Gastroenterology
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Randomized Controlled Trial Multicenter Study
Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study.
Simultaneous agonism of the μ-opioid receptor and antagonism of the δ-opioid receptor can reduce abdominal pain and diarrhea in patients with irritable bowel syndrome with diarrhea (IBS-D) without constipating side effects. We evaluated the efficacy and safety of a minimally absorbed, μ-opioid receptor agonist and δ-opioid receptor antagonist (eluxadoline) in a phase 2 study in patients with IBS-D. ⋯ In a phase 2 study of the mixed μ-opioid receptor agonist/δ-opioid receptor antagonist eluxadoline vs placebo in patients with IBS-D, patients given eluxadoline were significantly more likely to be clinical responders, based on a composite of improvement in abdominal pain and stool consistency. Further study of eluxadoline is warranted to assess its potential as a treatment for IBS-D.
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Colorectal tumors have a large degree of molecular heterogeneity. Three integrated pathways of carcinogenesis (ie, traditional, alternate, and serrated) have been proposed, based on specific combinations of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and mutations in BRAF and KRAS. We used resources from the population-based Iowa Women's Health Study (n = 41,836) to associate markers of colorectal tumors, integrated pathways, and clinical and pathology characteristics, including survival times. ⋯ We identified clinical and pathology features associated with molecularly defined CRC subtypes. However, additional studies are needed to determine how these features might influence prognosis.
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Tight junction dysregulation and epithelial damage contribute to barrier loss in patients with inflammatory bowel disease. However, the mechanisms that regulate these processes and their relative contributions to disease pathogenesis are not completely understood. We investigated these processes using colitis models in mice. ⋯ In immune-mediated inflammatory bowel disease models, TNFR2 signaling increases long MLCK expression, resulting in tight junction dysregulation, barrier loss, and induction of colitis. At advanced stages, colitis progresses by apoptosis and mucosal damage that result in tight junction- and MLCK-independent barrier loss. Therefore, barrier loss in immune-mediated colitis occurs via two temporally and morphologically distinct mechanisms. Differential targeting of these mechanisms can lead to improved inflammatory bowel disease therapies.
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Altered functions of microRNAs (miRNAs) have been associated with colorectal cancer (CRC). miR-212 is transcribed from a stable intron of a non-protein coding gene, and is reportedly down-regulated in different tumor types. We investigated the role of miR-212 in colorectal carcinogenesis and progression. ⋯ miR-212 is down-regulated in human CRC tissues via genetic and epigenetic mechanisms. miR-212 might prevent tumor progression by targeting MnSOD messenger RNA; reduction of miR-212 could be a prognostic marker for patients with CRC. miR-212 and MnSOD might also be therapeutic targets for cancer.