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1.
Ann Med ; 56(1): 2307504, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38465636

RESUMO

BACKGROUND: Despite the widespread administration of coronavirus disease 2019 (COVID-19) vaccines, the impact on patients with asymptomatic to mild illness remains unclear. Here, we aimed to assess the efficacy of various vaccine doses and types on the duration of isolation duration and discharge rates, the viral shedding duration, and negative rates in asymptomatic to mild COVID-19 patients. METHODS: We included adult patients at the Fangcang isolation centres in Pazhou or Yongning between November and December 2022. We analysed data on basic demographics, admission details, laboratory indicators and vaccination information. RESULTS: A total of 6560 infected patients were included (3584 from Pazhou and 2976 from Yongning). Of these, 90.6% received inactivated vaccines, 3.66% received recombinant SARS-CoV-2 spike protein subunit vaccines and 0.91% received adenovirus vaccines. Among the 6173 vaccinated individuals, 71.9% received a booster dose. By day 9, the isolation rate reached 50% among vaccinated patients. On day 7.5, the positive rate among vaccinated individuals reached 50%. CONCLUSIONS: Full vaccination was effective, with heterologous vaccines showing greater efficacy than inactivated vaccines alone. However, there was no significant difference in the vaccine protective effect 12 months after vaccination.


Assuntos
COVID-19 , Glicoproteína da Espícula de Coronavírus , Adulto , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos Retrospectivos , SARS-CoV-2 , Vacinação , Vacinas de Produtos Inativados
2.
Microbes Infect ; : 105307, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38309574

RESUMO

Bacterial DeoR family transcription regulators regulate multiple physiological processes. Little is known about the function of DeoR family regulators in streptococci. Here, we identified a novel DeoR family regulator, GlpR, from Streptococcus suis, a pathogen causing severe diseases in pigs and humans. GlpR was involved in glycerol utilization and exhibited specific signature residues at positions 30-31 (KV) which are crucial for DNA binding. Deletion of glpR (ΔglpR) showed a significant increase in relative growth rate in glycerol medium compared to the wild-type (WT) and complementary strains (CΔglpR). Employing RNA-seq analysis, ß-galactosidase activity analysis, and electrophoretic mobility shift assay, we discovered that GlpR directly represses the expression of glycerol metabolism-related genes pflB2, pflA1, and fsaA, encoding pyruvate formate-lyase and its activating enzyme, and fructose-6-phosphate aldolase, respectively. Compared to WT and CΔglpR, ΔglpR showed a reduced survival rate under oxidative stress and in murine macrophages and attenuated virulence in mice. GlpR probably enhances oxidative stress resistance and virulence in S. suis by functioning as a glycerol metabolic repressor decreasing energy consumption. These findings contribute to a better understanding of S. suis pathogenesis and enrich our knowledge of the biological functions of DeoR family regulators in streptococci.

3.
Toxicon ; 235: 107317, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37839739

RESUMO

Patients envenomed by snakes from the Viperidae and Elapidae families in China often have varying degrees of local tissue necrosis. Due to the relative clinical characteristics of local tissue necrosis and ulceration following envenoming, this study has analyzed the proteome of six snake venoms from the Viperidae and Elapidae family, and the toxin profiles of each snake were compared and correlated with the clinical manifestations that follow cytotoxic envenoming. Deinagkistrodon acutus and Naja atra envenomation induce severe ulceration, which is absent in Bungarus multicinctus envenomation and mild in the other three vipers. It is interesting to note that the proportion of c-type lectins (CTL) (20.63%) in Deinagkistrodon acutus venom was relatively high, which differs from the venom of other vipers. In addition, three-fingered toxin (3FTx) (2.15%) is present in the venom of Deinagkistrodon acutus, but has not been detected in the remaining three vipers. Snake venom metalloprotease (SVMP) (34.4%-44.7%), phospholipase A2 (PLA2) (9.81%-40.83%), and snake venom serine protease (SVSP) (9.44%-16.2%) represent the most abundant families of toxin in Viperidae venom. The Elapidae venom proteome was mainly composed of neurotoxins and cytotoxins, including 3FTx (39.28%-60.08%) and PLA2 (8.24%-58.95%) toxins, however, the proportion of CRISPS (26.36%) in Naja atra venom was relatively higher compared to Bungarus multicinctus venom. Significant differences in SVMP, SVSP, and 3FTx expression levels exist between the Viperidae and the Elapidae family. The main toxins responsible for the development of tissue necrosis and ulcerations following Viperidae envenoming are hematotoxins (SVSMP, SVSP) and myotoxins (PLA2). Deinagkistrodon acutus venom contains high levels of CTL and traces of 3FTx, leading to more severe local necrosis. However, Naja atra venom can also cause severe local necrosis through the effects of myotoxin (3FTx, CRISP, PLA2). Bungarus multicinctus venom does not contain myotoxins, resulting in pure systemic neurological manifestations no obvious necrosis of local tissue in patients.


Assuntos
Elapidae , Viperidae , Animais , Humanos , Elapidae/metabolismo , Viperidae/metabolismo , Neurotoxinas/metabolismo , Proteômica/métodos , Proteoma/metabolismo , Venenos de Serpentes/metabolismo , Venenos Elapídicos/toxicidade , Venenos Elapídicos/metabolismo , Naja naja/metabolismo , Fosfolipases A2/toxicidade , Fosfolipases A2/metabolismo
4.
Virulence ; 14(1): 2249789, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37621097

RESUMO

Streptococcus suis is a bacterium that can cause infections in pigs and humans. Although oxidative stress is common occurrence during bacterial growth and infection, the regulation networks of S. suis under oxidative stress remain poorly understood. To address this, we utilized RNA-Seq to reveal the transcriptional landscape of S. suis in response to H2O2 stress. We identified novel genes responsible for S. suis resistance to oxidative stress, including those involved in DNA repair or protection, and essential for the biosynthesis of amino acids and nucleic acids. In addition, we found that a novel aquaporin, Aagp, belonging to atypical aquaglyceroporins and widely distributed in diverse S. suis serotypes, plays a crucial role during H2O2 stress. By performing oxidative stress assays and measuring the intracellular H2O2 concentrations of the wild-type strain and Aagp mutants during H2O2 stress, we found that Aagp facilitated H2O2 efflux. Additionally, we found that Aagp might be involved in glycerol transport, as shown by the growth inhibition and H2O2 production in the presence of glycerol. Mice infection experiments indicated that Aagp contributed to S. suis virulence. This study contributes to understanding the mechanism of S. suis oxidative stress response, S. suis pathogenesis, and the function of aquaporins in prokaryotes.


Assuntos
Aquaporinas , Streptococcus suis , Humanos , Animais , Camundongos , Suínos , Peróxido de Hidrogênio/farmacologia , Streptococcus suis/genética , Glicerol , Virulência , Aquaporinas/genética
5.
Virulence ; 13(1): 781-793, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35481413

RESUMO

Streptococcus suis can cause severe infections in pigs and humans. The tonsils of pigs are major niches for S. suis, and different serotypes of S. suis can be found in the same tonsil. Pig tonsil colonization by S. suis is believed to be an important source of infection for humans and pigs. However, how S. suis competes for a stable tonsil niche is unknown. Here, we found that S. suis strain WUSS351, isolated from a healthy pig tonsil, is virulent and multidrug-resistant. The ABC transporter system SstFEG, conferring resistance to bacitracin, was reported to confer a competitive survival advantage in vivo. In addition, strain WUSS351 has several antimicrobial systems, including a novel type VII secretion system (T7SS), lantibiotic bacteriocin, and lactococcin972-like bacteriocin Lcn351. Bacterial competition experiments demonstrated T7SS-mediated cell contact-dependent antagonism of S. suis. Antibacterial activity analysis and 16S rRNA gene sequencing of the culture-independent and culture-dependent pig tonsillar microbiome revealed that Lcn351 mainly targets S. suis, one of the core microbiomes in pig tonsils. Taken together, our results revealed the mechanism of the stable persistence of S. suis in the tonsil niche, which might have important implications for S. suis epidemiology, potentially influencing strain prevalence and disease progression.


Assuntos
Bacteriocinas , Streptococcus suis , Animais , Antibacterianos/farmacologia , Bacteriocinas/genética , Bacteriocinas/farmacologia , Tonsila Palatina/microbiologia , RNA Ribossômico 16S , Suínos
6.
BMC Emerg Med ; 22(1): 9, 2022 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-35045831

RESUMO

BACKGROUND: Green pit vipers (GPVs), namely Trimeresurus albolabris and Trimeresurus stejnegeri accounts for most snakebites in Southern China. Green pit viper venom contains thrombin-like enzymes, resulting in defibrination syndrome. Using of clotting factor replacement after antivenom administration is controversial. The objective of this study was to investigate the effects of clotting factor replacement in coagulopathic patients with T. albolabris and T. stejnegeri bites after antivenom administration. METHODS: We retrospectively reviewed 123 patients who were bitten by T. albolabris and T. stejnegeri and were admitted to the Emergency Department of a hospital in Guangzhou, Southern China, from 2013 to 2019. Recovery of prothrombin time (PT) and fibrinogen level were compared among (1) fresh-frozen plasma (FFP) group; (2) cryoprecipitate (cryo) group; (3) FFP and cryo group; and (4) control group after antivenom administration. RESULTS: The incidence of coagulopathy was 31%. Persistent and late coagulopathy were the most common patterns among four groups. The median reduction in PT was 20.1 ± 31.2 s for FFP and cryo group. The median increase in fibrinogen level was very small: 0.05 ± 0.20 g/L for FFP group, 0.09 ± 0.37 g/L for cryo group and 0.07 ± 0.31 g/L for FFP and cryo group, respectively. The percentage of unimproved PT was markedly higher in the FFP and cryo group than the control group (P = 0.01 by log-rank test, P = 0.02 by Gehan-Breslow-Wilcoxon test). The percentage of unimproved fibrinogen level tended to be worse in the FFP and cryo group than the control group, but the different was marginal (P = 0.05 by Gehan-Breslow-Wilcoxon test, P = 0.07 by log-rank test). A total of 7.8% (7/90) of the patients in the clotting factor replacement groups developed anaphylaxis and heart failure. CONCLUSION: There is no improvement in coagulopathy profile in patients with T. albolabris and T. stejnegeri bites who received clotting factor replacement after antivenom administration. But the results from GPVs may not be generalized to other species of venomous snakes.


Assuntos
Mordeduras de Serpentes , Trimeresurus , Animais , Antivenenos/farmacologia , Antivenenos/uso terapêutico , Fatores de Coagulação Sanguínea/uso terapêutico , Fibrinogênio , Humanos , Estudos Retrospectivos , Mordeduras de Serpentes/tratamento farmacológico
7.
Transbound Emerg Dis ; 69(5): 2609-2620, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34871467

RESUMO

Streptococcus pasteurianus, an underreported opportunistic pathogen, is considered an increasingly recognized cause of meningitis and bacteremia in many animals and humans worldwide. However, except for some epidemiological studies, there is no report about the gene-deletion mutagenesis, virulence factors, reservoir niches or animal infection models for this pathogen. In this study, we first isolated an S. pasteurianus strain from a newly weaned piglet's brain with meningitis. The genomic sequence of this swine isolate WUSP067 shared high homology with that of two human strains. The comparative genome analysis showed that strain WUSP067 contained a fucose utilization cluster absent in human strains, and it shared 91% identity with that of an integrative and conjugative element (ICE) ICEssuZJ20091101-2 from Streptococcus suis, another important swine bacterial pathogen. Strain WUSP067 was resistant to erythromycin, tulathromycin, lincomycin, clindamycin, doxycycline and gentamycin, and ICEs are vehicles for harbouring antimicrobial resistance genes. The infection model was established using the 3-week-old newly weaned ICR mice. The 50% lethal dose value of strain WUSP067 was 4.0 × 107 colony-forming units per mouse. The infected mice showed severe signs of meningitis and pathological changes in brains. Furthermore, the capsule-deficient mutant was generated using natural transformation, and we showed that capsule was an essential virulence factor for S. pasteurianus. In addition, we found that tonsils and hilar lymph nodes of healthy pigs may be reservoir niches for this bacterium. Thus, our study provided valuable information about the pathogenetic characteristics and antimicrobial resistance of S. pasteurianus and paved the way for studying its pathogenesis.


Assuntos
Meningite , Doenças dos Roedores , Infecções Estreptocócicas , Streptococcus suis , Doenças dos Suínos , Animais , Clindamicina , Doxiciclina , Eritromicina , Fucose , Gentamicinas , Humanos , Meningite/veterinária , Camundongos , Camundongos Endogâmicos ICR , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/veterinária , Streptococcus , Streptococcus suis/genética , Suínos , Doenças dos Suínos/microbiologia , Fatores de Virulência/genética
8.
Vet Microbiol ; 259: 109149, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34147764

RESUMO

Streptococcus suis is a zoonotic pathogen that can cause invasive infections in humans and pigs. The S. suis cps31 strains (SS31) were frequently isolated from healthy or diseased pigs and one human infection case caused by SS31 was reported in Thailand in 2015. However, except for a few epidemiologic studies, little information is available for SS31. To characterize SS31, a total of 75 SS31 strains were analyzed, including 52 strains that were isolated from healthy or diseased pigs and 23 strains whose information was accessed from NCBI. The MLST analysis showed that SS31 exhibited high heterogeneity. The phylogenetic analysis and minimum core-genome (MCG) classification revealed that 75 strains were clustered into 3 lineages. Strains from NCBI mainly at Lineage 2 belong to MCG7-3, and most of strains from China at Lineage 3 belong to MCG7-2. This finding indicated that their evolutionary path was different. All SS31 strains were resistant to more than three classes of antimicrobial agents, and major antimicrobial resistance genes for strains from Lineage 3 were carried by prophages. This observation is different from the previous observation that integrative conjugative elements and integrative and mobilizable elements are major vehicles of antimicrobial resistance genes for S. suis. In addition to strains isolated from diseased pigs, seven of 47 strains isolated from clinically healthy pigs were also pathogenic in a zebrafish infection model. These findings reveal unique characteristics of SS31 and contribute to establishing public health surveillance for SS31 and clarifying the diversity of S. suis.


Assuntos
Antibacterianos/farmacologia , Filogenia , Infecções Estreptocócicas/veterinária , Streptococcus suis/efeitos dos fármacos , Streptococcus suis/patogenicidade , Animais , Farmacorresistência Bacteriana Múltipla , Evolução Molecular , Genótipo , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Infecções Estreptocócicas/microbiologia , Streptococcus suis/classificação , Streptococcus suis/genética , Suínos , Doenças dos Suínos/microbiologia , Virulência/genética , Peixe-Zebra
9.
Emerg Med Int ; 2020: 4973878, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343939

RESUMO

The purpose of this meta-analysis was to compare the efficacy and safety of prone versus supine position ventilation for adult acute respiratory distress syndrome (ARDS) patients. The electronic databases of PubMed, Embase, and the Cochrane Library were systematically searched from their inception up to September 2020. The relative risks (RRs) and weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were employed to calculate pooled outcomes using the random-effects models. Twelve randomized controlled trials that had recruited a total of 2264 adults with ARDS were selected for the final meta-analysis. The risk of mortality in patients who received prone position ventilation was 13% lower than for those who received supine ventilation, but this effect was not statistically significant (RR: 0.87; 95% CI: 0.75-1.00; P = 0.055). There were no significant differences between prone and supine position ventilation on the duration of mechanical ventilation (WMD: -0.22; P = 0.883) or ICU stays (WMD: -0.39; P = 0.738). The pooled RRs indicate that patients who received prone position ventilation had increased incidence of pressure scores (RR: 1.23; P = 0.003), displacement of a thoracotomy tube (RR: 3.14; P = 0.047), and endotracheal tube obstruction (RR: 2.45; P = 0.001). The results indicated that prone positioning during ventilation might have a beneficial effect on mortality, though incidence of several adverse events was significantly increased for these patients.

10.
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 , COVID-19 , 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 , SARS-CoV-2 , Adulto Jovem
11.
J Cell Physiol ; 235(4): 3447-3462, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31544976

RESUMO

Toll-like receptors (TLRs) are present in the ovaries and reproductive tract of various mammals. The biological function of TLR during ovulation is one of the main contents in the research of reproductive immunology. In this study, we found that messenger RNA levels of TLR1-TLR10 in granulosa cells were different, and TLRs and high mobility group box 1 (HMGB1) in granulosa cells of large follicles were significantly higher than those of small and middle follicles. Coimmunoprecipitation results showed that HMGB1 interacts with TLR2 in granulosa cells, especially large follicles. The result of immunohistochemistry showed that TLRs and HMGB1 were present in granulosa cell layer of ovarian follicles. We also found 25 mIU/ml follicle-stimulating hormone (FSH) significantly upregulated the expression of TLRs and HMGB1. These results suggest that TLR2/4 and HMGB1 in granulosa cells may be involved in the ovarian innate immune and ovarian follicular maturation, regulated by FSH. However, further research of the function and mechanisms of TLRs and HMGB1 in granulosa cells are needed.


Assuntos
Proteína HMGB1/genética , Folículo Ovariano/metabolismo , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Animais , Bovinos , Feminino , Hormônio Foliculoestimulante/genética , Células da Granulosa/metabolismo , Folículo Ovariano/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Progesterona/genética , Receptores Toll-Like/genética
12.
Ann Transl Med ; 7(12): 257, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31355224

RESUMO

BACKGROUND: For subjects with out-of-hospital cardiac arrest (OHCA), bag-valve mask (BVM), endotracheal intubation (ETI), and laryngeal mask airway (LMA) are the most common methods of ventilatory support; however, the best choice remains controversial. METHODS: A comprehensive search of online databases was performed. A traditional meta-analysis was performed to determine the risk ratio of BVM vs. LMA and ETI vs. LMA. Indirect treatment comparisons (ITCs) were conducted to compare BVM and ETI. RESULTS: A total of 13 full-text articles reporting the efficacy of BVM, ETI, and LMA were considered in this analysis. BVM and LMA had the same effect regarding return of spontaneous circulation (ROSC) (23% vs. 24%; RR =0.84), survival rate at admission (19% vs. 21%; RR =0.82) or discharge (6% vs. 4%; RR =0.61). ETI was superior to LMA in terms of ROSC (48% vs. 23%; RR =0.72) and survival rate at both admission (27% vs. 19%; RR =0.85) and discharge (12% vs. 4%; RR =0.90). BVM was inferior to ETI in terms of ROSC (24% vs. 48%; RR =0.86), survival to admission rate (21% vs. 27%; RR =1.037), and survival to discharge rate (6% vs. 12%; RR =1.476). CONCLUSIONS: ETI should be considered for airway management as early as possible, which can improve the subject's success rate of recovery and survival to admission rate. In future, large-scale, multi-center, randomized controlled studies should be conducted to evaluate the exact efficacy of BVM, ETI, and LMA for the first aid of subjects with OHCA.

13.
Heart Surg Forum ; 22(6): E432-E437, 2019 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-31895025

RESUMO

OBJECTIVE: The aim of this study was to observe the impacts of the specific cyclooxygenase-2 inhibitor celecoxib on cardiac structures, functions, and inflammatory factors during the process of pressure overload-induced myocardial hypertrophy. METHODS: Twenty-four male Sprague Dawley rats were randomly divided into 3 groups: the sham operation group, the surgery group, and the celecoxib group. The model was established according to the abdominal aortic coarctation method. RESULTS: At 16 weeks, rats in the celecoxib group were fed a celecoxib-mixed diet (10 mg/kg) for 8 consecutive weeks. At week 24 after model establishment, the cardiac structures and functions were observed; changes in the levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß, prostaglandin E2 (PGE2), C-reactive protein (CRP), and uric acid (UA) were detected; and the contents of Smad1/2/3 proteins (Smad1, Smad2, and Smad3)  were determined. Left ventricular mass index, the heart weight/body weight ratio, and TNF-α, TGF-ß, PGE2, CRP, and UA levels of the celecoxib group were all significantly decreased relative to those of the surgery group (P < .05); moreover, the cardiac functions were significantly improved compared to those of the surgery group (P < .05). CONCLUSIONS: These results show that inflammatory factors are involved in the myocardial hypertrophy process and that celecoxib may reverse myocardial hypertrophy through a variety of pathways.


Assuntos
Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Celecoxib/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Animais , Proteína C-Reativa/metabolismo , Cardiomegalia/sangue , Cardiomegalia/tratamento farmacológico , Dieta , Dinoprostona/sangue , Modelos Animais de Doenças , Esquema de Medicação , Coração/efeitos dos fármacos , Masculino , Tamanho do Órgão , Distribuição Aleatória , Ratos Sprague-Dawley , Receptores de Fatores de Crescimento Transformadores beta/sangue , Proteína Smad1/sangue , Proteína Smad2/sangue , Proteína Smad3/sangue , Fator de Necrose Tumoral alfa/sangue , Ácido Úrico/sangue
14.
Mol Med Rep ; 17(5): 6413-6424, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29512756

RESUMO

To investigate long noncoding (lnc)-RNA and mRNA expression profiles in post­cardiac arrest (CA) brains, an external transthoracic electrical current was applied for 8 min to induce CA (the CA group). A total of 4 rats received sham-operations and served as the blank control (BC) group. Upon return of spontaneous circulation (ROSC), lncRNA and mRNA expression in the rat cerebral cortex was assayed with high­throughput Agilent lncRNA and mRNA microarrays. In total, 37 lncRNAs were upregulated and 21 lncRNAs were downregulated in the CA group, and 258 mRNA transcripts were differentially expressed with 177 mRNAs upregulated and 81 mRNAs downregulated in the CA group. The differentially expressed lncRNAs in the CA group were co­expressed with thousands of mRNAs. The differentially expressed lncRNAs could be clustered into >100 signaling pathways and processes according to Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. The most common predicted functions involved metabolic pathways, protein synthesis, transport and degradation during CA­ROSC. CA­ROSC led to significant alterations in cerebral lncRNA and mRNA expression profiles. Thus, lncRNA­mRNA network interactions have the potential to regulate vital metabolic pathways and processes involved in CA-ROSC.


Assuntos
Encéfalo/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Parada Cardíaca/metabolismo , RNA Longo não Codificante/biossíntese , Animais , Encéfalo/patologia , Parada Cardíaca/genética , Parada Cardíaca/patologia , Masculino , RNA Longo não Codificante/genética , Ratos , Ratos Wistar
15.
Biochem Biophys Res Commun ; 495(1): 706-712, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29102631

RESUMO

Pulmonary fibrosis is responsible for the both short-term and long-term outcomes in patients with acute respiratory distress syndrome (ARDS). There is still no effective cure to improve prognosis. The purpose of this study was to investigate whether edaravone, a free radical scavenger, have anti-fibrosis effects in the rat model of ARDS associated early pulmonary fibrosis by lipopolysaccharide (LPS) administration. Rats were subjected to intravenous injection of LPS, and edaravone was given intraperitoneally after LPS administration daily for 7 consecutive days. LPS treatment rapidly increased lung histopathology abnormalities, coefficient of lung, hydroxyproline and collagen I levels, stimulated myofibroblast differentiation and induced expression of TGF-ß1 and activation of TGF-ß1/Smad3 signaling as early as day 7 after LPS injection. Moreover, LPS intoxication significantly increased the contents of malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), whereas it dramatically decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities from day 1 after LPS treatment. On the contrary, edaravone treatment ameliorated LPS-induced myofibroblast differentiation and pulmonary fibrosis, simultaneously, and attenuated LPS-stimulated oxidative stress and activation of TGF-ß1/Smad3 signaling. Collectively, edaravone may attenuate ARDS associated early pulmonary fibrosis through amelioration of oxidative stress and TGF-ß1/Smad3 signaling pathway. Edaravone may be a promising drug candidate for the treatment of ARDS-related pulmonary fibrosis in early period.


Assuntos
Antipirina/análogos & derivados , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Antipirina/administração & dosagem , Relação Dose-Resposta a Droga , Edaravone , Sequestradores de Radicais Livres/administração & dosagem , Lipopolissacarídeos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Síndrome do Desconforto Respiratório/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
16.
Cell Transplant ; 25(12): 2173-2185, 2016 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-27480476

RESUMO

The therapeutic benefits of bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation for ischemic stroke have been extensively demonstrated. However, studies on the optimal cell dose for intravenous administration are still limited. This study aimed to determine an appropriate cell dose for BM-MSC intravenous transplantation and to investigate the effect of cell dose on vascular remodeling in a rat model of ischemic stroke. BM-MSCs at doses of 5104 (low-dose group), 5105 (medium-dose group), and 2106 (high-dose group) were intravenously injected into rats at 72 h after ischemia. The therapeutic efficacy of BM-MSCs was evaluated by measuring infarct volume, vascular diameters, capillary area in the peri-infarct zone, level of basic fibroblast growth factor (bFGF) in the peri-infarct zone, and serum vascular endothelial growth factor (VEGF) level at 7 days after ischemia. Compared with the low-dose and control groups, medium-dose and high-dose BM-MSC transplantation significantly reduced the volume of the infarct area, enlarged the diameters of pial vessels and the basilar artery, and increased the capillary area in the peri-infarct zone of the cerebral cortex. Furthermore, transplanted BM-MSCs elevated the expressions of bFGF in the peri-infarct zone and the serum VEGF level. Administration of 5105 BM-MSCs is an appropriate cell dose for ischemic stroke therapy in rats. These findings may be helpful for designing future clinical trials.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Acidente Vascular Cerebral/terapia , Remodelação Vascular/fisiologia , Animais , Western Blotting , Encéfalo/metabolismo , Encéfalo/patologia , Infarto Cerebral/metabolismo , Infarto Cerebral/terapia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Fator 2 de Crescimento de Fibroblastos/metabolismo , Masculino , Células-Tronco Mesenquimais/citologia , Microscopia de Fluorescência , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
J Epidemiol ; 26(8): 433-9, 2016 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-26947952

RESUMO

BACKGROUND: Road-traffic injury (RTI) is a major public-health concern worldwide. However, the effectiveness of laws criminalizing drunk driving on the improvement of road safety in China is not known. METHODS: We collected daily aggregate data on RTIs from the Guangzhou First-Aid Service Command Center from 2009 to 2012. We performed an interrupted time-series analysis to evaluate the change in daily RTIs before (January 1, 2009, to April 30, 2011) and after (May 1, 2011, to December 31, 2012) the criminalization of drunk driving. We evaluated the impact of the intervention on RTIs using the overdispersed generalized additive model after adjusting for temporal trends, seasonality, day of the week, and holidays. Daytime/Nighttime RTIs, alcoholism, and non-traffic injuries were analyzed as comparison groups using the same model. RESULTS: From January 1, 2009, to December 31, 2012, we identified a total of 54 887 RTIs. The standardized daily number of RTIs was almost stable in the pre-intervention period but decreased gradually in the post-intervention period. After the intervention, the standardized daily RTIs decreased 9.6% (95% confidence interval [CI], 6.5%-12.8%). There were similar decreases for the daily daytime and nighttime RTIs. In contrast, the standardized daily cases of alcoholism increased 38.8% (95% CI, 35.1%-42.4%), and daily non-traffic injuries increased 3.6% (95% CI, 1.4%-5.8%). CONCLUSIONS: This time-series study provides scientific evidence suggesting that the criminalization of drunk driving from May 1, 2011, may have led to moderate reductions in RTIs in Guangzhou, China.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Condução de Veículo/legislação & jurisprudência , Dirigir sob a Influência/legislação & jurisprudência , Ferimentos e Lesões/prevenção & controle , China/epidemiologia , Humanos , Análise de Séries Temporais Interrompida , Saúde Pública , Ferimentos e Lesões/epidemiologia
18.
Int J Cardiol ; 177(2): 436-41, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25442978

RESUMO

BACKGROUND: Heart failure (HF) is a global public health problem of increasing importance. The association between acute exposure to air pollution and HF has been well established in developed countries, but little evidence was available in developing countries where air pollution levels were much higher. We conducted a time-series study to investigate the short-term association between air pollution and overall emergency ambulance dispatches (EAD) due to HF in Guangzhou, China. METHODS: Daily data of EAD due to HF from 1 January 2008 to 31 December 2012 were obtained from Guangzhou Emergency Center. We applied the over-dispersed Poisson generalized addictive model to analyze the associations after controlling for the seasonality, day of the week and weather conditions. RESULTS: We identified a total of 3375 EAD for HF. A 10-µg/m(3) increase in the present-day concentrations of particulate matter with an aerodynamic diameter of less than 10 µm, sulfur dioxide and nitrogen dioxide corresponded to increases of 3.54% [95% confidence interval (CI): 1.35%, 5.74%], 5.29% (95% CI: 2.28%, 8.30%) and 4.34% (95% CI: 1.71%, 6.97%) in daily EAD for HF, respectively. The effects of air pollution on acute HF were restricted on the concurrent day and in the cool seasons. CONCLUSIONS: Our results provided the first population-based evidence in Mainland China that outdoor air pollution could trigger the exacerbation of HF.


Assuntos
Poluição do Ar/efeitos adversos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Análise de Séries Temporais Interrompida/métodos , Material Particulado/efeitos adversos , Estações do Ano , China/epidemiologia , Insuficiência Cardíaca/diagnóstico , Humanos , Análise de Séries Temporais Interrompida/tendências , Material Particulado/análise , Fatores de Tempo
19.
Am J Emerg Med ; 31(12): 1638-45, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24060327

RESUMO

BACKGROUND: To investigate the therapeutic value of enhanced external counterpulsation (EECP) on recovery of cerebral blood flow following cardiac arrest (CA) and successful resumption of spontaneous circulation (ROSC) by cardiopulmonary resuscitation. METHODS: CA models were conducted using beagle dogs induced by alternating current. After successful ROSC by cardiopulmonary resuscitation, 16 dogs were randomly divided into the EECP and control group (n = 8 per group). Dogs underwent dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging at baseline prior to CA and during the 3 days following ROSC. Mean blood pressure, right common carotid artery blood flow, intracranial microcirculation and blood lactate levels were measured. Neurological outcome was assessed by the neurologic deficit score. Hematoxylin-eosin staining and transmission electron microscopy were performed for morphology and microconstruction of the cerebral cortex. RESULTS: The EECP group exhibited a significant elevation in right common carotid artery blood flow, intracranial microcirculation and a substantial decrease in blood lactate levels relative to the control group. Relative cerebral blood flow and volume were higher in the EECP group during the 3 days. Apparent diffusion coefficients were significantly higher in the EECP group on the first and third days. After ROSC, the neurologic deficit score was significantly higher in the control group compared to those in the EECP group during the three days of experiment. The cell swelling of neurons and increase of mitochondrial mass were more pronounced in the control group. CONCLUSION: EECP is beneficial for recovery of cerebral blood flow and attenuation of ischemic cerebral edema following CA and successful ROSC.


Assuntos
Reanimação Cardiopulmonar/métodos , Córtex Cerebral/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Contrapulsação/métodos , Parada Cardíaca/terapia , Animais , Artéria Carótida Primitiva/fisiologia , Estudos de Casos e Controles , Córtex Cerebral/patologia , Cães , Parada Cardíaca/sangue , Hemodinâmica , Ácido Láctico/sangue , Imageamento por Ressonância Magnética , Microcirculação/fisiologia , Microscopia Eletrônica de Transmissão , Distribuição Aleatória
20.
Exp Ther Med ; 4(4): 611-614, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23170113

RESUMO

The aim of this study was to investigate the effect of epidermal growth factor (EGF) on the lung fluid transport of rabbits with acute lung injury caused by endotoxin and evaluate its therapeutic action. A total of 24 rabbits were randomly divided into control, simple acute lung injury (ALI) and EGF only treatment groups. ALI rabbit models were constructed by the administration of endotoxin (lipopolysaccharide, LPS) and subsequent treatment with EGF. Arterial partial pressure of oxygen, lung pathomorphological changes and wet/dry weight (W/D) of the left lobe of lung tissue were observed at various time points. Results showed that following treatment with EGF, the breathing status of the rabbits continued to improve. An increase was noted in PaO(2) at 12 h after EGF treatment and 24 h later PaO(2) had significantly increased. A marked decrease was observed in the value of W/D and the exudation was reduced. The extrinsic EGF decreased the exudation of pulmonary capillaries and improved lung water transport. Our findings verified that epidermal growth factor had repaired the effect of ALI through continuous 48-h observation. Therefore, the present study demonstrated the therapeutic action of EGF.

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