer. The spleen as the central organ of immune cell regulation is anatomically directly connected to the visceral adipose tissue and the liver via the portal vein circulation. However, the inter-organ crosstalk and linkage between obesity-induced systemic, hepatic and splenic immune cell dysregulation is not clearly outlined. In this study blood, spleen, and liver immune cells of non-obese wildtype vs. leptin deficient obese BTBR mice were isolated and analyzed in terms of leukocyte composition by flow cytometry. Significant differences between circulating, spleen- and liver-resident immune cell distribution revealed, that obesity-induced hepatic and systemic immune cell dysregulation is distinct from splenic immune cell reprogramming. Fatty liver inflammation was associated with splenic myeloid derived suppressor cell (MDSC) and natural killer T cell (NKT) enrichment whereas loss of hepatic T and B cells was not reflected by the splenic lymphocyte landscape. Correlation analysis confirmed a selective strong positive correlation between spleen and liver MDSC and NKT cell distribution indicating that the spleen-liver axis modulates obesity-induced immune dysregulation in a cell-specific manner. Similar results were observed in a diet-induced obesity mouse model. These data provide novel insights into the role of the spleen-liver axis in obesity-induced inflammation and foster the understanding of obesity-associated complications such as fatty liver disease and cancer.
{"title":"The spleen-liver axis supports obesity-induced systemic and fatty liver inflammation via MDSC and NKT cell enrichment","authors":"Christina Brummer , Katrin Singer , Kathrin Renner , Christina Bruss , Claus Hellerbrand , Christoph Dorn , Simone Reichelt-Wurm , Wolfram Gronwald , Tobias Pukrop , Wolfgang Herr , Miriam Banas , Marina Kreutz","doi":"10.1016/j.mce.2025.112518","DOIUrl":"10.1016/j.mce.2025.112518","url":null,"abstract":"<div><div>Obesity promotes adipose tissue inflammation and leads to impaired local but also systemic immune cell homeostasis. This chronic low-grade inflammation plays a significant role in the development of obesity-associated secondary diseases such as metabolic associated fatty liver disease or cancer. The spleen as the central organ of immune cell regulation is anatomically directly connected to the visceral adipose tissue and the liver via the portal vein circulation. However, the inter-organ crosstalk and linkage between obesity-induced systemic, hepatic and splenic immune cell dysregulation is not clearly outlined. In this study blood, spleen, and liver immune cells of non-obese wildtype vs. leptin deficient obese BTBR mice were isolated and analyzed in terms of leukocyte composition by flow cytometry. Significant differences between circulating, spleen- and liver-resident immune cell distribution revealed, that obesity-induced hepatic and systemic immune cell dysregulation is distinct from splenic immune cell reprogramming. Fatty liver inflammation was associated with splenic myeloid derived suppressor cell (MDSC) and natural killer T cell (NKT) enrichment whereas loss of hepatic T and B cells was not reflected by the splenic lymphocyte landscape. Correlation analysis confirmed a selective strong positive correlation between spleen and liver MDSC and NKT cell distribution indicating that the spleen-liver axis modulates obesity-induced immune dysregulation in a cell-specific manner. Similar results were observed in a diet-induced obesity mouse model. These data provide novel insights into the role of the spleen-liver axis in obesity-induced inflammation and foster the understanding of obesity-associated complications such as fatty liver disease and cancer.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"601 ","pages":"Article 112518"},"PeriodicalIF":3.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-25DOI: 10.1016/j.mce.2025.112508
Bianka M. Zanini , Bianca M. Ávila , Jéssica D. Hense , Driele N. Garcia , Sarah Ashiqueali , Pâmela I.C. Alves , Thais L. Oliveira , Tiago V. Collares , Miguel A. Brieño-Enríquez , Jeffrey B. Mason , Michal M. Masternak , Augusto Schneider
Extracellular vesicles (EVs) of different sizes are secreted by cells and may contain microRNAs (miRNAs) among its cargo. These miRNAs in EVs can induce changes in gene expression and function of recipient cells. In different cells EVs content can change with age and physiological state affecting tissue function. Based on this, the aim of this study was to characterize the miRNA content and role of small EVs (sEVs) from cyclic female mice in the modulation of liver transcriptome in estropausal mice. Two-month-old female mice were induced to estropause using 4-vinylcyclohexene diepoxide (VCD). At six months of age, VCD-treated mice were divided into placebo group (VCD) and sEVs treated group (VCD + sEVs), which received 10 injections at 3-day intervals of sEVs isolated from serum of donor cyclic female mice. A group of cyclic mice also received placebo injection and served as controls (CTL). sEVs injection in mice undergoing estropause had no effect on body mass, insulin sensitivity or organ weight. We observed ten miRNAs differentially regulated in serum sEVs of VCD compared to CTL mice. In the liver we observed 931 genes differentially expressed in VCD + sEVs compared to VCD mice. Interestingly, eight pathways were up-regulated in liver by VCD treatment and down-regulated by sEVs treatment, indicating that sEVs from cyclic mice can reverse changes promoted by estropause in liver. The expression of Cyp4a12a, which is male-specific, was elevated in VCD females but not normalized by sEVs treatment. Our findings indicate that miRNA content in sEVs is regulated by estropause in mice independent of age. Additionally, treatment of estropausal mice with sEVs from cyclic mice can partially reverse changes in the liver transcriptome.
{"title":"Extracellular vesicles from cyclic mice modulate liver transcriptome in estroupause mice independent of age","authors":"Bianka M. Zanini , Bianca M. Ávila , Jéssica D. Hense , Driele N. Garcia , Sarah Ashiqueali , Pâmela I.C. Alves , Thais L. Oliveira , Tiago V. Collares , Miguel A. Brieño-Enríquez , Jeffrey B. Mason , Michal M. Masternak , Augusto Schneider","doi":"10.1016/j.mce.2025.112508","DOIUrl":"10.1016/j.mce.2025.112508","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) of different sizes are secreted by cells and may contain microRNAs (miRNAs) among its cargo. These miRNAs in EVs can induce changes in gene expression and function of recipient cells. In different cells EVs content can change with age and physiological state affecting tissue function. Based on this, the aim of this study was to characterize the miRNA content and role of small EVs (sEVs) from cyclic female mice in the modulation of liver transcriptome in estropausal mice. Two-month-old female mice were induced to estropause using 4-vinylcyclohexene diepoxide (VCD). At six months of age, VCD-treated mice were divided into placebo group (VCD) and sEVs treated group (VCD + sEVs), which received 10 injections at 3-day intervals of sEVs isolated from serum of donor cyclic female mice. A group of cyclic mice also received placebo injection and served as controls (CTL). sEVs injection in mice undergoing estropause had no effect on body mass, insulin sensitivity or organ weight. We observed ten miRNAs differentially regulated in serum sEVs of VCD compared to CTL mice. In the liver we observed 931 genes differentially expressed in VCD + sEVs compared to VCD mice. Interestingly, eight pathways were up-regulated in liver by VCD treatment and down-regulated by sEVs treatment, indicating that sEVs from cyclic mice can reverse changes promoted by estropause in liver. The expression of <em>Cyp4a12a</em>, which is male-specific, was elevated in VCD females but not normalized by sEVs treatment. Our findings indicate that miRNA content in sEVs is regulated by estropause in mice independent of age. Additionally, treatment of estropausal mice with sEVs from cyclic mice can partially reverse changes in the liver transcriptome.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112508"},"PeriodicalIF":3.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-21DOI: 10.1016/j.mce.2025.112507
Luara Jesus Ferrato , Thalles Fernando Rocha Ruiz , Lorena Gabriela de Souza , Gervásio Evangelista Brito-Filho , Simone Jacovaci Colleta , Ellen Cristina Rivas Leonel , Sebastião Roberto Taboga
The female prostate is a gland regulated by steroid hormones for homeostasis. Bisphenol A (BPA) is an endocrine disruptor related to the progression of malignant lesions in prostate. The aim of this study was to analyze the hormonal modulation and responsiveness of the prostate of aged female gerbils previously exposed to BPA. Females were exposed to 50 μg/kg/day during pregnancy and lactation, and the prostate was analyzed at 18 months of age. Control groups were included to normalize the analysis. The samples were analyzed using histological and immunohistochemical techniques for the expression of androgen (AR), estrogen (ERα and ERβ), prolactin (PRL), and progesterone (PR) receptors, as well as steroidogenic enzymes (5α-reductase and aromatase) and the proliferation (PHH3) and epigenetic (EZH2) markers. Protein quantification was also performed for the receptors and enzymes described, as well as morphological and morphometric analyses of the gland. The results showed an increase in the epithelial expression of AR and ERα and a decrease in the expression of ERβ in this compartment. In addition, a decrease in epithelial expression was observed for the 5α-reductase and aromatase in the prostate epithelium and an increase in the expression of PHH3 and EZH2. By Western blot analyses, significant differences were observed in the protein quantification of the receptors and enzymes described. Thus, the current study showed the role of BPA in intraprostatic hormonal modulation, through alterations in the expression of hormone receptors and the conversion of enzymes in the female prostate, which can lead to the progression of malignant lesions in this tissue.
{"title":"Bisphenol A exposure alters hormonal modulation and responsivity in the prostate of aged female gerbils","authors":"Luara Jesus Ferrato , Thalles Fernando Rocha Ruiz , Lorena Gabriela de Souza , Gervásio Evangelista Brito-Filho , Simone Jacovaci Colleta , Ellen Cristina Rivas Leonel , Sebastião Roberto Taboga","doi":"10.1016/j.mce.2025.112507","DOIUrl":"10.1016/j.mce.2025.112507","url":null,"abstract":"<div><div>The female prostate is a gland regulated by steroid hormones for homeostasis. Bisphenol A (BPA) is an endocrine disruptor related to the progression of malignant lesions in prostate. The aim of this study was to analyze the hormonal modulation and responsiveness of the prostate of aged female gerbils previously exposed to BPA. Females were exposed to 50 μg/kg/day during pregnancy and lactation, and the prostate was analyzed at 18 months of age. Control groups were included to normalize the analysis. The samples were analyzed using histological and immunohistochemical techniques for the expression of androgen (AR), estrogen (ERα and ERβ), prolactin (PRL), and progesterone (PR) receptors, as well as steroidogenic enzymes (5α-reductase and aromatase) and the proliferation (PHH3) and epigenetic (EZH2) markers. Protein quantification was also performed for the receptors and enzymes described, as well as morphological and morphometric analyses of the gland. The results showed an increase in the epithelial expression of AR and ERα and a decrease in the expression of ERβ in this compartment. In addition, a decrease in epithelial expression was observed for the 5α-reductase and aromatase in the prostate epithelium and an increase in the expression of PHH3 and EZH2. By Western blot analyses, significant differences were observed in the protein quantification of the receptors and enzymes described. Thus, the current study showed the role of BPA in intraprostatic hormonal modulation, through alterations in the expression of hormone receptors and the conversion of enzymes in the female prostate, which can lead to the progression of malignant lesions in this tissue.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112507"},"PeriodicalIF":3.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-19DOI: 10.1016/j.mce.2025.112504
Peter J. Fuller , Jun Yang , Morag J. Young , Timothy J. Cole
The mineralocorticoid receptor plays a central role in homeostasis, mediating the regulation by aldosterone of epithelial sodium transport. In addition, it regulates a range of responses in other tissues where it is likely responding to both mineralocorticoids and glucocorticoids. Structural, functional and evolutionary studies have provided insights into the mechanisms of receptor activation by agonist ligands and how interactions within the domains of the mineralocorticoid receptor may modulate the response to individual ligands including the mechanisms of antagonism. This review will discuss the current understanding, including recent insights into these interactions, with implications for an emerging array of novel non-steroidal compounds targeting the mineralocorticoid receptor; and highlight their relevance to ligand- or tissue-specificity as well as their suitability as therapeutic agents.
{"title":"Mechanisms of ligand-mediated modulation of mineralocorticoid receptor signaling","authors":"Peter J. Fuller , Jun Yang , Morag J. Young , Timothy J. Cole","doi":"10.1016/j.mce.2025.112504","DOIUrl":"10.1016/j.mce.2025.112504","url":null,"abstract":"<div><div>The mineralocorticoid receptor plays a central role in homeostasis, mediating the regulation by aldosterone of epithelial sodium transport. In addition, it regulates a range of responses in other tissues where it is likely responding to both mineralocorticoids and glucocorticoids. Structural, functional and evolutionary studies have provided insights into the mechanisms of receptor activation by agonist ligands and how interactions within the domains of the mineralocorticoid receptor may modulate the response to individual ligands including the mechanisms of antagonism. This review will discuss the current understanding, including recent insights into these interactions, with implications for an emerging array of novel non-steroidal compounds targeting the mineralocorticoid receptor; and highlight their relevance to ligand- or tissue-specificity as well as their suitability as therapeutic agents.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112504"},"PeriodicalIF":3.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-17DOI: 10.1016/j.mce.2025.112495
Renan Orellana-Walden , Ivan Martínez-Díaz , Lisbell Estrada
{"title":"New perspectives about the article “Dual inhibition of AKT and ERK1/2 pathways restores the expression of progesterone Receptor-B in endometriotic lesions through epigenetic mechanisms”","authors":"Renan Orellana-Walden , Ivan Martínez-Díaz , Lisbell Estrada","doi":"10.1016/j.mce.2025.112495","DOIUrl":"10.1016/j.mce.2025.112495","url":null,"abstract":"","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112495"},"PeriodicalIF":3.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The management of shock in critical care must transition from a predominantly hemodynamic approach to one that comprehensively addresses the biological intricacies of this complex multisystemic syndrome. A thorough understanding of the metabolic mechanisms involved in shock is pivotal for precise patient phenotyping and accurate risk stratification. Metabolomics, an emerging “-omics” approach, offers a powerful tool for unraveling the molecular underpinnings of shock. By analyzing the metabolic pathways within the cardiovascular system, metabolomics can elucidate the diverse mechanisms leading to circulatory insufficiency. This approach holds significant promise for identifying clinically actionable diagnostic and prognostic biomarkers, which can enhance individualized patient management and potentially prevent the progression to multi-organ failure. Improved insight into the metabolic alterations in shock may pave the way for novel therapeutic strategies and more targeted treatments, ultimately improving patient outcomes in critical care settings. This work provides a comprehensive overview of metabolomic investigations in shock, focusing on septic shock and the main metabolic pathways involved in cardiac and vascular dysfunction.
{"title":"Understanding metabolic remodeling in shock through metabolomics lenses","authors":"Zoé Demailly , Fabienne Tamion , Emmanuel Besnier , Soumeya Bekri , Abdellah Tebani","doi":"10.1016/j.mce.2025.112491","DOIUrl":"10.1016/j.mce.2025.112491","url":null,"abstract":"<div><div>The management of shock in critical care must transition from a predominantly hemodynamic approach to one that comprehensively addresses the biological intricacies of this complex multisystemic syndrome. A thorough understanding of the metabolic mechanisms involved in shock is pivotal for precise patient phenotyping and accurate risk stratification. Metabolomics, an emerging “-omics” approach, offers a powerful tool for unraveling the molecular underpinnings of shock. By analyzing the metabolic pathways within the cardiovascular system, metabolomics can elucidate the diverse mechanisms leading to circulatory insufficiency. This approach holds significant promise for identifying clinically actionable diagnostic and prognostic biomarkers, which can enhance individualized patient management and potentially prevent the progression to multi-organ failure. Improved insight into the metabolic alterations in shock may pave the way for novel therapeutic strategies and more targeted treatments, ultimately improving patient outcomes in critical care settings. This work provides a comprehensive overview of metabolomic investigations in shock, focusing on septic shock and the main metabolic pathways involved in cardiac and vascular dysfunction.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112491"},"PeriodicalIF":3.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-14DOI: 10.1016/j.mce.2025.112488
Elizabeth Cristina Miola , Fernanda Yamamoto Ricardo-da-Silva , Pedro Luiz Zonta de Freitas, Marina Vidal-dos-Santos, Luiz Felipe Pinho Moreira, Ana Cristina Breithaupt-Faloppa, Cristiano de Jesus Correia
Among transplantable organs, the intestine is one of the most challenging organs to transplant. While there is considerable research on the effects of brain death (BD), little is known about the specific intestinal changes that occur, particularly in females. Here we investigated the role of female sex hormones in the BD-induced intestinal inflammation, using an ovariectomy (OVx) model for sex hormones depletion. Wistar rats (female) were divided into four experimental groups: Control non-OVx – non-manipulated; Control-OVx –ovariectomized; BD non-OVx – animals submitted to BD (6h); BD-OVx –ovariectomized animals submitted to BD. OVx was performed 10 days before BD induction. non-OVx groups were chosen during proestrus phase (heat period). Inflammatory mediators and white blood cell count were quantified in the blood. Intestine tissue was sampled for histopathological analysis, myeloperoxidase (MPO) activity, Evans blue dye extravasation assay and immunohistochemistry. Results show higher intestinal injury in BD-OVx than BD non-OVx animals, presenting reduced crypt depth and increased serum inflammatory mediators. Independently from the previous hormonal status, BD increased intestinal inflammation, with higher leukocyte infiltration, MPO activity, ICAM-1 expression, and higher serum MIP-1α. In summary, BD modulates intestinal inflammation by increasing leukocyte mobilization. Whereas OVx, and its consequences on the female hormonal profile, influences homeostasis and BD-induced inflammation, increasing inflammatory mediators and altering intestinal morphology.
{"title":"The role of sex hormones in the intestinal injury after brain death using a surgical menopause model in rats","authors":"Elizabeth Cristina Miola , Fernanda Yamamoto Ricardo-da-Silva , Pedro Luiz Zonta de Freitas, Marina Vidal-dos-Santos, Luiz Felipe Pinho Moreira, Ana Cristina Breithaupt-Faloppa, Cristiano de Jesus Correia","doi":"10.1016/j.mce.2025.112488","DOIUrl":"10.1016/j.mce.2025.112488","url":null,"abstract":"<div><div>Among transplantable organs, the intestine is one of the most challenging organs to transplant. While there is considerable research on the effects of brain death (BD), little is known about the specific intestinal changes that occur, particularly in females. Here we investigated the role of female sex hormones in the BD-induced intestinal inflammation, using an ovariectomy (OVx) model for sex hormones depletion. Wistar rats (female) were divided into four experimental groups: Control non-OVx – non-manipulated; Control-OVx –ovariectomized; BD non-OVx – animals submitted to BD (6h); BD-OVx –ovariectomized animals submitted to BD. OVx was performed 10 days before BD induction. non-OVx groups were chosen during proestrus phase (heat period). Inflammatory mediators and white blood cell count were quantified in the blood. Intestine tissue was sampled for histopathological analysis, myeloperoxidase (MPO) activity, Evans blue dye extravasation assay and immunohistochemistry. Results show higher intestinal injury in BD-OVx than BD non-OVx animals, presenting reduced crypt depth and increased serum inflammatory mediators. Independently from the previous hormonal status, BD increased intestinal inflammation, with higher leukocyte infiltration, MPO activity, ICAM-1 expression, and higher serum MIP-1α. In summary, BD modulates intestinal inflammation by increasing leukocyte mobilization. Whereas OVx, and its consequences on the female hormonal profile, influences homeostasis and BD-induced inflammation, increasing inflammatory mediators and altering intestinal morphology.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112488"},"PeriodicalIF":3.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-14DOI: 10.1016/j.mce.2025.112494
Jithine J. Rajeswari, Geneece N.Y. Gilbert, Enezi Khalid, Mathilakath M. Vijayan
While central monoamines play a role in regulating stress-related locomotory activity, the modulation of monoamines by the corticosteroid stress axis in shaping acute behavioural responses are unclear. We investigated whether the corticotropin-releasing hormone receptor 1 (Crhr1) modulation of stress-related behavioral response involves monoamine regulation by subjecting Crhr1 knockout (crhr1−/−) zebrafish (Danio rerio) to an acute thermal stressor (TS: +5 °C above ambient for 60 min). The TS-induced cortisol response and hyper locomotory activity in the WT larvae was abolished in fish lacking Crhr1. However, both genotypes induced a heat shock protein response to the TS. The crhr1−/− larvae showed a region-specific difference in the distribution of serotonin (5-HT)- and tyrosine hydroxylase-positive cells in the brain. This corresponded with increases in whole-body transcript abundance of dopamine beta-hydroxylase, tryptophan hydroxylase 2, and solute carrier family 6-member 4a. Cotreatment with either epinephrine or 5-HT, but not cortisol, was able to rescue the TS-mediated hypo locomotory activity and thigmotaxis seen in the crhr1−/− larvae. Together, these results indicate that Crhr1 is essential not only for mediating the TS-induced hyperactivity but also for maintaining the basal locomotory activity and anxiogenic response during stress. The latter response depends on the central monoamine regulation by Crhr1 in zebrafish larvae.
{"title":"Brain monoamine changes modulate the corticotropin-releasing hormone receptor 1-mediated behavioural response to acute thermal stress in zebrafish larvae","authors":"Jithine J. Rajeswari, Geneece N.Y. Gilbert, Enezi Khalid, Mathilakath M. Vijayan","doi":"10.1016/j.mce.2025.112494","DOIUrl":"10.1016/j.mce.2025.112494","url":null,"abstract":"<div><div>While central monoamines play a role in regulating stress-related locomotory activity, the modulation of monoamines by the corticosteroid stress axis in shaping acute behavioural responses are unclear. We investigated whether the corticotropin-releasing hormone receptor 1 (Crhr1) modulation of stress-related behavioral response involves monoamine regulation by subjecting Crhr1 knockout (<em>crhr1</em><sup><em>−/−</em></sup>) zebrafish (<em>Danio rerio</em>) to an acute thermal stressor (TS: +5 °C above ambient for 60 min). The TS-induced cortisol response and hyper locomotory activity in the WT larvae was abolished in fish lacking Crhr1. However, both genotypes induced a heat shock protein response to the TS. The <em>crhr1</em><sup><em>−/−</em></sup> larvae showed a region-specific difference in the distribution of serotonin (5-HT)- and tyrosine hydroxylase-positive cells in the brain. This corresponded with increases in whole-body transcript abundance of dopamine beta-hydroxylase, tryptophan hydroxylase 2, and solute carrier family 6-member 4a. Cotreatment with either epinephrine or 5-HT, but not cortisol, was able to rescue the TS-mediated hypo locomotory activity and thigmotaxis seen in the <em>crhr1</em><sup><em>−/−</em></sup> larvae. Together, these results indicate that Crhr1 is essential not only for mediating the TS-induced hyperactivity but also for maintaining the basal locomotory activity and anxiogenic response during stress. The latter response depends on the central monoamine regulation by Crhr1 in zebrafish larvae.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112494"},"PeriodicalIF":3.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-12DOI: 10.1016/j.mce.2025.112492
Jessica D. Pereira , Fernanda M.V. Magalhães , Fabiana M.S. Tameirão , Frederico M. Soriani , Karina T. de O. S. Jorge , Fernando M. Reis , Ana Lúcia Cândido , Fábio V. Comim , Karina B. Gomes
Introduction
Polycystic Ovary Syndrome (PCOS) is one of the most common endocrinopathy in women of reproductive age. MicroRNA (miRNAs) are small non-coding RNAs related to the control of gene expression in biological fluids. Our study analyzed the expression of miRNAs related to inflammation in individuals with PCOS compared to controls.
Methods
Twenty patients with PCOS and 20 controls, matched by body mass index and age, were included in the study. The miRNAs evaluated were miRNA-30c-5p; miRNA-545-3p and miRNA-125a-5p.
Results
The expression of the miRNAs was similar between the two groups. A positive correlation was observed between the expression of miRNA-125a-5p and LDLc levels only in the PCOS group. Subsequent analysis of biological pathways showed that miRNA-125a -5p is significantly involved in the regulation of SREBP/SREBF pathways of cholesterol biosynthesis, glycolysis, insulin receptor signaling, oxidative stress-induced senescence and estrogen-dependent gene expression.
Conclusion
The results suggest that the miRNA-125a-5p shows a potential implication to the regulation of lipid biosynthesis and LDL-c levels in PCOS women.
{"title":"The possible regulatory role of miRNA-30c-5p, miRNA-545-3p and miRNA-125a-5p in women with polycystic ovary syndrome: A case-control study and signaling pathways","authors":"Jessica D. Pereira , Fernanda M.V. Magalhães , Fabiana M.S. Tameirão , Frederico M. Soriani , Karina T. de O. S. Jorge , Fernando M. Reis , Ana Lúcia Cândido , Fábio V. Comim , Karina B. Gomes","doi":"10.1016/j.mce.2025.112492","DOIUrl":"10.1016/j.mce.2025.112492","url":null,"abstract":"<div><h3>Introduction</h3><div>Polycystic Ovary Syndrome (PCOS) is one of the most common endocrinopathy in women of reproductive age. MicroRNA (miRNAs) are small non-coding RNAs related to the control of gene expression in biological fluids. Our study analyzed the expression of miRNAs related to inflammation in individuals with PCOS compared to controls.</div></div><div><h3>Methods</h3><div>Twenty patients with PCOS and 20 controls, matched by body mass index and age, were included in the study. The miRNAs evaluated were miRNA-30c-5p; miRNA-545-3p and miRNA-125a-5p.</div></div><div><h3>Results</h3><div>The expression of the miRNAs was similar between the two groups. A positive correlation was observed between the expression of miRNA-125a-5p and LDLc levels only in the PCOS group. Subsequent analysis of biological pathways showed that miRNA-125a -5p is significantly involved in the regulation of SREBP/SREBF pathways of cholesterol biosynthesis, glycolysis, insulin receptor signaling, oxidative stress-induced senescence and estrogen-dependent gene expression.</div></div><div><h3>Conclusion</h3><div>The results suggest that the miRNA-125a-5p shows a potential implication to the regulation of lipid biosynthesis and LDL-c levels in PCOS women.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112492"},"PeriodicalIF":3.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号