HES1 deficiency impairs development of human intestinal mesenchyme by suppressing WNT5A expression.

Serious intestinal side-effects that target the NOTCH-HES1 pathway in human cancer differentiation therapy make it necessary to understand the pathway at the human organ level. Herein, we endogenously introduced HES1-/- mutations into human embryonic stem cells (hESCs) and differentiated them into human intestinal organoids (HIO). The HES1-/- hESCs retained ES cell properties and showed gene expression patterns similar to those of wild-type hESCs when they differentiated into definitive endoderm and hindgut. During the formation of the HES1-/- lumen we noted an impaired development of mesenchymal cells in addition to the increased differentiation of secretory epithelium. RNA-Seq revealed that inhibited development of the mesenchymal cells may have been due to a downregulation of WNT5A signaling. Overexpression of HES1 and silencing of WNT5A in the intestinal fibroblast cell line CCD-18Co indicated that HES1 was involved in the activation of WNT5A-induced fibroblast growth and migration, suggesting the likelihood of the Notch pathway in epithelial-mesenchymal crosstalk. Our results facilitated the identification of more precise underlying molecular mechanisms displaying distinct roles in HES1 signaling in stromal and epithelial development in human intestinal mucosa.

Risks of vaptans in hypernatremia and serum sodium overcorrection: A systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: Serum sodium overcorrection and hypernatremia are significant health risks. We conducted a systematic review and meta-analysis to evaluate the risks of vaptans in hypernatremia and serum sodium overcorrection. METHODS: We searched PubMed, Embase, and CENTRAL for randomised controlled trials. We included studies comparing vaptans and placebo with data on hypernatremia and serum sodium overcorrection. The study quality was assessed using the Cochrane Collaboration's risk-of-bias assessment tool. Fixed-effect model meta-analysis was used to pool the data. Different analyses were performed to ensure the accuracy of the results. RESULTS: Twenty-eight studies were included in the meta-analysis of hypernatremia incidence. Treatment with vaptans resulted in a higher risk of hypernatremia than placebo (3.8% vs 1.0%, odds ratio [OR] 2.69; 95% confidence interval [CI] 1.97-3.68). The subgroup with baseline hyponatremia had a lower risk of hypernatremia incidence; however, the use of loop diuretics increased the risk. Fourteen studies were included in the analysis of the incidence of serum sodium overcorrection. A higher risk of serum sodium overcorrection was found in using vaptans vs placebo (4.4% vs 1.4%; OR 2.26; 95% CI 1.32-3.86). CONCLUSION: Vaptans showed higher risks in the incidence of hypernatremia and serum sodium overcorrection than placebo. In addition, combination with loop diuretics increased the risk of hypernatremia. The risk of serum sodium overcorrection should be concerned in patients with hyponatremia and normal serum sodium equally. Using a low dose of vaptans can reduce both risks.

SFI, a sex hormone binding globulin based nomogram for predicting non-alcoholic fatty liver disease in the Chinese population.

Background: The purpose of this study is to establish a novel nomogram model for accurate detection of non-alcoholic fatty liver disease (NAFLD) in the Chinese population based on sex hormone binding globulin (SHBG) and other routine laboratory tests. Methods: A total of 1417 participants (1003 testing and 414 validations) were enrolled into the study. Risk factors independently associated with NAFLD were identified and incorporated in the new nomogram, SFI. The performance of nomogram was assessed by analysis of receiver operating characteristic (ROC) curve, calibration curve, and decision curve. Results: We formulated a new nomogram incorporating four independent factors: SHBG, body mass index (BMI), ALT/AST, and triglycerides (TG). The nomogram achieved good indexes of area under ROC 0.898 (95% confidence interval 0.865-0.926) in predicting NAFLD, which was significantly superior to previously reported models of FLI, HSI, LFS, and LAP. The calibration curve and decision curve demonstrated high performance and clinical utility of the nomogram in predicting NAFLD. Conclusion: The nomogram SFI has high performance in predicting NAFLD in Chinese population and may be used as a cost-effective screening model to assess NAFLD in the general population.

Isolation and Characterization of Endomycorrhizal Fungi Associated with Growth Promotion of Blueberry Plants.

Despite their notable root mutualism with blueberries (Vaccinium spp.), studies related to Ericoid mycorrhizal (ERM) are relatively limited. In this study, we report the isolation of 14 endomycorrhizal fungi and their identification by fungal colony morphology characterization combined with PCR-amplified fungal internal transcribed spacer (ITS) sequence analyses. Six of the isolated strains were confirmed as beneficial mycorrhizal fungi for blueberry plants following inoculation. We observed the formation of typical ERM hyphae coil structures-which promote and nutritionally support growth-in blueberry seedlings and significant nitrogen and phosphorous content increases in diverse tissues. QRT-PCRs confirmed changes in VcPHT1s expression patterns. After the formation of ERM, PHT1-1 transcription in roots was upregulated by 1.4- to threefold, whilst expression of PHT1-3 and PHT1-4 in roots were downregulated 72% and 60%, respectively. Amino acid sequence analysis of all four VcPHT1s genes from the blueberry variety "Sharpblue" revealed an overall structural similarity of 67% and predicted transmembrane domains. Cloning and overexpression of PHT1-1 and PHT1-3 genes in transgenic Arabidopsis thaliana plants significantly enriched total phosphorus and chlorophyll content, confirming that PHT1-1 and PHT1-3 gene functions are associated with the transport and absorption of phosphorus.

Patient with neuromyelitis optica spectrum disorder combined with Sjögren's syndrome relapse free following tacrolimus treatment.

Tacrolimus, a novel immunosuppressant agent, has been widely used in organ transplantation and autoimmune diseases. We herein present a case of neuromyelitis optica spectrum disorder (NMOSD) combined with Sjögren's syndrome (SS) successfully treated with tacrolimus. This patient repeatedly presented with recurrent longitudinally extensive transverse myelitis. Her NMO-IgG and anti-SSA and anti-SSB antibodies were seropositive. Considering the frequency of relapses and severe disability, tacrolimus was initiated after failure of intravenous cyclophosphamide. Her status was steady for over 36 months after tacrolimus treatment. This report indicates that tacrolimus may be a potentially effective immunosuppressant for NMOSD with systemic autoimmune diseases.