RESUMO
In December 2019, coronavirus disease 2019 (COVID-19), which is caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan (Hubei province, China)1; it soon spread across the world. In this ongoing pandemic, public health concerns and the urgent need for effective therapeutic measures require a deep understanding of the epidemiology, transmissibility and pathogenesis of COVID-19. Here we analysed clinical, molecular and immunological data from 326 patients with confirmed SARS-CoV-2 infection in Shanghai. The genomic sequences of SARS-CoV-2, assembled from 112 high-quality samples together with sequences in the Global Initiative on Sharing All Influenza Data (GISAID) dataset, showed a stable evolution and suggested that there were two major lineages with differential exposure history during the early phase of the outbreak in Wuhan. Nevertheless, they exhibited similar virulence and clinical outcomes. Lymphocytopenia, especially reduced CD4+ and CD8+ T cell counts upon hospital admission, was predictive of disease progression. High levels of interleukin (IL)-6 and IL-8 during treatment were observed in patients with severe or critical disease and correlated with decreased lymphocyte count. The determinants of disease severity seemed to stem mostly from host factors such as age and lymphocytopenia (and its associated cytokine storm), whereas viral genetic variation did not significantly affect outcomes.
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Betacoronavirus/genética , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno/imunologia , Linfopenia/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Síndrome do Desconforto Respiratório/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Animais , Infecções Assintomáticas/epidemiologia , Betacoronavirus/classificação , Betacoronavirus/isolamento & purificação , COVID-19 , China/epidemiologia , Estudos de Coortes , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Estado Terminal/epidemiologia , Progressão da Doença , Evolução Molecular , Feminino , Variação Genética , Genoma Viral/genética , Hospitalização/estatística & dados numéricos , Humanos , Mediadores da Inflamação/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Interleucina-8/sangue , Interleucina-8/imunologia , Contagem de Linfócitos , Linfopenia/complicações , Masculino , Pessoa de Meia-Idade , Pandemias , Filogenia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Síndrome do Desconforto Respiratório/complicações , SARS-CoV-2 , Linfócitos T/citologia , Linfócitos T/imunologia , Fatores de Tempo , Resultado do Tratamento , Virulência/genética , Eliminação de Partículas Virais , Adulto Jovem , Zoonoses/transmissão , Zoonoses/virologiaRESUMO
Asymmetric PCR is widely used to produce single-stranded amplicons (ss-amplicons) for various downstream applications. However, conventional asymmetric PCR schemes are susceptible to events that affect primer availability, which can be exacerbated by multiplex amplification. In this study, a new multiplex asymmetric PCR approach that combines the amplification refractory mutation system (ARMS) with the homo-Tag-assisted nondimer system (HANDS) is described. ARMS-HANDS (A-H) PCR utilizes equimolar-tailed forward and reverse primers and an excess Tag primer. The tailed primer pairs initiate exponential symmetric amplification, whereas the Tag primer drives linear asymmetric amplification along fully matched strands but not one-nucleotide mismatched strands, thereby generating excess ss-amplicons. The production of ss-amplicons is validated using agarose gel electrophoresis, sequencing, and melting curve analysis. Primer dimer alleviation is confirmed by both the reduced Loss function value and a 20-fold higher sensitivity in an 11-plex A-H PCR assay than in an 11-plex conventional asymmetric PCR assay. Moreover, A-H PCR demonstrates unbiased amplification by its allele quantitative ability in correct identification of all 31 trisomy 21 samples among 342 clinical samples. A-H PCR is a new generation of multiplex asymmetric amplification approach with various applications, especially when sensitive and quantitative detection is required.
Assuntos
Reação em Cadeia da Polimerase Multiplex , Mutação , Humanos , Reação em Cadeia da Polimerase Multiplex/métodos , Primers do DNA/química , Síndrome de Down/genética , Síndrome de Down/diagnósticoRESUMO
Forests, the ancient wooden giants, are both symbols of natural beauty and reservoirs of carbon stocks. The current climate crisis has created an urgent need for an in-depth study of forest ecosystems and carbon stocks. Based on forest inventory data from field surveys and four bioclimatic zones [Zone 1 (Z1, humid forest), Zone 2 (Z2, semi-humid forest), Zone 3 (Z3, semi-humid to semi-arid forest-grassland), and Zone 4 (Z4, semi-arid typical grassland)], two methods [Method 1 (M1) and Method 2 (M2)] were used to estimate carbon stocks in forest ecosystems in Shaanxi Province, China, and explored the spatial patterns of carbon pools and potential influences. The total forest ecosystem carbon pool amounted to 520.80 Tg C, of which 53.60% was stored aboveground, 17.16% belowground, and 29.24% in soil (depth of 0-10 cm). Spatially, there were marked north-south gradients in both biomass (Z2 > Z3 > Z1 > Z4) and soil organic carbon densities (Z1 > Z2 > Z3 > Z4). The differences between aboveground and belowground biomass carbon density across broadleaf, needle-leaf, and broadleaf and needle-leaf mixed forest were not pronounced, while soil organic carbon density had the order of broadleaf (18.38 Mg C/ha) > needle-leaf (11.29 Mg C/ha) > broadleaf and needle-leaf mixed forest (10.33 Mg C/ha). Under an ideal scenario that excludes external factors, mainly forest growth, the sequestration potential of forest biomass by 2032 was estimated by M1 as 85.43 Tg, and by M2 to be substantially higher at 176.21 Tg. As of 2062, M1 estimated 155.97 Tg of sequestration potential for forest biomass. The spatial patterns of forest biomass and soil carbon density were closely related to climatic factors, and these relationships allowed the spatial division into two distinct climatic regions. Moreover, biomass carbon density was significantly correlated with the normalized difference vegetation index, soil silt, and elevation. This study provides key information for promoting the strategic shift from light-green to deep-green forest systems in Shannxi Province and updates the estimation methods of forest ecosystems' carbon pools based on field surveys.
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Biomassa , Sequestro de Carbono , Carbono , Ecossistema , Florestas , Solo , Carbono/análise , Solo/química , ChinaRESUMO
Through evolution, Hepatitis B Virus (HBV) developed highly intricate mechanisms exploiting host resources for its multiplication within a constrained genetic coding capacity. Yet a clear picture of viral hitchhiking of cellular processes with spatial resolution is still largely unsolved. Here, by leveraging bDNA-based fluorescence in situ hybridization (FISH) combined with immunofluorescence, we developed a microscopic approach for multiplex detection of viral nucleic acids and proteins, which enabled us to probe some of the key aspects of HBV life cycle. We confirmed the slow kinetics and revealed the high variability of viral replication at single-cell level. We directly visualized HBV minichromosome in contact with acetylated histone 3 and RNA polymerase II and observed HBV-induced degradation of Smc5/6 complex only in primary hepatocytes. We quantified the frequency of HBV pregenomic RNAs occupied by translating ribosome or capsids. Statistics at molecular level suggested a rapid translation phase followed by a slow encapsidation and maturation phase. Finally, the roles of microtubules (MTs) on nucleocapsid assembly and virion morphogenesis were analyzed. Disruption of MTs resulted in the perinuclear retention of nucleocapsid. Meanwhile, large multivesicular body (MVB) formation was significantly disturbed as evidenced by the increase in number and decrease in volume of CD63+ vesicles, thus inhibiting mature virion secretion. In conclusion, these data provided spatially resolved molecular snapshots in the context of specific subcellular activities. The heterogeneity observed at single-cell level afforded valuable molecular insights which are otherwise unavailable from bulk measurements.
Assuntos
DNA Viral/análise , Vírus da Hepatite B/fisiologia , Hepatite B/virologia , RNA Viral/análise , Frações Subcelulares/virologia , Montagem de Vírus , Replicação Viral , Células Hep G2 , Humanos , Análise Espaço-Temporal , VírionRESUMO
A Gram-negative, aerobic bacterial strain, designated LX-88T, was isolated from seleniferous soil in Enshi, Hubei Province, PR China. Strain LX-88Toxidized elemental selenium to selenite, and produced carotenoids but not bacteriochlorophyll. The isolate grew optimally at 28 °C, pH 8.0 and with 0.5â% (w/v) NaCl. Phylogenetic analysies of the organism's 16S rRNA and bacterial core gene set sequences indicated that LX-88T belongs to the genus Croceibacterium, and has the highest degree of 16S rRNA gene sequence similarity to Croceibacterium soli MN-1T (97.4â%). The LX-88T genome was 3.4 Mbp and had a G+C content of 63.6âmol%. The average nucleotide identity and digital DNA-DNA hybridization values showed low relatedness (below 95 and 70â%, respectively) between strain LX-88T and other strains in the genus Croceibacterium. Ubiquinone-10 was the predominant quinone. The polar lipid profile was dominated by diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, sphingoglycolipid, an unidentified aminolipid, an unidentified phospholipid and an unidentified lipid. The major fatty acid was summed feature 8 (C18â:â1 ω7c and/or C18â:â1 ω6c). These physiological and biochemical tests facilitated the differentiation of strain LX-88T from other members of the genus Croceibacterium. The results of this multifaceted taxonomic study indicate that strain LX-88T represents a novel species in the genus Croceibacterium, for which the name Croceibacterium selenioxidans sp. nov. is proposed. The type strain is LX-88T (=MCCC 1K08007T=LMG 32570T).
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Ácidos Graxos , Fosfolipídeos , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Composição de Bases , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Análise de Sequência de DNA , Fosfolipídeos/química , Ubiquinona/químicaRESUMO
Cucurbitacin B, a tetracyclic triterpenoid compound extracted from various plants, has been proven to exert a vital role in various diseases. However, the effect of cucurbitacin B on myocardial infarction (MI) and ischemia-reperfusion (I/R) injury is still relatively unclear. The main purpose of the present study was to investigate the effect of cucurbitacin B on cell apoptosis and oxidative damage after myocardial I/R injury in vitro and in vivo and elucidate the molecular mechanisms underlying its role. The 56-day-old adult mice and 1-day-old neonatal mice cardiomyocytes were used to construct I/R or oxygen-glucose deprivation/reoxygenation (OGD/R) injury models. The oxidative injury, western blot and TUNEL assay were performed to evaluate cardiomyocyte damage in the present study. In vitroï¼ we confirmed that cucurbitacin B could attenuate LDH release, oxidative stress and cell apoptosis in cardiomyocytes exposed to OGD/R. Besides, we confirmed in an adult I/R mouse model that cucurbitacin B can improve cardiac repair and block cell apoptosis in the acute phase (24 h) post-myocardial I/R injury, as well as promote long-term cardiac function and fiber scar area after 28 days of I/R. Mechanically, we clarify that cucurbitacin B exerts cardiomyocyte protective effects through activating the JAK2/STAT3 signaling pathway. In conclusion, our study elucidates for the first time the protective role of cucurbitacin B in cardiac I/R injury, which provides a novel perspective for better prevention of I/R injury through the JAK2/STAT3 signaling pathway.
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Traumatismo por Reperfusão Miocárdica , Triterpenos , Animais , Camundongos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Apoptose , Miócitos CardíacosRESUMO
The expression of various forms of hepatitis B virus (HBV) surface proteins regulates the release of mature virion, but whether they affect the release of other incomplete viral particles, such as naked capsid, is not clear. Here, by stable overexpression of large or middle/small hepatitis B surface proteins (LHBs, M/SHBs) in HepAD38 cells, we evaluated their effects on the release of complete and incomplete viral particles. Overproduction of LHBs inhibited the release of all surface proteins, which increased the ratio of naked capsids/virions. This effect was accompanied by the elevated extracellular HBV RNA. On the other hand, overexpression of M/SHBs greatly improved the secretion of enveloped viral and subviral particles. In situ visualization of viral DNA and LHBs revealed intracellular retention of mature virions when LHBs were overexpressed. These results indicate that the molecular decision on secretion of enveloped or unenveloped viral particles is modulated by the intracellular ratio of large, middle and small surface antigens. This mechanism may be relevant in the progression and resolution of HBV-induced chronic liver disease.
Assuntos
Vírus da Hepatite B , Hepatite B , Proteínas do Capsídeo/metabolismo , DNA Viral/genética , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Humanos , Proteínas de Membrana , Vírion/genética , Replicação ViralRESUMO
AIMS: Idiopathic membranous nephropathy (IMN) is a common cause of adult nephrotic syndrome. Currently, the diagnosis of IMN mainly depends on renal biopsy, which is invasive. What's more, markers already known for the clinical diagnosis of IMN are not sensitive enough. The present study aims to investigate the profiling of urinary exosomal circular RNAs (circRNAs) of IMN, and to look for a potential biomarker for diagnosis of IMN. METHODS: Urine exosomes were collected from patients with IMN and idiopathic nephrotic syndrome (INS), as well as healthy controls (HCs) by ultracentrifuge. A pairwise comparison between 5 IMN and 5 HC was performed by high-throughput sequencing. Enrichment analysis were performed to explore the potential functions of differentially expressed circRNAs in IMN. Among three differentially expressed circRNAs which may be involved in signaling pathways of pathogenesis of IMN and matched conserved mouse circRNAs, hsa_circ_0001250 was selected as the target circRNA after quantitative polymerase chain reaction among 23 IMN, 19 INS and 23HC. Sanger sequencing and RNase R digestion assay were performed to validated the ring-structure and sequence of hsa_circ_0001250. ROC (Receiver Operating Characteristic) curve correlation analysis was used to further validate the potential utility of hsa_circ_0001250 as a diagnostic biomarker of IMN. A circRNA-miRNA-mRNA network was constructed to reflect the relationship between hsa_circ_0001250 and its target miRNAs and mRNAs. RESULTS: 766 up-regulated and 283 down-regulated circRNAs were identified in IMN patients. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed signaling pathways of pathogenesis of IMN which the different expressed circRNAs may participate in. The ring-structure and the sequence of hsa_circ_0001250 were confirmed, the expression of hsa_circ_0001250 was validated significantly increased in IMN, relevant with high level of proteinuria. A circRNA-miRNA-mRNA network reflected that hsa_circ_0001250 may play a role in the pathogenesis of IMN by target hsa-miR-639 and hsa-miR-4449. CONCLUSION: We revealed the expression and functional profile of differentially expressed urinary exosomal circRNAs of IMN patients. Urinary exosomal hsa_circ_0001250 was tested as a potential biomarker of IMN and a predicted circRNA-miRNA-mRNA network was constructed.
Assuntos
Glomerulonefrite Membranosa , MicroRNAs , Síndrome Nefrótica , Animais , Camundongos , RNA Circular/genética , MicroRNAs/genética , RNA Mensageiro , Biomarcadores/análiseRESUMO
Based on the theory of circular polarization dichroism in electromagnetic fields, this paper studies the circular dichroism (CD) characteristics of metasurfaces. Using a stable silicon material, an innovative "double L-shaped" composite structure formed by two L crosses is proposed to improve CD. Under a wide spectrum with wavelengths of 1000-1500 nm, the left circularly polarized (LCP) and right circularly polarized (RCP) lights pass through the structure, and we study the influence of different structural parameters on the CD, in order to obtain the best structural parameters. These realize the cross polarization of left-right circularly polarized light. In addition, at the wavelength of 1302.63 nm, the LCP light illuminates the structure, which realizes the cross polarization of LCP light; that is, the structure realizes the function of a half-wave plate. The RCP light incident structure realizes the function of a filter. It has great application prospects in biological detection, half-wave plates, filters, and other fields.
RESUMO
Obesity is an important cause of diseases such as type 2 diabetes, non-alcoholic fatty liver and atherosclerosis. The use of ingredients extracted from traditional Chinese medicine for weight loss is now receiving more and more attention. Ginseng has been recorded since ancient times for the treatment of diabetes. The (20R)-Panaxadiol (PD) belongs to the ginseng diol type compounds, which are moderately bioavailable and may remain in the intestinal tract for a longer period of time. This study investigated the potential positive effect of PD in ob/ob mice and evaluated its effect against obesity. The ob/ob mice were administered PD for ten weeks. Our study showed that PD could improve obesity, glucose tolerance disorder, as well as gut dysbiosis. Panaxadiol decreased ob/ob mice's Firmicutes/Bacteroidetes (F/B). Furthermore, 16S rRNA gene sequencing of the fecal microbiota suggested that PD changed the composition of the gut microbiota in ob/ob mice and modulated specific bacteria such as lactobacillus, prevotellace and so on. Moreover, PD improved the intestinal wall integrity. In conclusion, our results suggest that (20R)-Panaxadiol, as an active ingredient of the traditional Chinese medicinal herb ginseng, may improve obesity to some extent via improving gut microbiota.
Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Panax , Animais , Diabetes Mellitus Tipo 2/complicações , Dieta Hiperlipídica , Ginsenosídeos , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , RNA Ribossômico 16S/genéticaRESUMO
Glomerulonephritis, also known as nephritis syndrome (nephritis for short), is a common kidney disease. Previous research has proved that microRNAs (miRNAs) frequently regulate various diseases including nephritis. Nonetheless, the biological function and molecular mechanism of miR-17-5p are unclear in nephritis. In the current study, RT-qPCR analysis showed that miR-17-5p was downregulated in Ang II-induced podocytes. Also, according to the results from RT-qPCR analysis, CCK-8 assay, flow cytometric analysis, western blot analysis, and ELISA miR-17-5p elevation alleviated Ang II-induced podocyte injury. Besides, luciferase reporter assay, western blot and RT-qPCR analyses revealed that SMOC2 was targeted by miR-17-5p in Ang II-induced podocytes. Additionally, rescue assays demonstrated that overexpressed SMOC2 counteracted the influence of overexpressed miR-17-5p on cell injury of Ang II-induced podocytes. Moreover, our data suggested that miR-17-5p-SMOC2 axis regulated TGFß and NF-κB signaling activation in Ang II-induced podocytes. SMOC2 regulated cell viability, apoptosis and extracellular matrix (ECM) deposition in Ang II-induced podocytes via TGFß signaling, and SMOC2 regulated inflammation in Ang II-induced podocytes through NF-κB signaling. Overall, our study demonstrated that miRNA-17-5p restrained the dysfunction of Ang-II induced podocytes by suppressing SMOC2 via the NF-κB and TGFß signaling.
Assuntos
MicroRNAs , Podócitos , Apoptose , Proteínas de Ligação ao Cálcio , Linhagem Celular , MicroRNAs/genética , NF-kappa B/genética , NF-kappa B/metabolismo , Podócitos/metabolismo , Fator de Crescimento Transformador betaRESUMO
OBJECTIVE: To assess the efficacy and safety of Aß-targeting agents for mild to moderate Alzheimer's disease. METHODS: The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform search portal were searched from their inception to April 2020. We generated pooled estimates using random effects meta-analyses. RESULTS: Nineteen randomised controlled trials, of which 17 had a low risk of bias, included 12 903 participants. The meta-analysis showed no difference in the cognitive subscale of Alzheimer's Disease Assessment Scale (ADAS-Cog) between anti-Aß drugs and placebo (mean difference (MD): 0.20, 95% CI -0.40 to 0.81; I 2=99.8%; minimal important difference 3.1-3.8 points, moderate-certainty evidence). For ADAS-Cog, results suggested that one drug that increases Aß clearance may differ in effect (MD: -0.96, 95% CI -0.99 to -0.92) from drugs that reduce Aß production (MD: 0.78, 95% CI 0.25 to 1.32) (interaction p<0.000001); this difference also existed in the outcome of MMSE and CDR-SOB. Compared with placebo, anti-Aß drug-related adverse events were as follows: anxiety, depression, diarrhoea, fatigue, rash, syncope and vomit. DISCUSSION: From current evidence, anti-Aß interventions are unlikely to have an important impact on slowing cognitive or functional decline. Although the subgroup analysis suggested possible benefits from Aß clearance drugs, the analysis has limited credibility, and a benefit from drugs that increase clearance, if real, is very small. TRIAL REGISTRATION NUMBER: PROSPERO registration number CRD42019126272.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Acitretina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Ansiedade/induzido quimicamente , Azepinas/uso terapêutico , Clioquinol/análogos & derivados , Clioquinol/uso terapêutico , Cobre/uso terapêutico , Óxidos S-Cíclicos/uso terapêutico , Depressão/induzido quimicamente , Diarreia/induzido quimicamente , Exantema/induzido quimicamente , Fadiga/induzido quimicamente , Flurbiprofeno/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Inositol/uso terapêutico , Testes de Estado Mental e Demência , Diferença Mínima Clinicamente Importante , Ácido Orótico/uso terapêutico , Oxidiazóis/uso terapêutico , Índice de Gravidade de Doença , Sulfonamidas/uso terapêutico , Síncope/induzido quimicamente , Tiadiazinas/uso terapêutico , Resultado do Tratamento , Vômito/induzido quimicamenteRESUMO
Hypoxia is a universal characteristic of solid tumor and involving cancer metastasis via epithelial-mesenchymal transition (EMT). Nobiletin (3',4',5,6,7,8-hexamethoxyflavone), a dietary polymethoxylated flavonoid found in citrus fruits, has been reported to have anticancer effects. However, the possible role of nobiletin in renal cell carcinoma (RCC) remains unclear. Thus, the aim of this study was to identify the effect of nobiletin on hypoxia-induced EMT in RCC cells. We found that nobiletin significantly inhibited the migration and invasion induced by hypoxia in RCC cells. In addition, nobiletin reversed the hypoxia-induced EMT process in RCC cells. Furthermore, nobiletin suppressed the activation of NF-κB and Wnt/ß-catenin signaling pathways in hypoxia-stimulated RCC cells. In conclusion, these findings demonstrate that nobiletin inhibits hypoxia-induced EMT in human RCC cells via the inactivation of the NF-κB and Wnt/ß-catenin signaling pathways.
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BACKGROUND This study aimed to investigate the renin-angiotensin system (RAS) and cardiometabolic status in mice fed a long-term high-fat diet (HFD). MATERIAL AND METHODS C57BL/6J mice were randomly assigned to the control group on a normal diet (ND) (n=15) and the HFD group (n=15). Serum biomarkers were measured, including total cholesterol (TC), triglyceride (TG), insulin, glycated hemoglobin (HbA1c), brain natriuretic peptide (BNP), renin, angiotensin-converting enzyme (ACE), angiotensin II (Ang-II), Ang-II type 1 receptor (AT1R), and aldosterone. Cardiac histology was measured by the cross-sectional area (CSA) of cardiomyocytes and collagen deposition. Levels of myocardial intercalated disc (ICD) proteins and mRNA were analyzed by Western blot and real-time quantitative polymerase chain reaction (RT-qPCR), respectively. The localization of ICD proteins was evaluated by immunohistochemistry (IHC). RESULTS Compared with ND, HFD resulted in increased blood glucose, body weight, TC, TG, HbA1c, insulin, and BNP and levels of serum ACE, Ang-II, aldosterone, AT1R, cardiomyocyte CSA, and interstitial collagen in the myocardium compared. Also, HFD significantly down-regulated connexin-43, and upregulated ß-catenin, N-cadherin, and plakoglobin in the hearts of HFD mice compared with ND mice. However, the deposition of ICD proteins was not changed in the hearts of HFD mice compared with ND mice. CONCLUSIONS Long-term HFD in mice resulted in left ventricular hypertrophy, interstitial fibrosis, dysregulation of RAS, and abnormal expression of ICD proteins compared with ND mice, but did not affect the distribution of cardiomyocyte ICD proteins. Long-term HFD resulted in cardiac remodeling and altered expression of ICD proteins through RAS activation.
Assuntos
Comportamento Alimentar , Sistema Renina-Angiotensina , Animais , Glicemia/metabolismo , Peso Corporal , Cardiomegalia/sangue , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Fibrose , Coração/fisiopatologia , Resistência à Insulina , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Remodelação VascularRESUMO
Obese individuals exhibit brain alterations of resting-state functional connectivity (RSFC) integrity of resting-state networks (RSNs) related to food intake. Bariatric surgery is currently the most effective treatment for combating morbid obesity. How bariatric surgery influences neurocircuitry is mostly unknown. Functional connectivity density (FCD) mapping was employed to calculate local (lFCD)/global (gFCD) voxelwise connectivity metrics in 22 obese participants who underwent functional magnetic resonance imaging before and 1 month after sleeve gastrectomy (SG), and in 19 obese controls (Ctr) without surgery but tested twice (baseline and 1-month later). Two factor (group, time) repeated measures ANOVA was used to assess main and interaction effects in lFCD/gFCD; regions of interest were identified for subsequent seed to voxel connectivity analyses to assess resting-state functional connectivity and to examine association with weight loss. Bariatric surgery significantly decreased lFCD in VMPFC, posterior cingulate cortex (PCC)/precuneus, and dorsal anterior cingulate cortex (dACC)/dorsomedial prefrontal cortex (DMPFC) and decreased gFCD in VMPFC, right dorsolateral prefrontal cortex (DLPFC) and right insula (pFWE < .05). lFCD decreased in VMPFC and PCC/precuneus correlated with reduction in BMI after surgery. Seed to voxel connectivity analyses showed the VMPFC had stronger connectivity with left DLPFC and weaker connectivity with hippocampus/parahippocampus, and PCC/precuneus had stronger connectivity with right caudate and left DLPFC after surgery. Bariatric surgery significantly decreased FCD in regions involved in self-referential processing (VMPFC, DMPFC, dACC, and precuneus), and interoception (insula), and changes in VMPFC/precuneus were associated with reduction in BMI suggesting a role in improving control of eating behaviors following surgery.
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Cirurgia Bariátrica , Córtex Cerebral/fisiopatologia , Conectoma/métodos , Ego , Função Executiva/fisiologia , Rede Nervosa/fisiopatologia , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/cirurgia , Adolescente , Adulto , Cirurgia Bariátrica/métodos , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Obesidade Mórbida/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Adulto JovemAssuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide Aguda , Leucemia Mieloide , Humanos , Crise Blástica/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mieloide/tratamento farmacológico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológicoRESUMO
Lipid droplets (LDs) are the main energy resource for porcine preimplantation embryonic development. PLIN3 has been implicated in LD formation and regulation. Therefore, this study aimed to detect the dynamic pattern of PLIN3 in pig oocytes and cumulus cells (CC) during in vitro maturation (IVM), and to determine the relationship between PLIN3 and LD content. IVM with cumulus-enclosed oocytes (CEO), cumulus-denuded oocytes (DO) and the CCs denuded from the corresponding oocytes (DCC) was performed in porcine follicular fluid (PFF) or PFF-free optimized medium. DO and the DCC were cultured together under the same conditions as described above, while the DO was named DTO and the DCC was named DTCC in this group. Firstly, our results revealed LDs distributed widely in oocytes and CC, while the PLIN3 protein coated these LDs and spread out ubiquitously in the cytoplasm. Secondly, not only the mRNA level but also at protein level of PLIN3 in immature naked oocytes (IO) was higher than that in matured CEO, DO and DTO. Although PLIN3 was expressed at lower levels in CC from immature oocytes (ICC), the protein level of PLIN3 was comparably higher in the ECC and DCC groups. The triglyceride (TG) content in CEO and DO was significantly less abundant compared with that in IO. Therefore, our results indicated that co-culturing of oocytes and CC might affect PLIN3 expression levels in CC but not in oocytes. Lipid accumulation in pig oocytes during maturation might be affected by PLIN3 cross-talk between oocytes and CC.
Assuntos
Células do Cúmulo/metabolismo , Técnicas de Maturação in Vitro de Oócitos/métodos , Oócitos/fisiologia , Perilipina-3/metabolismo , Animais , Técnicas de Cocultura , Feminino , Líquido Folicular , Oócitos/metabolismo , Perilipina-3/genética , Suínos , Triglicerídeos/metabolismoRESUMO
BACKGROUND: To investigate whether fluoxetine improves poststroke dysphagia and to detect the potential relationship between serum brain-derived neurotrophic factor (BDNF) levels and fluoxetine effects. METHODS: In this retrospective study, 159 stroke patients who met our study criteria were included. In total, 110 patients were placed in the control group, and 49 patients were placed in the fluoxetine group. Demographic and clinical characteristics of the patients were collected for the baseline assessment. Functional independence measure scores and American speech-language-hearing association/functional communication measures scores for swallowing were collected to evaluate the patients' swallowing function. Patients' serums were collected at weeks 1 and 3 after admission, and serum BDNF levels were measured by enzyme-linked immunosorbent assay. T test, chi-squared test, and general linear model analysis were performed to determine the differences between the two groups. RESULTS: A significantly higher improvement of swallowing function was observed in the fluoxetine group compared with that of the control group (Pâ¯=â¯.023). In addition, a general linear model analysis showed that the treatment of fluoxetine has a statistically significant effect on swallowing improvement after adjustment of swallowing score on admission, stroke types, and interval between the onset of stroke and admission (Pâ¯=â¯.022, R2â¯=â¯.46, adjusted R2â¯=â¯.446). There is no significant difference in the change of serum BDNF levels in the two groups (Pâ¯=â¯.269). CONCLUSIONS: This study suggests that treatment with fluoxetine in stroke patients with dysphagia may improve swallowing function. A placebo-controlled, randomized clinical trial is warranted to confirm this finding.
Assuntos
Transtornos de Deglutição/tratamento farmacológico , Deglutição/efeitos dos fármacos , Fluoxetina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Distribuição de Qui-Quadrado , Transtornos de Deglutição/sangue , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Feminino , Fluoxetina/efeitos adversos , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Plasticidade Neuronal/efeitos dos fármacos , Projetos Piloto , Recuperação de Função Fisiológica , Estudos Retrospectivos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Our previous study suggested that SEB exposure in pregnant rats could lead to the change of T cells subpopulation in both peripheral blood and thymus of the offspring rats. However, rarely is known about the influence of SEB exposure in pregnant rats on T cell subpopulation in the spleens of offspring rats. RESULTS: SEB was intravenously administered to the pregnant rats at gestational day 16 in this study. The percentages, in vivo and in vitro responses of CD4 and CD8 T cells were investigated with flow cytometry. The prenatal SEB exposure obviously increased splenic CD4 T cell percentages of both neonates and adult offspring rats, and obviously reduced splenic CD8 T cell percentages of both the fifth day neonates and adult offspring rats. After spleens in the adult offspring rats were re-stimulated with SEB in vivo or in vitro, in vivo SEB stimulation could lead to the marked decrease of splenic CD4 T cell percentage and the marked increase of splenic CD8 T cell percentage. While in vitro SEB stimulation to the cultured splenocytes markedly decreased the proliferation of the splenic lymphocytes and the CD4 T cell percentage, and had no influence on CD8 T cell percentage. CONCLUSION: The prenatal SEB exposure could alter the percentages of CD4/CD8 T cell subpopulation and the response of CD4 and CD8 T cells to the in vivo and in vitro secondary SEB stimulation in the splenocytes of adult offspring rats.
Assuntos
Enterotoxinas/administração & dosagem , Enterotoxinas/sangue , Enterotoxinas/imunologia , Enterotoxinas/farmacologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Baço/imunologia , Animais , Animais Recém-Nascidos , Sangue/imunologia , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Técnicas de Cultura de Células , Proliferação de Células , Feminino , Citometria de Fluxo , Injeções Intravenosas/métodos , Gravidez , Ratos , Ratos Sprague-Dawley , Linfócitos T/microbiologiaRESUMO
Hyperspectral imaging feature on potato leaves stressed by late blight was studied in the present paper. The experiment used 60 potato leaves. Among those 60 potato leaves, 48 leaves were vitro inoculated with pathogen of potato late blight, the rest 12 leaves were used as control samples. The leaves were observed for 7 continuous days before and after inoculated and samples including healthy and infested were acquired. Hyperspectral data of healthy and infected potato samples of different disease severity were obtained by the hyperspectral imaging system from 374 to 1,018 nm and then extract spectral data of region of interest (ROI) from those hyperspectral data by the ENVI software. In order to improve the signal-to-noise ratio, the spectral data were preprocessed using different pretreatment methods such as moving average smoothing, normalization, derivative, baseline etc. The least squares-support vector machine(LS-SVM) models were developed based on the raw and those preprocessed data. Among the nine models, the model that used the raw data and the data after the spectroscopic transformation performed best with the discrimination of 94.87%. It was demonstrated that it is realized to determine the potato late blight disease of different disease severity using hyperspectral imaging technique.