RESUMO
INTRODUCTION: The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. METHODS: This study used bidirectional Mendelian randomization (MR) analysis to explore the interactions between nine phenotypes associated with hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements. These measurements included total surface area (SA), average thickness (TH), and the SA and TH of 34 regions defined by the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. A false discovery rate adjustment was applied to the p-values (resulting in q-values) in the analyses of regional cortical structures. RESULTS: A total of 1,260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q=0.018) and the superior frontal lobe (q=0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q=0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 16 and 3 regions exhibited significant effects on blood pressure and AF risk, respectively (q<0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are associated with cognitive function and mood regulation. CONCLUSION: The detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.
RESUMO
Background: This study aims to investigate the association between nine tag single nucleotide polymorphisms (SNPs) in the C3 gene locus and the risk of coronary artery disease (CAD) as well as lipid levels in the Chinese population, and to further explore the interactions between SNPs and environmental factors that may be associated with CAD risk. Methods: A case-control study was conducted to investigate the association between CAD and C3 gene polymorphisms in a hospital setting. The study consisted of 944 CAD patients with a mean age of 55.97 ± 10.182 years and 897 non-CAD controls with a mean age of 55.94 ± 9.162 years. There were 565 males and 288 females in the CAD group and 583 males and 314 females in the control group. TagSNPs in the C3 gene were identified by employing the improved multiplex ligation detection reaction (iMLDR) technique, and multifactor dimensionality reduction (MDR) analysis was utilized to investigate the C3 gene-environment and gene-gene interactions in relation to the risk of CAD. Results: Results of the polymorphism study indicated that the CC genotype of rs7257062 was more frequent in the CAD group compared to the control group (10.9% vs 7.7%), with a statistically significant difference (p = 0.009). Moreover, the TT and CC + CT genotype groups of rs7257062 in the CAD subgroup showed a significant difference in terms of serum triglyceride levels (2.326 ± 1.889 vs 2.059 ± 1.447, p = 0.019). Analysis of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (ApoA), and apolipoprotein B (ApoB) levels revealed no significant differences between the TT and CC + CT genotypes. Furthermore, no significant differences in serum lipid levels were observed between genotypes of the other SNPs. Multivariable logistic analysis, controlling for gender, age, body mass index (BMI), triglycerides (TG), TC, HDL-C, LDL-C, ApoA and ApoB, demonstrated that rs7257062 was still an independent risk factor of CAD (OR = 1.499, 95% CI: 1.036-2.168, p = 0.032). MDR analysis revealed that the rs7257062 interacted significantly with environmental factors such as smoking, diabetes, hypertension, BMI, and TG (p < 0.05). Conclusions: The rs7257062 variation of the C3 gene could be linked to both lipid balance and the risk of CAD. It is conceivable that the interplay between C3 polymorphisms and environmental elements could account for the etiology of CAD.
RESUMO
Noradrenaline belongs to the monoamine system and is involved in cognition and emotional behaviors. Phox2a and Phox2b play essential but non-redundant roles during development of the locus coeruleus (LC), the main noradrenergic (NA) neuron center in the mammalian brain. The ubiquitin E3 ligase Rnf220 and its cofactor Zc4h2 participate in ventral neural tube patterning by modulating Shh/Gli signaling, and ZC4H2 mutation is associated with intellectual disability, although the mechanisms for this remain poorly understood. Here, we report that Zc4h2 and Rnf220 are required for the development of central NA neurons in the mouse brain. Both Zc4h2 and Rnf220 are expressed in developing LC-NA neurons. Although properly initiated at E10.5, the expression of genes associated with LC-NA neurons is not maintained at the later embryonic stages in mice with a deficiency of either Rnf220 or Zc4h2 In addition, we show that the Rnf220/Zc4h2 complex monoubiquitylates Phox2a/Phox2b, a process required for the full transcriptional activity of Phox2a/Phox2b. Our work reveals a role for Rnf220/Zc4h2 in regulating LC-NA neuron development, and this finding may be helpful for understanding the pathogenesis of ZC4H2 mutation-associated intellectual disability.
Assuntos
Neurônios Adrenérgicos/fisiologia , Proteínas de Homeodomínio/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Neurogênese/fisiologia , Proteínas Nucleares/fisiologia , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/fisiologia , Ubiquitinação/genética , Neurônios Adrenérgicos/metabolismo , Animais , Diferenciação Celular/genética , Embrião de Galinha , Embrião de Mamíferos , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Norepinefrina/metabolismoRESUMO
Soma spacing and dendritic arborization during brain development are key events for the establishment of proper neural circuitry and function. Transcription factor Satb2 is a molecular node in regulating the development of the cerebral cortex, as shown by the facts that Satb2 is required for the regionalization of retrosplenial cortex, the determination of callosal neuron fate, and the regulation of soma spacing and dendritic self-avoidance of cortical pyramidal neurons. In this study, we explored downstream effectors that mediate the Satb2-implicated soma spacing and dendritic self-avoidance. First, RNA-seq analysis of the cortex revealed differentially expressed genes between control and Satb2 CKO mice. Among them, EphA7 transcription was dramatically increased in layers II/III of Satb2 CKO cortex. Overexpression of EphA7 in the late-born cortical neurons of wild-type mice via in utero electroporation resulted in soma clumping and impaired self-avoidance of affected pyramidal neurons, which resembles the phenotypes caused by knockdown of Satb2 expression. Importantly, the phenotypes by Satb2 knockdown was rescued by reducing EphA7 expression in the cortex. Finally, ChIP and luciferase reporter assays indicated a direct suppression of EphA7 expression by Satb2. These findings provide new insights into the complexity of transcriptional regulation of the morphogenesis of cerebral cortex.
Assuntos
Córtex Cerebral , Neurônios , Animais , Corpo Celular/metabolismo , Córtex Cerebral/metabolismo , Proteínas de Ligação à Região de Interação com a Matriz , Camundongos , Neurônios/metabolismo , Células Piramidais/metabolismo , Receptor EphA7 , Fatores de Transcrição/metabolismoRESUMO
Pyriproxyfen is a juvenile hormone analogue. The physiological effects of its low-concentration drift during the process of controlling agricultural and forestry pests on non-target organisms in the ecological environment are unpredictable, especially the effects on organs that play a key role in biological function are worthy of attention. The silk gland is an important organ for silk-secreting insects. Herein, we studied the effects of trace pyriproxyfen on autophagy and apoptosis of the silk gland in the lepidopteran model insect, Bombyx mori (silkworm). After treating fifth instar silkworm larvae with pyriproxyfen for 24 h, we found significant shrinkage, vacuolization, and fragmentation in the posterior silk gland (PSG). In addition, the results of autophagy-related genes of ATG8 and TUNEL assay also demonstrated that autophagy and apoptosis in the PSG of the silkworm was induced by pyriproxyfen. RNA-Seq results showed that pyriproxyfen treatment resulted in the activation of juvenile hormone signaling pathway genes and inhibition of 20-hydroxyecdysone (20E) signaling pathway genes. Among the 1808 significantly differentially expressed genes, 796 were upregulated and 1012 were downregulated. Among them, 30 genes were identified for autophagy-related signaling pathways, such as NOD-like receptor signaling pathway and mTOR signaling pathway, and 30 genes were identified for apoptosis-related signaling pathways, such as P53 signaling pathway and TNF signaling pathway. Further qRT-PCR and in vitro gland culture studies showed that the autophagy-related genes Atg5, Atg6, Atg12, Atg16 and the apoptosis-related genes Aif, Dronc, Dredd, and Caspase1 were responsive to the treatment of pyriproxyfen, with transcription levels up-regulated from 24 to 72 h. In addition, ATG5, ATG6, and Dronc genes had a more direct response to pyriproxyfen treatment. These results suggested that pyriproxyfen treatment could disrupt the hormone regulation in silkworms, promoting autophagy and apoptosis in the PSG. This study provides more evidence for the research on the damage of juvenile hormone analogues to non-target organisms or organs in the environment, and provides reference information for the scientific and rational use of juvenile hormone pesticides.
Assuntos
Bombyx , Animais , Bombyx/fisiologia , Seda/genética , Seda/metabolismo , Seda/farmacologia , Apoptose , Larva/metabolismo , Autofagia , Hormônios Juvenis/farmacologia , Hormônios Juvenis/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismoRESUMO
Skeletal muscle dysfunction is a common comorbidity of chronic obstructive pulmonary disease (COPD), and the molecular mechanisms regarding to the pathogenesis of this disease have not been elucidated. In this study, a novel miR-145-5p was significantly upregulated in the serum collected from patients with COPD-associated muscle atrophy, in contrast with the normal participants. Then, we evidenced that silencing of miR-145-5p suppressed cell death and elongated cell survival during cell culture process. Consistently, upregulation of miR-145-5p induced cell apoptosis and restrain cell viability in the C2C12 cells, suggesting that miR-145-5p contributes to cell death. Further experiments evidenced that miR-145-5p decreased the expression levels of phosphorylated PI3K (p-PI3K), Akt (p-Akt) and mTOR (p-mTOR) to inactivate the PI3K/Akt/mTOR pathway, and this pathway was also reactivated by miR-145-5p ablation. Finally, we proved that the protective effects of miR-145-5p ablation were abrogated by co-treating cells with PI3K inhibitor LY294002. Taken together, we concluded that miR-145-5p promoted cell death to facilitate muscle dysfunctions via inactivating the PI3K/Akt/mTOR pathway.
Assuntos
MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Apoptose , Proliferação de Células , Humanos , Fibras Musculares Esqueléticas , Músculo Esquelético , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TORRESUMO
Pyriproxyfen is an insect growth regulator that is widely used in public health and pest control in agriculture. Our previous studies have shown that trace amounts of pyriproxyfen in the environment can cause serious toxic effects in the non-target insect silkworm, including failing to pupate, metamorphose and spin cocoons. However, it is unknown why pyriproxyfen not only has no lethal effects on fifth instar larvae but also tend to increase their body weight. The midgut is the main digestive organs of the silkworm, our results showed that the residual of pyriproxyfen in the silkworm at 24 h after 1 × 10-4 mg/L pyriproxyfen treatment caused severe damage to the midgut microvilli, goblet cells, and nuclei of the silkworm, but body weight and digestibility of the larval were both increased. In addition, pyriproxyfen significantly (p < 0.05) increased the activities of digestive enzymes (α-amylase, trehalase, trypsin and lipase) in the midgut of silkworm. However, it caused down-regulation of ecdysone synthesis-related genes at the end of the fifth instar silkworm, decreased ecdysone titer, and prolonged larval instar. At the same time, pyriproxyfen also activated transcription of detoxification enzymes-related genes such as the cytochrome P450 enzyme genes Cyp9a22 and Cyp15C1, the carboxylesterase genes CarE-8 and CarE-11, and the glutathione S-transferase gene GSTo2. This study elucidated a novel toxicological effect of pyriproxyfen to insects, which not only expands the understanding of the effects of juvenile hormone pesticides on lepidopteran insects but also provides a reference for exploring the ecological security of non-target organisms.
Assuntos
Bombyx , Animais , Ecdisona , Insetos , Hormônios Juvenis/toxicidade , Larva , Peso CorporalRESUMO
BACKGROUND: Although previous studies had confirmed the effectiveness and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), respectively, direct head-to-head comparison of SCIT vs SLIT is sparse. We aimed to compare the efficacy, safety, and compliance of SCIT and SLIT in allergic rhinitis (AR) children. METHODS: This study is a prospective, open-label, and single-center study performed between June 2017 and June 2018. A total of 325 children were grouped into SLIT, Alutard (SCIT1), and NovoHelisen Depot (NHD) (SCIT2) according to the parents' wishes. The adherence and reasons for dropout were recorded. The efficacy of SLIT and SCIT was evaluated by a combined symptom medication score. Adverse events (AEs) were recorded and graded during the whole treatment. RESULTS: The compliance rate was higher in the SCIT group compared with the SLIT group (P < .05). The total nasal symptom score (TNSS), rescue medication score (RMS), and symptom medication score (SMS) after 6-month, 12-month, and 2-year treatment were lower in the SCIT group compared with the SLIT group (P < .05). But the scores between the Alutard and NHD groups were not significantly different. The occurrence of AEs in the SCIT group was significantly higher compared with the SLIT group (P < .05). CONCLUSION: Our results suggested SCIT is more effective compared with SLIT to a certain degree, whereas SLIT had less AEs compared with SCIT. The AIT routes can be chosen according to personal specific conditions.
Assuntos
Rinite Alérgica , Imunoterapia Sublingual , Criança , Dessensibilização Imunológica , Humanos , Injeções Subcutâneas , Estudos Prospectivos , Rinite Alérgica/terapia , Resultado do TratamentoRESUMO
The use of graphene as a new type of electrode at molecular junctions has led to a renewal of molecular electronics. Indeed, the symmetry breaking induced by the graphene electrode yields different electronic behaviors at the molecular junction and in particular enhanced conductance for longer molecules. In this respect, several studies involving different molecular backbones and anchoring groups have been performed. Here in the same line, we consider oligopthiophene based hybrid gold-graphene junctions and we measure their electrical properties using the STM-I(s) method in order to determine their attenuation factor and the effect of specific anchoring groups. The results are supported by density functional theory (DFT) calculations, and exhibit a similar behavior to what is observed at alkane-based junctions.
RESUMO
Environmental residues of pryriproxyfen, a juvenile hormone analogue (JHA) type pesticide, may have on unintended consequences on non-target insects. However, the mechanism of pyriproxyfen action and silk protein synthesis in silkworms has not been reported. In the present study, we treated the silkworms with trace pyriproxyfen (1 × 10-4 mg/L) and found that the silkworm larvae showed no obvious poisoning symptoms, while the development of silk glands and cocoon-forming function were both seriously damaged due to the accumulation of pyriproxyfen in posterior silk gland (PSG). The titer of the juvenile hormone (JH) was increased, whereas the content of 20-hydroxyecdysone (20E) was reduced in pyriproxyfen-exposed hemolymph. Met2 is a component of the JH receptor complex and JH can promote its phosphorylation. We found Met2 and SRC were up-regulated in the larval stage after pyriproxyfen exposure, the JH-Met2/SRC complex led to the up-regulation of downstream genes Kr-h1, and Dimm, and then specifically inhibited the transcription of Fib-H. Meanwhile, the transcription of ecdysone inducible transcription factor Br-C Z4 was also inhibited by pyriproxyfen and resulted in the defects of metamorphosis. In conclusion, the trace pyriproxyfen could affect the metamorphosis and silk protein synthesis through the Met2-mediated pathway. Our study provided new evidence that Met2 might be a potential target gene of JHA in Lepidoptera.
Assuntos
Bombyx , Animais , Bombyx/genética , Proteínas de Insetos/genética , Hormônios Juvenis , Piridinas , SedaRESUMO
OBJECTIVE: This study was aimed to investigate the role of Toll-like receptor 4 (TLR4) in advanced glycation end products (AGEs)- induced macrophage polarization toward M1. METHODS: Isolated primary macrophages were exposed to prepared AGEs at concentrations of 0, 2.5, 5 and 10 µmol/L. Macrophages were also exposed to hydrogen peroxide (H2O2) which provided exogenous reactive oxygen species (ROS). Receptor for AGEs (RAGE) was over-expressed by a vector. Specific siRNA silencing TLR4 and inhibitor TAK-242 were used to pre-treat the macrophages. Intracellular ROS was determined by DCFH-DA. Immunofluorescence staining was used to evaluate the expression of inducible nitric oxide synthase (iNOS) which is the marker of M1 macrophage phenotype. Real-time PCR was used to assess the mRNA expression level of TLR4 and RAGE. Protein expression levels of cytoplasmic RAGE, TLR4, nuclear signal transducers and activators of transcription 1 (STAT1) and phosphorylation levels of cytoplasmic STAT1 were evaluated by Western blotting. ELISA was used to measure concentrations of interleukin 6 (IL6), IL12 and tumor necrosis factor (TNF)α in supernatant of cell culture medium of macrophages. RESULTS: AGEs significantly elevated intracellular ROS generation, expression levels of iNOS, cytoplasmic RAGE, TLR4, nuclear STAT1, phosphorylation levels of cytoplasmic STAT1, as well as IL6, IL12 and TNFα contents in a concentration-dependent manner. TLR4 silencing and inhibitor pre-treatment reduced expression levels of cytoplasmic RAGE, TLR4, phosphorylation of STAT1 and nuclear STAT1 in AGEs-exposed macrophages without affecting RAGE expression and intracellular ROS production levels. RAGE over-expression elevated both ROS and TLR4 expression levels in macrophages. TLR4 expression elevation was also found in H2O2-treat macrophages. CONCLUSION: AGEs induced macrophage polarization toward M1 via activating RAGE/ROS/TLR4/STAT1 signaling pathway.
Assuntos
Produtos Finais de Glicação Avançada/farmacologia , Macrófagos Peritoneais/fisiologia , Receptor 4 Toll-Like/metabolismo , Animais , Citocinas/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Peróxido de Hidrogênio/farmacologia , Ativação de Macrófagos , Macrófagos Peritoneais/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase Tipo II/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais , Sulfonamidas/farmacologia , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/genéticaRESUMO
PURPOSE: We investigated whether increased expression of activated mitogen-activated protein kinase (MAPK) kinases 1 (MEK1) restores ischemic post-conditioning (IPostC) protection in hypertrophic myocardium following ischemia/reperfusion (I/R) injury. METHODS: C57Bl/6 mice received recombinant adeno-associated virus type 9 (rAAV9)-mediated activated MEK1 gene delivery systemically, then following the induction of cardiac hypertrophy via transverse aortic constriction for 4 weeks. In a Langendorff model, hypertrophic hearts were subjected to 40 min/60 min I/R or with IPostC intervention consisting of 6 cycles of 10 s reperfusion and 10 s no-flow before a 60-min reperfusion. Hemodynamics, infarct size (IS), myocyte apoptosis and changes in expression of reperfusion injury salvage kinase (RISK) pathway were examined. RESULTS: rAAV9-MEK1 gene delivery led to a 4.3-fold and 2.7-fold increase in MEK1 mRNA and protein expression in the heart versus their control values. I/R resulted in a larger IS in hypertrophic than in non-hypertrophic hearts (52.3 ± 4.7% vs. 40.0 ± 2.5%, P < 0.05). IPostC mediated IS reduction in non-hypertrophic hearts (27.6 ± 2.6%, P < 0.05), while it had no significant effect in hypertrophic hearts (46.5 ± 3.1%, P=NS) compared with the IS in non-hypertrophic or hypertrophic hearts subjected to I/R injury only, respectively. Hemodynamic decline induced by I/R was preserved by IPostC in non-hypertrophic hearts but not in hypertrophic hearts. rAAV9-MEK1 gene delivery restored IPostC protection in hypertrophic hearts evidenced by reduced IS (32.0 ± 2.8% vs. 46.5 ± 3.1%) and cardiac cell apoptosis and largely preserved hemodynamic parameters. These protective effects were associated with significantly increased phosphorylation of ERK1/2 and ribosomal protein S6 kinases (p70S6K), but it had no influence on Akt and glycogen synthase kinase-3ß. CONCLUSION: These results demonstrated that rAAV9-mediated activated MEK1 expression restores IPostC protection in the hypertrophic heart against I/R injury through the activation of ERK pathway.
Assuntos
Dependovirus/genética , Técnicas de Transferência de Genes , Vetores Genéticos , Hipertrofia Ventricular Esquerda/terapia , Pós-Condicionamento Isquêmico , MAP Quinase Quinase 1/biossíntese , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/enzimologia , Animais , Apoptose , Modelos Animais de Doenças , Indução Enzimática , Hipertrofia Ventricular Esquerda/enzimologia , Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/patologia , Preparação de Coração Isolado , MAP Quinase Quinase 1/genética , Masculino , Camundongos Endogâmicos C57BL , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Fosforilação , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismoRESUMO
The single molecule conductance of hybrid platinum/alkanedithiol/graphene junctions has been investigated with a focus on understanding the influence of employing two very different contact types. We call this an "anti-symmetric" configuration, with the two different contacts here being platinum and graphene, which respectively provide very different electronic coupling to the alkanedithiol bridge. The conductance of these junctions is experimentally investigated by using a non-contact scanning tunneling microscopy (STM) based method called the I(s) technique. These experimental determinations are supported by density functional theory (DFT) calculations. These alkanedithiol bridging molecules conduct electric current through the highest occupied molecular orbital (HOMO), and junctions formed with Pt/graphene electrode pairs are slightly more conductive than those formed with Au/graphene electrodes which we previously investigated. This is consistent with the lower work function of gold than that of platinum. The measured conductance decays exponentially with the length of the molecular bridge with a low tunneling decay constant, which has a similar value for Pt/graphene and Au/graphene electrode pairs, respectively. These new results underline the importance of the coupling asymmetry between the two electrodes, more than the type of the metal electrode itself. Importantly, the tunneling decay constant is much lower than that of alkanedithiols with the symmetrical equivalent, i.e. identical metal electrodes. We attribute this difference to the relatively weak van der Waals coupling at the graphene interface and the strong bond dipole at the Pt-S interface, resulting in a decrease in the potential barrier at the interface.
RESUMO
Several studies have investigated the use of simple in vitro tests for the assessment of rabies antibody titers in serum samples from vaccinated human subjects, which would allow the effectiveness of rabies vaccination to be conveniently evaluated. To this end, a novel time-resolved fluoroimmunoassay (TRFIA) for the assessment of rabies antibody titers was established in this study for evaluating the effectiveness of protection against rabies. The TRFIA had a satisfactory limit of detection value (0.035 IU/mL) under optimal conditions. Additionally, the application of the TRFIA was demonstrated in 68 serum samples with satisfactory results. The coefficient variations (CVs) were all <10%, and the recoveries were in the range of 90-110%. The correlation coefficient of titer values obtained using the present TRFIA and the rapid fluorescent focus inhibition test (RFFIT) was 0.733, with a coincidence rate regarding the evaluation results (protected or not protected by vaccination) of 100%. The preliminary results confirmed that the TRFIA had a higher performance than an enzyme-linked immunosorbent assay (ELISA), and could potentially replace the ELISA. Based on these results, the novel TRFIA appears to be a convenient tool for the evaluation of rabies vaccination results based on serum samples from vaccinated human subjects.
Assuntos
Anticorpos Antivirais/imunologia , Fluorimunoensaio/métodos , Vacina Antirrábica/imunologia , Vírus da Raiva/imunologia , Raiva/imunologia , Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Raiva/diagnóstico , Raiva/virologia , Vacina Antirrábica/administração & dosagem , Vírus da Raiva/fisiologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores de Tempo , Vacinação/métodosRESUMO
A combined experimental and theoretical study on molecular junctions with asymmetry in both the electrode type and in the anchoring group type is presented. A scanning tunnelling microscope is used to create the "asymmetric" Au-S-(CH2 )n-COOH-graphene molecular junctions and determine their conductance. The measurements are combined with electron transport calculations based on density functional theory (DFT) to analyze the electrical conductance and its length attenuation factor from a series of junctions of different molecular length (n). These results show an unexpected trend with a rather high conductance and a smaller attenuation factor for the Au-S-(CH2 )n -COOH-graphene configuration compared to the equivalent junction with the "symmetrical" COOH contacting using the HOOC-(CH2 )n -COOH series. Owing to the effect of the graphene electrode, the attenuation factor is also smaller than the one obtained for Au/Au electrodes. These results are interpreted through the relative molecule/electrode couplings and molecular level alignments as determined with DFT calculations. In an asymmetric junction, the electrical current flows through the less resistive conductance channel, similarly to what is observed in the macroscopic regime.
RESUMO
OBJECTIVE: To investigate the use of antibiotics in children with community-acquired pneumonia (CAP) in multiple regions of China, and to provide a reference for CAP standard treatment and rational antibiotic use in children. METHODS: The medical data of 1 383 children with CAP who were hospitalized in the department of pediatrics in 10 grade A tertiary hospitals from 9 cities between April 14, 2014 and January 1, 2016 were reviewed, to analyze the status of antibiotic use in hospitalized children in North China, Northeast China, East China, and South China. RESULTS: The overall rate of antibiotic use in children with CAP was 89.08%, with 88.7% in North China, 95.5% in Northeast China, 83.3% in East China, and 86.6% in South China. The main types of antibiotics used were cephalosporins, macrolides, compound preparations of ß-lactam antibiotics, polyphosphoric broad-spectrum antibiotics and other ß-lactam antibiotics. The selection of antibiotics was generally rational, but antibiotics were still used in some patients with viral infection alone or a combined use of ≥2 kinds of antibiotics were noted in some patients with infection caused by one kind of pathogen. Irrational antibiotic use was observed in 131 children (10.63%). CONCLUSIONS: There are high rates of antibiotic use and irrational use of antibiotics among children with CAP. Standard management of antibiotic use in children with CAP should be strengthened.
Assuntos
Infecções Comunitárias Adquiridas , Antibacterianos/uso terapêutico , Criança , Criança Hospitalizada , China , Infecções Comunitárias Adquiridas/tratamento farmacológico , HumanosRESUMO
A fully metal-free molecular junction (MJ) has been built by using an electrochemically etched carbon fibre STM tip as the top electrode and graphene as the bottom electrode. The corresponding conductance values for 1,n-alkanediamine and 1,n-alkanedithiol (n = 2, 4, 6, 8 and 10) have been measured using the STM-I(s) technique. The tunnelling decay constant of the alkanediamine and alkanedithiol junctions with these carbon contacts is much lower than the corresponding metal contacted junctions of 0.24 and 0.38 per -CH2 unit, but the junction conductance with these carbon contacts is also lower. The carbon fibre tip can be considered a good candidate as an electrode. Compared with a gold tip, the carbon fibre tip leads to correspondingly lower molecular junction conductance.
RESUMO
BACKGROUND: This study aimed to evaluate the association of the metabolic syndrome (MetS) with various anthropometric and atherogenic parameters in adult Kazakh population in China. METHODS: Four thousand ninety-four Kazakhs were recruited since 2007 to 2010. MetS and its components were confirmed according to IDF criteria. Area under the curve (AUC) of each variable was compared. Sensitivity (Sen), specificity (Spe), shortest distance in receiver's operating characteristic curve (ROC) and cutoff of each variable to diagnose MetS were calculated. RESULTS: 28.6 % of men and 31.0 % of women had MetS in the Kazakh population. In men, WHtR had the highest AUC value 0.821, followed by BMI (0.801), TG/HDL-C (0.792), WHR (0.776) and BAI (0.666). In women, WHtR also had the highest AUC value (0.835), following by BMI (0.789), WHR (0.778), TG/HDL-C (0.778) and BAI (0.751). WHtR had the shortest ROC distance that was 0.37 and the optimal cutoff was 0.55 in men. In women, WHtR also had the shortest ROC distance of 0.35 and the optimal cutoff was 0.54. CONCLUSION: WHtR is the best predictor of MetS in both Kazakh men and women according to the IDF criteria.
RESUMO
BACKGROUND: In animal models, secreted frizzled related protein 1 (Sfrp1) inhibition of the Wnt signaling pathway is beneficial because Sfrp1 reduces myocardial apoptosis and prevents heart failure. The mechanisms mediating the cellular survival effect of Sfrp1 has not been completely elucidated. The present study was designed to investigate the possible protective actions of Sfrp1 on cardiac muscle cells using an in vitro model of ischemia/reperfusion, and to evaluate the possible involvement of the Wnt signaling pathway. METHODS: We used a recombinant AAV9 vector to deliver the Sfrp1 gene into H9C2 rat cardiomyoblasts and adopted an in vitro model of ischemia/reperfusion. Cell vitality was measured by CKK-8 and the trypan blue exclusion assay. Western blot was used to evaluate the expression of Dvl-1, ß-catenin, c-Myc, Bax, and Bcl-2. Flow cytometry analysis of cardiomyocyte apoptosis was performed. RESULTS: We confirmed that Sfrp1 significantly increased cell viability (assayed by trypan blue and CKK-8) and decreased apoptosis (assayed by flow cytometry analysis and the Bax/Bcl-2 ratio). These effects were partly attributable to the ability of Sfrp1 to down-regulate Wnt signaling pathway (assayed by Western blot to evaluate the expression of Dvl-1, ß-catenin, and c-Myc). Indeed, reactivation of the Wnt signaling pathway activity with the specific activator, Licl, reduced Sfrp1-induced cardioprotection during hypoxia and reoxygenation. CONCLUSIONS: The present study demonstrated that Sfrp1 directly protected H9C2 cells from hypoxia and reoxygenation-induced reperfusion injury and apoptosis through inhibition of the Wnt signaling pathway, and added new mechanistic insight regarding the cardioprotective role of Sfrp1 on ischemic damage.
Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Membrana/metabolismo , Miocárdio/metabolismo , Via de Sinalização Wnt , Animais , Apoptose , Hipóxia Celular/fisiologia , Linhagem Celular , Sobrevivência Celular , Regulação da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas de Membrana/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/citologia , Miocárdio/patologia , Ratos , Proteína X Associada a bcl-2/metabolismo , beta Catenina/metabolismoRESUMO
Adeno-associated virus (AAV) has become one of the most promising gene transfer tools for gene therapy. This work aims to evaluate tropism, gene transfer efficiency and safety of AAV9 vectors produced with recombinant baculovirus (rBac)-based system. AAV9-CMV-GFP and AAV9-CBA-GFP were produced using a rBac system, 1 × 10(11) particles of each vectors were administered intravenously (i.v.) into mice and animals were killed at 1, 2, 3, 4, 5 and 8 weeks after administration. The GFP expression in different organs was analyzed by fluorescence imaging and Western blot. Viral genomic quantities were measured using qPCR. In vitro transduction efficiency of AAV9 vectors in primary cardiomyocytes and hepatocytes was determined by flow cytometry. Toxicity of AAV9 vectors was evaluated by determining certain cardiac and liver injury biomarkers and renal function test in vivo and TUNEL analysis in vitro. The data showed that AAV9 viral particles packaged by the rBac system were fully functional in vivo and in vitro. The CMV promoter predominantly induced higher cardiac GFP transgene expression and DNA copy numbers while the CBA promoter resulted in robust GFP expression and high vector DNA copy numbers in mouse liver, both in a time-dependent increased manner. Such distinct preferential effects were also observed in the heart and liver as early as 3 and 5 days after co-infection. Both the AAV9-CMV and AAV9-CBA viral packages did not induce heart, liver and renal damage and cell apoptosis. These results indicated that AAV9-CMV can efficiently and safely direct cardiac gene transfer, whereas AAV9-CBA is preferential for liver gene delivery.