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1.
Mol Ther ; 32(5): 1561-1577, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38454607

RESUMO

Inflammation resolution is an essential process for preventing the development of chronic inflammatory diseases. However, the mechanisms that regulate inflammation resolution in psoriasis are not well understood. Here, we report that ANKRD22 is an endogenous negative orchestrator of psoriasiform inflammation because ANKRD22-deficient mice are more susceptible to IMQ-induced psoriasiform inflammation. Mechanistically, ANKRD22 deficiency leads to excessive activation of the TNFRII-NIK-mediated noncanonical NF-κB signaling pathway, resulting in the hyperproduction of IL-23 in DCs. This is due to ANKRD22 being a negative feedback regulator for NIK because it physically binds to and assists in the degradation of accumulated NIK. Clinically, ANKRD22 is negatively associated with IL-23A expression and psoriasis severity. Of greater significance, subcutaneous administration of an AAV carrying ANKRD22-overexpression vector effectively hastens the resolution of psoriasiform skin inflammation. Our findings suggest ANKRD22, an endogenous supervisor of NIK, is responsible for inflammation resolution in psoriasis, and may be explored in the context of psoriasis therapy.


Assuntos
Modelos Animais de Doenças , Interleucina-23 , Psoríase , Transdução de Sinais , Psoríase/metabolismo , Psoríase/patologia , Psoríase/terapia , Psoríase/etiologia , Psoríase/imunologia , Psoríase/genética , Psoríase/induzido quimicamente , Animais , Camundongos , Interleucina-23/metabolismo , Interleucina-23/genética , Humanos , Inflamação/metabolismo , Inflamação/patologia , Camundongos Knockout , Pele/patologia , Pele/metabolismo , Quinase Induzida por NF-kappaB , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , NF-kappa B/metabolismo
2.
Eur Respir J ; 59(2)2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34289974

RESUMO

The current pandemic of coronavirus disease 2019 (COVID-19) has affected >160 million individuals to date, and has caused millions of deaths worldwide, at least in part due to the unclarified pathophysiology of this disease. Identifying the underlying molecular mechanisms of COVID-19 is critical to overcome this pandemic. Metabolites mirror the disease progression of an individual and can provide extensive insights into their pathophysiological significance at each stage of disease. We provide a comprehensive view of metabolic characterisation of sera from COVID-19 patients at all stages using untargeted and targeted metabolomic analysis. As compared with the healthy controls, we observed different alteration patterns of circulating metabolites from the mild, severe and recovery stages, in both the discovery cohort and the validation cohort, which suggests that metabolic reprogramming of glucose metabolism and the urea cycle are potential pathological mechanisms for COVID-19 progression. Our findings suggest that targeting glucose metabolism and the urea cycle may be a viable approach to fight COVID-19 at various stages along the disease course.


Assuntos
COVID-19 , Estudos de Coortes , Humanos , Metabolômica , Pandemias , SARS-CoV-2
3.
Environ Res ; 208: 112703, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35016862

RESUMO

Neonicotinoid insecticides (NEOs) are commonly applied for pest control in China and around the world. Previous studies reported that NEOs are hepatotoxic to mammals. However, limited studies have explored the associations between NEOs exposure and liver disease. In the present study, we detected six parent NEOs (p-NEOs), including acetamiprid, thiacloprid, dinotefuran, clothianidin, imidacloprid, and thiamethoxam, and five characteristic metabolites (m-NEOs), including 5-hydroxy-imidacloprid, olefin-imidacloprid, N-desmethyl-acetamiprid, 1-methyl-3-(tetrahydro-3-furylmethyl) guanidine and 1-methyl-3-(tetrahydro-3-furyl methyl) urea, in blood samples collected from healthy donors (n = 100; females vs. males: 45 vs. 55; age: 22-91 years) and liver cancer patients (n = 274; females vs. males: 118 vs. 156; age: 11-88 years) in one hospital from Guangzhou city, South China. NEOs were frequently detected (61%-94%) in blood samples, with median concentrations ranging from 0.19 ng/mL to 1.28 ng/mL and 0.20 ng/mL to 2.03 ng/mL for healthy and liver cancer populations, respectively. olefin-imidacloprid was the most abundant NEOs in healthy and liver cancer populations, accounting for 23.4% and 20.7%, respectively. Significant positive correlations among most m-NEOs concentrations were found, and associations between m-NEOs and their corresponding p-NEOs were positively correlated. These findings indicated that the sources of m-NEOs were both endogenous and exogeneous. Females had higher median concentrations of NEOs and their metabolites than males. Moreover, the α-fetoprotein values and blood concentrations of target analytes (r = 0.428-0.601, p < 0.05) were positively correlated. Meanwhile, associations between the concentrations of p-NEOs and m-NEOs and liver cancer were found (odds ratio = 2.33-9.02, 95% confidence interval = 0.31-22.7, p < 0.05), indicating that human exposure to NEOs and their metabolites might increase the odds of liver cancer prevalence. Our work provided a new insight into the hepatotoxicity of NEOs and their metabolites, and human health risks of exposure to these pollutants warranted further studies.


Assuntos
Inseticidas , Neoplasias Hepáticas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , China/epidemiologia , Coleta de Dados , Feminino , Humanos , Inseticidas/análise , Inseticidas/toxicidade , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/epidemiologia , Masculino , Mamíferos , Pessoa de Meia-Idade , Neonicotinoides/toxicidade , Nitrocompostos/toxicidade , Adulto Jovem
4.
J Clin Microbiol ; 59(8): e0007921, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-33952598

RESUMO

While China experienced a peak and decline in coronavirus disease 2019 (COVID-19) cases at the start of 2020, regional outbreaks continuously emerged in subsequent months. Resurgences of COVID-19 have also been observed in many other countries. In Guangzhou, China, a small outbreak, involving less than 100 residents, emerged in March and April 2020, and comprehensive and near-real-time genomic surveillance of SARS-CoV-2 was conducted. When the numbers of confirmed cases among overseas travelers increased, public health measures were enhanced by shifting from self-quarantine to central quarantine and SARS-CoV-2 testing for all overseas travelers. In an analysis of 109 imported cases, we found diverse viral variants distributed in the global viral phylogeny, which were frequently shared within households but not among passengers on the same flight. In contrast to the viral diversity of imported cases, local transmission was predominately attributed to two specific variants imported from Africa, including local cases that reported no direct or indirect contact with imported cases. The introduction events of the virus were identified or deduced before the enhanced measures were taken. These results show the interventions were effective in containing the spread of SARS-CoV-2, and they rule out the possibility of cryptic transmission of viral variants from the first wave in January and February 2020. Our study provides evidence and emphasizes the importance of controls for overseas travelers in the context of the pandemic and exemplifies how viral genomic data can facilitate COVID-19 surveillance and inform public health mitigation strategies.


Assuntos
COVID-19 , SARS-CoV-2 , África , Teste para COVID-19 , China/epidemiologia , Genômica , Humanos
5.
Mol Cell Biochem ; 476(12): 4245-4263, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34351574

RESUMO

Kawasaki disease (KD) causes cardiovascular system injury in children. However, the pathogenic mechanisms of KD have not been well defined. Recently, strong correlation between aberrant microRNAs and KD nosogenesis has been revealed. A role of microRNA-197-3p (miR-197-3p) in the pathogenesis of KD is identified in the present study. Cell proliferation assay showed human coronary artery endothelial cells (HCAECs) were suppressed by serum from KD patients, which was correlated with high levels of miR-197-3p in both KD serum and HCAECs cultured with KD serum. The inhibition of HCAECs by miR-197-3p was confirmed by cells expressing miR-197-3p mimic and miR-197-3p inhibitor. Comparative proteomics analysis and Ingenuity Pathway Analysis (IPA) revealed TIMP3 as a potential target of miR-197-3p, which was demonstrated by western blot and dual-luciferase reporter assays. Subsequently, by detecting the endothelium damage markers THBS1, VWF, and HSPG2, the role of miR-197-3p/TIMP3 in KD-induced damage to HCAECs was confirmed, which was further validated by a KD mouse model in vivo. The expressions of miR-197-3p and its target, TIMP3, are dramatically variational in KD serum and HCAECs cultured with KD serum. Increased miR-197-3p induces HCAECs abnormal by restraining TIMP3 expression directly. Hence, dysregulation of miR-197-3p/TIMP3 expression in HCAECs may be an important mechanism in cardiovascular endothelium injury in KD patients, which offers a feasible therapeutic target for KD treatment.


Assuntos
Doença da Artéria Coronariana/patologia , Células Endoteliais/patologia , MicroRNAs/genética , Síndrome de Linfonodos Mucocutâneos/patologia , Proteoma/metabolismo , Inibidor Tecidual de Metaloproteinase-3/antagonistas & inibidores , Animais , Apoptose/fisiologia , Células Cultivadas , Pré-Escolar , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/metabolismo , Células Endoteliais/imunologia , Células Endoteliais/metabolismo , Feminino , Humanos , Lactente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/sangue , Síndrome de Linfonodos Mucocutâneos/etiologia , Síndrome de Linfonodos Mucocutâneos/metabolismo , Proteoma/análise , Inibidor Tecidual de Metaloproteinase-3/genética , Inibidor Tecidual de Metaloproteinase-3/metabolismo
6.
IUBMB Life ; 71(7): 891-900, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30724444

RESUMO

Kawasaki disease (KD) is a systemic vasculitis syndrome that leads to coronary artery aneurysm (CAA). While echocardiography is the most important imaging modality for coronary artery assessment, a specific diagnostic biomarker complementary for CAA has not been reported. We aimed to analyze the profiles of exosomal miRNAs extracted from the serum of KD patients and controls to identify candidate biomarkers for CAA. Serum samples from 39 healthy children, 42 CAA patients, 38 coronary artery dilatation (CAD) patients and 45 virus-infected patients including 24 EBV patients and 21 ADV patients were randomly selected. Next generation sequencing was used to analyze serum exosomal miRNA to detect differentially expressed miRNAs. Biomarker candidates were validated by qRT-PCR. One hundred (and) ninety-six differentially expressed miRNAs (DEMs) were detected in CAA patients and healthy children. There were 70 DEMs and 140 DEMs in CAA patients versus CAD patients, and in CAA patients versus virus-infected patients, respectively. We selected the three most upregulated (let-7i-3p, miR-17-3p, and miR-210-5p) and the three most downregulated miRNAs (miR-6743-5p, miR-1246, and miR-6834-5p) in the DEMs, which were expressed differentially in CAA patients versus healthy children, and in CAA patients versus virus-infected patients, not in virus-infected patients versus healthy children, as biomarker candidates. Excluded DEMs of CAD and virus-infected patients, let-7i-3p was detected by sequence data analysis as a biomarker candidate for CAA patients, and then validated by qRT-PCR in a larger set of clinical samples. As a biomarker candidate, let-7i-3p provides an additional means of diagnosing CAA patients. Additionally, miRNA biomarkers complement ultrasonic imaging, allowing for greater diagnostic precision. © 2019 IUBMB Life, 2019.


Assuntos
Biomarcadores/sangue , Aneurisma Coronário/complicações , Vasos Coronários/patologia , Exossomos/genética , MicroRNAs/genética , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , MicroRNAs/sangue , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/etiologia
7.
BMC Cardiovasc Disord ; 19(1): 21, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30654760

RESUMO

BACKGROUND: Kawasaki disease (KD) is an acute febrile childhood systemic vasculitis that disturbs coronary arteries. The pathogenesis remains unknown. The study of phosphorylated proteins helps to elucidate the relevant pathophysiological mechanisms of cardiovascular disease. However, few researches explored phosphorylated proteins in KD patients. METHODS: We compared phosphoprotein profiles of HCAECs stimulated by the serum of KD patients and normal children using iTRAQ technology, TiO2 enrichment phosphorylated peptide and MS analysis. Then we conducted the functional analysis by ClueGO and the biological interaction networking analysis by ReactomeFIViz. Western blotting was performed to identify the hub proteins. RESULTS: Our results revealed that phosphorylation of 148 proteins showed different intensities between the two HCAECs groups, which are enriched in MAPK, VEGFR, EGFR, Angiopoietin receptor, mTOR, FAK signaling pathway and so on. Through the Network Analyzer analysis, the hub proteins are CDKN1A, MAPK1 and POLR2A, which were experimentally validated. CONCLUSION: In summary, we provided evidence addressing the valuable phosphorylation signaling that could be useful resource to understand the molecular mechanism and the potential targets for novel therapy of KD.


Assuntos
Vasos Coronários/metabolismo , Células Endoteliais/metabolismo , Síndrome de Linfonodos Mucocutâneos/sangue , Proteínas/metabolismo , Proteômica/métodos , Estudos de Casos e Controles , Células Cultivadas , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Feminino , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Fosforilação , Mapas de Interação de Proteínas , Transdução de Sinais , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
8.
IUBMB Life ; 70(7): 678-690, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29727505

RESUMO

MicroRNAs (miRNAs) play key roles in the regulation of gene expression during multiple physiological processes, including early development, differentiation, and ageing. However, their involvement in age-related thymic involution is not clear. In this study, we profiled the global transcriptome and miRNAome of thymic epithelial cells in 1- and 3-month-old male and female mice, and predicted the possible transcription factors and target genes of the four most significantly differentially expressed miRNAs (DEMs) (miR-183-5p, miR-199b-5p, miR-205-5p, and miR-200b-3p) by performing bioinformatics analyses. We also evaluated the relationships between the significantly DEMs and mRNAs. We performed quantitative polymerase chain reaction to confirm the changes in the expression of the miRNAs and their predicted target genes. We found that miR-183-5p, miR-199b-5p, miR-205-5p, and miR-200b-3p can be used as a biomarker group for mouse thymus development and involution. In addition, the predicted target genes (Ptpn4, Slc2a9, Pkib, Pecam1, and Prkdc), which were identified by mRNA sequencing analysis, were mainly involved in growth, development, and accelerated senescence. In conclusion, miRNAs and their predicted target genes likely play important roles in thymus development and involution. To the best of our knowledge, this is the first study to systematically analyze the relevance of miRNAs and their targets by mRNA sequencing in mouse thymic epithelial cells. © 2018 IUBMB Life, 70(7):678-690, 2018.


Assuntos
Envelhecimento/genética , Células Epiteliais/fisiologia , MicroRNAs/genética , RNA Mensageiro/genética , Timo/citologia , Animais , Feminino , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Camundongos Endogâmicos BALB C , Mapas de Interação de Proteínas/genética , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Timo/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
9.
Cardiol Young ; 27(9): 1786-1796, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28803590

RESUMO

BACKGROUND: Kawasaki disease, which is characterised by systemic vasculitides accompanied by acute fever, is regularly treated by intravenous immunoglobulin to avoid lesion formation in the coronary artery; however, the mechanism of intravenous immunoglobulin therapy is unclear. Hence, we aimed to analyse the global expression profile of serum exosomal proteins before and after administering intravenous immunoglobulin. METHODS: Two-dimensional electrophoresis coupled with mass spectrometry analysis was used to identify the differentially expressed proteome of serum exosomes in patients with Kawasaki disease before and after intravenous immunoglobulin therapy. RESULTS: Our analysis revealed 69 differential protein spots in the Kawasaki disease group with changes larger than 1.5-fold and 59 differential ones in patients after intravenous immunoglobulin therapy compared with the control group. Gene ontology analysis revealed that the acute-phase response disappeared, the functions of the complement system and innate immune response were enhanced, and the antibacterial humoral response pathway of corticosteroids and cardioprotection emerged after administration of intravenous immunoglobulin. Further, we showed that complement C3 and apolipoprotein A-IV levels increased before and decreased after intravenous immunoglobulin therapy and that the insulin-like growth factor-binding protein complex acid labile subunit displayed reverse alteration before and after intravenous immunoglobulin therapy. These observations might be potential indicators of intravenous immunoglobulin function. CONCLUSIONS: Our results show the differential proteomic profile of serum exosomes of patients with Kawasaki disease before and after intravenous immunoglobulin therapy, such as complement C3, apolipoprotein A-IV, and insulin-like growth factor-binding protein complex acid labile subunit. These results may be useful in the identification of markers for monitoring intravenous immunoglobulin therapy in patients with Kawasaki disease.


Assuntos
Proteínas Sanguíneas/efeitos dos fármacos , Exossomos/efeitos dos fármacos , Imunoglobulinas Intravenosas/farmacologia , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/terapia , Apolipoproteínas A/efeitos dos fármacos , Biomarcadores/sangue , Proteínas Sanguíneas/análise , Estudos de Casos e Controles , Pré-Escolar , China , Complemento C3/efeitos dos fármacos , Eletroforese em Gel Bidimensional , Feminino , Hospitais Pediátricos , Humanos , Lactente , Masculino , Espectrometria de Massas , Síndrome de Linfonodos Mucocutâneos/imunologia , Proteômica
10.
Biochem Biophys Res Commun ; 447(1): 19-25, 2014 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-24690176

RESUMO

Kawasaki disease (KD) is a systemic vasculitis that mainly affects children younger than 5 years. The causal pathogen is unknown, therefore specific diagnostic biomarkers and therapy are unavailable. High-dose intravenous immunoglobulin (IVIG) is considered as the most effective therapy to reduce the prevalence of coronary artery lesion (CAL) in KD; however, it has side effects. This study aimed to (1) determine whether IVIG therapy is effective at the molecular level; (2) provide the first serum proteomic profile of KD under IVIG therapy; and (3) screen for monitoring biomarker candidates. We extracted serum proteins from samples of healthy individuals and from KD patients before and after IVIG therapy, and employed two-dimensional electrophoresis and MALDI-TOF/TOF mass spectrometry to identify differentially expressed proteins. The identifications were validated by Western blotting. We identified 29 differentially expressed proteins in KD patients and found that IVIG therapy restored most of these proteins to near-normal levels. Tracing the protein levels of single patients before and after IVIG therapy showed that the proteins, especially Transthyretin (TTR), are potential markers for therapeutic monitoring. Functional analyses of these proteins by PANTHER and String suggested that the key influence of KD lay in the immune system, which was targeted by IVIG.


Assuntos
Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Pré-Albumina/metabolismo , Proteoma/metabolismo , Biomarcadores/sangue , Pré-Escolar , Eletroforese em Gel Bidimensional , Humanos , Imunoglobulinas Intravenosas/administração & dosagem
11.
Pediatr Res ; 76(4): 347-54, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25029259

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a multifactor chronic lung disease that mainly affects premature infants. In this study, we investigate the preventive effects of Astragalus polysaccharides (APS) on BPD, and explore its potential molecular mechanisms. METHODS: Lung tissues of newborn Sprague-Dawley rats from the control group, the room air plus low-dose APS group, the room air plus high-dose APS group, the BPD model group, the low-dose APS group (20 mg/kg d), and the high-dose APS group (40 mg/kg d) were examined at the 4th, 10th, and 14th d of life. The pathomorphological change was evaluated by hematoxylin-eosin staining. The content levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by the assay kit. Moreover, the protein and/or mRNA expression levels of NF-κBp65, CD31, ICAM-1, and TNF-α were also detected by corresponding methods. RESULTS: APS decreased the inflammatory cells infiltrating compared with the BPD group. For the APS group, the activity of SOD was increased and the content of MDA was reduced compared with the BPD group at any time point. The protein and mRNA expression levels of NF-κBp65, ICAM-1, and TNF-α were all decreased, while the protein expression level of CD31 was increased in the APS-treated group, with the most significant difference of the high-dose group (P < 0.01) compared with the BPD group after birth on the 4th, 10th, and 14th d. CONCLUSION: APS can reduce airway remodeling and alveolar damage by its modulation of inflammatory mediators and antioxidation, suggesting some protective effects on BPD of neonatal rats.


Assuntos
Astrágalo/química , Displasia Broncopulmonar/prevenção & controle , Polissacarídeos/farmacologia , Animais , Animais Recém-Nascidos , Western Blotting , Líquido da Lavagem Broncoalveolar , Molécula 1 de Adesão Intercelular/genética , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Pulmão/metabolismo , Malondialdeído/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Superóxido Dismutase/metabolismo , Fator de Transcrição RelA/genética , Fator de Necrose Tumoral alfa/genética
12.
BMC Infect Dis ; 14: 506, 2014 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-25231540

RESUMO

BACKGROUND: Changes of miRNAs in exosome have been reported in different disease diagnosis and provided as potential biomarkers. In this study, we compared microRNA profile in exosomes in 5 MHFMD and 5 ESHFMD as well as in 5 healthy children. METHODS: Different expression of miRNAs in exosomes across all the three groups were screened using miRNA microarray method. Further validated test was conducted through quantitative real-time PCR assays with 54 exosome samples (18 ESHFMD, 18 MHFMD, and 18 healthy control). The judgment accuracy was then estimated by the receiver operating characteristic (ROC) curve analysis; and the specificity and sensitivity were evaluated by the multiple logistic regression analysis. RESULTS: There were 11 different miRNAs in exosomes of MHFMD and ESHFMD compared to healthy children, of which 4 were up-regulated and 7 were down-regulated. Further validation indicated that the 4 significant differentially expressed candidate miRNAs (miR-671-5p, miR-16-5p, miR-150-3p, and miR-4281) in exosome showed the same changes as in the microarray analysis, and the expression level of three miRNAs (miR-671-5p, miR-16-5p, and miR-150-3p) were significantly different between MHFMD or ESHFMD and the healthy controls. The accuracy of the test results were high with the under curve (AUC) value range from 0.79 to 1.00. They also provided a specificity of 72%-100% and a sensitivity of 78%-100%, which possessed ability to discriminate ESHFMD from MHFMD with the AUC value of 0.76-0.82. CONCLUSIONS: This study indicated that the exosomal miRNA from patients with different condition of HFMD express unique miRNA profiles. Exosomal miRNA expression profiles may provide supplemental biomarkers for diagnosing and subtyping HFMD infections.


Assuntos
Exossomos/metabolismo , Doença de Mão, Pé e Boca/diagnóstico , MicroRNAs/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Diagnóstico Diferencial , Exossomos/genética , Ontologia Genética , Doença de Mão, Pé e Boca/sangue , Doença de Mão, Pé e Boca/genética , Humanos , MicroRNAs/sangue , Anotação de Sequência Molecular , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Índice de Gravidade de Doença , Transcriptoma , Regulação para Cima
13.
Front Neurosci ; 18: 1398412, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38841096

RESUMO

Background: Observational studies have suggested associations between functional gastrointestinal disorders (FGIDs) and variations in the cerebral cortex. However, the causality of these relationships remains unclear, confounded by anxiety and depression. To clarify these causal relationships and explore the mediating roles of anxiety and depression, we applied univariate, multivariable, and mediation Mendelian randomization (MR) analyses. Method: We utilized genome-wide association study (GWAS) summary data from the FinnGen database and the ENIGMA consortium, identifying genetic variants associated with irritable bowel syndrome (IBS), functional dyspepsia (FD), and cerebral cortex structures. Data on anxiety and depression came from FinnGen and a large meta-analysis. Utilizing a bidirectional univariate MR approach, we explored correlations between FD, IBS, and cortex variations. Then, independent effects were assessed through multivariable MR. A meta-analysis of these results, incorporating data from two cohorts, aimed to increase precision. We also explored the potential mediating roles of anxiety and depression. Results: Our findings indicate a negative causal correlation between FD and the thickness of the rostral anterior cingulate cortex (rACC) across both global and regional adjustments (ß = -0.142, 95% confidence interval (CI): -0.209 to-0.074, P.FDR = 0.004; ß = -0.112, 95%CI: -0.163 to-0.006, P.FDR = 0.003) and a positive causal correlation with the globally adjusted thickness of the superior frontal gyrus (SFG) (ß = 0.107, 95%CI: 0.062 to 0.153, P.FDR = 0.001). The causal correlation with the rACC persisted after multiple variable adjustments (ß = -0.137, 95% CI: -0.187 to-0.087, P.FDR = 1.81 × 10-5; ß = -0.109, 95%CI: -0.158 to-0.06, P.FDR = 0.002). A significant causal association was found between globally adjusted surface area of the caudal anterior cingulate cortex (cACC) and IBS (odds ratio = 1.267, 95%CI: 1.128 to 1.424, P.FDR = 0.02). The analysis showed that neither anxiety nor depression mediated the relationship between FGIDs and cerebral cortex structures. Conclusion: Our research provides significant MR evidence of a bidirectional causal relationship between FGIDs and the cerebral cortex structures. This evidence not only confirms the two-way communication along the brain-gut axis but also illuminates the underlying pathophysiology, paving the way for identifying potential therapeutic approaches.

14.
PLoS One ; 19(3): e0298438, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38452033

RESUMO

OBJECTIVE: To assess the effectiveness of acupuncture for treating depression and anxiety in patients diagnosed with functional dyspepsia (FD). METHODS: PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, Sinomed, and VIP Database were searched until April 30, 2023 for Randomized Controlled Trials (RCTs) comparing acupuncture to placebo or drugs for symptom alleviation. Two independent reviewers conducted the study search, data extraction, and bias risk assessment using the Cochrane Risk of Bias tool. Mean difference (MD), risk ratio (RR), and corresponding 95% confidence intervals (CI) were computed. Subgroup and sensitivity analyses were also performed. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was employed to evaluate the evidence level. RESULTS: A total of 16 RCTs involving 1315 participants were included. Acupuncture demonstrated marked superiority over placebo (MD = -7.07, 95%CI: -11.03 to -3.10, very low quality evidence) in mitigating Self-Rating Anxiety Scale (SAS) scores and was found to be more effective in reducing Self-Rating Depression Scale (SDS) scores than either placebo (MD = -4.63, 95%CI: -6.28 to -2.98, low quality evidence) or first-line drugs (MD = -2.71, 95%CI: -5.19 to -0.23, very low quality evidence). In terms of attenuating Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) scores, acupuncture consistently outperformed both placebo (HAMA: MD = -2.58, 95%CI: -4.33 to -0.83, very low quality evidence; HAMD: MD = -1.89, 95%CI: -3.11 to -0.67, low quality evidence) and first-line drugs (HAMA: MD = -5.76, 95%CI: -10.18 to -1.35, very low quality evidence; HAMD: MD = -5.59, 95%CI: -7.59 to -3.59, very low quality evidence). However, no significant difference was observed between acupuncture and placebo in terms of improvement in Hospital Anxiety and Depression Scale (HADS) scores. CONCLUSIONS: Based on current clinical evidence, acupuncture might have a positive effect on depression and anxiety in patients with FD. Further large-sample, multi-center, high-quality RCTs validation are required, as the conclusion is limited by the quantity and quality of the included studies.


Assuntos
Terapia por Acupuntura , Ansiedade , Depressão , Dispepsia , Humanos , Ansiedade/terapia , Depressão/terapia , Dispepsia/terapia
15.
BMC Infect Dis ; 13: 383, 2013 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-23961958

RESUMO

BACKGROUND: To clarify the molecular mechanisms that participate in the severe hand, foot and mouth disease (HFMD) infected by Enterovirus 71 and to detect any related protein biomarkers, we performed proteomic analysis of protein extracts from 5 extremely severe HFMD children and 5 healthy children. METHODS: The protein profiles of them were compared using two-dimensional electrophoresis. Differentially expressed proteins were identified using mass spectrometry. Functional classifications of these proteins were based on the PANTHER. The interaction network of the differentially expressed protein was generated with Pathway Studio. RESULTS: A total of 38 differentially expressed proteins were identified. Functional classifications of these proteins indicated a series of altered cellular processes as a consequence of the severe HFMD. These results provided not only new insights into the pathogenesis of severe HFMD, but also implications of potential therapeutic designs. CONCLUSIONS: Our results suggested the possible pathways that could be the potential targets for novel therapy: viral protection, complement system and peroxide elimination.


Assuntos
Enterovirus Humano A/isolamento & purificação , Doença de Mão, Pé e Boca/sangue , Proteoma/análise , Proteínas Sanguíneas/análise , Western Blotting , Eletroforese em Gel Bidimensional , Humanos , Mapas de Interação de Proteínas , Proteômica , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
16.
Neuropsychiatr Dis Treat ; 19: 27-48, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36627885

RESUMO

Background: Inflammation is an important pathogenesis of vascular dementia (VaD), and the regulatory effect of acupuncture on neuroinflammation has received extensive attention. There is conflicting evidence regarding the efficacy and safety of acupuncture for postpartum VaD. This overview aims to systematically evaluate systematic reviews/meta-analyses (SRs/MAs) of acupuncture on VaD. Methods: From the establishment of the electronic database to August 2022, search and identify SRs/MAs on acupuncture treatment for VaD. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system were used to evaluate the methodological, reporting, and evidence quality of the included SRs/MAs. Results: Twelve SRs/MAs were included in this research, and the quality of methodological, reporting, and evidence for these SRs/MAs were not satisfactory. The shortcomings of these SRs/MAs mainly include lack of protocol registration, incomplete literature search, missing list of excluded literature, and high risk of bias of included original clinical trials. Conclusion: VaD patients may benefit from acupuncture therapy. However, the high risk of bias in original clinical trials and the low quality of SRs/MAs make evidence-based decisions less reliable.

17.
Zhongguo Zhen Jiu ; 43(3): 345-51, 2023 Mar 12.
Artigo em Zh | MEDLINE | ID: mdl-36858401

RESUMO

The development status of the first 11 inheritance studios of acupuncture and moxibustion academic schools is summarized. Aiming at the current problems, it is suggested to establish qualitative and quantitative evaluation standards and establish a fair and reasonable evaluation system, build a systematic scientific theory and excavate the inherent laws of the schools, implement standardized management of the schools and protect the personalized characteristics of the schools, open outpatient clinic of acupuncture and moxibustion schools and promote the characteristic diagnosis and treatment technology, to promote the inheritance and development of acupuncture and moxibustion academic schools.


Assuntos
Terapia por Acupuntura , Moxibustão , Instituições Acadêmicas
18.
Zhongguo Zhen Jiu ; 43(2): 217-22, 2023 Feb 12.
Artigo em Zh | MEDLINE | ID: mdl-36808519

RESUMO

Qilu acupuncture and moxibustion has promoted the formation and development of traditional Chinese medicine, which has a special historical position. By systematically collecting, sorting out and summarizing the characteristic acupuncture methods and academic ideas of several Qilu acupuncturists since the founding of the People's Republic of China, the understanding of the advantages and characteristics of Qilu modern acupuncture methods is deepened, aiming to exploring the inheritance and development pattern of Qilu acupuncture methods in the new era.


Assuntos
Terapia por Acupuntura , Acupuntura , Moxibustão , Humanos , Medicina Tradicional Chinesa , China
19.
Medicine (Baltimore) ; 102(35): e34678, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37657054

RESUMO

BACKGROUND: To evaluate the efficacy and safety of acupuncture by systematically reviewing the literature on colorectal cancer resection. METHODS: Seven electronic databases were searched from inception to February 28, 2023. Randomized controlled trials on acupuncture in patients after CRC resection were included. Two reviewers independently selected relevant trials, extracted data, and assessed the risk of bias. A random-effects meta-analysis model was used to obtain summary effect estimates. The data were pooled and analyzed using RevMan 5.3. The heterogeneity of selected studies was evaluated by evaluating the I-squared (I2) statistics. RESULTS: Twenty-two studies with 1878 patients were included. Results of the meta-analysis showed there was a low level evidence that acupuncture may improve early postoperative symptoms, such as time to first flatus (n = 876, MD -0.77h, 95% CI -1.22 to -0.33 h, I2 = 89%), time to first bowel movement (n = 671, MD -1.41h, 95% CI -2.20 to -0.63 h, I2 = 95%), time to first defecation (n = 556, MD -1.03h, 95% CI -1.88 to -0.18 h, I2 = 95%), and nausea/vomiting (n = 1488, RR 0.72, 95% CI 0.59-0.89, I2 = 49%) compared with usual care and sham acupuncture. However, there were no statistically significant differences in postoperative pain (n = 1188, MD-0.21, 95% CI -0.59 to 0.17, I2 = 74%). And there was no sufficient evidence of improving long-term functional outcomes. There was substantial heterogeneity across trials. The adverse events associated with acupuncture stimulation were minor in include studies. CONCLUSION SUBSECTIONS: There is currently low-level evidence supporting the use of acupuncture on postoperative symptoms for patients after colorectal cancer resection. More investigations should be established based on the STRICTA statement strictly.


Assuntos
Terapia por Acupuntura , Neoplasias Colorretais , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Dor Pós-Operatória , Bases de Dados Factuais , Neoplasias Colorretais/cirurgia
20.
Syst Rev ; 12(1): 231, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-38093392

RESUMO

OBJECTIVE: To perform an evidence-based evaluation of the clinical efficacy of Taijiquan, Baduanjin, Yijinjing and Wuqinxi in interventions for type 2 diabetes. DESIGN: A systematic review and network meta-analysis. METHODS: The comprehensive search included Chinese and other language databases such as the MEDLINE (PubMed), Web of Science, Excerpta Medica Database (Embase), The Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Scientific Journal Database, VIP and China Biomedical Literature Database (CBM). Clinical randomized controlled trials of four traditional Chinese exercise therapies in the treatment of type 2 diabetes, including Taijiquan, Baduanjin, Yijinjing and Wuqinxi, were retrieved. The search time was conducted from the establishment of the database to 30 October 2022. Two researchers screened the documents that met the inclusion criteria, extracted data according to the preset table and evaluated the methodological quality of the included studies according to the quality evaluation tools recommended by the Cochrane System Reviewer Manual V.5.1. The R language, Stata and ADDIS statistical software programs were used to conduct statistics and analysis of intervention measures. RESULTS: A total of 33 randomized controlled trials with 2609 patients were identified. All patients were from China. The results of the network meta-analysis showed that Taijiquan ranked the best for improving HbA1c, 2-h postprandial blood glucose (2hPG), low-density lipoprotein cholesterol (LDL-C) and insulin sensitivity index indicator levels; Yijinjing reduced fasting plasma glucose (FPG) and total cholesterol (TC) indicator levels for the best probability ranking; Baduanjin improved the triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) probability ranking the most. When the training period was less than 12 weeks, Baduanjin had better effects in improving 2hPG, TC, TG, HDL-C and LDL-C indicator levels. Taijiquan had better effects in reducing FPG levels. When the training period was 12 weeks, the effect of Yijinjing in improving FPG, HbAlc, TC and HDL-C levels was better than that in other traditional Chinese exercise, and Taijiquan had better effects in improving 2hPG, TG and LDL-C indicator levels. When the training period was longer than 12 weeks, Taijiquan had better effects in improving FPG, HbAlc, 2hPG and LDL-C indicator levels, and Baduanjin had better effects in improving TC, TG and HDL-C indicator levels. CONCLUSION: The four traditional Chinese exercise therapies can improve blood glucose levels, blood lipid levels and insulin-related indicators of type 2 diabetes to varying degrees. Studies have shown that Taijiquan has a better targeted treatment effect on type 2 diabetes. SYSTEMATIC REVIEW REGISTRATION: CRD42020214786. PROTOCOL PUBLISHED: We published the protocol article "Network meta-analysis of four kinds of traditional Chinese exercise therapy in the treatment of type 2 diabetes: Protocol for a systematic review" in the BMJ Open magazine 2021, Issue 11, Volume 7.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Glicemia , LDL-Colesterol/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Terapia por Exercício/métodos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Triglicerídeos
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