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BACKGROUND & AIMS: Dysregulated iron homeostasis plays an important role in the hepatic manifestation of metabolic-associated fatty liver disease (MAFLD). We investigated the causal effects of five iron metabolism markers, regular iron supplementation and MAFLD risk. METHODS: Genetic summary statistics were obtained from open genome-wide association study databases. Two-sample bidirectional Mendelian randomization analysis was performed to estimate the causal effect between iron status and MAFLD, including Mendelian randomization inverse-variance weighted, weighted median methods and Mendelian randomization-Egger regression. The Mendelian randomization-PRESSO outlier test, Cochran's Q test and Mendelian randomization-Egger regression were used to assess outliers, heterogeneity and pleiotropy respectively. RESULTS: Mendelian randomization inverse-variance weighted results showed that the genetically predicted per standard deviation increase in liver iron (Data set 2: odds ratio 1.193, 95% confidence interval [CI] 1.074-1.326, p = .001) was associated with an increased MAFLD risk, consistent with the weighted median estimates and Mendelian randomization-Egger regression, although Data set 1 was not significant. Mendelian randomization inverse-variance weighted analysis showed that genetically predicted MAFLD was significantly associated with increased serum ferritin levels in both datasets (Dataset 1: ß = .038, 95% CI = .014 to .062, p = .002; Dataset 2: ß = .081, 95% CI = .025 to .136, p = .004), and a similar result was observed with the weighted median methods for Dataset 2 instead of Mendelian randomization-Egger regression. CONCLUSIONS: This study uncovered genetically predicted causal associations between iron metabolism status and MAFLD. These findings underscore the need for improved guidelines for managing MAFLD risk by emphasizing hepatic iron levels as a risk factor and ferritin levels as a prognostic factor.
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Hepatopatías , Análisis de la Aleatorización Mendeliana , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Hierro , FerritinasRESUMEN
Since the outbreak of novel Coronavirus Pneumonia 2019 (COVID-19), the role of Almonds (Xingren) in the protection and treatment of COVID-19 is not clear. Network pharmacology and molecular docking were used to explore the potential mechanism and potential key targets of Xingren on COVID-19. A total of nine common targets between them were obtained, and these targets were involved in multiple related processes of GO and KEGG pathway enrichment analysis. Molecular docking showed that licochalcone B has the best binding energy (-9.33 kJ·mol-1 ) to PTGS2. They are maybe the important ingredient and key potential target. Its possible mechanism is to intervene anxiety disorder in the process of disease development, such as regulation of blood pressure, reactive oxygen species metabolic process, leishmaniasis peroxisome, and IL-17 signaling pathway. PRACTICAL APPLICATIONS: Xingren is a traditional Chinese medicine that has been used and developed in China for many years. It contains a variety of active ingredients and also has the functions of relieving cough, relieving asthma, enhancing human immunity, delaying aging, regulating blood lipids, nourishing brain, and improving intelligence. In this article, the possible mechanisms of action and important targets of Xingren in the prevention and treatment of COVID-19 were discussed through network pharmacology and molecular docking. We also found that active ingredient licochalcone B and the potential target PTGS2 are worthy of further research and analysis. At the same time, the study also provides a theoretical basis and reference for the prevention and treatment of COVID-19 and the development of new drugs.
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Tratamiento Farmacológico de COVID-19 , Chalconas , Ciclooxigenasa 2/genética , Medicamentos Herbarios Chinos , Humanos , Interleucina-17 , Simulación del Acoplamiento Molecular , Farmacología en Red , Especies Reactivas de OxígenoRESUMEN
BACKGROUND: Integration of medical insurance schemes has been prioritized as one of the key strategies to address inequity in China's health system. The first pilot attempt to integrate started in 2003 and later expanded nationwide. This study aims to assess its intended impact on inequity in inpatient service utilization and identify the main determinants contributing to its ineffectiveness. METHODS: A total of 49,365 respondents in the pilot integrated area and 77,165 respondents in the non-integration area were extracted from the Fifth National Health Services Survey. A comparative analysis was conducted between two types of areas. We calculate a concentration index (CI) and horizontal inequity index (HI) in inpatient service utilization and decompose the two indices. RESULTS: Insurance integration played a positive role in reducing inequality in inpatient service utilization to some extent. A 13.23% lower in HI, a decrease in unmet inpatient care and financial barriers to inpatient care in the pilot integrated area compared with the non-integration area; decomposition analysis showed that the Urban-Rural Residents Basic Medical Insurance, a type of integrated insurance, contributed 37.49% to reducing inequality in inpatient service utilization. However, it still could not offset the strong negative effect of income and other insurance schemes that have increased inequality. CONCLUSIONS: The earlier pilot attempt for integrating medical insurance was not enough to counteract the influence of factors which increased the inequality in inpatient service utilization. Further efforts to address the inequality should focus on widening access to financing, upgrading the risk pool, reducing gaps within and between insurance schemes, and providing broader chronic disease benefit packages. Social policies that target the needs of the poor with coordinated efforts from various levels and agencies of the government are urgently needed.
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Enfermedad Crónica/tendencias , Prestación Integrada de Atención de Salud/estadística & datos numéricos , Disparidades en Atención de Salud/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Adolescente , Adulto , Anciano , China , Utilización de Instalaciones y Servicios , Femenino , Humanos , Renta/estadística & datos numéricos , Seguro de Salud/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud/estadística & datos numéricos , Salud Rural/estadística & datos numéricos , Factores Socioeconómicos , Encuestas y Cuestionarios , Salud Urbana/estadística & datos numéricos , Adulto JovenRESUMEN
OBJECTIVES: To investigate the effects of glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, on liver function and steatosis in obese mice. METHODS: Male c57BL/6J mice (8 weeks old) were divided into high-fat-diet group (for obesity model construction) and chow diet group. 12 weeks later, mice of high-fat diet group were randomly divided into high-dose exenatide group [H group, intraperitoneal injection 0.02 µg/ (g·d) , high-fat-diet], low-dose exenatide group [L group, intraperitoneal injection 0.01 µg/ (g·d) , high-fat-diet], saline group (NS group, intraperitoneal injection of saline, high-fat-diet) , diet control group (D group, shifted to chow diet) and high-fat control group (M group, high-fat-diet) for 4-week treatments , respectively. The body mass and serum biochemical indicators of were detected. Liver tissues were stained with HE, and steatosis score was measured. RESULTS: After 4-week treatments, H group showed more body mass loss than L group and D group ( P<0.05). The serum alanine aminotransferase (ALT) level of NG group was higher than that of H, L, M, and NS groups ( P<0.05). Serum cholesterol and triglyceride declined to normal levels by diet intervention or drug treatment. High-dose exenatide treatment ran a risk of increasing serum uric acid level. The serum levels of aspartate aminotransferase (AST), glucose, homeostasis model assessment-insulin resistance (HOMA-IR), lipase, and amylase had no significant differences between groups (P>0.05). Hepatic steatosis score was reduced by diet intervention or drug treatment. CONCLUSIONS: High-dose exenatide treatment can effectively reduce body mass of obese mice, but it has little difference when compared with dietary intervention in improving blood fat and liver steatosis.
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Hígado Graso/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Obesidad/complicaciones , Péptidos/farmacología , Ponzoñas/farmacología , Animales , Dieta Alta en Grasa , Exenatida , Resistencia a la Insulina , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Triglicéridos/sangre , Ácido Úrico/sangreRESUMEN
BACKGROUND & OBJECTIVE: It is an effective way to induce radio-tolerant gene into hematopoietic cells in bone marrow for overcoming the suppression of radiotherapy on hematopoietic system. However, this also increases the radiation tolerance of tumor cells. This study was designed to investigate a method to specifically protect bone marrow cell from being damaged by radiation, along without increasing resistance of tumor cell to radiation. METHODS: The retrovirus vector of manganese superoxide dismutase (MnSOD) gene regulated by aminopeptidase N (APN) bone marrow-specific gene promoter was constructed and induced into myeloblastic KG1a and cancer cell BEL7402. MnSOD mRNA level was analyzed by PT-PCR; MnSOD activity in the cells was determined; the sensitivity of bone marrow cell and hepatic carcinoma cell to x-ray was detected by cell survival test; the cell apoptosis was analyzed with flow cytometry and fractural DNA electrophoresis. RESULTS: The MnSOD mRNA level and enzyme activity in KG1a cells transferred with the gene was obviously increased. Expression of MnSOD mRNA drove by APN myelo-specific promoter effectively inhibited apoptosis of KG1a cells induced by radiation and endowed KG1a cell line with the enhancement of tolerance to radiation, which increased by 3.7 folds compared to parental cells at the dose of 10 Gy. In contrast, the level of MnSOD mRNA, the enyme activity of MnSOD and the radiosensitivity had no significant change in BEL 7402 cells transduced with MnSOD gene. CONCLUSION: APN bone marrow-specific promoter could control MnSOD gene expression highly in myeloid cell and lower in cancer cell. In the process of killing of cancer cell by x-ray, MnSOD gene regulated by APN bone marrow-specific promoter could specifically protect myeloid cell. This study provides a new clue to solve the bone marrow suppression in high dose radiotherapy.