Several recent landmark papers describing N6-methyladenosine (m6A) RNA modifications have provided valuable new insights as to the importance of m6A in the RNA transcriptome and in furthering the understanding of RNA epigenetics. One endogenous enzyme responsible for demethylating RNA m6A, FTO, is highly expressed in the CNS and is likely involved in mRNA metabolism, splicing or other nuclear RNA processing events. microRNAs (miRNAs), a family of small, non-coding transcripts that bind to target mRNAs and inhibit subsequent translation, are highly expressed in the CNS and are associated with several neurological disorders, including epilepsy. miRNAs frequently bind to recognition sequences in the 3′UTR, a region that is also enriched for m6A. Certain specific miRNAs are upregulated by neuronal activity and are coupled to epileptogenesis; these miRNAs contain a consensus m6A site that if methylated could possibly regulate miRNA processing or function. This commentary highlights aspects from recent papers to propose a functional association between FTO, RNA epigenetics and epilepsy.

A defective tight junction (TJ) barrier is a key pathogenic factor for inflammatory bowel disease. Previously, we have shown that autophagy, a cell survival mechanism, enhances intestinal epithelial TJ barrier function. Autophagy-related protein-6 (ATG6/beclin 1), a key protein in the autophagy pathway, also plays a role in the endocytic pathway. The constitutive role of beclin 1 in the intestinal TJ barrier is not known. In Caco-2 cells, beclin 1 was found to be coimmunoprecipitated with the TJ protein occludin and colocalized with occludin on the membrane. Treatment of Caco-2 cells with beclin 1 peptide [transactivating regulatory protein (Tat)-beclin 1] reduced TJ barrier function. Activation of beclin 1 increased occludin endocytosis and reduced total occludin protein level. In contrast, beclin 1 siRNA transfection enhanced Caco-2 TJ barrier function. In pharmacologic and genetic autophagy inhibition studies, the constitutive function of beclin 1 in the TJ barrier was found to be autophagy independent. However, de novo induction of autophagy with starvation or rapamycin prevented Tat-beclin 1-induced increase in TJ permeability and reduction in occludin level. Induction of autophagy also resulted in reduced beclin 1-occludin association. In mouse colon, beclin 1 colocalized with occludin on the epithelial membrane. Perfusion of mouse colon with beclin 1 peptide caused an increase in colonic TJ permeability that was prevented by in vivo induction of autophagy. These findings show that beclin 1 plays a constitutive, autophagy-independent role in the regulation of intestinal TJ barrier function via endocytosis of occludin. Autophagy terminates constitutive beclin 1 function in the TJ barrier and enhances the TJ barrier.

An anomalous elongated pancreaticobiliary common channel encourages reflux up both the biliary tree and the pancreatic ductal system, resulting in progressive choledochal dilatation, cholangitis with ductal calculi, relapsing pancreatitis and malignant change. Transduodenal sphincteroplasty has been used to improve drainage from the abnormal channel. The use of endoscopic sphincterotomy (ES) to establish drainage and minimize the surgical risks is reported in six symptomatic patients with mild choledochal dilatation (common bile duct diameter less than 15 mm), a common channel less than 15 mm in length and a distal stenosis. This was successful in five patients, who have no further symptoms. ES failed in the only patient with an undilated common channel and this patient went on to have open surgery. We believe ES to be safe and effective in the treatment of selected cases of long common channel.

Artificial intelligence (AI) is a combination of different technologies that enable machines to sense, comprehend, and learn with human-like levels of intelligence. AI technology will eventually enhance human capability, provide machines genuine autonomy, and reduce errors, and increase productivity and efficiency. AI seems promising, and the field is full of invention, novel applications; however, the limitation of machine learning suggests a cautious optimism as the right strategy. AI is also becoming incorporated into medicine to improve patient care by speeding up processes and achieving greater accuracy for optimal patient care. AI using deep learning technology has been used to identify, differentiate catalog images in several medical fields including gastrointestinal endoscopy. The gastrointestinal endoscopy field involves endoscopic diagnoses and prognostication of various digestive diseases using image analysis with the help of various gastrointestinal endoscopic device systems. AI-based endoscopic systems can reliably detect and provide crucial information on gastrointestinal pathology based on their training and validation. These systems can make gastroenterology practice easier, faster, more reliable, and reduce inter-observer variability in the coming years. However, the thought that these systems will replace human decision making replace gastrointestinal endoscopists does not seem plausible in the near future. In this review, we discuss AI and associated various technological terminologies, evolving role in gastrointestinal endoscopy, and future possibilities.

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