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Background and Aims M2 phenotype macrophages are involved in the resolution of inflammation and intestinal repair. Exosomes are emerging as important mediators of intercellular communication in the mucosal microenvironment. Methods M2 macrophages were transfected with or without miR-590-3p. Exosomes derived from M2 macrophages were isolated and identified. Proliferation and wound healing were tested in vitro and compared between groups. The mechanism involving LATS1, and activation of YAP and β-catenin signalling was investigated by using plasmid transfection, western blotting, immunofluorescence, and luciferase reporter assays. The effect of exosomes in vivo was detected in DSS-induced murine colitis. Results First, we demonstrated that M2 macrophages promoted colonic epithelial cell proliferation in an exosome-dependent manner. Epithelial YAP mediated the effect of M2 macrophage-derived exosomes (M2-exos) in epithelial proliferation. Moreover, miR-590-3p, which was significantly enriched in M2-exos, could be transferred from macrophages into epithelial cells, resulting in the enhanced proliferation and wound healing of epithelial cells. Mechanistically, miR-590-3p suppressed the expression of LATS1 by binding to its coding sequence and subsequently activated the YAP/β-catenin-modulated transcription process to improve epithelial cell wound-healing ability. MiR-590-3p also inhibited the induction of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6. More importantly, repression miR-590-3p in M2-exos resulted with severer mucosal damage and impaired colon repair of mice compared with those in M2-exo-treated mice after DSS-induced colitis. Conclusion M2 macrophage-derived exosomal miR-590-3p reduces inflammatory signals and promotes epithelial regeneration by targeting LATS1 and subsequently activating YAP/β-catenin-regulated transcription, which could offer a new opportunity for clinical therapy for ulcerative colitis (UC).

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract, and about 60% of them are found in the stomach. With the widespread application of endoscopy and endoscopic ultrasonography (EUS), more and more gastric GISTs are being found in an early stage (with a relative small diameter and no metastasis), giving the chance of complete resection. Endoscopic resection such as endoscopic band ligation (EBL), endoscopic submucosal dissection (ESD), endoscopic submucosal excavation (ESE), endoscopic full-thickness resection (EFTR) and submucosal tunneling endoscopic resection (STER), is a minimally invasive method compared with the conventional surgical approaches (open or laparoscopic), and has been demonstrated to be safe and effective for treating gastric GISTs. This review summarizes the recent advances on endoscopic resection of gastric GISTs, aiming to provide a rational management strategy for gastric GISTs.

Abnormal immune regulation is a key feature of the complex pathogenic mechanism of ulcerative colitis (UC). In particular, macrophages and group 2 innate lymphoid cells (ILC2s) are important components of natural immunity that have been shown to play important roles in the pathogenesis of UC, as well as decreased E‐cadherin expression on the colonic mucosa. However, it remains unclear how these components interact with each other. In this study, we investigated the molecular mechanisms of UC mediated by macrophage‐derived exosomes. We showed for the first time that miR‐21a‐5p expression is increased in the peritoneal exosomes of mice with dextran sulphate sodium induced enteritis and that miR‐21a‐5p expression correlates negatively with E‐cadherin expression in enterocytes. Moreover, we confirmed that miR‐21a‐5p was mainly derived from M1 macrophages and demonstrated that KLRG1, a surface inhibitory receptor on ILC2s, participated in excessive ILC2 activation in UC by promoting GATA‐3. In conclusion, our results suggest molecular targets and provide a theoretical basis for elucidating the pathogenesis of UC and improving its treatment.

SummaryThe study is to determine the effects of milk powder on bone density and metabolism in healthy adolescents. Vitamin D and calcium supplements increased IGF-1 but did not affect bone mineralization or turnover. Higher vitamin D in combination with sufficient calcium supplementation in such populations requires attention.IntroductionBoth calcium and vitamin D play an important role in bone mineralization in adolescents.MethodsIn this one and a half-year randomized controlled trial, 232 participants (aged 12–15 years) were randomly assigned to three intervention groups receiving milk powder fortified with vitamin D 400 IU plus calcium 300, or 600, or 900 mg [Ca3D (n = 54), Ca6D (n = 56), and Ca9D (n = 49)], or one control group maintaining habitual diet [control (n = 73)]. Bone turnover markers, serum intact PTH, 25(OH)D, and IGF-1 levels were measured at baseline and one and a half years, and bone mineral contents and bone areal mineral density were measured by Dual-energy X-ray absorptiometry (DXA) at baseline, one year, and one and a half years.ResultsBaseline average serum 25(OH)D level and calcium intake were 29.4 nmol/L and 363.5 mg/day, respectively. There was a significant increase in bone turnover, total body, hip, lumbar spine bone mineral density (BMD), and total body BMC as well as slight fluctuations in 25(OH)D levels over one and a half years without between-group differences. Significantly decreased serum PTH level was only observed in the Ca6D group (31%, p < 0.0001), in which the intervention effect was also significant (p = 0.0029) compared with the control group. IGF-1 levels increased significantly in all intervention groups (18.5 to 22.8%, p < 0.05) but decreased in the control group (16.5%, p < 0.05), and the group by time interaction was also significant (p = 0.0029).ConclusionsOur study showed that in healthy adolescents with low vitamin D status and calcium intake, mild vitamin D and mild to modest calcium supplements increased IGF-1 but did not affect bone mineralization or turnover. Higher vitamin D in combination with sufficient calcium supplementation in such populations requires attention.