👤 Yu Mikami

Physical activity benefits health, whereas physical inactivity increases the risk of age-related conditions and adverse health outcomes. Kyotango City in Japan is known for its residents' longevity, and many centenarians live there. This study investigated the physical activity associations with physical function and body composition in older adults living in this area. Community-dwelling older adults (n = 727; mean age 74.1 years; 59.4% women) participated in this study. Multiple linear regression analyses were carried out to examine objectively-measured physical activity associations with physical function (handgrip strength, knee extension strength and maximum gait speed) and body composition (skeletal muscle mass index and whole-body phase angle), adjusting for potential confounders. Additionally, isotemporal substitution models were applied to estimate changes resulting from replacing sedentary behavior with light-intensity physical activity (LPA) and moderate-to-vigorous-intensity physical activity (MVPA). All physical function and body composition indicators were significantly associated with SB and MVPA (all P < 0.050). However, LPA was associated with only handgrip strength and body composition indicators. Replacing 30 min of SB per day with LPA was associated with a 0.176 kg increase in handgrip strength, 0.018 kg/m Older adults in a region of Japan known for longevity might maintain physical function and favorable body composition through engaging in abundant physical activity. Public health strategies should prioritize MVPA promotion while recognizing LPA's complementary role for physically inactive older adults. Geriatr Gerontol Int 2025; 25: 1511-1517. Show less

Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C. Data from 11,498 men and women aged 35-69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P < 5 × 10 We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex, and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively. The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking. Show less

The mTOR pathway is one of the key signal cascades in the pathogenesis of idiopathic pulmonary fibrosis. Previous studies have mainly focused on this pathway in the fibroblasts and/or myofibroblasts, but not in the epithelial cells. In this study, we sought to investigate the role of the mTOR pathway in lung epithelial cells in lung fibrosis. Using Show less

Statins decrease cholesteryl ester transfer protein (CETP) levels, which have been positively associated with hepatic lipid content as well as serum low density lipoproteins-cholesterol (LDL-C) levels. However, the relationship between the CETP status and statin-induced reductions in LDL-C levels has not yet been elucidated in detail. We herein examined the influence of the CETP status on the lipid-reducing effects of pitavastatin in hypercholesterolemic patients with type 2 diabetes mellitus as well as the molecular mechanism underlying pitavastatin-induced modifications in CETP levels. Fifty-three patients were treated with 2 mg of pitavastatin for 3 months. Serum levels of LDL-C, small dense (sd) LDL-C, and CETP were measured before and after the pitavastatin treatment. The effects of pitavastatin, T0901317, a specific agonist for liver X receptor (LXR) that reflects hepatic cholesterol contents, and LXR silencing on CETP mRNA expression in HepG2 cells were also examined by a real-time PCR assay. The pitavastatin treatment decreased LDL-C, sdLDL-C, and CETP levels by 39, 42, and 23%, respectively. Despite the absence of a significant association between CETP and LDL-C levels at baseline, baseline CETP levels and its percentage change were an independent positive determinant for the changes observed in LDL-C and sdLDL-C levels. The LXR activation with T0901317 (0.5 μM), an in vitro condition analogous to hepatic cholesterol accumulation, increased CETP mRNA levels in HepG2 cells by approximately 220%, while LXR silencing markedly diminished the increased expression of CETP. Pitavastatin (5 μM) decreased basal CETP mRNA levels by 21%, and this was completely reversed by T0901317. Baseline CETP levels may predict the lipid-reducing effects of pitavastatin. Pitavastatin-induced CETP reductions may be partially attributed to decreased LXR activity, predictable by the ensuing decline in hepatic cholesterol synthesis. UMIN Clinical Trials Registry ID UMIN000019020. Show less

Chronic kidney disease (CKD) is known to be one of the causes of cardiovascular disease and end-stage renal disease. Among the several treatable risk factors of CKD, that of dyslipidemia is relatively controversial. To clarify the association of polymorphisms in genes involved in lipid metabolism with the risk of CKD in the Japanese population, we used cross-sectional data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. A total of 3,268 men and women, aged 35-69 years, were selected from J-MICC Study participants for inclusion in this study. Twenty-eight candidate single nucleotide polymorphisms (SNPs) were selected in 17 genes associated with the risk of lipid metabolism disorders, and genotyping of the subjects was conducted using the multiplex PCR-based invader assay. The prevalence of CKD was determined for stages 3-5 (defined as estimated glomerular filtration rate <60 ml/min/1.73 m2). Logistic regression analysis revealed that SNPs APOA5 T - 1131C (rs662799), APOA5 T1259C (rs2266788), TOMM40 A/G (rs157580), and CETP TaqIB (rs708272) were significantly associated with CKD risk in those individuals genotyped, with age- and sex-adjusted odds ratios (ORs) per minor allele (and 95% confidence intervals (CIs)) of OR 1.22 (95% CI: 1.06-1.39), 1.19 (1.03-1.37), 1.27 (1.12-1.45), and 0.81 (0.71-0.92), respectively. Analysis of the gene-environment interaction revealed that body mass index (BMI) was a significant effect modifier for APOA5 T - 1131C (rs662799) and a marginally significant effect modifier for APOA5 T/C (rs2266788), with the interaction between BMI ≥30 and individuals with at least one minor allele of each genotype of OR 10.43 (95% CI: 1.29-84.19) and 3.36 (0.87-13.01), respectively. Four polymorphisms in APOA5, TOMM40, and CETP were shown to be significantly associated with CKD risk, and a significant interaction between the two APOA5 SNPs and BMI on CKD risk was also demonstrated. This suggests the future possibility of personalized risk estimation for this life-limiting disease. Show less

This study examined the associations of the APOA5 T-1131C (rs662799), G553T (Cys185Gly, rs2075291), GCK G-30A (rs1799884), GCKR A/G at intron 16 (rs780094) and T1403C (Leu446Pro, rs1260326) polymorphisms with serum lipid and glucose levels in Japanese, considering lifestyle factors. Study subjects were 2,191 participants (aged 35-69 years, 1,159 males) enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Dyslipidemia was defined as fasting serum triglycerides (FTG) ≥ 150 mg/dL and/or HDL-cholesterol (HDL-C) < 40 mg/dL, while dysglycemia was as fasting blood sugar (FBS) ≥ 110 mg/dL. When those with APOA5 -1131 T/T or 553 G/G were defined as references, those with APOA5 -1131 T/C, C/C or 553 G/T, T/T demonstrated significantly elevated risk of dyslipidemia (age- and sex-adjusted odds ratio: 1.77 [95% confidence interval:1.39-2.27], 3.35 [2.41-4.65], 2.23 [1.64-3.02] and 13.78 [3.44-55.18], respectively). Evaluation of FTG, HDL-C or FBS levels according to the genotype revealed that FTG and HDL-C levels were significantly associated with the APOA5 T-1131C and G553T polymorphisms, FTG with the GCKR rs780094 and rs1260326 polymorphisms, and FBS with the GCKR rs780094 and rs1260326 polymorphisms. Moreover, a significant positive interaction between APOA5 553 G/T+T/T genotypes and fat intake ≥ 25% of total energy for the risk of dyslipidemia was observed. Our cross-sectional study confirmed the essential roles of the polymorphisms of the APOA5, GCK and GCKR in the lipid or glucose metabolism disorders, and suggested the importance of fat intake control in the individualized prevention of dyslipidemia. Show less

Patients with intraductal papillary-mucinous neoplasm (IPMN) of the pancreas are likely to have a better prognosis than those with conventional pancreatic ductal adenocarcinoma. Recently there have been some reports on extrapancreatic malignant neoplasms (EPM) occurring in patients with IPMN. The purpose of this study was to discover the characteristic features of IPMN with EPM compared with IPMN without EPM. 61 patients with IPMN who underwent surgery at Tohoku University Hospital between 1988 and 2006 were retrospectively analyzed. The 61 patients with IPMN in this study comprised 25 with intraductal papillary-mucinous adenomas (IPMA) and 36 with intraductal papillary-mucinous carcinomas (IPMC) including 6 with invasive carcinomas. Synchronous and metachronous EPM were observed in 15 out of the 61 patients (24.6%). Three of these patients, including 2 with IPMA and 1 with invasive carcinoma associated with IPMC, died of the EPM. None of the features, including sex, age, smoking, family history, macroscopic types (main duct type or branch duct type), histological types (gastric, intestinal, pancreatobiliary or oncocytic), and aberrant expression of molecules including CDKN2A, TP53, SMAD4 and DUSP6, except for the histological diagnoses were associated with the occurrence of EPM, i.e., the EPM occurred more often in patients with IPMA (10 out of 25) than in those with IPMC (5 out of 36) in our series (p = 0.0199 by the chi(2) test, p = 0.0330 by Fisher's exact probability test, p = 0.0422 by Yates' correction). Patients with IPMA were more likely to have EPM than those with IPMC. Patients with IPMA are usually expected to have a fair prognosis but EPM could be fatal in some of them, so it must be noted during follow-up. Show less

Constitutive activation of the Wnt pathway as a result of APC, AXIN1 or CTNNB1 mutations has been found in most colorectal cancers. For a long time, this aberrant Wnt activation has been thought to be independent of upstream signals. However, recent studies indicate that upstream signals retain their ability to regulate the Wnt pathway even in the presence of downstream mutations. Wnt-2 is well known for its overexpression in colorectal cancer. Galectin-3 (Gal-3), a multifunctional carbohydrate binding protein implicated in a variety of biological functions, has recently been reported to interact with beta-catenin. In this study, we investigated roles of Wnt-2 and Gal-3 in the regulation of canonical Wnt/beta-catenin signaling. We found that siRNA silencing of either Wnt-2 or Gal-3 expression inhibited TCF-reporter activity, decreased cytosolic beta-catenin level and induced apoptosis in human colorectal cancer cells containing downstream mutations. More interestingly, we showed that inhibition of both Wnt-2 and Gal-3 had synergistic effects on suppressing canonical Wnt signaling and inducing apoptosis, suggesting that aberrant canonical Wnt/beta-catenin signaling in colorectal cancer can be regulated at multiple levels. The combined inhibition of Wnt-2 and Gal-3 may be of superior therapeutic advantage to inhibition by either one of them, giving rise to a potential development of novel drugs for the targeted treatment of colorectal cancer. Show less