MSCs-exosomes can promote macrophage M2 polarization via exosomal miR-21-5p through Mesenteric injection: a promising way to attenuate murine colitis.

BACKGROUND AND AIMS: Exosome-based therapies are gaining increasing attention, with growing evidence suggesting a link between alterations in mesentery adipose tissue (MAT) and intestinal disease in Crohn's disease (CD). However, the specific mechanism by which mesenchymal stem cells (MSCs)-Exos may alleviate colitis through targeting MAT remains not fully understood. METHODS: Human umbilical cord MSCs (HucMSCs) were cultured to isolate the corresponding exosomes (HucMSCs-Exos), which were confirmed by their morphology, size distribution, and expression of markers. In vivo, 2,4,6-trinitrobenzenesulfonic acid solution (TNBS) and dextran sodium sulfate (DSS) -induced mouse colitis models were used to detect the therapeutic effects of HucMSCs-Exos. ELISA, qRT-PCR, western blotting, and immunofluorescence determined the expression of key molecules. Luciferase reporter assay was used to confirm the relationship between miR-21-5p and SPRY2. RESULTS: Exosomes treatment through mesenteric injection demonstrated therapeutic effects on mesenteric inflammation and colitis. These therapeutic benefits were contingent on macrophages, significantly facilitating the M2 polarization of mesenteric macrophages. The expression data from GSE159814 and GSE211008 revealed that exosomal miR-21-5p was enriched in HucMSCs-Exos and could be delivered to macrophages. Additionally, the results indicated that miR-21-5p could directly target the 3'UTR of SPRY2 and activate the phosphorylation of ERK to modify macrophage phenotypes. Mechanistically, exosomal miR-21-5p derived from HucMSCs could promote macrophage M2 polarization via the SPRY2/ERK axis. CONCLUSION: Mesenteric injection of HucMSCs-Exos significantly alleviates mesenteric inflammation and colitis by promoting mesenteric macrophage M2 polarization, making it a promising approach to treat colitis and suggesting therapeutic potential role of exosomal miR-21-5p in CD.

Postoperative diarrhea in Crohn's disease: Pathogenesis, diagnosis, and therapy.

Diarrhea is a frequent symptom in postoperative patients with Crohn's diseases (CD), and several different mechanisms likely account for postoperative diarrhea in CD. A targeted strategy based on a comprehensive understanding of postoperative diarrhea is helpful for better postoperative recovery.

Stapled Antimesenteric Functional End-to-End Anastomosis Following Intestinal Resection for Crohn's Disease.

BACKGROUND: Anastomotic recurrence after bowel resection is problematic in patients with Crohn's disease. Antimesenteric functional end-to-end handsewn (Kono-S) anastomosis is associated with a low risk of anastomotic recurrence in patients with Crohn's disease. IMPACT OF INNOVATION: Kono-S anastomosis is effective but may be time-consuming. This study aimed to describe stapled antimesenteric functional end-to-end anastomosis for patients with Crohn's disease. TECHNOLOGY MATERIALS AND METHODS: The mesentery of the affected bowel segment was divided. A 5-cm-wide stapled functional end-to-end anastomosis was performed approximately 6 cm from the affected segment. The bowel was divided transversely exactly 90° to the intestinal lumen and the mesentery, and a supporting column was then constructed. PRELIMINARY RESULTS: From January 2018 to June 2021, 17 stapled antimesenteric functional end-to-end anastomoses were performed. The mean operative time was 106 (range, 80-135) minutes, and the time to construct the stapled antimesenteric functional end-to-end anastomosis was 21 (range, 18-28) minutes. The mean follow-up time was 8.9 (range, 1-15) months. In total, 10 patients underwent surveillance endoscopy. The average Rutgeerts score was 0.8 (range, 0-4), and the incidence of endoscopic recurrence was 11.8%. No postoperative mortality or anastomotic leakage was observed. CONCLUSION: Stapled antimesenteric functional end-to-end anastomosis may be a safe and time-saving procedure for patients with Crohn's disease. FUTURE DIRECTIONS: Further prospective studies with a large sample size are warranted.

Patients with Crohn's Disease Undergoing Abdominal Surgery: Clinical and Prognostic Evaluation Based on a Single-Center Cohort in China.

BACKGROUND: The incidence and prevalence of Crohn's disease (CD) are increasing in China, but there are few reports on the characteristics of patients requiring abdominal surgery. This study aimed to evaluate the clinical characteristics of these patients and the potential risk factors for postoperative complications and surgical recurrence. METHODS: In this observational, retrospective single-center cohort analysis, patients with CD who had undergone at least one abdominal surgery at our center from 2007 to 2020 were included. Data were collected from a prospectively maintained database. Clinical factors were assessed by logistic regression models, Kaplan-Meier methods, and Cox proportional hazards regression models. The predictive accuracy of the nomogram was determined by a concordance index (C-index) and calibration curve and was validated using bootstrap resampling. RESULTS: In the 1639 patients, clinical characteristics were evaluated. In a multivariable logistic regression model, penetrating behavior (P = 0.002), emergency surgery (P = 0.010), and smoking status (P = 0.015) were significantly associated with an increased risk of postoperative septic complications. In contrast, staged surgery (P = 0.009) was inversely associated with postoperative complications. Upper gastrointestinal disease (P = 0.042), penetrating behavior (P = 0.027), emergency at initial surgery (P < 0.001) were significantly associated with an increased risk of surgical recurrence after the index surgery in our Cox regression model, whereas staged surgery (P = 0.036) was significantly associated with a decreased risk. The C-index of the nomogram for predicting recurrence was 0.744 (P = 0.015), and calibration curves showed good agreement between predictions of 3, 5, and 10 years of recurrence and actual observations. CONCLUSIONS: There are several disease- and surgery-associated risk factors of postoperative adverse outcomes in patients with CD undergoing abdominal surgery. This is important in optimizing the management of CD which has evolved into a global disease with rising prevalence in newly industrialized countries including China.

Overexpression of ROD1 inhibits invasion of breast cancer cells by suppressing the translocation of ß-catenin into the nucleus.

The incidence of breast cancer is increasing throughout the world. Although significant progress has been made in diagnostic techniques and targeted therapies, the prognosis of breast cancer remains poor. Regulator of differentiation 1 (ROD1) may inhibit the development of several types of cancer. However, the role of ROD1 in breast cancer cells remains unknown. In the present study, western blot analysis and reverse transcription-quantitative polymerase chain reaction revealed that expression of ROD1 was significantly reduced in breast cancer cells. Overexpression of ROD1 reduced the proliferation rate, demonstrated using a Cell Counting Kit-8 assay. Additionally, the overexpression of ROD1 decreased the invasiveness of breast cancer cells, indicating that ROD1 may serve as a tumor suppressor. Additionally, the data suggested that ROD1 significantly suppressed the activity of Wnt luciferase reporter (TOP Flash) in MDA-MB-231 cells. Furthermore, it was demonstrated that ROD1 may interact with ß-catenin by using co-immunoprecipitation, resulting in suppression of ß-catenin migration into the nucleus. Notably, ROD1 demonstrated its anticancer effect by decreasing ß-catenin (Y333) phosphorylation in a nude mouse xenograft model. Overexpression of ROD1 may downregulate Ki67 protein levels, as determined by immunohistochemistry. These results indicated that ROD1 may be used as a therapeutic target in patients with breast cancer.

Migratory Fish Bone in the Thyroid Gland: Case Report and Literature Review.

INTRODUCTION: Foreign body stuck in the throat is a common emergency case, which can be removed by the endoscopic treatment. Fish bones are one of the common observed foreign bodies in the pharynx or cervical esophagus. Fish bones have a risk of damaging the mucosa when lodged in the upper digestive tract. Foreign bodies of fish bones located outside the laryngopharyngeal tissue are relatively unusual, and it is even more rare that they remain in the thyroid. It may cause local infection, abscess formation, large blood vessels rupture, and other serious life-threatening complications when the position of the fish bone migrates to the neck. We present a unique case of a 31-year-old woman in whom a fish bone was found in the thyroid. The fish bone had been removed successfully two months after the onset of symptoms. The relevant literature is reviewed and summarized. CASE PRESENTATION: A foreign body which is located in the neck area by swallowing is usually found in the emergency case. One of the commonest foreign bodies is the fish bone. The common presenting symptoms include foreign body (FB) sensation and or a sharp pain during swallowing. But we report a rare case in which a migratory fish bone stuck in the thyroid gland was found after 3 months. We retrieved previous literature and made a summary. CONCLUSIONS: Fish bones are not easy to be found as a foreign body. Surgeons should be aware that fish bones can become lodged in the thyroid gland. Combined with the history should be a wary fish bone to migrate to the case of the thyroid, to avoid misdiagnosis. To confirm the diagnosis, we can take ultrasound, computerized tomographic scanning (CT), and other tests.