Search

A recent single-cell survey of the small-intestinal epithelium suggests that mucosal pentraxin 2 (Mptx2) is a new Paneth cell marker, but its function and involved mechanism in the Paneth cell are still unknown. Therefore, we create Mptx2 knockout (Mptx2−/−) mice to investigate its precise effects on intestinal homeostasis using models of lipopolysaccharide (LPS), methicillin-resistant Staphylococcus aureus (MRSA) peritoneal infection, and dextran sulfate sodium (DSS)–induced intestinal injury and inflammation. We here find that Mptx2 is selectively expressed in Paneth cells in the small intestines of mice. Mptx2−/− mice have increased susceptibility to intestinal inflammation and injured. Mptx2 deficiency reduces Paneth cell count and expression of antimicrobial factors, leading to altered intestinal bacteria composition. Loss of Mptx2 aggravates MRSA infection–induced damage in the intestine while decreasing autophagy in Paneth cells. Mptx2−/− mice are more vulnerable to LPS-induced intestinal possibly due to inhibition of the autophagy/endoplasmic reticulum (ER) stress pathway. Mptx2−/− mice are susceptible to DSS-induced colitis that could be ameliorated by treatment with gentamicin or vancomycin antibiotics. In conclusion, Mptx2 is essential to maintain intestinal homeostasis potentially via regulation of autophagy in Paneth cells. Mucosal pentraxin 2 (Mptx2) is identified as a marker of Paneth cells, and its deficiency is shown to trigger microbiota dysbiosis and increased epithelial invasion by bacteria while also reducing secretory autophagy. [ABSTRACT FROM AUTHOR]

To investigate Mandarin Tone 2 production of disyllabic words of prelingually deafened children with a cochlear implant (CI) and a contralateral hearing aid (HA) and to evaluate the relationship between their demographic variables and tone-production ability. Thirty prelingually Mandarin-speaking preschoolers with CI+HA and 30 age-matched normal-hearing (NH) children participated in the study. Fourteen disyllabic words were recorded from each child. A total of 840 tokens (14 × 60) were then used in tone-perception tests in which four speech therapists participated. The production of T2-related disyllabic words of the bimodal group was significantly worse than that of the NH group, as reflected in the overall accuracy (88.57% ± 16.31% vs 99.29% ± 21.79%, p < 0.05), the accuracy of T1+T2 (93.33% vs 100%), the accuracy of T2+T1 (66.67 ± 37.91% vs 98.33 ± 9.13%), and the accuracy of T2+T4 (78.33 ± 33.95% vs 100%). In addition, the bimodal group showed significantly inferior production accuracy of T2+T1 than T2+T2 and T3+T2, p < 0.05. Both bimodal age and implantation age were significantly negatively correlated with the overall production accuracy, p < 0.05. For the error patterns, bimodal participants experienced more errors when T2 was in the first position of the tone combination, and T2 was most likely to be mispronounced as T1 and T3. Bimodal patients aged 3–5 have T2-related disyllabic lexical tone production defects, and their performances are related to tone combination, implantation age, and bimodal age. [ABSTRACT FROM AUTHOR]

Background: Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare and serious congenital disorder with poor outcomes, where a heterozygous missense mutation is present in the ACTG2 gene. Here, we aimed to investigate the pathogenesis of ACTG2 in MMIHS. Methods: A cohort with 20 patients with MMIHS was screened. Actg2R257C heterozygous mutant mice were generated using the CRISPR/Cas9 system. Gastrointestinal (GI) motility, voluntary urination, collagen gel contraction, and G‐actin/F‐actin analysis were performed. Key Results: The R257C variant of ACTG2 most frequently occurred in patients with MMIHS and demonstrated the typical symptoms of MMIHS. Actg2R257C heterozygous mutant mice had dilated intestines and bladders. The functional assay showed a prolonged total time of GI transit and decreased urine spot area. Collagen gel contraction assay and G‐actin/F‐actin analysis indicated that mutant mice showed reduced area of contraction of smooth muscle cells (SMCs) and impaired actin polymerization. Conclusions & Inferences: A mouse model demonstrating MMIHS‐like symptoms was generated. The Actg2R257C heterozygous variant impairs SMCs contraction by interfering with actin polymerization, leading to GI motility disorders. [ABSTRACT FROM AUTHOR]

Background: Thisstudy aimed to investigate the impact of fish oil–based lipid emulsion (FO) on enterohepatic injuries and intestinal microbiota in piglets of parenteral nutrition (PN). Methods: Newborn piglets were divided into three groups, including enteral diet (the controls), PN with 100% FO and PN with medium‐chain triglyceride/long‐chain triglyceride–based lipid emulsion (MCT/LCT) for 14 days. Serum biochemical indicators, hepatic and intestinal histology, and expression of genes associated with inflammation, oxidative stress, and lipid metabolism were measured. The bile acid (BA) profiles in serum and the taxonomic composition of the gut microbiome in different intestinal segments were analyzed. Results: Compared with MCT/LCT–piglets, FO reduced inflammation, promoted fatty acid oxidation, and decreased oxidative stress in the liver. In the intestine, FO decreased intestinal inflammation and intestinal permeability, leading to reduced lipopolysaccharide entry into the blood circulation relative to MCT/LCT–piglets. PN groups have dominant contents of Proteobacteria and Bacteroides, whereas the control group have Firmicutes at the phylum level. FO altered the taxonomic compositions of the gut microbiome in different segments, increased the relative abundance of Bacteroidaceae in ileum, and Rikenellaceae and Ruminococcaceae in the colon. FO treatment shifted BA composition ratio in serum and had a lower ratio of secondary BAs to primary BAs. Conclusion: FO alleviates PNLAD and intestinal injury by regulating the homeostasis of BAs' enterohepatic circulation and altering microbiota composition in different intestinal segments. [ABSTRACT FROM AUTHOR]

Background: The breakpoint cluster region (BCR) is a protein that originally forms a fusion protein with c‐Abl tyrosine kinase and induces leukemia. Researchers have shown that BCR is enriched in the central nervous system and may contribute to neurological disorders. We aimed to investigate the physiological function of BCR in neural development in the gastrointestinal (GI) tract and brain. Methods: Whole‐exome sequencing was used to screen for mutations in the BCR. Bcr knockout mice (Bcr−/−, ΔExon 2–22) were generated using the CRISPR/Cas9 system. Transit of carmine red dye and glass bead expulsion assays were used to record total and proximal GI transit and distal colonic transit. Key Results: In an infant with pediatric intestinal pseudo‐obstruction, we found a heterozygous de novo mutation (NM_004327.3:c.3072+1G>A) in BCR. Bcr deficiency mice (Bcr−/−) exhibited growth retardation and impaired gastrointestinal motility. Bcr−/− mice had a prolonged average total GI transit time with increased distal colonic transit and proximal GI transit in isolation. Morphology analysis indicated that Bcr−/− mice had a less number of neurons in the submucosal plexus and myenteric plexus. Bcr−/− mice exhibited apparent structural defects in the brain, particularly in the cortex. Additionally, Bcr− depletion in the mouse cortex altered the expression of Ras homologous (Rho) family small GTPases. Conclusions and Inferences: BCR mutations are associated with intestinal obstruction in children. Loss of Bcr can cause intestinal dysmotility and brain developmental defects may via regulation of Rho GTPases. [ABSTRACT FROM AUTHOR]