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Background: Diabetic kidney disease (DKD) is a serious microvascular complication of diabetes that affects both type 1 and type 2 diabetes patients at a high incidence rate. Naja Naja atra venom (NNAV) has been shown to have protective effects and improved renal function in diabetic rats. However, its mechanism of action is still unclear. This study aims to unravel the effectiveness and mechanisms of NNAV on DKD. Methods: We conducted in vitro experiments in which Human Kidney-2 (HK-2) cells were stimulated with high glucose, and exposed to varying concentrations of NNAV. Cell morphology, as well as α-SMA, TGF-ß1, and E-cadherin levels, were analyzed using immunofluorescence and western blot. In vivo experiments involved a diabetic rat model, where varying concentrations of cobra α-neurotoxin (CTX) were administrated via gastric treatment. We observed and noted pathomorphological changes, measured biochemical and oxidative stress indices, and used western blot to assess podocin and nephrin levels. Results: High glucose levels can induce a decrease in E-cadherin expression and an increase in α-SMA and transforming growth factor-ß1 (TGF-ß1) expression in HK-2 cells. NNAV can inhibit the transdifferentiation of HK-2 cells to myofibroblast (MyoF) in a high glucose environment and reduce the expression of TGF-ß1. Cobra α-neurotoxin (CTX) can reduce urine protein in diabetes model rats at an early stage, which is dose-independent and has a time application range. CTX can regulate the expression of nephrin and podocin. Conclusion: The present study indicates that CTX and NNAV attenuate STZ and high glucose-induced DKD. Its mechanisms of action are associated with inhibiting oxidative stress and TEMT. The study suggests that NNAV and CTX might be a potential therapeutic drug for treating DKD.
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INTRODUCTION AND OBJECTIVES: The development of hepatocellular carcinoma (HCC) is a multi-step process that accumulates genetic and epigenetic alterations, including changes in circular RNA (circRNA). This study aimed to understand the alterations in circRNA expression in HCC development and metastasis and to explore the biological functions of circRNA. MATERIALS AND METHODS: Ten pairs of adjacent chronic hepatitis tissues and HCC tissues from patients without venous metastases, and ten HCC tissues from patients with venous metastases were analyzed using human circRNA microarrays. Differentially expressed circRNAs were then validated by quantitative real-time PCR. In vitro and in vivo assays were performed to assess the roles of the circRNA in HCC progression. RNA pull-down assay, mass spectrometry analysis, and RNA-binding protein immunoprecipitation were conducted to explore the protein partners of the circRNA. RESULTS: CircRNA microarrays revealed that the expression patterns of circRNAs across the three groups were significantly different. Among these, hsa_circ_0098181 was validated to be lowly expressed and associated with poor prognosis in HCC patients. Ectopic expression of hsa_circ_0098181 delayed HCC metastasis in vitro and in vivo. Mechanistically, hsa_circ_0098181 sequestered eukaryotic translation elongation factor 2 (eEF2) and dissociated eEF2 from filamentous actin (F-actin) to prevent F-actin formation, which blocked activation of the Hippo signaling pathway. In addition, the RNA binding protein Quaking-5 bound directly to hsa_circ_0098181 and induced its biogenesis. CONCLUSIONS: Our study reveals changes in circRNA expression from chronic hepatitis, primary HCC, to metastatic HCC. Further, the QKI5-hsa_circ_0098181-eEF2-Hippo signaling pathway exerts a regulatory role in HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Humans , Carcinoma, Hepatocellular/pathology , RNA, Circular/genetics , Liver Neoplasms/pathology , Peptide Elongation Factor 2/genetics , Peptide Elongation Factor 2/metabolism , Hippo Signaling Pathway , Actins/metabolism , Hepatitis, Chronic , MicroRNAs/genetics , Gene Expression Regulation, NeoplasticABSTRACT
ABSTRACT The impact of traditional public health emergencies on the comprehensive education of medical students in colleges and universities is mainly reflected in the test of comprehensive literacy. Based on this, this paper studies the construction of a public health emergency impact analysis platform from a medical perspective and cloud computing. From the platform's database construction, event collection methods, impact evaluation rules and other aspects to achieve accurate analysis of the impact of emergencies, using the cloud computing method for comprehensive analysis and evaluation, the algorithm can analyze and intelligently classify information data on the Internet in the process of multiple input, and respond to potential public health emergencies according to cloud computing technology, in order to analyze the impact on the comprehensive quality of medical students. The experimental results show that the public health emergency analysis platform has the advantages of high feasibility and high data utilization, and can effectively improve the impact of public health emergencies on the comprehensive literacy of medical students.
RESUMO O impacto das tradicionais emergências de saúde pública sobre a formação integral de estudantes de medicina em faculdades e universidades reflete-se principalmente no teste de formação integral. Com base nisso, este documento estuda a construção da plataforma de análise de impacto de emergência de saúde pública sob a perspectiva médica e computação em nuvem. A partir da construção da base de dados da plataforma, foram desenvolvidos métodos de coleta de eventos, regras de avaliação de impacto e outros aspectos para obter uma análise precisa do impacto das emergências, usando o método de computação em nuvem para análise e avaliação. O algoritmo pode realizar a análise e classificação inteligente de dados de informação na Internet no processo de introdução múltipla, e responder a possíveis emergências de saúde pública de acordo com a tecnologia de computação em nuvem a fim de analisar o impacto sobre a qualificação dos estudantes de medicina. Os resultados experimentais mostram que a plataforma de análise de emergências de saúde pública tem as vantagens de alta viabilidade e alta utilização de dados, pode melhorar efetivamente o impacto das emergências de saúde pública na formação integral dos estudantes de medicina.
RESUMEN El impacto de las emergencias de salud pública tradicionales en la educación integral de los estudiantes de medicina en los colegios y universidades se refleja principalmente en la prueba de comprensión de textos. Con base en esto, este trabajo estudia la construcción de una plataforma de análisis de impacto de emergencias en salud pública desde una perspectiva médica y de computación en la nube. A partir de la construcción de la base de datos de la plataforma, los métodos de recolección de eventos, las reglas de evaluación de impacto y otros aspectos para lograr un análisis preciso del impacto de las emergencias, utilizando el método de computación en la nube para un análisis y evaluación integral, el algoritmo puede analizar y clasificar de manera inteligente los datos de información en Internet en el proceso de entrada múltiple. También puede responder a potenciales emergencias de salud pública de acuerdo con la tecnología de computación en la nube, con el fin de analizar el impacto en la calidad integral de los estudiantes de medicina. Los resultados experimentales muestran que la plataforma de análisis de emergencias de salud pública tiene las ventajas de alta viabilidad y alta utilización de datos, y puede mejorar de manera efectiva el impacto de las emergencias de salud pública en la comprensión de textos de los estudiantes de medicina.
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Humans , Medical Informatics , Biomedical Technology , Education, Medical , Emergency Medicine/education , Narrative Medicine , AlgorithmsABSTRACT
OBJECTIVE: To examine the distribution and impact of diabetes, glycaemic status, and related factors, in a predominantly black adult Caribbean population. METHODS: The study included 4709 people, or 84% of a simple random sample of Barbadian-born citizens aged 40-84 years, examined between 1988 and 1992 and re-assessed 4 years later. Diabetes was evaluated according to physician-diagnosis and glycosylated haemoglobin (GHb). Associations were assessed by logistic regression analyses, cumulative mortality by product-limit methods and death-rate ratios by Cox proportional hazards regression. RESULTS: Among the 4314 black participants, the prevalence of known diabetes, predominantly type 2, was 9.1% at 40-49 years of age and increased to 24.0% at 70-79 years. The overall prevalence was 17.5%, while it was 12.5% in mixed (black/ white; n = 184) and 6.0% in white/other participants (n = 133), only 0.3% had younger-onset. Additionally, 2% had GHb >10% (>2 SD over the mean) without diabetes history. Sulphonylureas were the most frequent treatment, while insulin use was infrequent. In black participants, diabetes was positively associated with age (OR = 1.03 per year; 95% CI : 1.02-1.04), diabetes family history (OR = 2.85, 95% CI : 2.39-3.40), hypertension (OR = 1.71, 95% CI : 1.42-2.05), obesity (BMI > or = 25 kg/m(2); OR = 1.74, 95% CI : 1.44-2.10), and high waist-hip ratio (WHR > or = 0.92; OR = 1.29, 95% CI : 1.09-1.53). Ocular co-morbidities were increased among people with diabetes, as was 4-year-mortality (death rate ratio = 1.42, 95% CI : 1.10-1.83). There was a 9% increase in mortality for each 1% increase in GHb (death rate ratio = 1.09, 95% CI : 1.04-1.15). CONCLUSIONS: A markedly high prevalence of diabetes existed in the adult black population, affecting almost one in five people and increasing morbidity and mortality. Prevention strategies are urgently needed to reduce the adverse implications of diabetes in this and similar populations.
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Black People , Diabetes Mellitus, Type 2/ethnology , Adult , Age of Onset , Aged , Aged, 80 and over , Barbados , Glycated Hemoglobin/analysis , Humans , Middle Aged , PrevalenceABSTRACT
OBJECTIVE: To measure the 4-year risk of open-angle glaucoma (OAG) in a black population. DESIGN: Population-based cohort study with 4 years of follow up. SETTING: Simple random sample of residents of Barbados, West Indies, aged 40 years or older. PARTICIPANTS: A total of 3427 members of the cohort (85 percent of those eligible). MAIN OUTCOME MEASURE: Development of glaucoma visual field defects and optic disc damage, confirmed by automated perimetry, independent fundus photographic gradings, and standardized opthalmologic examinations. RESULTS: The 4-year risk of OAG in black participants was 2.2 percent (95 percent confidence interval, 1.7 percent-2.8 percent), based on 67 newly developed cases of OAG. Incidence rates increased from 1.2 percent at ages 40 to 49 years to 4.2 percent at ages of 70 years or more, tending to be higher in men than women (2.7 percent vs 1.9 percent). About half of the incident cases were undiagnosed previously, and the rest were receiving OAG treatment. Of the 67 new cases of OAG, 32 had intraocular pressure of 21 mm HG or less at baseline (1.2 percent incidence) and 35 had higher pressures (9 percent incidence). Risk was the highest among persons classified as having suspect OAG at baseline (26.1 percent), followed by those with ocular hypertension (4.9 percent and lowest in the remining population (0.8 percent). CONCLUSIONS: This longitudinal study provides new information on OAG risk, as well as the first incidence measurement in a black population. Although intraocular pressure increased risk, about half of the new cases had baseline pressures of 21 mm Hg or less. Results substantiate the high OAG risk in the population of African origin, especially in older adults; the relative role of intraocular pressure; and the considerable underdetecion of new disease after 4 years of follow-up. (AU)