المؤلفون: Jianping Weng, Daizhi Yang, Ping Ling, Sihui Luo, Xueying Zheng, Jiajun Zhao, Qin Huang, Xinhua Xiao, Mei Zhang, Nan Gu, Ji Hu, Fang Liu, Jing Lu, Zhiguang Zhou, Jinhua Yan

المصدر: The Journal of Clinical Endocrinology and Metabolism

مصطلحات موضوعية: HBA1c target, Adult, Blood Glucose, medicine.medical_specialty, China, Time Factors, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Pregnancy in Diabetics, Context (language use), Gestational Age, Glycemic Control, Biochemistry, chemistry.chemical_compound, Endocrinology, Pregnancy, Internal medicine, Diabetes mellitus, glycated hemoglobin A1c, Medicine, Humans, Online Only Articles, Clinical Research Articles, Glycemic, Glycated Hemoglobin, Type 1 diabetes, Continuous glucose monitoring, business.industry, Obstetrics, Blood Glucose Self-Monitoring, Biochemistry (medical), Postpartum Period, nutritional and metabolic diseases, medicine.disease, type 1, Diabetes Mellitus, Type 1, chemistry, time in range, diabetes mellitus, Female, Glycated hemoglobin, business, AcademicSubjects/MED00250

الوصف: ContextContinuous glucose monitoring (CGM) overcomes the limitations of glycated hemoglobin (HbA1c).ObjectiveThis study aimed to investigate the relationship between CGM metrics and laboratory HbA1c in pregnant women with type 1 diabetes.MethodsAn observational study enrolled pregnant women with type 1 diabetes who wore CGM devices during pregnancy and postpartum from 11 hospitals in China from January 2015 to June 2019. CGM data were collected to calculate time in range (TIR), time above range (TAR), time below range (TBR), and glycemic variability parameters. Relationships between the CGM metrics and HbA1c were explored. Linear and curvilinear regressions were conducted to investigate the best-fitting model to clarify the influence of HbA1c on the TIR-HbA1c relationship during pregnancy.ResultsA total of 272 CGM data and corresponding HbA1c from 98 pregnant women with type 1 diabetes and their clinical characteristics were analyzed in this study. Mean HbA1c and TIR were 6.49 ± 1.29% and 76.16 ± 17.97% during pregnancy, respectively. HbA1c was moderately correlated with TIR3.5-7.8(R = –0.429, P = .001), mean glucose (R = 0.405, P = .001) and TAR7.8 (R = 0.435, P = .001), but was weakly correlated with TBR3.5 (R = 0.034, P = .001) during pregnancy. On average, a 1% (11 mmol/mol) decrease in HbA1c corresponded to an 8.5% increase in TIR3.5–7.8. During pregnancy, HbA1c of 6.0%, 6.5%, and 7.0% were equivalent to a TIR3.5–7.8 of 78%, 74%, and 69%, respectively.ConclusionWe found there was a moderate correlation between HbA1c and TIR3.5–7.8 during pregnancy. To achieve the HbA1c target of less than 6.0%, pregnant women with type 1 diabetes should strive for a TIR3.5–7.8 of greater than 78% (18 hours 43 minutes) during pregnancy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5052da6c8f793c04093aabf5c14a5653Test
http://europepmc.org/articles/PMC8530704Test

المؤلفون: Kenneth D. Roth, Valentina Pirro, Kevin L. Duffin, Jonathan M. Wilson, Yanzhu Lin, Jill A. Willency, Axel Haupt, Paul L. Milligan, Christopher B. Newgard, Giacomo Ruotolo

المصدر: The Journal of Clinical Endocrinology & Metabolism. 107:363-378

مصطلحات موضوعية: Adult, Blood Glucose, Male, medicine.medical_specialty, Injections, Subcutaneous, Recombinant Fusion Proteins, Endocrinology, Diabetes and Metabolism, Metabolite, Clinical Biochemistry, Glucagon-Like Peptides, Gastric Inhibitory Polypeptide, Type 2 diabetes, Placebo, Biochemistry, Glucagon-Like Peptide-1 Receptor, Receptors, Gastrointestinal Hormone, Young Adult, chemistry.chemical_compound, Endocrinology, Insulin resistance, Glucagon-Like Peptide 1, Weight loss, Internal medicine, Diabetes mellitus, Weight Loss, medicine, Humans, Hypoglycemic Agents, Metabolomics, Triglycerides, Aged, Glycemic, Glycated Hemoglobin, business.industry, Biochemistry (medical), Middle Aged, medicine.disease, Immunoglobulin Fc Fragments, Diabetes Mellitus, Type 2, chemistry, Female, Dulaglutide, medicine.symptom, business, medicine.drug

الوصف: Context Tirzepatide substantially reduced hemoglobin A1c (HbA1c) and body weight in subjects with type 2 diabetes (T2D) compared with the glucagon-like peptide 1 receptor agonist dulaglutide. Improved glycemic control was associated with lower circulating triglycerides and lipoprotein markers and improved markers of beta-cell function and insulin resistance (IR), effects only partially attributable to weight loss. Objective Assess plasma metabolome changes mediated by tirzepatide. Design Phase 2b trial participants were randomly assigned to receive weekly subcutaneous tirzepatide, dulaglutide, or placebo for 26 weeks. Post hoc exploratory metabolomics and lipidomics analyses were performed. Setting Post hoc analysis. Participants 259 subjects with T2D. Intervention(s) Tirzepatide (1, 5, 10, 15 mg), dulaglutide (1.5 mg), or placebo. Main Outcome Measure(s) Changes in metabolite levels in response to tirzepatide were assessed against baseline levels, dulaglutide, and placebo using multiplicity correction. Results At 26 weeks, a higher dose tirzepatide modulated a cluster of metabolites and lipids associated with IR, obesity, and future T2D risk. Branched-chain amino acids, direct catabolic products glutamate, 3-hydroxyisobutyrate, branched-chain ketoacids, and indirect byproducts such as 2-hydroxybutyrate decreased compared to baseline and placebo. Changes were significantly larger with tirzepatide compared with dulaglutide and directly proportional to reductions of HbA1c, homeostatic model assessment 2-IR indices, and proinsulin levels. Proportional to metabolite changes, triglycerides and diglycerides were lowered significantly compared to baseline, dulaglutide, and placebo, with a bias toward shorter and highly saturated species. Conclusions Tirzepatide reduces body weight and improves glycemic control and uniquely modulates metabolites associated with T2D risk and metabolic dysregulation in a direction consistent with improved metabolic health.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3140a92fd3671aef505b0ff756594a2cTest
https://doi.org/10.1210/clinem/dgab722Test

المؤلفون: Yueming Song, Xin He, Xi Yang, Kun Shi, Yong Huang, Juehan Wang, Limin Liu, Ce Zhu, Ganjun Feng, Jingcheng Wang, Leizhen Huang

المصدر: Oxidative Medicine and Cellular Longevity, Vol 2021 (2021)
Oxidative Medicine and Cellular Longevity

مصطلحات موضوعية: Adult, Male, MAPK/ERK pathway, Aging, Article Subject, Apoptosis, Intervertebral Disc Degeneration, Biology, Biochemistry, chemistry.chemical_compound, Downregulation and upregulation, In vivo, microRNA, medicine, Animals, Humans, STC1, Aged, Mitogen-Activated Protein Kinase 1, QH573-671, Vascular Endothelial Growth Factors, Intervertebral disc, Cell Biology, General Medicine, Middle Aged, Rats, Up-Regulation, Cell biology, Vascular endothelial growth factor, MicroRNAs, medicine.anatomical_structure, chemistry, Female, Cytology, Signal Transduction, Research Article

الوصف: Aims. Accumulating evidence reported that the microRNA (miRNA) took an important role in intervertebral disc degeneration (IDD). In this study, we revealed a novel miRNA regulatory mechanism in IDD. Main Methods. The miRNA microarray analyses of human degenerated and normal disc samples were employed to screen out the target miRNA. In vitro and in vivo experiments were conducted to verify the regulatory effect of miR-101-3p. Key Findings. The expression level of miR-101-3p was significantly decreased in the degenerated disc samples which were confirmed by qRT-PCR. Moreover, the miR-101-3p expression level was changed dynamically according to the disc degeneration grade. Upregulation of miR-101-3p expression level inhibited cell apoptosis. Furthermore, stanniocalcin-1 (STC1) was selected to be the target gene of miR-101-3p according to the bioinformatic algorithms. Mechanically, upregulation of miR-101-3p significantly decreased the expression of STC1, vascular endothelial growth factor (VEGF), and MAPK pathway expression levels. Therapeutically, in vivo experiment on IDD rat model illustrated that agomir-101-3p could effectively suspend IDD. Significance. Our findings demonstrated that miR-101-3p alleviated IDD process through the STC1/VEGF/MAPK pathway.

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الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b819441873b03d859c1f092c406c12d5Test
https://doi.org/10.1155/2021/1073458Test

المؤلفون: Kim C Donaghue, Bruce R. King, D Jane Holmes-Walker, Craig Jefferies, Meng Tuck Mok, P Shane Hamblin, Melissa Chee, Timothy W. Jones, Helen L. Barrett, Elizabeth E Davis, Arul Earnest, Benjamin J Wheeler, Richard O. Sinnott, Stephanie R. Johnson, Anthony Zimmermann, Glenn M. Ward, Fergus J. Cameron, P. Gerry Fegan, Jenny Couper, Maria E. Craig, Philip Bergman, Peter G. Colman

المصدر: The Journal of Clinical Endocrinology & Metabolism. 106:133-142

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Adolescent, Databases, Factual, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Overweight, Community Networks, Biochemistry, Body Mass Index, Young Adult, chemistry.chemical_compound, Endocrinology, Risk Factors, Interquartile range, Internal medicine, Diabetes mellitus, Humans, Medicine, Longitudinal Studies, Child, Creatinine, Type 1 diabetes, Australasia, business.industry, Cholesterol, Biochemistry (medical), Age Factors, medicine.disease, Diabetes Mellitus, Type 1, Blood pressure, chemistry, Cardiovascular Diseases, Heart Disease Risk Factors, Child, Preschool, Female, medicine.symptom, business, Body mass index, Diabetic Angiopathies

الوصف: Context Cardiovascular disease occurs prematurely in type 1 diabetes. The additional risk of overweight is not well characterized. Objective The primary aim was to measure the impact of body mass index (BMI) in youth with type 1 diabetes on cardiovascular risk factors. The secondary aim was to identify other determinants of cardiovascular risk. Design Observational longitudinal study of 7061 youth with type 1 diabetes followed for median 7.3 (interquartile range [IQR] 4-11) years over 41 (IQR 29-56) visits until March 2019. Setting 15 tertiary care diabetes centers in the Australasian Diabetes Data Network. Participants were aged 2 to 25 years at baseline, with at least 2 measurements of BMI and blood pressure. Main Outcome Measure Standardized systolic and diastolic blood pressure scores and non–high-density lipoprotein (HDL) cholesterol were co-primary outcomes. Urinary albumin/creatinine ratio was the secondary outcome. Results BMI z-score related independently to standardized blood pressure z- scores and non-HDL cholesterol. An increase in 1 BMI z-score related to an average increase in systolic/diastolic blood pressure of 3.8/1.4 mmHg and an increase in non-HDL cholesterol (coefficient + 0.16 mmol/L, 95% confidence interval [CI], 0.13-0.18; P Conclusions BMI had a modest independent effect on cardiovascular risk. Females and Indigenous Australians in particular had a more adverse risk profile.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::298c7db71620ae79ee854b42d6648800Test
https://doi.org/10.1210/clinem/dgaa727Test

المؤلفون: Alessandra Gandolfi, Sabrina Costa, Paolo Monti, Roberta Sara Catalano, Emanuele Bosi, Amelia Caretto, Vito Lampasona, Marina Scavini, Lorenzo Piemonti, Valeria Sordi, Chiara Molinari, Silvia Pellegrini, Andrea Laurenzi, Andrea Mario Bolla, Eleonora Bianconi, Elisa Borgonovo

المساهمون: Bolla, Andrea Mario, Gandolfi, Alessandra, Borgonovo, Elisa, Laurenzi, Andrea, Caretto, Amelia, Molinari, Chiara, Catalano, Roberta Sara, Bianconi, Eleonora, Monti, Paolo, Sordi, Valeria, Pellegrini, Silvia, Lampasona, Vito, Costa, Sabrina, Scavini, Marina, Bosi, Emanuele, Piemonti, Lorenzo

المصدر: The Journal of Clinical Endocrinology & Metabolism. 106:e507-e519

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Placebo, Biochemistry, Gastroenterology, law.invention, Placebos, Young Adult, chemistry.chemical_compound, Endocrinology, Double-Blind Method, Randomized controlled trial, law, DPP-4 inhibitors, Insulin-Secreting Cells, Internal medicine, medicine, Humans, Vildagliptin, Glycemic, Sirolimus, Type 1 diabetes, rapamycin, C-peptide, business.industry, Insulin, Biochemistry (medical), Recovery of Function, long-standing type 1 diabetes, Middle Aged, medicine.disease, Diabetes Mellitus, Type 1, Treatment Outcome, Italy, chemistry, vildagliptin, Drug Therapy, Combination, Female, Glycated hemoglobin, insulin antibody, business, medicine.drug

الوصف: Aim The aim of this study was to investigate whether treatment with rapamycin plus vildagliptin restores β-cell function in patients with long-standing type 1 diabetes. Methods A phase 2, single-center, randomized, double-blind, placebo-controlled study was conducted in long-standing type 1 diabetes patients randomly assigned (1:1:1) to 4 weeks of rapamycin (group 2), 4 weeks of rapamycin plus 12 weeks of vildagliptin (group 3), or double placebo (group 1). The primary outcome was the proportion of participants with a positive response to the Mixed-Meal Tolerance Test (C-peptide at 90 minutes > 0.2 nmol/L) at weeks 4 and 12. Secondary end points included insulin requirement, standard measures of glycemic control, and hormonal and immunological profile. Results Fifty-five patients were randomly assigned to group 1 (n = 18), group 2 (n = 19), or group 3 (n = 18). No patient in any group showed a positive C-peptide response, and there was no significant difference at 4 and 12 weeks for the primary outcome. At 4 weeks, insulin requirement decreased from 0.54 to 0.48 U/kg/day in group 2 (P = .013), from 0.59 to 0.51 U/kg/day in group 3 (P Conclusions Rapamycin reduced insulin requirement, but did not restore β-cell function in patients with long-standing type 1 diabetes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6512efb97aed11c147655230b7222e7Test
https://doi.org/10.1210/clinem/dgaa791Test

المؤلفون: Vallo Volke, Keiu Heinla, Eero Vasar, Tuuli Sedman

المصدر: Hormone and Metabolic Research. 53:402-407

مصطلحات موضوعية: Adult, Male, Hypothalamo-Hypophyseal System, medicine.medical_specialty, Adolescent, Hydrocortisone, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Pituitary-Adrenal System, 030209 endocrinology & metabolism, Stimulation, Biochemistry, Glucagon-Like Peptide-1 Receptor, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Therapeutic index, Internal medicine, Renin–angiotensin system, Humans, Medicine, Receptor, Aldosterone, Glucagon-like peptide 1 receptor, business.industry, Biochemistry (medical), General Medicine, Middle Aged, Healthy Volunteers, chemistry, Ambulatory, Exenatide, Female, business, 030217 neurology & neurosurgery, Follow-Up Studies, medicine.drug

الوصف: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are antidiabetic drugs with effects beyond antihyperglycemic action. The aim of the study was to examine whether a single dose of exenatide could be used as a stimulation test for the pituitary-adrenal axis. We carried out a single-group, open-label pilot clinical trial in an ambulatory setting. Ten healthy volunteers of both sexes with body weight>65 kg and age between 18–50 years were recruited. After fasting for 12 hours the subjects received 10 μg of exenatide solution subcutaneously. Blood samples were taken before the administration of exenatide and up to 150 minutes thereafter. The primary outcome was the maximal level of cortisol after the administration of exenatide. Single administration of exenatide 10 μg resulted in a modest increase in ACTH and cortisol levels, as compared to untreated values, and a decrease in blood glucose levels. Remarkably, a robust suppression of both renin and aldosterone levels occurred. We showed that acute administration of exenatide in a full therapeutic dose modestly stimulates the hypothalamic-pituitary-adrenal axis but inhibits the renin-aldosterone system. Further research is warranted to confirm this finding in the placebo-controlled study.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::149b814c82d922838be804b633c5d5f0Test
https://doi.org/10.1055/a-1498-7098Test

المؤلفون: Shin-Yu Lin, Chia Chi Chuang, Hung Tsung Wu, Kuan-Yu Chen, Chi-Tai Fang, Ming Wei Lin, Szu Chi Chen, Ching-Hua Kuo, Chun Heng Kuo, Han Chun Kuo, Hung-Yuan Li, Kang-Chih Fan, Chien-Nan Lee

المصدر: The Journal of Clinical Endocrinology & Metabolism. 106:e3461-e3472

مصطلحات موضوعية: Adult, 0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Linoleic acid, Clinical Biochemistry, Taiwan, 030209 endocrinology & metabolism, Context (language use), Fatty Acids, Nonesterified, Biochemistry, Cohort Studies, Fetal Development, Palmitic acid, 03 medical and health sciences, Insulin-like growth factor, chemistry.chemical_compound, Fetus, 0302 clinical medicine, Endocrinology, Insulin-Like Growth Factor II, Pregnancy, Internal medicine, Diabetes mellitus, Humans, Medicine, Insulin-Like Growth Factor I, Triglycerides, business.industry, Biochemistry (medical), Fetal Blood, medicine.disease, Lipids, Pathophysiology, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, 030104 developmental biology, chemistry, Cord blood, Female, business

الوصف: Context Maternal lipids during pregnancy and placental growth factors are associated with excess fetal growth. However, how these factors interact to increase the risk of delivering large-for-gestational-age (LGA) neonates remains unclear. In this study, we investigated the relationship between maternal plasma triglycerides (TGs) and free fatty acids (FFAs) during pregnancy, cord blood insulin-like growth factors (IGF), and LGA. Objective In a cell model, we studied the effect of different FAs on placental IGF-1 secretion. Methods This cohort study included pregnant women with term pregnancy and without diabetes or hypertensive disorders in pregnancy. Maternal fasting plasma TGs and FFAs were measured in the second trimester. Cord blood IGF-1, IGF-2, and IGF binding protein-1 and protein-3 were measured at the time of delivery. A human trophoblast cell line, 3A-sub-E, was used to evaluate the effect of different FFAs on placental IGF-1 secretion. Results We recruited 598 pregnant women–neonate pairs. Maternal plasma TG (180 mg/dL [152.5-185.5 mg/dL] vs 166 mg/dL [133-206 mg/dL], P = .04) and cord blood IGF-1 concentrations (72.7 ± 23.0 vs 54.1 ± 22.8 ng/mL, P < .001) were higher in the LGA group and were significantly associated with birth weight z score. Maternal plasma free palmitic acid (PA) and stearic acid (SA), but not oleic acid (OA) or linoleic acid (LA), were significantly associated with cord blood IGF-1 concentrations. In 3A-sub-E cells, treatment with PA, SA, and LA, but not OA, induced IGF-1 expression and secretion. Conclusion Certain FFAs can induce placental IGF-1 secretion, which suggests a potential pathophysiology linking maternal plasma lipids and LGA.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::620aa714f24a448756c6ba84c91080e5Test
https://doi.org/10.1210/clinem/dgab364Test

المؤلفون: Kinga Németh, Lilla Reiniger, Borbála Szabó, Hajnalka Rajnai, Henriett Butz, Lilla Krokker, Katalin Mészáros, Attila Patócs, Sándor Czirják, Ildikó Krencz, Nikolette Szücs, Katalin Karaszi

المصدر: The Journal of Clinical Endocrinology & Metabolism. 105:2015-2026

مصطلحات موضوعية: Adult, DNA (Cytosine-5-)-Methyltransferase 1, Male, medicine.medical_specialty, Adenoma, Proliferation index, Ubiquitin-Protein Ligases, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Decitabine, Biochemistry, DNA methyltransferase, Dioxygenases, Epigenesis, Genetic, Young Adult, chemistry.chemical_compound, Endocrinology, Pituitary adenoma, Proto-Oncogene Proteins, Internal medicine, Biomarkers, Tumor, medicine, Humans, Pituitary Neoplasms, Aged, Cell Proliferation, Aged, 80 and over, Biochemistry (medical), Tet methylcytosine dioxygenase 1, DNA, Neoplasm, DNA Methylation, Middle Aged, Prognosis, medicine.disease, Demethylating agent, DNA-Binding Proteins, Neuroendocrine Tumors, chemistry, Case-Control Studies, 5-Methylcytosine, DNMT1, Cancer research, Female, Follow-Up Studies, medicine.drug

الوصف: Background Cytosine intermediaries 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), epigenetic hallmarks, have never been investigated in pituitary neuroendocrine tumors (PitNET). Objective To examine methylation-demethylation status of global deoxyribonucleic acid (DNA) in PitNET tissues and to assess its correlation with clinical and biological parameters. Materials and Methods Altogether, 57 PitNET and 25 corresponding plasma samples were collected. 5mC and 5hmC were investigated using liquid chromatography–tandem mass spectrometry. Expression of DNA methyltransferase 1 (DNMT1); tet methylcytosine dioxygenase 1 through 3 (TET1-3); and ubiquitin-like, containing PHD and RING finger domains 1 and 2 (UHRF1-2) were measured by reverse transcription–polymerase chain reaction. Levels of 5hmC and UHRF1-2 were explored by immunohistochemistry. Effect of demethylating agent decitabine was tested on pituitary cell lines. Results 5hmC/5mC ratio was higher in less differentiated PitNET samples. A negative correlation between Ki-67 proliferation index and 5hmC, 5hmC to 5mC ratio were revealed. Higher 5mC was observed in SF-1 + gonadotroph adenomas with a higher Ki-67 index. Expressions of TET2 and TET3 were significantly higher in adenomas with higher proliferation rate. UHRF1 showed gradually increased expression in higher proliferative adenoma samples, and a significant positive correlation was detected between UHRF2 expression and 5hmC level. Decitabine treatment significantly decreased 5mC and increased 5hmC levels in both cell lines, accompanied with decreased cell viability and proliferation. Conclusion The demethylation process negatively correlated with proliferation rate and the ratio of 5hmC to 5mC was higher in less differentiated adenomas. Therefore, epigenetic markers can be potential biomarkers for PitNET behavior. Altering the epigenome in adenoma cells by decitabine decreased proliferation, suggesting that this treatment might be a novel medical treatment for PitNET.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::192d75572724e066ef5fcd90b46c5c18Test
https://doi.org/10.1210/clinem/dgaa156Test

المؤلفون: Anton M. Jetten, Andrzej Slominski, Wojciech Jóźwicki, Anna A. Brożyna

المصدر: Exp Dermatol

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Skin Neoplasms, Retinoic acid, Dermatology, Biology, T-Lymphocytes, Regulatory, Biochemistry, Calcitriol receptor, Article, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, CYP24A1, medicine, Humans, Single-Blind Method, Lymphocytes, Vitamin D3 24-Hydroxylase, Receptor, Melanoma, Molecular Biology, Aged, 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, Aged, 80 and over, Cell Nucleus, Orphan receptor, FOXP3, Nuclear Receptor Subfamily 1, Group F, Member 1, Middle Aged, Nuclear Receptor Subfamily 1, Group F, Member 3, Hypoxia-Inducible Factor 1, alpha Subunit, medicine.disease, Cell Hypoxia, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, 030104 developmental biology, chemistry, Nuclear receptor, Cancer research, Receptors, Calcitriol, Female

الوصف: We analysed the correlation between the expression of HIF-1α (hypoxia-inducible factor 1 alpha), the nuclear receptors: VDR (vitamin D receptor), RORα (retinoic acid receptor-related orphan receptor alpha), and RORγ and CYP24A1 (cytochrome P450 family 24 subfamily A member 1) and CYP27B1 (cytochrome P450 family 27 subfamily B member 1), enzymes involved in vitamin D metabolism. In primary and metastatic melanomas, VDR negatively correlated with nuclear HIF-1α expression (r = -.2273, P = .0302; r = -.5081, P = .0011). Furthermore, the highest HIF-1α expression was observed in pT3-pT4 VDR-negative melanomas. A comparative analysis of immunostained HIF-1α and CYP27B1 and CYP24A1 showed lack of correlation between these parameters both in primary tumors and melanoma metastases. In contrast, RORα expression correlated positively with nuclear HIF-1α expression in primary and metastatic lesions (r = .2438, P = .0175; r = .3662, P = .0166). Comparable levels of HIF-1α expression pattern was observed in localized and advanced melanomas. RORγ in primary melanomas correlated also positively with nuclear HIF-1α expression (r = .2743, P = .0129). HIF-1α expression was the lowest in localized RORγ-negative melanomas. In addition, HIF-1α expression correlated with RORγ-positive lymphocytes in melanoma metastases. We further found that in metastatic lymph nodes FoxP3 immunostaining correlated positively with HIF-1α and RORγ expression in melanoma cells (r = .3667; P = .0327; r = .4208, P = .0129). In summary, our study indicates that the expression of VDR, RORα and RORγ in melanomas is related to hypoxia and/or HIF1-α activity, which also affects FoxP3 expression in metastatic melanoma. Therefore, the hypoxia can affect tumor biology by changing nuclear receptors expression and molecular pathways regulated by nuclear receptors and immune responses.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e3aa44913d2ff840a9108510f572a732Test
https://doi.org/10.1111/exd.14002Test

المؤلفون: Franco Bernini, Maria Pia Adorni, Francesca Zimetti, Daniela Galimberti, Paolo Caffarra, Cinzia Marchi, Marco Spallazzi, Nicoletta Ronda, Federica Barocco

المصدر: Journal of Lipid Research, Vol 60, Iss 8, Pp 1449-1456 (2019)
J Lipid Res

مصطلحات موضوعية: 0301 basic medicine, Apolipoprotein E, Adult, Male, medicine.medical_specialty, apolipoprotein A-I, QD415-436, 030204 cardiovascular system & hematology, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Cerebrospinal fluid, Alzheimer Disease, Internal medicine, medicine, Dementia, Humans, ATP Binding Cassette Transporter, Subfamily G, Member 1, Aged, apolipoprotein E, ATP-binding cassette A1, Amyloid beta-Peptides, biology, Cholesterol, business.industry, Neurodegeneration, ATP-binding cassette G1, Cell Biology, Middle Aged, apolipoprotein E4, medicine.disease, Pathophysiology, Peptide Fragments, 030104 developmental biology, chemistry, ABCA1, biology.protein, cardiovascular system, Female, lipids (amino acids, peptides, and proteins), Efflux, business, Patient-Oriented and Epidemiological Research, apolipoproteins, ATP Binding Cassette Transporter 1

الوصف: HDL-like particles in human cerebrospinal fluid (CSF) promote the efflux of cholesterol from astrocytes toward the neurons that rely on this supply for their functions. We evaluated whether cell cholesterol efflux capacity of CSF (CSF-CEC) is impaired in Alzheimer's disease (AD) by analyzing AD (n = 37) patients, non-AD dementia (non-AD DEM; n = 16) patients, and control subjects (n = 39). As expected, AD patients showed reduced CSF Aβ 1-42, increased total and phosphorylated tau, and a higher frequency of the apoe4 genotype. ABCA1- and ABCG1-mediated CSF-CEC was markedly reduced in AD (−73% and −33%, respectively) but not in non-AD DEM patients, in which a reduced passive diffusion CEC (−40%) was observed. Non-AD DEM patients displayed lower CSF apoE concentrations (−24%) compared with controls, while apoA-I levels were similar among groups. No differences in CSF-CEC were found by stratifying subjects for apoe4 status. ABCG1 CSF-CEC positively correlated with Aβ 1-42 (r = 0.305, P = 0.025), while ABCA1 CSF-CEC inversely correlated with total and phosphorylated tau (r = −0.348, P = 0.018 and r = −0.294, P = 0.048, respectively). The CSF-CEC impairment and the correlation with the neurobiochemical markers suggest a pathophysiological link between CSF HDL-like particle dysfunction and neurodegeneration in AD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c32af647e6d95ae13ea957fc028bbe95Test
http://www.sciencedirect.com/science/article/pii/S0022227520322392Test