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Objective: This systematic review aims to evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) lipoarabinomannan (LAM) assays in detecting tuberculous meningitis (TBM). Methods: A systematic review search was conducted in PubMed and five other databases up to April 2023. Studies that evaluated the diagnostic accuracy of CSF LAM assays were included with either definitive or composite reference standard used as the preferred reference standard. The quality of the included studies was assessed using the QUADAS-2 tool. We performed a bivariate random-effects meta-analysis and calculated the summary diagnostic statistics. Results: A total of six studies, including a sample size of 999, were included in the final analysis. The pooled sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of CSF LAM for diagnosing TBM were determined to be 0.44 (95% CI: 0.31-0.58), 0.89 (95% CI: 0.81-0.93), and 0.76 (95% CI: 0.73-0.80), respectively. Significant heterogeneity was observed in both sensitivity (Q = 73.82, p < 0.01; I2 = 86.45, 95%CI: 79.64-93.27) and specificity (Q = 95.34, p < 0.01; I2 = 89.51, 95% CI: 84.61-94.42). Regression analysis indicated that the study design (retrospective vs. prospective) was associated with the heterogeneity of pooled sensitivity and specificity (all p < 0.05). Conclusion: Although more prospective studies are required to validate the role of the CSF LAM assay, current evidence supports that the performance of the CSF LAM assay is unsatisfactory for the TBM diagnosis. Additionally, the optimization of the CSF LAM assay (e.g., improvements in CSF collection and preparation methods) should be considered to improve its performance.
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Tuberculose Meníngea , Humanos , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/líquido cefalorraquidiano , Estudos Prospectivos , Estudos Retrospectivos , Lipopolissacarídeos/líquido cefalorraquidianoRESUMO
Background: Previous cohort studies have found an association between Bacillus Calmette-Guérin (BCG) administration and incident dementia. In the systematic review and meta-analysis, we aimed to summarize the current evidence of the effect of BCG use on the risk of developing dementia. Methods: We searched six databases until 20 May 2023 for studies investigating the risk of dementia and BCG administration. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were pooled in the meta-analysis. Meta-regression, subgroup, and sensitivity analysis were conducted as well. Results: Of the 4,043 records initially evaluated, five articles were included for final analysis, with a total of 45,407 bladder cancer (BC) patients. All five studies were evaluated and rated as with high quality, and a low possibility of publication bias was indicated. A significant association between BCG and the incidence of dementia in BC patients was found in all five studies. Although a high heterogeneity (I2 = 84.5%, p < 0.001) was observed, the pooled HR was 0.55 (0.42-0.73), indicating that BCG exposure or treatment reduced the risk of incident dementia by 45%. Moreover, the sensitivity analysis showed good robustness of the overall effect with no serious publication bias. Conclusion: BCG administration is associated with a significantly lower risk of developing dementia. However, an epidemiological cohort is needed to establish a relationship between BCG use and incident dementia in the normal population. Once the relationship is confirmed, more people may benefit from the association. Systematic review registration: identifier: CRD42023428317.
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BACKGROUND: The actual positive rate of interferon gamma release assays (IGRAs) in patients with nontuberculous mycobacteria (NTM) infections remains unclear. This review and meta-analysis present the prevalence of positive IGRAs (T-SPOT.TB and QuantiFERON [QFT] tests) among patients infected with NTM isolates (with or without ESAT-6/CFP-10). METHODS: Several databases, including PubMed, Scopus, Embase, and Web of Science were searched (until June 18th, 2022). Studies that had the following data were included: (1) results of T-SPOT.TB, QuantiFERON (QFT) test, or both, (2) NTM species, and (3) NTM diseases, or NTM colonization. The metaprop command that incorporates a Freeman-Tukey double arcsine transformation is used for pooling proportions. RESULTS: A total of 11 articles (n = 929) were deemed eligible for inclusion. Meta-analysis identified that the overall pooled positive and indeterminate rates of IGRA results in patients with NTM infections was 16% and 5%, respectively. Subgroup analysis showed that the positive rate of IGRAs in patients infected with NTM (without ESAT-6/CFP-10) was 7% (95% CI, 1%-18%), and 44% (95%CI, 22%-68%) in patients infected with NTM (with ESAT-6/CFP-10). In addition, the indeterminate rate of QFT (7%, 95% CI: 4%-12%) was higher than that of T-SPOT.TB (0%; 95% CI, 0%-2%) among the overall population with NTM infections. CONCLUSIONS: The IGRAs have a moderate positive rate for the diagnosis of NTM (expressing ESAT-6/CFP-10) infections, and a significant indeterminate rate is observed among the overall population infected with NTM. However, these findings should be interpreted with caution because of the high heterogeneity among studies.
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Testes de Liberação de Interferon-gama , Infecções por Mycobacterium não Tuberculosas , Humanos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Pacientes , Bases de Dados FactuaisRESUMO
Objectives: Accumulating evidence are available on the efficacy of high-dose isoniazid (INH) for multidrug-resistant tuberculosis (MDR-TB) treatment. We aimed to perform a systematic review and meta-analysis to compare clinical efficacy and safety outcomes of high-dose INH- containing therapy against other regimes. Methods: We searched the following databases PubMed, Embase, Scopus, Web of Science, CINAHL, the Cochrane Library, and ClinicalTrials.gov. We considered and included any studies comparing treatment success, treatment unsuccess, or adverse events in patients with MDR-TB treated with high-dose INH (>300 mg/day or >5 mg/kg/day). Results: Of a total of 3,749 citations screened, 19 studies were included, accounting for 5,103 subjects, the risk of bias was low in all studies. The pooled treatment success, death, and adverse events of high-dose INH-containing therapy was 76.5% (95% CI: 70.9%-81.8%; I2: 92.03%), 7.1% (95% CI: 5.3%-9.1%; I2: 73.75%), and 61.1% (95% CI: 43.0%-77.8%; I2: 98.23%), respectively. The high-dose INH administration is associated with significantly higher treatment success (RR: 1.13, 95% CI: 1.04-1.22; p < 0.01) and a lower risk of death (RR: 0.45, 95% CI: 0.32-0.63; p < 0.01). However, in terms of other outcomes (such as adverse events, and culture conversion rate), no difference was observed between high-dose INH and other treatment options (all p > 0.05). In addition, no publication bias was observed. Conclusion: In MDR-TB patients, high-dose INH administration is associated with a favorable outcome and acceptable adverse-event profile. Systematic review registration: identifier CRD42023438080.
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PURPOSE: To characterize the clinical and mycological features of favus of scrotum due to Trichophyton rubrum. METHODS: A single-site prospective study was carried out in an outpatient dermatology clinic. Microscopic examination and fungal culture were done using skin scrapings. Scales on the scrotum were stained with PAS and visualized by microscopy, including in vivo reflectance confocal microscopy (RCM). Two strains were analyzed by RAPD typing. Scutular lesions were fixed for scanning electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: Cultures of the scale from the scrotum and/or groin in all patients showed a growth of T. rubrum. T. rubrum strains from scrotum and groins in one patient were demonstrated as the same strain by RAPD typing. The average age of patients was 34.1 ± 12.78 years. The mean course was 8.2 ± 5.07 days. All the patients received only topical treatment for 2 weeks without recurrence. Direct smear, calcofluor-white staining and in vivo RCM study of the scrotal favus in patients showed a massive number of septate branching hyphae, while fewer septate hyphae in scales in the groin. Abundant hyphae were found only in the outer layer of the stratum corneum of the scrotum under SEM and TEM with intact bilateral cell walls, and normal nucleus, liposomes and reticulum. Few distorted hyphae structures, cell wall degeneration, degenerated cytoplasm and the autophagy phenomenon could be seen in scales from groin under TEM. CONCLUSIONS: Scrotal favus due to T. rubrum is still a true infection, which most often occurred in immunocompetent patients.
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Escroto/microbiologia , Escroto/patologia , Tinha Favosa/diagnóstico , Tinha Favosa/patologia , Trichophyton/isolamento & purificação , Adolescente , Adulto , Antifúngicos/administração & dosagem , Humanos , Masculino , Técnicas Microbiológicas , Microscopia Confocal , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Pacientes Ambulatoriais , Estudos Prospectivos , Tinha Favosa/tratamento farmacológico , Tinha Favosa/microbiologia , Adulto JovemRESUMO
Vitiligo, an acquired pigmentary disorder of the skin, is characterized by a chronic and progressive loss of melanocyte from the epidermis and follicular reservoir. Growth factor of surrounding cells impacted on melanocytes survival. In this study, lower level of IGF-1 in the lesion was found than that in the donor area of vitiligo patients. IGF-1 improved activation of Nrf2, and inhibited ROS generation and endoplasmic reticulum dilation in HaCaT. C57BL/6 mice were treated with 5% H2O2, and combined with 50⯵g/kg of IGF-1 pre-treatment or not once every day for 50 consecutive days. After 50 days, IGF-1 obviously ameliorated depigmentation of mice skin and reduced hair follicle length, skin thickness and Tyrosinase induced by H2O2. Moreover, IGF-1 significantly suppressed CD8+ T cells infiltration in mice skin, inhibited the production of IL-2 and IFN-γ, and decreased the expression of CXCL10 and CXCR3. Thus, the results indicated that IGF-1 could resist oxidative damage to HaCaT, suppress CD8+ T cells infiltration and pro-inflammatory cytokines secretion, and suppresses the thinning of epidermal layer in vivo. It suggests that IGF-1 inhibits oxidative damage to HaCaT and immunosuppressive effects on CD8+ T cells proliferation and activation to resist depigmentation induced by H2O2. This disclosed its multiple roles in the vitiligo, and shed a light on developing the application potential for IGF-1 in vitiligo.
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Fator de Crescimento Insulin-Like I/farmacologia , Vitiligo/tratamento farmacológico , Animais , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular , Movimento Celular/imunologia , Humanos , Peróxido de Hidrogênio/farmacologia , Tolerância Imunológica/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/fisiologia , Ativação Linfocitária/imunologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Pigmentação/efeitos dos fármacosRESUMO
Transcriptome changes of biofilm-forming Staphylococcus epidermidis response to total alkaloids of Sophorea alopecuroides was observed. Bioinformatic analyses were further used to compare the differential gene expression between control and the treated samples. It was found that 282 genes were differentially expressed, with 92 up-regulated and 190 down-regulated. These involved down-regulation of the sulfur metabolism pathway. It was suggested that inhibitory effects on Staphylococcus epidermidis and its biofilm formation of the total alkaloids of S. alopecuroides was mainly due to the regulation of the sulfur metabolism pathways of S. epidermidis.
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Alcaloides/farmacologia , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Sophora/química , Staphylococcus epidermidis/efeitos dos fármacos , Transcriptoma , Proteínas de Bactérias/genética , Biologia Computacional , Regulação Bacteriana da Expressão Gênica , Redes e Vias Metabólicas , Staphylococcus epidermidis/genética , Enxofre/metabolismoRESUMO
OBJECTIVE: To determine the impact on tyrosinase expression and export from endoplasmic reticulum by inhibition of 26S proteasome. METHODS: Western blot was used to detect 26S proteasome from 8 vitiligo patients and 4 healthy controls. Melanocytes were incubated with proteasome inhibitor (lactacystin) and further detected as follows: cell survival by MTT assay, proteasome activity with fluorescence, ultrastructure observation with electron microscope, co-localization of tyrosinase and calreticulin (endoplasmic reticulum marker) by confocal laser scanning microscopy and 26S proteasome and tyrosinase with Western blot. RESULTS: The 26S proteasome expression level from lesions of vitiligo (1.05 ± 0.40) was significantly lower than the donor sites (1.82 ± 0.88) and the healthy controls (1.88 ± 0.16) (P < 0.05). But no significant difference existed between the latter two groups (P > 0.05). Compared to the untreated group, a 12-h incubation of 10 µmol/L lactacystin showed inhibitory effects on melanocytes (0.999 ± 0.110 vs 1.372 ± 0.127, P < 0.05) and significantly decreased proteasome activity (0.234 ± 0.019 vs 1, P < 0.01). Expansion rate of endoplasmic reticulum in the lactacystin group (1.91 ± 0.17) was significantly higher than that of the untreated cells (1.17 ± 0.11) (P < 0.05). More tyrosinase co-localized with calreticulin in endoplasmic reticulum in lactacystin-treated cells was observed than that of the untreated group. Compared with the untreated group, significantly decreased levels of tyrosinase (146 ± 10 vs 269 ± 8, P < 0.01) and tyrosinase activity (0.159 ± 0.017 vs 0.221 ± 0.019, P < 0.01) were shown in the lactacystin group (P < 0.05). CONCLUSIONS: Significantly decrease of 26S proteasome is found in lesions of vitiligo patients. Inhibition of 26S proteasome may lead to expansion of endoplasmic reticulum of melanocytes, impact export of tyrosinase from melanocyte endoplasmic reticulum and expression of tyrosinase.
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Acetilcisteína/análogos & derivados , Retículo Endoplasmático/metabolismo , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Acetilcisteína/farmacologia , Adulto , Estudos de Casos e Controles , Células Cultivadas , Inibidores de Cisteína Proteinase/farmacologia , Feminino , Humanos , Masculino , Melanócitos/citologia , Vitiligo/metabolismo , Vitiligo/patologia , Adulto JovemRESUMO
We here investigated the efficiency of autologous melanocyte transplantation of 23 vitiligo patients by focusing on perilesional skin homing CD8+ T lymphocytes, and studied the potential effect of dermal mesenchymal stem cells (DMSCs) on CD8+ T cell activities in vitro. Out of 23 patients with the autologous melanocyte transplantation, 12 patients (52.17%) had an excellent re-pigmentation, 6 patients (26.09%) had a good re-pigmentation, 5 patients (21.74%) had a fair or poor re-pigmentation. CD8+ T cells infiltrating was observed in the perilesional vitiligo area of all patients. Importantly, the efficiency of the transplantation was closely associated with skin-homing CD8+ T cell activities. The patients with high number of perilesional CD8+ T cells or high level of cytokines/chemokines were associated with poor re-pigmentation efficiency. For in-vitro experiments, we successfully isolated and characterized human DMSCs and skin-homing CD8+ T cells. We established DMSCs and CD8+ T cell co-culture system, where DMSCs possessed significant inhibitory effects against skin homing CD8+ T lymphocytes. DMSCs inhibited CD8+ T cells proliferation, induced them apoptosis and regulated their cytokines/chemokines production. Our results suggest that vitiligo patients' autologous melanocytes transplantation efficiency might be predicted by perilesional skin-homing CD8+ T cell activities, and DMSCs might be used as auxiliary agent to improve transplantation efficacy.
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Linfócitos T CD8-Positivos/imunologia , Transplante de Células , Melanócitos/transplante , Células-Tronco Mesenquimais/citologia , Pele/citologia , Pele/imunologia , Vitiligo/cirurgia , Adulto , Apoptose , Linfócitos T CD8-Positivos/patologia , Proliferação de Células , Quimiocinas/biossíntese , Quimiocinas/metabolismo , Epiderme/imunologia , Epiderme/metabolismo , Epiderme/patologia , Feminino , Regulação da Expressão Gênica/imunologia , Humanos , Masculino , Pigmentação/imunologia , Pele/metabolismo , Pele/patologia , Transplante Autólogo , Vitiligo/imunologia , Vitiligo/metabolismoRESUMO
The aim of this study was to investigate the diagnostic value of superoxide dismutase (SOD) in tuberculous pleural effusions (TPEs) and malignant pleural effusions (MPEs). Pleural effusion (PE) samples from 100 patients were classified on the basis of diagnosis as TPE (n=57) and MPE (n=43). The activity of SOD was determined by pyrolgallol assay. A significant difference was observed in SOD activity (P<0.01) between TPE and MPE, levels of being significantly higher in TPE compared to MPE. With a threshold value of 41 U/L, the area under the ROC curve was 0.653, SOD had a sensitivity of 61.4% and a specificity of 61.0% for differential diagnosis. Thus, SOD activity in PE was not a good biomarker in differentiating TPE and MPE. To the best of our knowledge, five SOD isoforms may be present in PE. Identification of which SOD contributes to the difference of SOD level between TPE and MPE is very important for illustrating mechanisms and improving the differential diagnostic value.
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Derrame Pleural Maligno/diagnóstico , Superóxido Dismutase , Tuberculose Pleural/diagnóstico , Biomarcadores/análise , Biomarcadores/sangue , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Superóxido Dismutase/análise , Superóxido Dismutase/sangueRESUMO
OBJECTIVE: To explore the inhibition effect of RNA interference on the ICP4 expression and DNA replication of herpes simplex virus type 2 (HSV2). METHODS: Four pairs of siRNA targeted to HSV2 ICP4 gene and negative control siRNA were synthetized by chemical method, named as siRNA-1, siRNA-2, siRNA-3, siRNA-4 and siRNA-N respecticely. HSV2 HG52 was used to attack Vero cell after transfection overnight. Vero cell and supernatant were collected at 1d, 2d, 3d, 4d and 5d after virus attacking. Flurogenic quantitative reverse transcription polymerase chain reaction (FQ-RT-PCR)was used to detect the expression of HSV2 ICP4 mRNA, flurogenic quantitative polymerase chain reaction(FG-PCR) was used to detect the expression of HSV2 DNA and Western-Blot was used to detect the expression of HSV2 ICP4 protein. RESULTS: All the four pairs of siRNA could significantly inhibit the expression of HSV2 ICP4 mRNA and protein, especially siRNA-2. The above siRNAs could significantly decrease HSV2 DNA copy number,too. CONCLUSION: siRNAs targeted to HSV2 ICP4 gene could significantly inhibit expression of HSV2 ICP4 mRNA and protein, and decrease HSV2 DNA copy number, suggesting that siRNA can inhibit HSV2 DNA replication through silencing ICP4 gene.
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Regulação Viral da Expressão Gênica/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Interferência de RNA/efeitos dos fármacos , RNA Interferente Pequeno/farmacologia , Regulação Viral da Expressão Gênica/genética , Inativação Gênica/fisiologia , Herpesvirus Humano 2/genética , Interferência de RNA/imunologia , RNA Viral/efeitos dos fármacos , RNA Viral/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: To investigate the roles of InnVit (FBX011) gene in melanocytes by detecting the expression of InnVit gene in vitiligo and analyzing the impact of InnVit gene on morphology of endoplasmic reticulum (ER) and the tyrosinase export from ER. METHODS: The lesion tissues and the donor tissues were collected from 10 vitiligo patients to examine the InnVit gene expression by immunohistochemistry. Synthesized specific siRNA and constructed plasmid P3XF-P120 were separately transfected into cells for the silence and over-expression of InnVit gene with lipofectamine(TM) 2000. The untreated cells were used as control. Morphology of ER of cells from the above three groups was observed under electron microscope. Co-localization of tyrosinase and calreticulin was identified by confocal laser scanning microscopy. InnVit, tyrosinase and calreticulin were examined by Western blot. RESULTS: In vitiligo patients, the expression of InnVit gene in the lesions was markedly lower than that in the donor tissues. The normal morphology of ER was found in the untreated and the plasmid groups whereas inflated ER was shown in siRNA group. And the relative inflation rate in siRNA group (1.97 +/- 0.48) was higher than that in the untreated group (1.28 +/- 0.09) and plasmid group (1.24 +/- 0.13) (both P = 0.001). In the untreated and the plasmid groups, tyrosinase was expressed beyond the scope marked by ER marker protein calreticulin partly, but co-localized with calreticulin in ER in the siRNA group. Western blot showed that, contrast to the untreated group (0.320 +/- 0.020), a lower expression level of InnVit in the siRNA group (0.030 +/- 0.004, P = 0.001) and a higher expression of InnVit in the plasmid group were shown (0.710 +/- 0.040, P = 0.001). No significant difference about the expression level of calreticulin was observed among the three groups (P > 0.05). As compared with the untreated group (0.350 +/- 0.030), a higher tyrosinase level in the siRNA group (1.040 +/- 0.060, P = 0.001) and in the plasmid group (0.720 +/- 0.030, P = 0.001) was found. And the former was higher than the latter (P = 0.001). CONCLUSION: A lower expression of InnVit is observed in the lesion tissues than in the donor tissues from vitiligo patients. The InnVit gene can have an impact on the morphology of ER and tyrosinase export from ER. And it may further affect the function of melanocytes.
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Retículo Endoplasmático/metabolismo , Proteínas F-Box/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Proteína-Arginina N-Metiltransferases/metabolismo , Vitiligo/genética , Adulto , Células Cultivadas , Retículo Endoplasmático/genética , Retículo Endoplasmático/patologia , Feminino , Humanos , Masculino , Melanócitos/citologia , Melanócitos/metabolismo , RNA Interferente Pequeno/genética , Pele/patologia , Vitiligo/metabolismo , Adulto JovemRESUMO
OBJECTIVE: To investigate whether abnormal translocation of nuclear factor-E2 related factor 2 (Nrf2) exists in the lesion of vitiligo. METHODS: Skin specimens from 8 vitiligo patients and 3 healthy controls were collected, half of them underwent laser co-focal microscopy to detect the Nrf2 location and half of them underwent cell culture. Blister fluid was collected form the 8 vitiligo patients and skin donor sites to detect the levels of serum superoxide dismutase (SOD), catalase (CAT), and malonyldialdehyde (MDA) by using detection kit. Expression of Nrf2 in epidermal cell of the 8 vitiligo patients and primary epidermal cell of the 3 healthy controls was identified with cell immunofluorescence histochemistry method. The nuclear and cytoplasmic proteins of all above samples were isolated to be identified by Western blotting. RESULTS: The levels of SOD and CAT in the lesion tissue were significantly lower than those in the skin donor site. The levels of MDA in the lesion tissue were significantly higher than those in the skin donor sites (both P < 0.05). Immunofluorescence histochemistry, showed that Nrf2 was predominantly cytoplasmic in the epidermal cells in the lesion, while Nrf2 expression could be seen in both the cytoplasm and nucleus in the epidermal cells in the normal skin donor sites and skins of the healthy controls. Western blotting showed that the nuclear Nrf2 level in the vitiligo skin lesion was (0.11 +/- 0.03), significantly lower than that in the normal skin donor site (0.27 +/- 0.06) and in the skins of the healthy controls (0.32 +/- 0.02) (both P < 0.01). However, there was no significant difference in the Nrf2 level of in cytoplasm among the three types of tissues (0.63 +/- 0.04, 0.61 +/- 0.03, and 0.65 +/- 0.04, all P > 0.05). CONCLUSION: Nrf2 does not translocate from cytoplasm into the nucleus in the lesion of vitiligo patients.
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Fator 2 Relacionado a NF-E2/metabolismo , Pele/metabolismo , Vitiligo/metabolismo , Adulto , Catalase/metabolismo , Núcleo Celular , Feminino , Humanos , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo , Pele/patologia , Superóxido Dismutase/biossíntese , Transativadores , Vitiligo/patologiaRESUMO
OBJECTIVE: To investigate the association of the single nucleotide polymorphisms (SNPs) in Nrf2 promoter region with the susceptibility to risk of vitiligo. METHODS: Samples of peripheral blood were collected from 300 vitiligo patients and 300 healthy persons. The genotypes of -686A/G, -684G/A, and -650C/A were detected by direct-sequencing. Genotyping of variable number of tandem repeat (VNTR) was performed by gene scan analysis with an ABI 310 Sequencer. Genetic and allelic frequencies were analyzed by Chi-square test and the risk was evaluated by calculating OR and 95% CI. RESULTS: There was statistical significant difference in genotypic and allelic frequencies of -650C/A between the vitiligo group and healthy control group (P < 0.05), and A -650 allele was associated with risk for vitiligo statistically significantly (OR = 1.724, 95% CI: 1.345-2.211, chi2 = 18.096, P < 0.01). Homozygote of A allele increased the risk for vitiligo obviously (OR = 2.902, 95% CI: 1.624-5.188, P < 0.01). No significant difference was found in other three polymorphisms between the two groups. CONCLUSION: polymorphism of Nrf2 promoter region -650C/A was associated with the development of vitiligo and A -650 allele may be one of risk factors for vitiligo.
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Fator 2 Relacionado a NF-E2/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Vitiligo/genética , Adulto , Alelos , Sequência de Bases , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Fatores de RiscoRESUMO
Vitiligo is an acquired pigmentary disorder and its pathogenesis remains unclear. Oxidative stress is considered to be the initial pathogenic event in the melanocyte destruction. NF-E2-related factor2 (Nrf2) is a transcription factor regulating the expression of detoxifying and antioxidant genes. To investigate the association of the Nrf2 gene promoter polymorphisms with vitiligo in Chinese Han population, the genotypes of -686A/G, -684G/A and -650C/A and the genotyping of variable number of tandem repeat were detected. The data were analysed by the chi-square test and the risk was evaluated by calculating OR and 95% CI. There was statistically significant difference in genotypic and allelic frequencies of -650C/A between the two groups (P < 0.05). A(-650) allele was significantly associated with the risk for vitiligo (OR = 1.724, chi(2) = 18.096). Polymorphism of the Nrf2 gene promoter at -650C/A was associated with the development of vitiligo and A(-650) allele may be one of the risk factors.
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Fator 2 Relacionado a NF-E2/genética , Polimorfismo Genético , Vitiligo/genética , Adolescente , Adulto , Fatores Etários , Povo Asiático , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Fatores Sexuais , Sequências de Repetição em Tandem/genética , Vitiligo/patologia , Adulto JovemRESUMO
OBJECTIVE: To express the epitope peptide of human tyrosinase (TYR), and discuss the application of the peptide in detecting autoantibody of the vitiligo patients. METHODS: The epitope areas 240 - 255, 289 - 294, 295 - 300, 435 - 447, and 461 - 479 of human TYR were synthesized and connected to the vector pGEM-T. The target gene was cloned to the prokaryotic expression vector pGEX-4T-2, which was then transferred to Escherichia coli BL21 host cells. Isopropy-beta-D-thiogalactoside (IPTG) was used to induce the protein expression that was examined with SDS-PAGE and Western blotting. Indirect ELISA was conducted to detect the antigenicity of the peptide in 100 blood specimens of active vitiligo patients and 30 healthy controls. RESULTS: The recombinant expression vector was constructed successfully. The SDS-PAGE and Western blotting results showed expression of the recombinant protein in E. coli. The amount of the recombinant protein reached about 70% of the total mass of bacterial protein with PAGE analysis system. With the glutathione S-transferase (GST) purification kit, the purity of recombinant protein reached over 90%. Indirect ELISA showed that reaction with the target protein was negative in all the 30 healthy controls and was positive in 64 of the 100 active vitiligo patients. CONCLUSION: The epitope peptide of human TRY is expressed successfully, and it has antigenicity in the serum of vitiligo patients.
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Epitopos/imunologia , Monofenol Mono-Oxigenase/imunologia , Peptídeos/imunologia , Vitiligo/imunologia , Adolescente , Adulto , Western Blotting , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Epitopos/genética , Escherichia coli/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monofenol Mono-Oxigenase/química , Peptídeos/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Vitiligo/genéticaRESUMO
G-protein coupled receptors (GPCRs) represent one of the most important classes of drug targets for pharmaceutical industry and play important roles in cellular signal transduction. Predicting the coupling specificity of GPCRs to G-proteins is vital for further understanding the mechanism of signal transduction and the function of the receptors within a cell, which can provide new clues for pharmaceutical research and development. In this study, the features of amino acid compositions and physiochemical properties of the full-length GPCR sequences have been analyzed and extracted. Based on these features, classifiers have been developed to predict the coupling specificity of GPCRs to G-proteins using support vector machines. The testing results show that this method could obtain better prediction accuracy.