BACKGROUND Obesity is associated with an increased risk of developing Crohn’s disease(CD),higher disease activity,and comparatively worse clinical outcomes.AIM To investigate the role of mesenteric adipose tissue-der...BACKGROUND Obesity is associated with an increased risk of developing Crohn’s disease(CD),higher disease activity,and comparatively worse clinical outcomes.AIM To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals.METHODS First,we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis.We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1(MALAT1)in mesenteric adipose tissue-derived exosomes and the colon.Next,we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6(ATF6)axis.Finally,we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid(TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways.RESULTS High-fat diet was found to aggravate TNBS-induced colitis in mice.The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased.The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway.This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p.CONCLUSION Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice,which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.展开更多
Gastric metastases from lung adenocarcinoma are rare. Because gastric metastasis grossly resembles advanced gastric cancer, it is difficult to diagnose gastric metastasis especially when the histology of the primary l...Gastric metastases from lung adenocarcinoma are rare. Because gastric metastasis grossly resembles advanced gastric cancer, it is difficult to diagnose gastric metastasis especially when the histology of the primary lung cancer is adenocarcinoma. We describe a case of gastric metastasis from primary lung adenocarcinoma mimicking Borrmann type Ⅳ primary gastric cancer. A 68-year-old man with known lung adenocarcinoma with multiple bone metastases had been experiencing progressive epigastric pain and dyspepsia over one year. Esophagogastroduodenoscopy revealed linitis plasticalike lesions in the fundus of the stomach. Pathologic examination revealed a moderately differentiated adenocarcinoma with submucosal infiltration. Positive immunohistochemical staining for thyroid transcription factor-1(TTF-1) and napsin A(Nap-A) confirmed that the metastasis was pulmonary in origin. The patient had been treated with palliative chemotherapy for the lung cancer and had lived for over fifteen months after the diagnosis of gastric metastasis. Clinicians should be aware of the possibility of gastric metastasis in patients with primary lung adenocarcinoma, and additional immunohistochemical staining for Nap-A as well as TTF-1 may help in differentiating its origin.展开更多
基金Supported by the National Natural Science Foundation of China,No.81770574the Natural Science Foundation of Zhejiang Province,No.LZ21H030002 and No.LY21H030005.
文摘BACKGROUND Obesity is associated with an increased risk of developing Crohn’s disease(CD),higher disease activity,and comparatively worse clinical outcomes.AIM To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals.METHODS First,we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis.We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1(MALAT1)in mesenteric adipose tissue-derived exosomes and the colon.Next,we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6(ATF6)axis.Finally,we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid(TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways.RESULTS High-fat diet was found to aggravate TNBS-induced colitis in mice.The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased.The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway.This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p.CONCLUSION Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice,which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.
文摘Gastric metastases from lung adenocarcinoma are rare. Because gastric metastasis grossly resembles advanced gastric cancer, it is difficult to diagnose gastric metastasis especially when the histology of the primary lung cancer is adenocarcinoma. We describe a case of gastric metastasis from primary lung adenocarcinoma mimicking Borrmann type Ⅳ primary gastric cancer. A 68-year-old man with known lung adenocarcinoma with multiple bone metastases had been experiencing progressive epigastric pain and dyspepsia over one year. Esophagogastroduodenoscopy revealed linitis plasticalike lesions in the fundus of the stomach. Pathologic examination revealed a moderately differentiated adenocarcinoma with submucosal infiltration. Positive immunohistochemical staining for thyroid transcription factor-1(TTF-1) and napsin A(Nap-A) confirmed that the metastasis was pulmonary in origin. The patient had been treated with palliative chemotherapy for the lung cancer and had lived for over fifteen months after the diagnosis of gastric metastasis. Clinicians should be aware of the possibility of gastric metastasis in patients with primary lung adenocarcinoma, and additional immunohistochemical staining for Nap-A as well as TTF-1 may help in differentiating its origin.
