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1.
Clin Rheumatol ; 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32557257

RESUMO

OBJECTIVES: To explore the associations of FKBP4 and FKBP5 gene polymorphisms with disease susceptibility, glucocorticoid (GC) efficacy, anxiety, depression, and health-related quality of life (HRQOL) in systemic lupus erythematosus (SLE) patients. METHODS: All subjects were collected from the First and the Second Affiliated Hospital of Anhui Medical University in Hefei, China, during 2011 to 2015. In the case-control study, 541 SLE patients and 543 controls were recruited. In the follow-up study, 466 patients completed the 12-week follow-up and then were divided into GC-sensitive and GC-insensitive groups. Genotyping was determined using Multiplex SNaPshot technique. Data were analyzed using chi-square test and univariate and multivariate logistic regression analyses. RESULTS: rs4713904, rs9368878, and rs7757037 of FKBP5 were associated with depression in SLE patients (rs4713904, PBH = 0.037; rs9368878, PBH = 0.001; rs7757037, PBH = 0.003). Moreover, rs4713904 was associated with GC efficacy in males with SLE (PBH = 0.011). The rs755658 of FKBP5 was associated with improvement in social function (PBH = 0.022) and mental component summary (PBH = 0.028). The rs4713907 of FKBP5 was related to improvement in total score of SF-36, bodily pain, and mental component summary score (all PBH = 0.018). Furthermore, the rs12582595 of FKBP4 was correlated with general health improvement (PBH = 0.033). No associations were seen between FKBP4/FKBP5 gene polymorphisms and SLE susceptibility and anxiety. CONCLUSIONS: FKBP5 gene polymorphisms may be associated with depression and GC efficacy of SLE patients. Meanwhile, the genetic polymorphisms of FKBP4 and FKBP5 genes may be associated with HRQOL improvement in SLE patients.Key Points• FKBP5 gene polymorphisms were associated with depression of SLE patients.• FKBP5 gene polymorphisms were associated with GC efficacy of SLE patients.• FKBP5 gene polymorphisms were associated with HRQOL improvement in SLE patients.• FKBP4 gene polymorphisms were associated with HRQOL improvement in SLE patients.

2.
J Clin Rheumatol ; 26(4): 134-141, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32453286

RESUMO

OBJECTIVES: The aim of this study is to investigate whether heat shock protein 70 (Hsp70) gene polymorphisms are implicated in systemic lupus erythematous (SLE) susceptibility, the efficacy of glucocorticoids (GCs) treatment, and improvement of health-related quality of life. METHODS: A total of 499 SLE patients and 499 controls were included in a case-control study, and 468 SLE patients treated with GCs for 12 weeks were involved in a follow-up study. Patients who completed the 12-week follow-up were divided into GCs-sensitive and GCs-insensitive group by using the SLE disease activity index. The SF-36 was used to evaluate the health-related quality of life of SLE patients, and genotyping was performed by improved multiplex ligation detection reaction. RESULTS: rs2075800 was associated with SLE susceptibility (adjusted odds ratio [ORadj], 1.437; 95% confidence interval [CI], 1.113-1.855; Padj = 0.005; PBH = 0.020 by dominant model; ORadj, 1.602; 95% CI, 1.072-2.395; Padj = 0.022; PBH = 0.029 by TT vs CC model; ORadj = 1.396; 95% CI = 1.067-1.826; Padj = 0.015; PBH = 0.029 by TC vs CC model). In the follow-up study, rs2075799 was associated with the improvement in mental health (p = 0.004, PBH = 0.044), but we failed to find any association between the efficacy of GCs and Hsp70 gene polymorphisms. CONCLUSIONS: Hsp70 gene polymorphisms may be associated with susceptibility to SLE and improvement of mental health in Chinese Han population.

3.
Int Immunopharmacol ; 73: 515-526, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173973

RESUMO

In a previous study, we showed that octreotide alleviate hepatic fibrosis. However, its underlying molecular mechanisms are still poorly understood. In the current study, rats with CCl4-induced liver injury and Hepatic Stellate Cells (HSCs) were employed for in vitro and in vivo studies to observe the effects of octreotide on progression of liver fibrosis. The results in rats indicated that octreotide remarkably alleviated hepatic injury. The treated rats showed improved pathological manifestations and reduced liver indicators, e.g., liver weight, liver index and liver hydroxyproline (Hyp) content. Additionally, activities of serum total bilirubin (TBIL), aspartate transaminase (AST) and alanine transaminase (ALT), and serum levels of hyaluronic acid (HA), laminin (LN), type IV collagen (IV-C) and procollagen III peptide (PIIIP) also decreased. Furthermore, releasing inflammatory factors and proliferation of activated HSCs under different treatments were detected in which levels of IL-1ß, IL-6, TNF-α decreased and hepatocytes proliferative capacity reduced through Bcl-2/Bax-dependent apoptosis. Finally, our results demonstrated that octreotide was able to exert an inhibitory effect on the activation of HSCs regulating the PI3K/AKT signaling pathway. In summary, our study corroborated that octreotide could prevent liver fibrosis probably via modulating Bcl-2/Bax and PI3K/AKT signaling pathway.


Assuntos
Cirrose Hepática/tratamento farmacológico , Octreotida/uso terapêutico , Animais , Tetracloreto de Carbono , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Citocinas/genética , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Masculino , Octreotida/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
4.
J Clin Rheumatol ; 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30768443

RESUMO

OBJECTIVES: The aim of this study is to investigate whether heat shock protein 70 (Hsp70) gene polymorphisms are implicated in systemic lupus erythematous (SLE) susceptibility, the efficacy of glucocorticoids (GCs) treatment, and improvement of health-related quality of life. METHODS: A total of 499 SLE patients and 499 controls were included in a case-control study, and 468 SLE patients treated with GCs for 12 weeks were involved in a follow-up study. Patients who completed the 12-week follow-up were divided into GCs-sensitive and GCs-insensitive group by using the SLE disease activity index. The SF-36 was used to evaluate the health-related quality of life of SLE patients, and genotyping was performed by improved multiplex ligation detection reaction. RESULTS: rs2075800 was associated with SLE susceptibility (adjusted odds ratio [ORadj], 1.437; 95% confidence interval [CI], 1.113-1.855; Padj = 0.005; PBH = 0.020 by dominant model; ORadj, 1.602; 95% CI, 1.072-2.395; Padj = 0.022; PBH = 0.029 by TT vs CC model; ORadj = 1.396; 95% CI = 1.067-1.826; Padj = 0.015; PBH = 0.029 by TC vs CC model). In the follow-up study, rs2075799 was associated with the improvement in mental health (p = 0.004, PBH = 0.044), but we failed to find any association between the efficacy of GCs and Hsp70 gene polymorphisms. CONCLUSIONS: Hsp70 gene polymorphisms may be associated with susceptibility to SLE and improvement of mental health in Chinese Han population.

5.
Microb Pathog ; 127: 352-358, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30572014

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex, chronic autoimmune disease, and oestrogen is considered to be a predisposing factor for SLE. Although some studies are conducted to explore the association between oestrogen receptor alpha (ERα) gene polymorphisms and SLE susceptibility, their results are inconsistent. METHODS: Meta-analysis was conducted to confirm whether ERα gene polymorphisms were associated with SLE susceptibility, and the strength of association was anticipated by pooled ORs with 95% CIs. Stata software package version 12.0 was used to calculate all the statistical analyses. RESULTS: Twelve studies included 2494 cases and 4176 controls were incorporated in our meta-analysis. A significant association was found for ERα PvuII polymorphism in the overall population (CC+CT vs TT: OR = 1.334, 95% CI = 1.195-1.490, P < 0.001; CC vs TT: OR = 1.401, 95% CI = 1.096-1.791, P = 0.007; CT vs TT: OR = 1.284, 95% CI = 1.141-1.444, P < 0.001; C vs T: OR = 1.221, 95% CI = 1.084-1.375, P = 0.001), while there was no significant association for ERα XbaI polymorphism. Besides, in stratification analyses by ethnicity, the PvuII polymorphism was associated with an increased risk of SLE in Asians (CC+CT vs TT: OR = 1.379, 95% CI = 1.203-1.581, P < 0.001; CT vs TT: OR = 1.308, 95% CI = 1.130-1.515, P < 0.001; C vs T: OR = 1.240, 95% CI = 1.052-1.462, P = 0.010), while for ESR1 XbaI polymorphism, a significantly increased risk of SLE susceptibility was found in Asians (GA vs AA: OR = 1.271, 95% CI = 1.101-1.467, P = 0.001). CONCLUSION: Our meta-analysis indicated that the ERα PvuII polymorphism was significantly associated with SLE susceptibility in the overall and Asian populations, while the ERα XbaI GA genotype only played a key role in SLE susceptibility in Asian populations.


Assuntos
Receptor alfa de Estrogênio/genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Grupo com Ancestrais do Continente Asiático , Grupo com Ancestrais do Continente Europeu , Genótipo , Humanos , Polimorfismo Genético , Medição de Risco
6.
Int Immunopharmacol ; 63: 183-190, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30098497

RESUMO

Fibrosis is the common results from an excessive wound-healing response to chronic liver injury. Otreotide (OCT), an analogue of somatostatin, was reported to have an anti-hepatic fibrosis effect. However, its anti-fibrosis mechanisms have not been well characterized to date. The present study aimed to investigate the protective effects of OCT on carbon tetrachloride (CCl4)-induced rat liver fibrosis and activation and proliferation of transforming growth factor-ß1 (TGF-ß1)-treated hepatic stellate cells (HSCs) and explore its anti-hepatofibrotic mechanisms. Our results indicated that treatment with OCT markedly down-regulated the protein and mRNA expression of liver fibrosis markers including α-smooth muscle actin (α-SMA) and collagen I in CCl4-induced rat model of liver fibrosis, accompanied by decreasing aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (TBIL) activities and increasing the serum level of albumin (ALB). In addition, in vitro results revealed that OCT inhibited the activation and proliferation of TGF-ß1-treated LX-2 cells in a concentration-dependent manner and decreased in parallel the expression of Wnt1, ß-catenin, c-Myc and cyclin D1, indicating that OCT might attenuate liver fibrosis, at least in part, by inhibiting Wnt/ß-catenin signaling pathway. Overall, these results provide a novel anti-fibrotic mechanism of OCT, which might be associated with its ability to repress Wnt/ß-catenin signaling pathway.


Assuntos
Ciclina D1/metabolismo , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/metabolismo , Octreotida/farmacologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Tetracloreto de Carbono , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Humanos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Masculino , Octreotida/uso terapêutico , Ratos Sprague-Dawley
7.
Genes Genomics ; 40(10): 1069-1079, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29907909

RESUMO

Although the current glucocorticoids (GCs) treatment for systemic lupus erythematosus (SLE) is effective to a certain extent, the difference in therapeutic effect between patients is still a widespread problem. Some patients can have repeated attacks that greatly diminish their quality of life. This study was conducted to investigate the relationship between HSP90AA2 polymorphisms and disease susceptibility, GCs efficacy and health-related quality of life (HRQoL) in Chinese SLE patients. A case-control study was performed in 470 SLE patients and 470 normal controls. Then, 444 patients in the case group were followed up for 12 weeks to observe efficacy of GCs and improvement of HRQoL. Two single nucleotide polymorphisms (SNPs) of HSP90AA2 were selected for genotyping: rs1826330 and rs6484340. HRQoL was assessed using the SF-36 questionnaire. The minor T allele of rs1826330 and the TT haplotype formed by rs1826330 and rs6484340 showed associations with decreased SLE risk (T allele: PBH = 0.022; TT haplotype: PBH = 0.033). A significant association between rs6484340 and improvement of HRQoL was revealed in the follow-up study. Five subscales of SF-36 were appeared to be influenced by rs6484340: total score of SF-36 (additive model: PBH = 0.026), physical function (additive model: PBH = 0.026), role-physical (recessive model: PBH = 0.041), mental health (dominant model: PBH = 0.047), and physical component summary (additive model: PBH = 0.026). No statistical significance was found between HSP90AA2 gene polymorphisms and GCs efficacy. These results revealed a genetic association between HSP90AA2 and SLE. Remarkably, HSP90AA2 has an impact on the improvement of HRQoL in Chinese population with SLE.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Glucocorticoides/uso terapêutico , Proteínas de Choque Térmico HSP90/genética , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Qualidade de Vida/psicologia , Adulto , Estudos de Casos e Controles , China , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/psicologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
8.
Am J Clin Exp Immunol ; 7(2): 27-39, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29755855

RESUMO

Objective: The aim of this study was to investigate the associations between HSP90B1 gene polymorphisms and the efficacy of glucocorticoids (GCs) and the improvement of health-related quality of life (HRQoL) in Anhui patients with systemic lupus erythematosus (SLE). Method: A total of 305 patients with SLE were recruited to the study. These patients were treated with GCs for 12 weeks and classified into two groups (sensitivity and insensitivity) according to the response to GCs measured by the scores on SLE disease activity index (SLEDAI). The HRQoL of SLE patients were evaluated by 36-item Short Form Health Survey (SF-36) at baseline and 12 weeks respectively. HapMap database and Haploview software were used to select HSP90B1 gene tag single nucleotide polymorphisms (SNPs). Benjamini & Hochberg (BH) method based on false discovery rate (FDR) was used for multiple testing correction. Results: A total of 291 patients were included in final data analysis with 14 patients excluded due to loss to follow-up. Among these patients, 160 patients were sensitive to GCs and 131 patients were insensitive to GCs. Twelve tag SNPs of HSP90B1 gene were selected. The rs12426382 polymorphism was associated with the efficacy of GCs (dominant model: crude OR=0.514, 95% CI=0.321-0.824, P=0.006; adjusted OR=0.513, 95% CI=0.317-0.831, P=0.007). After BH correction, there was no association between rs12426382 polymorphism and efficacy of GCs (PBH =0.084). In haplotype analysis, the haplotype CCCGAACATCCC (OR=2.273, 95% CI=1.248-4.139, P=0.006) and CTGGGACGTTC (OR=0.436, 95% CI=0.208-0.916, P=0.025) showed significant associations with the efficacy of GCs. After corrected by BH method, CCCGAACATCCC was still associated with the efficacy of GCs (PBH =0.048). The rs3794241, rs1165681, rs2722188, rs3794240 and rs10861147 polymorphisms were associated with the improvement of HRQoL among SLE patients (P < 0.05). But no association existed after the correction of BH method (P > 0.05). Conclusions: The results of this study demonstrated that HSP90B1 genetic polymorphisms might be associated with the efficacy of GCs, but not associated with the improvement of HRQoL in Anhui population with SLE.

9.
Springerplus ; 5: 222, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27026916

RESUMO

Heat shock protein 90 (HSP90) is an important glucocorticoid receptor (GR) chaperone protein, and is supposed to be the key factor in regulating glucocorticoids (GCs) effects. The aim of the present study was to explore whether single nucleotide polymorphisms (SNPs) within HSP90AA1 gene affect the response of systemic lupus erythematosus (SLE) patients to GCs treatment. Two hundred and forty-five SLE patients were treated with GCs (prednisone) for 12 weeks. SLE disease activity index (SLEDAI) was used to assess the response of SLE patients to GCs treatment, and patients were classified into sensitive group and insensitive group. HapMap database and Haploview software were used to select tag SNPs. Tag SNPs were genotyped by using multiplex SNaPshot method. Univariate and multivariate logistic regression analyses were used to discriminate the impact of SNPs of HSP90AA1 gene on the response of SLE patients to GCs treatment. Two hundred and thirty three SLE patients finished the 12-week follow-up. Of these patients, 128 patients were included in sensitive group, and 105 patients were included in insensitive group. Seven tag SNPs were selected within HSP90AA1 gene. We detected significant associations for rs7160651 (dominant model: crude OR 0.514, 95 % CI 0.297-0.890, P = 0.018; adjusted OR 0.518, 95 % CI 0.293-0.916, P = 0.024), rs10873531 (dominant model: crude OR 0.516, 95 % CI 0.305-0.876, P = 0.014; adjusted OR 0.522, 95 % CI 0.304-0.898, P = 0.019) and rs2298877 (dominant model: crude OR 0.543, 95 % CI 0.317-0.928, P = 0.026, adjusted OR 0.558, 95 % CI 0.323-0.967, P = 0.037) polymorphisms, but not for other polymorphisms (P > 0.05). The present study demonstrates that HSP90AA1 gene SNPs may affect the response of SLE patients to GCs treatment.

10.
Clin Rheumatol ; 34(9): 1537-44, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26255187

RESUMO

In our previous study, we found that glucocorticoid receptor (GR) gene genetic polymorphisms may play a major role in the efficacy of glucocorticoids (GCs) in Chinese systemic lupus erythematosus (SLE) patients. The aim of this study is to explore the association of GR gene genetic polymorphisms and improvement of health-related quality of life (HRQOL) in Chinese SLE patients treated with GCs. A total of 195 Chinese SLE patients were treated with GCs for 12 weeks. The HRQOL of patients was measured with the Medical Outcomes Study Short Form-36 (SF-36) at baseline and 12 weeks. Polymorphisms of GR gene were genotyped by using multiplex SNaPshot method. One hundred eighty-four patients (94.36 %) completed the 12-week follow-up. Twenty-three single-nucleotide polymorphisms of GR gene were genotyped. There was a significant association between rs10482672 polymorphism and improvement in physical function (P = 0.043), general health (P = 0.024), and social function (P = 0.013). The rs12656106 polymorphism was associated with improvement in the total score of SF-36 (P = 0.014), physical function (P = 0.013), general health (P = 0.010), vitality (P = 0.015), social function (P = 0.004), physical component summary (P = 0.016), and mental component summary (P = 0.014). The rs4912905 polymorphism was associated with improvement in bodily pain (P = 0.040) and general health (P = 0.038). The rs4912911 polymorphism was associated with improvement in general health (P = 0.026) and vitality (P = 0.027). The rs4986593 polymorphism was associated with improvement in bodily pain (P = 0.034). The rs7719514 polymorphism was associated with improvement in vitality (P = 0.002) and mental component summary (P = 0.041). We also found a significant association between rs9324924 polymorphism and improvement in physical function (P = 0.040), bodily pain (P = 0.007), and general health (P = 0.019). These results indicate that there may be an association of GR gene rs10482672, rs12656106, rs4912905, rs4912911, rs4986593, rs7719514, and rs9324924 polymorphisms with improvement of HRQOL in Chinese SLE patients treated with GCs.


Assuntos
Glucocorticoides/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Polimorfismo de Nucleotídeo Único/genética , Prednisona/uso terapêutico , Qualidade de Vida , Receptores de Glucocorticoides/genética , Adulto , Antirreumáticos/uso terapêutico , Grupo com Ancestrais do Continente Asiático , China , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Adulto Jovem
11.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 35(11): 1335-9, 2015 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-26775481

RESUMO

OBJECTIVE: To observe blood uric acid levels and Goldstein grading, as well as their correlation in Wilson's disease (WD) patients with different Chinese medical syndrome types. METHODS: Totally 906 WD patients in line with inclusive criteria were assigned to 6 groups, i.e., the heart spirit confused by phlegm group (HSCP, 26 cases), the phlegm-fire disturbing heart group (PFDH, 90 cases), the retention of damp-heat group (RDH, 113 cases), deficiency of qi and blood group (DQB, 168 cases), the deficiency of Gan-yin and Shen-yin group (DGYSY, 327 cases), the deficiency of Gan and Shen group (DGS, 182 cases) due to different Chinese medical syndrome types. Recruited were another 160 healthy subjects having similar ages and diet structures, who came for medical examinations, as the healthy control group. Venous blood was collected from the medial cubital vein of each-patient on an empty stomach in early mornings to detect blood uric acid levels. Results Blood uric acid levels were lower in each syndrome type group than in the healthy control group (146.08 +/- 67.24 micromol/L in the HSCP group; 157.08 +/- 69.77 micromol/L in the PFDH group; 162.58 +/- 97.72 micromol/L in the RDH group; 156.20 +/- 62.63 micromol/L in the DQB group; 161.83 +/- 111.23 micromol/L in the DGYSY group; 194.41 +/- 90.01 micromol/L in the DGS group; 242.39 +/- 87.55 micromol/L in the healthy control group, P < 0.01). Blood uric acid levels were higher in the DGYSY group than in the other 5 syndrome groups (P < 0.01). Correlation analyses between Goldstein grading and blood uric acid showed that, along with increased Goldstein grade (that was aggravating disease conditions), WD patients' blood uric acid levels decreased (P < 0.01). CONCLUSIONS: WD patient's blood uric acid levels decreased more. Blood uric acid levels and Goldstein grading were different in various Chinese medical syndrome types. Blood uric acid levels had certain value in assessing the severity of WD.


Assuntos
Degeneração Hepatolenticular/diagnóstico , Medicina Tradicional Chinesa , Ácido Úrico/sangue , Grupo com Ancestrais do Continente Asiático , Coração , Degeneração Hepatolenticular/sangue , Degeneração Hepatolenticular/classificação , Humanos , Síndrome
12.
Immunopharmacol Immunotoxicol ; 36(6): 397-403, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25204222

RESUMO

OBJECTIVE: To investigated whether CBS3830, a highly selectively inhibitor of p38MAPK, could ameliorate inflammation and intimal hyperplasia in arterialized vein grafts (AVGs). METHODS: Sixty male Sprague-Dawley rats underwent a reversed right jugular vein to common carotid artery interposition graft and were randomly treatment with vehicle (control) or single-dose (3 mg/kg, preoperative) or double-dose (3 mg/kg, preoperative and 4 d postoperative) CBS3830. Twenty rats underwent sham operation. The levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were determined by ELISA. Vein grafts were analyzed by intimal/medial morphometry, proliferating cell nuclear antigen (PCNA) expression, and p38MAPK phosphorylation. RESULTS: TNF-α, IL-1ß, and IL-6 gradually increased then slowly decreased in AVG rats. However, at 4 d and 7 d, TNF-α levels decreased by 37.5% and 29.5% (p = 0.003, 0.05, respectively) in the single-dose CBS3830 group, and by 37.6% and 32.5%, respectively (both p = 0.003) in the double-dose group compared with those of control. IL-1ß levels significantly reduced at 4 d and 14 d in both dosage groups. IL-6 levels significantly reduced at 7 d in both groups. Intima and medial thickening were significantly reduced in both dosage treated groups at 7, 14, and 28 d (all p = 0.000) compared to the controls. Further study showed CBS3830 inhibited p38MAPK phosphorylation and decreased PCNA expression. CONCLUSIONS: CBS3830 significantly decreases inflammation and intimal hyperplasia in AVGs.


Assuntos
Anti-Inflamatórios/farmacologia , Proliferação de Células/efeitos dos fármacos , Dibenzocicloeptenos/farmacologia , Veias Jugulares/transplante , Túnica Íntima/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Relação Dose-Resposta a Droga , Oclusão de Enxerto Vascular/enzimologia , Oclusão de Enxerto Vascular/imunologia , Oclusão de Enxerto Vascular/patologia , Oclusão de Enxerto Vascular/prevenção & controle , Hiperplasia , Imunidade Inata/efeitos dos fármacos , Veias Jugulares/enzimologia , Veias Jugulares/imunologia , Veias Jugulares/patologia , Masculino , Antígeno Nuclear de Célula em Proliferação/biossíntese , Ratos Sprague-Dawley , Túnica Íntima/enzimologia , Túnica Íntima/imunologia , Túnica Íntima/patologia
13.
Clin Exp Rheumatol ; 32(5): 697-704, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25068378

RESUMO

OBJECTIVES: This paper aims to investigate the influence of single-nucleotide polymorphisms (SNPs) in the receptor of activator of nuclear factor kappaB ligand (RANKL) gene (TNFSF11) and osteoprotegerin (OPG) gene (TNFRSF11B) on bone and joint injury in patients with rheumatoid arthritis (RA). METHODS: Two hundred RA patients and 201 matched controls were analysed by case-control design, and their samples were genotyped. Bone mineral density (BMD) and serum OPG and RANKL levels were measured. Clinical and laboratory parameters were recorded, and the radiographic changes in both hands of RA were evaluated by Sharp's method. RESULTS: Our results showed no significant differences in the distribution frequency of the alleles and genotypes of TNFRSF11B (rs2073618 and rs3102735) and TNFSF11 (rs2277438) between the RA group and controls (p>0.05). Compared to patients with TNFSF11 (rs2277438) AA or GG genotype, RA with TNFSF11 (rs2277438) AG genotype had significantly decreased BMD values at lumbar spine 3, lumbar spine 4, lumbar spine 2-4 (p<0.05-0.01), and apparently elevated Sharp scores (p<0.05), respectively. The RA group showed significantly higher serum levels of RANKL, RANKL/OPG ratio and a lower serum level of OPG than that of the controls (p<0.05-0.0001). RA patients with RANKL-rs2277438 heterozygotic genotype (AG) had significantly increased serum levels of RANKL (p<0.05), compared to homozygotic genotype (AA or GG). CONCLUSIONS: These results indicate that SNP of TNFRSF11B (rs2073618 and rs3102735) and TNFSF11 (rs2277438) may not be susceptibility factors for RA in Chinese Han population. SNP of TNFSF11 (rs2277438) may have an important influence on bone and joint injury in RA.


Assuntos
Artrite Reumatoide/genética , Osso e Ossos/diagnóstico por imagem , Articulações/patologia , Osteoprotegerina/genética , Polimorfismo de Nucleotídeo Único , Ligante RANK/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/sangue , Artrite Reumatoide/etnologia , Artrografia , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores/sangue , Densidade Óssea , Osso e Ossos/metabolismo , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Articulações/metabolismo , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/sangue , Fenótipo , Ligante RANK/sangue , Adulto Jovem
14.
J Infect ; 69(1): 75-80, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24631780

RESUMO

OBJECTIVES: To evaluate the correlation between IL-10 gene polymorphisms and hepatitis B infection. METHODS: Tag single nucleotide polymorphisms (SNPs) were used to investigate the relationship between IL-10 gene polymorphisms and susceptibility to chronic hepatitis B virus (HBV) infection by comparing 996 chronic HBV infection cases to 301 acute infection controls. RESULTS: This study found that rs3024490 G/T allele, located in the intron 1 region and highly prevalent in Chinese populations, was significantly different between the chronic HBV infection cases and the acute infection controls in single allele analysis, genetic models analysis, and haplotypes analysis. CONCLUSIONS: This suggested that the rs3024490 within IL-10 was associated with susceptibility to chronic hepatitis B in a Chinese Han population.


Assuntos
Predisposição Genética para Doença , Hepatite B Crônica/genética , Hepatite B Crônica/imunologia , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Adulto , Grupo com Ancestrais do Continente Asiático , Humanos , Masculino
15.
Rheumatol Int ; 34(3): 347-56, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24264010

RESUMO

Systemic lupus erythematosus (SLE) is a severe complex rheumatic disease, but good estimate of its prevalence and risk factors is lacking in China. The aim of the study was to explore the prevalence of SLE and risk factors in rural areas of Anhui Province of China. Eleven counties were randomly selected in Anhui Province, and then, 15% of the villages in selected counties were randomly sampled as study sites. Patients with SLE were identified through two phases. Based on the cases identified, a population-based case-control study was designed to examine risk factors associated with SLE. A total of 1,253,832 individuals and identified 471 SLE cases were surveyed. Crude and age-standardized prevalence were estimated at 37.56 and 36.03 per 100,000 persons, respectively. Gender difference in the prevalence of SLE was significant (P = 4.62 × 10(-76)), and the age-standardized prevalence was 6.17 for males and 67.78 for females per 100,000 persons. The distribution of SLE prevalence was significant by age group (P = 1.78 × 10(-53)), and the peak prevalence was observed at 40-50 years. Multiple environmental factors were associated with SLE, including birth conditions, sweet food, cooking oil, taste, fruit consumption, sunlight exposure, quality of sleep, physical activities, drinking water, residence, negative life events, hepatitis B vaccine, age of menarche, and age at birth of first child (P < 0.05). Our large population-based epidemiological survey estimated the prevalence of SLE at 37.56 per 100,000 persons. Multiple environmental factors were associated with the development of SLE.


Assuntos
Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/epidemiologia , População Rural/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Estudos de Casos e Controles , Criança , Pré-Escolar , China/epidemiologia , Análise por Conglomerados , Meio Ambiente , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
16.
World J Gastroenterol ; 19(40): 6888-93, 2013 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-24187466

RESUMO

AIM: To identify the relationship between tag single nucleotide polymorphisms (tag SNPs) of interleukin-6 (IL-6) gene and susceptibility to chronic hepatitis B virus (HBV) infection in a Han Chinese population. METHODS: We performed a case-control study of 501 Chinese patients with chronic HBV infection and 301 self-limiting HBV-infected individuals as controls. Genomic DNA was isolated from the whole blood of all subjects using phenol/chloroform with MaXtract high-density tubes. Tag SNPs were identified using genotype data from the panel (Han Chinese in Beijing) of the phase II HapMap Project. Four tag SNPs in IL-6 (rs17147230A/T, rs2066992G/T, rs2069837A/G and rs2069852A/G) were genotyped by the Multiplex Snapshot technique. The genotype and allele frequencies were calculated and analyzed. RESULTS: Five haplotypes were involved in the analysis, with frequencies higher than 0.03. One of the haplotypes, TTAA, was significantly different between the two groups. Overall haplotype P values were: ATAA, P = 0.605, OR (95%CI) = 1.056 (0.860-1.297); TGAG, P = 0.385, OR (95%CI) = 1.179 (0.813-1.709); TGGG, P = 0.549, OR (95%CI) = 1.087 (0.827-1.429); TTAA, P = 0.004, OR (95%CI) = 0.655 (0.491-0.873); TTAG, P = 0.266, OR (95%CI) = 1.272 (0.832-1.944). However, the four SNPs showed no significant genotype/allele associations with susceptibility to chronic HBV infection. Overall allele P values were: rs17147230, P = 0.696, OR (95%CI) = 1.041 (0.850-1.276); rs2066992, P = 0.460, OR (95%CI) = 1.090 (0.868-1.369); rs2069837, P = 0.898, OR (95%CI) = 0.983 (0.759-1.274); rs2069852, P = 0.165, OR (95%CI) = 0.859 (0.693-1.064). Overall genotype P values were: rs17147230, P = 0.625; rs2066992, P = 0.500; rs2069837, P = 0.853; and rs2069852, P = 0.380. CONCLUSION: The four tag SNPs of IL-6 gene may be associated with susceptibility to chronic HBV infection in the Han Chinese population.


Assuntos
Hepatite B Crônica/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/etnologia , Hepatite B Crônica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Fatores de Risco
17.
Genet Test Mol Biomarkers ; 17(12): 926-31, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24093803

RESUMO

AIM: Polymorphisms of xeroderma pigmentosum complementation group C (XPC) are thought to have significant effects on prostate cancer (PCa) risk. The aim of our study was to evaluate the impact of XPC gene polymorphisms on PCa risk by using a meta-analysis. METHODS: Data were collected from the following electronic databases: PubMed, EMBASE, Elsevier Science Direct, Cochrane Library, and CNKI, with the last report up to April 30, 2013. Odds ratios with 95% confidence intervals were used to assess the strength of the association. RESULTS: A total of five separate case-control studies (1966 cases and 1970 controls) were included in this meta-analysis. Meta-analysis was performed for the rs2228001 and PAT+/-polymorphisms. We did not detect a significant association between rs2228001 polymorphism and PCa (p>0.05). Similar results were found in stratification analyses by ethnicity and tumor stage. We detected a significant association of PAT+/-polymorphism with PCa (p<0.05). In stratification analysis, we did not detect a significant association of PAT+/-polymorphism with risk of bone metastasis in PCa patients (p>0.05). CONCLUSION: These analyses suggest that XPC gene PAT+/-polymorphism, but not rs2228001, likely contributes to susceptibility to PCa.


Assuntos
Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Proteínas de Neoplasias/genética , Polimorfismo Genético , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Humanos , Masculino , PubMed , Fatores de Risco
18.
Autoimmunity ; 46(8): 531-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24151836

RESUMO

The response to glucocorticoids (GCs) for patients with systemic lupus erythematosus (SLE) is characterized by wide interindividual variability, with a significant number of patients who have no response. We analyzed whether genetic polymorphisms within glucocorticoid receptor (GR) gene are related to variability in the efficacy of GCs in Chinese population with SLE. A cohort of 220 patients with SLE was studied. These patients were treated with GCs (prednisone) for 12 weeks. The efficacy of GCs was measured with the scores on SLE disease activity index (SLEDAI). Patients were classified into two groups (sensitive and insensitive) according to their response to GCs. Polymorphisms of GR gene were genotyped by using multiplex SNaPshot method. A total of 212 patients (96.4%) were included in the final data analyses. Of these patients, 110 patients were considered sensitive to GCs, and 102 patients were considered insensitive to GCs. Eighteen tag single nucleotide polymorphisms (SNPs) of GR gene were selected. Significant associations were seen for rs4912905 (dominant model: crude OR = 0.410, 95%CI = 0.233-0.722, p = 0.002; adjusted OR = 0.419, 95%CI = 0.233-0.754, p = 0.004), rs17100234 (dominant model: crude OR = 0.521, 95%CI = 0.282-0.963, p = 0.038; adjusted OR = 0.520, 95%CI = 0.279-0.970, p = 0.040) and rs7701443 (recessive model: crude OR = 2.736, 95%CI = 1.183-6.331, p = 0.019; adjusted OR = 2.639, 95%CI = 1.116-6.239, p = 0.027) in GR gene, but not for other polymorphisms (p > 0.05). The results of the present study suggest that GR genetic polymorphisms may play a major role in the efficacy of GCs in Chinese population with SLE.


Assuntos
Glucocorticoides/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Receptores de Glucocorticoides/genética , Adulto , Alelos , Feminino , Estudos de Associação Genética , Genótipo , Glucocorticoides/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
19.
Inflammation ; 36(6): 1424-30, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23839650

RESUMO

Although glucocorticoids (GCs) are effective in inducing remission in systemic lupus erythematosus (SLE) patients, there is a significant variation in response to therapeutic GCs, and some patients do not achieve full remission. The aim of this study was to explore the impact of environmental factors on the efficacy of GCs in a Chinese population with SLE. This was a prospective cohort study, and a total of 260 SLE patients treated with GCs (prednisone) were followed up for 12 weeks. The efficacy of GCs was measured with the scores on SLE disease activity index. Environmental factors were collected using a questionnaire. Single-variable analysis and multivariate logistic regression analysis were used to discriminate the impact of environmental factors on the efficacy of GCs. Two hundred forty-seven patients (95.00 %) completed the 12-week follow-up. Among these patients, 131 (53.04 %) were classified into sensitive group and 116 (46.96 %) were classified into insensitive group. Results from logistic analysis showed that the following environmental factors were significantly associated with decreased efficacy of GCs: high salt intake (OR = 3.464, 95%CI = 1.481-8.102, P = 0.004), introverted personality (OR = 3.550, 95%CI = 1.901-6.628, P < 0.0001), experience with negative life events (OR = 5.526, 95%CI = 1.612-18.946, P = 0.007), and history of allergy (OR = 2.966, 95%CI = 1.312-6.704, P = 0.009). These results indicate that environmental factors, including salt intake, personality, experience with negative life events, and history of allergy, may play an important role in the efficacy of GCs in the Chinese population with SLE.


Assuntos
Exposição Ambiental/efeitos adversos , Glucocorticoides/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Prednisona/uso terapêutico , Adulto , China , Estudos de Coortes , Feminino , Humanos , Hipersensibilidade , Acontecimentos que Mudam a Vida , Masculino , Personalidade , Estudos Prospectivos , Cloreto de Sódio , Inquéritos e Questionários
20.
World J Gastroenterol ; 19(24): 3883-91, 2013 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-23840129

RESUMO

AIM: To assess endoscopic papillary balloon dilatation (EPBD) and endoscopic sphincteropapillotomy (EST) for common bile duct (CBD) stone removal using a meta-analysis. METHODS: Randomized controlled trials published from 1990 to 2012 comparing EPBD with EST for CBD stone removal were evaluated. This meta-analysis was performed to estimate short-term and long-term complications of these two treatments. The fixed random effect model or random effect model was established to analysis the data. Results were obtained by analyzing the relative risk, odds ratio, and 95%CI for a given comparison using RevMan 5.1. Statistical significance was defined as P < 0.05. Risk of bias was evaluated using a funnel plot. RESULTS: Of the 1975 patients analyzed, 980 of them were treated with EPBD and 995 were treated with EST. Of the patient population, patients in the EPBD group were younger (OR = -1.16, 95%CI: -1.49 to 0.84, P < 0.01). There were no significant differences in gender proportion, average size of stones, number of gallstones, previous cholecystectomy, the incidence of duodenal diverticulum, CBD diameter or the total follow-up time between EST and EPBD groups. Compared with EST, the total stone clearance in the EPBD group decreased (OR = 0.64, 95%CI: 0.42 to 0.96, P = 0.03), the use of stone extraction baskets significantly increased (OR = 1.91, 95%CI: 1.41 to 2.59, P < 0.01), and the incidence of pancreatitis significantly increased (OR = 2.79, 95%CI: 1.74 to 4.45, P < 0.0001). The incidence of bleeding (OR = 0.12, 95%CI: 0.04 to 0.34, P < 0.01) and cholecystitis (OR = 0.41, 95%CI: 0.20 to 0.84, P = 0.02) significantly decreased. The stone recurrence rate also was significantly reduced in EPBD (OR = 0.48, 95%CI: 0.26 to 0.90, P = 0.02). There were no significant differences between the two groups with the incidence of stone removal at first attempt, hours of operation, total short-term complications and infection, perforation, or acute cholangitis. CONCLUSION: Although the incidence of pancreatitis was higher, the overall stone clearance rate and risk of bleeding was lower with EPBD compared to EST.


Assuntos
Cateterismo/métodos , Endoscopia Gastrointestinal/métodos , Cálculos Biliares/cirurgia , Esfinterotomia Endoscópica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo/instrumentação , Endoscopia Gastrointestinal/instrumentação , Feminino , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/epidemiologia , Fatores de Risco , Esfinterotomia Endoscópica/instrumentação , Resultado do Tratamento
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