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1.
BMC Vet Res ; 16(1): 6, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910824

RESUMO

BACKGROUND: Porcine circovirus type 2 (PCV2) is the pathogen of porcine circovirus associated diseases (PCVAD) and one of the main pathogens in the global pig industry, which has brought huge economic losses to the pig industry. In recent years, there has been limited research on the prevalence of PCV2 in Henan Province. This study investigated the genotype and evolution of PCV2 in this area. RESULTS: We collected 117 clinical samples from different regions of Henan Province from 2015 to 2018. Here, we found that the PCV2 infection rate of PCV2 was 62.4%. Thirty-seven positive clinical samples were selected to amplify the complete genome of PCV2 and were sequenced. Based on the phylogenetic analysis of PCV2 ORF2 and complete genome, it was found that the 37 newly detected strains belonged to PCV2a (3 of 37), PCV2b (21 of 37) and PCV2d (13 of 37), indicating the predominant prevalence of PCV2b and PCV2d strains. In addition, we compared the amino acid sequences and found several amino acid mutation sites among different genotypes. Furthermore, the results of selective pressure analysis showed that there were 5 positive selection sites. CONCLUSIONS: This study indicated the genetic diversity, molecular epidemiology and evolution of PCV2 genotypes in Henan Province during 2015-2018.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31913999

RESUMO

BACKGROUND: The role of partner types in modifying HIV seroconversion risk among men who have sex with men (MSM) is complex. We sought to understand the role of regular sexual partners and risky sexual behavior in contributing to incident HIV infection among MSM. METHODS: From July 2011 to August 2017, we recruited HIV-negative men who reported having anal or oral homosexual encounters in the past 6 months, following them every 3 months for two visits. We collected sociodemographic and behavioral characteristics by self-administrated questionnaire. HIV status was confirmed by sequential rapid test and confirmatory test. We used multivariable Cox regression to identify risk factors and interaction models to evaluate the relative excess risk between relevant variables. RESULTS: Among 1218 participants, HIV seroconversion rate was 3.66/100 person-years. HIV seroconversion was associated with lower educational attainment (adjusted hazards ratio [aHR]=1.73, 95%CI: 1.06-2.81), having had penetrative sex with male before age of 18 (aHR=2.44, 95%CI: 1.20-4.99), not using condoms in the last sexual encounter (aHR=2.19, 95%CI: 1.29-3.71), having regular but not committed partners (aHR=3.33, 95%CI: 1.77-6.93). Among 890 (73%) of men reported having regular partners, HIV seroconversion was more frequent in men whose stable partners were not committed as boyfriends (aHR=3.31, 95%CI: 1.73-6.36) and in men having unprotected anal sex (aHR=2.61, 95%CI: 1.42-4.80). Interaction between these two factors was observed (relative excess risk of interaction=4.53). CONCLUSIONS: Incidence among MSM in China was high; unprotected sex with steady, but not committed partners was associated with increased seroconversion risk. It is imperative to expand safer sex education and training for MSM to reduce unsafe sexual behaviors, including awareness that casual partners are not the only source of infection.

3.
J Cell Mol Med ; 24(1): 4-12, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31568632

RESUMO

The transient receptor potential melastatin-related 2 (TRPM2) channel, a reactive oxygen species (ROS)-sensitive cation channel, has been well recognized for being an important and common mechanism that confers the susceptibility to ROS-induced cell death. An elevated level of ROS is a salient feature of ischaemia-reperfusion, chronic cerebral hypo-perfusion and neonatal hypoxia-ischaemia. The TRPM2 channel is expressed in hippocampus, cortex and striatum, the brain regions that are critical for cognitive functions. In this review, we examine the recent studies that combine pharmacological and/or genetic interventions with using in vitro and in vivo models to demonstrate a crucial role of the TRPM2 channel in brain damage by ischaemia-reperfusion, chronic cerebral hypo-perfusion and neonatal hypoxic-ischaemia. We also discuss the current understanding of the underlying TRPM2-dependent cellular and molecular mechanisms. These new findings lead to the hypothesis of targeting the TRPM2 channel as a potential novel therapeutic strategy to alleviate brain damage and cognitive dysfunction caused by these conditions.

4.
Pest Manag Sci ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31785067

RESUMO

BACKGROUND: Early blight caused by Alternaria spp. is amongst the most important diseases in potato. Demethylation inhibitor (DMI) fungicides are widely used to control the disease but long-term use may decrease its control efficacy due to fungicide resistance. This study investigated the occurrence of difenoconazole resistance in Alternaria spp. and molecular resistant mechanisms. RESULTS: EC50 values of 160 isolates to difenoconazole ranged from 0.026 µg mL-1 to 15.506 µg mL-1 and the frequency of difenoconazole sensitivity formed a non-normal distribution curve with a major and a minor peak. Isolates with EC50 values of 4.121 and 5.461 µg mL-1 were not controlled effectively at fungicide doses of 50 and 100 µg mL-1 . Cross-resistance was observed between DMI fungicides difenoconazole and propiconazole, but not between difenoconazole and other fungicide groups, including boscalid, iprodione, or carbendazim. The CYP51gene was 1673 bp encoding 525 amino acids in length and contained two introns. All sensitive and resistant isolates had the identical amino acid sequence of CYP51, with the exception of one resistant isolate carrying a mutation of R511W. A 6 bp insertion in the upstream region was observed in half of the resistant isolates. In the absence of propiconazole, the relative expression of CYP51 was not significantly different in sensitive and resistant isolates. In the presence of difenoconazole, expression of CYP51 gene was induced significantly in the DMI-resistant isolates but not in the sensitive ones. CONCLUSION: Induced expression of CYP51 in resistant isolates exposed to difenoconazole is an important determinant for DMI resistance in potato pathogens Alternaria sect. © 2019 Society of Chemical Industry.

5.
Microbiologyopen ; : e965, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31808296

RESUMO

Fermentation, also known as aging, is vital for enhancing the quality of flue-cured tobacco leaves (FTLs). Aged FTLs demonstrate high-quality sensory characteristics, while unaged FTLs do not. Microbes play important roles in the FTL fermentation process. However, the eukaryotic microbial community diversity is poorly understood, as are microbial associations within FTLs. We aimed to characterize and compare the microbiota associated with two important categories, fresh and strong flavor style FTLs, and to reveal correlations between the microbial taxa within them. Based on 16S and 18S rRNA Illumina MiSeq sequencing, the community richness and diversity of prokaryotes were almost as high as that of eukaryotes. The dominant microbes of FTLs belonged to seven genera, including Pseudomonas, Bacillus, Methylobacterium, Acinetobacter, Sphingomonas, Neophaeosphaeria, and Cladosporium, of the Proteobacteria, Firmicutes, and Ascomycota phyla. According to partial least square discriminant analysis (PLS-DA), Xanthomonas, Franconibacter, Massilia, Quadrisphaera, Staphylococcus, Cladosporium, Lodderomyces, Symmetrospora, Golovinomyces, and Dioszegia were significantly positively correlated with fresh flavor style FTLs, while Xenophilus, Fusarium, unclassified Ustilaginaceae, Tilletiopsis, Cryphonectria, Colletotrichum, and Cyanodermella were significantly positively correlated with strong flavor style FTLs. Network analysis identified seven hubs, Aureimonas, Kocuria, Massilia, Brachybacterium, Clostridium, Dietzia, and Vishniacozyma, that may play important roles in FTL ecosystem stability, which may be destroyed by Myrmecridium. FTL microbiota was found to be correlated with flavor style. Species present in lower numbers than the dominant microbes might be used as microbial markers to discriminate different flavor style samples and to stabilize FTL microbial communities. This research advances our understanding of FTL microbiota and describes a means of discriminating between fresh and strong flavor FTLs based on their respective stable microbiota.

6.
Front Pharmacol ; 10: 1304, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31780935

RESUMO

Organs and tissues and their constituent cells are physiologically submitted to diverse types of mechanical forces or stress, one common sequence of which is release of intracellular ATP into extracellular space. Extracellular ATP is a well-established autocrine or paracrine signaling molecule that regulates multiple cell functions and mediates cell-to-cell communications via activating the purinergic P2 receptors, more specifically, ligand-gated ion channel P2X receptors and some of the G-protein-coupled P2Y receptors. The molecular mechanisms that sense mechanical and transduce forces to trigger ATP release are poorly understood. The Piezo1, a newly identified mechanosensing ion channel, shows widespread expression and confers mechanosensitivity in many different types of cells. In this mini-review, we briefly introduce the Piezo1 channel and discuss the evidence that supports its important role in the mechanoregulation of diverse cell functions and, more specifically, critical engagement of ATP release and subsequent P2 receptor activation in Piezo1 channel-dependent mechanoregulation. Such ATP release-mediated coupling of the Piezo1 channel and P2 receptors may serve a signaling mechanism that is more common than we currently understand in transducing mechanical information to regulation of the attendant cell functions in various organs and tissues.

7.
Int J Mol Sci ; 20(21)2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31694199

RESUMO

Toxoplasma gondii is an intracellular parasite that infects humans and other warm-blooded animals. Exosomes are endocytic-derived vesicles released by cells, representing an important mode of intercellular communication. In exosomes, specific molecules of proteins, lipids, and mRNAs or miRNAs have been detected, some of which are capable of transferring biologically active molecules to recipient cells. Dendritic cells (DCs) are the only antigen-presenting cells (APCs) that activate the initial immune response. In this study, high-throughput sequencing was used to analyze the exosomal miRNA profile of DC2.4 cells infected with Toxoplasma gondii for 28 h, compared with those of uninfected DC2.4 cells. Differential exosomal miRNAs (DEmiRs) from these two cell groups were analyzed. Through high-throughput sequencing, 3434 DEmiRs were obtained, and 12 stably enriched DEmiRNAs were verified by Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) and selected for further analysis. The target genes of these 12 miRNAs were predicted with online analysis software and subjected to bioinformatics analyses including protein-protein interaction (PPI) network analysis, key driver analysis (KDA), gene ontology (GO) enrichment, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. These DEmiRs were found to be associated with a variety of biological processes and signaling pathways involved in host ubiquitin system, innate immunity, biosynthesis, and transferase activity and could be potential biomarkers for T. gondii infection.

8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 999-1001, 2019 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-31598945

RESUMO

OBJECTIVE: To detect the disease-causing mutation in a family with hereditary spherocytosis type Ⅰ. METHODS: Genomic DNA was extracted from peripheral blood samples of the proband and his relatives. Next-generation sequencing was used to detect the mutations of relevant genes. Suspected pathogenic mutation was verified by Sanger sequencing. RESULTS: The proband was found to harbor a novel frameshifting mutation in the coding region of ANK1 gene, which has resulted in abnormal structure or function of the protein. The mutation was confirmed by Sanger sequencing, with both his father and brother found to have carried the same mutation. CONCLUSION: The c.247delG mutation of proband hereditary spherocytosis typeⅠin this family due to mutation of the ANK1 gene..


Assuntos
Anquirinas/genética , Esferocitose Hereditária/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mutação , Fases de Leitura Aberta
9.
J Clin Transl Hepatol ; 7(3): 213-220, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31608212

RESUMO

Background and Aims: Ravidasvir (RDV) is a new generation pangenotypic hepatitis C virus (HCV) NS5A inhibitor, with high barrier to baseline resistance-associated species. This is the first phase 2/3 study conducted in Mainland China confirming the efficacy and safety of RDV + ritonavir-boosted danoprevir + ribavirin for 12 weeks in treatment-naïve noncirrhotic patients with genotype 1 infection in a large population. Methods: In this multicenter, randomized, double-blinded, placebo-controlled phase 2/3 trial (NCT03362814), we enrolled 424 treatment-naïve, noncirrhotic adult HCV genotype 1 patients. All patients were randomized at 3:1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day (body weight <75/≥75 kg) (n = 318) or placebo (n = 106) for 12 weeks. The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment, and the safety was evaluated and compared between treatment and placebo groups. Results: The overall rate of sustained virological response at 12 weeks after treatment is 99% (306/309, 95%, CI: 97%-100%) under per protocol set analysis. All patients harboring baseline NS5A resistance-associated species in the treatment group (76/76, per protocol set) achieved sustained virological response at 12 weeks after treatment. No treatment-related serious adverse events were reported. Laboratory abnormalities showed mild or moderate severity (grade 1 and grade 2) in liver function tests. Conclusions: In treatment-naïve, noncirrhotic HCV Chinese patients infected with HCV genotype 1, all-oral regimen of RDV + ritonavir-boosted danoprevir + ribavirin for 12 weeks was highly efficacious, safe, and well tolerated.

10.
Front Physiol ; 10: 1077, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496957

RESUMO

Lipophagy degrades lipid droplets (LDs) through the lysosomal degradative pathway, thus plays important roles in regulating lipid metabolism in mammals. However, information on the existence and functions of lipophagy in fish lipid metabolism is still limited. In the present study, we confirmed the existence of lipophagy by observing the structures of LDs sequestered in autophagic vacuoles in the zebrafish liver cell line (ZFL) via electronic microscopy. Moreover, starved cells increased the mRNA expression of the microtubule-associated protein 1A/1B light chain 3 beta (LC3), which is a marker protein for autophagy and protein conversion from LC3-I to LC3-II. Inhibiting autophagy with chloroquine increased significantly the LDs content and decreased fatty acid ß-oxidation and esterification activities in the ZFL cells cultured in the fed state. Furthermore, inhibiting autophagy function downregulated the mRNA expression of the genes and their proteins related to lipid metabolism. Altogether, the present study verified the existence of lipophagy and its essential regulatory roles in lipid metabolism in fish cells.

11.
Neurochem Res ; 44(11): 2506-2516, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31486012

RESUMO

Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) has recently been shown to promote oxidative stress and inflammation in the peripheral tissues, contributing to the pathogenesis of many diseases. Here we examined whether pre-existing higher circulating TMAO would influence cognitive function in aged rats after anesthetic sevoflurane exposure. Aged rats received vehicle or TMAO treatment for 3 weeks. After 2 weeks of treatment, these animals were exposed to either control or 2.6% sevoflurane for 4 h. One week after exposure, freezing as measured by fear conditioning test, microglia activity, proinflammatory cytokine expression and NADPH oxidase-dependent reactive oxygen species (ROS) production in the hippocampus (a key brain structure involved in learning and memory) were comparable between vehicle-treated rats exposed to control and vehicle-treated rats exposed to sevoflurane. TMAO treatment, which increased plasma TMAO before and 1 week after control or sevoflurane exposure, significantly reduced freezing to contextual fear conditioning, which was associated with increases in microglia activity, proinflammatory cytokine expression and NADPH oxidase-dependent ROS production in the hippocampus in rats exposed to sevoflurane but not in rats exposed to control. Moreover, hippocampal expression of antioxidant enzyme methionine sulfoxide reductase A (MsrA) was reduced by TMAO treatment in both groups, and TMAO-induced reduction in MsrA expression was negatively correlated with increased proinflammatory cytokine expression in rats exposed to SEV. These findings suggest that pre-existing higher circulating TMAO downregulates antioxidant enzyme MsrA in the hippocampus, which may sensitize the hippocampus to oxidative stress, resulting in microglia-mediated neuroinflammation and cognitive impairment in aged rats after sevoflurane exposure.

12.
J Oleo Sci ; 68(9): 931-937, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31413242

RESUMO

The essential oil extracted from roots and rhizomes of Ligusticum jeholense Nakai et Kitagawa was investigated for its chemical composition by GC-MS analysis, and evaluated for its contact toxicity and repellency against Tribolium castaneum and Lasioderma serricorne, along with some of its individual components. The essential oil was rich in aromatics (65.34%) with low molecular weight. Major components included sedanolide (33.95%), 3-butylidenephthalide (18.76%), spathulenol (8.90%) and myristicin (6.76%). The results of bioassays indicated that the essential oil of L. jeholense and 3-butylidenephthalide possessed significant repellent activities against T. castaneum at 2 and 4 h post-exposure. Meanwhile, 3-butylidenephthalide had potent contact toxicity against L. serricorne (LD50 = 13.64 µg/adult). The minor component n-butylbenzene in the oil was highly toxic to T. castaneum (LD50 = 23.99 µg/adult) and L. serricorne (LD50 = 7.86 µg/adult) in contact assays, but failed to repel these beetles at all testing concentrations. Spathulenol and myristicin exerted good insecticidal and repellent effects on the two target insects. This work suggests that the essential oil of L. jeholense has promising potential for development as natural insecticide or repellent to control pest damage in warehouses.


Assuntos
Derivados de Benzeno/farmacologia , Repelentes de Insetos/farmacologia , Inseticidas/farmacologia , Óleos Voláteis/farmacologia , Anidridos Ftálicos/farmacologia , Tribolium/efeitos dos fármacos , Animais , Ligusticum/química , Óleos Voláteis/análise , Óleos Voláteis/toxicidade
13.
Nanoscale ; 11(32): 15083-15090, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31380538

RESUMO

The solar-to-electric conversion efficiency of mesoscopic solar cells is highly dependent on electron extraction under solar irradiation and determines the charge recombination processes within devices. Boosting charge transfer via building energy level alignment has been proved to be a promising method to enhance the output power of solar cells. In the current work, we present the successful fabrication of functional biomass-converted carbon quantum dots with graded energy levels by doping nitrogen or sulphur atoms from lotus root powder. When employed as light absorbers for mesoscopic solar cells, light harvesting and electron extraction can be markedly increased arising from the band alignment of graded carbon quantum dots, yielding maximal power conversion efficiencies of 0.158% and 0.208% for bi- and tri-cascaded photovoltaics, respectively. The primary results demonstrate that the employment of an energy-graded architecture is a promising strategy to optimize the device output. Following this line of thought, we further fabricate a co-sensitized device by integrating graded carbon quantum dots with N719 dyes to enhance the electron extraction capability. The final device yields an efficiency as high as 9.04%, showing the potential application of carbon quantum dots in high-performance solar cells.


Assuntos
Carbono/química , Pontos Quânticos/química , Energia Solar , Biomassa , Fontes de Energia Elétrica , Teoria Quântica
14.
PLoS Negl Trop Dis ; 13(7): e0007590, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31306427

RESUMO

BACKGROUND: The entomopathogenic fungus Beauveria bassiana has been widely used to kill mosquito larvae and adults in the laboratory and field. However, its slow action of killing has hampered its widespread application. In our study, the B. bassiana fungus was genetically modified to express the Bacillus thuringiensis (Bt) toxin Cyt2Ba to improve its efficacy in killing mosquitoes. METHODOLOGY/PRINCIPAL FINDINGS: The efficacy of the wild type (WT) of B. bassiana and a transgenic strain expressing Cyt2Ba toxin (Bb-Cyt2Ba) was evaluated against larval and adult Aedes mosquitoes (Aedes aegypti and Aedes albopictus) using insect bioassays. The Bb-Cyt2Ba displayed increased virulence against larval and adult Aedes mosquitoes compared with the WT: for Ae. aegypti adults, the median lethal time (LT50) was decreased by 33% at the concentration of 1× 108 conidia/ml, 19% at 1× 107 conidia/ml and 47% at 1× 106 conidia/ml. The LT50 for Ae. albopictus adults was reduced by 20%, 23% and 29% at the same concentrations, respectively. The LT50 for Ae. aegypti larvae was decreased by 42% at 1× 107 conidia/ml and 25% at 1× 106 conidia/ml, and that for Ae. albopictus larvae was reduced by 33% and 31% at the same concentrations, respectively. In addition, infection with Bb-Cyt2Ba resulted in a dramatic reduction in the fecundity of Aedes mosquitoes. CONCLUSIONS/SIGNIFICANCE: In conclusion, our study demonstrated that the virulence of B. bassiana against mosquitoes can be significantly improved by introducing the Bt toxin gene Cyt2Ba into the genome to express the exogenous toxin in the fungus. The transgenic strain Bb-Cyt2Ba significantly reduced the survival and fecundity of Ae. aegypti and Ae. albopictus compared with the WT strain, which suggested that this recombinant B. bassiana has great potential for use in mosquito control.


Assuntos
Aedes/microbiologia , Bacillus thuringiensis/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/toxicidade , Toxinas Bacterianas/genética , Toxinas Bacterianas/toxicidade , Beauveria/genética , Endotoxinas/genética , Endotoxinas/toxicidade , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/toxicidade , Controle Biológico de Vetores/métodos , Animais , Feminino , Fertilidade , Regulação Fúngica da Expressão Gênica , Instabilidade Genômica , Larva/microbiologia , Controle de Mosquitos/métodos , Proteínas Recombinantes , Esporos Fúngicos , Virulência/genética
15.
J Mol Cell Biol ; 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31237951

RESUMO

The endocrine regulatory roles of the hypothalamic-pituitary-adrenocortical (HPA) axis on anxiety-like behavior and metabolic status have been found throughout animal taxa. However, the precise effects of the balancing adrenal corticosteroid biosynthesis under the influence of adrenocorticotrophic hormone (ACTH), a pro-opiomelanocortin (POMC)-derived peptide, on animal energy expenditure and somatic growth remain unknown. POMC has also been identified as one of the candidate loci for polycystic ovary syndrome (PCOS) which features hyperandrogenism and some prevalence of obesity in patients. Here we show that zebrafish lacking functional POMCa exhibit similar phenotypes of stress response and body weight gain but not obesity as observed in mammalian models. In contrast with the impaired anorexigenic signaling cascade of melanocyte-stimulating hormones (MSHs) and leptin, which are responsible for their obesity-prone weight gain observed in various pomc mutant mammals, analyses with our pomca mutant series indicate that ACTH is the key regulator for the phenotype with enhanced somatic growth without obesity in pomca-deficient zebrafish. Hypocortisolism associated with hyperandrogenism has been observed in the pomca-deficient zebrafish, with enhanced activation of mTORC1, reutilization of amino acids and fatty acid ß-oxidation are observed in the muscle tissue of the pomca-deficient fish. After reducing hyperandrogenism by crossing our pomca mutant fish with a cyp17a1-deficient background, the phenotype of enhanced somatic growth in pomca-deficient fish was no longer observed. Thus, our work also demonstrated that the role of POMCa in stress response seems to be conserved in vertebrates, whereas its effect on adipostasis is unique to teleosts.

17.
Behav Brain Res ; 368: 111902, 2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-30980850

RESUMO

Surgical trauma can cause brain oxidative stress and neuroinflammation, leading to postoperative cognitive dysfunction (POCD), especially in the elderly. Additionally, the pre-existing risk factors may enhance POCD. Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) has recently been shown to contribute to the pathogenesis of many diseases by increasing oxidative stress and inflammation in the peripheral tissues. Here we examined whether the presence of elevated circulating TMAO would influence surgery-induced cognitive decline. Aged rats were treated with vehicle or TMAO for 3 weeks. After two weeks of treatment, these rats underwent sham-operation or laparotomy. One week after surgery, rats underwent laparotomy exhibited hippocampal-dependent cognitive dysfunction as evidenced by reduced contextual freezing time, which was associated with elevated plasma proinflammatory cytokine levels, increased microglia-mediated neuroinflammation and reactive oxygen species (ROS) production in the hippocampus. Treatment with TMAO, which elevated plasma TMAO before and 1 week after surgery, further increased microglia-mediated neuroinflammation and ROS production in the hippocampus, resulting in exaggerated cognitive dysfunction in laparotomy group but not in sham-operation group. Moreover, TMAO treatment decreased expression of antioxidant enzyme methionine sulfoxide reductase (Msr) A in both groups. The results suggest that the presence of elevated circulating TMAO downregulates antioxidant enzyme MsrA in the hippocampus, which may increase the susceptibility to surgery-induced oxidative stress, contributing to exaggerations of neuroinflammation and cognitive decline in aged rats following surgery. Interventions to reduce circulating TMAO in the perioperative period may be a novel strategy to prevent the exaggeration of cognitive decline in elderly patients with high circulating TMAO.

18.
Hum Vaccin Immunother ; 15(11): 2637-2643, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30932729

RESUMO

We assessed how an awareness of influenza vaccination might influence both the willingness of pregnant women to be vaccinated and the readiness of obstetricians to recommend antenatal influenza vaccination in Beijing, China. From March to April 2016, we surveyed pregnant women who were attending antenatal clinics at eight hospitals in Beijing, along with obstetricians at the same clinics. Demographic, attitudinal, and behavioral information regarding influenza vaccination were collected using structured questionnaires. Consent and completed questionnaires were obtained from 988 of 1009 pregnant women and 165 of 173 obstetricians. Only 113 (11.4%) pregnant women reported being willing to receive an influenza vaccine during their pregnancies. Willingness to receive an influenza vaccination was positively associated with ever having a history of vaccination or influenza (aOR=6.74, 95%CI: 1.72-26.4, P=0.006), perceiving benefits of vaccination (aOR=1.67, 95%CI: 1.00-2.79, P=0.050), and having a higher level of influenza knowledge (aOR=82.2, 95%CI: 21.7-311.1, P<0.001). Among obstetricians, only 19.4% reported being willing to recommend influenza vaccination to their pregnant patients and 15.2% reported knowledge that influenza vaccination during pregnancy was recommended by China's National Health Commission. Neither pregnant women nor their obstetricians were aware of Chinese government recommendations that antenatal influenza vaccination should be encouraged and provided. Pregnant women and their obstetricians were ill-informed of the relevant evidence. It is in emergent need to train and disseminate the updated evidence on influenza vaccination to obstetricians. It also warranted more high-quality trials regarding influenza vaccination during pregnancy to address public concern.

19.
Artigo em Inglês | MEDLINE | ID: mdl-30914037

RESUMO

BACKGROUND: Obese patients are more sensitive to myocardial ischemia, which has been linked with high mortality rates. The following study investigates the effects of impaired macrophage Migration Inhibitory Factor (MIF)/AMP-Activated Protein Kinase (AMPK) activation on increased susceptibility to myocardial ischemia/reperfusion (I/R) in high-fat diet-induced obesity. METHODS: Male C57BL/6J mice were fed with a normal diet (10% kcal as fat, lean group) or a high-fat diet (60kcal as fat, obese group) for 12 consecutive weeks. To detect the MIF expression and AMPK activation in response to I/R in isolated hearts from lean and obese mice, myocardial samples were collected from left ventricular areas at different time points. To determine whether MIF supplementation is protective against I/R injury, recombined MIF (10 ng/mL) was applied before ischemia. Myocardial infarct size was estimated by triphenyltetrazolium staining. Western blot was used to detect myocardial MIF expression, AMPK activation and membrane glucose transporter 4 (Glut4) expression. RESULTS: The expression of MIF was remarkably higher in obese group compared to lean group. Ischemia increased myocardial MIF expression and phosphorylation of AMPK in lean mice, whereas it had no significant effect on obese mice. Furthermore, administration of recombinant MIF increased ischemic AMPK activation and membrane Glut4 expression in both lean and obese mice, while it reduced the infarct size in lean mice only. CONCLUSION: An impaired MIF/AMPK activation response and consequent reduced membrane Glut4 expression may play an important role in increasing myocardial susceptibility to I/R in obesity.

20.
Mol Med Rep ; 19(5): 3815-3822, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896803

RESUMO

Post­operative cognitive dysfunction is a common complication after anesthesia and surgery. Sevoflurane (SEV), a widely used inhalational anesthetic, can exaggerate neuroinflammation and cause cognitive dysfunction under chronic intermittent hypoxia (CIH) conditions by downregulating hippocampal peroxisome proliferator­activated receptor­Î³ (PPAR­Î³). In the present study, it was examined whether treatment with PPAR­Î³ agonist pioglitazone (PIO) is beneficial in counteracting SEV­induced neuroinflammation and cognitive decline in a rat model of CIH. Rats were exposed to CIH for 4 weeks. After 2 weeks of CIH, these animals underwent either 2.6% SEV or control (CON) exposure for 4 h. PIO (60 mg/kg) or vehicle (VEH) was administered orally twice daily for 2 weeks, starting one day prior to SEV or CON exposure. Compared with CIH­CON+VEH rats, CIH­SEV+VEH rats exhibited significant cognitive decline as indicated by increased latency to locate the hidden platform and shorter dwell­time in the goal quadrant in the Morris Water Maze task. Molecular studies revealed that CIH­SEV+VEH rats had increased proinflammatory cytokine expression and microglial activation in the hippocampus, which were associated with decreased PPAR­Î³ activity. Notably, SEV­induced cognitive decline and increases in proinflammatory cytokine expression and microglial activation were prevented by PIO, which increased hippocampal PPAR­Î³ activity. PIO also increased hippocampal PPAR­Î³ activity in CIH­CON rats but did not alter proinflammatory cytokine expression and microglial activation as well as cognitive function. Additionally, expression of hippocampal PPAR­α and PPAR­ß, two other PPAR isotypes, were comparable among the groups. These data suggest that PIO prevents SEV­induced exaggeration of neuroinflammation and cognitive decline under CIH conditions by upregulating hippocampal PPAR­Î³. PIO may have the potential to prevent anesthetic SEV­induced cognitive decline in surgical patients with obstructive sleep apnea.


Assuntos
Disfunção Cognitiva/prevenção & controle , Hipóxia/fisiopatologia , Inflamação/prevenção & controle , Neuroimunomodulação/efeitos dos fármacos , PPAR gama/metabolismo , Pioglitazona/farmacologia , Sevoflurano/toxicidade , Animais , Doença Crônica , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/patologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Hipoglicemiantes/farmacologia , Inflamação/induzido quimicamente , Inflamação/patologia , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Inibidores da Agregação de Plaquetas/toxicidade , Ratos , Ratos Sprague-Dawley
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