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1.
Hum Vaccin Immunother ; : 1-9, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32429793

RESUMO

Debate continues regarding the need for a booster vaccination in children who received a universal infant hepatitis B virus (HBV) vaccination. The aim was to explore the need and the strategies for the booster HBV vaccination. 8-year prospective cohort study was conducted among children aged 5-15 years in 2009-2010 in Zhejiang Province. The participants were divided into groups A (<0.1 mIU/mL), B (0.1 to < 1 mIU/mL) and C (1 to <10 mIU/mL) according to the pre-booster anti-HBs antibody levels. 5 µg (group I), 10 µg (group II), 20 µg hepatitis B vaccines (group III) or 5 µg hepatitis A and B (HAB) vaccines (group IV) with 0-1-6-month schedule were randomly administered to children negative for all markers. Blood samples were collected at baseline HBV marker testing, 1 month after the first dose, 1 month, 1 year, 5 years and 8 years after the third dose. Among 4170 children, 2326 (55.8%) were negative for all HBV markers. Group II showed the highest seropositive rates of 92.8%, 99.7%, 97.6%, 90.3% and 83.4% with GMTs of 4194.5 mIU/ml, 4163.9 mIU/ml, 466.9 mIU/ml, 190.6 mIU/ml, 122.6 mIU/ml from 1 month after dose 1 to 8 years after dose 3, respectively (P < .01). Participants in group C showed seropositive rates of 98.9%, 99.9%, 99.5%, 95.5%, 92.8% after the revaccination with GMTs of 6519.6 mIU/ml, 5267.4 mIU/ml, 547.1 mIU/ml, 249.5 mIU/ml, 155.3 mIU/ml, respectively, higher than group A and B (P < .001), except 1 month after the third dose. The 10 µg of HBV vaccine with a 0-1-6-month booster regimen may elicit robust responses and persist for 8 years or longer. Additionally, 1-dose revaccination maybe suitable for children with 1 to < 10 mIU/ml anti-HBs titers.

2.
Int Immunopharmacol ; 85: 106558, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32450532

RESUMO

To investigate the main transcriptional and biological changes of human host during low and highly pathogenic avian H7N9 influenza virus infection and to analyze the possible causes of escalated virulence and the systematic progression of H7N9 virus infection, we utilized whole transcriptome sequencing (RNA-chip and RNA-seq) and other biomolecular methods to analyze and verify remarkable changes of host cells during these two subtypes of H7N9 influenza viruses infection. Whole transcriptome analysis showed the global profiles of differentially expressed genes (DEGs) and identified 458 DEGs associated with major changes in biological processes of the host cells after infection with 2017 HPAI H7N9 virus versus 2013 LPAI H7N9 virus, mainly including drastically increased defense responses to viruses (e.g. negative regulation of viral gene replication), IFNs related pathways, immune response/native immune response, and inflammatory response. Genes of programmed cell death 1 (PD-1) pathways were found changed remarkably and several highly correlated non-coding RNAs were identified. The results suggested that HPAI H7N9 virus induces stronger immune response and suppressing response than LPAI H7N9. Meanwhile, PD-1/PD-Ls signaling pathways work together in regulating host responses including antiviral defense, lethal inflammation caused by the virus and immune response, thus contribute to the high pathogenicity of 2017H7N9 virus that can be regulated by non-coding RNAs. The present study represents a comprehensive understanding and good reference of regulation of pathogenicity of H7N9 virus even other fatal viruses and correlated host immune responses.

3.
Medicine (Baltimore) ; 99(20): e19894, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443291

RESUMO

RATIONALE: Pyopneumopericardium related to bungee jumping is a rare occurrence in the current antibiotic era. We present a case of esophagus-seeded Streptococcus sanguinis pyopneumopericardium in a young man with tuberculosis who had just completed bungee jumping. PATIENT CONCERN: A 27-year-old man was hospitalized with a 1-day history of fever, chest tightness, and intermittent sharp chest pain after bungee jumping for the first time. DIAGNOSES: Clinical examinations, thoracentesis, and pericardiocentesis revealed pyopneumopericardium, pyopneumomediastinum, and suppurative pleurisy secondary to bungee-jumping-related traumas. Pericardial fluid cultures were positive for S sanguinis, and Mycobacterium tuberculosis complex genetic test was positive in both sputum and pleural effusion. INTERVENTIONS: The patient improved with drainage and comprehensive antimicrobial therapy. OUTCOMES: The patient developed constrictive pericarditis and underwent pericardiectomy after 6 months of anti-tuberculosis treatment. During the 6-month follow-up after surgery, he recovered uneventfully. LESSONS: This case adds to the long list of bungee-jumping complications. Early diagnosis to initiate appropriate therapy is critical for pyopneumopericardium patients to achieve good outcomes.

4.
Emerg Microbes Infect ; 9(1): 962-975, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32267217

RESUMO

The H7N9 virus mutated in 2017, resulting in new cases of highly pathogenic avian influenza (HPAI) H7N9 virus infection. H7N9 was found in a viraemic patient in Guangdong province, China. The present study aimed to clarify the pathogenic characteristics of HPAI H7N9. Virus was isolated from the plasma and sputum of the patient with HPAI H7N9. Liquid phase chip technology was used to detect the plasma cytokines from the infected patient and healthy controls. Mice were infected with strains A/Guangdong/GZ8H002/2017(H7N9) and A/Zhejiang/DTID-ZJU01/2013(H7N9) to observe the virus's pathogenic characteristics. Serum and brain tissue were collected at 2, 4, and 6 days after infection. The viruses in serum and brain tissue were detected and isolated. The two strains were infected into A549 cells, exosomes were extracted, and virus genes in the exosomes were assessed. Live virus was isolated from the patient's plasma. An acute cytokine storm was detected during the whole course of the disease. In animal experiments, A/Guangdong/GZ8H002/2017(H7N9) was more pathogenic than A/Zhejiang /DTID-ZJU01/2013(H7N9) and resulted in the death of mice. Live virus was isolated from infected mouse serum. Virus infection was also detected in the brain of mice. Under viral stress, A549 cells secreted exosomes containing the entire viral genome. The viraemic patient was confirmed to have an HPAI H7N9 infection. A/Guangdong/GZ8H002/2017(H7N9) showed significantly enhanced toxicity. Patient deaths might result from cytokine storms and brain infections. Extrapulmonary tissue infection might occur via the exosome pathway. The determined pathogenic characteristics of HPAI H7N9 will contribute to its future treatment.

5.
Gut ; 69(6): 1002-1009, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32213556

RESUMO

OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus , Trato Gastrointestinal , Pandemias , Pneumonia Viral , Adulto , China , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Feminino , Trato Gastrointestinal/fisiopatologia , Trato Gastrointestinal/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Fatores de Risco
6.
BMJ ; 368: m606, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075786

RESUMO

OBJECTIVE: To study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for coronavirus disease 2019 (covid-2019). DESIGN: Retrospective case series. SETTING: Seven hospitals in Zhejiang province, China. PARTICIPANTS: 62 patients admitted to hospital with laboratory confirmed SARS-Cov-2 infection. Data were collected from 10 January 2020 to 26 January 2020. MAIN OUTCOME MEASURES: Clinical data, collected using a standardised case report form, such as temperature, history of exposure, incubation period. If information was not clear, the working group in Hangzhou contacted the doctor responsible for treating the patient for clarification. RESULTS: Of the 62 patients studied (median age 41 years), only one was admitted to an intensive care unit, and no patients died during the study. According to research, none of the infected patients in Zhejiang province were ever exposed to the Huanan seafood market, the original source of the virus; all studied cases were infected by human to human transmission. The most common symptoms at onset of illness were fever in 48 (77%) patients, cough in 50 (81%), expectoration in 35 (56%), headache in 21 (34%), myalgia or fatigue in 32 (52%), diarrhoea in 3 (8%), and haemoptysis in 2 (3%). Only two patients (3%) developed shortness of breath on admission. The median time from exposure to onset of illness was 4 days (interquartile range 3-5 days), and from onset of symptoms to first hospital admission was 2 (1-4) days. CONCLUSION: As of early February 2020, compared with patients initially infected with SARS-Cov-2 in Wuhan, the symptoms of patients in Zhejiang province are relatively mild.


Assuntos
Infecções por Coronavirus/diagnóstico , Síndrome Respiratória Aguda Grave/diagnóstico , Adolescente , Adulto , Criança , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Tosse/virologia , Feminino , Febre/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Radiografia Torácica , Estudos Retrospectivos , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/transmissão , Síndrome Respiratória Aguda Grave/virologia , Tomografia Computadorizada por Raios X , Adulto Jovem
7.
N Engl J Med ; 382(18): 1708-1720, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32109013

RESUMO

BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).


Assuntos
Betacoronavirus , Infecções por Coronavirus , Surtos de Doenças , Pandemias , Pneumonia Viral , Adolescente , Adulto , Idoso , Criança , China/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Feminino , Febre/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Adulto Jovem
8.
Biomed Res Int ; 2019: 3757149, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31871940

RESUMO

Background: Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ALCF) is a complicated syndrome with extremely high short-term mortality. The artificial liver support system (ALSS) may improve the liver function for patients with HBV-ACLF, but the data on its short-term outcomes are insufficient in China. Methods: We recruited HBV-ACLF patients in this nationwide, multicenter, retrospective study. Patients with HBV-ACLF were diagnosed by the COSSH-ACLF criteria. Propensity score matching (PSM) analysis was used to generate compared pairs. The short-term (28/90 days) survival rates between the standard medical therapy (SMT) group and ALSS group were calculated using a Kaplan-Meier graph. Result: In total, 790 patients with HBV-ACLF were included in this retrospective study; 412 patients received SMT only (SMT group), and 378 patients received SMT and ALSS treatment (ALSS group). PSM generated 310 pairs and eliminated the baseline differences between the two groups (p > 0.05 for all baseline variables). The probabilities of survival on day 28 were 65.2% (205/310) in the ALSS group and 59.0% (185/310) in the SMT group; on day 90, they were 51.0% (163/310) and 42.3% (136/310). The short-term (28/90 days) survival rates of the ALSS group were significantly higher than those of the SMT group (p=0.0452 and p=0.0187, respectively). Compared to receiving SMT alone, treatment with ALSS was associated with a significant reduction in serum bilirubin levels and the model for end-stage liver disease (MELD) scores at day 7 and day 28. Multivariate logistic regression analysis revealed that older age, high total bilirubin (T-Bil), low albumin, high ALT, high MELD scores, and high COSSH-ACLF grade were independent baseline factors associated with poor prognosis. Conclusions: This retrospective study found that compared to SMT, the ALSS improved the short-term (28/90 days) survival rates and laboratory parameters in HBV-ACLF patients. The ALSS had a better therapeutic effect than SMT for patients with HBV-ACLF in China.


Assuntos
Insuficiência Hepática Crônica Agudizada/etiologia , Insuficiência Hepática Crônica Agudizada/terapia , Hepatite B/complicações , Fígado Artificial , Insuficiência Hepática Crônica Agudizada/mortalidade , Adulto , Idoso , Bilirrubina/sangue , China , Feminino , Vírus da Hepatite B/patogenicidade , Humanos , Testes de Função Hepática/métodos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida/tendências
9.
World J Gastroenterol ; 25(41): 6190-6204, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31745380

RESUMO

BACKGROUND: Acute liver failure (ALF) is a significant and complex hepatic insult that may rapidly progress to life-threatening conditions. Recently, menstrual blood stem cells (MenSCs) have been identified as a group of easily accessible mesenchymal stem cells with the advantages of non-invasive acquisition, low immunogenicity, a greater capacity of self-renewal and multi-lineage differentiation, making them promising candidates for stem cell-based therapy to revolutionize the treatment strategies for liver failure. AIM: To investigate the therapeutic potential of MenSCs for treating ALF in pigs and to dynamically trace the biodistribution of transplanted cells. METHODS: MenSCs were labeled in vitro with PKH26, a lipophilic fluorescent dye. The treatment group received immediate transplantation of PKH26-labelled MenSCs (2.5 × 106/kg) via the portal vein after D-galactosamine injection, and the control group underwent sham operation. The survival time, liver function, and hepatic pathological changes were compared between the two groups. Three major organs (liver, lungs and spleen) were extracted from animals and imaged directly with the In vivo Imaging System (IVIS) at the predetermined time points. The regions of interest were drawn to quantify the cell uptake in different organs. RESULTS: The labelling procedure did not affect the morphology, viability or multipotential differentiation of MenSCs. Biochemical analysis showed that the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and prothrombin time (PT) measured at selected time points 24 h after transplantation were significantly decreased in the treatment group (P < 0.05). The survival time of ALF animals was prolonged in the treatment group compared with the control group (75.75 ± 5.11 h vs 53.75 ± 2.37 h, log rank, P < 0.001). The liver pathological tissue in the MenSC treatment group showed obviously increased numbers of remaining hepatocytes and a comparatively slight necrotic degree and area. In addition, the IVIS imaging revealed that PKH26-positive MenSCs were clearly retained in the liver initially and then diffused through the systemic circulation. Interestingly, the signal intensity in the liver increased obviously at 36 h, which corresponded to the biochemical result that liver function deteriorated most rapidly at 24 - 36 h. CONCLUSION: Our study demonstrates the therapeutic efficacy and homing ability of transplanted MenSCs in a large animal model of ALF and suggests that MenSC transplantation could be a promising strategy for treating ALF.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31704080

RESUMO

BACKGROUND: For its better differentiated hepatocyte phenotype, C3A cell line has been utilized in bioartificial liver system. However, up to now, there are only a few of studies working at the metabolic alternations of C3A cells under the culture conditions with liver failure plasma, which mainly focus on carbohydrate metabolism, total protein synthesis and ureagenesis. In this study, we investigated the effects of acute liver failure plasma on the growth and biological functions of C3A cells, especially on CYP450 enzymes. METHODS: C3A cells were treated with fresh DMEM medium containing 10% FBS, fresh DMEM medium containing 10% normal plasma and acute liver failure plasma, respectively. After incubation, the C3A cells were assessed for cell viabilities, lactate dehydrogenase leakage, gene transcription, protein levels, albumin secretion, ammonia metabolism and CYP450 enzyme activities. RESULTS: Cell viabilities decreased 15%, and lactate dehydrogenase leakage had 1.3-fold elevation in acute liver failure plasma group. Gene transcription exhibited up-regulation, down-regulation or stability for different hepatic genes. In contrast, protein expression levels for several CYP450 enzymes kept constant, while the CYP450 enzyme activities decreased or remained stable. Albumin secretion reduced about 48%, and ammonia accumulation increased approximately 41%. CONCLUSIONS: C3A cells cultured with acute liver failure plasma showed mild inhibition of cell viabilities, reduction of albumin secretion, and increase of ammonia accumulation. Furthermore, CYP450 enzymes demonstrated various alterations on gene transcription, protein expression and enzyme activities.

12.
Cytotechnology ; 71(6): 1053-1061, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31559514

RESUMO

Enterovirus 71 (EV71) infection can cause hand-foot-and-mouth disease (HFMD). Inactivated EV71 vaccine was effective to prevent EV71 derived HFMD. A highly efficient and economical process for producing EV71 is needed. In our study, the epidemic strain of EV71 (EV71-2013ZJHFMD) was obtained and purified. The Vero cells were cultured for production of EV71. The mini-bioreactor vessel (Amprotein Inc., China) packed with a 0.6 g polymer fiber carrier was used to determine the best seeding cell density, multiplicity of infection (MOI) and temperature. Then the optimized procedure was further applied in a 10 L disposable perfusion bioreactor ACPB (AmProtein Current Perfusion Bioreactor). The Vero cell culture and viral titer were monitored. The seeding density of 1.5 × 107 cells per 0.6 g disk was considered to be the most appropriate for the culture. The best MOI was 0.1 and the temperature was 32 °C. The total cell number increased from 1.5 × 109 to 3.0 × 1010. The maximum viral titers reached 1.0 × 108/mL 3 days post-infection in our optimized special culture procedure (serum-free during the harvest period, supplemented with 0.25% Lactalbumin Hydrolysate). The total volume of the harvested supernatant was 25 L and the total virus yield was 1.93 × 1012. The procedure using Vero cells grown on polymer fiber paper carriers was effective for the large-scale production of EV71.

13.
World J Gastroenterol ; 25(33): 4999-5016, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31543689

RESUMO

BACKGROUND: Diarrhea is a major infectious cause of childhood morbidity and mortality worldwide. In clinical trials, Lactobacillus rhamnosus GG ATCC 53013 (LGG) has been used to treat diarrhea. However, recent randomized controlled trials (RCTs) found no evidence of a beneficial effect of LGG treatment. AIM: To evaluate the efficacy of LGG in treating acute diarrhea in children. METHODS: The EMBASE, MEDLINE, PubMed, Web of Science databases, and the Cochrane Central Register of Controlled Trials were searched up to April 2019 for meta-analyses and RCTs. The Cochrane Review Manager was used to analyze the relevant data. RESULTS: Nineteen RCTs met the inclusion criteria and showed that compared with the control group, LGG administration notably reduced the diarrhea duration [mean difference (MD) -24.02 h, 95% confidence interval (CI) (-36.58, -11.45)]. More effective results were detected at a high dose ≥ 1010 CFU per day [MD -22.56 h, 95%CI (-36.41, -8.72)] vs a lower dose. A similar reduction was found in Asian and European patients [MD -24.42 h, 95%CI (-47.01, -1.82); MD -32.02 h, 95%CI (-49.26, -14.79), respectively]. A reduced duration of diarrhea was confirmed in LGG participants with diarrhea for less than 3 d at enrollment [MD -15.83 h, 95%CI (-20.68, -10.98)]. High-dose LGG effectively reduced the duration of rotavirus-induced diarrhea [MD -31.05 h, 95%CI (-50.31, -11.80)] and the stool number per day [MD -1.08, 95%CI (-1.87, -0.28)]. CONCLUSION: High-dose LGG therapy reduces the duration of diarrhea and the stool number per day. Intervention at the early stage is recommended. Future trials are expected to verify the effectiveness of LGG treatment.


Assuntos
Diarreia/terapia , Lactobacillus rhamnosus , Probióticos/administração & dosagem , Criança , Diarreia/diagnóstico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Fatores de Tempo , Tempo para o Tratamento , Resultado do Tratamento
14.
Front Microbiol ; 10: 1751, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417535

RESUMO

Bacillus cereus (B. cereus) functions as a probiotic in animals, but the underlying mechanisms remain unclear. We aim to evaluate the protective effects and definite mechanism by which orally administered B. cereus prevents D-galactosamine (D-GalN)-induced liver injury in rats. Twenty-one Sprague-Dawley rats were equally assigned into three groups (N = 7 animals per group). B. cereus ATCC11778 (2 × 109 colony-forming units/ml) was administered to the B. cereus group via gavage, and phosphate-buffered saline was administered to the positive control (PC) and negative control (NC) groups for 2 weeks. The PC and B. cereus groups received 1.1 g/kg D-GalN via an intraperitoneal injection to induce liver injury. The blood, terminal ileum, liver, kidney and mesenteric lymph nodes (MLNs) were collected for histological examinations and to evaluate bacterial translocation. Liver function was also determined. Fecal samples were collected for deep sequencing of the 16S rRNA on an Illumina MiSeq platform. B. cereus significantly attenuated D-GalN-induced liver injury and improved serum alanine aminotransferase (ALT) and serum cholinesterase levels (P < 0.05 and P < 0.01, respectively). B. cereus modulated cytokine secretion, as indicated by the elevated levels of the anti-inflammatory cytokine interleukin-10 (IL-10) in both the liver and plasma (P < 0.05 and P < 0.01, respectively) and the substantially decreased levels of the cytokine IL-13 in the liver (P < 0.05). Pretreatment with B. cereus attenuated anoxygenic bacterial translocation in the veins (P < 0.05) and liver (P < 0.05) and upregulated the expression of the tight junction protein 1. The gut microbiota from the B. cereus group clustered separately from that of the PC group, with an increase in species of the Ruminococcaceae and Peptococcaceae families and a decrease in those of the Parabacteroides, Paraprevotella, and Desulfovibrio families. The potential probiotic B. cereus attenuated liver injury by restoring the gut flora balance and enhancing the intestinal barrier function.

15.
Front Microbiol ; 10: 1518, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333622

RESUMO

Emerging evidence suggests that altered intestinal microbiota plays an important role in the pathogenesis of many liver diseases, mainly by promoting inflammation via the "intestinal microbiota-immunity-liver" axis. We aimed to investigate the fecal microbiome of liver recipients with abnormal/normal liver function using 16S rRNA gene sequencing. Fecal samples were collected from 90 liver recipients [42 with abnormal liver function (Group LT_A) and 48 with normal liver function (Group LT_N)] and 61 age- and gender-matched healthy controls (HCs). Fecal microbiomes were analyzed for comparative composition, diversity, and richness of microbial communities. Principal coordinates analysis successfully distinguished the fecal microbiomes of recipients in Group LT_A from healthy subjects, with the significant decrease of fecal microbiome diversity in recipients in Group LT_A. Other than a higher relative abundance of opportunistic pathogens such as Klebsiella and Escherichia/Shigella in all liver recipients, the main difference in gut microbiome composition between liver recipients and HC was the lower relative abundance of beneficial butyrate-producing bacteria in the recipients. Importantly, we established a fecal microbiome index (specific alterations in Staphylococcus and Prevotella) that could be used to distinguish Group LT_A from Group LT_N, with an area under the receiver operating characteristic curve value of 0.801 and sensitivity and specificity values of 0.771 and 0.786, respectively. These findings revealed unique gut microbial characteristics of liver recipients with abnormal and normal liver functions, and identified fecal microbial risk indicators of abnormal liver function in liver recipients.

16.
Hepatobiliary Pancreat Dis Int ; 18(3): 237-241, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31029554

RESUMO

BACKGROUND: Cirrhotic patients are susceptible to Clostridium difficile infection (CDI), however, the high risk factors are not clear. The present study aimed to identify the risk factors in cirrhotic patients with CDI. METHODS: A total of 526 cirrhotic patients admitted to our hospital between May 2015 and October 2015 were included in this study. Stool samples were collected upon admission for the detection of CDI and toxin. CDI was monitored during the hospital stay. In total, 34 cases showed CDI. Then we analyzed the effects of age, sex, C. difficile colonization (CDC), multiple hospitalization, extended hospital stay, elevation of total bilirubin (TBIL), creatinine (Cr), Child-Pugh grade C, hepatic encephalopathy, hepatorenal syndrome, upper gastrointestinal hemorrhage, and exposure of antibiotics and proton pump inhibitor (PPI) on the CDI in cirrhotic patients. RESULTS: Patients in the CDI group had more frequent CDC, multiple hospitalization, and extended hospital stay compared to those in the non-C. difficile infection (NCDI) group. Patients in the CDI group had higher TBIL and Cr, and higher frequency of Child-Pugh grade C, hepatic encephalopathy, upper gastrointestinal hemorrhage compared with those in the NCDI group. Multiple logistic regression analysis indicated that age >60 years (OR=1.689; 95% CI: 1.135-3.128), multiple hospitalization (OR=3.346; 95% CI: 1.392-8.043), length of hospital stay >20 days (OR=1.564; 95% CI: 1.113-2.563), hypoproteinemia (OR=4.962; 95% CI: 2.053-11.996), CDC (OR=18.410; 95% CI: 6.898-49.136), hepatic encephalopathy (OR=1.357; 95% CI: 1.154-2.368), and exposure of antibiotics (OR=1.865; 95% CI: 1.213-2.863) and PPI (OR=3.125; 95% CI: 1.818-7.548) were risk factors of CDI. CONCLUSIONS: Age >60 years, multiple hospitalization, length of hospital stay >20 days, hypoproteinemia, CDC, hepatic encephalopathy, and exposure of antibiotics and PPI were risk factors for CDI in cirrhotic patients. These may contribute to the early diagnosis and monitoring of CDI in clinical practice.


Assuntos
Infecções por Clostridium/microbiologia , Cirrose Hepática/complicações , Adulto , Idoso , Antibacterianos/efeitos adversos , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/terapia , Feminino , Encefalopatia Hepática/etiologia , Humanos , Tempo de Internação , Cirrose Hepática/diagnóstico , Cirrose Hepática/terapia , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Readmissão do Paciente , Prognóstico , Inibidores da Bomba de Prótons/efeitos adversos , Medição de Risco , Fatores de Risco
17.
World J Gastroenterol ; 25(8): 941-954, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30833800

RESUMO

BACKGROUND: Fibrosis is the single most important predictor of significant morbidity and mortality in patients with chronic liver disease. Established non-invasive tests for monitoring fibrosis are lacking, and new biomarkers of liver fibrosis and function are needed. AIM: To depict the process of liver fibrosis and look for novel biomarkers for diagnosis and monitoring fibrosis progression. METHODS: CCl4 was used to establish the rat liver fibrosis model. Liver fibrosis process was measured by liver chemical tests, liver histopathology, and Masson's trichrome staining. The expression levels of two fibrotic markers including α-smooth muscle actin and transforming growth factor ß1 were assessed using immunohistochemistry and real-time polymerase chain reaction. Dynamic changes in metabolic profiles and biomarker concentrations in rat serum during liver fibrosis progression were investigated using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The discriminatory capability of potential biomarkers was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: To investigate the dynamic changes of metabolites during the process of liver fibrosis, sera from control and fibrosis model rats based on pathological results were analyzed at five different time points. We investigated the association of liver fibrosis with 21 metabolites including hydroxyethyl glycine, L-threonine, indoleacrylic acid, ß-muricholic acid (ß-MCA), cervonoyl ethanolamide (CEA), phosphatidylcholines, and lysophosphatidylcholines. Two metabolites, CEA and ß-MCA, differed significantly in the fibrosis model rats compared to controls (P < 0.05) and showed prognostic value for fibrosis. ROC curve analyses performed to calculate the area under the curve (AUC) revealed that CEA and ß-MCA differed significantly in the fibrosis group compared to controls with AUC values exceeding 0.8, and can clearly differentiate early stage from late stage fibrosis or cirrhosis. CONCLUSION: This study identified two novel biomarkers of fibrosis, CEA and ß-MCA, which were effective for diagnosing fibrosis in an animal model.


Assuntos
Cirrose Hepática/metabolismo , Fígado/patologia , Metabolômica/métodos , Animais , Área Sob a Curva , Biomarcadores/metabolismo , Ácidos Cólicos/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Modelos Animais de Doenças , Progressão da Doença , Etanolaminas/metabolismo , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Testes de Função Hepática , Metaboloma , Prognóstico , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos
19.
Front Microbiol ; 9: 2724, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30483236

RESUMO

Ebolavirus (EBOV) life cycle involves interactions with numerous host factors, but it remains poorly understood, as does pathogenesis. Herein, we synthesized 65 siRNAs targeting host genes mostly connected with aspects of the negative-sense RNA virus life cycle (including viral entry, uncoating, fusion, replication, assembly, and budding). We produced EBOV transcription- and replication-competent virus-like particles (trVLPs) to mimic the EBOV life cycle. After screening host factors associated with the trVLP life cycle, we assessed interactions of host proteins with trVLP glycoprotein (GP), VP40, and RNA by co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP). The results demonstrate that RNAi silencing with 11 siRNAs (ANXA5, ARFGAP1, FLT4, GRP78, HSPA1A, HSP90AB1, HSPA8, MAPK11, MEK2, NTRK1, and YWHAZ) decreased the replication efficiency of trVLPs. Co-IP revealed nine candidate host proteins (FLT4, GRP78, HSPA1A, HSP90AB1, HSPA8, MAPK11, MEK2, NTRK1, and YWHAZ) potentially interacting with trVLP GP, and four (ANXA5, GRP78, HSPA1A, and HSP90AB1) potentially interacting with trVLP VP40. Ch-IP identified nine candidate host proteins (ANXA5, ARFGAP1, FLT4, GRP78, HSPA1A, HSP90AB1, MAPK11, MEK2, and NTRK1) interacting with trVLP RNA. This study was based on trVLP and could not replace live ebolavirus entirely; in particular, the interaction between trVLP RNA and host proteins cannot be assumed to be identical in live virus. However, the results provide valuable information for further studies and deepen our understanding of essential host factors involved in the EBOV life cycle.

20.
Cell Physiol Biochem ; 50(3): 1055-1067, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30355918

RESUMO

BACKGROUND/AIMS: Monoclonal antibodies (mAbs) are presently the most promising treatment against Ebola virus disease (EVD), and cocktail of two or more antibodies likely confers protection through complementary mechanisms. Zaire Ebolavirus (EBOV) glycoprotein (GP) and viral protein 40 (VP40) are targets for designing neutralizing antibodies. Currently, the antiviral therapeutics of mAb-cocktails are still limited solely to anti-GP antibodies,there is no Abs cocktail against Zaire EBOV GP and VP40, which both have important interactions with host cellular membrane. METHODS: We used hybridoma technology to produce anti-Zaire EBOV GP mAb against GP receptor binding domain, and anti-Zaire EBOV VP40 mAbs against the N-terminal domain, the C-terminal domain, respectively; synthesized Zaire EBOV transcription and replication competent virus like particles (trVLPs), which model even all aspects of the EBOV life cycles in order to evaluate the anti-viral effect of mAbs. Then, we characterized the anti- Zaire EBOV trVLPs effect of anti-GP and VP40 mAbs in vitro by real time-PCR, immunofluorescence assay and western blot analysis. RESULTS: Our results demonstrate that anti-GP or anti-VP40 mAbs effectively inhibit trVLPs replication. The cocktails of anti-GP and anti-VP40 mAbs, or between anti-VP40 mAbs, had synergistic anti-trVLPs effect. Meanwhile, the detailed DNA and amino acid sequences of the mAbs were checked. CONCLUSION: The study verifies neutralizing efficacy of anti-GP or anti-VP40 mAb, report promising cocktail of anti-GP and anti-VP40 mAb, or cocktail of two anti-VP40 mAbs. To our knowledge, this is the first account to report the important anti-viral effect of cocktails of anti-GP and anti-VP40 mAbs in vitro.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Ebolavirus/metabolismo , Glicoproteínas/imunologia , Proteínas Virais/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/química , Anticorpos Antivirais/química , Reações Antígeno-Anticorpo , Glicoproteínas/genética , Glicoproteínas/metabolismo , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Virais/genética , Proteínas Virais/metabolismo
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