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1.
Int Immunopharmacol ; 126: 111204, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38016343

RESUMO

Glycolysis is a key pathway in cellular glucose metabolism for energy supply and regulates immune cell activation. Whether glycolysis is involved in the activation of NOD-like receptor family protein 3 (NLRP3) inflammasomes during Treponema pallidum (T. pallidum) infection is unclear. In this study, the effect of T. pallidum membrane protein Tp47 on NLRP3 inflammasome activation in rabbit peritoneal macrophages was analysed and the role of glycolysis in NLRP3 inflammasome activation was explored. The results showed that Tp47 promoted NLRP3, caspase-1, and IL-1ß mRNA expression in macrophages, enhanced glycolysis and glycolytic capacity of macrophage, and promoted the production of macrophage glycolytic metabolites citrate, phosphoenolpyruvate, and lactate. The M2 pyruvate kinase (PKM2) inhibitor shikonin down-regulated the Tp47-promoted NLRP3, caspase-1, and IL-1ß mRNA expression in macrophages, and suppressed the Tp47-enhanced glycolysis and glycolytic capacity. Similarly, si-PKM2 significantly inhibited Tp47-promoted NLRP3, caspase-1, and IL-1ß mRNA expression and the Tp47-enhanced glycolysis and glycolytic capacity in macrophages. In conclusion, Tp47 activated NLRP3 inflammasomes via PKM2-dependent glycolysis and provided a new perspective on the effect of T. pallidum infection on host macrophages, which would contribute to the understanding of the infection mechanism and host immune mechanism of T. pallidum.


Assuntos
Inflamassomos , Treponema pallidum , Animais , Coelhos , Inflamassomos/metabolismo , Treponema pallidum/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR/metabolismo , Macrófagos , Proteínas Recombinantes/farmacologia , Caspase 1/metabolismo , RNA Mensageiro/metabolismo , Glicólise , Interleucina-1beta/metabolismo
2.
Comb Chem High Throughput Screen ; 26(15): 2738-2748, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37066775

RESUMO

BACKGROUND: Acute Liver Failure (ALF) is a difficult problem to solve in clinical practice. The presence of non-SMC condensin I complex subunit G (NCAPG) has previously been linked to vascular invasion of digestive system tumors, foreshadowing poor prognosis. Its role in ALF biology, however, remains unknown. This article explores the role of NCAPG as a potential biomarker candidate for the accurate diagnosis and targeted treatment of ALF. METHODS: The study included transcription data (GSE14668, GSE38941, GSE62029, GSE96851, and GSE120652) of ALF, normal tissues, and clinical samples, where NCAPG was selected as the differential gene by the "DESeq2" R package to analyze the immune cell functions and signal pathways. Furthermore, RT-qPCR and Western blot analyses were used to confirm the RNA and protein levels of NCAPG in ALF cell models, respectively. RESULTS: Bioinformatics analysis revealed that NACPG was up-regulated in ALF tissues, and the functional signaling pathway was primarily associated with immune infiltration. Based on the results of clinical samples, we suggest that NCAPG was overexpressed in ALF tissues. We also found that the expression of NCAPG increased with the degree of liver injury in vitro. Enrichment analysis suggested that NCAPG influenced ALF as a PI3K/AKT pathway activator. CONCLUSION: Our study suggests that NCAPG is a preliminary tool for the diagnosis of ALF. It can affect ALF via the PI3K/AKT pathway and is a potential therapeutic target to improve prognosis.


Assuntos
Biomarcadores , Proteínas de Ciclo Celular , Falência Hepática Aguda , Humanos , Proteínas de Ciclo Celular/genética , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/genética , Falência Hepática Aguda/terapia , Neoplasias Hepáticas/patologia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt
3.
J Infect Public Health ; 15(12): 1494-1496, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36413872

RESUMO

To evaluate the application of cycle threshold (Ct) values of coronavirus disease 2019 (COVID-19) patients in predicting epidemic dynamics and monitoring surface contamination. The Ct value of reverse transcriptase-polymerase chain reaction for SARS­CoV-2 from COVID-19 patients inbound overseas in Xiamen, China was collected from October 2020 to December 2021, and the correlation of patients' Ct values with epidemic dynamics and surface contamination was evaluated. The results showed that there was an extreme inverse correlation of positivity rate in the current calendar month (ORF1ab, r = -0.692, P = 0.004; N,r = -0.629, P = 0.012) and the following calendar month (ORF1ab,r = -0.801, P = 0.001; N,r = -0.620, P = 0.018) with the median Ct values. Ct value showed better performance for monitoring surface contamination, with the area under the curve value 0.808(95 %CI: 0.748-0.869) for ORF1ab and 0.807(95 %CI:0.746-0.868) for the N gene. The patients' ORF1ab Ct value< 29.09 or N Ct value< 28.03 were 11.25 times and 10.48 times more likely to result in surface contamination than those with ORF1ab Ct value ≥ 29.09 or N Ct value≥ 28.03 (OR:11.25,95 % CI: 5.52-22.35; OR:10.48,95 % CI:5.29-20.70). Ct values were associated with the positivity rate in the current or following calendar month and predicted the epidemic dynamics. The Ct values can be used as a predictor for monitoring surface contamination to develop public health responses to COVID-19.


Assuntos
COVID-19 , Epidemias , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Saúde Pública
4.
J Clin Lab Anal ; 36(1): e24185, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34919739

RESUMO

BACKGROUND: Tuberculosis poses a severe threat to human health. At present, compared with the traditional diagnostic methods for tuberculosis pleural effusion, such as Löwenstein-Jensen culture, pleural biopsy, and Ziehl-Neelsen smear microscopy, Xpert MTB/RIF was regarded as an emerging technology for its efficiency. The Xpert MTB/RIF accuracy for tuberculous pleural effusion diagnosis was evaluated in this systematic study. MATERIALS AND METHODS: We searched the relevant literature published before January 2021 in PubMed, Cochrane, EMBASE, and Web of Science databases. Utilizing Review Manager 5.3 software, the quality of the included literature was evaluated based on the Quality Assessment of Diagnostic Accuracy Studies criteria. Sensitivity, specificity, and the summary receiver operating characteristic curves were plotted and analyzed with Metadisc 1.40 software. We used Stata 12.0 software to evaluate the publication bias of this study. RESULTS: Eighteen articles were identified in total. The sensitivity of Xpert MTB/RIF in the pleural effusion was 0.24, and specificity was 1.00, respectively. The area under the summary receiver operating characteristic curve was 0.9737, which indicated that the overall accuracy of the Xpert MTB/RIF was high. In addition, based on the Deeks funnel plot, no publication bias of the study was found. CONCLUSION: Xpert MTB/RIF is a rapid method with high specificity but relatively low sensitivity for detecting Mycobacterium tuberculosis in pleural effusion. Its less sensitivity made it difficult to be used clinically, but the high specificity suggests that it can be used as a specific diagnostic method for tuberculous pleural effusion.


Assuntos
Mycobacterium tuberculosis/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico , Derrame Pleural/microbiologia , Tuberculose/diagnóstico , Humanos , Curva ROC , Padrões de Referência , Sensibilidade e Especificidade
5.
Cancer Cell Int ; 21(1): 22, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407468

RESUMO

BACKGROUND: The role of methylcrotonoyl-CoA carboxylase 2 (MCCC2) in the development of tumors is well-established, and the involvement of leucine in the liver is well-known. However, the role of MCCC2 and the correlation between MCCC2 and leucine in the progression of hepatocellular carcinoma (HCC) have not yet been reported. METHODS: In this study, the Gepia database was used to evaluate the prognostic value of MCCC2 in HCC. The expression and localization of MCCC2 in HCC cells were determined by western blot and immunofluorescence assays. Flow cytometry and CCK-8 and transwell assays were carried out to explore the effect of MCCC2 on cell proliferation, migration, and invasion. In addition, mass spectrometry analysis was used to predict the potential cell function of MCCC2 in HCC. RESULTS: We found that the expression of MCCC2 increased in HCC tissues and that high expression of MCCC2 could predict poor outcomes in HCC patients. Knockdown expression of MCCC2 in HCC cells could reduce cell proliferation, migration, and invasion ability in vitro and could inhibit HCC cell proliferation in vivo. Interestingly, we found that HCC cells transfected with MCCC2-sgRNA failed to respond to leucine deprivation. Meanwhile, leucine deprivation inhibited cell proliferation, migration, and invasion in HCC cells where MCCC2 was present rather than in cells where MCCC2 was absent. In addition, knockdown of MCCC2 significantly reduced the glycolysis markers, glucose consumption, lactate secretion, and acetyl-CoA level, which is a product of leucine metabolism. Furthermore, we found that MCCC2 promotes the activation of ERK. Profiling the MCCC2 binding proteins revealed that MCCC2-associated proteins are enriched in biological processes, such as protein metabolism, energy pathway, and metabolism in HCC cells. CONCLUSIONS: Our findings revealed that MCCC2 plays a critical role in the development of HCC, and the leucine metabolism pathway might be a novel target in HCC treatment.

6.
Chinese Journal of School Health ; (12): 1184-1188, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-886614

RESUMO

Objective@#To understand the impact of violent video games exposure, self control level and coping style on aggressive behavior of junior high school students in Shanghai, and provide a basis for future interventions to effectively reduce adolescents aggressive behavior.@*Methods@#Cluster sampling was used to select 1 886 students of 4 public middle schools in Shanghai from May to June 2019. The data was collected included Violent Video Game Use Habits Questionnaire, Buss & Perry aggression questionnaire, Adolescent Self Control Dual System Scale and Simple Coping Style Questionnaire.@*Results@#According to the potential profile analysis, the level of aggressive behavior of junior school students in Shanghai could be divided into four groups, which was low aggressive group,middle aggressive group one, middle aggressive group two and high aggressive group according to level of aggregate. After controlling for gender and age, multivariate Logistic regression showed that exposure to violent video games, impulse system and negative response were risk factors for aggressive behavior( P <0.05); using low aggressive group as control group,the OR of violent video games in other three groups were 1.26, 1.30 and 1.70 respectively. The OR of impulse system were 2.96 , 4.40 and 6.84 respectively. The OR of negative response were 1.17, 1.42 and 1.74 respectively. Positive response was a protective factor( P <0.05). Using low aggressive group as control group, the OR of positive in other three groups were 0.82, 0.52 and 0.49 respectively.@*Conclusion@#Violent video game exposure, impulsive system and negative coping style can increase the level of aggressive behavior of junior high school students, while positive coping style can reduce the level of aggression of junior middle school students.

7.
Anal Biochem ; 611: 113950, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-32919941

RESUMO

BACKGROUND: The aim of the study was to assess the analytical performance of the HISCL NT-proBNP assay, a newly developed chemiluminescence immunoassay, for the detection of NT-proBNP. METHODS: The within-run and total imprecision of the NT-proBNP assay were determined with HISCL cardiac marker controls. The linear ranges of the NT-proBNP assays were evaluated based on the CLSI EP6-A document using selected serum samples. Two hundred serum samples were evaluated to compare the HISCL NT-proBNP and Elecsys NT-proBNP assays. Five additional high NT-proBNP concentrations serum samples were evaluated to assess if there was high-dose hook effect in the HISCL NT-proBNP assay. RESULTS: The total and within-run imprecision values of the HISCL NT-proBNP assay were 5.85%, 0.81%, 2.56% and 0.54% and 6.07%, 0.73%, 2.61% and 0.59% at 6.1, 129.83, 3732.84and39737.33 pg/ml, respectively. The assay was verified to be linear for NT-proBNP levels ranging between 6.1 and 39737.33 pg/ml. The assay comparison showed that HISCL NT-proBNP = 0.9803 × Elecsys NT-proBNP -4.383. The sensitivity of HISCL NT-proBNP was 87.23%, and the specificity was 85.61%. The AUC of HISCL NT-proBNP (0.90 (95% CI, 0.86-0.93)) did not differ from that of Elecsys NT-proBNP(0.89 (95% CI, 0.85-0.93)) (P = 0.638). The results of five high NT-proBNP concentrations samples (44448, 54206, 55634, 55728 and 109406 pg/ml, measured with the Elecsys NT-proBNP assay) tested with HISCL NT-proBNP assay were all displayed with ">40000 pg/ml". CONCLUSIONS: The HISCL NT-proBNP chemiluminescence immunoassay showed good analytical and diagnostic performance for the detection of NT-proBNP and could be used in routine clinical practice.


Assuntos
Medições Luminescentes , Peptídeo Natriurético Encefálico/análise , Fragmentos de Peptídeos/análise , Humanos , Imunoensaio
8.
Exp Ther Med ; 20(4): 3816-3822, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32855731

RESUMO

Peripheral blood lymphocyte subsets have been reported to be useful as prognostic and/or diagnostic markers for patients with cancer. However, the clinical value of peripheral blood lymphocyte subsets in gastric cancer (GC) has remained elusive. In the present study, peripheral CD3+, CD4+ and CD8+ T lymphocytes, B cells (CD19+), regulatory T cells (Tregs; CD4+CD25+CD127-) and natural killer (NK) cells (CD3-CDl6+CD56+) were detected by flow cytometry in 122 patients with GC, 80 healthy donors (HDs) and 80 patients with gastric ulcer (GU). NK cells (CD56+) were detected by immunohistochemical (IHC) analysis in 20 GC and three GU tissue samples. A receiver-operating characteristic (ROC) curve was used to determine the threshold of the peripheral NK cell level and survival analysis was performed to assess its prognostic value in patients with GC. The results indicated that the peripheral NK cell proportion in patients with GC (18.77%) was significantly higher than that in the HD (12.19%) and GU (12.74%) groups. IHC analysis suggested that the NK level in GC tumor samples was correlated with that in paired serum samples. ROC curve analysis indicated that the peripheral NK cell level (15.16%) was able to effectively identify patients with GC, a diagnostic sensitivity of 75.41% and a specificity of 77.45% were determined. Multivariate logistic regression analysis revealed that the peripheral NK cell level was independently associated with the T stage and survival analysis demonstrated that high levels of peripheral NK cells were associated with poor prognosis of patients with GC. In conclusion, the peripheral NK cell level may be a diagnostic and prognostic marker for patients with GC.

9.
J Exp Clin Cancer Res ; 39(1): 123, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32605589

RESUMO

BACKGROUND: 3-Hydroxy butyrate dehydrogenase 2 (BDH2) is a short-chain dehydrogenase/reductase family member that plays a key role in the development and pathogenesis of human cancers. However, the role of BDH2 in gastric cancer (GC) remains largely unclear. Our study aimed to ascertain the regulatory mechanisms of BDH2 in GC, which could be used to develop new therapeutic strategies. METHODS: Western blotting, immunohistochemistry, and RT-PCR were used to investigate the expression of BDH2 in GC specimens and cell lines. Its correlation with the clinicopathological characteristics and prognosis of GC patients was analysed. Functional assays, such as CCK-8 and TUNEL assays, transmission electron microscopy, and an in vivo tumour growth assay, were performed to examine the proliferation, apoptosis, and autophagy of GC cells. Related molecular mechanisms were clarified by luciferase reporter, coimmunoprecipitation, and ubiquitination assays. RESULTS: BDH2 was markedly downregulated in GC tissues and cells, and the low expression of BDH2 was associated with poor survival of GC patients. Functionally, BDH2 overexpression significantly induced apoptosis and autophagy in vitro and in vivo. Mechanistically, BDH2 promoted Keap1 interaction with Nrf2 to increase the ubiquitination level of Nrf2. Ubiquitination/degradation of Nrf2 inhibited the activity of ARE to increase accumulation of reactive oxygen species (ROS), thereby inhibiting the phosphorylation levels of AktSer473 and mTORSer2448. CONCLUSIONS: Our study indicates that BDH2 is an important tumour suppressor in GC. BDH2 regulates intracellular ROS levels to mediate the PI3K/Akt/mTOR pathway through Keap1/Nrf2/ARE signalling, thereby inhibiting the growth of GC.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Hidroxibutirato Desidrogenase/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/patologia , Ubiquitina/metabolismo , Animais , Apoptose , Autofagia , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Feminino , Humanos , Hidroxibutirato Desidrogenase/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2/genética , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Taxa de Sobrevida , Células Tumorais Cultivadas , Ubiquitinação , Ensaios Antitumorais Modelo de Xenoenxerto
10.
J Cell Mol Med ; 24(14): 7959-7967, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32510753

RESUMO

Methyl-CpG-binding protein 2 (MeCP2) is an important epigenetic regulator for normal neuronal maturation and brain glial cell function. Additionally, MeCP2 is also involved in a variety of cancers, such as breast, prostate, lung, liver and colorectal. However, whether MeCP2 contributes to the progression of breast cancer remains unknown. In the present study, we investigated the role of MeCP2 in cell proliferation, migration and invasion in vitro. We found that knockdown of MeCP2 inhibited expression of epithelial-mesenchymal transition (EMT)-related markers in breast cancer cell lines. In conclusion, our study suggests that MeCP2 inhibits proliferation and invasion through suppression of the EMT pathway in breast cancer.


Assuntos
Neoplasias da Mama/genética , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Proteína 2 de Ligação a Metil-CpG/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Proteína 2 de Ligação a Metil-CpG/metabolismo
11.
J Cell Mol Med ; 24(13): 7637-7651, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32436333

RESUMO

The mechanism by which miR-605-3p regulates hepatocellular carcinoma (HCC) metastasis has not been clarified. In this study, we found that miR-605-3p was down-regulated in HCC and that low miR-605-3p expression was associated with tumour thrombus and tumour satellites. HCC patients with low miR-605-3p expression showed shorter overall survival and disease-free survival after surgery. Overexpression of miR-605-3p inhibited epithelial-mesenchymal transition and metastasis of HCC through NF-κB signalling by directly inhibiting expression of TRAF6, while silencing of miR-605-3p had the opposite effect. We also found that SNHG16 directly bound to miR-605-3p as a competing endogenous RNA. Mechanistically, high expression of SNHG16 promoted binding to miR-605-3p and inhibited its activity, which led to up-regulation of TRAF6 and sustained activation of the NF-κB pathway, which in turn promoted epithelial-mesenchymal transition and metastasis of HCC. TRAF6 increased SNHG16 promoter activity by activating NF-κB, thereby promoting the transcriptional expression of SNHG16 and forming a positive feedback loop that aggravated HCC malignancy. Our findings reveal a mechanism for the sustained activation of the SNHG16/miR-605-3p/TRAF6/NF-κB feedback loop in HCC and provide a potential target for a new HCC treatment strategy.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Retroalimentação Fisiológica , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , NF-kappa B/metabolismo , RNA Longo não Codificante/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Intervalo Livre de Doença , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Prognóstico , RNA Longo não Codificante/genética
12.
Sci Rep ; 9(1): 19691, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31873168

RESUMO

Self-heating effect is a major limitation in achieving the full performance potential of high power GaN power devices. In this work, we reported a micro-trench structure fabricated on the silicon substrate of an AlGaN/GaN high electron mobility transistor (HEMT) via deep reactive ion etching, which was subsequently filled with high thermal conductive material, copper using the electroplating process. From the current-voltage characteristics, the saturation drain current was improved by approximately 17% with the copper filled micro-trench structure due to efficient heat dissipation. The IDS difference between the pulse and DC bias measurement was about 21% at high bias VDS due to the self-heating effect. In contrast, the difference was reduced to approximately 8% for the devices with the implementation of the proposed structure. Using Micro-Raman thermometry, we showed that temperature near the drain edge of the channel can be lowered by approximately ~22 °C in a HEMT operating at ~10.6 Wmm-1 after the implementation of the trench structure. An effective method for the improvement of thermal management to enhance the performance of GaN-on-Silicon HEMTs was demonstrated.

13.
Eur Neurol ; 80(1-2): 82-86, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30343296

RESUMO

BACKGROUND: The differential diagnosis of general paresis (GP) and non-neurosyphilis (NS) dementia is not clearly defined. The present study examined the differences in clinical and laboratory features of GP and non-NS dementia. MATERIALS AND METHODS: We retrospectively examined clinical and laboratory features of 85 GP patients and 196 non-NS dementia patients. Data were collected from Zhongshan Hospital between June 2005 and June 2014. RESULTS: The GP group had a higher percentage of males (83.53%, 71/85) and younger median age ([52 [interquartile range 47.0-61.0] vs. 76 [68.3-82.0] years) than the non-NS dementia group. GP have higher Mini-Mental State Examination (MMSE; Z = -5.809; p = 0.000) than non-NS dementia. Distribution of CDR scores were significantly higher in the non-NS group than GP group (χ2 = 29.153; p = 0.000). The laboratory findings showed significantly different total cholesterol (CH), low-density lipoprotein CH and homocysteine levels between the 2 groups. Serologic testing for syphilis revealed that the GP group had higher seropositive rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) rates than the non-NS dementia group (96.47% [82/85] vs. 0.51% [1/196], Z = -2.663, p = 0.008; 100% [85/85] vs. 1.02% [2/196], Z = -2.663, p = 0.008). Interestingly, cerebrospinal fluid (CSF) biochemical indices, including pleocytosis rates, increased protein levels, and positive RPR and TPPA rates in the GP group were higher than that in the non-NS dementia group. CONCLUSIONS: Based on these preliminary data, patients with clinically evident symptoms of dementia, especially middle-aged males, should undergo blood tests for syphilis. All patients with positive serology results should undergo CSF examinations to diagnose GP dementia before further pharmaceutical and behavioral interventions.


Assuntos
Demência/diagnóstico , Neurossífilis/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Demência/sangue , Demência/líquido cefalorraquidiano , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Neurossífilis/sangue , Neurossífilis/líquido cefalorraquidiano , Estudos Retrospectivos , Testes Sorológicos , Treponema pallidum
14.
BMC Immunol ; 19(1): 28, 2018 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-30217146

RESUMO

BACKGROUND: The involvement of inflammasome activation and macrophage polarization during the process of syphilis infection remains unknown. In this study, A series of experiments were performed using human macrophages to research the role of NLRP3 inflammasome regulation in interleukin (IL)-1ß production and its influence on macrophage polarization triggered by T. pallidum. RESULTS: The results showed that in M0 macrophages treated with T. pallidum, the M1-associated markers inducible nitric oxide synthase (iNOS), IL-1ß and TNF-α were upregulated, and the M2-associated markers CD206 and IL-10 were downregulated. In addition, we observed NLRP3 inflammasome activation and IL-1ß secretion in T. pallidum-treated macrophages, and the observed production of IL-1ß occurred in a dose- and time-dependent manner. Moreover, the secretion of IL-1ß by macrophages after T. pallidum treatment was notably reduced by anti-NLRP3 siRNA and caspase-1 inhibitor treatment. NAC, KCl, and CA074-ME treatment also suppressed IL-1ß release from T. pallidum-treated macrophages. CONCLUSIONS: These findings showed that T. pallidum induces M0 macrophages to undergo M1 macrophage polarization and elevate IL-1ß secretion through NLRP3. Moreover, the process of NLRP3 inflammasome activation and IL-1ß production in macrophages in response to T. pallidum infection involves K+ efflux, mitochondrial ROS production and cathepsin release. This study provides a new insight into the innate immune response to T. pallidum infection.


Assuntos
Polaridade Celular/imunologia , Inflamassomos/imunologia , Interleucina-1beta/biossíntese , Ativação de Macrófagos , Macrófagos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sífilis/imunologia , Treponema pallidum/imunologia , Catepsinas/metabolismo , Linhagem Celular Tumoral , Humanos , Imunidade Inata , Espécies Reativas de Oxigênio/metabolismo , Células THP-1
15.
BMC Infect Dis ; 18(1): 101, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29490620

RESUMO

BACKGROUND: The inflammasome responses in Treponema pallidum infection have been poorly understood to date. This study aimed to investigate the expression of the nucleotide-binding leucine-rich receptor protein 3 (NLRP3) inflammasome in the development of tissue inflammation in rabbits infected with T. pallidum. METHODS: Forty-five rabbits were randomly assigned to a blank group or an infection group, and the latter was divided into no benzathine penicillin G (BPG) and BPG treatment subgroups. Rabbits in the infection group were injected intradermally with 0.1 mL of a 107/mL T. pallidum suspension at 10 marked sites along the back, and the blank group was treated with normal saline. The BPG treatment subgroup received 200,000 U of BPG administered intramuscularly twice, at 14 d and 21 d post-infection. The development of lesions was observed, and biopsies of the injection site and various organs, including the kidney, liver, spleen, lung, and testis, were obtained for NLRP3, caspase-1, and interleukin-1ß (IL-1ß) mRNA analysis during infection. Blood was also collected for the determination of IL-1ß concentration. RESULTS: Rabbits infected with T. pallidum (both the BPG treatment and no BPG treatment subgroups), exhibited NLRP3 inflammasome activation and IL-1ß secretion in cutaneous lesions, showing a trend in elevation to decline; NLRP3 mRNA expression reached a peak at 18 d in the BPG treatment subgroup and 21 d in the no BPG treatment subgroup and returned to "normal" levels [vs. the blank group (P > 0.05)] at 42 d post-infection. The trend was similar to the change in cutaneous lesions in the infected rabbits, which reached a peak at 16 d in the BPG treatment subgroup and 18 d in the no BPG treatment subgroup. NLRP3, caspase-1, and IL-1ß mRNA expression levels were slightly different in different organs. NLRP3 inflammasome activation was also observed in the kidney, liver, lung, spleen and testis. IL-1ß expression was observed in the kidney, liver, lung and spleen; however, there was no detectable level of IL-1ß in the testes of the infected rabbits. CONCLUSIONS: This study established a clear link between NLRP3 inflammasome activation and the development of tissue inflammation in rabbits infected with T. pallidum. BPG therapy imperceptibly adjusted syphilitic inflammation.


Assuntos
Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sífilis/patologia , Animais , Caspase 1/genética , Caspase 1/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/análise , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Rim/metabolismo , Fígado/metabolismo , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Penicilina G Benzatina/uso terapêutico , RNA Mensageiro/metabolismo , Coelhos , Sífilis/tratamento farmacológico , Sífilis/microbiologia , Sífilis/veterinária , Treponema pallidum/genética , Treponema pallidum/isolamento & purificação
16.
J Child Psychol Psychiatry ; 57(1): 74-83, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26072932

RESUMO

BACKGROUND: Tourette syndrome (TS) is a common tic disorder in children and adolescents. There is preliminary evidence that herbal medicine may possess the potential to treat tics. The purpose of this study was to formally evaluate the efficacy and safety of 5-Ling Granule (5-LGr), a proprietary polyherbal product, for the treatment of patients with TS in comparison with tiapride and placebo. METHODS: In this multisite, double-blind, double-dummy, randomized, placebo-controlled trial, 603 patients with TS aged 5-18 years were randomly assigned to treatment with placebo (n = 117), tiapride (n = 123, 200-400 mg/day) or 5-LGr (n = 363, 15-22.5 g/day) for 8 weeks. The primary outcome was measured using the Yale Global Tic Severity Scale (YGTSS) and its subscales, total tic Score (TTS) and tic-related impairment. Incidence of adverse events was compared among the three groups. RESULTS: While tics of all patients were reduced over time, 5-LGr and tiapride treatment produced significantly greater improvement on the YGTSS overall scale and subscale for TTS and impairment at endpoint than the placebo. Seventy-four percentage of patients in the 5-LGr arm and 68.3% in the tiapride arm had clinical response and these rates of response were significantly higher than those on placebo (44.0%, p < .001). The incidence of overall adverse events was significantly fewer for patients on placebo and 5-LGr compared to tiapride (11.2% and 13.8% vs. 26.0%, p = .002); in particular physical tiredness, dizziness and sleep disturbance. CONCLUSIONS: The clinical efficacy of 5-LGr is comparable to tiapride in reducing tics. Its safety profile is better than tiapride. 5-LGr can be considered a safe and effective therapy for TS (Trial registration: www.clinicaltrials.gov: NCT01501695).

17.
Zhongguo Zhong Yao Za Zhi ; 41(16): 3100-3106, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-28920356

RESUMO

To evaluate the efficacy and safety of Choudongning (CDN)capsule in children with Tourette's syndrome of spleen deficiency and phlegm accumulation through a randomized double-blind three-arm controlled phase Ⅲ study in 588 patients from 8 hospitals. The included patients were randomly divided into test group, positive control group and placebo group at the ratio of 3∶1∶1. Patients in the test group orally took CDN capsules and simulated Tiapridal tablets; the patients in positive control group took Tiapridal tablets and simulated CDN capsules; whereas the patients in placebo group orally took the simulated agents of the above two drugs. The treatment course was 6 weeks for three groups. The global grading rates, YGTSS scores and its factor scores, the degree of social function damage, as well as traditional Chinese medicine syndrome efficacy were evaluated as the outcome measures on efficacy. The AEs/ADRs, vital signs and laboratory testing were observed as outcome measures on safety. The total effective rate of YGTSS was 75.92% in the test group, 72.65% in the positive control group, and 37.29% in the placebo group. Non inferiority test stands between the test group and the positive control group, and they were superior to placebo group in efficacy with statistical difference. Significant difference had also been found among the 3 groups in YGTSS tics score, motor tics score, vocal tics, degree of social function damage and traditional Chinese medicine syndrome efficacy. During the study, there were 5 (1.42%)ADRs in the test group, 10 (8.55%)in the positive control group and 3 (2.54%)in the placebo group. The incidence of ADRs in the test group was lower than that in the positive control group, with statistical difference. It is clear to say that CDN capsule can effectively treat the Tourette's syndrome of spleen deficiency and phlegm accumulation. Its efficacy is not inferior to the commonly used Tiapridal tablets, with even less adverse reactions, so it has clinical application value.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Síndrome de Tourette/tratamento farmacológico , Cápsulas , Criança , Método Duplo-Cego , Humanos , Medicina Tradicional Chinesa , Baço/fisiopatologia , Resultado do Tratamento
19.
J Neurol Sci ; 350(1-2): 79-83, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25703276

RESUMO

BACKGROUND: No gold standard currently exists for the diagnosis of general paresis (GP), thus often resulting in unnecessarily delayed therapeutic decision. METHODS: A retrospective chart review was performed for 85 inpatients with GP in Zhongshan Hospital, Medical College of Xiamen University, and the characteristics of their clinical profiles, serum and cerebrospinal fluid (CSF) examinations, neuroimaging examination, and electroencephalogram (EEG) data were analyzed. RESULTS: Among the 85 GP patients, the clinical symptoms that were frequently observed upon admission included a variety of psychiatric-behavioral symptoms and varying degrees of cognitive impairment. All of the patients had positive serum Treponema pallidum particle agglutination (TPPA) assays, 96.47% of the patients had positive CSF TPPA assays, and 41.18% of the patients had both CSF pleocytosis and elevated CSF protein levels. Focal atrophy in one cerebral region or in multiple regions was evident in neuroimages. The EEG data primarily showed slightly abnormal EEG activity. CONCLUSION: These results demonstrate the complexity of the clinical characteristics of GP and highlight the importance of early diagnosis.


Assuntos
Neurossífilis/sangue , Neurossífilis/diagnóstico , Treponema pallidum/isolamento & purificação , Adulto , Idoso , Eletroencefalografia/tendências , Feminino , Humanos , Imageamento por Ressonância Magnética/tendências , Masculino , Pessoa de Meia-Idade , Neurossífilis/fisiopatologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/tendências
20.
J Clin Microbiol ; 53(4): 1371-4, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25631792

RESUMO

We developed a new Boson chemiluminescence immunoassay (CIA) and evaluated its application with cross-sectional analyses. Our results indicated that the Boson CIA demonstrated strong discriminatory power in diagnosing syphilis and that it can be used as a first-line screening test for syphilis serodiagnosis using the European Centre for Disease Prevention and Control algorithm or as a confirmatory test when combined with a patient's clinical history.


Assuntos
Algoritmos , Medições Luminescentes/métodos , Sífilis/diagnóstico , China/epidemiologia , Humanos , Sensibilidade e Especificidade , Sífilis/epidemiologia
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