RESUMO
Endothelial dysfunction in brain endothelial cells contributes to vasogenic cerebral edema and increased mortality after various neurological diseases. The postsynaptic density protein Homer1 plays an important role in neuronal synaptic activity and is extensively involved in neurological disorders. The present study investigated the role of Homer1 in modulating cell survival using an in vitro endothelial dysfunction model in murine brain endothelial cells (mBECs). Treatment with tert-butyl hydroperoxide (t-BHP) induced a dose-dependent toxicity in mBECs, with no effects on Homer1 expression and distribution. Knockdown of Homer1 using specific siRNA significantly alleviated lactate dehydrogenase (LDH) release, increased cell viability, and ultimately decreased apoptosis after t-BHP treatment. Moreover, Homer1 knockdown attenuated t-BHP-induced ROS generation, lipid peroxidation and mitochondrial dysfunction, as evidenced by loss of mitochondrial membrane potential (MMP), ATP synthesis collapse and mitochondrial swelling. The results of Ca(2+) imaging showed that Homer1 was involved in inositol trisphosphate receptors (IP3R)- and ryanodine receptor (RyR)-mediated intracellular Ca(2+) release, and also mediated t-BHP-induced Ca(2+) release from the endoplasmic reticulum (ER). In addition, knockdown of Homer1 significantly prevented activation of ER stress markers induced by t-BHP exposure. All these results showed that Homer1 is involved in t-BHP-induced endothelial dysfunction in mBECs, and may be an ideal candidate for searching gene intervention strategy for preventing endothelial oxidative stress in vitro.
Assuntos
Encéfalo/fisiologia , Sinalização do Cálcio/fisiologia , Cálcio/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Proteínas de Arcabouço Homer/metabolismo , terc-Butil Hidroperóxido/farmacocinética , Animais , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Homeostase/efeitos dos fármacos , Homeostase/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , terc-Butil Hidroperóxido/farmacologiaRESUMO
Locusta migratoria manilensis is one of the most important agricultural pests in China. The locust has high fecundity and consumes large quantities of food, causing severe damage to diverse crops such as corn, sorghum, and rice. Immunity against pathogens and reproductive success are two important components of individual fitness, and many insects have a trade-off between reproduction and immunity when resources are limited, which may be an important target for pest control. In this study, adult females L. migratoria manilensis were treated with different concentrations (5 × 106 spores/mL or 2 × 107 spores/mL) of the entomopathogenic fungus Paranosema locustae. Effects of input to immunity on reproduction were studied by measuring feeding amount, enzyme activity, vitellogenin (Vg) and vitellogenin receptor (VgR) production, ovary development, and oviposition amount. When infected by P. locustae, feeding rate and phenol oxidase and lysozyme activities increased, mRNA expression of Vg and VgR genes decreased, and yolk deposition was blocked. Weight of ovaries decreased, with significant decreases in egg, length and weight.Thus, locusts used nutritive input required for reproduction to resist invasion by microsporidia. This leads to a decrease in expression of Vg and VgR genes inhibited ovarian development, and greatly decreased total fecundity. P. locustae at 2 × 107 spores/mL had a more obvious inhibitory effect on the ovarian development in migratory locusts. This study provides a detailed trade-off between reproduction and immune input of the female, which provides a reliable basis to find pest targets for biological control from those trade-off processes.
Assuntos
Locusta migratoria , Microsporídios , Animais , Feminino , Locusta migratoria/genética , Locusta migratoria/microbiologia , Oviposição , ReproduçãoRESUMO
BACKGROUND: Until January 18, 2021, coronavirus disease-2019 (COVID-19) has infected more than 93 million individuals and has caused a certain degree of panic. Viral pneumonia caused by common viruses such as respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses have been more common in children. However, the incidence of COVID-19 in children was significantly lower than that in adults. The purpose of this study was to describe the clinical manifestations, treatment and outcomes of COVID-19 in children compared with those of other sources of viral pneumonia diagnosed during the COVID-19 outbreak. METHODS: Children with COVID-19 and viral pneumonia admitted to 20 hospitals were enrolled in this retrospective multi-center cohort study. A total of 64 children with COVID-19 were defined as the COVID-19 cohort, of which 40 children who developed pneumonia were defined as the COVID-19 pneumonia cohort. Another 284 children with pneumonia caused by other viruses were defined as the viral pneumonia cohort. The epidemiologic, clinical, and laboratory findings were compared by Kolmogorov-Smirnov test, t-test, Mann-Whitney U test and Contingency table method. Drug usage, immunotherapy, blood transfusion, and need for oxygen support were collected as the treatment indexes. Mortality, intensive care needs and symptomatic duration were collected as the outcome indicators. RESULTS: Compared with the viral pneumonia cohort, children in the COVID-19 cohort were mostly exposed to family members confirmed to have COVID-19 (53/64 vs. 23/284), were of older median age (6.3 vs. 3.2 years), and had a higher proportion of ground-glass opacity (GGO) on computed tomography (18/40 vs. 0/38, P < 0.001). Children in the COVID-19 pneumonia cohort had a lower proportion of severe cases (1/40 vs. 38/284, P = 0.048), and lower cases with high fever (3/40 vs. 167/284, P < 0.001), requiring intensive care (1/40 vs. 32/284, P < 0.047) and with shorter symptomatic duration (median 5 vs. 8 d, P < 0.001). The proportion of cases with evaluated inflammatory indicators, biochemical indicators related to organ or tissue damage, D-dimer and secondary bacterial infection were lower in the COVID-19 pneumonia cohort than those in the viral pneumonia cohort (P < 0.05). No statistical differences were found in the duration of positive PCR results from pharyngeal swabs in 25 children with COVID-19 who received antiviral drugs (lopinavir-ritonavir, ribavirin, and arbidol) as compared with duration in 39 children without antiviral therapy [median 10 vs. 9 d, P = 0.885]. CONCLUSION: The symptoms and severity of COVID-19 pneumonia in children were no more severe than those in children with other viral pneumonia. Lopinavir-ritonavir, ribavirin and arbidol do not shorten the duration of positive PCR results from pharyngeal swabs in children with COVID-19. During the COVID-19 outbreak, attention also must be given to children with infection by other pathogens infection.
Assuntos
COVID-19/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Adolescente , COVID-19/fisiopatologia , COVID-19/terapia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/fisiopatologia , Síndrome Respiratória Aguda Grave/terapia , Índice de Gravidade de DoençaRESUMO
Fusarium head blight (FHB) and crown rot (CR) are two wheat diseases caused by the same Fusarium pathogens. Progress towards CR resistance could benefit from FHB-resistant germplasm if the same genes are involved in resistance to these two different diseases. Two independent studies were conducted to investigate the relationship between host resistances to these two diseases. In the first study 32 genotypes were assessed and no significant correlation between their reactions to FHB and CR was detected. The second study was based on a QTL analysis of a doubled haploid population derived from a variety with resistance to both diseases. Results from this study showed that loci conferring resistance to FHB and CR are located on different chromosomes. Together, these results suggest that, despite a common aetiology, different host genes are involved in the resistance against FHB and CR in wheat. Thus, although it is possible that genes affecting both diseases may exist in other germplasm or under different conditions, separate screening seems to be needed in identifying sources of CR resistance.
Assuntos
Pão , Fusarium/fisiologia , Imunidade Inata/genética , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Triticum/genética , Triticum/microbiologia , Mapeamento Cromossômico , Segregação de Cromossomos/genética , Marcadores Genéticos , Genótipo , Haploidia , Doenças das Plantas/microbiologia , Locos de Características Quantitativas/genética , Triticum/anatomia & histologia , Triticum/imunologiaRESUMO
Intrahepatic cholangiocarcinoma (ICC) is a rare hepatobiliary malignancy arising from the epithelial cells of the intrahepatic bile ducts. The increased incidence of ICC worldwide may reflect both a true increase and the earlier detection of the disease. Despite the advances in modern surgical care, the curative chance for ICC remained suboptimal: tumor-free margins are hard to achieve due to tumor locations, and technical challenges and recurrence, either local or distant, may hamper the resectability in a large number of patients. Lymph node involvement and vascular invasions are considered negative predictive factors for survival of ICC patients. This review discusses the epidemiology, risk factors and surgical management of ICCs, and mainly focuses on outcomes and factors associated with surgical treatment.
RESUMO
OBJECTIVES: To assess the overall qualities of published surgical meta-analysis and predictive factors for high qualities. STUDY DESIGN AND SETTING: All meta-analyses pertinent to surgical procedures published in year 2013 were selected from PubMed and EMBASE. The characteristics of the included meta-analyses were collected, and their reporting and methodologic qualities were assessed by the PRISMA (27 items) and AMSTAR (11 items) checklists, respectively. Independent predictive factors associated with these two qualities were evaluated by univariate and multivariate analyses. RESULTS: Hundred ninety-seven meta-analyses representing 10 surgical subspecialties were included. The mean PRISMA and AMSTAR adherences (by items) were 22.2 ± 2.4 and 7.8 ± 1.2, respectively, and a positive linear correlation was found between them with an R(2) of 0.793. Those meta-analyses conducted by the first authors having meta-analysis publication previously had significantly higher reporting and methodologic qualities than those who did not (P = 0.002 and P = 0.001). Meanwhile, there were also significant differences in these two qualities between studies published in Q1-ranked and (Q2 + Q3)-ranked journals as rated by the SCImago indicator (P < 0.001 and P < 0.001). On multivariate analyses, region of origin (non-Asia vs. Asia), publishing experience of first authors (ever vs. never), rank of publishing journals (Q1 vs. Q2 + Q3), and preregistration (presence vs. absence) were independently associated with superior reporting and methodologic qualities. CONCLUSIONS: The reporting and methodologic qualities of current surgical meta-analyses remained suboptimal, and first authors' experience and ranking of publishing journals were independently associated with both qualities. Preregistration might be an effective measure to improve the quality of meta-analyses, which deserves more attention from future study conductors.