المؤلفون: Yuan, Tze-An, Yourk, Vandy, Farhat, Ali, Guo, Katherine L, Garcia, Angela, Meyskens, Frank L, Liu-Smith, Feng

المصدر: International journal of molecular sciences. 21(5)

مصطلحات موضوعية: Humans, Melanoma, Receptor, IGF Type 1, Insulin-Like Growth Factor I, Estrogen Receptor alpha, Estrogen Receptor beta, Prognosis, Risk Factors, Case-Control Studies, Follow-Up Studies, Genotype, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Adolescent, Adult, Aged, Middle Aged, Child, Child, Preschool, Infant, Infant, Newborn, Female, Male, Young Adult, Biomarkers, Tumor, cutaneous melanoma, estrogen receptors, gender disparities, genetic variants, insulin-like growth factor 1, insulin-like growth factor 1 receptor, Estrogen, Clinical Research, Cancer, Genetics, 2.1 Biological and endogenous factors, Chemical Physics, Other Chemical Sciences, Other Biological Sciences

الوصف: The mechanism of gender disparity in cutaneous melanoma incidence remains unclear. Steroid hormones including estrogens have long been implicated in the course of melanoma, but the conclusion is controversial. Estrogen receptors (ERs) and insulin-like growth factor 1 receptor (IGF1R) show extensive crosstalk in cancer development, but how the ER/IGF1R network impacts melanoma is currently unclear. Here we studied the melanoma associations of selected SNPs from the ER/IGF1R network. Part of the International Genes, Environment, and Melanoma (GEM) cohort was used as a discovery set, and the Gene Environment Association Studies Initiative (GENEVA) dataset served as a validation set. Based on the associations with other malignant disease conditions, thirteen single nucleotide polymorphism (SNP) variants in ESR1, ESR2, IGF1, and IGF1R were selected for candidate gene association analyses. The rs1520220 in IGF1 and rs2229765 in IGF1R variants were significantly associated with melanoma risk in the GEM dataset after Benjamini-Hochberg multiple comparison correction, although they were not validated in the GENEVA set. The discrepancy may be caused by the multiple melanoma characteristics in the GEM patients. Further analysis of gender disparity was carried out for IGF1 and IGF1R SNPs in the GEM dataset. The GG phenotype in IGF1 rs1520220 (recessive model) presented an increased risk of melanoma (OR = 8.11, 95% CI: 2.20, 52.5, p = 0.006) in men but a significant opposite effect in women (OR = 0.15, 95% CI: 0.018, 0.86, p = 0.045). The AA genotype in IGF1R rs2229765 (recessive model) showed a significant protective effect in men (OR = 0.24, 95% CI: 0.07, 0.64, p = 0.008) and no effect in women. Results from the current study are warranted for further validation.

الوصول الحر: https://escholarship.org/uc/item/8xw1f78mTest

المؤلفون: Kudryashova, Tatiana V, Shen, Yuanjun, Pena, Andressa, Cronin, Emily, Okorie, Evelyn, Goncharov, Dmitry A, Goncharova, Elena A

المصدر: International Journal of Molecular Sciences. 19(10)

مصطلحات موضوعية: Biochemistry and Cell Biology, Biological Sciences, Medicinal and Biomolecular Chemistry, Chemical Sciences, Microbiology, Rare Diseases, Lung, Cardiovascular, Activins, Adult, Antibodies, Cell Proliferation, Culture Media, Conditioned, Female, Humans, Hypertension, Pulmonary, Intercellular Signaling Peptides and Proteins, Male, Middle Aged, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Phosphorylation, Pulmonary Artery, Signal Transduction, Smad2 Protein, Smad3 Protein, Solubility, Transforming Growth Factor beta, Up-Regulation, Young Adult, pulmonary arterial hypertension, human smooth muscle cells, TGF-beta, Activin A, Gremlin 1, therapeutic antibody, Smad proteins, PDGF-BB, growth, proliferation, TGF-β, Other Chemical Sciences, Genetics, Other Biological Sciences, Chemical Physics, Biochemistry and cell biology, Medicinal and biomolecular chemistry

الوصف: Increased growth and proliferation of distal pulmonary artery vascular smooth muscle cells (PAVSMC) is an important pathological component of pulmonary arterial hypertension (PAH). Transforming Growth Factor-β (TGF-β) superfamily plays a critical role in PAH, but relative impacts of self-secreted Activin A, Gremlin1, and TGF-β on PAH PAVSMC growth and proliferation are not studied. Here we report that hyper-proliferative human PAH PAVSMC have elevated secretion of TGF-β1 and, to a lesser extent, Activin A, but not Gremlin 1, and significantly reduced Ser465/467-Smad2 and Ser423/425-Smad3 phosphorylation compared to controls. Media, conditioned by PAH PAVSMC, markedly increased Ser465/467-Smad2, Ser423/425-Smad3, and Ser463/465-Smad1/5 phosphorylation, up-regulated Akt, ERK1/2, and p38 MAPK, and induced significant proliferation of non-diseased PAVSMC. Inhibitory anti-Activin A antibody reduced PAH PAVSMC growth without affecting canonical (Smads) or non-canonical (Akt, ERK1/2, p38 MAPK) effectors. Inhibitory anti-TGF-β antibody significantly reduced P-Smad3, P-ERK1/2 and proliferation of PAH PAVSMC, while anti-Gremlin 1 had no anti-proliferative effect. PDGF-BB diminished inhibitory effects of anti-Activin A and anti-TGF-β antibodies. None of the antibodies affected growth and proliferation of non-diseased PAVSMC induced by PAH PAVSMC-secreted factors. Together, these data demonstrate that human PAH PAVSMC have secretory, proliferative phenotype that could be targeted by anti-Activin A and anti-TGF-β antibodies; potential cross-talk with PDGF-BB should be considered while developing therapeutic interventions.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8jb8v3h1Test

المؤلفون: Noo Ri Lee, Beom Jun Kim, Kyong Oh Shin, Eun Jung Kim, Gareth G. Lavery, Hyun Jee Hwang, Kyungho Park, Young Bin Lee, Solam Lee, Chung Hyeok Lee, Eung Ho Choi, Sung Jay Choe

المصدر: International Journal of Molecular Sciences
Volume 22
Issue 11
International Journal of Molecular Sciences, Vol 22, Iss 5750, p 5750 (2021)

مصطلحات موضوعية: 0301 basic medicine, Male, 11-beta-hydroxysteroid dehydrogenase type 1, 030207 dermatology & venereal diseases, chemistry.chemical_compound, Mice, 0302 clinical medicine, Corticosterone, 11β-hydroxysteroid dehydrogenase type 1, Biology (General), Spectroscopy, Barrier function, Mice, Knockout, biology, integumentary system, glucocorticoids, General Medicine, Middle Aged, Computer Science Applications, Chemistry, Knockout mouse, Cytokines, Female, Inflammation Mediators, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Adult, medicine.medical_specialty, endocrine system, QH301-705.5, Catalysis, Permeability, Article, Inorganic Chemistry, 03 medical and health sciences, Young Adult, Lipid biosynthesis, Internal medicine, medicine, Animals, Humans, Physical and Theoretical Chemistry, Molecular Biology, QD1-999, Aged, Transepidermal water loss, Organic Chemistry, Hairless, Skin Aging, 030104 developmental biology, Endocrinology, chemistry, Gene Expression Regulation, biology.protein, Cortisone, Epidermis, barrier function, Biomarkers, epidermal lipids

الوصف: Inactive cortisone is converted into active cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Excessive levels of active glucocorticoids could deteriorate skin barrier function
barrier impairment is also observed in aged skin. In this study, we aimed to determine whether permeability barrier impairment in the aged skin could be related to increased 11β-HSD1 expression. Aged humans (n = 10) showed increased cortisol in the stratum corneum (SC) and oral epithelium, compared to young subjects (n = 10). 11β-HSD1 expression (as assessed via immunohistochemical staining) was higher in the aged murine skin. Aged hairless mice (56-week-old, n = 5) manifested greater transepidermal water loss, lower SC hydration, and higher levels of serum inflammatory cytokines than the young mice (8-week-old, n = 5). Aged 11β-HSD1 knockout mice (n = 11), 11β-HSD1 inhibitor (INHI)-treated aged wild type (WT) mice (n = 5) and young WT mice (n = 10) exhibited reduced SC corticosterone level. Corneodesmosome density was low in WT aged mice (n = 5), but high in aged 11β-HSD1 knockout and aged INHI-treated WT mice. Aged mice exhibited lower SC lipid levels
this effect was reversed by INHI treatment. Therefore, upregulation of 11β-HSD1 in the aged skin increases the active-glucocorticoid levels
this suppresses SC lipid biosynthesis, leading to impaired epidermal permeability barrier.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6f8084c8f5c816d4e38a571e81ad199fTest
https://pubmed.ncbi.nlm.nih.gov/34072239Test

المؤلفون: Anna Pawłowska, Bartłomiej Barczyński, Iwona Wertel, Agnieszka Kwiatkowska, Rafał Tarkowski, Dorota Suszczyk, Jan Kotarski, Agata Chudzik

المصدر: International Journal of Molecular Sciences
Volume 22
Issue 21
International Journal of Molecular Sciences, Vol 22, Iss 11563, p 11563 (2021)

مصطلحات موضوعية: Myeloid, medicine.medical_treatment, Carcinoma, Ovarian Epithelial, B7-H1 Antigen, Medicine, Ascitic Fluid, Biology (General), Spectroscopy, Aged, 80 and over, Ovarian Neoplasms, medicine.diagnostic_test, biology, General Medicine, Middle Aged, Prognosis, Computer Science Applications, Chemistry, medicine.anatomical_structure, ovarian cancer, Female, immunotherapy, Adult, QH301-705.5, Antigen-Presenting Cells, Catalysis, Article, Flow cytometry, Inorganic Chemistry, Young Adult, PD-L1, Humans, tumor microenvironment, Physical and Theoretical Chemistry, Antigen-presenting cell, Molecular Biology, QD1-999, Aged, Tumor microenvironment, business.industry, Peritoneal fluid, Organic Chemistry, Immunotherapy, Dendritic Cells, programmed cell death pathway, medicine.disease, Programmed Cell Death 1 Ligand 2 Protein, biology.protein, Cancer research, immune suppression, business, Ovarian cancer

الوصف: The latest literature demonstrates the predominant role of the programmed cell death axis (PD-1/PD-L1/PD-L2) in ovarian cancer (OC) pathogenesis. However, data concerning this issue is ambiguous. Our research aimed to evaluate the clinical importance of PD-L1/PD-L2 expression in OC environments. We evaluated the role of PD-L1/PD-L2 in OC patients (n = 53). The analysis was performed via flow cytometry on myeloid (mDCs) and plasmacytoid dendritic cells (pDCs) and monocytes/macrophages (MO/MA) in peripheral blood, peritoneal fluid (PF), and tumor tissue (TT). The data were correlated with clinicopathological characteristics and prognosis of OC patients. The concentration of soluble PD-L1 (sPD-L1) and PD-1 in the plasma and PF were determined by ELISA. We established an accumulation of PD-L1+/PD-L2+ mDCs, pDCs, and MA in the tumor microenvironment. We showed an elevated level of sPD-L1 in the PF of OC patients in comparison to plasma and healthy subjects. sPD-L1 levels in PF showed a positive relationship with Ca125 concentration. Moreover, we established an association between higher sPD-L1 levels in PF and shorter survival of OC patients. An accumulation of PD-L1+/PD-L2+ mDCs, pDCs, and MA in the TT and high sPD-L1 levels in PF could represent the hallmark of immune regulation in OC patients.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::14a8fc4cef4054f54c194e1ff23cad38Test
http://europepmc.org/articles/PMC8583913Test

المؤلفون: Anna Hymos, Wojciech Załuska, Iwona Smarz-Widelska, Ewelina Grywalska, Krzysztof Gosik, Paulina Niedźwiedzka-Rystwej, Izabela Korona-Glowniak, Jacek Roliński, Jarosław Ludian, Sebastian Mertowski

المصدر: International Journal of Molecular Sciences
Volume 21
Issue 21
International Journal of Molecular Sciences, Vol 21, Iss 8001, p 8001 (2020)

مصطلحات موضوعية: 0301 basic medicine, Male, Epstein-Barr Virus Infections, T-Lymphocytes, Programmed Cell Death 1 Receptor, medicine.disease_cause, B7-H1 Antigen, lcsh:Chemistry, Epstein–Barr virus, immunology, 0302 clinical medicine, PD-1, CD8+ T lymphocyte, lcsh:QH301-705.5, Spectroscopy, B-Lymphocytes, medicine.diagnostic_test, biology, CD19+ B lymphocyte, Glomerulonephritis, General Medicine, Middle Aged, programmed cell death protein 1, Computer Science Applications, Up-Regulation, 030220 oncology & carcinogenesis, Female, Adult, PD-L1, Programmed cell death, programmed death-ligand 1, Peripheral blood mononuclear cell, Catalysis, Virus, Article, Flow cytometry, Inorganic Chemistry, 03 medical and health sciences, Young Adult, Antigen, EBV, medicine, Humans, Physical and Theoretical Chemistry, Molecular Biology, Aged, CD4+ T lymphocyte, business.industry, Organic Chemistry, medicine.disease, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, ROC Curve, Case-Control Studies, Immunology, biology.protein, Leukocytes, Mononuclear, business, glomerulonephritis

الوصف: Alterations to the programmed cell death protein-1 (PD-1) pathway were previously shown to be involved in a poorer prognosis for patients with proliferative glomerulonephritis (PGN). Here, we investigated the association between several infectious agents and the expression of PD-1 and its ligand (PD-L1) on T and B lymphocytes in patients with PGN and nonproliferative glomerulonephritis (NPGN). A cohort of 45 newly-diagnosed patients (23 with PGN and 22 with NPGN) and 20 healthy volunteers was enrolled. The percentage of peripheral blood mononuclear cells expressing PD-1 and PD-L1 antigens was determined by flow cytometry. We found PD-1 and PD-L1 expression on T and B lymphocytes was higher in PGN patients than in NPGN patients and controls. We also found that reactivation of the Epstein-Barr virus (EBV) correlated with the expression of PD-1/PD-L1 antigens in patients with PGN. Further receiver operating characteristic analysis indicated that PD-1 expression could distinguish EBV-positive PGN patients from those with NPGN or healthy controls. The use of PD-1 expression as a non-invasive marker of PGN should be further investigated.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::372c9bec7d09fa587bba4d66a2497702Test

المؤلفون: Anna Chiara Frigo, Perry M. Elliott, Domenico Corrado, Marco Cason, Cristina Basso, Petros Syrris, Rudy Celeghin, Gaetano Thiene, Maria Bueno Marinas, Barbara Bauce, Kalliopi Pilichou, Riccardo Bariani, Joanna Jager

المصدر: International Journal of Molecular Sciences, Vol 21, Iss 4, p 1536 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 4

مصطلحات موضوعية: Male, 0301 basic medicine, Proband, Oncology, Cardiomyopathy, Disease, 030204 cardiovascular system & hematology, Cohort Studies, lcsh:Chemistry, 0302 clinical medicine, Child, lcsh:QH301-705.5, Arrhythmogenic Right Ventricular Dysplasia, Spectroscopy, Brugada syndrome, Arrhythmogenic Cardiomyopathy 2, Biomarker 3, MicroRNA 1, Hypertrophic cardiomyopathy, Dilated cardiomyopathy, General Medicine, biomarker 3, Middle Aged, microrna 1, Computer Science Applications, Female, Signal Transduction, Adult, medicine.medical_specialty, arrhythmogenic cardiomyopathy 2, Myocarditis, Adolescent, Article, Catalysis, Inorganic Chemistry, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Physical and Theoretical Chemistry, Molecular Biology, Aged, Genetic heterogeneity, business.industry, Gene Expression Profiling, Myocardium, Organic Chemistry, medicine.disease, MicroRNAs, 030104 developmental biology, ROC Curve, lcsh:Biology (General), lcsh:QD1-999, business, Biomarkers

الوصف: Arrhythmogenic Cardiomyopathy (AC) is a clinically and genetically heterogeneous myocardial disease. Half of AC patients harbour private desmosomal gene variants. Although microRNAs (miRNAs) have emerged as key regulator molecules in cardiovascular diseases and their involvement, correlated to phenotypic variability or to non-invasive biomarkers, has been advanced also in AC, no data are available in larger disease cohorts. Here, we propose the largest AC cohort unbiased by technical and biological factors. MiRNA profiling on nine right ventricular tissue, nine blood samples of AC patients, and four controls highlighted 10 differentially expressed miRNAs in common. Six of these were validated in a 90-AC patient cohort independent from genetic status: miR-122-5p, miR-133a-3p, miR-133b, miR-142-3p, miR-182-5p, and miR-183-5p. This six-miRNA set showed high discriminatory diagnostic power in AC patients when compared to controls (AUC-0.995), non-affected family members of AC probands carrying a desmosomal pathogenic variant (AUC-0.825), and other cardiomyopathy groups (Hypertrophic Cardiomyopathy: AUC-0.804, Dilated Cardiomyopathy: AUC-0.917, Brugada Syndrome: AUC-0.981, myocarditis: AUC-0.978). AC-related signalling pathways were targeted by this set of miRNAs. A unique set of six-miRNAs was found both in heart-tissue and blood samples of AC probands, supporting its involvement in disease pathogenesis and its possible role as a non-invasive AC diagnostic biomarker.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bf87c4d1b0d6e9788709a473a5d50bd6Test
https://www.mdpi.com/1422-0067/21/4/1536Test

المؤلفون: Rustam H. Ziganshin, Arkadii K. Beilin, Alexandra L. Rippa, Ekaterina A. Vorotelyak, A. V. Vasiliev, Maxim M. Perfilov, Nadezhda A. Evtushenko, Nadya G. Gurskaya, Elena V. Alpeeva, Anastasiya V. Kosykh, E. B. Dashinimaev

المصدر: International Journal of Molecular Sciences
Volume 22
Issue 8
International Journal of Molecular Sciences, Vol 22, Iss 3809, p 3809 (2021)

مصطلحات موضوعية: Keratinocytes, Male, Proteomics, Fluorescent Antibody Technique, Cre recombination, immortalization, fibroblast, Extracellular matrix, lcsh:Chemistry, Gene Order, COL7A1, Transgenes, Child, Homologous Recombination, Telomerase, lcsh:QH301-705.5, Cellular Senescence, Spectroscopy, Cell Line, Transformed, Polycomb Repressive Complex 1, RDEB, Chemistry, General Medicine, Middle Aged, Immunohistochemistry, Epidermolysis Bullosa Dystrophica, Computer Science Applications, Cell biology, medicine.anatomical_structure, Gene Knockdown Techniques, Female, Keratinocyte, hTERT, bmi-1, Adult, secretomes, Adolescent, Genetic Vectors, Primary Cell Culture, keratinocyte, Article, Catalysis, Inorganic Chemistry, Young Adult, stratification, Dermis, medicine, Humans, Physical and Theoretical Chemistry, Progenitor cell, Fibroblast, Molecular Biology, Cell Proliferation, Integrases, Organic Chemistry, Fibroblasts, lcsh:Biology (General), lcsh:QD1-999, Cell culture, Mutation, Ectopic expression, 3D skin equivalent, Immortalised cell line, Biomarkers

الوصف: The recessive form of dystrophic epidermolysis bullosa (RDEB) is a crippling disease caused by impairments in the junctions of the dermis and the basement membrane of the epidermis. Using ectopic expression of hTERT/hTERT + BMI-1 in primary cells, we developed expansible cultures of RDEB fibroblasts and keratinocytes. We showed that they display the properties of their founders, including morphology, contraction ability and expression of the respective specific markers including reduced secretion of type VII collagen (C7). The immortalized keratinocytes retained normal stratification in 3D skin equivalents. The comparison of secreted protein patterns from immortalized RDEB and healthy keratinocytes revealed the differences in the contents of the extracellular matrix that were earlier observed specifically for RDEB. We demonstrated the possibility to reverse the genotype of immortalized cells to the state closer to the progenitors by the Cre-dependent hTERT switch off. Increased β-galactosidase activity and reduced proliferation of fibroblasts were shown after splitting out of transgenes. We anticipate our cell lines to be tractable models for studying RDEB from the level of single-cell changes to the evaluation of 3D skin equivalents. Our approach permits the creation of standardized and expandable models of RDEB that can be compared with the models based on primary cell cultures.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6a71ac837e97a830f60a22e9d9c78f7eTest

المؤلفون: Dejan B. Budimirovic, Dean F. Wong, David S. Russell, Samuel D. Martin, Ayon Nandi, Thomas W. Sedlak, Danna Jennings, John Seibyl, Olivier Barret, Keith J. Slifer, James Robert Brašić

المصدر: International Journal of Molecular Sciences
Volume 22
Issue 6
International Journal of Molecular Sciences, Vol 22, Iss 2863, p 2863 (2021)

مصطلحات موضوعية: Male, Autism Spectrum Disorder, animal diseases, Caudate nucleus, Pilot Projects, Bioinformatics, lcsh:Chemistry, Pathogenesis, Medicine, positron emission tomography (PET), lcsh:QH301-705.5, Spectroscopy, Cerebral Cortex, Metabotropic glutamate receptor 5, Putamen, neurodevelopmental disorders, Brain, General Medicine, Middle Aged, radiotracer, Computer Science Applications, fragile X mental retardation 1 gene (FMR1), Fragile X syndrome, cortex, Autism spectrum disorder, putamen, Female, Adult, Adolescent, Receptor, Metabotropic Glutamate 5, Thalamus, Article, Catalysis, Inorganic Chemistry, Young Adult, thalamus, mental disorders, Animals, Humans, Physical and Theoretical Chemistry, Molecular Biology, business.industry, Organic Chemistry, binding potential, caudate nucleus, cingulate, medicine.disease, lcsh:Biology (General), lcsh:QD1-999, nervous system, Metabotropic glutamate receptor, Fragile X Syndrome, Positron-Emission Tomography, business

الوصف: Multiple lines of evidence suggest that dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR5) plays a role in the pathogenesis of autism spectrum disorder (ASD). Yet animal and human investigations of mGluR5 expression provide conflicting findings about the nature of dysregulation of cerebral mGluR5 pathways in subtypes of ASD. The demonstration of reduced mGluR5 expression throughout the living brains of men with fragile X syndrome (FXS), the most common known single-gene cause of ASD, provides a clue to examine mGluR5 expression in ASD. We aimed to (A) compare and contrast mGluR5 expression in idiopathic autism spectrum disorder (IASD), FXS, and typical development (TD) and (B) show the value of positron emission tomography (PET) for the application of precision medicine for the diagnosis and treatment of individuals with IASD, FXS, and related conditions. Two teams of investigators independently administered 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB), a novel, specific mGluR5 PET ligand to quantitatively measure the density and the distribution of mGluR5s in the brain regions, to participants of both sexes with IASD and TD and men with FXS. In contrast to participants with TD, mGluR5 expression was significantly increased in the cortical regions of participants with IASD and significantly reduced in all regions of men with FXS. These results suggest the feasibility of this protocol as a valuable tool to measure mGluR5 expression in clinical trials of individuals with IASD and FXS and related conditions.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::beeecd03e12fc46f8cc22068fe492cbcTest

المؤلفون: Jih-Jin Tsai, Po Lin Chen, Yu Chih Lo, Yu Wen Chien, Guey Chuen Perng, Irwin Puc, Tzu Chuan Ho, Amrita Vats, Ko Lun Yen

المصدر: International Journal of Molecular Sciences, Vol 22, Iss 2879, p 2879 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 6

مصطلحات موضوعية: 0301 basic medicine, Male, medicine.medical_treatment, Interleukin 1 receptor, type II, Disease, Severity of Illness Index, Dengue fever, lcsh:Chemistry, 0302 clinical medicine, Receptors, Interleukin-1 Type II, CD154, lcsh:QH301-705.5, Spectroscopy, Aged, 80 and over, General Medicine, Middle Aged, Computer Science Applications, Interleukin-10, Cytokine, Tumor necrosis factor alpha, Female, biomarker prediction, Adult, Adolescent, CD14, 030231 tropical medicine, Catalysis, Severe dengue, Article, Inorganic Chemistry, 03 medical and health sciences, Young Adult, medicine, Humans, Physical and Theoretical Chemistry, Molecular Biology, severe dengue, Aged, business.industry, Organic Chemistry, Dengue Virus, medicine.disease, dengue, cytokines, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Immunology, business, Transcriptome, Biomarkers, flaviviruses

الوصف: Clinical presentations of dengue fever (DF) are diverse and non-specific, causing unpredictable progression and outcomes. Its progression and severity have been associated with cytokine levels alteration. In this study, dengue patients were classified into groups following the 2009 WHO dengue classification scheme to investigate the cytokine signature at different severity of the disease: dengue without warning sign symptoms (A)
dengue with warning signs (B)
severe dengue (C)
other fever (OF) and healthy (Healthy). We analyzed 23 different cytokines simultaneously, namely IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-33, CD14, CD54, CD62E, CD62L, CD62p, CD106, CD121b, CD154, CD178, GM-CSF, IFN-g, MIF, ST2 and TNF from patients admitted to National Cheng Kung University Hospital during the 2015 Taiwan dengue outbreak. Cytokines TNF, CD54, CD62E, CD62L, CD62P, GM-CSF, IL-1b, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-17A, INF-g and MIF were elevated while CD106, CD154, IL-4 and L-33 were decreased when compared to the control. IL-10 demonstrated to be a potential diagnostic marker for DF (H and A group
AUC = 0.944, H and OF group
AUC = 0.969). CD121b demonstrated to be predictive of the SD (A and B group
AUC = 0.744, B and C group
AUC = 0.775). Our results demonstrate the cytokine profile changes during the progression of dengue and highlight possible biomarkers for optimizing effective intervention strategies.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f73d721f1bfb5ed94c28f9b599d21f0dTest
https://www.mdpi.com/1422-0067/22/6/2879Test

المؤلفون: Rina Meidan, Nina Schmid, Artur Mayerhofer, Kim-Gwendolyn Dietrich, Doris Mayr, Ignasi Forné, Magdalena Szymanska, Alexander Burges

المصدر: International Journal of Molecular Sciences, Vol 22, Iss 2047, p 2047 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 4

مصطلحات موضوعية: 0301 basic medicine, Cell, lcsh:Chemistry, 0302 clinical medicine, Sirtuin 1, Sirtuin 3, RNA, Small Interfering, lcsh:QH301-705.5, Spectroscopy, Granulosa Cell Tumor, Aged, 80 and over, siRNA silencing, General Medicine, Middle Aged, Computer Science Applications, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Sirtuin, Adult, Programmed cell death, SIRT3, Adolescent, Carbazoles, Down-Regulation, Biology, Heterocyclic Compounds, 2-Ring, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Young Adult, Cell Line, Tumor, medicine, Humans, Proliferation Marker, Gene Silencing, RNA, Messenger, Physical and Theoretical Chemistry, Molecular Biology, Aged, Cell growth, Organic Chemistry, EX 527, KGN, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Apoptosis, Cancer research, biology.protein

الوصف: Sirtuins (SIRTs) are NAD+-dependent deacetylases that regulate proliferation and cell death. In the human ovary, granulosa cells express sirtuin 1 (SIRT1), which has also been detected in human tumors derived from granulosa cells, i.e., granulosa cell tumors (GCTs), and in KGN cells. KGN cells are an established cellular model for the majority of GCTs and were used to explore the role of SIRT1. The SIRT1 activator SRT2104 increased cell proliferation. By contrast, the inhibitor EX527 reduced cell numbers, without inducing apoptosis. These results were supported by the outcome of siRNA-mediated silencing studies. A tissue microarray containing 92 GCTs revealed nuclear and/or cytoplasmic SIRT1 staining in the majority of the samples, and also, SIRT2-7 were detected in most samples. The expression of SIRT1–7 was not correlated with the survival of the patients
however, SIRT3 and SIRT7 expression was significantly correlated with the proliferation marker Ki-67, implying roles in tumor cell proliferation. SIRT3 was identified by a proteomic analysis as the most abundant SIRT in KGN. The results of the siRNA-silencing experiments indicate involvement of SIRT3 in proliferation. Thus, several SIRTs are expressed by GCTs, and SIRT1 and SIRT3 are involved in the growth regulation of KGN. If transferable to GCTs in situ, these SIRTs may represent novel drug targets.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bdd05533800a40d355743143c69dc3a2Test
https://pubmed.ncbi.nlm.nih.gov/33669567Test