Alcoholic liver disease (ALD) encompasses conditions ranging from simple steatosis to cirrhosis and even liver cancer.It has gained significant global attention in recent years.Despite this, effective pharmacological treatments for ALD remain elusive, and the core mechanisms underlying the disease are not yet fully comprehended.S100A16, a newly identified calcium-binding protein, is linked to lipid metabolism.Our research has discovered elevated levels of the S100A16 protein in both serum and liver tissue of ALD patients.A similar surge in hepatic S100A16 expression was noted in a Gao-binge alcohol feeding mouse model.S100a16 knockdown alleviated ethanol-induced liver injury, steatosis and inflammation.Conversely, S100a16 transgenic mice showed aggravating phenomenon.Mechanistically, we identify mesencephalic astrocyte-derived neurotrophic factor (MANF) as a regulated entity downstream of S100a16 deletion.MANF inhibited ER-stress signal transduction induced by alcohol stimulation.Meanwhile, MANF silencing suppressed the inhibition effect of S100a16 knockout on ethanol-induced lipid droplets accumulation in primary hepatocytes.Our data suggested that S100a16 deletion protects mice against alcoholic liver lipid accumulation and inflammation dependent on upregulating MANF and inhibiting ER stress.This offers a potential therapeutic avenue for ALD treatment.
High-carbohydrate (HC) diets decrease the intestinal levels of sodium acetate (SA) and sodium butyrate (SB) and impair the gut health of largemouth bass; however, SA and SB have been shown to enhance immunity and improve intestinal health in farmed animals. Thus, the present study was to investigate the effects of dietary SA and SB on HC diet-induced intestinal injury and the potential mechanisms in juvenile largemouth bass. The experiment set five isonitrogenous and isolipidic diets, including a low-carbohydrate diet (9% starch) (LC), a high carbohydrate diet (18% starch) (HC), and the HC diet supplemented with 2 g/kg SA (HCSA), 2 g/kg SB (HCSB) or a combination of 1 g/kg SA and 1 g/kg SB (HCSASB). The feeding experiment was conducted for 8 weeks. A total of 525 juvenile largemouth bass with an initial body weight of 7.00 ± 0.20 g were used. The results showed that dietary SA and SB improved the weight gain rate and specific growth rate (
Introduction: Bronchopulmonary dysplasia (BPD) is a life-threatening lung illness that affects premature infants and has a high incidence and mortality. Using interpretable machine learning, we aimed to investigate the involvement of endoplasmic reticulum (ER) stress-related genes (ERSGs) in BPD patients. Methods: We evaluated the expression profiles of endoplasmic reticulum stress-related genes and immune features in bronchopulmonary dysplasia using the GSE32472 dataset. The endoplasmic reticulum stress-related gene-based molecular clusters and associated immune cell infiltration were studied using 62 bronchopulmonary dysplasia samples. Cluster-specific differentially expressed genes (DEGs) were identified utilizing the WGCNA technique. The optimum machine model was applied after comparing its performance with that of the generalized linear model, the extreme Gradient Boosting, the support vector machine (SVM) model, and the random forest model. Validation of the prediction efficiency was done by the use of a calibration curve, nomogram, decision curve analysis, and an external data set. Results: The bronchopulmonary dysplasia samples were compared to the control samples, and the dysregulated endoplasmic reticulum stress-related genes and activated immunological responses were analyzed. In bronchopulmonary dysplasia, two distinct molecular clusters associated with endoplasmic reticulum stress were identified. The analysis of immune cell infiltration indicated a considerable difference in levels of immunity between the various clusters. As measured by residual and root mean square error, as well as the area under the curve, the support vector machine machine model showed the greatest discriminative capacity. In the end, an support vector machine model integrating five genes was developed, and its performance was shown to be excellent on an external validation dataset. The effectiveness in predicting bronchopulmonary dysplasia subtypes was further established by decision curves, calibration curves, and nomogram analyses. Conclusion: We developed a potential prediction model to assess the risk of endoplasmic reticulum stress subtypes and the clinical outcomes of bronchopulmonary dysplasia patients, and our work comprehensively revealed the complex association between endoplasmic reticulum stress and bronchopulmonary dysplasia.
Abstract Background: Thyroid cancer is the most common malignant tumor of the endocrine system. Long non-coding RNAs (lncRNAs) have been demonstrated as novel biomarkers for cancer prognosis. Methods: In this study, we performed differential expression analysis of lncRNA expression profiles in GEO datasets. LASSO regression analysis was conducted to identify lncRNA-based prognosis model that can predict progression-free survival in thyroid cancer patients from The Cancer Genome Atlas (TCGA). Further functional analysis revealed the potential biological functions of the lncRNAs. Results: A risk score model based on six lncRNA biomarkers were established after LASSO Cox regression analysis. The prognostic value of the 6-lncRNA prognosis model was successfully validated and ROC curves was analysed. Patients were classified into high- and low-risk groups using the 6-lncRNA signature-based risk score. Patients in the low-risk group had significantly better progression-free survival than high-risk group. The result of multivariate analysis showed that the six-lncRNA signature was independent from clinical features such as age, gender and stage. GO and KEGG enrichment analysis and estimation of immune infiltration suggested that the lncRNAs might closely associated with tumorigenesis. Conclusion: Our study has constructed a novel six-lncRNA prognosis model to improve progression-free survival prediction in patients with thyroid cancer.
Background: Exercise improves function, reduces disability, maintains independence, and improves quality of life for low-grade glioma (LGG) patients. Exercise can also improve the effectiveness of cancer treatment. The goal of this research was to find potential exercise related genes that may be used to predict exercise levels and may be used as a biomarker for cancer outcomes. Methods: The GSE111551 database was thoroughly examined in this research, and the resulting conclusion of exercise-related genes was reached. The protein interaction network (PPI) was used to examine the differentially expressed genes (DEGs). Then the exercise-related gene TLR1 was chosen. The expression, methylation degree, prognosis, and immune relevance of TLR1 were investigated using bioinformatics. In addition, we verified the role of TLR1 in Glioma cell lines. Results: LGG patients with reduced TLR1 expression and hypermethylation had a better overall survival (OS) and progression free survival (PFS), using the TCGA database. Low TLR1 expression and hypermethylation of TLR1 were found to be independent biomarkers for OS using Cox regression. Furthermore, the CGGA database was used to confirm the prognostic function of TLR1 in this cancer. Finally, most methylation sites of TLR1 were strongly correlated with immune infiltration and immune checkpoint. Then, reducing TLR1 expression substantially slowed the cell cycle and decreased LGG cell proliferation, emigration, and infiltration in vitro. Conclusions: Exercise-related gene TLR1 has the potential to be a useful prognostic biomarker, and it is thought to be involved in immune cell infiltration and immunotherapy in LGG.
Objective Lipoprotein glomerulopathy (LPG) is a rare disorder characterized by the development of glomerular lipoprotein thrombosis. LPG exhibits familial aggregation, with mutations in the apolipoprotein E (APOE) gene identified as the leading cause of this disease. This study aimed to investigate APOE gene mutations and the clinicopathological features in eleven LPG patients.
Glioblastoma (GBM) is one of the most lethal forms of human cancer, with very few long-term survivors. In addition to surgery, chemotherapy is still an important strategy. Unfortunately, GBM chemotherapy faces two main challenges: first, in GBM, epidermal growth factor receptor (EGFR) overexpression results in chemoresistance; second, temozolomide (TMZ) lacks target specificity, which can lead to a reduction in the concentration and side effects in GBM. Nowadays, with the development of nanomedicine systems for applications in tumor therapies, increasing anticancer efficacy and reducing side effects with multi-drug delivery are huge advantages. In this study, pH-sensitive and GBM-targeting nanovesicle (Tf-PEG-PAE(SS)) was fabricated. The chemotherapy drug (TMZ) and EGFR inhibitor (EGFR-siRNA) were co-encapsulated in the nanocarrier, and their anticancer outcomes were investigated in detail. In vitro experiments have shown that the nanocarrier transports TMZ and EGFR-siRNA efficiently into U87 cells, causing a vigorous apoptotic response by silencing the proliferative EGFR gene and increasing the drug concentration of TMZ simultaneously. An experimental study in mice bearing orthotropic glioma revealed that the accumulated nanocarriers in the tumor site could inhibit the tumor growth and prolong the mice survival remarkably through the intracranial injection of Tf-PEG-PAE(SS)/TMZ@siEGFR. The drug co-delivery system could extend the blood circulation time and offer a new strategy to treat glioblastoma.
<b><i>Background:</i></b> The current study aimed to evaluate the associations between podocyte injury and clinicopathological features in renal thrombotic microangiopathy (TMA) based on a Chinese cohort, which might be underscored in this disease. <b><i>Methods:</i></b> The clinical, laboratory, and renal histopathological data of patients with renal biopsy-proven TMA from 2000 to 2015 in our institute were collected. Foot process effacement (FPE) was quantified by foot process width (FPW) by electron microscopy. Podocytes in the renal specimens were also detected by stainings for podocyte-specific markers, including Wilms tumor 1 (WT-1), synaptopodin, and podocalyxin. The associations between FPW and clinico-histopathological data were further analyzed. A composite end-point was defined by all-cause death or end-stage renal disease to address the predictive value of FPW. <b><i>Results:</i></b> Sixty-three patients with renal biopsy-proven TMA were enrolled. The FPW of renal TMA patients was 1,090 ± 637 nm (range, 572–4,748 nm), which was significantly higher than the normal range in our center (<i>p</i> = 0.005). By immunohistochemistry and immunofluorescence assays, we found decreased expressions of synaptopodin, podocalyxin, and WT-1 and continued stainings of WT-1 in some podocytes without detectable synaptopodin stainings in the areas of sclerotic tufts and cellular crescents. The FPW value was correlated with the serum albumin concentration (<i>r</i><sub>s</sub> = −0.281, <i>p</i> = 0.026), proteinuria amount (<i>r</i><sub>s</sub> = 0.255, <i>p</i> = 0.047), serum creatinine levels (<i>r</i><sub>s</sub> = 0.339, <i>p</i> = 0.007), and eGFR (<i>r</i><sub>s</sub> = −0.335, <i>p</i> = 0.007). According to ROC curve analysis, the optimal cutoff level of FPW for predicting the composite end-point was 869 nm. In patients with FPW ≥ 869 nm, FPW levels were further correlated with the severity of mesangiolysis (<i>r</i><sub>s</sub> = 0.351, <i>p</i> = 0.033) and glomerulosclerosis (<i>r</i><sub>s</sub> = 0.369, <i>p</i> = 0.025) in pathological evaluations. Patients without clinical remission also had higher FPW than those with remission (1,240 ± 793 vs. 925 ± 344 nm, <i>p</i> = 0.013). The multivariate Cox hazard model showed that FPW ≥ 869 nm was an independent risk factor for the composite end-point (hazard ratio: 3.64, 95% CI: 1.37–9.66, <i>p</i> = 0.009). <b><i>Conclusion:</i></b> The podocyte injury was prevalent and the FPW levels were closely associated with clinicopathological features, especially prognosis, in renal TMA patients.
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