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1.
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.

2.
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.

3.
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
4.
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
5.
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.

6.
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
7.
Medicine (Baltimore) ; 97(38): e12403, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30235711

RESUMO

Hepatitis C virus (HCV) is one of the most important virus as the cause of liver disease in China. The aim of the present study was to explore whether sofosbuvir and ribavirin-based treatment can cure patients with chronic hepatitis C in eastern China. We examined a cohort of HCV-monoinfected patients and 9 patients agreed to participate in our treatment and research. The patients were diagnosed with chronic hepatitis C with or without cirrhosis. Nine patients including 4 female and 5 male met the requirements for selection and were willing to participate in this experiment. Sofosbuvir and ribavirin-based treatment with or without interferon was given to the patients. Viral loads, cytokines, and chemokines were recorded during treatment and after treatment. After 2 weeks of sofosbuvir and ribavirin-based treatment, the viral load of patients decreased to limits of detection. Eight patients were cured. Patients had rapid virological response (RVR) with undetectable viral load at week 4 and sustained virological response (SVR). The interferon-inducible protein-10 (IP-10) decreased after the treatment. However, the patient with cirrhosis failed, as the virus reappeared during SVR4. At the same time, the IP-10 dramatically increased as the relapse of the HCV virus. In summary, the IP-10 has the potential to be the biomarker for the prognostic of HCV.


Assuntos
Antivirais/administração & dosagem , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Adulto , China , Quimioterapia Combinada , Feminino , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resposta Viral Sustentada , Carga Viral , Adulto Jovem
8.
Int J Endocrinol ; 2018: 2314769, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30151008

RESUMO

The present study evaluated the potential combined effects of NAFLD and MetS on the development of osteoporosis. The relationship between NAFLD and MetS and osteoporosis was assessed in 938 postmenopausal female participants. Moderate and severe NAFLDs were combined as significant NAFLD (SNAFLD). All the subjects were divided into 4 subgroups based on the status of SNAFLD and MetS. Relative excess risk of interaction (RERI), attributable proportion (AP) of interaction, and synergy index (SI) were used to investigate the additive interaction of those two factors. NAFLD, SNAFLD, and MetS were independent factors for osteoporosis with the adjustment of age and other confounders. The incidence of osteoporosis in MetS (+) SNAFLD (+) group was significantly higher than that in other three groups. RERI was 2.556 (95% CI = 0.475-4.636), AP was 0.454 (95% CI = 0.201-0.706), and SI was 2.231 (95% CI = 1.124 to 4.428), indicating the significant combined interaction of SNAFLD and MetS on the development of osteoporosis. SNAFLD and MetS are independent risk factors for osteoporosis in postmenopausal females, respectively. Moreover, SNAFLD and MetS have an additive effect on the development of osteoporosis.

9.
Appl Microbiol Biotechnol ; 102(15): 6469-6477, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29858958

RESUMO

Recombinant adenoviral (Ad) vectors are highly efficient gene transfer vectors widely used in vaccine development and immunotherapy. To promote the industrial application of Ad vectors, studies focusing on reducing the cost of manufacturing, shortening the preclinical research period, and improving the quality of products are needed. Here, we describe a highly efficient and economical process for producing Ad vector in a novel, single-use bioreactor system suitable for clinical trials. A mini-bioreactor was used for parameter optimization and development of medium replacement protocols for Ad5-GFP production before scale-up. HEK293 cell culture and virus infection were monitored in a disposable AmProtein Current Perfusion Bioreactor and Bioflo310 bioreactor using optimized parameters and medium replacement protocols. The total cell number increased from 2.0 × 109 to 3.2 × 1010 after 6 days of culture. The total number of viral particles obtained in a single batch was 1.2 × 1015. These results demonstrate the efficiency and suitability of this system for Ad vector production for research and GMP applications.


Assuntos
Adenoviridae/fisiologia , Reatores Biológicos , Técnicas de Cultura de Células/instrumentação , Terapia Genética/instrumentação , Vetores Genéticos/fisiologia , Microbiologia Industrial/instrumentação , Microbiologia Industrial/métodos , Células HEK293 , Humanos
10.
Cell Physiol Biochem ; 46(2): 633-643, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29617693

RESUMO

BACKGROUND/AIMS: Since the first case of novel H7N9 infection was reported, China has experienced five epidemics of H7N9. During the fifth wave, a highly pathogenic H7N9 strain emerged. In order to assess whether the H7N9 vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) was effective in protecting against highly pathogenic H7N9, we conducted this study. METHODS: Groups of mice were immunized twice by intraperitoneal injection with 500 µl of either split vaccine alone or MF59-adjuvanted vaccine. Serum was collected 2 weeks after the second vaccine booster. The hemagglutinin inhibition test was conducted on vaccine seed and highly pathogenic H7N9 to evaluate the neutralization of highly pathogenic H7N9. We also immunized mice and challenged them with highly pathogenic H7N9. Mice were observed for illness, weight loss, and death at 1 week and 2 weeks post-infection. Then, the mice were sacrificed and lungs were removed. Antibody responses were assessed and pathological changes in the lung tissue were evaluated. RESULTS: The ability of serum to neutralize highly pathogenic H7N9 was reduced. In mice, highly pathogenic H7N9 was more virulent than A/Zhejiang/DTID-ZJU01/2013(H7N9). After challenge with highly pathogenic H7N9, all mice died while mice challenged with A/Zhejiang/DTID-ZJU01/2013(H7N9) all recovered. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine was able to protect against infection with highly pathogenic H7N9 in mice, with or without MF59. Moreover, H7N9 vaccine adjuvanted with MF59 produced high antibody levels, which lead to better protection. CONCLUSIONS: The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) is effective in protecting against highly pathogenic H7N9. H7N9 vaccine adjuvanted with MF59 offers better protection against infection with highly pathogenic H7N9. In order to make the H7N9 vaccine applicable to humans, further clinical trials are required to evaluate MF59 adjuvanted vaccine. Meanwhile, the vaccine strain should be updated based on the highly pathogenic H7N9 gene sequence.


Assuntos
Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Cães , Ensaio de Imunoadsorção Enzimática , Feminino , Hemaglutininas/análise , Hemaglutininas/imunologia , Pulmão/patologia , Pulmão/virologia , Células Madin Darby de Rim Canino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Infecções por Orthomyxoviridae/imunologia , Polissorbatos , RNA Viral/genética , RNA Viral/isolamento & purificação , RNA Viral/metabolismo , Esqualeno/imunologia
11.
Sci Rep ; 8(1): 972, 2018 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-29343809

RESUMO

Whether smoking and metabolic syndrome (MetS) can affect colorectal carcinoma (CRC) prognosis remains debatable. Therefore, the present study aimed to examine the individual and combined effects of smoking and MetS on the prognosis of patients with localized CRC, including stage I to III disease. The relationship among smoking status, MetS, and CRC was assessed in 838 Chinese male patients. Cox proportional hazards regression analysis was used to evaluate CRC prognosis adjusted for clinicopathological variables. Relative excess risk of interaction (RERI), attributable proportion (AP), and synergy index (SI) were used to evaluate additive interactions between smoking and MetS. The presence of MetS was an independent risk factor for low rates of recurrence-free survival (RFS) but not for overall survival (OS). However, smoking was independently associated with both poor RFS and OS. Furthermore, the recurrence risk for current smokers with MetS was 1.62 times as high as the sum of risks in patients exposed to each risk factor alone. In conclusion, current smoking habit is a risk factor for both recurrence and cancer-specific mortality in CRC patients, while MetS is an independent predictor for CRC recurrence. Furthermore, these two factors have an additive effect on the recurrence risk of CRC.


Assuntos
Neoplasias Colorretais/etiologia , Síndrome Metabólica/complicações , Recidiva Local de Neoplasia/etiologia , Fumar/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Neoplasias Colorretais/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco
12.
Oncotarget ; 8(33): 55750-55759, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28903457

RESUMO

Ebola haemorrhagic fever causes deadly disease in humans and non-human primates resulting from infection with the Ebola virus (EBOV) genus of the family Filoviridae. However, the mechanisms of EBOV lifecycle in host cells, including viral entry, membrane fusion, RNP formation, GP-tetherin interaction, and VP40-inner leaflet association remain poorly understood. This review describes the biological functions of EBOV proteins and their roles in the lifecycle, summarizes the factors related to EBOV proteins or RNA expression throughout the different phases, and reviews advances with regards to the molecular events and mechanisms of the EBOV lifecycle. Furthermore, the review outlines the aspects remain unclear that urgently need to be solved in future research.

13.
Cell Physiol Biochem ; 37(5): 1641-58, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26535889

RESUMO

Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD) in humans and non-human primates (NHPs). Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs), vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV)-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirusx2206;VP30, recombinant cytomegalovirus (CMV)-based vaccines, recombinant rabies virus (RABV)-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV)-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD.


Assuntos
Vacinas contra Ebola/imunologia , Ebolavirus/genética , Doença pelo Vírus Ebola/prevenção & controle , Ebolavirus/metabolismo , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Doença pelo Vírus Ebola/patologia , Doença pelo Vírus Ebola/virologia , Humanos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Vacinas de Partículas Semelhantes a Vírus/genética , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/metabolismo , Proteínas Virais/genética , Proteínas Virais/imunologia , Proteínas Virais/metabolismo
14.
Int J Infect Dis ; 41: 3-5, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26482389

RESUMO

In January 2015, there was an outbreak of avian-origin influenza A (H7N9) virus in Zhejiang Province, China. A 45-year-old man was admitted to the First Affiliated Hospital of Zhejiang University with a high fever that had lasted 7 days, chills, and a cough with yellow sputum. Laboratory testing confirmed infection with the H7N9 virus, likely obtained from contact with poultry at a local live poultry market. A large dense shadow was apparent in the patient's left lung at the time of admission. Treatment with oseltamivir (75mg twice daily) did not improve the patient's condition. The decision was made to try using convalescent plasma to treat the infection. Convalescent plasma was administered 3 days after the patient was admitted to the hospital and led to a marked improvement. To our knowledge, this is the first report of the successful use of convalescent plasma to treat a case of H7N9 infection in China. These results suggest that the combination of convalescent plasma and antiviral drugs may be effective for the treatment of avian-origin H7N9 infection.


Assuntos
Transfusão de Componentes Sanguíneos , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Influenza Humana/terapia , Influenza Humana/virologia , Plasma , Antivirais/uso terapêutico , China/epidemiologia , Surtos de Doenças , Humanos , Masculino , Pessoa de Meia-Idade , Oseltamivir/uso terapêutico
15.
Int J Infect Dis ; 29: 254-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25462187

RESUMO

OBJECTIVES: In the winter of 2013, people were facing the risk of human-to-human transmission of the re-emerging influenza A(H7N9) virus. We report herein information on the clinical features of two patients from the same family infected with this virus, the genomic sequences of the viruses harbored, and antiviral drug sensitivity. METHODS: Clinical and epidemiological data of two patients from the same family were collected and analyzed. Sequencing was done for the viruses isolated from these two patients and one epidemiologically related chicken, and the sequences of the eight gene segments of the viruses were analyzed phylogenetically. The sensitivity of the viruses to antiviral drug treatment was determined by neuraminidase inhibitor susceptibility test. RESULTS: The two patients from one family cluster shared the same symptoms but had different outcomes, and had a strong epidemiological link. Three strains, two from these two patients and one from the chicken, were isolated. Genome sequencing and analyses of phylogenetic trees demonstrated that the two viruses were almost identical. We noted the presence of the PB2 E627K amino acid substitution that was not present in isolates from the first wave, as well as two new mutations in the NA gene and six in the PB2 gene. Drug sensitivity testing showed that the new isolates were resistant to oseltamivir but sensitive to peramivir. CONCLUSIONS: The two patients from one family cluster were probable human-to-human transmission cases. The new isolates were sensitive to peramivir but showed reduced sensitivity to oseltamivir.


Assuntos
Subtipo H7N9 do Vírus da Influenza A/efeitos dos fármacos , Subtipo H7N9 do Vírus da Influenza A/genética , Influenza Humana/virologia , Substituição de Aminoácidos , Antivirais/farmacologia , China , Farmacorresistência Viral , Feminino , Genoma Viral , Humanos , Subtipo H7N9 do Vírus da Influenza A/classificação , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Oseltamivir/farmacologia , Filogenia
16.
Neuropharmacology ; 59(1-2): 70-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20381504

RESUMO

Icariin (ICA) has neuroprotection in oxygen-glucose deprivation (OGD) neurons by increasing Sirtuin1 (SIRT1). However, little is known about the role of ICA on stroke. SIRT1 is a class III histone deacetylase and activates peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) which stimulates mitochondrial activity. This study aims to investigate the expression of SIRT1 and PGC-1alpha during ICA's neuroprotection against ischemia. In vivo, behavioral test, infarct size and brain water content were evaluated on middle cerebral artery occlusion (MCAO) mouse models treated by ICA/saline. In vitro, primary cortical neurons were tortured by OGD in the presence of ICA or SIRT1 inhibitor III or PGC-1alpha siRNA. Cell viability and mortality were measured by MTT and flow cytometer assay. Knockdown efficiency of PGC-1alpha siRNA was measured by real time PCR. Expressions of SIRT1 and PGC-1alpha were also investigated. In result, neurological scores, infarct size and brain edema were all significantly improved, the cortical expressions of SIRT1 and PGC-1alpha were higher with ICA compared to the control (P < 0.05), and reversed by SIRT1 inhibitor III/PGC-1alpha siRNA. In conclusion, ICA protects against brain ischemic injury by increasing the SIRT1 and PGC-1alpha expression, potentially to be a neuroprotectant for ischemic brain injury.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Flavonoides/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Sirtuína 1/metabolismo , Transativadores/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Edema Encefálico/tratamento farmacológico , Edema Encefálico/metabolismo , Edema Encefálico/patologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/prevenção & controle , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Flavonoides/administração & dosagem , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/administração & dosagem , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Distribuição Aleatória , Sirtuína 1/antagonistas & inibidores , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Fatores de Transcrição
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