All-optical polarization scrambler based on polarization beam splitting with an amplified fiber ring.

Optical-fiber-based polarization scramblers can reduce the impact of polarization sensitive performance of various optical fiber systems. Here, we propose a simple and efficient polarization scrambler based on an all-optical Mach-Zehnder structure by combining a polarization beam splitter and an amplified fiber ring. To totally decoherence one polarization split beam, a fiber ring together with an amplifier is incorporated. The ratio of two orthogonal beams can be controlled by varying the amplification factor, and we observe different evolution trajectories of the output state of polarizations on the Poincaré sphere. When the amplification factor exceeds a certain threshold, the scrambler system exhibits nearly ideal polarization scrambling behavior. A commercial single wavelength laser with a linewidth of 3 MHz is utilized to characterize the scrambling performance. We found that when the sampling rate is 1.6 MSa/s, a scrambling speed up to 2000krad/s can be obtained for the average degree of polarization being less than 0.1. We also exploit these random polarization fluctuations to generate random binary numbers, indicating that the proposed technique is a good candidate for a random bit generator.

Paeonol inhibits the malignancy of Apatinib-resistant gastric cancer cells via LINC00665/miR-665/MAPK1 axis.

BACKGROUND: Paeonol is the extractive of Paeonia suffruticosa Andr and is reported to reverse the chemotherapy resistance of cancer cells. The present study explores the role of paeonol in inhibiting the malignant biological behaviors of Apatinib-resistant gastric cancer (GC) cells. METHODS: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was adopted to screen the target genes of paeonol, and the STRING database was employed to construct a protein-protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the target genes was performed employing DAVID online database. The expressions of these target genes in GC tissues and para-cancerous tissues were analyzed with GEPIA database, and GEO datasets (GSE109476 and GSE93415) were utilized to analyze differentially expressed lncRNAs and miRNAs in GC tissues and para-cancerous tissues. The expressions of LINC00665, miR-665 and MAPK1 mRNA in Apatinib-resistant GC cells were detected through quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) assay was conducted to detect cell proliferation; Transwell assays were employed to detect cell migration and invasion, and TdT-mediated dUTP nick end labeling (TUNEL) assay was utilized to detect cell apoptosis. Dual-luciferase reporter gene assay was performed to detect the binding relationships between miR-665 and LINC00665, as well as between miR-665 and MAPK1 mRNA. The expressions of MAPK1 protein and glycolysis-associated proteins (GLUT1, LDHB and HK2) were detected by Western blot. Additionally, a tumor xenograft mice model was constructed to evaluate the effects of paeonol on lung metastasis. RESULTS: Paeonol could inhibit the proliferation, migration, invasion and glycolysis, and promote the apoptosis of Apatinib-resistant GC cells. TCMSP database suggested that Paeonol had 17 target genes, and 17 target genes were mainly enriched in signaling pathways related to apoptosis, glucose and lipid metabolism, etc.; GEPIA database suggests that MAPK1, among the 17 target genes, was markedly elevated in GC tissues. Paeonol could decrease LINC00665 and MAPK1 expressions in GC cells but increase the expression of miR-665. LINC00665 overexpression, MAPK1 overexpression or inhibition of miR-665 could abolish the inhibitive effects of paeonol on the malignant phenotypes of Apatinib-resistant GC cells. miR-665 is verified as an upstream regulator of MAPK1 and a target of LINC00665. Additionally, paeonol could significantly inhibit the lung metastasis in the tumor xenograft mice model. CONCLUSIONS: Paeonol can inhibit the malignancy of Apatinib-resistant GC cells through LINC00665/miR-665/MAPK1 axis. For the first time, our study imply that paeonol may be a potential drug to reverse Apatinib-resistant of GC cells.

MicroRNA-665-3p exacerbates nonalcoholic fatty liver disease in mice.

Oxidative stress and chronic inflammation are major culprits of nonalcoholic fatty liver disease (NAFLD). MicroRNA-665-3p (miR-665-3p) is implicated in regulating inflammation and oxidative stress; however, its role and molecular basis in NAFLD remain elusive. Herein, we measured a significant upregulation of miR-665-3p level in the liver and primary hepatocytes upon high fat diet (HFD) or 0.5 mmol/L palmitic acid plus 1.0 mmol/L oleic acid stimulation, and the elevated miR-665-3p expression aggravated oxidative stress, inflammation and NAFLD progression in mice. In contrast, miR-665-3p inhibition by the miR-665-3p antagomir significantly prevented HFD-induced oxidative stress, inflammation and hepatic dysfunction in vivo. Manipulation of miR-665-3p in primary hepatocytes also caused similar phenotypic alterations in vitro. Mechanistically, we demonstrated that miR-665-3p directly bound to the 3'-untranslated region of fibronectin type III domain-containing 5 (FNDC5) to downregulate its expression and inactivated the downstream AMP-activated protein kinase alpha (AMPKα) pathway, thereby facilitating oxidative stress, inflammation and NAFLD progression. Our findings identify miR-665-3p as an endogenous positive regulator of NAFLD via inactivating FNDC5/AMPKα pathway, and inhibiting miR-665-3p may provide novel therapeutic strategies to treat NAFLD.

Effect of a deep learning-based system on the miss rate of gastric neoplasms during upper gastrointestinal endoscopy: a single-centre, tandem, randomised controlled trial.

BACKGROUND: White light endoscopy is a pivotal first-line tool for the detection of gastric neoplasms. However, gastric neoplasms can be missed during upper gastrointestinal endoscopy due to the subtle nature of these lesions and varying skill among endoscopists. Here, we aimed to evaluate the effect of an artificial intelligence (AI) system designed to detect focal lesions and diagnose gastric neoplasms on reducing the miss rate of gastric neoplasms in clinical practice. METHODS: This single-centre, randomised controlled, tandem trial was done at Renmin Hospital of Wuhan University, China. We recruited consecutive patients (≥18 years old) undergoing routine upper gastrointestinal endoscopy for screening, surveillance, or investigation of symptoms. Same-day tandem upper gastrointestinal endoscopy was done where patients first underwent either AI-assisted (AI-first) or routine (routine-first) white light endoscopy, followed immediately by the other procedure, with targeted biopsies for all detected lesions taken at the end of the second examination. Patients were randomly assigned (1:1) to the AI-first or routine-first group using a computer-generated random numerical series and block randomisation (block size of four). Endoscopists were not blinded to randomisation status, whereas patients and pathologists were. The primary endpoint was the miss rate of gastric neoplasms and the analysis was done per protocol. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR2000034453, and has been completed. FINDINGS: Between July 6, 2020, and Dec 11, 2020, 907 patients were randomly assigned to the AI-first group and 905 to the routine-first group. The gastric neoplasm miss rate was significantly lower in the AI-first group than in the routine-first group (6·1%, 95% CI 1·6-17·9 [3/49] vs 27·3%, 15·5-43·0 [12/44]; relative risk 0·224, 95% CI 0·068-0·744; p=0·015). The only reported adverse event was bleeding from a target lesion after biopsy. INTERPRETATION: The use of an AI system during upper gastrointestinal endoscopy significantly reduced the gastric neoplasm miss rate. AI-assisted endoscopy has the potential to improve the yield of gastric neoplasms by endoscopists. FUNDING: The Project of Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision and the Hubei Province Major Science and Technology Innovation Project.

Association between genetic variants in ZNF365 and inflammatory bowel disease risk in Caucasians: a meta-analysis and trial sequential analysis.

OBJECTIVE: The published studies regarding the relationships between zinc finger 365 (ZNF365) polymorphisms and inflammatory bowel disease (IBD) risk in Caucasians have yielded conflicting results. Therefore, we performed a meta-analysis to clarify this issue. METHODS: The Electronic databases of PubMed, Web of Science, Wiley Online Library, and EMBASE were searched for eligible studies up to 31 November 2020. The quality of eligible studies was evaluated using the Newcastle-Ottawa Scale. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) under different genetic models were calculated to assess the strength of associations. RESULTS: A total of 22 relevant case-control studies with 9542 ulcerative colitis (UC) patients and 13,886 controls, as well as 13,651 Crohn's disease (CD) patients and 15,256 controls, were involved in our meta-analysis. rs10761659 polymorphism significantly decreased CD and UC risk (except for the heterozygous model and the dominant model in UC), and rs10995271 polymorphism was significantly associated with UC (except for the heterozygous model and dominant model) rather than CD. CONCLUSIONS: The meta-analysis demonstrated that the rs10761659 polymorphism might be a protective factor for both UC and CD in Caucasians, while the rs10995271 polymorphism might be a risk factor for UC rather than CD in Caucasians.

MicroRNA-137-3p Improves Nonalcoholic Fatty Liver Disease through Activating AMPKα.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide and can develop to nonalcoholic steatohepatitis and later hepatic cirrhosis with a high prevalence to hepatocellular carcinoma. Oxidative stress and chronic hepatic inflammation are implicated in the pathogenesis of NAFLD. MicroRNA-137-3p (miR-137-3p) are associated with oxidative stress and inflammation; however, its role and mechanism in NAFLD remain unclear. Mice were fed with a high-fat diet (HFD) for 24 weeks to establish the NAFLD model. To overexpress or suppress hepatic miR-137-3p expression, mice were intraperitoneally injected with the agomir, antagomir, or respective controls of miR-137-3p at a dose of 100 mg/kg weekly for 6 consecutive weeks before the mice were sacrificed. To validate the involvement of AMP-activated protein kinase alpha (AMPKα) or cAMP-specific phosphodiesterase 4D (PDE4D), HFD mice were intraperitoneally injected with 20 mg/kg compound C or 0.5 mg/kg rolipram every other day for 8 consecutive weeks before the mice were sacrificed. Hepatic miR-137-3p expression was significantly decreased in mice upon HFD stimulation. miR-137-3p agomir alleviated, while miR-137-3p antagomir facilitated HFD-induced oxidative stress, inflammation, and hepatic dysfunction in mice. Mechanistically, we revealed that miR-137-3p is directly bound to the 3'-untranslated region of PDE4D and subsequently increased hepatic cAMP level and protein kinase A activity, thereby activating the downstream AMPKα pathway. In summary, miR-137-3p improves NAFLD through activating AMPKα and it is a promising therapeutic candidate to treat NAFLD.

IRE1α-JNK pathway-mediated autophagy promotes cell survival in response to endoplasmic reticulum stress during the initial phase of hepatic steatosis.

AIMS: It has been widely reported that autophagy and inositol-requiring enzyme-1α (IRE1α)-c-Jun N-terminal kinase (JNK) pathway was involved in cell survival under endoplasmic reticulum (ER) stress, but their specific roles in hepatic steatosis remain unclear. This study aimed to determine the interaction between autophagy and IRE1α-JNK pathway on cell survival in response to ER stress during the initial phase of hepatic steatosis. METHODS: Hepatic steatosis was induced in HepG2 cells by supplementing oleic acid (OA). Lipid accumulation was evaluated by BODIPY493/503 staining. ER stress and IRE1α-JNK signaling were investigated by western blot. Autophagy was monitored by western blot, GFP-LC3 plasmid and immunofluorescence staining, while apoptosis was determined by western blotting, Annexin-V-FITC/PI staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. KEY FINDINGS: Aggravated lipid accumulation was found under increased ER stress during the initial phase of hepatic steatosis. Meanwhile, an increase of autophagy and no alteration of apoptosis were observed under increased ER stress. Interestingly, autophagy was induced by ER stress, while autophagy suppression led to an increase of apoptosis in response to ER stress Moreover, further study showed that IRE1α-JNK pathway was activated after ER stress and consequently induced autophagy, which promoted cell survival in the initial phase of hepatic steatosis. SIGNIFICANCE: We conclude that IRE1α-JNK pathway was activated during ER stress in the initial phase of hepatic steatosis and promoted cell survival by enhancing autophagy. Targeting IRE1α-JNK-autophagy signaling may provide new insight into preventive strategies for hepatic steatosis.

Association between IL12B polymorphisms and inflammatory bowel disease in Caucasian population: A meta-analysis.

BACKGROUND: Published studies on association between IL12B (G/A) rs10045431, (T/C)rs6887695 polymorphisms and inflammatory bowel disease (IBD) risk in Caucasian population have yielded conflicting results. The aim of this study was to potentially provide more reliable conclusions by conducting a meta-analysis. METHODS: Published studies concerned association between IL12B rs10045431, rs6887695 polymorphisms and IBD were searched from the Wiley Online Library, PubMed, Web of Science and the CNKI database. The odds ratio (OR) with 95% confidence interval (CI) was calculated to evaluate the strength of the relationship. The false positive report probabilities (FPRPs) test and trial sequential analysis (TSA) was performed to investigated the reliability of results. RESULTS: A total of 20 studies comprising 10761 Crohn's disease (CD), 10921 ulcerative colitis (UC) and 18381 controls were included in this meta-analysis. Overall, the pooled results showed that IL12B rs6887695 polymorphism significantly increased both CD and UC risk under all model, while IL12B rs10045431 polymorphism dramatically decreased both CD and UC risk under all model. FPRP and TSA demonstrated that above associations was confirmed in the present study. CONCLUSION: The results of meta-analysis indicate IL12B rs10045431 and rs6887695 polymorphisms significantly associate with IBD in Caucasian population.

Association between PTGER4 polymorphisms and inflammatory bowel disease risk in Caucasian: A meta-analysis.

BACKGROUND: The results from previous studies on association between prostaglandin E receptor 4 (PTGER4) polymorphisms and inflammatory bowel disease (IBD) risk in Caucasian were conflict. The present study aimed to investigate the genetic association by conducting a meta-analysis. METHODS: Systematic literature search was conducted through Wiley Online Library, Chinese National Knowledge Infrastructure (CNKI), and PubMed databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to investigate the associations between rs4613763 T/C, 17234657T/G polymorphisms, and IBD risk in Caucasian. RESULTS: Twenty case-control studies consisting of 18,495 Crohn disease (CD) patients and 4203 ulcerative colitis (UC) patients, as well as 26,063 controls were included in this meta-analysis. The rs4613763T/C polymorphism had obvious influence on CD, UC risk in Caucasian. However, rs17234657T/G polymorphism had obvious influence on CD but not UC in Caucasian. CONCLUSION: This meta-analysis suggested that both the rs4613763 T/C, rs17234657T/G polymorphisms had obvious influence on risk of CD in Caucasian. In addition, rs4613763 T/C, polymorphism had obvious influence on risk of UC in Caucasian.

Ursodeoxycholic acid alleviates nonalcoholic fatty liver disease by inhibiting apoptosis and improving autophagy via activating AMPK.

Ursodeoxycholic acid (UDCA), first identified in bear bile, was widely used in cholestatic liver diseases. Our previous studies have suggested UDCA may exert favorable influence on hepatic steatosis. However, the molecular mechanism remains elusive. Given the role of autophagy and apoptosis dysregulation in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and pharmacological effects of UDCA on modulating autophagy, apoptosis. we sought to investigate whether UDCA had therapeutic effect on NAFLD and its mechanism of modulating autophagy, apoptosis. Our finding revealed that UDCA exerted obviously favorable influence on hepatic steatosis in NAFLD rats by activating AMP-activated protein kinase (AMPK). Mechanistic studies indicated UDCA inhibited apoptosis and improved autophagy by influencing Bcl-2/Beclin-1 and Bcl-2/Bax complex interaction. Importantly, above-mentioned influence of UDCA on autophagy, apoptosis and Bcl-2/Beclin-1, Bcl-2/Bax complex interaction in NAFLD were partly counteracted by AMPK inhibitor compound C(CC). In conclusion, UDCA exerts favorable influence on hepatic steatosis in NAFLD rats, which is attributable to apoptosis inhibition and autophagy induction by influencing Bcl-2/Beclin-1 complex and Bcl-2/Bax complex interaction via activating AMPK, indicating that UDCA may be a promising therapeutic target for NAFLD.

The role of the miR-21-5p-mediated inflammatory pathway in ulcerative colitis.

Ulcerative colitis (UC), a major type of inflammatory bowel disease, is also a chronic non-specific intestinal inflammation condition of unknown etiology. The pathogenesis of UC is closely associated with immune abnormalities, inflammatory damage and genetics. The present study aimed to explore the effects of microRNA (miR)-21-5p on the interleukin-6 (IL-6) receptor (IL6R)/signal transducer and activator of transcription (STAT3) signal pathway in UC, in order to identify a highly effective treatment for UC. A total of 45 patients with UC and 45 healthy controls were recruited for the present study. The expression levels of miR-21-5p and STAT3 in the sera of patients with UC and healthy controls were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A UC rat model was established using dextran sulfate sodium. Following lipopolysaccharide (LPS) treatment, RAW264.7 cells were transfected with a miR-21-5p inhibitor. The levels of morphological damage and apoptosis of the colonic mucosal epithelial tissue were investigated using hematoxylin and eosin staining and a TUNEL staining assay, and then the colon macroscopic damage index and disease activity index were measured in rats. Western blot analysis was used to detect the protein expression levels of IL6R, STAT3, intracellular adhesion molecule 1 (ICAM-1), NF-κB, cleaved caspase-3, cleaved caspase-9 and Fas ligand (FasL). RT-qPCR detected the mRNA expression levels of miR-21-5p, IL6R, STAT3, ICAM-1, NF-κB, caspase-3, caspase-9 and FasL. An ELISA was performed to measure the levels of inflammatory cytokines. The viability and apoptosis levels of RAW264.7 cells were examined using MTT and flow cytometry assays. Additionally, STAT3 was investigated as a direct target of miR-21-5p in RAW264.7 cells using a dual-luciferase reporter assay. The results of the present study demonstrated that inflammation and apoptotic markers were revealed to be significantly downregulated following transfection with miR-21-5p inhibitors in RAW264.7 cells induced by LPS, and that cell viability was increased. Furthermore, STAT3 was confirmed to be a target of miR-21-5p in RAW264.7 cells. Collectively, these data demonstrated that miR-21-5p inhibition mediated the IL-6/STAT3 pathway in UC rats to decrease the levels of inflammation and apoptosis in RAW264.7 cells, and suggested that miR-21-5p may be an important therapy target in human UC.

Homo Sapiens Circular RNA 0079993 (hsa_circ_0079993) of the POLR2J4 Gene Acts as an Oncogene in Colorectal Cancer Through the microRNA-203a-3p.1 and CREB1 Axis.

BACKGROUND Worldwide, dietary changes have resulted in an increased incidence of colorectal cancer (CRC). Circular RNAs (circRNAs) are involved in tumorigenesis of several human tumors, but their role in CRC remains unknown. This study aimed to investigate the expression and effects of Homo sapiens (hsa)_circ_0079993 of POLR2J4 and its impact on CRC. MATERIAL AND METHODS Paired CRC tissue and adjacent normal colorectal tissue samples (N=41), and HCT116 and SW620 human CRC cells were studied. The expression of circ_0079993 and its parental gene, POLR2J4, were examined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Two small-interfering RNAs (siRNAs) against circ_0079993 were used to silence circ_0079993 expression in HCT116 and SW620 CRC cells. Cell proliferation was evaluated using the cell counting kit-8 (CCK-8) assay, colony formation, and in vivo tumor growth assays. The target miRNAs of circ_0079993 was predicted using TargetScan, and the interaction between circ_0079993 and its target miRNAs were verified by the dual-luciferase reporter (DLR) assay. RESULTS In CRC tissue POLR2J4 expression was reduced, and circ_0079993 expression was increased compared with normal tissue. Knockdown of circ_0079993 significantly inhibited the proliferation of CRC cells in vitro. Also, circ_0079993 was predicted to sponge multiple miRNAs, miR-203a-3p.1 was verified as a target of circ_0079993, and circ_0079993 indirectly regulated mRNA expression of the CREB1 gene by sponging miR-203a-3p.1 in CRC cells. The use of anti-miR-203a-3p.1 reversed the inhibitory effects of circ_0079993 knockdown on CRC cell proliferation. CONCLUSIONS The findings supported that hsa_circ_0079993 acts as an oncogene in CRC through the miRNA-203a-3p.1/CREB1 axis.

Long non-coding XIAP-AS1 regulates cell proliferation, invasion and cell cycle in colon cancer.

Colon cancer is one of the most commonly diagnosed and deadly cancers worldwide. Further understanding of the biological mechanisms is important for exploring the molecular biomarkers and therapeutic targets of this disease. Dysregulation of long non-coding RNAs (lncRNAs) has been reported to be associated with the development and progression of various cancers. XIAP-AS1 is a novel lncRNA, which can regulate apoptosis in gastric cancer cells. However, the role of XIAP-AS1 in colorectal cancer (CRC) remains unclear. In this study, we found that XIAP-AS1 expression was significantly increased in CRC tissues and its expression showed a positive correlation with TNM stage and cumulative survival rate of CRC. To investigate whether XIAP-AS1 regulates the progression of CRC, we knocked down its expression in several CRC cell lines. CCK-8 assays showed that XIAP-AS1 knockdown remarkably suppressed CRC cell growth and arrested the cell cycle at the G0/G1 phase (flow cytometric analysis). Furthermore, XIAP-AS1 knockdown also remarkably blocked cell invasion of colon cancer cells by regulating the expression of EMT markers, such as E-cadherin, ZO-1, vimentin, and N-cadherin. Importantly, we found that XIAP-AS1 knockdown significantly reduced STAT3 phosphorylation. Overall, this study suggests that lncRNA XIAP-AS1 might serve as a potential oncogene for colon cancer.

Alcohol-Related Liver Disease Is Rarely Detected at Early Stages Compared With Liver Diseases of Other Etiologies Worldwide.

BACKGROUND & AIMS: Despite recent advances in treatment of viral hepatitis, liver-related mortality is high, possibly owing to the large burden of advanced alcohol-related liver disease (ALD). We investigated whether patients with ALD are initially seen at later stages of disease development than patients with hepatitis C virus (HCV) infection or other etiologies. METHODS: We performed a cross-sectional study of 3453 consecutive patients with either early or advanced liver disease (1699 patients with early and 1754 with advanced liver disease) seen at 17 tertiary care liver or gastrointestinal units worldwide, from August 2015 through March 2017. We collected anthropometric, etiology, and clinical information, as well as and model for end-stage liver disease scores. We used unconditional logistic regression to estimate the odds ratios for evaluation at late stages of the disease progression. RESULTS: Of the patients analyzed, 81% had 1 etiology of liver disease and 17% had 2 etiologies of liver disease. Of patients seen at early stages for a single etiology, 31% had HCV infection, 21% had hepatitis B virus infection, and 17% had nonalcoholic fatty liver disease, whereas only 3.8% had ALD. In contrast, 29% of patients seen for advanced disease had ALD. Patients with ALD were more likely to be seen at specialized centers, with advanced-stage disease, compared with patients with HCV-associated liver disease (odds ratio, 14.1; 95% CI, 10.5-18.9; P < .001). Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. These patients had significantly more visits to health care providers, with more advanced disease, compared with patients without excess alcohol use. The mean model for end-stage liver disease score for patients with advanced ALD (score, 16) was higher than for patients with advanced liver disease not associated with excess alcohol use (score, 13) (P < .01). CONCLUSIONS: In a cross-sectional analysis of patients with liver disease worldwide, we found that patients with ALD are seen with more advanced-stage disease than patients with HCV-associated liver disease. Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. Early detection and referral programs are needed for patients with ALD worldwide.

Identification of 8-miRNAs as biomarkers for nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) poses serious threats to humans. Several studies have studied the biomarkers associated with NAFLD; however, the results vary because of the differences in the sequencing platform, sample selection, and filter conditions. This study aimed to explore the key microRNAs (miRNAs) of NAFLD by a systematic bioinformatics analysis. A total of 10 qualified NAFLD miRNA data sets were selected through a literature review. Signature miRNAs were identified by overlap comparison. The target genes of miRNAs were predicted by TargetScan software and functional enrichment, and transcription factor (TF) binding analysis of target genes was carried out by the database for annotation, visualization, and integrated discovery and Tfacts database, respectively. A total of three upregulated miRNAs and five downregulated miRNAs were identified in the NAFLD tissue. The target genes of upregulated miRNAs mainly enriched in the RNA polymerase II promoter transcriptional regulation, chromatin remodeling process, and O-glycan synthesis, circadian rhythm, and endocytosis; the target genes of downregulated miRNAs mainly enriched in the transcriptional regulation of DNA as a template, negative regulation process of protein phosphorylation, and Fc epsilon RI signaling pathways, Ras signaling pathways and the interaction between cytokines and cytokines. Besides, 136 interactions were formed between 62 TFs and 45 target genes of upregulated miRNA, whereas 157 interactions were formed between 72 TFs and 45 target genes of downregulated miRNA. Both contained 102 TFs, and 32 TFs were present in both target genes. To summarize, we identified an eight-miRNA set as a signature for NAFLD, which will benefit the clinical treatment of NAFLD.

MiR-490-5p inhibits the stemness of hepatocellular carcinoma cells by targeting ECT2.

To explore the targeting relationship between miR-490-5p and ECT2 in hepatocellular carcinoma (HCC) and the influences of miR-490-5p and ECT2 on the stemness of HCC cells. The expressions of miR-490-5p and ECT2 in HCC tissues and adjacent tissues were identified by quantitative real-time polymerase chain reaction (qRT-PCR). The relationships between the expression levels of miR-490-5p/ ECT2 and the overall/disease-free survival (OS/DFS) of patients with HCC were evaluated using correlative curves. In addition, the targeting relationship between miR-490-5p and ECT2 was predicted by TargetScan and verified by dual-luciferase reporter assay. Plasmid transfection was used for overexpression of ECT2 in HepG2 cells, and transfection efficiency was verified by qRT-PCR. Cell Counting Kit-8 assay and cell sphere-formation assay were conducted to detect the proliferation and sphere-formation ability of HCC cells, respectively. Cell populations with different cell transfections were sorted using flow cytometry. The expression levels of proteins in the stem cell signaling pathway were determined using Western blot analysis. MiR-490-5p was remarkably downregulated, yet ECT2 was upregulated in HCC tissues compared with adjacent tissues. MiR-490-5p expression was positively correlated with OS and DFS of patients with HCC, which were otherwise negatively correlated with ECT2 expression. ECT2 was validated to be the downstream target of miR-490-5p. Overexpression of miR-490-5p restrained the sphere formation ability, stemness, and proliferation of HCC cells. MiR-490-5p repressed the stemness of HCC cells through inhibiting the expression of ECT2. MiR-490-5p may be an underlying therapeutic target in HCC treatment.

Tissue Factor Coagulant Activity is Regulated by the Plasma Membrane Microenvironment.

BACKGROUND: Tissue factor (TF) can be present in a non-coagulant and coagulant form. Whether the coagulant activity is affected by the plasma membrane microenvironment is unexplored. OBJECTIVE: This article studies the presence and coagulant activity of human TF in plasma membrane micro-domains. METHODS: Plasma membranes were isolated from human MIA PaCa2 cells, MDA-MB-231 cells and human vascular smooth muscle cells by Percoll gradient ultracentrifugation after cell disruption. Plasma membranes were fractionated by OptiPrep gradient ultracentrifugation, and the presence of TF, flotillin, caveolin, clathrin, protein disulphide isomerase (PDI), TF pathway inhibitor (TFPI) and phosphatidylserine (PS) were determined. RESULTS: Plasma membranes contain two detergent-resistant membrane (DRM) compartments differing in density and biochemical composition. High-density DRMs (DRM-H) have a density (ρ) of 1.15 to 1.20 g/mL and contain clathrin, whereas low-density DRMs (DRM-L) have a density between 1.09 and 1.13 g/mL and do not contain clathrin. Both DRMs contain TF, flotillin and caveolin. PDI is detectable in DRM-H, TFPI is not detectable in either DMR-H or DRM-L and PS is detectable in DRM-L. The DRM-H-associated TF (> 95% of the TF antigen) lacks detectable coagulant activity, whereas the DRM-L-associated TF triggers coagulation. This coagulant activity is inhibited by lactadherin and thus PS-dependent, but seemed insensitive to 16F16, an inhibitor of PDI. CONCLUSION: Non-coagulant and coagulant TF are present within different types of DRMs in the plasma membrane, and the composition of these DRMs may affect the TF coagulant activity.

p53 expression in patients with ulcerative colitis - associated with dysplasia and carcinoma: a systematic meta-analysis.

BACKGROUND: Tumor suppressor gene p53 expression has been reported in patients with ulcerative colitis (UC). However, the correlation between p53 expression and UC remains controversial. The aim of this meta-analysis was to investigate the association between p53 expression and different pathological types of UC. METHODS: Publications were searched in the PubMed, Embase, EBSCO, Wangfang, and CNKI databases. The overall odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were summarized in this study. RESULTS: Final 19 papers were identified in this meta-analysis, including 1068 patients with UC and 130 normal tissue samples. Immunohistochemical p53 expression was significantly higher in UC without dysplasia and carcinoma (UC group) compared to normal tissue samples (OR = 3.14, P = 0.001), higher in UC with dysplasia than in UC group (OR = 10.76, P < 0.001), and higher in UC with colorectal cancer (CRC) than in UC with dysplasia (OR = 1.69, P = 0.035). Subgroup analysis of ethnicity (UC group vs. normal tissues) showed that p53 expression was correlated with UC in Asians, but not in Caucasians. When UC with dysplasia was compared to UC group, p53 expression was linked to UC with dysplasia among both Asians and Caucasians. When UC-CRC was compared to UC with dysplasia, p53 expression was not associated with UC-CRC in both Caucasians and Asians. CONCLUSIONS: p53 expression was closely associated with UC-CRC development. p53 expression showed different ethnic characteristics among different pathological types of UC.

Intraluminal pressure patterns in the human colon assessed by high-resolution manometry.

Assessment of colonic motor dysfunction is rarely done because of inadequate methodology and lack of knowledge about normal motor patterns. Here we report on elucidation of intraluminal pressure patterns using High Resolution Colonic Manometry during a baseline period and in response to a meal, in 15 patients with constipation, chronically dependent on laxatives, 5 healthy volunteers and 9 patients with minor, transient, IBS-like symptoms but no sign of constipation. Simultaneous pressure waves (SPWs) were the most prominent propulsive motor pattern, associated with gas expulsion and anal sphincter relaxation, inferred to be associated with fast propagating contractions. Isolated pressure transients occurred in most sensors, ranging in amplitude from 5-230 mmHg. Rhythmic haustral boundary pressure transients occurred at sensors about 4-5 cm apart. Synchronized haustral pressure waves, covering 3-5 cm of the colon occurred to create a characteristic intrahaustral cyclic motor pattern at 3-6 cycles/min, propagating in mixed direction. This activity abruptly alternated with erratic patterns resembling the segmentation motor pattern of the small intestine. High amplitude propagating pressure waves (HAPWs) were too rare to contribute to function assessment in most subjects. Most patients, dependent on laxatives for defecation, were able to generate normal motor patterns in response to a meal.