Background/Aims: Irritable bowel syndrome with diarrhoea (IBS-D) is a chronic, functional bowel disorder characterized by abdominal pain or diarrhoea and altered bowel habits, which correlate with intestinal hyperpermeability. MicroRNAs (miRNAs) are involved in regulating intestinal permeability in IBS-D. However, the role of miRNAs in regulating intestinal permeability and protecting the epithelial barrier remains unclear. Our goals were to (i) identify differential expression of miRNAs and their targets in the distal colon of IBS-D rats; (ii) verify in vitro whether occludin (OCLN) and zonula occludens 1 (ZO1/TJP1) were direct targets of miR-144 and were down-regulated in IBS-D rats; and (iii) determine whether down-regulation of miR-144 in vitro could reverse the pathological hallmarks of intestinal hyperpermeability via targeting OCLN and ZO1. Methods: The IBS-D rat model was established using 4% acetic acid and evaluated by haematoxylin-eosin (HE) staining. The distal colon was obtained in order to perform miRNA microarray analysis and to isolate and culture colonic epithelial cells. When differential expression of miRNA was found, the results were verified by qRT-PCR, and the target genes were further explored by bioinformatics analysis. Correlation analyses were carried out to compare the expression of miRNA and target genes. Then, mutants, miRNA mimics and inhibitors of the target genes were constructed and transfected to colonic epithelial cells. qRT-PCR, western blotting, enzyme-linked immunosorbent assays (ELISAs) and dual-luciferase assays were used to investigate the expression of miR-144 and OCLN, ZO1 in IBS-D rats. Results: There were 8 up-regulated and 18 down-regulated miRNAs identified in the IBS-D rat model. Of these, miR-144 was markedly up-regulated and resulted in the down-regulation of OCLN and ZO1 expression. Overexpression of miR-144 by transfection of miR-144 precursor markedly inhibited the expression of OCLN and ZO1. Further studies confirmed that OCLN and ZO1 were direct targets of miR-144. Additionally, intestinal hyperpermeability was enhanced by miR-144 up-regulation and attenuated by miR-144 down-regulation in IBS-D rat colonic epithelial cells. Moreover, rescue experiments showed that overexpression of OCLN and ZO1 significantly eliminated the inhibitory effect of miR-144, which showed a stronger effect on the attenuation of intestinal hyperpermeability. Conclusion: Up-regulation of miR-144 could promote intestinal hyperpermeability and impair the protective effect of the epithelial barrier by directly targeting OCLN and ZO1. miR-144 is likely a key regulator of intestinal hyperpermeability and could be a potential therapeutic target for IBS-D.

BackgroundThis review aims to critically appraise and compare the measurement properties of inflammatory bowel disease (IBD)-specific health-related quality of life instruments.MethodsMedline, EMBASE and ISI Web of Knowledge were searched from their inception to May 2016. IBD-specific instruments for patients with Crohn’s disease, ulcerative colitis or IBD were enrolled. The basic characteristics and domains of the instruments were collected. The methodological quality of measurement properties and measurement properties of the instruments were assessed.ResultsFifteen IBD-specific instruments were included, which included twelve instruments for adult IBD patients and three for paediatric IBD patients. All of the instruments were developed in North American and European countries. The following common domains were identified: IBD-related symptoms, physical, emotional and social domain. The methodological quality was satisfactory for content validity; fair in internal consistency, reliability, structural validity, hypotheses testing and criterion validity; and poor in measurement error, cross-cultural validity and responsiveness. For adult IBD patients, the IBDQ-32 and its short version (SIBDQ) had good measurement properties and were the most widely used worldwide. For paediatric IBD patients, the IMPACT-III had good measurement properties and had more translated versions.ConclusionsMost methodological quality should be promoted, especially measurement error, cross-cultural validity and responsiveness. The IBDQ-32 was the most widely used instrument with good reliability and validity, followed by the SIBDQ and IMPACT-III. Further validation studies are necessary to support the use of other instruments.Electronic supplementary materialThe online version of this article (10.1186/s12955-017-0753-2) contains supplementary material, which is available to authorized users.

We performed this review to clarify which dietary and lifestyle factors are related to gastroesophageal reflux disease. Through a systematic search of the PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Chinese BioMedical Literature (CBM) databases, we identified articles with clear definitions of GERD, including nonerosive gastroesophageal reflux disease (NERD), reflux esophagitis (RE) and Barrett’s esophagus (BE), that included dietary and lifestyle factors as independent factors affecting the onset of GERD (expressed as odds ratios (ORs) or relative risks (RRs) and 95% confidence intervals (CIs)). Due to heterogeneity among the studies, we used descriptive statistical analyses to analyze and synthesize each outcome based on the disease type. In total, 72 articles were included, conducted in ten Western countries (26 articles in total) and nine Eastern countries (46 articles in total). We categorized dietary factors into 20 items and lifestyle factors into 11 items. GERD is related to many irregular dietary and lifestyle habits (such as a habit of midnight snacking: OR=5.08, 95% CI 4.03–6.4; skipping breakfast: OR=2.7, 95% CI 2.17–3.35; eating quickly: OR=4.06, 95% CI 3.11–5.29; eating very hot foods: OR=1.81, 95% CI 1.37–2.4; and eating beyond fullness: OR=2.85, 95% CI 2.18–3.73). Vegetarian diets (consumption of nonvegetarian food (no/yes); OR=0.34, 95% CI 0.211–0.545) and no intake of meat (OR=0.841, 95% CI 0.715–0.990) were negatively related to GERD, while meat (daily meat, fish, and egg intake: OR=1.088, 95% CI 1.042-1.135) and fat (high–fat diet: OR=7.568, 95% CI 4.557–8.908) consumption were positively related to GERD. An interval of less than three hours between dinner and bedtime (OR=7.45, 95% CI 3.38–16.4) was positively related to GERD, and proper physical exercise (physical exercise >30 minutes (>3 times/week): OR=0.7, 95% CI 0.6–0.9) was negatively correlated with GERD. Smoking (OR=1.19, 95% CI 1.12–1.264), alcohol consumption (OR=1.278, 95% CI 1.207–1.353) and mental state (poor mental state: OR=1.278, 95% CI 1.207–1.353) were positively correlated with GERD. RE (vitamin C: OR=0.46, 95% CI=0.24–0.90) and BE (vitamin C: OR=0.44,95% CI 0.2-0.98; vitamin E: OR=0.46, 95% CI 0.26–0.83) were generally negatively correlated with antioxidant intake. In conclusion, many dietary and lifestyle factors affect the onset of GERD, and these factors differ among regions and disease types. These findings need to be further confirmed in subsequent studies.

Background/AimsMicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown.MethodsWe established the IBS-D rat model and evaluated it using the nociceptive visceral hypersensitivity test, myeloperoxidase activity assay, restraint stress-induced defecation, and electromyographic (EMG) activity. The distal colon was subjected to miRNA microarray analysis followed by isolation and culture of colonic epithelial cells (CECs). Bioinformatic analysis and further experiments, including dual luciferase assays, quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay, were used to detect the expression of miRNAs and how it regulates visceral hypersensitivity in IBS-D rats.ResultsThe IBS-D rat model was successfully established. A total of 24 miRNAs were differentially expressed in the distal colon of IBS-D rats; 9 were upregulated and 15 were downregulated. Among them, the most significant upregulation was miR-200a, accompanied by downregulation of cannabinoid receptor 1 (CNR1) and serotonin transporter (SERT). MiR-200a mimic markedly inhibited the expression of CNR1/SERT. Bioinformatic analysis and luciferase assay confirmed that CNR1/SERT are direct targets of miR-200a. Rescue experiments that overexpressed CNR1/SERT significantly abolished the inhibitory effect of miR-200a on the IBS-D rats CECs.ConclusionsThis study suggests that miR-200a could induce visceral hyperalgesia by targeting the downregulation of CNR1 and SERT, aggravating or leading to the development and progression of IBS-D. MiR-200a may be a regulator of visceral hypersensitivity, which provides potential targets for the treatment of IBS-D.

Chronic renal failure (CRF) threatens human health greatly and attracts worldwide concerns of health professionals in the public health sector. In our preliminary study, we found that Compound capsule (Shengqing Jiangzhuo Capsule, SQJZJN) had a significant therapeutic effect on CRF. Quercetin is one of the main components of this Compound capsule. In this study, we investigated the effect of Quercetin monomer on CRF and the regulation of PI3k/Akt pathway. Network pharmacology analysis methods were employed to analyze the SQJZJN/Quercetin/PIK3R1 network relationships. In this study, a CRF rat model was prepared using the gavage adenine solution method and detected the indicators of Creatinine (Cr), Blood Urea Nitrogen (BUN), and Uric Acid (UA). After treating the rat model with Quercetin and PIK3R1-interfering lentivirus, respectively, we observed the changes on the histological morphology of the kidney and detected apoptosis using TUNEL staining. Gene and protein expression associated with renal function were detected using qPCR, WB and immunofluorescence. Quercetin was identified as the main ingredient of SQJZJN by the network pharmacological screening and Quercetin at 1.5 and 3 g/(kg.d) concentrations could effectively alleviate the CRF symptoms, reduce the levels of Cr, BUN, and UA, and markedly inhibit cell apoptosis demonstrated by the intragastric administration. Furthermore, the protein expression of p-PI3K, p-AKT, NLRP3, caspase1, AQP1, and AQP2 in all groups was detected by immunofluorescence and western blot assays, indicating that Quercetin could reduce the expression of NLRP3, caspase1, p-PI3k, and p-Akt, and increase the expression of AQP1 and AQP2 in the renal tissues of CRF rats. Being labeled with biotin and incubated with the total protein extracted from kidney tissues, Quercetin could bind to PIK3R1. Following the PIK3R1 interference lentivirus was injected into the CRF model rats by tail vein, the CRF symptoms were effectively alleviated in the PIK3R1 interference group, consistent with the effect of Quercetin. Taken together, Quercetin, a major component of SQJZJN, might minimize renal fibrosis and apoptosis in CRF rats by inhibiting the PI3k/Akt pathway through targeting PIK3R1. By regulating AQP1 and AQP2, both water retention and toxin accumulation were reduced.

BackgroundSerum exosomal microRNAs (miRNAs) have been suggested as novel biomarkers for various diseases, especially gastric cancer (GC). But circulating biomarkers for Chronic atrophic gastritis (CAG) which is defined as precancrerous lesions of GC remain largely elusive. To investigate serum exosomal miRNAs that are differently expressed in CAG patients and Chronic nonatrophic gastritis (CNAG) may be helpful for its diagnosis and therapy.MethodsPatients were recruited according to the diagnosis and exclusioncriteria. RNA was extracted from serum exosomes of 30 CAG and 30 CNAG patients. The miRNA expression profiles were analyzed by next generation sequencing and were validated by qRT-PCR. Receiver operating characteristic (ROC) analysis has been used to evaluate the diagnostic value.Results30 CAG patients and 30 CNAG patients were recruited in our study. sRNA-seq results showed that hsa-miR-3591-3p, − 122-3p, and − 122-5p of the top 10 miRNAs (hsa-miR-148a-3p, − 122-3p, − 486-3p, −451a, − 122-5p, − 3591-3p, − 486-5p, −151a-3p, −92a-3p, −320a) were significantly upregulated in exosomes from CAG patients versus those from CNAG patients, but hsa-miR-451a, −151a-3p, and -92a-3p were significantly downregulated. Furthermore, qRT-PCR analysis confirmed that hsa-miR-122-5p and hsa-miR-122-3p were significantly upregulated in CAG samples, but hsa-miR-122-3p hadnot a steable expression. ROC curves showed that the AUC for hsa-miR-122-5p was 0.67 (95% CI 0.52–0.82, SE 62%, SP 86%). A sum of the four miRNAs (panel 1, hsa-miR-122-5p, −451a, −151a-3p, and -92a-3p) did not significantly improve the diagnostic potential (AUC 0.63, 95% CI 0.47 to 0.78). Correlation analysis showed that the expression of hsa-miR-122-5p differed significantly between patients based on atrophic (Moderate atrophic vs. Absent, P value was 0.036.) and IM (compare moderate-severe, absent and mild P values were 0.001 and 0.014, respectively). However, there were no differences between groups based on age, gender, dysplasia, or chronic or active inflammation.ConclusionThese results suggested that hsa-miR-122-5p in serum exosomes might serve as a potential biomarker for CAG diagnosis.Trial registrationChinese Clinical Trial Registy (ChiCTR-IOR-16008027, Date of Registration:2016-03-01).Electronic supplementary materialThe online version of this article (10.1186/s12885-019-5328-7) contains supplementary material, which is available to authorized users.

Background Hepatocellular carcinoma (HCC) is one of the most universal malignant liver tumors worldwide. However, there were no systematic studies to establish glycolysis‑related gene pairs (GRGPs) signatures for the patients with HCC. Therefore, the study aimed to establish novel GRGPs signatures to better predict the prognosis of HCC. Methods Based on the data from Gene Expression Omnibus, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium databases, glycolysis-related mRNAs were used to construct GRGPs. Cox regression was applied to establish a seventeen GRGPs signature in TCGA dataset, which was verified in two validation (European and American, and Asian) datasets. Results Seventeen prognostic GRGPs (HMMR_PFKFB1, CHST1_GYS2, MERTK_GYS2, GPC1_GYS2, LDHA_GOT2, IDUA_GNPDA1, IDUA_ME2, IDUA_G6PD, IDUA_GPC1, MPI_GPC1, SDC2_LDHA, PRPS1_PLOD2, GALK1_IER3, MET_PLOD2, GUSB_IGFBP3, IL13RA1_IGFBP3 and CYB5A_IGFBP3) were identified to be significantly progressive factors for the patients with HCC in the TCGA dataset, which constituted a GRGPs signature. The patients with HCC were classified into low-risk group and high-risk group based on the GRGPs signature. The GRGPs signature was a significantly independent prognostic indicator for the patients with HCC in TCGA (log-rank P = 2.898e−14). Consistent with the TCGA dataset, the patients in low-risk group had a longer OS in two validation datasets (European and American: P = 1.143e−02, and Asian: P = 6.342e−08). Additionally, the GRGPs signature was also validated as a significantly independent prognostic indicator in two validation datasets. Conclusion The seventeen GRGPs and their signature might be molecular biomarkers and therapeutic targets for the patients with HCC.

The aim of this study was to develop and validate the large intestine dampness-heat syndrome questionnaire (LIDHSQ) for patients with ulcerative colitis (UC). The domains and items of the LIDHSQ were developed according to standard procedures, namely, construct definition, item generation, language testing, content validity, pilot study, and validation study. At first, a total of 20 items in 3 domains were generated based on literature review and expert consultation. After the item selection, the LIDHSQ contains 11 items in three domains: disease-related domain (diarrhoea, abdominal pain, bloody purulent stool, and mucus stool), heat domain (fever, dry mouth, red tongue, yellow fur, and anal burning), and dampness domain (greasy fur and defecation disorder). The Cronbach's alphas of all domains were greater than 0.6. All of the intraclass correlation coefficients were greater than 0.8. The LIDHSQ and domain scores of the patients with LIDHS were higher than those of the patients with other syndromes (P < 0.001). The area under the receiver operating characteristic curve of the LIDHSQ was 0.900, with a 95% confidence interval of 0.872–0.928. When the cut-off value of the LIDHSQ was ≥ 7, the sensitivity and specificity were 0.867 and 0.854, respectively. The LIDHSQ is valid and reliable for measuring LIDHS in UC patients with good diagnostic efficacy. We recommend the use of the LIDHSQ in Chinese UC patients.