RESUMO
The present study was carried out to evolve an effective treatment strategy for chronic obstructive pulmonary disease (COPD). Astaxanthin (AS) is abundantly present in red pigments of crustaceans, and has also been proven to have considerable biological activities. The anti-inflammatory effect of AS was evaluated in lipopolysaccharide (LPS)-exposed RAW264.7 macrophages. It was found that AS markedly inhibited elevation of NO and pro-inflammatory mediators. Moreover, it downregulated iNOS in LPS-stimulated RAW264.7 cells, suppressed the release of pro-inflammatory cytokines, and decreased ROS levels in mice exposed to cigarette smoke (CS) and LPS. These results imply that AS has therapeutic and prophylactic potential in the airway inflammatory response associated with COPD.
Assuntos
Heme Oxigenase-1/biossíntese , Pneumonia/tratamento farmacológico , Pneumonia/etiologia , Fumar/efeitos adversos , Animais , Líquido da Lavagem Broncoalveolar , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Indução Enzimática/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Pulmão/enzimologia , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Pneumonia/genética , Pneumonia/patologia , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Xantofilas/química , Xantofilas/farmacologia , Xantofilas/uso terapêuticoRESUMO
Regulatory T cells (Tregs) suppress excessive immune responses and are potential therapeutic targets in autoimmune disease and organ transplantation rejection. However, their role in renal ischemia-reperfusion injury (IRI) is unclear. Levels of Tregs and expression of CXCR3 in Tregs were analyzed to investigate their function in the early phase of renal IRI. Mice were randomly divided into Sham, IRI, and anti-CD25 (PC61) + IRI groups. The PC61 + IRI group was established by i.p. injection of PC61 monoclonal antibody (mAb) to deplete Tregs before renal ischemia. CD4(+)CD25(+)Foxp3(+) Tregs and CXCR3 on Tregs were analyzed by flow cytometry. Blood urea nitrogen (BUN), serum creatinine (Scr) levels, and tubular necrosis scores, all measures of kidney injury, were greater in the IRI group than in the Sham group. Numbers of Tregs were increased at 72 h after reperfusion in kidney. PC61 mAb preconditioning decreased the numbers of Tregs and aggravated kidney injury. There was no expression of CXCR3 on Tregs in normal kidney, while it expanded at 72 h after reperfusion and inversely correlated with BUN, Scr, and kidney histology score. This indicated that recruitment of Tregs into the kidney was related to the recovery of renal function after IRI and CXCR3 might be involved in the migration of Tregs.
Assuntos
Antígenos CD4/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Nefropatias/imunologia , Rim/imunologia , Receptores CXCR3/metabolismo , Traumatismo por Reperfusão/imunologia , Linfócitos T Reguladores/fisiologia , Animais , Citometria de Fluxo , Rim/patologia , Nefropatias/patologia , Masculino , Camundongos , Traumatismo por Reperfusão/patologia , Linfócitos T Reguladores/imunologiaRESUMO
Ischemia reperfusion injury (IRI) is critical in the pathogenesis of acute renal failure and graft rejection. Regulatory T cells (Tregs) suppress excessive immune responses in IRI. We investigated the role of CD4(+)CD25(high)CD127(low) Tregs in the early phase of renal IRI pathogenesis in a mouse model. CD4(+)CD25(high)CD127(low) Tregs in the kidney, tubular necrosis scores, and renal function were measured 24 or 72 h after reperfusion. PC61, an anti-CD25 monoclonal antibody, was used to deplete Tregs before renal ischemia to confirm the effect of these Tregs. CD4(+)CD25(high)CD127(low) Tregs were expanded 24 and 72 h after reperfusion. Depletion of CD4(+)CD25(high)CD127(low) Tregs was associated with worsening of renal function and histology, particularly at 72 h after reperfusion. These results indicated that expansion of CD4(+)CD25(high)CD127(low) Tregs in the early phase of renal IRI may participate in tissue repair. These data reveal new insights into the pathogenesis of ischemic acute renal failure and a novel therapeutic approach.
Assuntos
Rim/irrigação sanguínea , Regeneração/imunologia , Traumatismo por Reperfusão/imunologia , Linfócitos T Reguladores/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Antígenos CD4/imunologia , Células Dendríticas/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Subunidade alfa de Receptor de Interleucina-7/imunologia , Rim/imunologia , Leucócitos Mononucleares/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologiaRESUMO
OBJECTIVE: PARP inhibitors combined with antiangiogenic drugs have been reported to improve outcomes in BRCA wild-type ovarian cancer patients, the mechanism of the combination is unclear. In this study, we explored the mechanism of apatinib combined with olaparib in the treatment of ovarian cancer. METHODS: In this study, human ovarian cancer cell lines A2780 and OVCAR3 were used as experimental objects, and the expression of ferroptosis-related protein GPX4 after treatment with apatinib and olaparib was detected by Western blot. The SuperPred database was used to predict the target of the combined action of apatinib and olaparib, and the predicted results were verified by Western blot experiment to explore the mechanism of ferroptosis induced by apatinib and olaparib. RESULTS: Apatinib combined with olaparib-induced ferroptosis in p53 wild-type cells, and p53 mutant cells developed drug resistance. The p53 activator RITA sensitized drug-resistant cells to ferroptosis induced by apatinib combined with olaparib. Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis. CONCLUSION: This discovery revealed the specific mechanism of ferroptosis induced by apatinib combined with olaparib in p53 wild-type ovarian cancer cells and provided a theoretical basis for the clinical combined use of apatinib and olaparib in p53 wild-type ovarian cancer patients.
Assuntos
Ferroptose , Neoplasias Ovarianas , Feminino , Humanos , Apoptose , Linhagem Celular Tumoral , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
OBJECTIVE: Persistent T-cell activation is frequently observed in granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis). T-cell activation is usually balanced by negative costimulatory molecules. The negative costimulator programmed death receptor-1 (PD-1) and its relevance to T-cell immunity have not been studied so far in GPA. Thus it is the aim of the study to characterize the role of PD-1 in GPA. METHODS: Thirty-two patients suffering from GPA and 19 age-matched healthy controls (HCs) were enrolled. T-lymphocyte subsets from peripheral blood were analysed by flow cytometry for the expression of PD-1. The frequency of memory T cells and T cells producing pro-inflammatory cytokines was determined. Renal biopsies from GPA patients were stained for CD3 and PD-1. RESULTS: PD-1 expression was increased on T-helper cells (Th cells) from GPA patients as compared with HCs. In addition, parameters of persistent T-cell activation and production of pro-inflammatory cytokines were positively associated with numbers of PD-1(+) Th cells in patients but not in HCs. Latent infection with CMV seemed to enhance PD-1 expression on CD4(+) and CD4(+)CD25(-) T cells. Interestingly, expression of PD-1 on CD4(+)CD25(+)T cells was inversely correlated with relapse rate. Importantly, lesional T cells were mostly lacking PD-1. CONCLUSIONS: The expression of the negative costimulator PD-1 is altered in GPA and might counterbalance persistent T-cell activation.
Assuntos
Granulomatose com Poliangiite/imunologia , Imunidade Celular , Ativação Linfocitária/imunologia , Receptor de Morte Celular Programada 1/biossíntese , Linfócitos T/metabolismo , Biópsia , Proliferação de Células , Feminino , Citometria de Fluxo , Granulomatose com Poliangiite/metabolismo , Granulomatose com Poliangiite/patologia , Humanos , Imuno-Histoquímica , Líquido Intracelular/metabolismo , Rim/imunologia , Rim/metabolismo , Rim/patologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T/imunologiaRESUMO
BACKGROUND/AIMS: The purpose of this study is to present the surgical treatment of hepatic alveolar echinococcosis and evaluate the treatment outcomes. METHODOLOGY: A retrospective analysis was made on 50 patients admitted between 2000 and 2008. All the patients were divided into two groups, 26 patients for the radical surgery group and 24 for the palliative surgery group. RESULTS: In the palliative surgery group, 10 patients died during the follow-up period, 2 patients presented with brain metastasis and 4 patients with lung metastasis, 1 patient had multiple lesions in the liver, 1 patient who received left hepatectomy had a new lesion in caudate lobe of the liver, 4 patients had postoperative jaundice, 3 had cholangitis and 4 patients had biliary leaks. There were also 3 patients lost in the follow-up period. In the radical surgery group, 22 patients were alive and asymptomatic without recurrence during the follow-up period, 3 patients had recurrent cholangitis and 4 patients had biliary leaks. Three patients were lost during the followup period in this group. CONCLUSIONS: Radical resection appears to be best treatment of hepatic alveolar echinococcosis and palliative operation may cause a series of severe complications leading to death.
Assuntos
Equinococose Hepática/cirurgia , Hepatectomia , Adolescente , Adulto , Equinococose Hepática/diagnóstico , Equinococose Hepática/mortalidade , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
A theoretical examination of the structural, elastic, electronic and optical properties of the chalcogenide perovskite BaZrS3 under pressures of 0 and 20â GPa was performed using density functional theory ab initio calculations. The lattice constants of the BaZrS3 structure are well reproduced from our first-principles calculations and are in excellent agreement with experimental measurements. Moreover, the values of mechanical parameters, such as the elastic constant, increased under applied pressure. The electronic parameters indicate that the chalcogenide perovskite BaZrS3 has a direct band gap of 1.75â eV. To understand the optical response, the real and imaginary parts of the dielectric function of BaZrS3 have been studied, as well as the absorption coefficient, reflectivity and extinction coefficient. The induced pressure is found to enhance the optical parameters in the different energy regions. Our calculations predict that the studied chalcogenide perovskite BaZrS3 could be a candidate in photovoltaic, optoelectronic and mechanical applications.
RESUMO
A bimannich-based TZBM containing a thiazole ring was obtained by synthesis of mannich bases. TZBM featured a stable structure at 260 °C, and corrosion inhibition effect on carbon steel in a gas-liquid environment with Cl- + H2S + CO2 at 180 °C. By analyzing the weight loss of steel exposed to different TZBM concentrations, the coverages of the inhibitor adsorbed on the surfaces were determined, and the results conformed to Langmuir isotherm model. Furthermore, the negative Gibbs free energy indicated that the adsorption was a spontaneous process.
RESUMO
BACKGROUND: Mutations of EGFR and K-ras are biomarkers for predicting the efficacy of targeting agents in non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). Data on the gene mutation status of EGFR and K-ras in Chinese patients with CRC are limited. METHODS: EGFR mutations in exon 18-21 and K-ras mutations in exon 1 and 2 were detected in tumor samples from 101 Chinese patients with CRC by polymerase chain reaction and Sanger sequencing. [corrected] The relationship between patients' characteristics and survival time and gene mutation status were analyzed using the Statistical Package for the Social Sciences. RESULTS: Only two samples (2.0%) had EGFR mutations in exon 18 or 21, and 33 of 101 samples (32.7%) had K-ras mutations in codon 12, 13, 45, 69, or 80. Univariate analysis suggested that differentiation might be correlated with K-ras mutations (p = 0.05), which was confirmed by a logistic regression model (p = 0.04). The median overall survival (OS) and median survival after metastasis were 44.0 and 18.0 months, respectively, in the mutant K-ras group, and 53.3 and 19.0 months, respectively, in the wild K-ras group. K-ras mutation was not an independent prognostic factor for OS or survival after metastasis (p = 0.79 and 0.78, respectively). CONCLUSIONS: In Chinese patients with CRC, EGFR mutations were rare, and K-ras mutations were similar to those of Europeans. New mutations in codons 45, 69, and 80 were found in the Chinese population. Poor differentiation was an independent factor related to K-ras mutations.
Assuntos
Povo Asiático/genética , Neoplasias Colorretais/genética , Genes erbB-1/genética , Genes ras/genética , Mutação , Sequência de Bases , China , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de SobrevidaRESUMO
BACKGROUND: There was an outbreak of COVID-19 towards the end of 2019 in China, which spread all over the world rapidly. The Chinese healthcare system is facing a big challenge where hospital workers are experiencing enormous psychological pressure. This study aimed to (1) investigate the psychological status of hospital workers and (2) provide references for psychological crisis intervention in the future. METHOD: An online survey was conducted to collect sociodemographic features, epidemic-related factors, results of PHQ-9, GAD-7, PHQ-15, suicidal and self-harm ideation (SSI), and the score of stress and support scales. Chi-square test, t-test, non-parametric, and logistic regression analysis were used to detect the risk factors to psychological effect and SSI. RESULTS: 8817 hospital workers participated in this online survey. The prevalence of depression, anxiety, somatic symptoms, and SSI were 30.2%, 20.7%, 46.2%, and 6.5%, respectively. Logistic regression analysis showed that female, single, Tujia minority, educational background of junior or below, designated or county hospital, need for psychological assistance before or during the epidemic, unconfident about defeating COVID-19, ignorance about the epidemic, willingness of attending parties, and poor self-rated health condition were independent factors associated with high-level depression, somatic symptom, and SSI among hospital workers (P<0.05). LIMITATIONS: This cross-sectional study cannot reveal the causality, and voluntary participation could be prone to selection bias. A modified epidemic-related stress and support scale without standardization was used. The number of hospital workers in each hospital was unavailable. CONCLUSION: There were a high level of psychological impact and SSI among hospital workers, which needed to be addressed. County hospital workers were more severe and easier to be neglected. More studies on cognitive and behavioral subsequence after a public health disaster among hospital workers are needed.
Assuntos
Betacoronavirus , Infecções por Coronavirus , Pessoal de Saúde/psicologia , Pandemias , Pneumonia Viral , Ansiedade/psicologia , COVID-19 , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Estudos Transversais , Depressão/psicologia , Epidemias , Feminino , Humanos , Masculino , Questionário de Saúde do Paciente , Pneumonia Viral/epidemiologia , Prevalência , SARS-CoV-2 , Ideação SuicidaRESUMO
Recently, the global malaria control has achieved remarkable results, and the epidemic map of malaria has gradually shrinked. However, in the past two years, the number of malaria deaths remained at a high level, and the incidence of malaria has even risen, leading to the stagnant of malaria elimination. The main reasons include lacking of the well monitoring and response system, sensitivity declining of antimalarial drugs, the spread of insecticide resistance, and the reduction of financial support. This paper introduces the progress and challenges of global malaria elimination, summarizes the current strategies and major interventions, and provides the corresponding response.
Assuntos
Saúde Global , Malária , Antimaláricos , Saúde Global/tendências , Humanos , Incidência , Resistência a Inseticidas , Malária/epidemiologia , Malária/prevenção & controleRESUMO
Malaria is one of the most serious mosquito-borne infectious diseases in the world. The global malaria control progress has stalled in recent years, which is largely due to the biological threats from the malaria pathogen Plasmodium and the vector Anopheles mosquitoes. This article provides an overview of biological threats to global malaria elimination, including antimalarial drug resistance, deletions in the malaria rapid diagnostic test target P. falciparum histidine-rich protein 2/3 (Pfhrp2/3) genes, vector insecticide resistance and emergence of invasive vector species, so as to provide insights into malaria and vector research and the formulation and adjustment of the malaria control and elimination strategy.
RESUMO
OBJECTIVE: To understand the malaria epidemic situation and characteristics in Jiangsu Province in 2017, so as to provide the evidence for formulating the targeted strategy of malaria elimination. METHODS: The data of malaria cases in Jiangsu Province in 2016 were collected from China's Routine Diseases Surveillance Information System (CRDSIS). RESULTS: Totally, 239 imported malaria cases were reported in Jiangsu Province in 2017, and the cases decreased by 22.40% compared to 308 cases in 2015. Except 2 malaria case caused by blood transfusion, the rest patients were all imported. Among them, there were 163 falciparum malaria cases, 21 vivax malaria cases, 11 quartan malaria cases, 43 ovale malaria cases, and 1 mixed infection case (Plasmodium falciparum and P. ovale). The numbers of imported cases of Nantong (39 cases, 16.32%), Suzhou (26 cases, 10.88%), Taizhou (25 cases, 10.46%), Huai'an (24 cases, 10.04%), and Lianyungang (22 cases, 9.21%) ranked in the top 5 cities across Jiangsu Province, the malaria cases in the five cities accounted for 56.90% (136/239). The infection source areas of the imported malaria cases included Africa (225 cases), Asia (8 cases), Oceania (2 cases), and South America (2 cases). CONCLUSIONS: Jiangsu Province has no local malaria cases for 6 consecutive years. Despite the imported cases in 2017 decreased some-what compared to that in 2016, it is still necessary to strengthen the surveillance of imported malaria cases and improve malaria diagnosis and treatment in the whole province.
Assuntos
Doenças Transmissíveis Importadas , Malária , China/epidemiologia , Doenças Transmissíveis Importadas/epidemiologia , Doenças Transmissíveis Importadas/parasitologia , Erradicação de Doenças , Humanos , Malária/epidemiologia , Malária/parasitologia , Plasmodium , Vigilância da População , PrevalênciaRESUMO
OBJECTIVE: To establish a recombinase-aided isothermal amplification (RAA) assay for detection of Cryptosporidium. METHODS: Based on Cryptosporidium-specific 18S rRNA selected as the target gene to be detected, and the primer sequences and fluorescent probes designed using the software Amplfix, and a fluorescent RAA assay was established and optimized. The fluorescent RAA assay was performed to detect 18S RNA target sequence-contained recombinant plasmids at various copies, genomic DNA of Cryptosporidium oocysts at various concentrations, and genomic DNA extracted from various numbers of Cryptosporidium oocysts to assess the sensitivity of the assay, and to detect genomic DNA extracted from Cryptosporidium oocysts, Giardia lamblia cysts, Schistosoma japonicum eggs, Ascaris lumbricoides eggs, Clonorchis sinensis eggs, Salmonella and Shigella to determine the specificity of the assay. RESULTS: A fluorescent RAA assay was successfully established, which was effective to amplify the specific 18S RNA gene fragments of Cryptosporidium within 20 min at 39 â. The lowest limits of the fluorescent RAA assay were 102 copies/µL for detection of 18S RNA target sequence-contained recombinant plasmids at various copies, 1 pg/µL for detection of genomic DNA of Cryptosporidium oocysts at various concentrations, and one Cryptosporidium oocyst/µL for detection of genomic DNA extracted from various numbers of Cryptosporidium oocysts, and the fluorescent RAA assay was all negative for detection of genomic DNA from G. lamblia cysts, S. japonicum eggs, A. lumbricoides eggs, C. sinensis eggs, Salmonella and Shigella. CONCLUSIONS: A novel fluorescent RAA assay is successfully established, which is simple, rapid, sensitive and specific to detect genomic DNA of Cryptosporidium oocysts.
Assuntos
Cryptosporidium , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Amplificação de Ácido Nucleico/normas , Cryptosporidium/genética , DNA de Protozoário/genética , Limite de Detecção , Oocistos , RNA Ribossômico 18S/genética , Recombinases/metabolismo , Sensibilidade e EspecificidadeRESUMO
Objective:To screen the interacting protein of ubiquitin-conjugating enzyme E2S(UBE2S)and construct the hepatocellular carcinoma(HCC)based on UBE2S interacting protein prognosis model(UIPM),and to discuss the value of UIPM in assessing the prognosis of the HCC patients.Methods:Co-immunoprecipitation(Co-IP)was used to screen the protein complexes binding to Flag-UBE2S.After validation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting methods;liquid chromatography-mass spectrometer(LC-MS)was used to identify the UBE2S interacting proteins;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were conducted on these proteins;the prognosis-related proteins from The Cancer Genome Atlas(TCGA)were cross-referenced with UBE2S interacting proteins by survival package of R software;the key proteins were extracted through LASSO regression analysis to build the UIPM;the prognostic model risk scoring formula was established.The HCC patients in TCGA were divided into high risk group and low risk group based on median value of the risk scores.The predictive accuracy of UIPM was evaluated by receiver operating characteristic curve(ROC),and the predictive accuracy was further validated by International Cancer Genome Consortium(ICGC)Database;univariate regression analysis and multivariate Cox regression analysis were used to detect whether the UIPM risk score was an independent prognostic factor for HCC.Furthermore,the nomogram model was built.Results:A total of 97 UBE2S interacting proteins were identified through Co-IP combined with LC-MS analysis.The GO functional enrichment analysis and KEGG signaling pathway enrichment analysis results showed that the interacting proteins were closely associated with cysteine-type endopeptidase activity,oxidative stress,and cell death.The TCGA revealed 5 163 HCC prognosis-related proteins;after intersecting with UBE2S interacting proteins,40 prognosis-related interacting proteins were found.Seven key proteins were determined through LASSO regression analysis,including UBE2S,heat shock protein family A member 8(HSPA8),heterogeneous nuclear ribonucleoprotein H1(HNRNPH1),chaperonin containing TCP1 subunit 3(CCT3),eukaryotic translation initiation factor 2 subunit 1(EIF2S1),receptor for activated C kinase 1(RACK1),and actin related protein 2/3 complex subunit 4(ARPC4),and the UIPM was constructed.There was significant difference in survival rate of the patients between high risk group and low risk group(P<0.05).The ROC curve analysis results showed the area under ROC curve(AUC)values of UIPM for predicting 1-year,2-year,and 3-year survival risk scores of the HCC patients were all greater than 0.7,indicating the model had high predictive accuracy.This was also confirmed by ICGC Database data.The univariate and multivariate Cox regression analysis results showed that the UIPM risk score was an independent prognostic risk factor for the HCC patients(P<0.05).The nomogram results showed good consistency between predicted survival rate and actual survival rate of the patient.Conclusion:A total of 97 interacting proteins that interact with UBE2S may promote the occurence and devolopment of HCC through oxidative stress and dysregulation of ferroptosis pathways.The UIPM risk score is an independent risk factor for the prognosis of HCC and can be used to predict the outcomes of the patients.UBE2S,HSPA8,HNRNPH1,CCT3,EIF2S1,RACK1,and ARPC4 could be regarded as the new biomarkers and therapeutic targets for HCC.
RESUMO
Objective To identify the differentially expressed genes and pathways of bone marrow-derived mast cells(BMMCs)of mice induced by IL-3 and IL-3+stem cell factor(SCF)using bioinformatics analysis,which may provide a foundation for in vitro culture and functional study of mast cells(MC).Methods The matrix data of GSE35332 dataset in IL-3 and IL-3+SCF induced BMMCs was downloaded from the GEO database,and the R software was applied to screen differentially expressed genes(DEGs).The gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of EDGs were performed based on the online tool DAVID database.The protein interaction network was constructed by STRING database and hub genes were screened through MCODE plugin of the Cytoscape software.Results The GSE35332 data set was analyzed by R software,and 1 339 DEGs were screened,including 723 up-regulated genes and 616 down-regulated genes.A total of 6 hub genes were screened through the MCODE plugin of Cytoscape software,namely Psmd8,Psmd6,Psmd14,Psmc4,Psma6 and Psma3.GO and KEGG analysis showed that the hub genes were concentrated in proteolysis,antigen processing and presentation of exogenous peptide antigen via MHC class I,proteasome-mediated ubiquitin-dependent protein catabolism process,and Epstein-Barr virus infection.Conclusion This study found that there were significant differences in BMMCs gene expression profiles in mice induced by two modes and 6 hub genes participated in ubiquitin-dependent protein decomposition process through bioinformatics based on the GEO database,providing help for further research on MC vitro culture and function.
RESUMO
Objective To investigate the prevalence of Enterobius vermicularis infections among children in China from 2016 to 2021, so as to provide insights into enterobiasis control and formulation of the enterobiasis control strategy among children. Methods Publications pertaining to the prevalence of E. vermicularis infections among children were retrieved from Wanfang Data, CNKI, VIP and PubMed databases published from January 2016 to June 2023. Eligible publications were screened according to inclusion and exclusion criteria, and the publication bias was evaluated using the assessment tool for prevalence studies proposed by the Joanna Briggs Institute Evidence-Based Practice Resources in Australia. The study period, study areas, study subjects, sample size and number of infections were extracted from publications, and a pooled analysis was performed using a meta-analysis. A meta-regression analysis was performed with the prevalence of E. vermicularis infections as an independent variable, and sample size, source of samples, study area, study method, geographical area and province as dependent variables to identify the source of the study heterogeneity. Results A total of 66 studies were included, covering 23 provinces (municipalities, autonomous regions) in China, and with the investigations conducted between 2016 and 2021. Meta-analysis showed that the pooled prevalence of E. vermicularis infections was 4.5% [95% confidence interval (CI): (3.1%, 6.0%)] among children in China from 2016 to 2021, and the annual prevalence was 4.1% [95% CI: (2.2%, 6.5%)], 4.2% [95% CI: (2.4%, 6.6%)], 4.2% [95% CI: (2.2%, 6.8%)], 3.2% [95% CI: (1.5%, 5.4%)], 2.3% [95% CI: (0.9%, 4.3%)] and 1.1% [95% CI: (0.4%, 2.1%)] from 2016 to 2021. The pooled prevalence of E. vermicularis infections was 4.9% [95% CI: (3.4%, 6.8%)] in studies with a sample size of < 5 000 cases, which was higher than that in studies with a sample size of 5 000 cases and higher [2.1%, 95% CI: (0.2%, 3.6%)], and the pooled prevalence of E. vermicularis infections was 5.2% [95% CI: (2.9%, 8.2%)] among subjects from schools, which was higher than that among subjects from communities [4.2%, 95% CI: (2.7%, 6.0%)]. The pooled prevalence of E. vermicularis infections was 4.4% [95% CI: (2.8%, 6.2%)] among children included in comprehensive surveillance, which was higher than that among children included in specific surveillance [4.8%, 95% CI: (2.6%, 7.7%)], and the pooled prevalence of E. vermicularis infections was 5.7% [95% CI: (3.8%, 7.8%)] among children included in county-level surveys, which was higher than that among children included in city-[4.8%, 95% CI: (2.3%, 8.0%)] and province-level surveys [1.8%, 95% CI: (0.3%, 4.7%)]. In addition, the pooled prevalence of E. vermicularis infections was higher among children in southern China [11.3%, 95% CI: (7.5%, 15.7%)] than that in central China [5.2%, 95% CI: (2.8%, 8.2%)], eastern China [5.2%, 95% CI: (2.8%, 8.2%)] and southwestern China [2.6%, 95% CI: (1.4%, 4.1%)]. Meta-regression analysis identified geographical area and survey province as factors affecting the study heterogeneity. Conclusions Currently, the overall prevalence of E. vermicularis infections is moderate among children in China, and the prevalence varies greatly in regions, with a high prevalence rate in southern China and presence of small-scale clusters. Enterobiasis surveillance and health education pertaining to enterobiasis control are required with adaptations to local circumstance to reduce the prevalence of E. vermicularis infections among children.
RESUMO
BACKGROUND:Clinical skin wound healing continues to be a significant concern,and tissue repair research has moved to the forefront with the development of biomaterials with immunomodulatory properties.Therefore,it is crucial to research wound dressings that have immunomodulatory properties. OBJECTIVE:To prepare chitosan hydrogels that have been modified by arginine with different configurations and assess their capacity to speed up wound healing in a rat animal model. METHODS:(1)In vitro trial:Chitosan modified by pure L-arginine,pure D-arginine,and L-arginine and D-arginine was synthesized by EDC/NHS system,which was then crosslinked with aldehyde-modified four-arm polyethylene glycol.Different chitosan-based hydrogels(CS-L,CS-D,and CS-DL)were finally formed via the Schiff base reaction.Three kinds of hydrogel extracts were co-cultured with fibroblasts respectively.Hydrogel cytocompatibility was assessed using the CCK-8 assay and live/dead staining.The effect of hydrogel on the migration capacity of fibroblasts was assessed by using a scratch test.Three kinds of hydrogels were incubated with rat erythrocyte suspension respectively to evaluate the hemocompatibility of the hydrogels.The hydrogel extract was co-cultured with RAW264.7 macrophages to test the hydrogels'capacity to enhance macrophage NO generation and polarize macrophage phenotype.(2)In vivo experiment:A total of 36 adult SD rats were divided into 4 groups with 9 rats in each group by the random number table method.Two full-layer skin defect wounds of 2 cm×2 cm were made on the back of each rat.Normal saline was added to the wounds of the control group,and corresponding hydrogel was added to the wounds of the CS-L,CS-D,and CS-DL groups,respectively,and then bandaged and fixed.The wound healing was observed regularly after operation.Hematoxylin-eosin staining was performed at 3,10,and 21 days after operation.The samples were collected 10 days after operation and M2 macrophage immunofluorescence staining was performed. RESULTS AND CONCLUSION:(1)In vitro experiments:Under scanning electron microscopy,the three kinds of hydrogels exhibited obvious interpenetrating network structures with pore sizes ranging from 70-200 μm.The three kinds of hydrogels have good swelling performance,degradation performance,self-healing performance,and suitable mechanical strength.The three kinds of hydrogels had good cytocompatibility and hemocompatibility and could promote the migration of fibroblasts.All three kinds of hydrogels had the ability to promote the polarization of macrophages,and CS-D hydrogels had the strongest ability to promote the polarization of macrophages.CS-L hydrogel could significantly promote the production of NO in macrophages.(2)In vivo experiment:3 and 10 days after operation,the wound healing rate in the CS-L and CS-D groups was higher than that in the control group(P<0.05).After 21 days,the wound healing rate of the three hydrogel groups was higher than that of the control group.Hematoxylin-eosin staining displayed that a large number of inflammatory cells were infiltrated in the wound tissue of rats in all groups,accompanied by neovessels and fibroblasts 3 days after operation.10 days after operation,there was still more inflammatory cell infiltration in the wound of the control group,and the inflammation of the other three groups was improved,especially the decrease of inflammatory cells in the CS-D group was more obvious.21 days after operation,the wound epithelium of each group was well repaired,and there was basically no inflammatory cell infiltration in the CS-L and CS-D groups,while there was still a small amount of inflammatory cell infiltration in the control group.Immunofluorescence staining revealed that the number of M2-type macrophages in the CS-D group was higher than that in the other three groups(P<0.05).(3)The results conclude that chitosan hydrogels modified by different configurations of arginine can promote wound healing through different mechanisms.
RESUMO
Objective:To establish auto verification rules for the routine coagulation assays,and to provide reference for clinical laboratories to improve the quality and efficiency of results verification.Methods:A total of 24,510 specimens of sodium citrate anticoagulation routine coagulation test from the laboratory departments of eight hospitals including the First Medical Center,Chinese PLA General Hospital during January to March 2020 were collected and randomly divided into a rule establishment group and a rule verification group,with 6,670 specimens in the rule establishment group,including 2,056 Delta checks,and 17,840 specimens in the rule validation group,including 3,210 Delta checks.The activities of prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(Fib),thrombin time(TT),D-dimer(DD)and/or antithrombin(AT)were detected by Stago STA R Max automatic coagulation analyzer and supporting reagents.Taking the manual verification results as the standard,the auto verification and manual false negative rate(invalid verification),false positive rate(invalid interception),pass rate,positive coincidence rate,negative coincidence rate,verification consistency rate and specimen turnaround time(TAT)of the two groups were calculated.Results:The auto verification rules and the application process were preliminarily established,including internal quality control,alarm information,auto verification scope,critical value and deviation value inspection.In the rule establishment group,the single item pass rate was 82.6%-92.4%,and the overall pass rate was 73.8%.The consistency rate between auto verification and manual verification was 98.2%,and the positive coincidence rate and negative coincidence rate were 24.4%and 73.8%,respectively.In the rule verification group,the single item pass rate was 86.4%-91.5%,and the overall review pass rate was 71.5%.By simulating the application of auto verification rules,the average TAT of two hospitals among the eight hospitals was shortened by 1.5 hours and 2.1 hours,respectively.Conclusion:The application of auto verification rules can reduce workload of manual verification,and significantly shorten the TAT,and improve the report efficiency of the laboratory.
RESUMO
Homocysteine (Hcy) is an independent risk factor for cardiovascular disease, but the molecular mechanisms causing atherosclerosis in monocytes remain poorly characterized. The objective of the present study was to investigate the effects of Hcy on DNA methylation of PPARalpha,gamma and the underlying mechanism of PPARalpha,gamma expression that was induced by Hcy in monocytes. About 50, 100, 200, and 500 microM Hcy were added to the monocytes cultured for 48 h. PPARalpha,gamma that acted as lipid sensors and bind with mM affinities to ligands of antiatherosclerosis were determined by real-time reverse transcription-polymerase chain reaction and Western blotting in monocytes. Here, we used a high-throughput quantitative methylation assay that utilizes fluorescence-based real-time polymerase chain reaction to determine the levels of the PPARalpha,gamma DNA methylation. S-adenosylmethionine (SAM) level and S-adenosylhomocysteine (SAH) level were detected by high performance liquid chromatography. Results indicated that the levels of PPARalpha,gamma promoter methylation in monocytes cultured with Hcy were increased in comparison with the control group, and the peak was in the 100 muM Hcy group, however, a dose-dependent increase with increasing Hcy was not seen. Hcy also decreased mRNA and protein levels of PPARalpha,gamma in monocytes. Further, with the addition of Hcy, the levels of SAH were elevated, the levels of SAM and the ratio of SAM/SAH were lower, and the activity of C-5MT-ase was increased. In conclusion, these results suggest that PPARalpha,gamma DNA methylation induced by Hcy may represent an important mechanism to explain atherosclerosis, which may become a therapeutic target for preventing atherosclerosis induced by Hcy.