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2.
Acta Parasitol ; 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35175460

RESUMO

PURPOSE: Strongyloidiasis is mainly prevalent in developing countries with poor economic and sanitary conditions. The clinical manifestations of Strongyloides stercoralis infection are complex and diverse, lacking specificity, which can easily lead to misdiagnosis and delayed treatment. METHODS: An elderly male patient, repeated cough and expectoration for 4 years, with exacerbation and dyspnea for 10 days, was admitted to hospital. Sputum culture and smear were taken for examination. Nematode larvae were found under the microscope. Nematodes were also found in feces. RESULTS: Upon confirmation, the patient was diagnosed with a pulmonary infection caused by Strongyloides stercoralis. After treatment with albendazole, the symptoms improved, and the patient was discharged. CONCLUSION: In this case report, combination of microscopic examination of sputum and alveolar lavage fluid and CT scan were used to quickly identify the cause of the patient, it provides a diagnostic basis and method for clinical treatment.

3.
BMC Genomics ; 23(1): 20, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34996351

RESUMO

BACKGROUND: Carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) causes serious infections with significant morbidity and mortality. However, the epidemiology and transmission mechanisms of CR-hvKP and the corresponding carbapenem-resistant plasmids require further investigation. Herein, we have characterized an ST11 K. pneumoniae strain EBSI041 from the blood sample encoding both hypervirulence and carbapenem resistance phenotypes from a patient in Egypt. RESULTS: K. pneumoniae strain EBSI041 showed multidrug-resistance phenotypes, where it was highly resistant to almost all tested antibiotics including carbapenems. And hypervirulence phenotypes of EBSI041 was confirmed by the model of Galleria mellonella infection. Whole-genome sequencing analysis showed that the hybrid plasmid pEBSI041-1 carried a set of virulence factors rmpA, rmpA2, iucABCD and iutA, and six resistance genes aph(3')-VI, armA, msr(E), mph(E), qnrS, and sul2. Besides, blaOXA-48 and blaSHV-12 were harboured in a novel conjugative IncL-type plasmid pEBSI041-2. The blaKPC-2-carrying plasmid pEBSI041-3, a non-conjugative plasmid lacking the conjugative transfer genes, could be transferred with the help of pEBSI041-2, and the two plasmids could fuse into a new plasmid during co-transfer. Moreover, the emergence of the p16HN-263_KPC-like plasmids is likely due to the integration of pEBSI041-3 and pEBSI041-4 via IS26-mediated rearrangement. CONCLUSION: To the best of our knowledge, this is the first report on the complete genome sequence of KPC-2- and OXA-48-coproducing hypervirulent K. pneumoniae from Egypt. These results give new insights into the adaptation and evolution of K. pneumoniae during nosocomial infections.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Egito , Humanos , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , Plasmídeos/genética , beta-Lactamases/genética
4.
Front Immunol ; 12: 731876, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867952

RESUMO

Background: The differential diagnosis between tuberculous meningitis (TBM) and bacterial meningitis (BM) remains challenging in clinical practice. This study aimed to establish a diagnostic model that could accurately distinguish TBM from BM. Methods: Patients with TBM or BM were recruited between January 2017 and January 2021 at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort). The detection for indicators involved in cerebrospinal fluid (CSF) and T-SPOT assay were performed simultaneously. Multivariate logistic regression was used to create a diagnostic model. Results: A total of 174 patients (76 TBM and 98 BM) and another 105 cases (39 TBM and 66 BM) were enrolled from Qiaokou cohort and Caidian cohort, respectively. Significantly higher level of CSF lymphocyte proportion while significantly lower levels of CSF chlorine, nucleated cell count, and neutrophil proportion were observed in TBM group when comparing with those in BM group. However, receiver operating characteristic (ROC) curve analysis showed that the areas under the ROC curve (AUCs) produced by these indicators were all under 0.8. Meanwhile, tuberculosis-specific antigen/phytohemagglutinin (TBAg/PHA) ratio yielded an AUC of 0.889 (95% CI, 0.840-0.938) in distinguishing TBM from BM, with a sensitivity of 68.42% (95% CI, 57.30%-77.77%) and a specificity of 92.86% (95% CI, 85.98%-96.50%) when a cutoff value of 0.163 was used. Consequently, we successfully established a diagnostic model based on the combination of TBAg/PHA ratio, CSF chlorine, CSF nucleated cell count, and CSF lymphocyte proportion for discrimination between TBM and BM. The established model showed good performance in differentiating TBM from BM (AUC: 0.949; 95% CI, 0.921-0.978), with 81.58% (95% CI, 71.42%-88.70%) sensitivity and 91.84% (95% CI, 84.71%-95.81%) specificity. The performance of the diagnostic model obtained in Qiaokou cohort was further validated in Caidian cohort. The diagnostic model in Caidian cohort produced an AUC of 0.923 (95% CI, 0.867-0.980) with 79.49% (95% CI, 64.47%-89.22%) sensitivity and 90.91% (95% CI, 81.55%-95.77%) specificity. Conclusions: The diagnostic model established based on the combination of four indicators had excellent utility in the discrimination between TBM and BM.


Assuntos
Meningites Bacterianas/diagnóstico , Tuberculose Meníngea/diagnóstico , Adulto , Antígenos de Bactérias/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Líquido Cefalorraquidiano/citologia , Líquido Cefalorraquidiano/imunologia , Líquido Cefalorraquidiano/microbiologia , China , Estudos de Coortes , Diagnóstico Diferencial , ELISPOT/métodos , Feminino , Humanos , Interferon gama/sangue , Masculino , Meningites Bacterianas/sangue , Meningites Bacterianas/líquido cefalorraquidiano , Pessoa de Meia-Idade , Modelos Biológicos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Meníngea/sangue , Tuberculose Meníngea/líquido cefalorraquidiano
5.
Front Microbiol ; 12: 774492, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956138

RESUMO

Type I and type II CRISPR-Cas systems are employed to evade host immunity by targeting interference of bacteria's own genes. Although Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, possesses integrated type III-A CRISPR-Cas system, its role in mycobacteria remains obscure. Here, we observed that seven cas genes (csm2∼5, cas10, cas6) were upregulated in Mycobacterium bovis BCG under oxidative stress treatment, indicating the role of type III-A CRISPR-Cas system in oxidative stress. To explore the functional role of type III-A CRISPR-Cas system, TCC (Type III-A CRISPR-Cas system, including cas6, cas10, and csm2-6) mutant was generated. Deletion of TCC results in increased sensitivity in response to hydrogen peroxide and reduced cell envelope integrity. Analysis of RNA-seq dataset revealed that TCC impacted on the oxidation-reduction process and the composition of cell wall which is essential for mycobacterial envelop integrity. Moreover, disrupting TCC led to poor intracellular survival in vivo and in vitro. Finally, we showed for the first time that TCC contributed to the regulation of regulatory T cell population, supporting a role of TCC in modulating host immunity. Our finding reveals the important role of TCC in cell envelop homeostasis. Our work also highlights type III-A CRISPR-Cas system as an important factor for intracellular survival and host immunoregulation in mycobacteria, thus may be a potential target for therapy.

6.
Pharmacol Res ; 172: 105846, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34438063

RESUMO

Early onset and progression of liver diseases can be driven by aberrant transcriptional regulation. Different transcriptional regulation processes, such as RNA/DNA methylation, histone modification, and ncRNA-mediated targeting, can regulate biological processes in healthy cells, as well also under various pathological conditions, especially liver disease. Numerous studies over the past decades have demonstrated that liver disease has a strong epigenetic component. Therefore, the epigenetic basis of liver disease has challenged our knowledge of epigenetics, and epigenetics field has undergone an important transformation: from a biological phenomenon to an emerging focus of disease research. Furthermore, inhibitors of different epigenetic regulators, such as m6A-related factors, are being explored as potential candidates for preventing and treating liver diseases. In the present review, we summarize and discuss the current knowledge of five distinct but interconnected and interdependent epigenetic processes in the context of hepatic diseases: RNA methylation, DNA methylation, histone methylation, miRNAs, and lncRNAs. Finally, we discuss the potential therapeutic implications and future challenges and ongoing research in the field. Our review also provides a perspective for identifying therapeutic targets and new hepatic biomarkers of liver disease, bringing precision research and disease therapy to the modern era of epigenetics.


Assuntos
Hepatopatias/genética , RNA Longo não Codificante , Adenosina/análogos & derivados , Animais , Epigênese Genética , Humanos , Hepatopatias/terapia , Fatores de Risco
7.
Clin Biochem ; 97: 54-61, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34453893

RESUMO

OBJECTIVES: Detection of antibodies to multiple SARS-CoV-2 antigens in a single assay could increase diagnostic accuracy, differentiate vaccination from natural disease, and aid in retrospective exposure determination. Correlation of binding antibody assessment in clinical assays with neutralizing antibodies is needed to better understand the humoral response to SARS-CoV-2 infection and establish of correlates of protection. METHODS: A cohort of 752 samples was used to assess specificity, sensitivity, and comparison to 6 other Conformitè Europëenne serologic assays for the BioRad SARS-CoV-2 IgG multiplex assay which measures receptor binding domain IgG (RBD), spike-S1 IgG (S1), spike-S2 IgG (S2), and nucleocapsid IgG (N). A subset of serial specimens from 14 patients was also tested for neutralizing antibodies (n = 61). RESULTS: Specificity for RBD and S1 IgG was 99.4% (n = 170) and 100% for S2 and N IgG (n = 170) in a cohort selected for probable interference. Overall assay concordance with other assays was >93% for IgG and total antibody assays and reached 100% sensitivity for clinical concordance at >14 days as a multiplex assay. RBD and S1 binding antibody positivity demonstrated 79-95% agreement with the presence of neutralizing antibodies. CONCLUSIONS: The BioRad SARS-CoV-2 IgG assay is comparable to existing assays, and achieved 100% sensitivity when all markers were included. The ability to measure antibodies against spike and nucleocapsid proteins simultaneously may be advantageous for complex clinical presentations, epidemiologic research, and in decisions regarding infection prevention strategies. Additional independent validations are needed to further determine binding antibody and neutralizing antibody correlations.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Teste Sorológico para COVID-19/métodos , SARS-CoV-2/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/sangue , COVID-19/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia
8.
Pathogens ; 10(6)2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34204122

RESUMO

Seroprevalence studies are important for understanding the dynamics of local virus transmission and evaluating community immunity. To assess the seroprevalence for SARS-CoV-2 in Allegheny County, an urban/suburban county in Western PA, 393 human blood samples collected in Fall 2020 and February 2021 were examined for spike protein receptor-binding domain (RBD) and nucleocapsid protein (N) antibodies. All RBD-positive samples were evaluated for virus-specific neutralization activity. Our results showed a seroprevalence of 5.5% by RBD ELISA, 4.5% by N ELISA, and 2.5% for both in Fall 2020, which increased to 24.7% by RBD ELISA, 14.9% by N ELISA, and 12.9% for both in February 2021. Neutralization titer was significantly correlated with RBD titer but not with N titer. Using these two assays, we were able to distinguish infected from vaccinated individuals. In the February cohort, higher median income and white race were associated with serological findings consistent with vaccination. This study demonstrates a 4.5-fold increase in SARS-CoV-2 seroprevalence from Fall 2020 to February 2021 in Allegheny County, PA, due to increased incidence of both natural disease and vaccination. Future seroprevalence studies will need to include the effect of vaccination on assay results and incorporate non-vaccine antigens in serological assessments.

9.
mSphere ; 6(3)2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011682

RESUMO

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates in Egyptian hospitals has been reported. However, the genetic basis and analysis of the plasmids associated with carbapenem-resistant hypervirulent K. pneumoniae (CR-HvKP) in Egypt have not been presented. Therefore, we attempted to decipher the plasmid sequences that are responsible for transferring the determinants of carbapenem resistance, particularly bla NDM-1 and bla KPC-2 Out of 34 K. pneumoniae isolates collected from two tertiary hospitals in Egypt, 31 were CRKP. Whole-genome sequencing revealed that our isolates were related to 13 different sequence types (STs). The most prevalent ST was ST101, followed by ST383 and ST11. Among the CRKP isolates, one isolate named EBSI036 has been reassessed by Nanopore sequencing. Genetic environment analysis showed that EBSI036 carried 20 antibiotic resistance genes and was identified as a CR-HvKP strain: it harbored four plasmids, namely, pEBSI036-1-NDM-VIR, pEBSI036-2-KPC, pEBSI036-3, and pEBSI036-4. The two carbapenemase genes bla NDM-1 and bla KPC-2 were located on plasmids pEBSI036-1-NDM-VIR and pEBSI036-2-KPC, respectively. The IncFIB:IncHI1B hybrid plasmid pEBSI036-1-NDM-VIR also carried some virulence factors, including the regulator of the mucoid phenotype (rmpA), the regulator of mucoid phenotype 2 (rmpA2), and aerobactin (iucABCD and iutA). Thus, we set out in this study to analyze in depth the genetic basis of the pEBSI036-1-NDM-VIR and pEBSI036-2-KPC plasmids. We report a high-risk clone ST11 KL47 serotype of a CR-HvKP strain isolated from the blood of a 60-year-old hospitalized female patient from the intensive care unit (ICU) in a tertiary care hospital in Egypt, which showed the cohabitation of a novel hybrid plasmid coharboring the bla NDM-1 and virulence genes and a bla KPC-2-carrying plasmid.IMPORTANCE CRKP has been registered in the critical priority tier by the World Health Organization and has become a significant menace to public health. The emergence of CR-HvKP is of great concern in terms of both disease and treatment. In-depth analysis of the carbapenemase-encoding and virulence plasmids may provide insight into ongoing recombination and evolution of virulence and multidrug resistance in K. pneumoniae Thus, this study serves to alert contagious disease clinicians to the presence of hypervirulence in CRKP isolates in Egyptian hospitals.


Assuntos
Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/patogenicidade , Plasmídeos/genética , Fatores de Virulência/genética , beta-Lactamases/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Egito , Feminino , Humanos , Lactente , Recém-Nascido , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem
10.
ACS Appl Mater Interfaces ; 13(18): 20995-21006, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33930273

RESUMO

COVID-19 has been diffusely pandemic around the world, characterized by massive morbidity and mortality. One of the remarkable threats associated with mortality may be the uncontrolled inflammatory processes, which were induced by SARS-CoV-2 in infected patients. As there are no specific drugs, exploiting safe and effective treatment strategies is an instant requirement to dwindle viral damage and relieve extreme inflammation simultaneously. Here, highly biocompatible glycyrrhizic acid (GA) nanoparticles (GANPs) were synthesized based on GA. In vitro investigations revealed that GANPs inhibit the proliferation of the murine coronavirus MHV-A59 and reduce proinflammatory cytokine production caused by MHV-A59 or the N protein of SARS-CoV-2. In an MHV-A59-induced surrogate mouse model of COVID-19, GANPs specifically target areas with severe inflammation, such as the lungs, which appeared to improve the accumulation of GANPs and enhance the effectiveness of the treatment. Further, GANPs also exert antiviral and anti-inflammatory effects, relieving organ damage and conferring a significant survival advantage to infected mice. Such a novel therapeutic agent can be readily manufactured into feasible treatment for COVID-19.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Ácido Glicirrízico/uso terapêutico , Inflamação/tratamento farmacológico , Nanopartículas/uso terapêutico , Viroses/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Antioxidantes/uso terapêutico , Antivirais/química , COVID-19/tratamento farmacológico , Proteínas do Nucleocapsídeo de Coronavírus/farmacologia , Citocinas/metabolismo , Feminino , Ácido Glicirrízico/química , Humanos , Fígado/patologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Vírus da Hepatite Murina/efeitos dos fármacos , Nanopartículas/química , Fosfoproteínas/farmacologia , Células RAW 264.7 , SARS-CoV-2/química , Células THP-1 , Carga Viral/efeitos dos fármacos , Viroses/patologia , Replicação Viral/efeitos dos fármacos
11.
Exp Ther Med ; 21(1): 24, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33262810

RESUMO

A severe immune response in patients with coronavirus disease 2019 (COVID-19) can cause a potentially lethal unconstrained inflammatory cytokine storm, known as cytokine release syndrome (CRS). The present study provides an overview of the biology underlying CRS and how targeted inhibition of interleukin (IL)-6 signaling may improve outcomes and the survival of patients suffering from COVID-19. Preliminary clinical results have indicated that antagonism of the IL-6 receptor (IL-6R), including with the FDA-approved humanized monoclonal antibody tocilizumab, can improve the outcomes of patients with severe or critical COVID-19 while maintaining a good safety profile. The available clinical data support the expansion of clinical trials using IL-6R targeting inhibitors for severe and critical COVID-19 treatment.

12.
Exp Ther Med ; 20(3): 1943-1952, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32782503

RESUMO

The present study aimed to investigate the association between drug resistance and class I, II and III integrons in Acinetobacter baumannii (ABA). Multilocus sequence typing (MLST) is a tool used to analyze the homology among house-keeping gene clusters in ABA and ABA prevalence and further provides a theoretical basis for hospitals to control ABA infections. A total of 96 clinical isolates of non-repeating ABA were harvested, including 74 carbapenem-resistant ABA (CRABA) and 22 non-CRABA strains, and used for bacterial identification and drug susceptibility analysis. Variable regions were sequenced and analyzed. Then, 7 pairs of housekeeping genes were amplified and sequenced via MLST and sequence alignment was performed against the Pub MLST database to determine sequence types (STs) strains and construct different genotypic evolutionary diagrams. The detection rate of CRABA class I integrons was 13.51% (10/74); no class II and III integrons were detected. However, class I, II and III integrons were not detected in non-CRABA strains. The variable regions of 9 of 10 class I integrons were amplified and 10 gene cassettes including aacC1, aac1, aadDA1, aadA1a, aacA4, dfrA17, aadA5, aadA1, aadA22 and aadA23 were associated with drug resistance. The 96 ABA strains were divided into 21 STs: 74 CRABA strains containing 9 STs, primarily ST208 and ST1145 and 22 non-CRABA strains containing 18 STs, primarily ST1145. Class I integrons are a critical factor underlying drug resistance in ABA. CRABA and non-CRABA strains differ significantly; the former primarily contained ST208 and ST1145, and the latter contained ST1145. Most STs were concentrated in intensive care units (ICUs) and the department of Neurology, with the patients from the ICUs being the most susceptible to bacterial infection. In the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, ABA is potentially horizontally transmitted and MLST can be used for clinical ABA genotyping.

13.
Cardiovasc Diagn Ther ; 10(3): 520-525, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32695631

RESUMO

BACKGROUND: Atherosclerosis is one of the most common cardiovascular and cerebrovascular diseases. This study aimed to explore the correlation between gene polymorphism of human apolipoprotein E (ApoE) and lipoprotein-associated phospholipase A2 (Lp-PLA2). METHODS: A total of 220 patients with atherosclerotic cardiovascular disease who were treated in our hospital from June 2016 to March 2017 were enrolled in this study and assigned as the atherosclerotic cardiovascular disease group and 193 patients who were treated contemporaneously in our hospital but had no atherosclerotic cardiovascular disease were enrolled and assigned as the control group. Gene polymorphism of ApoE was detected by PCR-fluorescent probe technique and the level of Lp-PLA2 was detected by ELISA. RESULTS: There were a total of 5 genotypes of ApoE in these two groups, which were E2/3, E3/3, E3/4, E2/4, and E4/4. E2/2 was not found in any of the patients. E3/3 made up the majority in both groups. There was no significant difference between the proportion of genotypes and frequencies of alleles in the two groups (P>0.05). There was no difference between LP-PLA2 among the different genotypes in these two groups (P>0.05). CONCLUSIONS: We cannot conclude that ApoE gene polymorphism is related to atherosclerotic cardiovascular and cerebrovascular diseases. And it cannot be concluded that ApoE gene polymorphism is related to Lp-PLA2 level.

14.
J Immunol ; 203(10): 2614-2620, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31578271

RESUMO

Mucosal-associated invariant T (MAIT) cells play a key role in local and systemic immune responses. Studies suggest that type 2 diabetes (T2D) is associated with alterations in the human MAIT cell response. However, the mechanisms that regulate the survival and homeostasis of human MAIT cells are poorly defined. In this study, we demonstrate that the costimulatory TNF superfamily receptor OX40 was highly expressed in MAIT cells of patients with T2D. Compared with OX40-negative MAIT cells, OX40-positive MAIT cells showed a high activation and a memory phenotype. Surprisingly, OX40 expression was negatively correlated with the frequency of MAIT cells in the peripheral blood of T2D patients. Increased cleaved caspase-3 levels were observed in OX40+-expressing MAIT cells in T2D patients. In vitro, activated OX40 signaling by recombinant OX40L protein promoted caspase-3 activation and apoptosis of MAIT cells. Inhibition of caspase-3 restored apoptosis of MAIT cells induced by OX40 signaling. These results identify OX40 as an amplifier of activation-induced cell death of human blood MAIT cells and shed new light on the regulation of MAIT cells in the phase of immune responses in T2D.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Células T Invariantes Associadas à Mucosa/metabolismo , Receptores OX40/metabolismo , Adulto , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Estudos de Coortes , Feminino , Humanos , Memória Imunológica , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Células T Invariantes Associadas à Mucosa/imunologia , Ligante OX40/farmacologia , Fenótipo , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos
15.
Open Med (Wars) ; 14: 324-330, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30997395

RESUMO

Objective: To investigate the predictive value of clinical variables on the poor prognosis at 90-day follow-up from acute stroke onset, and compare the diagnostic performance between back propagation artificial neural networks (BP ANNs) and Logistic regression (LR) models in predicting the prognosis. Methods: We studied the association between clinical variables and the functional recovery of 435 acute ischemic stroke patients. The patients were divided into 2 groups according to modified Rankin Scale scores evaluated on the 90th day after stroke onset. Both BP ANNs and LR models were established for predicting the poor outcome and their diagnostic performance were compared by receiver operating curve. Results: Age, free fatty acid, homocysteine and alkaline phosphatase were closely related with the poor outcome in acute ischemic stroke patients and finally enrolled in models. The accuracy, sensitivity and specificity of BP ANNs were 80.15%, 75.64% and 82.07% respectively. For the LR model, the accuracy, sensitivity and specificity was 70.61%, 88.46% and 63.04% respectively. The area under the ROC curve of the BP ANNs and LR model was 0.881and 0.809. Conclusions: Both BP ANNs and LR model were promising for the prediction of poor outcome by combining age, free fatty acid, homocysteine and alkaline phosphatase. However, BP ANNs model showed better performance than LR model in predicting the prognosis.

16.
Mol Biotechnol ; 60(4): 245-250, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29468521

RESUMO

To identify the importance of IRAK2 kinase activity in TLR-mediated signaling pathways, we constructed a retroviral vector harboring either a mouse IRAK2 gene (IRAK2-WT) or with its mutant with loss of function of its ATP-binding site (IRAK2-KD). Further, we comparatively analyzed for the gain of function and modulations in TLR-mediated signaling pathways in IRAK2 knockout (IRAK2-KO) macrophages upon introduction of the IRAK2-WT retroviral constructs. The pBS/IRAK2-KD with the ATP-binding site mutation in IRAK2 was obtained by using site-specific mutagenesis. The recombinants were identified with appropriate double digestion and sequence analysis. The recombinant vector constructs were transfected by lipofection into phoenix packaging cells. The viral vectors (107 cfu/mL) with the construct were allowed to infect IRAK2-KO macrophages. The results showed that IRAK2-WT gene overexpressed in the IRAK2-KO macrophages exhibited a modified IRAK2 expression upon LPS induction. However, the modification was absent with IRAK2-KD construct on LPS stimulation; instead, the IRAK2 protein stability was reduced considerably. The results further show that the LPS-induced effect on the stability of IRAK2 is dependent of IRAK4 stimulation.


Assuntos
Quinases Associadas a Receptores de Interleucina-1/genética , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Mutação , Retroviridae/genética , Trifosfato de Adenosina/metabolismo , Animais , Sítios de Ligação , Células Cultivadas , Quinases Associadas a Receptores de Interleucina-1/química , Lipopolissacarídeos/efeitos adversos , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Receptores Toll-Like/metabolismo
17.
Int J Med Sci ; 14(13): 1368-1374, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29200950

RESUMO

Background:Pseudomonas aeruginosa can cause disease and also can be isolated from the skin of healthy people. Additionally, it exhibits certain antimicrobial effects against other microorganisms.Methods: We collected 60 strains of P. aeruginosa and screened their antimicrobial effects against Staphylococcus aureus (ATCC 25923) using the filter paper-disk method, the cross-streaking method and the co-culture method and then evaluated the antimicrobial activity of the chloroform-isolated S. aureus extracts against methicillin-resistant S. aureus (MRSA, Gram-positive cocci), vancomycin intermediate-resistant S. aureus (VISA, Gram-positive cocci), Corynebacterium spp. (CS, Gram-positive bacilli), Acinetobacter baumannii (AB, Gram-negative bacilli), Moraxella catarrhalis (MC, Gram-negative diplococcus), Candida albicans (CA, fungi), Candida tropicalis (CT, fungi), Candida glabrata (CG, fungi) and Candida parapsilosis (CP, fungi). Results: The PA06 and PA46 strains have strong antimicrobial effects. High-performance liquid chromatography (HPLC) analysis revealed that the major components of PA06 and PA46 that exhibit antimicrobial activity are functionally similar to phenazine-1-carboxylic acid (PCA) and pyocyanin. Preparative HPLC was performed to separate and isolate the 4 major potential antimicrobial components: PA06ER10, PA06ER16, PA06ER23 and PA06ER31. Further, the molecular masses of PA06ER10 (260.1), PA06ER16 (274.1), PA06ER23 (286.1) and PA06ER31 (318.2) were determined by electrospray ionization (ESI) mass spectrometry. Conclusion:P. aeruginosa can produce small molecules with potential antimicrobial activities against MRSA, VISA, CS, MC, CA, CT, CG and CP but not against AB.


Assuntos
Anti-Infecciosos/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pseudomonas aeruginosa/química , Infecções Estafilocócicas/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/patogenicidade , Anti-Infecciosos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade , Extratos Celulares/química , Extratos Celulares/farmacologia , Corynebacterium/efeitos dos fármacos , Corynebacterium/patogenicidade , Humanos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologia , Resistência a Vancomicina/efeitos dos fármacos
18.
Mol Immunol ; 90: 219-226, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28843171

RESUMO

Cytoplasmic alkalinization and extracellular adenosine triphosphate (ATP) signals are required for migration of chemokineactivated neutrophils, but the precise functions remain unclear. In this work, the effect of the plasma membrane-expressed F0F1-ATP synthase (FATPase) on human neutrophils was examined. We found F-ATPase to be involved in cytoplasm proton extrusion and extracellular ATP generation. Oligomycin A, an F-ATPase inhibitor that blocks proton transfer, inhibited cytoplasmic alkalinization, extracellular ATP generation, adhesion and chemotaxis in N-formyl-Met-Leu-Phe (fMLP)-stimulated neutrophils; however, adenosine diphosphate (ADP), a substrate and activator of F-ATPase, had the opposite effect. Further analysis revealed that cell surface F-ATPase can translocate to the leading edge of directional fMLP-stimulated neutrophils toward ADP hydrolyzed from pannexin 1 channel-released ATP, followed by F-ATPase-catalyzed ATP regeneration using ADP and protons transferred from the cytoplasm. Therefore, the membrane-expressed F-ATPase regulates human neutrophil migration via cytoplasm proton extrusion and extracellular ATP generation.


Assuntos
Trifosfato de Adenosina/biossíntese , Quimiotaxia de Leucócito/fisiologia , Neutrófilos/fisiologia , ATPases Translocadoras de Prótons/metabolismo , Difosfato de Adenosina/farmacologia , Adulto , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Células Cultivadas , Quimiotaxia de Leucócito/efeitos dos fármacos , Conexinas/metabolismo , Humanos , Potencial da Membrana Mitocondrial/fisiologia , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Proteínas do Tecido Nervoso/metabolismo , Oligomicinas/farmacologia , ATPases Translocadoras de Prótons/antagonistas & inibidores
19.
Exp Ther Med ; 7(6): 1516-1520, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24926335

RESUMO

The aim of the present study was to investigate the inhibitory effect of Pseudomonas aeruginosa (PA) on pathogenic fungi, including Candida albicans (CA), Candida tropicalis (CT), Candida glabrata (CG), Candida parapsilosis (CP) and Candida krusei (CK), in vitro and in vivo. In total, 24 PA strains were collected from clinical specimens and identified by Gram staining, oxidase production and the API 20NE system. Cross-streak, disk diffusion and co-culture methods were used to observe the inhibitory effect of PA. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to analyze differences in the bacterial proteins of PA. A blood infection model in mice was used to evaluate the effect of PA on fungi in vivo. The in vitro and in vivo results demonstrated that a number of PA isolates exhibited a marked inhibitory effect on pathogenic fungi, including CA, CT, CP, CG and CK, while other PA strains exhibited no effect. Therefore, PA exhibits an inhibitory effect on pathogenic fungi and this activity may be important in the treatment of patients. It was hypothesized that PA secretes various types of proteins to suppress the growth of fungal filaments, which subsequently inhibits pathogenic fungi.

20.
Microb Pathog ; 71-72: 56-61, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24746531

RESUMO

Sepsis induced by Staphylococcus aureus has worse outcome with the appearance of methicillin-resistant Staphylococcus aureus (MRSA) because of multi-resistance to a large group of antibiotics, which may lead to death from septic shock. Pathogenesis of S. aureus infections are involved in the production of a wide variety of virulence factors. MgrA, a noval global regulator, is a member of the MarR (multiple antibiotic resistance regulator)/SarA (staphylococcal accessory regulator A) family proteins, which plays a key role in regulating the expression of major virulence factors in S. aureus. In the present study, by using a murine model of sepsis, we investigated the role of mgrA in onset and progression of S. aureus induced sepsis. We found that mice inoculated with wild-type strain Newman had significantly higher mortality (p = 0.029), more weight lost, more bacterial load in blood, spleen and kidney, more intense inflammation response, and worse histopathology than mice inoculated with mgrA knockout strain. Our results has provided evidence that mgrA is a global regulator in S. aureus, and play an important role in S. aureus sepsis, could increase mortality and accelerate the onset and development of sepsis.


Assuntos
Proteínas de Bactérias/metabolismo , Progressão da Doença , Sepse/patologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/patogenicidade , Fatores de Virulência/metabolismo , Animais , Carga Bacteriana , Proteínas de Bactérias/genética , Sangue/microbiologia , Peso Corporal , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Rim/microbiologia , Masculino , Camundongos Endogâmicos BALB C , Sepse/microbiologia , Baço/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Análise de Sobrevida , Fatores de Virulência/genética
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