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The ubiquitin-proteasome system (UPS) degrades soluble proteins and small aggregates, whereas macroautophagy (autophagy herein) eliminates larger protein aggregates, tangles and even whole organelles in a lysosome-dependent manner. VCP/p97 was implicated in both pathways. VCP/p97 mutations cause a rare multisystem disease called IBMPFD (Inclusion Body Myopathy with Paget’s Disease and Frontotemporal Dementia). Here, we studied the role IBMPFD-related mutants of VCP/p97 in autophagy. In contrast with the wild-type VCP/p97 protein or R155C or R191Q mutants, the P137L mutant was aggregate-prone. We showed that, unlike commonly studied R155C or R191Q mutants, the P137L mutant protein stimulated both autophagosome and autolysosome formation. Moreover, P137L mutant protein itself was a substrate of autophagy. Starvation- and mTOR inhibition-induced autophagy led to the degradation of the P137L mutant protein, while preserving the wild-type and functional VCP/p97. Strikingly, similar to the P137L mutant, other IBMPFD-related VCP/p97 mutants, namely R93C and G157R mutants induced autophagosome and autolysosome formation; and G157R mutant formed aggregates that could be cleared by autophagy. Therefore, cellular phenotypes caused by P137L mutant expression were not isolated observations, and some other IBMPFD disease-related VCP/p97 mutations could lead to similar outcomes. Our results indicate that cellular mechanisms leading to IBMPFD disease may be various, and underline the importance of studying different disease-associated mutations in order to better understand human pathologies and tailor mutation-specific treatment strategies.

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Background: It is important to resume regular functions of the digestive system as soon as possible after surgery. It has been reported that chewing gum can be used in this regard. Objectives: This study aimed to evaluate the effect of chewing gum on nausea-vomiting and bowel function in surgical patients. Methods: A total of 60 patients with cholecystectomy and herniotomy (30 controls [non-chewing gum] and 30 interventions [chewing gum]) were enrolled in this controlled experimental study. The intervention group was provided to chew gum 3 times for 15 - 30 minutes with a 2-hour interval. Both control and intervention groups were evaluated 6 and 24 hours after being taken to the surgical service using the nausea-vomiting, intestinal functions monitoring form. Results: A statistically significant difference was found between the control and intervention groups 0 - 6 hours after surgery (χ2 = 4.320, P < 0.05). The intervention group was found to be discharged earlier than the control group (χ² = 4.286, P < 0.05; Z = -2.053, P < 0.05), and the difference was significant. It was found that the intervention group suffered 5.09 times less vomiting compared to the control group 0 - 6 hours after surgery. Conclusions: The positive effects of chewing gum on nausea, vomiting, intestinal function, and early discharge were found. It is recommended that chewing gum be included in nursing interventions for patients after surgery.