RESUMO
Lipid droplets are unique lipid storage organelles in hepatocytes. Lipophagy is a key mechanism of selective degradation of lipid droplets through lysosomes. It plays a crucial role in the prevention of metabolic liver disease, including nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD), and is a potential therapeutic target for treating these dysfunctions. In this review, we highlighted recent research and discussed advances in key proteins and molecular mechanisms related to lipophagy in liver disease. Reactive oxygen species (ROS) is an inevitable product of metabolism in alcohol-treated or high-fat-treated cells. Under this light, the potential role of ROS in autophagy in lipid droplet removal was initially explored to provide insights into the link between oxidative stress and metabolic liver disease. Subsequently, the current measures and drugs that treat NAFLD and AFLD through lipophagy regulation were summarized. The complexity of molecular mechanisms underlying lipophagy in hepatocytes and the need for further studies for their elucidation, as well as the status and limitations of current therapeutic measures and drugs, were also discussed.
Assuntos
Fígado Gorduroso Alcoólico , Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fígado Gorduroso Alcoólico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Metabolismo dos Lipídeos/fisiologia , Fígado/metabolismo , Autofagia/fisiologia , Doenças Metabólicas/metabolismo , Gotículas Lipídicas/metabolismoRESUMO
Bagasse cellulose, an industrial waste byproduct of sugar production, was demonstrated to be a viable solid support for a solid-phase ionic oxidation catalyst enabling organic solvent-free aqueous reaction conditions and facile catalyst recovery. Bagasse cellulose-supported quaternary ammonium peroxyphosphotungstate was synthesized from bagasse cellulose-supported quaternary ammonium chloride, phosphotungstic acid, and hydrogen peroxide. The chemical structure of this material was characterized by SEM, XRD, FT-IR, XPS, and 13C NMR, revealing stability of the cellulose matrix to the catalyst loading conditions and effective dispersion of the acicular catalyst crystals throughout the matrix. High catalytic activity of this synthetic complex was demonstrated in the oxidation of cyclohexene to 1,2-cyclohexanediol with hydrogen peroxide in the absence of solvent. Optimized conditions providing trans-1,2-cyclohexanediol with 86.2 % selectivity were 12 wt% catalyst and 4 mL/g 30 % H2O2 (vs. cyclohexene) at 50 °C for 10 h.
Assuntos
Celulose , Cicloexenos , Oxirredução , Compostos de Amônio Quaternário , Solventes , Celulose/química , Catálise , Cicloexenos/química , Compostos de Amônio Quaternário/química , Solventes/química , Peróxido de Hidrogênio/químicaRESUMO
PURPOSE: Keratin 14 (KRT14) is hypothesized to be involved in the pathogenesis of renal cell carcinoma (RCC) based on its tumorigenic role in various cancers and its relationship with the prognosis of other urinary system malignancies. This study aimed to evaluate the correlation of KRT14 with tumor properties and prognosis in RCC patients. METHODS: Data from 180 RCC patients who received tumor resection were retrospectively reviewed. The KRT14 was assessed by immunohistochemistry (IHC) staining in tumor tissues and non-tumor tissues. RESULTS: KRT14 was insufficiently expressed in both tumor and non-tumor tissues, with median (interquartile range) IHC score of 2.0 (0.0-3.4) and 1.0 (0.0-2.0), respectively. While it was relatively higher in tumor versus non-tumor tissues (P < 0.001). Besides, tumor KRT14 was positively correlated with the pathological grade (P = 0.038), tumor size (P = 0.012), T stage (P = 0.006), and TNM stage (P = 0.018). Interestingly, tumor KRT14 high predicted shorter accumulating recurrence-free survival (RFS) (P = 0.003) and accumulating overall survival (OS) (P = 0.001), which was further verified by the multivariate Cox's regression analysis (both P < 0.05). Furthermore, tumor KRT14 high estimated shorter RFS and OS from the Gene Expression Profiling Interactive Analysis and Human Protein ATLAS databases (all P < 0.05). Subgroup analyses indicated that the correlation of tumor KRT14 with accumulating RFS and accumulating OS was more pronounced in RCC patients with better physical status (such as age < 65 years and better eastern cooperative oncology group performance status) and higher tumor stages (such as higher pathological grade). CONCLUSION: High KRT14 in tumor tissue could reflect an advanced tumor features and unsatisfying survival in RCC patients.
Assuntos
Carcinoma de Células Renais , Queratina-14 , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Seguimentos , Idoso , Queratina-14/análise , Estadiamento de Neoplasias , Fatores de Tempo , Taxa de Sobrevida , Imuno-Histoquímica , Biomarcadores Tumorais/metabolismoRESUMO
Background: Stigmatization and poor social support are challenges faced by individuals living with HIV or sexually transmitted disease, which can have a profound negative impact on their healthcare. Mother-to-child transmission of either HIV or syphilis can lead to adverse maternal and fetal outcomes. The aim of this study was to investigate stigmatization and social support of pregnant women with HIV or syphilis in eastern China. Methods: This was an explanatory sequential mixed-method study conducted in Zhejiang province, China in 2019. Stigmatization, social support, and the associated factors toward HIV or syphilis were evaluated using questionnaires. The social support rating scale was used to evaluate social support, where a score <25% was defined as poor social support. A logistic regression model was used to explore the association between stigmatization and poor social support. Results: A total of 448 women (HIV positive, N = 93; syphilis, N = 355) were recruited in this study. Higher stigmatization was observed in pregnant women with HIV compared to those with syphilis (53.76% vs. 24.36%, p < 0.001), and poorer social support was observed in women with HIV compared with those with syphilis (40.86% vs. 19.86%, p < 0.001), with significant distributions of the total social support scores (Z = -1.976, p = 0.048) and scores on objectivity (Z = -2.036, p = 0.042) and subjectivity (Z = -2.500, p = 0.012). Similar social support among HIV or syphilis pregnant women was observed in medical healthcare facilities. In multivariable logistic model analysis, stigmatization (OR adj = 2.927; 95%CI, 1.714-4.996; p < 0.001) and ethnic minority (OR adj = 2.373; 95%CI, 1.113-5.056; p = 0.025) were negatively associated with social support. Interestingly, employment status was associated with improved social support (OR adj = 0.345; 95%CI, 0.180-0.662; p = 0.001). Conclusion: Stigmatization among pregnant women with HIV or syphilis remains high. We demonstrated that stigmatization was a significant predictor of low social support in pregnant women with HIV or syphilis. The support shown in medical facilities was similar toward pregnant women with HIV or syphilis. Implementation of stigmatization eradication and social support strategies targeting pregnant women with HIV or syphilis may therefore improve the dual elimination of mother-to-child transmission service.
Assuntos
Infecções por HIV , Complicações Infecciosas na Gravidez , Estigma Social , Apoio Social , Sífilis , China/epidemiologia , Etnicidade , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Humanos , Transmissão Vertical de Doenças Infecciosas , Grupos Minoritários , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/psicologia , Gestantes , Sífilis/epidemiologia , Sífilis/psicologiaRESUMO
The incidence of liver diseases has been increasing steadily. However, it has some shortcomings, such as high cost and organ donor scarcity. The application of stem cell research has brought new ideas for the treatment of liver diseases. Therefore, it is particularly important to clarify the molecular and regulatory mechanisms of differentiation of bone marrow-derived stem cells (BMSCs) into liver cells. Herein, we screened differentially expressed genes between hepatocytes and untreated BMSCs to identify the genes responsible for the differentiation of BMSCs into hepatocytes. GSE30419 gene microarray data of BMSCs and GSE72088 gene microarray data of primary hepatocytes were obtained from the Gene Expression Omnibus database. Transcriptome Analysis Console software showed that 1896 genes were upregulated and 2506 were downregulated in hepatocytes as compared with BMSCs. Hub genes were analyzed using the STRING and Cytoscape v 3.8.2, revealing that twenty-four hub genes, play a pivotal role in the differentiation of BMSCs into hepatocytes. The expression of the hub genes in the BMSCs and hepatocytes was verified by reverse transcription-quantitative PCR (RT-qPCR). Next, the target miRNAs of hub genes were predicted, and then the lncRNAs regulating miRNAs was discovered, thus forming the lncRNA-miRNA-mRNA interaction chain. The results indicate that the lncRNA-miRNA-mRNA interaction chain may play an important role in the differentiation of BMSCs into hepatocytes, which provides a new therapeutic target for liver disease treatment.
Assuntos
MicroRNAs , RNA Longo não Codificante , RNA Longo não Codificante/genética , Medula Óssea/metabolismo , RNA Mensageiro/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Hepatócitos/metabolismo , Biomarcadores , Células-Tronco/metabolismo , Redes Reguladoras de GenesRESUMO
Objective: To develop and validate a prediction model for identifying pregnant women at risk of developing pregnancy-induced hypertension (PIH) to guide treatment decision and classification of management. Methods: This study retrospectively enrolled 907 consecutive pregnant women with de novo hypertension from the Antenatal Care Center of Henan Provincial People's Hospital between June 1, 2018 and May 31, 2019. The cohort was randomly divided into two subgroups: the development cohort (n = 635) and validation cohort (n = 272). Univariate analysis and backward elimination of multivariate logistic regression analyses were utilized to identify predictive factors, and a nomogram was established. The performance was assessed using the area under the curve (AUC), the mean AUC of k-fold cross-validation, and calibration plots. Based on the classification and regression tree model, risk classification was performed. Results: The score included five commonly available predictors: body mass index, proteinuria, age, uric acid, and mean arterial pressure (BPAUM score). When applied to internal validation, the score revealed good discrimination with stratified fivefold cross-validation in the development cohort (AUC = 0.91) and validation cohort (AUC: 0.89) at fixed 10% false-positive rates, and the calibration plots showed good calibration. The total score point was divided into three risk classifications: low risk (0 - 179 points), medium risk (179 - 204 points), and high risk (>204 points). Conclusions: This study established a prediction model for predicting PIH, which could be used in clinical decision-making to improve maternal health and birth outcomes.