RESUMO
Many studies have evaluated the correlation between peptidylarginine deiminase 4 (PADI4) -92C/G polymorphism and rheumatoid arthritis (RA), but the results remain inconclusive. Therefore, we performed a meta-analysis in the Chinese population to provide comprehensive data on the association between PADI4 -92C/G polymorphism and RA. Eligible studies published before May 2016 were identified in PubMed and Chinese databases. The strengths of these associations were assessed by pooled odds ratios (OR) and 95% confidence interval (CI). Eight studies documenting a total of 1351 RA cases and 1585 controls were included in this meta-analysis. In the overall analysis, a significant association between the PADI4 -92C/G polymorphism and RA was found in the Chinese population (G vs C: OR=1.32, 95%CI=1.02-1.71; GG+CG vs CC: OR=1.75, 95%CI=1.20-2.53). The subgroup analyses stratified by geographic area(s) and source of controls revealed significant results in South China, in hospital-based studies and population-based studies. In summary, this meta-analysis suggested that PADI4 -92C/G polymorphism may be associated with the RA incidence in the Chinese population, especially for South China. Further studies conducted on other ethnic groups are required for definite conclusions.
Assuntos
Artrite Reumatoide/enzimologia , Artrite Reumatoide/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Desiminases de Arginina em Proteínas/genética , China , Intervalos de Confiança , Humanos , Razão de Chances , Proteína-Arginina Desiminase do Tipo 4 , Fatores de RiscoRESUMO
This study aimed to investigate the correlation between age-related macular degeneration (AMD) of the liver-kidney yin-deficiency type and complement factor H (CFH) polymorphism, and to determine whether the C allele of the T1277C (Y402H) variant is a risk factor for this condition. We performed a case-control investigation of 60 patients with liver-kidney yin-deficiency AMD and 60 normal control subjects. Peripheral blood was collected from each participant for DNA extraction. Following amplification by polymerase chain reaction, the DNA samples were sequenced, and polymorphism of the CFH gene was examined. Data were analyzed with the chi-square test, with P < 0.05 signifying statistical significance. The frequency of the C allele was significantly higher in the wet than in the dry AMD group (P = 0.044). In addition, the TC and CC genotypes were markedly more common in the former than in the control group (P = 0.013), and there was a significant difference in the distribution of the T and C alleles between wet AMD patients and control subjects (P < 0.05). Based on this, we conclude that liver-kidney yin-deficiency AMD is associated with the C allele and TC and CC genotypes of the CFH Y402H polymorphism. Among patients with this condition, CFH genotypes were normally distributed. The principal CFH genotypes that induce liver-kidney yin-deficiency AMD are the mutant homozygote CC and heterozygote TC forms. Moreover, C allele carriers are at higher risk of developing this disease.
Assuntos
Fator H do Complemento/genética , Predisposição Genética para Doença , Degeneração Macular/genética , Deficiência da Energia Yin/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Estudos de Associação Genética , Genótipo , Heterozigoto , Homozigoto , Humanos , Rim/patologia , Fígado/patologia , Degeneração Macular/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Deficiência da Energia Yin/patologiaRESUMO
The ability of mammals to resist body fat accumulation is linked to their ability to expand the number of "brown adipocytes" within white fat depots. All-trans retinoic acid (t-RA) and peroxi-some proliferator-activated receptor-α (PPARα) have been implicated in "browning-like" or "browning" programs, respectively. However, a PPARα-agonist (WY14643) failed to regulate the expression of the uncoupling protein 1(UCP1) gene unless combined with retinoic acid. This study investigated the effects of the PPARα-agonist WY14643 combined with t-RA, on the "browning" of white adipocytes in mice mediated by UCP1, and the molecular mechanisms involved in this process. We compared the effects of WY14643 alone and WY14643 combined with t-RA or the p38 MAPK-inhibitor, SB203580, on white adipocytes after 24 h using the expression of UCP1, detected with RT-PCR and western blot. We also determined the mechanism by which p38 MAPK and phospho-p38 MAPK influence the process of "brown-ing" using western blot. All concentrations of WY14643 failed to in-duce UCP1 mRNA expression, protein expression, or phosphorylation of p38 MAPK (P < 0.05). WY14643 combined with t-RA was observed to induce UCP1 mRNA expression, protein expression, and phosphory-lation of p38 MAPK (P < 0.05). SB203580 combined with WY14643 and t-RA suppressed UCP1 mRNA expression, protein expression, and p38 MAPK phosphorylation (P < 0.05). WY14643 combined with t-RA can induce the transformation of white adipocytes to brown adipocytes through activation of the p38 MAPK signaling pathway.
Assuntos
Adipócitos Marrons/efeitos dos fármacos , Adipócitos Brancos/efeitos dos fármacos , Pirimidinas/farmacologia , RNA Mensageiro/genética , Tretinoína/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Células 3T3-L1 , Adipócitos Marrons/citologia , Adipócitos Marrons/metabolismo , Adipócitos Brancos/citologia , Adipócitos Brancos/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Sinergismo Farmacológico , Regulação da Expressão Gênica , Imidazóis/farmacologia , Canais Iônicos/genética , Canais Iônicos/metabolismo , Masculino , Camundongos , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , PPAR alfa/agonistas , PPAR alfa/genética , PPAR alfa/metabolismo , Fosforilação/efeitos dos fármacos , Piridinas/farmacologia , RNA Mensageiro/metabolismo , Transdução de Sinais , Proteína Desacopladora 1 , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
Lacrimal duct obstruction is a common eye disease, and obstruction of the nasolacrimal duct accounts for over 50% of these cases. Nasolacrimal duct obstruction is usually treated surgically. Lacrimal retrograde catheterization is a novel surgical approach with a high success rate and a relatively high recurrence rate. In this study, we examined the postoperative pathological changes in the lower nasolacrimal duct mucosa at multiple time points (2, 4, 6, 8, 10, 12, and 14 weeks) after retrograde lacrimal dilated drainage tube implantation in rabbits. One side of the nasolacrimal duct was obstructed in 14 rabbits. Compared to the control side, the 2-, 4-, 6-, and 8-week groups presented no obvious changes in hematoxylin and eosin (H&E)-stained tissue. The 10-week group presented isolated granulomas. The 12- and 14-week groups presented scattered granulomas. The granulomas were smaller and the density of fibroblasts was lower in the 12-week group compared with the 14-week group. Transforming growth factor-ß1 immunohistochemistry resulted in strong immunoreactivity in the 14-week group and weak immunoreactivity in the 12-week group, and the difference was statistically significant (P < 0.05). Fibroblast apoptosis was observed in the 4- and 6-week groups, and disorganized fibers were observed in the 10-week group. Most fibroblasts in the 12- and 14-week groups were the active type with mechanocytes. Granulomas were induced after a long time by the implantation of silicone tubes in rabbits. Thus, recurrent obstructions of the nasolacrimal duct may be caused by granulomas, progressive fibrosis, and/or adhesion of the surrounding tissues.
Assuntos
Cateterismo , Mucosa/patologia , Ducto Nasolacrimal/patologia , Animais , Drenagem , Feminino , Granuloma/patologia , Inflamação/patologia , Masculino , Ducto Nasolacrimal/cirurgia , Coelhos , Fatores de TempoRESUMO
Genome-wide association studies in several ethnic groups have reported that polymorphisms of the telomerase reverse transcriptase (TERT) and cleft lip and palate transmembrane 1-like (CLPTM1L) genes, located on 5p15.33, are associated with susceptibility to lung cancer. However, whether genetic variants of TERT-CLPTM1L are associated with an increased risk of lung cancer in the Chinese Han population is unknown. This study examined associations between five single nucleotide polymorphisms (SNPs) of TERT-CLPTM1L (rs402710, rs401681, rs465498, rs4975616, and rs2736100) and lung cancer in a Chinese Han population in the Hubei Province. The five SNPs were detected using the Sequenom MassArray(®) iPLEX System in 304 lung cancer patients and 319 controls. Of the five SNPs, rs4975616 did not conform to Hardy-Weinberg equilibrium in the controls. Only rs2736100 was significantly (P = 0.034) associated with an increased risk of lung cancer. In the linkage disequilibrium analyses, a block of strong linkage disequilibrium was observed between rs401681 and rs465498 (D' = 0.986; r(2) = 0.546). No linkage disequilibrium between rs2736100 and the other three SNPs was found. In the haplotype analyses, the frequencies of the TTCT haplotype in rs402710, rs401681, rs465498, and rs2736100 differed significantly between case and control subjects (odds ratio = 0.56; 95% confidence interval, 0.36-0.88; P = 0.012). The results of this study suggested that rs2736100 on TERT-CLPTM1L indicates a poor prognosis for lung cancer in the Chinese Han population.
Assuntos
Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Telomerase/genética , Adulto , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Estudos de Associação Genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-IdadeRESUMO
Lumbar intervertebral disc degeneration (IDD) is a common clinical pathology and has become a focus for research in recent years. Matrix metalloproteinases (MMPs) are enzymes responsible for the degradation of almost all extracellular matrix proteins (ECM). The over-expression of MMPs or tissue inhibitors of metalloproteinases (TIMPs) may disrupt the dynamic balance of the ECM. Therefore, in the current study, the expression levels of MMP-1 and TIMP-1 in lumbar IDD patients were evaluated in an attempt to elucidate their role in IDD pathogenesis and progression. In total, 60 IDD patients were recruited as the experimental group, along with 20 cases of lumbar vertebral injury without disc degeneration as the control group. Preoperative venous blood samples were collected, and intervertebral disc tissues were collected from the lesion during surgery. Serum and tissue levels of MMP-1 and TIMP-1 were quantified by enzyme-linked immunosorbent assay and immunohistochemical staining, respectively. Serum and tissue MMP-1 levels in IDD patients were significantly higher than those in the control group (P < 0.05). Additionally, sub-group analysis revealed that severe IDD patients had higher MMP-1 levels compared with mild or moderate IDD patients (P < 0.05). However, there were no significant differences in TIMP- 1 levels in either the serum or tissues of IDD patients compared to patients in the control group (P > 0.05). These results demonstrate that MMP-1 expression is increased in IDD, with higher expression observed in more severe cases, whereas TIMP-1 expression was similarly expressed in both normal and degenerated discs.
Assuntos
Degeneração do Disco Intervertebral/enzimologia , Metaloproteinase 1 da Matriz/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Adulto , Idoso , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/patologia , Região Lombossacral/patologia , Masculino , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Pessoa de Meia-Idade , Radiografia , Inibidor Tecidual de Metaloproteinase-1/genética , Adulto JovemRESUMO
Interleukin 18 (IL-18), as a member of IL-1 superfamily, is an important pleiotropic cytokine that modulates Th1 immune responses. In this report, we cloned and identified a homolog of IL-18 in giant panda (Ailuropoda melanoleuca) (designated as AmIL-18) from peripheral blood mononuclear cells stimulated with lipopolysaccharide. The open readin g frame of AmIL-18 cDNA is 579 bp encoding a deduced protein of 192 amino acids. AmIL-18 gDNA fragments contained 5 exons and 4 introns. The amino acid sequence of AmIL-18 shared 23.9 to 87.0% identity with other species. To evaluate the effects of AmIL-18 on the immune response, we expressed the recombinant AmIL-18 in Escherichia coli BL21 (DE3). The fusion protein PET-AmIL-18 was purified by nickel affinity column chromatography and verified by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot analysis. The biological function of purified PET-AmIL-18 was determined on mouse splenocytes by quantitative real-time polymerase chain reaction. INF-γ and other cytokines were increased when stimulated by PET-AmIL-18, particularly when combined with recombinant human interleukin 12, while a Th2-type cytokine, interleukin-4, was strikingly suppressed. These results will provide information for the potential use of recombinant proteins to manipulate the immune response in giant pandas and facilitate the study to protect this treasured species.