RESUMO
Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Assuntos
COVID-19 , Transtornos do Olfato , Feminino , Humanos , Adolescente , SARS-CoV-2 , Olfato , COVID-19/complicações , Estudos Transversais , Vacinas contra COVID-19 , Incidência , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/etiologia , Distúrbios do Paladar/epidemiologia , Distúrbios do Paladar/etiologia , PrognósticoRESUMO
Bone fractures or bones subjected to open conduction and internal fixation are easily infected by bacteria; bacterial lipopolysaccharide (LPS) has been recognized as an important pathogenic factor affecting bone fracture healing. Therefore, the effect of LPS on bone metabolism is relevant for bone healing. In this study, we investigated the effect of LPS on the expression of Toll-like receptor (TLR)-4 (an LPS receptor) by using real-time quantitative PCR and western blotting. We also examined the regulatory role of LPS in osteoblast differentiation by measuring the ALP activity, matrix mineralization, and ALP, OCN, and Runx2 mRNA (essential factors affecting osteoblast differentiation) expression in LPS-treated mouse osteoblast MC3T3-E1 cells. We also evaluated the effect of TLR-4 on LPS-mediated inhibition of osteoblast differentiation using RNA interference. LPS promotes TLR-4 mRNA and protein expression in MC3T3-E1 cells (P < 0.05, P < 0.01 or P < 0.001), and inhibits osteoblast differentiation by downregulating matrix mineralization and ALP activity (P < 0.05, P < 0.01 or P < 0.001), and suppressing the expression ALP, OCN, and Runx2 mRNA in MC3T3-E1 cells (P < 0.05 or P < 0.01). Conversely, RNAi-mediated TLR-4 knockdown abrogates the LPS-mediated inhibition of osteoblast differentiation (P < 0.05 or P < 0.01). In summary, LPS was shown to inhibit osteoblast differentiation by suppressing the expression of ALP, OCN, and Runx2 in a TLR-4-dependent manner. The results of this study may provide insights into the signal pathway of LPS-induced bone loss or delayed bone fracture healing.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Fraturas Ósseas/genética , Osteoblastos/metabolismo , Receptor 4 Toll-Like/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Animais , Linhagem Celular , Subunidade alfa 1 de Fator de Ligação ao Core/biossíntese , Fraturas Ósseas/tratamento farmacológico , Fraturas Ósseas/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Lipopolissacarídeos/administração & dosagem , Proteínas de Membrana/biossíntese , Camundongos , Osteoblastos/patologia , Osteogênese/efeitos dos fármacos , RNA Mensageiro/genética , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genéticaRESUMO
ErbB2 is a vital breast cancer gene and its overexpression has a decisive role in breast tumor initiation and malignant progression. However, the molecular mechanisms that underlie ErbB2 dysregulation in breast cancer cells remain incompletely understood. In this study, we found that ErbB2 expression is inversely correlated with the level of miR-155, a well-documented oncogenic miRNA, in ErbB2-positive breast tumors. We further determined that miR-155 potently suppresses ErbB2 in breast cancer cells. Mechanistically, miR-155 acts to downregulate ErbB2 via two distinct mechanisms. First, miR-155 represses ErbB2 transcription by targeting HDAC2, a transcriptional activator of ErbB2. Second, miR-155 directly targets ErbB2 via a regulatory element in its coding region. Intriguingly, miR-155 is upregulated by trastuzumab and in turn leads to a reduction of ErbB2 expression in trastuzumab-treated ErbB2-positive breast cancer cells. Functional studies showed that miR-155 inhibits ErbB2-induced malignant transformation of human breast epithelial cells. Thus, our findings reveal an intriguing miR-155-ErbB2 context in regulating the malignant transformation of breast epithelial cells, and thereby indicate a novel mode of action for miR-155 in ErbB2-positive breast cancer.
Assuntos
Neoplasias da Mama/genética , Transformação Celular Neoplásica/genética , Células Epiteliais/metabolismo , MicroRNAs/genética , Receptor ErbB-2/genética , Regiões 3' não Traduzidas , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Células Epiteliais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Xenoenxertos , Histona Desacetilase 2/genética , Histona Desacetilases/genética , Humanos , Camundongos , Modelos Biológicos , Biossíntese de Proteínas , Interferência de RNA , RNA Mensageiro/genética , Sequências Reguladoras de Ácido Nucleico , Proteínas Repressoras/genética , Trastuzumab/farmacologiaRESUMO
The US2 protein has been reported to contribute to duck enteritis virus (DEV) infection; however, its kinetics and localization during infection, and whether it is a component of virion, have not been previously reported. To elucidate the function of DEV US2, US2 was amplified by polymerase chain reaction (PCR) and inserted into pET-32a(+); this was expressed, the recombinant US2 protein was purified, and a polyclonal antibody generated. In addition, the kinetics and localization of the US2 gene and protein were determined by quantitative real-time fluorescent PCR, ganciclovir (GCV), and cycloheximide (CHX) treatment, western-blot, and indirect immunofluorescence assay. The packaging of US2 into DEV virions was revealed by a protease protection assay. US2 was found to be transcribed 24 h post-infection (pi) and peaked at 72 h pi; the US2 protein was detected 48 h pi, except in the presence of GCV or CHX. US2 was packed into virions and also localized to the plasma membrane and cytoplasm in infected cells. The results showed that the DEV US2 is a late gene, and that its encoding protein could be a tegument component localized mainly in the cytoplasm. This study provides useful data for the further analysis of DEV US2, including an explanation for the genetic conservation among alphaherpesviruses.
Assuntos
Mardivirus/genética , Proteínas do Envelope Viral/genética , Animais , Linhagem Celular , Patos , Fibroblastos , Expressão Gênica , Mardivirus/efeitos dos fármacos , Transporte Proteico , Proteínas Recombinantes , Proteínas do Envelope Viral/isolamento & purificação , Proteínas do Envelope Viral/metabolismo , VírionRESUMO
MicroRNAs (miRNAs) are thought to play a role in cancer development. We conducted a case-control study to investigate the association between polymorphisms in miR-149C>T and hepatocellular carcinoma (HCC) risk. Duplex polymerase chain reaction with the confronting 2-pair primers were taken to genotype miR-149C>T. The association between genotype frequencies of miR-149C>T and risk of HCC was estimated as odds ratios (ORs) and 95% confidence intervals (95%CIs) using conditional regression analysis. Logistical regression analysis showed that the miR-149 CC genotype and C allele were associated with risk of HCC, with adjusted ORs (95%CI) of 2.07 (1.32-3.26) and 1.42 (1.06-2.12), respectively. Using the TT+TC genotype as a reference, individuals carrying the CC genotype were associated with non-significant increased risk of HCC, adjusted OR (95%CI) of 1.37 (0.91-2.07). Subgroup analysis showed that HBV-infected subjects carrying the miR-149 TC+CC genotype (OR=5.85, 95%CI=2.49-13.77) had an increased risk of HCC. In summary, our study found that miRNA-149C>T polymorphism is associated with risk of HCC, especially in HBV-infected patients.
Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Povo Asiático , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , China , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Fatores de Risco , Carga TumoralRESUMO
Duck hepatitis A virus (DHAV) is an infectious pathogen causing fatal duck viral hepatitis in ducklings. Although both the inactivated vaccines and live attenuated vaccines have been used to protect ducklings, DHAV-1 and DHAV-3 still cause significant serious damage to the duck industry in China and South Korea. For rapid detection, differentiation, and epidemic investigation of DHAV in China, a genotype-specific 1-step duplex reverse-transcription (RT) PCR assay was established in this study. The sensitivity and specificity of the developed RT-PCR assay was evaluated with nucleic acids extracted from 2 DHAV reference strains, and 9 other infectious viruses and bacteria. The genotype-specific primers amplified different size DNA fragments encompassing the complete VP1 gene of the DHAV-1 or DHAV-3. The assay detected the liver samples collected from experimentally infected ducklings and dead ducklings collected from different regions of China. Sequence analysis of these DNA fragments indicated that VP1 sequences of DHAV-1 can be used to distinguish wild type and vaccine strains. The phylogenetic analysis of VP1 sequences indicated that the developed RT-PCR assay can be used for epidemic investigation of DHAV-1 and DHAV-3. The developed RT-PCR assay can be used as a specific molecular tool for simultaneous detection, differentiation, and sequencing the VP1 gene of DHAV-1 and DHAV-3, which can be used for understanding the epidemiology and evolution of DHAV.
Assuntos
Patos , Vírus da Hepatite A/genética , Hepatite A/veterinária , Doenças das Aves Domésticas/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Proteínas Estruturais Virais/genética , Virologia/métodos , Animais , Hepatite A/virologia , Vírus da Hepatite A/classificação , Vírus da Hepatite A/isolamento & purificação , Vírus da Hepatite A/metabolismo , Dados de Sequência Molecular , Filogenia , Sensibilidade e Especificidade , Análise de Sequência de DNA/veterinária , Proteínas Estruturais Virais/metabolismoRESUMO
The objective of this research is to investigate the plasma pharmacokinetics and bio-distribution of liposomal daunorubicin plus tamoxifen in breast cancer murine models through intravenous administration. Daunorubicin and tamoxifen plasma levels in pharmacokinetics studies were determined using HPLC. Biodistributions of various carriers loaded with a cyanine dye (cy7) were evaluated using in vivo imaging. After administration, free daunorubicin and tamoxifen were rapidly cleared out from the blood following a two-compartment kinetic model. The clearances and AUC (0-∞) of daunorubicin were (means ± SD): 0.028 ± 0.005 L h-1 kg-1 and 367.489 ± 56.979 µg mL-1 h-1 (liposomes), and 2.235 ± 0.347 L h-1 kg-1 and 4.546 ± 0.704 µg mL-1 h-1 (free drug). By ex vivo imaging 24 h after injection, the fluorescence intensity of liposomal cy7 plus tamoxifen in tumor region was obviously higher than that of free liposomal cy7. In conclusion, tamoxifen can improve pharmacokinetics profile of liposomal daunorubicin with enhanced therapy for breast cancer.
RESUMO
AIMS/HYPOTHESIS: Sirtuin-1 (SIRT1) is a potential therapeutic target to combat insulin resistance and type 2 diabetes. This study aims to identify a microRNA (miRNA) targeting SIRT1 to regulate hepatic insulin sensitivity. METHODS: Luciferase assay combined with mutation and immunoblotting was used to screen and verify the bioinformatically predicted miRNAs. miRNA and mRNA levels were measured by real-time PCR. Insulin signalling was detected by immunoblotting and glycogen synthesis. Involvement of SIRT1 was studied with adenovirus, inhibitor and SIRT1-deficient hepatocytes. The role of miR-181a in vivo was explored with adenovirus and locked nucleic acid antisense oligonucleotides. RESULTS: miR-181a targets the 3' untranslated region (3'UTR) of Sirt1 mRNA through a miR-181a binding site, and downregulates SIRT1 protein abundance at the translational level. miR-181a is increased in insulin-resistant cultured hepatocytes and liver, and in the serum of diabetic patients. Overexpression of miR-181a decreases SIRT1 protein levels and activity, and causes insulin resistance in hepatic cells. Inhibition of miR-181a by antisense oligonucleotides increases SIRT1 protein levels and activity, and improves insulin sensitivity in hepatocytes. Ectopic expression of SIRT1 abrogates the effect of miR-181a on insulin sensitivity, and inhibition of SIRT1 activity or SIRT1 deficiency markedly attenuated the improvement in insulin sensitivity induced by antisense miR-181a. In addition, overexpression of miR-181a by adenovirus impairs hepatic insulin signalling, and intraperitoneal injection of locked nucleic acid antisense oligonucleotides for miR-181a improves glucose homeostasis in diet-induced obesity mice. CONCLUSIONS/INTERPRETATION: miR-181a regulates SIRT1 and improves hepatic insulin sensitivity. Inhibition of miR-181a might be a potential new strategy for treating insulin resistance and type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Regulação para Baixo , Resistência à Insulina , Fígado/metabolismo , MicroRNAs/metabolismo , Sirtuína 1/metabolismo , Regulação para Cima , Regiões 3' não Traduzidas/genética , Animais , Células Cultivadas , Diabetes Mellitus Tipo 2/genética , Humanos , Immunoblotting , Camundongos , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Sirtuína 1/genéticaRESUMO
We studied the effects of dietary oxidized oils on serum lipid metabolic indices, estradiol level, and the gene expression of apolipoprotein B-100 and apolipoprotein VLDL-II in laying hens. Hy-Line Grey hens (280 ± 10 d old; average egg production, 90.0 ± 2.5%) were allotted to 1 of 4 dietary treatments, which were supplemented with 0 (control group), 1% (low oxidized group), 2% (moderately oxidized group), or 4% (highly oxidized group) thermally oxidized soybean oil. Each treatment contained 6 replicates, with 12 birds each. The feeding trial lasted for 30 d. Laying performance data were recorded weekly. Other indices were measured on d 0, 2, 6, 14, and 30 of the feeding trial. Hens in the moderately and highly oxidized groups had significantly lowered feed conversion ratios (P < 0.05). Those in the highly oxidized group also had decreased concentrations of serum very low density lipoprotein cholesterol on d 30 (P < 0.05) compared with the very low density lipoprotein cholesterol of hens in the moderately oxidized group. Hens in the moderately oxidized group had significantly increased expression of apolipoprotein B-100 (P < 0.05) from d 6 to 30. Consequently, hepatic triglyceride increased in this group on d 30 (P < 0.05). Serum triglyceride decreased in the moderately oxidized group on d 30 (P < 0.05), which may have been caused by the activation of peroxisome proliferator-activating receptor α. Serum estradiol levels were not significantly affected by oxidized oils at any time of measurement, but were significantly different between d 0 and 30 within the moderately oxidized group. This fact indicated that the effect of oxidized oils on apolipoprotein B-100 might partially be a cumulative result of the increasing secretion of estradiol. The results suggested that oxidized oil may affect the performance of laying hens through the regulation of apolipoproteins and estradiol.
Assuntos
Apolipoproteínas/metabolismo , Galinhas , Gorduras Insaturadas na Dieta/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Apolipoproteínas/genética , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Gorduras Insaturadas na Dieta/análise , Estradiol/sangue , Feminino , Lipídeos/sangue , Fígado/metabolismo , OxirreduçãoRESUMO
Murine forestomach carcinoma (cell line MFC), ascitic hepatoma (cell line H22) and sarcoma (cell line S180) solid tumor models were used to test the anti-tumor effect of Trichinella spiralis in vivo. Mice previously infected by oral administration of 400 viable T. spiralis larvae per mouse for 7 days were grafted with various solid tumor cell lines. Other groups of tumor-bearing mice were given caudal vein injection of crude extracts of adult and newborn larvae at 17.5, 35.0 or 70.0 mg kg(-1). These treatments to inhibit tumor growth were dose-dependent (p<0.05). The anti-proliferative activity of crude T. spiralis extract was examined in vitro at 0.035, 0.070 or 0.140 mg ml(-1) using MFC, H22, S180, human chronic myeloid leukemia cell line (K562) and hepatoma cell line (H7402), tumor cell proliferation in vitro was measured by methyl thiazolium stain and was inhibited in dose-dependent manner (p<0.05). At the same doses, crude T. spiralis extracts induced apoptosis of K562 and H7402 as detected by DNA fragmentation. Cell cycle analysis indicated that crude T. spiralis extracts, at 0.140 mg ml(-1), arrested the cell cycle of K562 and H7402 in G1 or S phase. It is concluded that T. spiralis contains anti-tumor active agent.
Assuntos
Neoplasias Experimentais/imunologia , Neoplasias Experimentais/parasitologia , Trichinella spiralis/fisiologia , Triquinelose/imunologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Fragmentação do DNA , Humanos , Camundongos , Extratos de Tecidos/química , Extratos de Tecidos/farmacologia , Trichinella spiralis/químicaRESUMO
A soluble form of cytotoxic T-lymphocyte-associated antigen-4 (sCTLA-4) was recently found and shown to possess a downregulatory function as a membrane-bound CTLA-4 molecule. The purpose of the study was to investigate the expression of sCTLA-4 molecule in patients with systemic lupus erythematosus (SLE). One hundred patients with SLE and 40 age- and sex-matched healthy individuals were enrolled in the study. The results showed that patients with SLE have significantly higher levels of sCTLA-4 in sera than healthy controls (21.6 +/- 12.3 ng/ml versus 5.9 +/- 5.4 ng/ml, P < 0.001). Increased expression of sCTLA-4 mRNA in peripheral blood mononuclear cells (PBMCs) was also found in SLE patients. However, we could not find a statistically significant correlation between the serum levels of sCTLA-4 and lupus disease activities. The reported CTLA-4 gene polymorphism in promoter region at position -318 did not affect the levels of sCTLA-4. To the best of our knowledge, this is the first report showing that patients with SLE have increased sCTLA-4 expression. However, the mechanism and role of increased sCTLA-4 in the pathogenesis of SLE remains elucidated.
Assuntos
Antígenos de Diferenciação/sangue , Imunoconjugados , Lúpus Eritematoso Sistêmico/imunologia , Abatacepte , Antígenos CD , Antígenos de Diferenciação/genética , Sequência de Bases , Antígeno CTLA-4 , Estudos de Casos e Controles , Feminino , Expressão Gênica , Humanos , Lúpus Eritematoso Sistêmico/genética , Masculino , Polimorfismo Genético , Regiões Promotoras Genéticas , RNA Mensageiro/sangue , RNA Mensageiro/genética , SolubilidadeRESUMO
Production of CCR5 expression and MIP-1alpha, a ligand of CCR5, by CD4+ T cells from patients with rheumatoid arthritis (RA) were studied. We analysed further the influence of IL-15 stimulation, CD40/CD40 ligand (CD40L) interaction and CCR5 promotor polymorphism. One hundred and fifty-five RA patients and another 155 age- and sex-matched healthy individuals were enrolled. Peripheral CD4+ and double negative (DN) T cells from patients had lower portions of CCR5, whereas synovial CD4+ and DN T cells showed a much higher CCR5 expression. IL-15 significantly up-regulated the expression of CCR5 on purified CD4+ T cells. CD40L expression on synovial CD4+ T cells was increased greatly in CCR5+ portions by IL-15. MIP-1alpha production by synovial CD4+ T cells was also enhanced by IL-15. Co-culture of CD40 expressing synovial fibroblasts with IL-15-activated synovial CD4+ T cells significantly increased MIP-1alpha production. Expression of CCR5 on patients' CD4+ T cells was not influenced by the promotor polymorphism of CCR5 gene. Taken together, these data suggest CCR5+CD4+ T cells infiltrate the inflamed synovium and IL-15 up-regulates CCR5 and CD40L expression further and enhance MIP-1alpha production in synovial CD4+ T cells. Production of MIP-1alpha by synovial fibroblasts is significantly increased by engagement of CD40 with CD40L. Synovial microenvironment plays a potential role in regulation of CCR5+CD4+ T cells in rheumatoid joints.
Assuntos
Artrite Reumatoide/imunologia , Linfócitos T CD4-Positivos/metabolismo , Proteínas Inflamatórias de Macrófagos/biossíntese , Receptores CCR5/metabolismo , Membrana Sinovial/imunologia , Artrite Reumatoide/genética , Antígenos CD40/metabolismo , Ligante de CD40/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Quimiocina CCL3 , Quimiocina CCL4 , Citometria de Fluxo , Imunofluorescência , Genótipo , Humanos , Interleucina-15/farmacologia , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Isoformas de Proteínas/análise , Isoformas de Proteínas/biossíntese , Receptores CCR5/genética , Estatísticas não ParamétricasRESUMO
Cytotoxic T lymphocyte associated antigen 4 (CTLA-4), a structural homologue of CD28, has been reported to be an important negative regulator of autoimmune diseases. Recent studies showed that CTLA-4 gene polymorphism was associated with several kinds of human autoimmune diseases, suggesting that CTLA-4 gene is probably a general susceptibility gene to autoimmune disease. The present study was conducted in Chinese to determine whether there is any association of the CTLA-4 gene polymorphism with the development of systemic lupus erythematosus (SLE). CTLA-4 gene polymorphism in promoter and exon 1 was detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method in 81 patients with SLE and 81 normal controls. The results showed that there were no statistically significant differences in both exon 1 and promoter gene polymorphism between SLE patients and normal controls. The preliminary study does not suggest an association of the known polymorphism in exon 1 and promoter of CTLA-4 gene with Chinese SLE. However, SLE is a very heterogeneous syndrome and CTLA-4 gene polymorphism might correlate with some specific clinical features. To exploring this possibility, subgroup analysis in more patients needs to be performed.
Assuntos
Antígenos de Diferenciação/genética , Imunoconjugados , Lúpus Eritematoso Sistêmico/genética , Polimorfismo Genético , Regiões Promotoras Genéticas/genética , Abatacepte , Antígenos CD , Povo Asiático/genética , Antígeno CTLA-4 , Éxons/genética , Frequência do Gene , Genótipo , Humanos , FenótipoRESUMO
Churg-Strauss syndrome (CSS), or allergic granulomatous angiitis, is an uncommon vasculitic syndrome that is found mainly in middle-aged adults. We describe a 15-year-old girl with CSS, diagnosed by histological findings and characteristic clinical features. The patient experienced two episodes of catastrophic gastrointestinal vasculitis, resulting in resection of 150 cm of small intestine and right hemicolectomy. Colonoscopic examination showed multiple colonic ulcers with active bleeding. The clinical course of the patient was grave and refractory to the therapy of steroid and cytotoxic drugs. In the world literature only two patients with multiple colonic ulcers caused by CSS have been reported, and very rare cases of childhood-onset CSS have been published. We reviewed CSS in children and found that the prognosis was poorer than that in adults.
Assuntos
Síndrome de Churg-Strauss/complicações , Doenças do Colo/etiologia , Mucosa Intestinal/patologia , Úlcera/etiologia , Adolescente , Biópsia por Agulha , Síndrome de Churg-Strauss/diagnóstico , Doenças do Colo/tratamento farmacológico , Doenças do Colo/patologia , Feminino , Humanos , Metilprednisolona/administração & dosagem , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Úlcera/patologiaRESUMO
Augmented and prolonged expression of CD40 ligand (CD40L) was recently reported in lymphoid cells from human lupus patients, suggesting that CD40/CD40L pathway was involved in the pathogenesis of systemic autoimmune diseases. This study was thus designed to study the expression of CD40 and CD40L among cell populations within inflammatory joints of patients with rheumatoid arthritis (RA). The result showed that most B cells and monocytes in synovial fluids (SF) expressed CD40. Cultured synovial fibroblasts also stained positive for CD40. Regarding CD40L, we found that T cells as well as B cells could express CD40L. Compared with normal controls, RA patients had higher levels of CD40L+ T cells (8.71 +/- 17.69% vs 1.74 +/- 2.30%, P > 0.05) and CD40L+ B cells (7.71 +/- 7.64% vs 1.12 +/- 1.59% P < 0.05). After in vitro stimulation, T cells from RA patients had higher and longer CD40L expression than T cells from normal peripheral blood. For investigating the effect of CD40 expressed on synovial fibroblasts on TNF-alpha production in joint compartment, we used anti-CD40 antibody to bind CD40 on fibroblasts for one hour and then co-cultured with synovial fluid mononuclear cells. We found that the levels of TNF-alpha decreased in the presence of anti-CD40 antibody. We concluded that there was an intrinsic hyperexpression of CD40L on lymphoid cells within rheumatoid joints, and synovial fibroblasts could contribute to articular inflammation through surface CD40 molecule.
Assuntos
Artrite Reumatoide/imunologia , Antígenos CD40/imunologia , Ligante de CD40/imunologia , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Artrite Reumatoide/metabolismo , Linfócitos B/imunologia , Fibroblastos/imunologia , Fibroblastos/metabolismo , Humanos , Monócitos/imunologia , Líquido Sinovial/imunologia , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Since the CTLA-4 molecule expressed on activated T lymphocytes has recently been suggested to be an important negative regulator in autoimmune diseases, this study was undertaken to investigate the expression and function of CTLA-4 on synovial T cells from patients with rheumatoid arthritis. CTLA-4-expressing T cells were detected using a dual fluorescence flow cytometric method. Only a small percentage of peripheral blood T cells from patients with rheumatoid arthritis had detectable surface CTLA-4 expression (mean +/- SD, 1. 89 +/- 1.92%). However, the levels of CTLA-4-positive T cells was increased significantly in rheumatoid synovial fluids (5.44 +/- 4. 96%) and synovial membranes (28.76 +/- 14.30%). To explore the role of CTLA-4 molecule in the inflammation of rheumatoid joints, CTLA-4 was blocked with anti-CTLA-4 antibody to assess its effects on the production of tumour necrosis factor alpha and interleukin 1beta in synovial fluid mononuclear cell culture. The addition of anti-CTLA-4 antibody enhanced the production of tumour necrosis factor alpha and interleukin 1beta in a dose-dependent manner. The data suggest that the expression of CTLA-4 plays a down-regulatory role in rheumatoid articular inflammation. We thus concluded that CTLA-4 was up-regulated on synovial T cells from patients with RA, and the increased CTLA-4 expression might exert a down-regulation effect on tumour necrosis factor alpha and interleukin 1beta production.
Assuntos
Antígenos de Diferenciação/biossíntese , Artrite Reumatoide/imunologia , Regulação para Baixo , Imunoconjugados , Membrana Sinovial/imunologia , Linfócitos T/imunologia , Abatacepte , Adulto , Idoso , Antígenos CD , Antígeno CTLA-4 , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Interleucina-1/biossíntese , Masculino , Pessoa de Meia-Idade , Líquido Sinovial/citologia , Líquido Sinovial/imunologia , Membrana Sinovial/citologia , Linfócitos T/citologia , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/biossínteseRESUMO
CTLA-4 is a cell surface molecule expressed on activated T cells that is suggested to deliver a negative signal for T cell activation. Since CTLA-4 might be a negative regulator of autoimmune diseases, we investigated its expression on T cells from 20 patients with systemic lupus erythematosus (SLE) by flow cytometric analysis and RT-PCR. We found that although CTLA-4 mRNA was readily detected in all patients and controls, only a very minor subset of T cells expressed detectable surface CTLA-4 molecules in both groups. But patients with SLE had significantly increased percentages of CTLA-4-positive T cells compared with normal controls, implying at least that there was no apparent defective expression of CTLA-4 molecule in human lupus. The kinetics of CTLA-4 expression on T cells stimulated in vitro with PMA plus ionomycin were similar in normal controls and patients with SLE. The expression of CTLA-4 molecules after stimulation increased gradually and peaked at 72 hr. However, the induction of CTLA-4 expression on patients' T cells appeared to be weaker than that of normal individuals. Whether this reflects impaired downregulation by CTLA-4 molecules in SLE patients needs to be clarified further.
Assuntos
Antígenos de Diferenciação/biossíntese , Imunoconjugados , Lúpus Eritematoso Sistêmico/sangue , Linfócitos T/metabolismo , Abatacepte , Antígenos CD , Antígenos de Diferenciação/genética , Antígenos de Superfície/biossíntese , Antígeno CTLA-4 , Feminino , Humanos , Ionomicina/farmacologia , Cinética , Leucócitos Mononucleares/metabolismo , Masculino , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/efeitos dos fármacos , Acetato de Tetradecanoilforbol/farmacologia , Regulação para CimaRESUMO
Murine hepatitis virus strain 3 (MHV-3) produces a host-strain-dependent spectrum of disease. The development of liver necrosis has been shown to be related to production of a unique macrophage procoagulant activity (PCA), encoded by the gene fgl-2, in susceptible mice. These studies were designed to examine the influence of Th1/Th2 cells on resistance/susceptibility and production of macrophage procoagulant activity (PCA) in resistant (A/J) and susceptible (Balb/cJ) strains of mice following infection with MHV-3. Immunization of A/J mice with MHV-3 induced a Th1 cellular immune response and one Th1 cell line (3F9.1) protected susceptible mice and inhibited production of PCA by macrophages both in vitro and in vivo. In contrast, immunization of Balb/cJ mice with an attenuated variant of MHV-3 derived from passaging MHV-3 in YAC-1 cells resulted in a Th2 response. Transfer of spleen cells and T cell lines from immunized Balb/cJ mice failed to protect naive susceptible syngeneic mice from infection with MHV-3 and augmented production of IL-1 beta, TNF-alpha and PCA by macrophages to MHV-3 in vitro. Serum from immunized Balb/cJ mice contained high titered neutralizing antibody which protected naive Balb/cJ animals from lethal primary MHV-3 infection. These results demonstrate that susceptible Balb/cJ mice generate a Th2 response following MHV-3 infection and that these Th2 cells neither inhibit MHV-3-induced macrophage PCA production nor protect naive mice from MHV-3 infection. The results suggest that antibody protects against primary infection, but could not eradicate ongoing infection. Ribavirin, a synthetic guanosine analogue prolonged survival to MHV-3 infection, inhibited production and transcription of the macrophage pro-inflammatory cytokines IL-1 beta and TNF-alpha and Th2 cytokines while preserving Th1 cytokine production. Thus, this data defines the differential role of Th1/Th2 lymphocytes in primary and secondary MHV-3 infection and further defines the importance of macrophage inflammatory mediators in the pathogenesis of MHV-3 infection.
Assuntos
Anticorpos Antivirais/imunologia , Infecções por Coronavirus/imunologia , Vírus da Hepatite Murina/imunologia , Células Th1/imunologia , Células Th2/imunologia , Animais , Antivirais/farmacologia , Células Cultivadas , Feminino , Imunidade Inata/imunologia , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Vírus da Hepatite Murina/efeitos dos fármacos , Ribavirina/farmacologiaRESUMO
We describe an unusual case of selective IgA deficiency complicated by recurrent vasculitis of the central nervous system (CNS). The patient suffered from two episodes of CNS vasculitis, one of which was located in the cerebrum and the other in the cerebellum. The vasculitic process resulted in brain tumor-like lesions shown by computed tomography. There was no evidence of associated connective tissue diseases. Vasculitis in other organs or tissues was not noted. This is the first detailed description in the English literature of pathologically proven CNS vasculitis in a patient with selective IgA deficiency. Our report demonstrates that isolated CNS angiitis can be a rare clinical feature of selective IgA deficiency.