Background and aims: The activation of the peroxisome proliferator-activated receptor c (PPARc) that forms heterodimers with retinoid X receptors (RXRs) elicits an antineoplastic effect on colorectal cancer. It was previously reported that the accumulation of the non-functional phosphorylated form of RXRa (p-RXRa) interfered with its signalling and promoted the growth of hepatoma cells. In this study the effects of p-RXRa on the ability of RXRa and PPARc ligands to inhibit growth in colon cancer cells was examined. Methods: The effects of the combination of the PPARc ligand ciglitazone and the RXRa lignad 9-cis-retinoic acid (RA) on inhibition of cell growth in Caco2 human colon cancer cells which express high levels of p-RXRa protein were examined Results: The RXRa protein was phospholylated and also accumulated in human colon cancer tissue samples as well as human colon cancer cell lines. When the phosphorylation of RXRa was inhibited by the MEK inhibitor PD98059 or by transfection with a point-mutated RXRa, which mimicked the unphosphorylated form, the combination of 9-cisRA and ciglitazone synergistically inhibited the cell growth and induced apoptosis. The combined treatment with these agents also caused a decrease in the expression levels of both cyclooxygenase-2 (COX-2) and c-Jun proteins and mRNAs. Reporter assays indicated that this combination induced the transcriptional activity of the peroxisome proliferator-responsive element promoter and also inhibited that of the AP-1 promoter. Conclusion: A malfunction of RXRa due to phosphorylation is associated with colorectal cancer. Therefore, the inhibition of phosphorylation of RXRa and the activation of the RXR-PPARc heterodimer by their respective ligands may be useful in the chemoprevention and/or treatment of colorectal cancer.

Objective. We have previously demonstrated that reactive oxygen species (ROS) are involved in cartilage degradation. Decreased size of hyaluronan (HA), the major macromolecule in synovial fluid, to which it imparts viscosity, is reported in patients with arthritis. The purpose of this study was to determine the alteration in the molecular weight range of HA as a result of mechanical deformation loaded on the chondrocytes, as well as the involvement of ROS in this action.Methods. ROS were generated via the oxidation of hypoxanthine by xanthine oxidase. Cyclic tensile stretch was loaded using a vacuum-operated instrument. Levels of HA were measured using a sandwich enzyme-binding assay. Superoxide dismutase (SOD) activity and ROS were measured using water-soluble tetrazolium and a chemiluminescent probe, respectively.Results. ROS depolymerized HA molecules. Cyclic tensile stretch depolymerized HA and induced ROS. SOD inhibited not only ROS induction but also HA depolymerization caused by the mechanical stress.Conclusion. ROS play an important role in mechanical stress-induced HA depolymerization.

IMPORTANCEReports on dermatomyositis (DM) sine dermatitis (DMSD) are scarce, and the concept of the disease has not been widely accepted.OBJECTIVE To confirm the existence of DMSD, determine its prevalence, and characterize its serologic features. DESIGN, SETTING, AND PARTICIPANTSThis is a cohort study that reviewed clinical information, laboratory data, and muscle pathology slides from January 2009 to August 2019. We further assessed the follow-up data of 14 patients with DMSD. The median (interquartile range) follow-up period was 34 (16-64) months. Muscle biopsy samples, along with clinical information and laboratory data, were sent to a referral center for muscle diseases in Japan for diagnosis. Of patients whose myopathologic diagnosis was made at the National Center of Neurology and Psychiatry between January 2009 and August 2019, 199 patients were eligible for inclusion. These patients underwent full investigation for DM-specific autoantibodies (against transcriptional intermediary factor γ, Mi-2, melanoma differentiation-associated gene 5, nuclear matrix protein 2 [NXP-2], and small ubiquitin-like modifier activating enzyme ); however, 17 patients were excluded because their muscle fibers did not express myxovirus resistance protein A, a sensitive and specific marker of DM muscle pathology. MAIN OUTCOMES AND MEASURESDiagnosis of DMSD was based on the absence of a skin rash at the time of muscle biopsy. RESULTSOf the 182 patients, 93 were women (51%) and 46 were children (25%) (<18 years). Fourteen patients (8%) had DMSD and none were clinically diagnosed with DM. Among the 14 patients with DMSD, 12 (86%) were positive for anti-NXP-2 autoantibodies, while the remaining 2 were positive for anti-transcriptional intermediary factor γ and anti-Mi-2 autoantibodies, respectively. Only 28% of patients (47 of 168) with a skin rash were positive for anti-NXP-2 autoantibodies, indicating a significant association between anti-NXP-2 autoantibodies and DMSD (86% [12 of 14] vs 28% [47 of 168]; P < .001). This association was also supported by multivariable models adjusted for disease duration (odds ratio, 126.47; 95% CI, 11.42-1400.64; P < .001).CONCLUSIONS AND RELEVANCE Dermatomyositis sine dermatitis does exist and accounts for 8% of patients with DM confirmed with muscle biopsy. Dermatomyositis sine dermatitis is significantly associated with anti-NXP-2 autoantibodies, which contrasts with anti-MDA5 DM, which is typically clinically amyopathic in presentation. It is essential to distinguish DMSD from other types of myositis because DM-specific therapies that are currently under development, including Janus kinase inhibitors, may be effective for DMSD.

A transmural air leak was observed in 13 % of the patients undergoing ESD. Larger resection size, prolonged procedure time, and exposure of the muscularis propria on the ulcer base were risk factors for transmural air leak, but the outcome of patients with this complication was good.

The present study provides evidence of a conservative obesity paradox among older Japanese people, using the appropriate body mass index cut-off points for Asian populations. In particular, obese older men tend to have a lower risk of all-cause mortality. Geriatr Gerontol Int 2017; 17: 1257-1264.