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1.
Rev. bras. ginecol. obstet ; 43(9): 682-689, Sept. 2021. graf
Article in English | LILACS | ID: biblio-1351778

ABSTRACT

Abstract Objective The aim of the present study was to compare the local and systemic expression of the factors linked to the interferon alpha (IFN-α) activation pathway in different degrees of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods A total of 128 patients with CIN I, CIN II, CIN III and cervical cancer was evaluated. The real-time polymerase chain reaction (RT-PCR) technique was used to evaluate the gene expression of IFNR1, IFNR2, IFN-α, oligoadenylate synthase (2'5′OAS), cytokine signal suppressor 1 (SOCS) 1, SOCS3, signal transducer and transcription activator 1 (STAT1), and IRF9 from 128 biopsies. A total of 46 out of 128 samples were evaluated by flow cytometry for IFNAR1, IFNAR2, STAT1, IRF7 and IFN-α in peripheral blood cells. Results Patients with CIN II and III (63 samples) had a low local expression of IFNR1, but not IFNR2. Patients with some degree of injury showed high expression of SOCS1 and SOCS3. Systemically, patients with CIN II and III (20 samples) had a significant increase in IFNR1, IFNR2, STAT1, IRF7, and IFN-α in helper, cytotoxic T lymphocytes, and in monocytes. Conclusion Patients with high-grade lesions have increased systemic expression of IFN-α and its activation pathways in helper and cytotoxic T lymphocytes, as well as in monocytes due to an exacerbation of the immune response in these patients. This phenomenon is not accompanied by resolution of the lesion due to a defect in the IFN-α activation pathway that revealed by low local IFNAR1 expression and high local expression of SOCS1 and SOCS3.


Resumo Objetivo O objetivo do presente estudo foi comparar a expressão local e sistêmica dos fatores ligados à via de ativação do interferon alfa (IFN-α) em diferentes graus de neoplasia intraepitelial cervical (NIC) e câncer cervical (CA) Métodos Foram avaliados 128 pacientes com NIC I, NIC II, NIC III e CA. A técnica de reação de cadeia de polimerase em tempo real (RT-PCR, na sigla em inglês) foi realizada para avaliar a expressão gênica do receptor de interferon (IFNR) 1, IFNR2, IFN-α, 2′-5′- oligoadenilato sintetase (2′5′OAS), supressor de sinalização de citocina (SOCS)1, SOCS3, transdutor de sinal e ativador de transcrição 1 (STAT1) e fator regulador de interferon 9 (IRF9) das 128 biópsias. Das 128 amostras, 46 foram avaliadas por citometria de fluxo para IFNAR1, IFNAR2, STAT1, IRF7 e IFN-α em células de sangue periférico. Resultados Pacientes com NIC II e III (63 amostras) tiveram baixa expressão local de IFNR1 mas não de IFNR2. Pacientes com algum grau de lesão apresentaram alta expressão de SOCS1 e SOCS3. Sistemicamente, os pacientes com NIC II e III (20 amostras) tiveram um aumento significativo de IFNR1, IFNR2, STAT1, IRF7 e IFN-α em linfócitos T auxiliares, citotóxicos e monócitos. Conclusão Pacientes com lesões de alto grau apresentam expressão sistêmica aumentada de IFN-α e suas vias de ativação em linfócitos T auxiliares e citotóxicos, bem como em monócitos, devido à exacerbação da resposta imune nesses pacientes. Este fenômeno não é acompanhado pela resolução da lesão devido a um defeito na via de ativação do IFN-α que é revelado pela baixa expressão local de IFNR1 e alta expressão local de SOCS1 e SOCS3.


Subject(s)
Humans , Female , Uterine Cervical Neoplasms/genetics , Cervical Intraepithelial Neoplasia/genetics , Interferon-alpha , Suppressor of Cytokine Signaling Proteins/metabolism
2.
Article in Chinese | WPRIM | ID: wpr-776656

ABSTRACT

OBJECTIVE@#To investigate the association between suppressor of cytokine signaling (SOCS) hypomethylation and T helper 17 (Th17) cell/regulatory T (Treg) cell imbalance in children with Henoch-Schönlein purpura (HSP) and the immune pathogenesis of HSP.@*METHODS@#A total of 32 children in the acute stage of HSP who were hospitalized from May 2014 to January 2015 were enrolled as subjects, and 28 children who underwent physical examination were enrolled as normal control group. ELISA was used to measure the plasma level of interleukin-6 (IL-6). Flow cytometry was used to measure the percentages of CD4 IL-17A T cells (Th17 cells) and CD4CD25 Treg cells (Treg cells) in peripheral blood and mean fluorescence intensity (MFI) for phosphorylated-STAT3 (pSTAT3) protein in CD4 T cells. Quantitative real-time PCR was used to measure the mRNA expression of suppressor of cytokine signaling-1 (SOCS1) and suppressor of cytokine signaling-3 (SOCS3) in CD4 T cells. High-resolution melting (HRM) was used to evaluate the methylation level of the CpG islands in SOCS1 exon 2 and the CpG islands of the potential bind sites for STAT3 in the 5'-untranslated region (5'-UTR) of SOCS3 in peripheral blood mononucleated cells.@*RESULTS@#Compared with the normal control group, the HSP group had significant increases in plasma IL-6 concentration and MFI for pSTAT3 in CD4 T cells, as well as a significant increase in the percentage of Th17 cells and a significant reduction in the percentage of Treg cells (P<0.05). The HSP group had significantly higher mRNA expression of SOCS1 and SOCS3 in peripheral blood mononucleated cells than the normal control group (P<0.05). In the HSP group, the mRNA expression of SOCS1 and SOCS3 was negatively correlated with Th17/Treg ratio (P<0.05). The HSP group had hypomethylation of the CpG islands in SOCS1 exon 2 and the potential binding site for STAT3 in SOCS3 5'-UTR, while the normal control group had complete demethylation.@*CONCLUSIONS@#Low relative expression of SOCS1 and SOCS3 caused by hypomethylation may be a factor for Th17/Treg imbalance in children with HSP.


Subject(s)
Child , Humans , Interleukin-6 , Lymphocyte Count , IgA Vasculitis , Suppressor of Cytokine Signaling Proteins , T-Lymphocytes, Regulatory , Th17 Cells
3.
Pesqui. vet. bras ; 38(10): 1972-1980, out. 2018. tab, ilus
Article in English | LILACS, VETINDEX | ID: biblio-976388

ABSTRACT

The inflammatory infiltrate in the tumor microenvironment, particularly in mammary tumors, has aroused great interest in oncology, to play different roles in the progression or tumor regression dependent on the types and cell subsets involved. The present study aimed to evaluate (1) the occurrence and intensity of macrophage infiltration in the mammary carcinoma microenvironment, (2) the expression of SOCS1 and SOCS3 proteins in tumor associated macrophages, (3) any association between these parameters and tumor development, as well as survival rates in female dogs. Twenty-two female dogs diagnosed as carcinoma arising in a mixed tumor (CMT) by histopathology were divided into two groups following mastectomy: dogs without metastasis (CMT(-)=11) and those with metastasis (CMT(+)=11). The following parameters were analyzed: tumor size, lymph node metastasis, clinical stage, histological grade, distribution and intensity of inflammatory infiltrate, tumor macrophage quantification by immunohistochemical analysis of SOCS1 and SOCS3 expression, and immunophenotyping of peripheral blood leukocytes by flow cytometry. Dogs with the higher proportions of macrophages in the inflammatory infiltrate (≥400/tumor) also had higher survival rates in comparison with dogs with less macrophages. Immunostaining revealed higher proportions of SOCS3-positive macrophages in dogs without lymph node metastasis, while SOCS1-positive macrophages were predominant in dogs with metastasis (p<0.05). Multivariate analysis found associations between survival rate and clinical staging (p=0.025), histological grade (p=0.007), and the expression of MHC-CI in circulating monocytes (p=0.018). Higher SOCS3 expression in activated macrophages within the inflammatory infiltrate were considered indicative of an antitumor immune response, improved clinicopathological parameters and longer survival, whereas SOCS1-related activation was associated with tumor progression, metastasis development and reduced survival in female dogs with mammary carcinomas.(AU)


O infiltrado inflamatório no microambiente tumoral, particularmente nos tumores mamários, tem despertado grande interesse na oncologia, por desempenhar diferentes funções na progressão ou regressão tumoral, dependendo dos tipos e subtipos celulares envolvidos. O presente estudo teve como objetivo avaliar: (1) a ocorrência e a intensidade do infiltrado macrofágico no microambiente do carcinoma mamário; (2) a expressão das proteínas SOCS1 e SOCS3 nos macrófagos associados ao tumor; (3) qualquer associação relacionada ao prognóstico entre estes parâmetros e o desenvolvimento tumoral, assim como a taxa de sobrevida. Vinte e duas cadelas diagnosticadas com carcinoma em tumor misto (CTM) por exame histopatológico foram divididas em dois grupos após a mastectomia: cadelas sem metástase (CTM(-)=11) e cadelas com metástase (CTM(+)=11). Foram analisados os seguintes parâmetros: tamanho do tumor, metástase para linfonodo, estadiamento clínico, grau histológico, distribuição e intensidade do infiltrado inflamatório, quantificação dos macrófagos tumorais por análise imuno-histoquímica da expressão de SOCS1 e SOCS3, e imunofenotipagem dos leucócitos (monócitos e linfócitos) do sangue periférico por citometria de fluxo. Cadelas que apresentavam maiores proporções de macrófagos no infiltrado inflamatório (≥400/tumor) também tiveram maior taxa de sobrevida em comparação àquelas com menos macrófagos. A imunomarcação revelou maiores proporções de macrófagos SOCS3-positivos em cães sem metástase para linfonodo, enquanto que macrófagos SOCS1-positivos foram predominantes naqueles com metástase (p<0,05). A análise multivariada identificou associações entre a taxa de sobrevida e o estadiamento clínico (p=0,025), grau histológico (p=0,007) e a expressão de MHC-CI em monócitos circulantes (p=0,018). A maior expressão de SOCS3 nos macrófagos ativados foi considerada indicativa de uma resposta imune antitumoral, melhores parâmetros clínicos e maior taxa de sobrevida, ao passo que a ativação relacionada com SOCS1 foi associada à progressão tumoral, desenvolvimento de metástase e redução na taxa de sobrevida em cadelas com carcinoma mamário.(AU)


Subject(s)
Animals , Female , Dogs , Carcinoma/pathology , Carcinoma/veterinary , Mammary Neoplasms, Animal/pathology , Suppressor of Cytokine Signaling Proteins , Dogs , Suppressor of Cytokine Signaling 1 Protein , Suppressor of Cytokine Signaling 3 Protein
4.
Braz. j. infect. dis ; 20(4): 379-383, July-Aug. 2016. tab, graf
Article in English | LILACS | ID: biblio-828128

ABSTRACT

Abstract Background In the current study we aimed to find out the impact of cytokine-inducible Src homology 2 domain protein (CISH) gene polymorphisms on the risk of pulmonary tuberculosis (PTB) in a sample of Iranian population. Materials and methods Polymorphisms of CISH rs2239751, rs414171, and rs6768300 were determined in 200 PTB patients and 200 healthy subjects using T-ARMS-PCR or PCR-RFLP method. Results The results showed that rs414171 A>T genotypes significantly decreased the risk of PTB (OR = 0.16, 95% CI = 0.10–0.27, p < 0.0001, AT vs AA; OR = 0.31, 95% CI = 0.14–0.68, p < 0.0001, TT vs AA; OR = 0.19, 95% CI = 0.12–0.29, p < 0.0001, AT+TT vs AA; OR = 0.29, 95%CI = 0.20–0.42, p < 0.0001, T vs A). For rs6768300, the findings indicated that this variant decreased the risk of PTB (OR = 0.52, 95% CI = 0.33–0.82, p = 0.005, CG vs GG; OR = 0.57, 95% CI = 0.38–0.87, p = 0.012, C vs G). No significant association was observed between CISH rs2239751 polymorphism and risk/protection of PTB. Conclusion Our findings indicated that CISH rs414171 and rs6768300 variants might be associated with protection from PTB.


Subject(s)
Humans , Male , Female , Middle Aged , Tuberculosis, Pulmonary/genetics , Genetic Predisposition to Disease/genetics , Suppressor of Cytokine Signaling Proteins/genetics , Case-Control Studies , Reverse Transcriptase Polymerase Chain Reaction , Gene Frequency , Genotype , Iran
5.
Article in Chinese | WPRIM | ID: wpr-360028

ABSTRACT

<p><b>OBJECTIVE</b>To explore the mRNA expression level of Notch1 and ASB2 in bone marrow mononuclear cells of patients with P210(+) chronic myeloid leukemia and the correlation between Notch signaling pathway and ubiquitination in chronic myeloid leukemia, so as to provide the valuable information for investigating the pathogenesis of chronic myeloid leukemia and clinical treatment.</p><p><b>METHODS</b>Bone marrow was collected from 32 patients with newly diagnosed chronic myeloid leukemia and 34 non-hematopathic and healthy individuals (control group), respectively. The mRNA expression levels of Notch1 and ASB2 were detected by real-time quantitative PCR.</p><p><b>RESULTS</b>The expression of Notch1 mRNA in CML patients were significantly different from that of healthy individuals group (t=36.3, P<0.01), which was 337.8 times of the healthy individuals. Moreover, the expression level of ASB2 mRNA in CML group was significantly higher than that in healthy individuals (t=19.4, P<0.01). The mRNA expression of Notch1 and ASB2 gene was positive correlation (r=0.504, P<0.01).</p><p><b>CONCLUSION</b>The aberrant expression of Notch1 and Asb2 exists in patients with P210 positive CML, which may be involved in incidence and development of CML.</p>


Subject(s)
Bone Marrow , Metabolism , Case-Control Studies , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Genetics , Metabolism , RNA, Messenger , Genetics , Metabolism , Receptor, Notch1 , Genetics , Metabolism , Signal Transduction , Suppressor of Cytokine Signaling Proteins , Genetics , Metabolism
6.
Article in Chinese | WPRIM | ID: wpr-328323

ABSTRACT

<p><b>OBJECTIVE</b>To observe mainfestations of syndrome and biochemical indices of hypertensive model rats with excessive accumulation of phlegm-dampness syndrome (EAPDS), and to explore its possible pathological mechanism.</p><p><b>METHODS</b>EAPDS rat model was prepared in 50 Wistar rats by feeding with high fat forage. Meanwhile, a normal control group consisting of 10 Wistar rats was set up by feeding with normal forage. After 25-week continuous feeding, 22 rats with body weight (BW) and blood pressure (BP) exceeding 25% those of the control group were selected as a model group. BW, BP, blood lipids, and related serological indicators were detected in all rats. Morphological changes of target organs were observed. mRNA expression levels of leptin receptor (LepR), Janus kinase2 (Jak2), signal transducer and activator of transcription 3 (Stat3), suppressor of cytokine signaling-3 (Socs3), angiotensin II receptor type 1 (AT1), angiotensin II receptor type 2 (AT2), phosphatidylinositol 3 kinase (P13K), serine threonine kinase (Akt), nuclear factor of kappa B (NF-κBp65), inhibitor of nuclear factor kappa-B kinase α (IKKα), NF-kappa-B inhibitor β (lKKβ), NF-kappa-B inhibitor α (IKBα), and AMP-activated protein kinase (AMPK) were detected by quantitative real-time PCR (qPCR). Expression levels of AT1 and LepR in aorta were detected by immunohistochemical assay and Western blot respectively.</p><p><b>RESULTS</b>Compared with the control group, BW, BP, and blood lipids increased; serum levels of leptin (Lep) , Ang II, Hcy, ET-1, TNF-α, IL-6, and p2-MG increased, but NO decreased in the model group (P < 0.05, P < 0.01). Aortal endothelial injury and smooth muscle cell proliferation occurred in the model group, accompanied with heart and renal injury. Compared with the control group, mRNA expression levels of LepR, Jak2, Stat3, Socs3, AT1 , PI3K, Akt, NF-κB p65, IKKβ, IKBα, and AMPK in aorta were up-regulated significantly (P < 0.05), while the expression of IKKa decreased (P < 0.05). Immunohistochem- ical staining showed, brownish yellow deposit of AT1 and LepR was obviously increased, with more extensively positive distribution. Western blot results showed, as compared with the control group, protein expression levels of AT1 and LepR obviously increased in the model group (P < 0.05).</p><p><b>CONCLUSIONS</b>Model rats exhibited typical syndromes of EAPDS. They put up weight with fat abdomen, gloomy hair, poor appetite, hypersomnia, lowered activities , reduced food intake, loose stool, dark red tongue, white tongue with white, thick, greasy fur. Lep could be taken as one of objective indicators for evaluating hypertension rat model with EAPDS.</p>


Subject(s)
Animals , Aorta , Cell Proliferation , Disease Models, Animal , Hypertension , I-kappa B Proteins , Interleukin-6 , Leptin , Blood , NF-KappaB Inhibitor alpha , NF-kappa B , Phosphatidylinositol 3-Kinases , Rats , Rats, Wistar , Suppressor of Cytokine Signaling Proteins , Transcription Factor RelA , Tumor Necrosis Factor-alpha
7.
Chinese Journal of Hepatology ; (12): 171-174, 2015.
Article in Chinese | WPRIM | ID: wpr-337023

ABSTRACT

<p><b>OBJECTIVE</b>To study the mechanism underlying the effect of the SOCS3 rs4969170 A/G alleles on the occurrence of insulin resistance (IR) in patients with chronic hepatitis C.</p><p><b>METHODS</b>The promoter region of the SOCS3 gene was amplified by PCR,and luciferase expression vectors were constructed and transfected into HepG2,Huh7 cell lines.The relative luciferase activity of each expression vector was assessed by the dual luciferase reporter gene assay system.Western blotting was used to detect SOCS3 protein expression in PBMCs from groups of patients with the rs4969170 AA and AG genotypes.The state of IR in eight patients was evaluated by determining their HOMA-IR.</p><p><b>RESULTS</b>The pGL3-A, PGL3-G and pGL3-control vectors showed significantly different luciferase expression in the HepG2 cells (0.121 00 ± 0.022 07,0.027 00+/-0.012 49 and 0.043 33 ± 0.005 51; F =48.068, P=0.001) and in the Huh7 cell lines (0.164 70 ± 0.007 10,0.027 33 ± 0.017 04 and 0.033 67 ± 0.014 98; F =115.137, P=0.001). The expression of SOCS3 protein was significantly higher in the rs4969170 AA genotype group than in the AG genotype group (1.22 ± 0.40 vs. 0.30 ± 0.19; t =4.149, P=0.006).The IR index of patients with the rs4969170 AA genotype and the AG genotype was 4.11 ± 2.62 and 1.47 ± 1.01 respectively.There were three patients with IR in the rs4969170 AA genotype group and one in the rs4969170 AG group. There was no statistically significant difference between the two genotype groups (t=1.881, P=0.109).</p><p><b>CONCLUSIONS</b>The SOCS3 rs4969170 A haplotype may enhance transcriptional activity of the gene promoter to regulate gene expression, thereby increasing intracellular SOCS3 protein level and ultimately interfering with insulin signaling and causing IR in patients with chronic hepatitis C.</p>


Subject(s)
Cell Line, Tumor , Genes, Reporter , Genotype , Haplotypes , Hepatitis C, Chronic , Humans , Insulin Resistance , Luciferases , Polymorphism, Single Nucleotide , Suppressor of Cytokine Signaling 3 Protein , Suppressor of Cytokine Signaling Proteins
8.
Article in English | WPRIM | ID: wpr-142453

ABSTRACT

Abnormal levels of microRNA (miR)-155, which regulate inflammation and immune responses, have been demonstrated in the colonic mucosa of patients with inflammatory bowel diseases (IBD), although its role in disease pathophysiology is unknown. We investigated the role of miR-155 in the acquisition and maintenance of an activated phenotype by intestinal myofibroblasts (IMF), a key cell population contributing to mucosal damage in IBD. IMF were isolated from colonic biopsies of healthy controls, ulcerative colitis (UC) and Crohn's disease (CD) patients. MiR-155 in IMF was quantified by quantitative reverse transcription-PCR in basal condition and following exposure to TNF-alpha, interleukin (IL)-1beta, lipopolysaccharide (LPS) or TGF-beta1. The effects of miR-155 mimic or inhibitor transfection on cytokine release and suppressor of cytokine signaling 1 (SOCS1) expression were assessed by enzyme-linked immunosorbent assay and western blot, respectively. Regulation of the target gene SOCS1 expression by miR-155 was assessed using luciferase reporter construct. We found that miR-155 was significantly upregulated in UC as compared with control- and CD-derived IMF. Moreover, TNF-alpha and LPS, but not TGF-beta1 and IL-1beta, significantly increased miR-155 expression in IMF. Ectopic expression of miR-155 in control IMF augmented cytokines release, whereas it downregulated SOCS1 expression. MiR-155 knockdown in UC-IMF reduced cytokine production and enhanced SOCS1 expression. Luciferase reporter assay demonstrated that miR-155 directly targets SOCS1. Moreover, silencing of SOCS1 in control IMF significantly increased IL-6 and IL-8 release. In all, our data suggest that inflammatory mediators induce miR-155 expression in IMF of patients with UC. By downregulating the expression of SOCS1, miR-155 wires IMF inflammatory phenotype.


Subject(s)
Adult , Aged , Cells, Cultured , Colitis, Ulcerative/genetics , Cytokines/immunology , Female , Gene Expression Regulation , Humans , Intestinal Mucosa/immunology , Male , MicroRNAs/genetics , Middle Aged , Myofibroblasts/immunology , Suppressor of Cytokine Signaling Proteins/genetics , Tumor Necrosis Factor-alpha/immunology , Up-Regulation , Young Adult
9.
Article in English | WPRIM | ID: wpr-142452

ABSTRACT

Abnormal levels of microRNA (miR)-155, which regulate inflammation and immune responses, have been demonstrated in the colonic mucosa of patients with inflammatory bowel diseases (IBD), although its role in disease pathophysiology is unknown. We investigated the role of miR-155 in the acquisition and maintenance of an activated phenotype by intestinal myofibroblasts (IMF), a key cell population contributing to mucosal damage in IBD. IMF were isolated from colonic biopsies of healthy controls, ulcerative colitis (UC) and Crohn's disease (CD) patients. MiR-155 in IMF was quantified by quantitative reverse transcription-PCR in basal condition and following exposure to TNF-alpha, interleukin (IL)-1beta, lipopolysaccharide (LPS) or TGF-beta1. The effects of miR-155 mimic or inhibitor transfection on cytokine release and suppressor of cytokine signaling 1 (SOCS1) expression were assessed by enzyme-linked immunosorbent assay and western blot, respectively. Regulation of the target gene SOCS1 expression by miR-155 was assessed using luciferase reporter construct. We found that miR-155 was significantly upregulated in UC as compared with control- and CD-derived IMF. Moreover, TNF-alpha and LPS, but not TGF-beta1 and IL-1beta, significantly increased miR-155 expression in IMF. Ectopic expression of miR-155 in control IMF augmented cytokines release, whereas it downregulated SOCS1 expression. MiR-155 knockdown in UC-IMF reduced cytokine production and enhanced SOCS1 expression. Luciferase reporter assay demonstrated that miR-155 directly targets SOCS1. Moreover, silencing of SOCS1 in control IMF significantly increased IL-6 and IL-8 release. In all, our data suggest that inflammatory mediators induce miR-155 expression in IMF of patients with UC. By downregulating the expression of SOCS1, miR-155 wires IMF inflammatory phenotype.


Subject(s)
Adult , Aged , Cells, Cultured , Colitis, Ulcerative/genetics , Cytokines/immunology , Female , Gene Expression Regulation , Humans , Intestinal Mucosa/immunology , Male , MicroRNAs/genetics , Middle Aged , Myofibroblasts/immunology , Suppressor of Cytokine Signaling Proteins/genetics , Tumor Necrosis Factor-alpha/immunology , Up-Regulation , Young Adult
10.
Article in English | WPRIM | ID: wpr-250400

ABSTRACT

Liopxin A4 (LXA4) is considered to be a crucial modulator in the inflammatory responses. In the present study, we aimed to study the effect of LXA4 on the inflammatory cytokines production induced by lipopolysaccharide (LPS) and the possible mechanism in normal human epidermal keratinocytes (NHEKs). NHEKs were isolated and cultured. The expression of toll-like receptor 4 (TLR4), LXA4 receptor (ALXR) and aryl hydrocarbon receptor (AhR) in NHEKs was detected by reverse transcription polymerase chain reaction (RT-PCR). The mRNA and protein levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were determined in NHEKs stimulated by LPS (10 μg/mL) with or without preincubation with LXA4 (100 nmol/L) for 30 min by real-time quantitative PCR (real-time qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The expression levels of tumor necrosis factor receptor-associated factor 6 (TRAF6) and suppressors of cytokine signaling 2 (SOCS2) mRNAs and proteins, and nuclear translocation of NF-kB-p65 were measured by real-time qPCR and Western blotting, respectively. The results showed that NHEKs expressed TLR4, ALXR and AhR. LXA4 significantly inhibited the mRNA and protein expression levels of TNF-α, IL-1β and TRAF6 induced by LPS in NHEKs, and LXA4 obviously increased the expression of SOCS2 at mRNA and protein levels. The nuclear NF-kB-p65 protein expression induced by LPS was inhibited after preincubation with LXA4 in NHEKs. It was concluded that LXA4 inhibits the LPS-induced production of TNF-α and IL-1β in NHEKs by up-regulating SOCS2 and down-regulating TRAF6.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Pharmacology , Cells, Cultured , Gene Expression Regulation , Humans , Keratinocytes , Lipopolysaccharides , Pharmacology , Lipoxins , Pharmacology , NF-kappa B , Genetics , Metabolism , Suppressor of Cytokine Signaling Proteins , Genetics , Metabolism , TNF Receptor-Associated Factor 6 , Genetics , Metabolism , Toll-Like Receptor 4 , Genetics , Metabolism , Tumor Necrosis Factor-alpha , Genetics , Metabolism
11.
Article in Chinese | WPRIM | ID: wpr-357285

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of DNA methyhransferase l (DNMT1) gene silencing on methylation of suppressor of cytokine signaling (SOCS-1) in multiple myeloma RPMI 8226 cells.</p><p><b>METHODS</b>Recombinant plasmid pshRNA-DNMTl was transfected into multiple myeloma RPMI 8226 cells by lipofectamine 2000. RT-PCR and Western blot were used to detect the mRNA and protein expression of DNMTl in RPMI 8226 cells respectively before and after transfection. Methylation-specific polymerase chain reaction was used to detect the methylation level change of SOCS-1 gene in RPMI8226 cells transfected.</p><p><b>RESULTS</b>DNMTl targeted short hairpin RNA(shRNA) was successfully inserted into the plasmid vector pshRNA. RT-PCR results showed that the relative mRNA expression level of DNMTI gene in RPMI 8226 cells transfected with pshRNA was 0.176±0.004 which was significantly lower than that in cells transfected by empty vector (0.956±0.033, P<0.01). Western blot analysis showed that the relative expression level of DNMT1 protein of RPMI 8226 cells transfected by pshRNA was 0.065±0.014, which was significantly lower than that in transfected cells by empty vector(0.415±0.027) (P<0.05). These results indicated that the recombinant plasmid pshRNA could effectively knock down the expression of DNMT1 gene in RPMI 8226 cells. Methylation analysis showed that the methylation level of SOCS-1 gene was obviously reduced after transfection.</p><p><b>CONCLUSION</b>DNMT1 gene in RPMI 8226 cell can be silenced by shRNA. DNMT1 gene silencing can significantly induce SOCS-1 gene hypomethylation, which indicates that DNMT1 may play an important role in the process of SOCS-1 hypermethylation.</p>


Subject(s)
Cell Line, Tumor , DNA Methylation , Gene Silencing , Genetic Vectors , Humans , Multiple Myeloma , RNA, Messenger , RNA, Small Interfering , Repressor Proteins , Suppressor of Cytokine Signaling 1 Protein , Suppressor of Cytokine Signaling Proteins , Transfection
12.
Rev. bras. enferm ; 67(5): 722-729, Sep-Oct/2014. tab
Article in Portuguese | LILACS, BDENF | ID: lil-731212

ABSTRACT

Objetivou-se estimar o tempo de decisão para procura de atendimento (TD) para homens e mulheres com infarto agudo do miocárdio (IAM); analisar a influência de variáveis ambientais no TD e a interação entre gênero e variáveis ambientais para o desfecho TD. Estudo transversal, envolvendo cem pacientes, entrevistados em hospitais de Salvador. Na análise dos dados empregou-se o Qui-quadrado ou Exato de Fisher e o Modelo de Regressão Linear Robusto. Predominou o IAM ocorrido no domicílio, familiares no entorno, e os pacientes sendo alvo de ações equivocadas. Observou-se TD elevado para mulheres (0,9h) e homens (1,4h). Aqueles em casa no início dos sintomas tiveram maior TD, comparados aos no trabalho e menor em relação aos em via pública (p=0,047). Houve interação estatisticamente significante entre gênero e viver acompanhado; e entre gênero e ter companheiro e filhos no entorno, para o desfecho TD. O cuidar em enfermagem focalizado nas especificidades de fatores ambientais e de gênero pode otimizar o atendimento precoce.


The purpose was to estimate the decision time (DT) for searching for attendance for men and women suffering from acute myocardial infarction (AMI); and to analyze the influence of surrounding variables in the DT. Transversal study, involving one hundred patients interviewed in hospitals of Salvador-BA, Brazil. For data analysis, it was used the chi-squared or Fisher’s exact test, and the Robust Linear Regression Model. AMI at the home predominated, with family members and patients receiving mistaken actions. A high DT was observed both, for women (0.9h) and men (1.4h). Those at home during the initial symptoms had higher DT, compared to those at work; and lower in relation to those in public spaces (p=0.047). Statistically significant interaction occurred among gender and the fact of living with company; and among gender and having a companion and children, for the outcome of the DT. Nursing care focused on the specificity of surrounding factors and gender can optimize early attendance.


Se objetivó estimar el tiempo de decisión para buscar atendimiento (TD) para hombres y mujeres con infarto agudo de miocardio (IAM); analizar la influencia de variables ambientales en TD y la interacción entre genero y variables ambientales para el desfecho del TD. Estudio transversal, envolviendo cien pacientes entrevistados en hospitales de Salvador-BA, Brasil. En el análisis se utilizó el chi-cuadrado o el Teste Exacto de Fisher y el Modelo de Regresión Linear Robusto. Predominó el IAM en el domicilio, familiares en el entorno y con pacientes siendo objeto de acciones equivocadas. Se observó TD elevados para mujeres (0,9h) y hombres (1,4h). Aquellos en sus casas en el inicio de los síntomas tuvieron mayor TD, comparados a los en el trabajo, y menor en relación aquellos en vía pública (p=0,047). Hubo interacción estadísticamente significante entre genero y vivir acompañado y entre genero y tener compañero e hijos en el entorno, para el desfecho del TD. El cuidar en enfermería focalizado en especificidades de factores ambientales y de géneros puede optimizar el atendimiento precoce.


Subject(s)
Animals , Male , Rats , Growth Hormone/pharmacology , /pharmacology , Lipopolysaccharides/toxicity , Repressor Proteins , Transcription Factors , Tumor Necrosis Factor-alpha/pharmacology , Drug Resistance , Insulin-Like Growth Factor I/genetics , Proteins/genetics , Rats, Sprague-Dawley , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Somatotropin/genetics , Suppressor of Cytokine Signaling Proteins
13.
Article in English | WPRIM | ID: wpr-351073

ABSTRACT

Recently, suppressor of cytokine signaling-3 (SOCS3) has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway which is relevant in inflammatory response, while its functions in acute liver failure and HBV-induced acute-on-chronic liver failure (HBV-ACLF) have not been fully elucidated. In this study, we explored the role of SOCS3 in the development of mouse hepatitis virus strain 3 (MHV-3)-induced acute liver failure and its expression in liver and peripheral blood mononuclear cells (PBMCs) of patients with HBV-ACLF. Inflammation-related gene expression was detected by real-time PCR, immunohistochemistry and Western blotting. The correlation between SOCS3 level and liver injury was studied. Our results showed that the SOCS3 expression was significantly elevated in both the liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic hepatitis B (CHB). Moreover, a time course study showed that SOCS3 level was increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro-inflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were also increased significantly at 72 h post-infection. There was a close correlation between hepatic SOCS3 level and IL-6, and the severity of liver injury defined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respectively. These data suggested that SOCS3 may play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and HBV-ACLF.


Subject(s)
Adult , Alanine Transaminase , Blood , Animals , Aspartate Aminotransferases , Blood , Blotting, Western , End Stage Liver Disease , Genetics , Pathology , Virology , Female , Gene Expression , Hepatitis, Viral, Animal , Genetics , Pathology , Virology , Host-Pathogen Interactions , Humans , Interleukin-1beta , Genetics , Metabolism , Interleukin-6 , Genetics , Metabolism , Leukocytes, Mononuclear , Metabolism , Virology , Liver Failure, Acute , Genetics , Pathology , Virology , Male , Mice, Inbred BALB C , Middle Aged , Murine hepatitis virus , Physiology , Reverse Transcriptase Polymerase Chain Reaction , Severity of Illness Index , Suppressor of Cytokine Signaling 3 Protein , Suppressor of Cytokine Signaling Proteins , Blood , Genetics , Metabolism , Tumor Necrosis Factor-alpha , Genetics , Metabolism , Young Adult
14.
Article in Chinese | WPRIM | ID: wpr-356897

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the association between rs414171 single nucleotide polymorphisms (SNP) of cytokine- inducible src homology 2 domain protein (CISH) and the susceptibility to chronic hepatitis B.</p><p><b>METHODS</b>A total of 233 Chinese Han patients with chronic hepatitis B and 148 age- and sex-matched healthy controls were enrolled in this case-control study. The SNP rs414171 was genotyped by Sequenom MassArray-IPLEX to analyze the relationship between rs414171 and chronic hepatitis B.</p><p><b>RESULTS</b>The distribution of SNP rs414171 allele and genotype frequencies showed no significant difference between the patients and healthy controls (P>0.05).</p><p><b>CONCLUSION</b>CISH rs414171 is not significantly associated with the susceptibility to chronic hepatitis B in Chinese Han population.</p>


Subject(s)
Adult , Alleles , Asians , Genetics , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Hepatitis B, Chronic , Genetics , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Suppressor of Cytokine Signaling Proteins , Genetics
15.
Article in Chinese | WPRIM | ID: wpr-312994

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the regulation trend of Jinxin Oral Liquid (JXOL) on the expression of negative regulatory factor of TLR3 signaling pathway SOCS1 in the lung tissue of RSV infected BALB/c mice at different time points.</p><p><b>METHODS</b>Totally 75 BALB/c mice were randomly divided into 5 groups, i.e., the normal control group, the model group, the ribavirin group, the high dose JXOL group, and the equivalent dose JXOL group, 15 in each group. Each group had 3 intervention ways (I, II, and III) with 5 mice treated in each group. BALB/c mice were nasally infected with respiratory syncytial virus (RSV), and treated by different intervention ways. After intervention, mice were killed and their lung tissues were sampled, mRNA expression levels of RSV-M, SOCS1, and IFN-β were detected by Real time PCR. The expression of SOCSl at the protein level was detected by Western blot.</p><p><b>RESULTS</b>Compared with the normal control group, the mRNA expression level of SOCS1 and IFN-β, and the protein expression level of SOCS1 increased significantly in the model group intervened by intervention I and II (all P < 0.01), but the mRNA expression level of IFN-β decreased significantly in model group intervened by intervention III (P < 0.01). Compared with the model group, the mRNA expression level of RSV-M all significantly decreased in the high dose JXOL group and the equivalent dose JXOL group intervened by 3 intervention ways (all P < 0.01). The mRNA expression level of SOCS1 significantly decreased in the high dose JXOL group intervened by intervention I and III and the equivalent dose JXOL group intervened by 3 intervention ways (all P < 0.01). The mRNA expression level of IFN-β significantly decreased in the high dose JXOL group intervened by intervention I and II and the equivalent dose JXOL group intervened by intervention I (all P < 0.01), while it significantly increased in the high dose JXOL group intervened by intervention III and the equivalent dose JXOL group intervened by intervention III (all P < 0.01). The protein expression level of SOCS1 significantly decreased in the high dose JXOL group intervened by intervention I and the equivalent dose JXOL group intervened by 3 intervention ways (all P < 0.01), while it significantly increased in the high dose JXOL group intervened by intervention III (all P < 0.01). Compared with the high dose JXOL group, the mRNA expression level of RSV-M decreased significantly in the equivalent dose JXOL group intervened by intervention I and II (P < 0.01). The mRNA expression level of SOCS1 and IFN-β decreased significantly in the equivalent dose JXOL group intervened by intervention I (P < 0.01), but the mRNA expression level of IFN-β increased significantly in the equivalent dose JXOL group intervened by intervention II and III (all P < 0.01). The protein expression level of SOCS1 decreased significantly in the equivalent dose JXOL group intervened by 3 intervention ways (all P < 0.01).</p><p><b>CONCLUSIONS</b>JXOL could inhibit the expression of SOCS1 in the lung tissue of RSV infected BALB/c mice at different time points. Its regulatory effect might be associated with promoting the expression of interferon type I and further fighting against RSV.</p>


Subject(s)
Animals , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Lung , Metabolism , Mice , Mice, Inbred BALB C , RNA, Messenger , Respiratory Syncytial Virus Infections , Drug Therapy , Metabolism , Respiratory Syncytial Viruses , Ribavirin , Signal Transduction , Suppressor of Cytokine Signaling 1 Protein , Suppressor of Cytokine Signaling Proteins , Metabolism , Toll-Like Receptor 3 , Metabolism
16.
Article in English | WPRIM | ID: wpr-194864

ABSTRACT

Cows with different Insulin-like Growth Factor-I (IGF-I) concentrations showed comparable expression levels of hepatic growth hormone receptor (GHR). Suppressor of cytokine signaling 2 (SOCS2), could be responsible for additional inhibition of the GHR signal cascade. The aims were to monitor cows with high or low antepartal IGF-I concentrations (IGF-I(high) or IGF-I(low)), evaluate the interrelationships of endocrine endpoints, and measure hepatic SOCS2 expression. Dairy cows (n = 20) were selected (240 to 254 days after artificial insemination (AI)). Blood samples were drawn daily (day -17 until calving) and IGF-I, GH, insulin, thyroid hormones, estradiol, and progesterone concentrations were measured. Liver biopsies were taken (day 264 +/- 1 after AI and postpartum) to measure mRNA expression (IGF-I, IGFBP-2, IGFBP-3, IGFBP-4, acid labile subunit (ALS), SOCS2, deiodinase1, GHR1A). IGF-I concentrations in the two groups were different (p 0.05). Thyroxine levels and ALS expression were higher in the IGF-I(high) cows compared to IGF-I(low) cows. Estradiol concentration tended to be greater in the IGF-I(low) group (p = 0.06). It was hypothesized that low IGF-I levels are associated with enhanced SOCS2 expression although this could not be decisively confirmed by the present study.


Subject(s)
Animals , Cattle , Estradiol/blood , Female , Growth Hormone/blood , Insulin/blood , Insulin-Like Growth Factor Binding Protein 2/analysis , Insulin-Like Growth Factor Binding Protein 3/analysis , Insulin-Like Growth Factor Binding Protein 4/analysis , Insulin-Like Growth Factor I/analysis , Liver/chemistry , Pregnancy/metabolism , Pregnancy, Animal/metabolism , Progesterone/blood , Suppressor of Cytokine Signaling Proteins/analysis , Thyroid Hormones/blood
17.
Article in Chinese | WPRIM | ID: wpr-285934

ABSTRACT

<p><b>OBJECTIVE</b>To explore whether the polymorphism of suppressor of cytokine signaling-3 (SOCS-3) and dyslipidemia are correlated in Uygur females.</p><p><b>METHODS</b>A total of 1379 Uygur females from Xinjiang Uygur Autonomous Region were enrolled in this study. Three single nucleotide polymorphisms (SNPs), namely rs12953258, rs4969168, and rs9914220, were analyzed after being genotyped.</p><p><b>RESULTS</b>Of these three SNPs, the frequency distribution of rs12953258 sites was found to be significantly different between dyslipidemia group and normal group (P=0.032). The frequency distribution of rs12953258 sites between the high-density lipoprotein-cholesterol (HDL-C) abnormal group and normal group also showed significant difference (P=0.029). Logistic regression analysis showed that the genotype AA of rs12953258 was a risk factor for dyslipidemia among the Uygur females [CC vs. AA:OR=3.271,95%CI(1.092-9.797), P=0.034]. The genotype AA of rs12953258 might be related to the decreased high HDL-C and increased trigleceride, whereas the genotype AA coupled with abnormal body mass index (BMI) were more likely to be linked with the higher prevalence of dyslipidemia in Uygur females.</p><p><b>CONCLUSIONS</b>The polymorphism of SOCS-3 is correlated to the dyslipidemia in Uygur females in Xinjiang. Carriers of Genotype AA of rs12953258 coupled with abnormal BMI are more susceptible to dyslipidemia.</p>


Subject(s)
Adult , Asians , Genetics , China , Epidemiology , Dyslipidemias , Ethnology , Genetics , Female , Humans , Male , Middle Aged , Polymorphism, Genetic , Prevalence , Suppressor of Cytokine Signaling 3 Protein , Suppressor of Cytokine Signaling Proteins , Genetics
18.
Chinese Medical Journal ; (24): 2117-2120, 2014.
Article in English | WPRIM | ID: wpr-241714

ABSTRACT

<p><b>BACKGROUND</b>Idiopathic pulmonary fibrosis (IPF) is a progressive diffuse parenchymal disease with a poor prognosis. A variety of cytokines and chemokines are involved in its pathophysiology. The aim of this study was to evaluate the clinical features in IPF patients with the expression of suppressor of cytokine signaling 1 (SOCS-1), which acts as a negative regulator of cytokine signaling.</p><p><b>METHODS</b>IPF patients (n = 20) and healthy controls (n = 16) were included in this study. The expression of SOCS-1 was analyzed in peripheral blood mononuclear cells (PBMC) of subjects using RT-PCR. Interleukin 4 (IL-4), transforming growth factor β1 (TGF-β1) and type I collagen expression were also analyzed in each individual using enzyme-linked immunosorbent assay (ELISA). The clinical characteristics of IPF patients were delineated. These results were analyzed by SPSS13.0 statistics software.</p><p><b>RESULTS</b>SOCS-1 mRNA expression was significantly decreased in the PBMC of IPF patients compared with healthy controls; serum levels of IL-4 and TGF-β1 were higher in IPF patients. The patients with lower expression of SOCS-1 developed lower percentage of forced vital capacity (FVC%) and DLCO/VA. A patients' SOCS-1 mRNA level was negatively correlated with serum levels of IL-4, and negatively correlated with their high-resolution computed tomography (HRCT) scores.</p><p><b>CONCLUSIONS</b>SOCS-1 mRNA can be detected in PBMC, and it is down-regulated in IPF patients. The expression of SOCS-1 is associated with the severity of IPF patients' symptoms, so it might be the predictor of disease severity. SOCS-1 might play an important role in IPF by reducing the expression of the T helper type 2 (Th2) cell-related cytokine IL-4.</p>


Subject(s)
Adult , Aged , Aged, 80 and over , Enzyme-Linked Immunosorbent Assay , Female , Humans , Idiopathic Pulmonary Fibrosis , Metabolism , Interleukin-4 , Metabolism , Leukocytes, Mononuclear , Metabolism , Male , Middle Aged , Suppressor of Cytokine Signaling 1 Protein , Suppressor of Cytokine Signaling Proteins , Genetics , Metabolism , Transforming Growth Factor beta1 , Metabolism
19.
Chinese Medical Journal ; (24): 1691-1695, 2014.
Article in English | WPRIM | ID: wpr-248127

ABSTRACT

<p><b>BACKGROUND</b>Some hepatitis B extracellular antigen (HBeAg)-positive chronic hepatitis B (CHB) patients in their immune active phase can clear the virus spontaneously and enter into an inactive hepatitis B virus (HBV) carrier state, indicating a benign prognosis. In this study, the association between cytokine-inducible SRC homology 2 domain protein (CISH) gene polymorphisms at -292 (rs414171) and the spontaneous clearance of HBV in HBeAg-positive CHB patients in immune the active phase was investigated.</p><p><b>METHODS</b>Seventy HBeAg-positive CHB patients in the immune active phase were followed up for 76 weeks without antiviral therapy. The alanine transaminase, aspartate transaminase, HBV DNA, HBeAg and hepatitis B extracellular antibody levels were tested regularly. At week 76, 27 patients were classified into group A (HBV DNA level below 2 104 IU/ml and the value of HBeAg declined below 10% of the baseline at week 76), and 43 patients were classified into group B (HBV DNA level higher than 2×10(4) IU/ml or the value of HBeAg did not decline substantially at week 76). CISH (rs414171) polymorphisms were also tested using the iPLEX system.</p><p><b>RESULTS</b>The HBV DNA levels at week 12 were significantly greater in group B compared with group A (group A: (6.87±1.40) log10IU/ml; group B: (7.61±1.38) log10IU/ml, P = 0.034) and the HBeAg values were greater in group B at week 28 compared with group A (P = 0.001). The differences in HBV DNA and HBeAg values increased between the groups over time. Sixteen patients in group A and 11 in group B were genotype AA. Those with genotype AT or TT included 11 in group A and 31 in group B (AA vs. AT and TT, odds ratio 4.10 (95% confidence interval: 1.462-11.491), P = 0.006).</p><p><b>CONCLUSION</b>CISH gene polymorphisms at -292 (rs414171) are associated with HBV clearance in HBeAg-positive CHB patients in the immune active phase, and AA is a favorable genotype for this effect.</p>


Subject(s)
Adolescent , Adult , Aged , Female , Genotype , Hepatitis B e Antigens , Metabolism , Hepatitis B virus , Genetics , Allergy and Immunology , Hepatitis B, Chronic , Allergy and Immunology , Humans , Male , Middle Aged , Polymorphism, Genetic , Genetics , Suppressor of Cytokine Signaling Proteins , Genetics , Young Adult
20.
Article in Chinese | WPRIM | ID: wpr-254482

ABSTRACT

<p><b>OBJECTIVE</b>To assess the association of suppressor of cytokine signaling 3 (SOCS3) gene polymorphisms with insulin resistance (IR) in Xinjiang Uygur population.</p><p><b>METHODS</b>A cross-sectional study on metabolic diseases, e.g., obesity, was conducted on ethnic Uygurs in Hetian, Xinjiang of China. A total of 1292 Uygur individuals were enrolled. The sample size for IR subjects [homeostasis model assessment for insulin resistance (HOMA-IR) ≥ 2.96] was 323, whereas that for non-IR controls was 969 (HOMA-IR < 2.96). Representative variations were selected from database and genotyped with TaqMan polymerase chain reaction method. For the relatively isolated population from a homogeneous environment, a case-control study was conducted to assess the association between variations of SOCS3 gene and IR.</p><p><b>RESULTS</b>A significant difference in genotype distribution of rs4969168 was detected between IR and control groups in males (chi square =7.216, P=0.027). Although the IR-related quantitative phenotypes did not significantly differ between individuals with GG, AG and AA genotypes of rs4969168 in the overall, male and female population (P > 0.05), the mean of body mass index and the median of fasting insulin increased in individuals with GG, AG, AA genotypes in males. Haplotype 2 (rs12953258C-rs4969168A-rs9914220C) was significantly associated with a higher prevalence of IR in males (P=0.023). Logistic regression analysis indicated that AG genotype of rs4969168 variation is a protective factor for IR in males (OR=1.772, 95% confidence interval: 1.081-2.906, P=0.023).</p><p><b>CONCLUSION</b>Our study suggested that the rs4969168 polymorphism of SOCS3 gene is associated with IR in ethnic Uygur population from Xinjiang, China.</p>


Subject(s)
Case-Control Studies , China , Ethnology , Cross-Sectional Studies , Ethnicity , Genetics , Female , Genotype , Humans , Insulin Resistance , Logistic Models , Male , Polymorphism, Genetic , Suppressor of Cytokine Signaling 3 Protein , Suppressor of Cytokine Signaling Proteins , Genetics
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