Lifestyle choices such as the intake of sweets, history of diseases, and genetic variants seem to play a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). To explore which genetic Show more
Lifestyle choices such as the intake of sweets, history of diseases, and genetic variants seem to play a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). To explore which genetic and environmental factors are associated with NAFLD in a Chinese Han population, we conducted this study. We collected the medical reports, lifestyle details, and blood samples of individuals and used the polymerase chain reaction-ligase detection reaction method to genotype the single-nucleotide polymorphism (SNPs) from the 2113 eligible people. The GG genotype of the additive model of rs7493 in the PON2, the CC genotype of the additive and recessive models of rs7593130 in the ADCY3, together with dyslipidemia, regular intake of egg and sweets and hypertension, increased the risk of NAFLD (adjusted OR > 1, Show less
To explore the effect of miR-335-5p/ADCY3 interaction on the lymphocyte function in the patients with aplastic anemia (AA). Blood samples were collected from 22 healthy volunteers (HC) and 50 AA patie Show more
To explore the effect of miR-335-5p/ADCY3 interaction on the lymphocyte function in the patients with aplastic anemia (AA). Blood samples were collected from 22 healthy volunteers (HC) and 50 AA patients including 38 severe AA (SAA) and 12 non-severe AA (NSAA). Peripheral blood mononuclear cells (PBMNC) were isolated. The expression of miR-335-5p and ADCY3 mRNA was detected by using RT-PCR. Negative control miR-335-5p (NC group) and miR-335-5p mimic (mimic group) were transfected to AA-PBMNC by using RNAimax reagent, respectively. The proliferative ability, activation and cytokines of CD4 The expression of miR-335-5p was significantly downregulated in SAA-PBMNC and NSAA-PBMNC compared with HC-PBMNC (0.08±0.01 vs 0.74±0.10, P＜0.01; 0.17±0.02 vs 0.74±0.10, P＜0.01). Meanwhile, the expression of miR-335-5p in SAA-PBMNC was very statistically significantly lower than that in NSAA-PBMNC (P＜0.01). Compared with NC group, upregulation of miR-335-5p in vitro could significantly inhibited the proliferation of CD4 The expression of miR-335-5p was significantly downregulated in AA, and that correlates with disease severity. Up-regulating miR-335-5p can correct the hyperimmune status in AA patients by targeting ADCY3. These changes may relates with the strengthen of inhibition for targeted gene ADCY3. Show less
no PDFDOI: 10.19746/j.cnki.issn.1009-2137.2020.03.032
Fructus has motivation effect on gastrointestinal tract. Hesperidin is extracts of Fructus, and we attempted to prove its effects on improving the gastrointestinal transmission function and determine Show more
Fructus has motivation effect on gastrointestinal tract. Hesperidin is extracts of Fructus, and we attempted to prove its effects on improving the gastrointestinal transmission function and determine the possible mechanisms by a loperamide-induced slow transit constipation (STC) model. Constipation phenotypes were measured in rats with Lop-induced constipation after treatment with hesperidin. The amounts and water content of stool were significantly higher in the hesperidin-treated group than the loperamide-induced model group, whereas food intake was maintained at constant levels. Moreover, intestinal transit rate was increased in the treatment group of hesperidin. Histological alteration was detected by H&E staining, we found that the colon smooth muscle cells and neuron cells of the rats were increased, and the infiltration of inflammatory cells was decreased in the hesperidin-treated group compared with the loperamide-induced model group. 5-Hydroxytryptamine (5-HT) receptor4 fluorescence intensity and intracellular-free calcium ions in colon tissue were increased, and relative protein of cAMP/PKA pathway and p-cAMP response component-binding protein (CREB) pathway were upregulated in the hesperidin-treated group compared with the loperamide-induced model group. Further, SMCs from colon tissue of rats were cultured and identified. We found hesperidin could significantly promote tegaserod-induced increase of 5-HTR4 fluorescence intensity, intracellular calcium ions, relative protein of cAMP/PKA pathway and p-CREB pathway, and cell proliferation and inhibit GR113808-induced decrease of 5-HTR4 fluorescence intensity, 5-HTR4 pathway-related proteins (ADCY3, cAMP, PKA, and p-CREB), intracellular calcium ions, and cell proliferation. The analysis of our data suggested that hesperidin could obviously improve the gastrointestinal transmission function in loperamide-induced STC rat model via increasing the 5-HTR4 and intracellular-free calcium ions to enhance the expression of relative protein of cAMP/PKA pathway and p-CREB pathway. Hesperidin could be used in the treatment of STC, and our data not only provide experimental basis for the treatment of STC in hesperidin but also provides a theoretical reference for clinical treatment. Show less
Concentric and eccentric cardiac hypertrophy are associated with pressure and volume overload, respectively, in cardiovascular disease both conferring an increased risk of heart failure. These contras Show more
Concentric and eccentric cardiac hypertrophy are associated with pressure and volume overload, respectively, in cardiovascular disease both conferring an increased risk of heart failure. These contrasting forms of hypertrophy are characterized by asymmetrical growth of the cardiac myocyte in mainly width or length, respectively. The molecular mechanisms determining myocyte preferential growth in width versus length remain poorly understood. Identification of the mechanisms governing asymmetrical myocyte growth could provide new therapeutic targets for the prevention or treatment of heart failure. Primary adult rat ventricular myocytes, adeno-associated virus (AAV)-mediated gene delivery in mice, and human tissue samples were used to define a regulatory pathway controlling pathological myocyte hypertrophy. Chromatin immunoprecipitation assays with sequencing and precision nuclear run-on sequencing were used to define a transcriptional mechanism. We report that asymmetrical cardiac myocyte hypertrophy is modulated by SRF (serum response factor) phosphorylation, constituting an epigenomic switch balancing the growth in width versus length of adult ventricular myocytes in vitro and in vivo. SRF Ser We have identified a new molecular switch, namely mAKAPβ signalosome-regulated SRF phosphorylation, that controls a transcriptional program responsible for modulating changes in cardiac myocyte morphology that occur secondary to pathological stressors. Complementary AAV-based gene therapies constitute rationally-designed strategies for a new translational modality for heart failure. Show less
Increasing evidence shows that Angptl4 affects proteinuria in podocytes injured kidney disease, however, whether there is a relationship between Angptl4 and IgA nephropathy (IgAN) has not been studied Show more
Increasing evidence shows that Angptl4 affects proteinuria in podocytes injured kidney disease, however, whether there is a relationship between Angptl4 and IgA nephropathy (IgAN) has not been studied yet. Plasma and urine samples were obtained from 71 patients with IgAN and 61 healthy controls. Glomeruli from six renal biopsy specimens (three IgAN patients and three healthy controls) were separated by RNA-Seq. Differentially expressed genes (DEGs) related to podocytes and Angptl4 between IgAN patients and healthy controls were performed using the Limma package. Gene set enrichment analysis was used to determine whether there was a statistically significant difference between the two groups. STRING was used to create a protein-protein interaction network of DEGs. Association analysis between Angptl4 levels and clinical features of IgAN was performed. Thirty-three podocyte-related and twenty-three Angpt4-related DEGs were found between IgAN patients and healthy controls. By overlapping the genes, Our findings show that Angptl4 levels in plasma and urine are related to podocyte damage and, therefore, may be a promising tool for assessing the severity of IgAN patients to identify and reverse the progression to ESRD. Show less
Epigenetic regulation of gene expression has been reported in the pathogenesis of metabolic disorders such as diabetes and liver steatosis in humans. However, the molecular mechanisms of fatty liver h Show more
Epigenetic regulation of gene expression has been reported in the pathogenesis of metabolic disorders such as diabetes and liver steatosis in humans. However, the molecular mechanisms of fatty liver hemorrhagic syndrome (FLHS) in chickens have been rarely studied. H3K27ac chromatin immunoprecipitation coupled with high-throughput sequencing and high-throughput RNA sequencing was performed to compare genome-wide H3K27ac profiles and transcriptomes of liver tissue between healthy and FLHS chickens. In total, 1,321 differential H3K27ac regions and 443 differentially expressed genes were identified (| log2Fold change| ≥ 1 and Show less
Cervical cancer (CC) is one of the most common gynaecological cancers. The gene signature is believed to be reliable for predicting cancer patient survival. However, there is no relevant study on the Show more
Cervical cancer (CC) is one of the most common gynaecological cancers. The gene signature is believed to be reliable for predicting cancer patient survival. However, there is no relevant study on the relationship between the glycolysis-related gene (GRG) signature and overall survival (OS) of patients with CC. We extracted the mRNA expression profiles of 306 tumour and 13 normal tissues from the University of California Santa Cruz (UCSC) Database. Then, we screened out differentially expressed glycolysis-related genes (DEGRGs) among these mRNAs. All patients were randomly divided into training cohort and validation cohort according to the ratio of 7: 3. Next, univariate and multivariate Cox regression analyses were carried out to select the GRG with predictive ability for the prognosis of the training cohort. Additionally, risk score model was constructed and validated it in the validation cohort. Six mRNAs were obtained that were associated with patient survival. The filtered mRNAs were classified into the protective type (GOT1) and the risk type (HSPA5, ANGPTL4, PFKM, IER3 and PFKFB4). Additionally, by constructing the prognostic risk score model, we found that the OS of the high-risk group was notably poorer, which showed good predictive ability both in training cohort and validation cohort. And the six-gene signature is a prognostic indicator independent of clinicopathological features. Through the verification of PCR, the results showed that compared with the normal cervial tissuses, the expression level of six mRNAs were significantly higher in the CC tissue, which was consistent with our findings. We constructed a glycolysis-related six-gene signature to predict the prognosis of patients with CC using bioinformatics methods. We provide a thorough comprehension of the effect of glycolysis in patients with CC and provide new targets and ideas for individualized treatment. Show less
In dairy cows, fatty liver is one of the most common metabolic diseases that occurs during the periparturient period. Angiopoietin-like protein 4 (ANGPTL4) is a well-known downstream target of peroxis Show more
In dairy cows, fatty liver is one of the most common metabolic diseases that occurs during the periparturient period. Angiopoietin-like protein 4 (ANGPTL4) is a well-known downstream target of peroxisome proliferator-activated receptors (PPARs), which regulate the glucose and fatty acid metabolisms. The inhibition of lipoprotein lipase (LPL) activity interferes with the storage of triglycerides (TG) in adipocytes, which plays an essential role in lipid metabolism in rodents. However, it remains unclear whether ANGPTL4 is involved in the pathological process of fatty liver in dairy cows as a result of the regulation of the hepatocellular lipid transport system. This study intended to investigate the effect of ANGPTL4 on the very-low-density lipoprotein (VLDL) assembly and secretion in bovine hepatocytes. Bovine hepatocytes were isolated using a modified two-step perfusion and collagenase digestion process, and treated with different concentrations of ANGPTL4 (0, 4, 12, and 24 ng/ml) for 24 hr. The results showed that a high concentration of ANGPTL4 could significantly increase the extracellular concentration of VLDL while reducing the intracellular content of TG. Thus, it was confirmed that ANGPTL4 could promote the transport of TG in the form of VLDL by partially regulating the expression of related proteins in hepatocytes, thereby contributing to the partial adaptive regulation of lipid transport in dairy cows. Show less
Uterine carcinosarcoma (UCS) is a type of rare and aggressive tumor. The standard treatment for UCS involves surgical treatment followed by radiochemotherapy. Clinical outcomes of UCS patients are poo Show more
Uterine carcinosarcoma (UCS) is a type of rare and aggressive tumor. The standard treatment for UCS involves surgical treatment followed by radiochemotherapy. Clinical outcomes of UCS patients are poor due to high metastasis and relapse rate. Therefore, new targeted therapy strategies for UCS are needed. Because UCS is highly heterogenous, it is critical to identify and develop prognostic biomarkers to distinguish molecular subtypes of UCS for better treatment guidance. Using gene expression profiles and clinical follow-up data, we developed an online consensus survival analysis tool named OSucs. This web tool allows researchers to conveniently analyze the prognostic abilities of candidate genes in UCS. To test the reliability of this server, we analyzed five previously reported prognostic biomarkers, all of which showed significant prognostic impacts. In addition, ETV4 (ETS variant transcription factor 4), ANGPTL4 (Angiopoietin-like protein 4), HIST1H1C (Histone cluster 1 H1 family member c) and CTSV (Cathepsin V) showed prognostic potential in a molecular subtype-specific manner. We built a platform for researchers to analyze if genes have prognostic potentials in UCS. Show less
Angiopoietin-like protein 4 (ANGPTL4) is an adipokine that plays an important role in energy homoeostasis and lipid and lipoprotein metabolism. This study was designed to determine the effect of an ex Show more
Angiopoietin-like protein 4 (ANGPTL4) is an adipokine that plays an important role in energy homoeostasis and lipid and lipoprotein metabolism. This study was designed to determine the effect of an exercise plus weight loss intervention on ANGPTL4 expression and its relationship with metabolic health. Thirty-five obese sedentary men ( Show less
Traditional Chinese medicine Tongxinluo (TXL) has been widely used to treat coronary artery disease in China, since it could reduce myocardial infarct size and ischemia/reperfusion injury in both non- Show more
Traditional Chinese medicine Tongxinluo (TXL) has been widely used to treat coronary artery disease in China, since it could reduce myocardial infarct size and ischemia/reperfusion injury in both non-diabetic and diabetic conditions. It has been shown that TXL could regulate peroxisome proliferator activated receptor-α (PPAR-α), a positive modulator of angiopoietin-like 4 (Angptl4), in diabetic rats. Endothelial junction substructure components, such as VE-cadherin, are involved in the protection of reperfusion injury. Thus, we hypothesized cell-intrinsic and endothelial-specific Angptl4 mediated the protection of TXL on endothelial barrier under high glucose condition against ischemia/reperfusion-injury via PPAR-α pathway. Incubated with high glucose medium, the human cardiac microvascular endothelial cells (HCMECs) were then exposed to oxygen-glucose-serum deprivation (2 hours) and restoration (2 hours) stimulation, with or without TXL, insulin, or rhAngptl4 pretreatment. TXL, insulin, and rhAngptl4 had similar protective effects on the endothelial barrier. TXL treatment reversed the endothelial barrier breakdown in HCMECs significantly as identified by decreasing endothelial permeability, upregulating the expression of JAM-A, VE-cadherin, and integrin-α5 and increasing the membrane location of VE-cadherin and integrin-α5, and these effects of TXL were as effective as insulin and rhAngptl4. However, Angptl4 knock-down with small interfering RNA (siRNA) interference and PPAR-α inhibitor MK886 partially abrogated these beneficial effects of TXL. Western blotting also revealed that similar with insulin, TXL upregulated the expression of Angptl4 in HCMECs, which could be inhibited by Angptl4 siRNA or MK886 exposure. TXL treatment increased PPAR-α activity, which could be diminished by MK886 but not by Angptl4 siRNA. These data suggest cell-intrinsic and endothelial-specific Angptl4 mediates the protection of TXL against endothelial barrier breakdown during oxygen-glucose-serum deprivation and restoration under high glucose condition partly via the PPAR-α/Angptl4 pathway. Show less
The aim of the present study was to analyze the expression levels of angiopoietin-like 4 (ANGPTL4) in breast cancer to investigate the association between ANGPTL4 and breast cancer. Immunohistochemist Show more
The aim of the present study was to analyze the expression levels of angiopoietin-like 4 (ANGPTL4) in breast cancer to investigate the association between ANGPTL4 and breast cancer. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tissues, including 205 invasive ductal carcinoma (IDC) of no special type, 40 normal breast, 40 atypical ductal hyperplasia (ADH) and 40 ductal carcinomas Show less
Insufficient endometrial angiogenesis during peri-implantation impairs endometrial receptivity (ER), which contributes to recurrent implantation failure (RIF) during in vitro fertilization and embryo Show more
Insufficient endometrial angiogenesis during peri-implantation impairs endometrial receptivity (ER), which contributes to recurrent implantation failure (RIF) during in vitro fertilization and embryo transfer (IVF-ET). Angiopoietin-like protein 4 (ANGPTL4) acts as a multifunctional secretory protein and is involved in the regulation of lipid metabolism and angiogenesis in various tissues including the endometrium. Herein, we found decreased ANGPTL4 expression in endometrial tissue and serum during peri-implantation period in 18 RIF-affected women with elevated uterine arterial impedance (UAI) compared with the pregnancy controls. ANGPTL4 and peroxisome proliferator-activated receptor gamma (PPARγ) expression were up-regulated upon decidualization on human endometrial stromal cells (HESCs). Rosiglitazone promoted the expression of ANGPTL4 in HESCs and human umbilical vein endothelial cells (HUVECs) via PPARγ. ANGPTL4 promoted the proliferation, migration and angiogenesis of HUVECs in vitro. Our results suggest that decreased abundance of ANGPTL4 in endometrial tissues impairs the endometrial receptivity via restraining endometrial angiogenesis during decidualization; while rosiglitazone-induced ANGPTL4 up-regulation in hESCs and HUVECs through PPARγ. Therefore, ANGPTL4 could be a potential therapeutic approach for some RIF-affected women with elevated UAI. Show less
Podocyte injury plays a vital role in proteinuria and nephrotic syndrome. Calcineurin (CaN) inhibitors are effective in reducing proteinuria. However, their molecular mechanism is still not fully unde Show more
RNA-sequencing was performed to explore the bovine liver transcriptomes of Holstein cows to detect potential functional genes related to lactation and milk composition traits in dairy cattle. The bovi Show more
RNA-sequencing was performed to explore the bovine liver transcriptomes of Holstein cows to detect potential functional genes related to lactation and milk composition traits in dairy cattle. The bovine transcriptomes of the nine liver samples from three Holstein cows during dry period (50-d prepartum), early lactation (10-d postpartum), and peak of lactation (60-d postpartum) were sequenced using the Illumina HiSeq 2500 platform. A total of 204, 147 and 81 differentially expressed genes (DEGs, p < 0.05, false discovery rate q < 0.05) were detected in early lactation vs. dry period, peak of lactation vs. dry period, and peak of lactation vs. early lactation comparison groups, respectively. Gene ontology and KEGG pathway analysis showed that these DEGs were significantly enriched in specific biological processes related to metabolic and biosynthetic and signaling pathways of PPAR, AMPK and p53 (p < 0.05). Ten genes were identified as promising candidates affecting milk yield, milk protein and fat traits in dairy cattle by using an integrated analysis of differential gene expression, previously reported quantitative trait loci (QTL), data from genome-wide association studies (GWAS), and biological function information. These genes were APOC2, PPP1R3B, PKLR, ODC1, DUSP1, LMNA, GALE, ANGPTL4, LPIN1 and CDKN1A. This study explored the complexity of the liver transcriptome across three lactation periods in dairy cattle by performing RNA sequencing. Integrated analysis of DEGs and reported QTL and GWAS data allowed us to find ten key candidate genes influencing milk production traits. Show less
Hyperlipidemia is the most important early atherosclerosis and coronary artery disease (CAD) indicator. Angiopoietin-like proteins (ANGPTLs) 3, 4, and 8 are lipid dysfunction markers that may be linke Show more
Hyperlipidemia is the most important early atherosclerosis and coronary artery disease (CAD) indicator. Angiopoietin-like proteins (ANGPTLs) 3, 4, and 8 are lipid dysfunction markers that may be linked to CAD. We investigated whether these circulating ANGPTLs are associated with CAD in patients with obstructive sleep apnea (OSA). A total of 327 individuals participated in this study: 221 patients with OSA and CAD, 50 patients with OSA alone, and 56 controls. The Gensini Score was used to assess the severity of CAD. Serum ANGPTL3, ANGPTL4, and ANGPTL8 were measured in all subjects using Human Magnetic Luminex Screening Assay. The independent association between levels of ANGPTLs and CAD was evaluated by multivariate regression analysis. Serum ANGPTL3 levels were significantly higher in patients suffering from OSA and CAD compared with patients having OSA alone (46.97 ± 13.89 vs 38.25 ± 15.94 ng/ml, P < 0.001). Univariate analysis demonstrated that ANGPTL3 was a risk factor for CAD (OR = 1.72/10 ng ANGPTL3, 95% CI, 1.29-2.28, P < 0.001). In addition, multivariate analysis revealed that ANGPTL3 was independently associated with the presence of CAD (OR = 1.74/10 ng ANGPTL3, 95% CI, 1.29-2.35, P < 0.001) even after adjusting for cofounding factors. Furthermore, circulating ANGPTL3 levels were positively associated with triglyceride (r = 0.16, P = 0.01) and total cholesterol (r = 0.14, P = 0.02) levels, while ANGPTL3 levels had no significant correlation with the severity of CAD. No significant associations were found between the levels of ANGPTL4 and ANGPTL8 and CAD even after adjusting for established risk factors. Elevated levels of ANGPTL3 were independently associated with a higher likelihood of CAD in patients with OSA. It may be a novel biomarker for OSA patients at high risk of developing cardiovascular diseases. Show less
Clear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of kidney with high mortality. The pathogenesis of ccRCC is complicated and effective prognostic predictors for clinical prac Show more
Clear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of kidney with high mortality. The pathogenesis of ccRCC is complicated and effective prognostic predictors for clinical practice are still limited. This study aimed to identify significant genes with prognostic influence in ccRCC via bioinformatics analysis. Four gene expression profiles were acquired from the Gene Expression Omnibus (GEO) database, including 168 ccRCC tissues and 143 normal tissues. Common differentially expressed genes (DEGs) between ccRCC tissues and normal kidney tissues were screened out. Then gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were investigated. Protein-protein interaction (PPI) network of the common DEGs was diagrammed and analyzed. Kaplan-Meier analysis was conducted to identify genes with prognostic influence in ccRCC. Gene Expression Profiling Interactive Analysis (GEPIA) was finally applied to validating differential expression of genes. Ninety-nine common DEGs between ccRCC tissues and normal kidney tissues were eventually screened out (P<0.05, |log FC| >2). GO functional analysis showed that the down-regulated genes were enriched in excretion, negative regulation of cell proliferation, heparin binding and cellular response to BMP stimulus, etc. KEGG pathway analysis indicated that the common DEGs were particularly enriched in HIF-1 signaling pathway and aldosterone-regulated sodium reabsorption. Seven core DEGs were distinguished through PPI network analysis, of which 6 core genes Our study shows that high expression of Show less
There has been little investigation carried out into the activity of immune-related genes in the prognosis of non-small cell lung cancer (NSCLC). Our study set out to analyze the correlation between t Show more
There has been little investigation carried out into the activity of immune-related genes in the prognosis of non-small cell lung cancer (NSCLC). Our study set out to analyze the correlation between the differential expression of immune genes and NSCLC prognosis by screening the differential expression of immune genes. Based on the immune genes identified, we aimed to construct a prognostic risk model and explore some novel molecules which have predictive potential for therapeutic effect and prognosis in lung cancer. Immune gene transcriptome data and clinical data of NSCLC samples were extracted from TCGA database, and transcription factors in the ImmPort dataset were obtained. The data were divided into two groups: normal tissues and tumor tissues. The expression levels of immune genes were compared using the edgeR algorithm, and then differential expression analysis was performed. The survival analysis was carried out by combining differential immune genes with clinical survival time, so that the immune genes influencing the prognosis of NSCLC could be determined. A risk score was calculated based on the expression levels of the immune genes related to the prognosis of NSCLC and their corresponding coefficients to construct a prognostic risk model. This model was used to calculate patient risk scores and perform clinical correlation analysis. The selected molecules were further verified by clinical samples. By comparing NSCLC tissues with normal tissues, a total of 6,778 differentially expressed genes were found (P<0.05), of which 490 were differential immune-related genes. Survival analysis determined 28 differential immune genes to be associated with prognosis (P<0.05). We calculated the patient risk value based on the immune gene prognosis model. The survival curve was drawn according to the patient risk score and showed that the survival prognosis was significantly different for the high-risk and the low-risk groups (P<0.05). The area under the receiver operating characteristic (ROC) curve (AUC) was 0.723, which represented a relatively high true-positive rate. All of the results proved the reliability of our immune gene risk prognostic model. After drawing the risk curve, S100A16, IGKV4, S100P, ANGPTL4, SEMA4B, and LGR4 were found to be the high-risk immune genes in NSCLC. Clinical correlation analysis of survival-related differential immune genes revealed that in patients with lymph node metastasis, ANGPTL4 was positively correlated with T stage, S100a16 and SEMA4B were upregulated, and VIPR1 was downregulated. Further analysis revealed that VIPR1 was decreased in metastatic lung cancer compared to non-metastatic lung cancer. Furthermore, the real-time PCR detection of the clinical samples showed that S100A16 expression in lung cancer was increased, while VIPR1 expression in lung cancer was downregulated, which was consistent with the results of our bioinformatics analysis. Based on big data from the TCGA and ImmPort databases, our study analyzed the relationship between differential expression of immune-related genes and clinical data, and constructed a prognostic model based on the immune genes identified. Two novel molecules, S100A16 and VIPR1, were verified to possibly have significant biological function in NSCLC. Our research may provide us with new insight into the immune genes by which the malignant biological behavior of NSCLC is mediated. Show less
Bushen Huoxue formula (BSHXF) is a Chinese herbal prescription composed of eleven herbs widely used to treat psychological stress-induced premature ovarian insufficiency (POI) in clinical. However, th Show more
Bushen Huoxue formula (BSHXF) is a Chinese herbal prescription composed of eleven herbs widely used to treat psychological stress-induced premature ovarian insufficiency (POI) in clinical. However, the underlying mechanism is still unclear. The purpose of this study was to clarify the underlying molecular mechanisms of BSHXF in the treatment of psychological stress-induced POI. The rat model was induced by corticosterone (CORT, 40mg/kg). Drugs were administered to rats once daily for 21 days. The serum E Our results indicate that BSHXF can improve ovarian disfunction. The levels of serum FSH were signally enhanced in model group compared to control group. As respected, BSHXF treatment for 3 weeks led to the decreased FSH levels than the model group. The concentrations of AMH showed an obvious decrease in the model group and were increased by BSHXF treatment. Moreover, the size and number of follicles in the BSHXF groups were similar to those in the control group. The proteomic screened out that Np4 and Angptl4 were simultaneously enriched by GO and KEGG, thus these two proteins were chosen for further study. These findings revealed that BSHXF might regulate the expression of Np4 and Angptl4 to improve psychological stress-induced POI. Show less
Enhancer of zeste homolog 2 (EZH2) is associated with ulcerative colitis development. However, the mechanism of EZH2 in ulcerative colitis progression remains unclear. Lipopolysaccharide (LPS)-treated Show more
Enhancer of zeste homolog 2 (EZH2) is associated with ulcerative colitis development. However, the mechanism of EZH2 in ulcerative colitis progression remains unclear. Lipopolysaccharide (LPS)-treated Caco-2 cells and dextran sodium sulfate (DSS)-treated mice were used as model of ulcerative colitis. The levels of EZH2, angiopoietin-like 4 (ANGPTL4) and cyclic adenosine monophosphate response element-binding protein 1 (CREB1) were tested via quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell viability and apoptosis was measured via 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide or flow cytometry. The abundances of inflammatory cytokines were examined via qRT-PCR and enzyme-linked immunosorbent assay. The association between EZH2 and ANGPTL4 was explored via chromatin immunoprecipitation. The colon damage in DSS-treated mice was investigated by colon length, histological analysis, inflammatory response and apoptosis. LPS induced viability inhibition, inflammatory response and apoptosis in Caco-2 cells. EZH2 expression was increased but ANGPTL4 and CREB1 levels were decreased in LPS-challenged Caco-2 cells. Overexpression of ANGPTL4 or CREB1 suppressed LPS-induced damage in Caco-2 cells. EZH2 could target ANGPTL4 to mediate CREB1 expression. Inhibition of EZH2 suppressed LPS-caused injury. Moreover, knockdown of ANNGPTL4 or CREB1 attenuated the role of EZH2 inhibition. DSS caused the reduced colon length and increased inflammatory response as well as apoptosis. EZH2 expression was up-regulated but ANGPTL4 and CREB1 expression were down-regulated in DSS-treated mice. Inhibition of EZH2 declined LPS-induced injury in Caco-2 cells by mediating ANGPTL4 and CREB1, indicating the potential of EZH2 in treatment of ulcerative colitis. Show less
Tanshinol A, which is derived from a traditional Chinese herbal Radix Salviae Miltiorrhizae is indicative of a hypolipidemic candidate. Therefore, we aim to validate its hypolipidemic activity of tans Show more
Tanshinol A, which is derived from a traditional Chinese herbal Radix Salviae Miltiorrhizae is indicative of a hypolipidemic candidate. Therefore, we aim to validate its hypolipidemic activity of tanshinol A and explore its mechanism in triton-1339W-induced hyperlipidemic mice model, which possess multiply pathogenesis for endogenous lipid metabolism disorder. Experimental hyperlipidemia mice are treated with or without tanshinol A (i.g. 40, 20, 10 mg/kg), and blood and liver tissue were collected for validating its hypolipidemic and hepatic protective effect, and hepatic mRNA expression profile, which was associated with lipid metabolism dysfunction and liver injury, was detected by RT-qPCR. As results show, triton-1339W-induced abnormal of serum TC, TAG, HDL-C, LDL-C, SOD, MDA, GOT, and GPT is remarkably attenuated by tanshinol A. In pathological experiment, triton-1339W-induced hepatocellular ballooning degeneration, irregular central vein congestion, and inflammation infiltration are alleviated by tanshinol A. Correspondingly, hepatic mRNA expression of Atf4, Fgf21, Vldlr, Nqo1, Pdk4, and Angptl4, which are genes regulating lipemic-oxidative injury, are significantly increased by tanshinol A by 2~6 fold. Abcg5, Cd36, and Apob, which are responsible for cholesterol metabolism, are mildly upregulated. Noticeably, triton-1339W-suppressed expressions of Ptgs2/Il10, which are genes responsible for acute inflammation resolution in liver injury, are remarkably increased by tanshinol A. Conclusively, tanshinol A exerted hypolipidemic effect and hepatoprotective effect through restoring triton-1339W-suppressed mRNA expression, which may be involved in Atf4/Fgf21/Vldlr and Ptgs2/Il-10 signaling pathways. Show less
Tumour cells interfere with normal immune functions by affecting the expression of some immune-related genes, which play roles in the prognosis of cancer patients. In recent years, immunotherapy for t Show more
Tumour cells interfere with normal immune functions by affecting the expression of some immune-related genes, which play roles in the prognosis of cancer patients. In recent years, immunotherapy for tumours has been widely studied, but a practical prognostic model based on immune-related genes in lung adenocarcinoma comparable to existing model has not been established and reported. We first obtained publicly accessible lung adenocarcinoma RNA expression data from The Cancer Genome Atlas (TCGA) for differential gene expression analysis and then filtered immune-related genes based on the ImmPort database. By using the lasso algorithm and multivariate Cox Proportional-Hazards (CoxPH) regression analysis, we identified candidate genes for model development and validation. The robustness of the model was further examined by comparing the model with three established gene models. Gene expression data from a total of 524 lung adenocarcinoma patients from TCGA were used for model development. We identified four biomarkers (MAP3K8, CCL20, VEGFC, and ANGPTL4) that could predict overall survival in lung adenocarcinoma (HR = 1.98, 95% CI 1.48 to 2.64, P = 4.19e-06) and this model could be used as a classifier for the evaluation of low-risk and high-risk groups. This model was validated with independent microarray data and was highly comparable with previously reported gene expression signatures for lung adenocarcinoma prognosis. In this study, we identified a practical and robust four-gene prognostic model based on an immune gene dataset with cross-platform compatibility. This model has potential value in improving TNM staging for survival predictions in patients with lung adenocarcinoma. The study provides a method of immune relevant gene prognosis model and the identification of immune gene classifier for the prediction of lung adenocarcinoma prognosis with RNA sequencing and microarray compatibility. Show less
Hypertriglyceridemia is a risk factor for a series of diseases, such as cardiovascular disease (CVD), diabetes and nonalcoholic fatty liver disease (NAFLD). Angiopoietin-like proteins (ANGPTLs) family Show more
Hypertriglyceridemia is a risk factor for a series of diseases, such as cardiovascular disease (CVD), diabetes and nonalcoholic fatty liver disease (NAFLD). Angiopoietin-like proteins (ANGPTLs) family, especially ANGPTL3, ANGPTL4 and ANGPTL8, which regulate lipoprotein lipase (LPL) activity, play pivotal roles in triglyceride (TG) metabolism and related diseases/complications. There are many transcriptional and post-transcriptional factors that participate in physiological and pathological regulation of ANGPTLs to affect triglyceride metabolism. This review is intended to focus on the similarity and difference in the expression, structural features, regulation profile of the three ANGPTLs and inhibitory models for LPL. Description of the regulatory factors of ANGPTLs and the properties in regulating the lipid metabolism involved in the underlying mechanisms in pathological effects on diseases will provide potential therapeutic approaches for the treatment of dyslipidemia related diseases. Show less
Distinguishing between different types of thyroid cancers (TC) remains challenging in clinical laboratories. As different tumor types require different clinical interventions, it is necessary to estab Show more
Distinguishing between different types of thyroid cancers (TC) remains challenging in clinical laboratories. As different tumor types require different clinical interventions, it is necessary to establish new methods for accurate diagnosis of TC. Proteomic analysis of the human serum was performed through data-independent acquisition mass spectrometry for 29 patients with TC (stages I-IV): 13 cases of papillary TC (PTC), 10 cases of medullary TC (MTC), and six cases follicular TC (FTC). In addition, 15 patients with benign thyroid nodules (TNs) and 10 healthy controls (HCs) were included in this study. Subsequently, 17 differentially expressed proteins were identified in 291 patients with TC, including 247 with PTC, 38 with MTC, and six with FTC, and 69 patients with benign TNs and 176 with HC, using enzyme-linked immunosorbent assays. In total, 517 proteins were detected in the serum samples using an Orbitrap Q-Exactive-plus mass spectrometer. The amyloid beta A4 protein, apolipoprotein A-IV, gelsolin, contactin-1, gamma-glutamyl hydrolase, and complement factor H-related protein 1 (CFHR1) were selected for further analysis. The median serum CFHR1 levels were significantly higher in the MTC and FTC groups than in the PTC and control groups ( CFHR1 may serve as a novel biomarker to distinguish PTC from MTC with high sensitivity and specificity. Show less
Preterm birth severely threatens neonatal health and life. Although the detailed mechanism of preterm birth is not well understood, accurately predicting preterm birth can help people make preparation Show more
Preterm birth severely threatens neonatal health and life. Although the detailed mechanism of preterm birth is not well understood, accurately predicting preterm birth can help people make preparations in advance, greatly reducing the subsequent health risk of neonates. Therefore, in this study, we aimed to identify potential protein biomarkers of preterm birth in amniotic fluid (AF). We first enrolled pregnant subjects and collected their AF samples when they underwent amniocentesis at the second trimester of gestation. After delivery, the collected AF samples were classified into a full-term birth (sample size n = 21) set or preterm birth (n = 36) set, followed by 2-D DIGE and MS/MS assays. By doing so, we identified seven potential protein biomarkers of preterm birth, three of which were further validated in all samples with ELISA, including Apolipoprotein A-IV (Apoa4), Lumican (Lum) and Kininogen-1 (Kng1). As a result, all three potential biomarkers were significantly differently expressed between preterm and full-term birth AF samples. Furthermore, without prior classification, we found that these three biomarkers were positively correlated with gestation age (correlation coefficient ranging from 0.25 to 0.38) and were able to predict the occurrence of preterm birth. In this study, by examining amniotic fluid, we identified three biomarker proteins that may facilitate the identification of preterm birth. There three proteins were never reported to be related to preterm birth. Their pathogenesis roles in preterm birth deserve further investigations by using in vitro cell model or in vivo animal model assays. Show less
The fabrication of electrochemical biosensors to directly, rapidly and ultrasensitively detect disease markers in urine or blood samples has become a new and competitive challenge in the field of sens Show more
The fabrication of electrochemical biosensors to directly, rapidly and ultrasensitively detect disease markers in urine or blood samples has become a new and competitive challenge in the field of sensor research. In this paper, a novel electrochemical immunosensor with high selectivity and sensitivity for the detection of the depression marker human apolipoprotein A4 (Apo-A4) was successfully constructed using zeolite imidazole ester metal organic skeleton-nitrogen doped graphene composites (ZIF-8@N-Gr). To this end, because of the higher surface area and biocompatibility, ZIF-8 with abundant biomolecular binding sites provided a good microenvironment for effectively immobilizing antigens. ZIF-8@N-Gr presented a flake structure, as the electrode displayed excellent electrical conductivity, which enhanced the electron transfer and significantly amplified the current signal of the immunosensor. More importantly, these immunosensors are capable of assaying human apolipoprotein A4 (Apo-A4) in 100% serum without suffering from any significant biological interference. Under optimized experimental conditions, the sensor was used for the analysis of whole serum samples and presented a wide linear range from 1.47 × 10 Show less
Long noncoding RNAs (lncRNAs) are currently considered to have a vital and wide range of biological functions, but the molecular mechanism underlying triglycerides metabolism remains poorly understood Show more
Long noncoding RNAs (lncRNAs) are currently considered to have a vital and wide range of biological functions, but the molecular mechanism underlying triglycerides metabolism remains poorly understood. This study aims to identify novel lncRNAs differentially expressed in rat livers with hypertriglyceridemia and elucidated the function role in TG metabolism. Differentially expressions of lncRNAs in rat livers with hypertriglyceridemia were identified by transcriptome sequencing and validated by real-time PCR. The role of lnc19959.2 in triglyceride metabolism was assessed both in vitro and in vivo. RNA pulldown and RIP assays were conducted to evaluate the interactions between lnc19959.2 and its target proteins. ChIP and Dual report assays were performed to detect the interactions between transcription factors and promoters of its target genes. We identified a novel lncRNA, and lnc19959.2 was upregulated in rat livers with hypertriglyceridemia. The knockdown of lnc19959.2 has profound TG lowering effects in vitro and in vivo. Subsequently, the genome-wide analysis identified that the knockdown of lnc19959.2 caused the deregulation of many genes during TG homeostasis. Further mechanism studies revealed that lnc19959.2 upregulated ApoA4 expression via ubiquitinated transcription inhibitor factor Purb, while it specifically interacted with hnRNPA2B1 to downregulate the expression of Cpt1a, Tm7sf2, and Gpam, respectively. In the upstream pathway, palmitate acid upregulated CCAAT/Enhancer-Binding Protein Beta (Cebpb) and facilitated its binding to the promoter of lnc19959.2, which resulted in significant promotion of lnc19959.2 transcriptional activity. Our findings provide novel insights into a new layer regulatory complexity of an lncRNA modulating triglyceride homeostasis by a novel lncRNA lnc19959.2. Show less
The application of tetracycline (TET) is very common in medical treatment, fisheries, and animal husbandry, resulting in its frequent detection with abundant concentrations in the aquatic environment. Show more
The application of tetracycline (TET) is very common in medical treatment, fisheries, and animal husbandry, resulting in its frequent detection with abundant concentrations in the aquatic environment. Though the effects of TET on zebrafish (Danio rerio) at embryonic and larval stages have been reported, there is very limited information on the possible long-term effect on aquatic fishes at the juvenile stage, especially at environmentally relevant levels. In this study, we have exposed juvenile zebrafish to two levels of TET at 1 and 100 µg/L for one month until their adulthood. The result showed that both levels of TET can significantly increase the body weight of the zebrafish, while there is no change in the body length. TET exposure also affected the liver microstructure by lipid vacuoles generation and global lipidomics analysis revealed a significant upregulation in hepatic triglyceride (TAG) levels. The metabolomics analysis showed great dysregulations in hepatic metabolic pathways including linoleic acid metabolism, tyrosine metabolism, and methionine metabolism, which are known to be linked with increased body weight gain through hepatic lipid accumulation. The hepatic gene expression involved in lipid transport (e.g., apoa4 and fabp11) and lipogenic factors (e.g., ppar) have been significantly upregulated in the livers of TET exposed zebrafish. Interestingly, the 16 rRNA gene sequence-based zebrafish gut microbial community analysis revealed an enhanced community diversity and altered microbial community composition upon TET exposure. To our knowledge, this is the first study showing that TET exposure can increase the body weight in juvenile zebrafish and the study on the ecotoxicity of antibiotic occurrences in the aquatic system can be further warranted. Show less
Strokes usually results in long-term disability and death, and they occur worldwide. Recently, increased research on both on the physiopathological mechanisms and the transcriptome during stroke progr Show more
Strokes usually results in long-term disability and death, and they occur worldwide. Recently, increased research on both on the physiopathological mechanisms and the transcriptome during stroke progression, have highlighted the relationship between stroke progression and immunity, with a special focus on inflammation. Here, we applied proteome analysis to a middle carotid artery occlusion (MCAO) mouse model at 0 h, 6 h, 12 h and 24 h, in which proteome profiling was performed with 23 samples, and 41 differentially expressed proteins (DEPs) were identified. Bioinformatics studies on our data revealed the importance of the immune response and particularly identified the inflammatory response, cytokine- cytokine receptor interactions, the innate immune response and reactive oxygen species (ROS) during stroke progression. In addition, we compared our data with multiple gene expression omnibus (GEO) datasets with and without a time series, in which similar pathways were identified, and three proteins, C3, Apoa4 and S100a9, were highlighted as markers or drug targets for stroke; these three proteins were significantly upregulated in the MCAO model, both in our proteomic data and in the GEO database. Show less
Olanzapine is commonly used to treat schizophrenia. However, long-term administration of olanzapine causes metabolic side effects, such as insulin resistance (IR), which seriously affects patients' qu Show more
Olanzapine is commonly used to treat schizophrenia. However, long-term administration of olanzapine causes metabolic side effects, such as insulin resistance (IR), which seriously affects patients' quality of life. Both diagnostic and prognostic markers are urgently needed to increase patient compliance. We applied isobaric tags for relative and absolute quantitation (iTRAQ) labeling combined with 2D LC/MS/MS technology to identify the differentially expressed proteins in olanzapine-induced IR rats. A total of 3194 proteins were identified from rat adipose tissues, and 270 differentially expressed proteins were screened out with a ratio threshold >1.5-fold or <0.67-fold. Based on a bioinformatics analysis and literature search, we selected six candidates (MYH1, MYL2, Cp, FABP4, apoA-IV, and Ywhaz) from a set of 270 proteins and verified these proteins by western blot; the expression of these proteins coincided with the LC-MS/MS results. Finally, the biological roles of FABP4 and apoA-IV, which are two novel IR-related proteins identified in the present study, were verified in 3T3-L1 cells. These data suggest that these two proteins acted on olanzapine-induced IR via the IRS-1/AKT signaling pathway. Our results provide a dataset of potential targets to explore the mechanism in olanzapine-induced IR and reveal the new roles of FABP4 and apoA-IV in olanzapine-induced IR. SIGNIFICANCE: The proteomic analysis of this study revealed the target associated with olanzapine-induced IR and provided relevant insights into the molecular functions, biological processes, and signaling pathways in these targets. Protein MYH1, MYL2, Cp, FABP4, apoA-IV, and Ywhaz may be potential biomarkers, and protein FABP4 and apoA-IV were considered as promising targets in olanzapineinduced IR. Therefore, if the performance of the proposed biomarkers is further confirmed, these proteins can provide powerful targets for exploring the mechanism of olanzapine-induced IR. Show less