No abstract

Translocase of outer mitochondrial membrane 20 (TOMM20) plays an essential role as a receptor for proteins targeted to mitochondria. TOMM20 was shown to be overexpressed in various cancers. However, the oncological function and therapeutic potential for TOMM20 in cancer remains largely unexplored. The purpose of this study was to elucidate the underlying molecular mechanism of TOMM20’s contribution to tumorigenesis and to explore the possibility of its therapeutic potential using colorectal cancer as a model. The results show that TOMM20 overexpression resulted in an increase in cell proliferation, migration, and invasion of colorectal cancer (CRC) cells, while siRNA-mediated inhibition of TOMM20 resulted in significant decreases in cell proliferation, migration, and invasion. TOMM20 expression directly impacted the mitochondrial function including ATP production and maintenance of membrane potential, which contributed to tumorigenic cellular activities including regulation of S phase cell cycle and apoptosis. TOMM20 was overexpressed in CRC compared to the normal tissues and increased expression of TOMM20 to be associated with malignant characteristics including a higher number of lymph nodes and perineural invasion in CRC. Notably, knockdown of TOMM20 in the xenograft mouse model resulted in a significant reduction of tumor growth. This is the first report demonstrating a relationship between TOMM20 and tumorigenesis in colorectal cancer and providing promising evidence for the potential for TOMM20 to serve as a new therapeutic target of colorectal cancer.

The precise mechanisms of acute damage and the role of gastric mucosal blood flow in gastric mucosal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs) remain uncertain. The aim of this study was to evaluate the preventive effect of rebamipide on gastric mucosal injury and reduction of gastric mucosal blood flow (GMBF) after ibuprofen administration. Twenty healthy volunteers were randomized two groups. The rebamipide group took ibuprofen, 1800 mg/day, and rebamipide, 100 mg t.i.d., for 7 days. The placebo group took ibuprofen, 1800 mg/day. The numbers of gastric ulcer subjects were three in the placebo group and zero in the rebamipide group. The mean modified Lanza score after ibuprofen administration was significantly higher in the placebo group than the rebamipide group (2.9+/-1.7 vs. 1.3+/-1.0, respectively; P=0.032). The GMBF of the placebo group was significantly decreased at antrum from baseline, from 2.8+/-0.5 to 2.0+/-0.5 tissue perfusion units (P=0.005). There was no difference in GMBF change in the rebamipide group. Gastric mucosal injury was correlated with GMBF reduction in antrum (r=-0.677, P=0.001). In conclusion, it is suggested that the decrease in GMBF may have been associated with NSAID-induced gastric mucosal injury, and rebamipide may have prevented NSIAD-induced gastric mucosal injury by maintaining GMBF in healthy subjects.

Background and PurposeObstructive sleep apnea (OSA) is associated with cerebral white-matter changes (WMC), but the underlying mechanisms are not completely understood. Our aim was to identify the cardiovascular autonomic characteristics during sleep that are associated with cerebral WMC in OSA patients.MethodsWe recruited subjects from our sleep-center database who underwent both polysomnography and brain MRI within a 1-year period. Sixty patients who had OSA with WMC (OSA+WMC), 44 patients who had OSA without WMC (OSA−WMC), and 31 control subjects who had neither OSA nor WMC were analyzed. Linear and nonlinear indices of heart-rate variability (HRV) were analyzed in each group according to different sleep stages and also over the entire sleeping period.ResultsAmong the nonlinear HRV indices, the Poincaré ratio (SD12) during the entire sleep period was significantly increased in the OSA+WMC group, even after age adjustment. Meanwhile, detrended fluctuation analysis 1 during non-rapid-eye-movement sleep tended to be lowest in the OSA+WMC group. These indices were altered regardless of the presence of hypertension or diabetes. In the subgroup analysis of middle-aged OSA patients, approximate entropy during rapid-eye-movement sleep was significantly lower in OSA+WMC patients than in OSA−WMC patients. Overall, the nonlinear HRV indices suggest that sympathetic activity was higher in the OSA+WMC group than in the OSA−WMC and control groups.ConclusionsOur findings suggest that dysregulation of HRV, especially overactivation of sympathetic tone, could be a pathophysiologic mechanism underlying the development of WMC in OSA patients.

The microRNAs (miRNAs) are a class of small non-coding RNA molecules that play important roles in cellular processes by regulating gene expression at the post-transcriptional level. In skin biology, several miRNAs have been shown to be associated with differentiation, migration and apoptosis of keratinocytes, and regulation of the hair cycle. Although the biological role of miR-330-5p has been reported in several cancers and cells, the function and molecular mechanism of miR-330-5p in skin keratinocytes have not been identified. In this study, we found that miR-330-5p inhibited the proliferation and migration of mouse keratinocytes. Among the candidate target genes of miR-330-5p searched using microarray analysis, we found that the expression of Pdia3 was directly regulated by miR-330-5p in the mouse keratinocyte. Moreover, inhibition of Pdia3 expression caused decreased proliferation and migration ability of mouse keratinocytes. Additionally, expressions of miR-330-5p and Pdia3 displayed an inverse correlation with respect to the hair cycle stage. These results indicated that regulation of Pdia3 expression by miR-330-5p is important in maintaining the hair cycle through regulation of the proliferation and migration capability of keratinocytes.

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The aim of this study was to evaluate the efficacy of levofloxacin and rifaximin based quadruple regimen as first-line treatment for Helicobacter pylori infection. A prospectively randomized, double-blinded, parallel group, comparative study was performed. Three hundred consecutive H. pylori positive patients were randomized to receive: omeprazole, amoxicillin, clarithromycin (OAC); omeprazole, amoxicillin, levofloxacin (OAL); and omeprazole, amoxicillin, levofloxacin, rifaximin (OAL-R). The eradication rates in the intention to treat (ITT) and per protocol (PP) analyses were: OAC, 77.8% and 85.6%; OAL, 65.3% and 73.6%; and OAL-R, 74.5% and 80.2%. The eradication rate achieved with OAC was higher than with OAL on the ITT (P = 0.05) and PP analysis (P = 0.04). OAL-R regimen was not inferior to OAC. The frequency of moderate to severe adverse effects was significantly higher in OAC treatment group. Especially, diarrhea was most common complaint, and there was a significantly low rate of moderate to severe diarrhea with the rifaximin containing regimen. In conclusion, the levofloxacin and rifaximin based regimen comes up to the standard triple therapy, but has a limited efficacy in a Korean cohort. The rifaximin containing regimen has a very high safety profile for H. pylori eradication therapy.

A 40 mg b.i.d. dose of pantoprazole is sufficient to maintain pH > 6.0 in Korean patients, except for patients with extensive metabolizing CYP2C19 genotypes.