👤 Hisashi Saji

Cerebral small vessel disease (SVD) is prevalent in older adults with type 2 diabetes and contributes to an elevated risk of cognitive decline. Although physical activity (PA) is a potentially modifiable factor in SVD prevention, previous findings remain inconsistent, particularly regarding activity intensity. This study aimed to investigate the association between accelerometer-measured PA and SVD severity in older adults with type 2 diabetes. This cross-sectional study analyzed 66 adults aged ≥70 years with type 2 diabetes. PA was objectively measured using a tri-axial accelerometer over 14 days. Time spent in sedentary behavior (≤1.5 metabolic equivalents [METs]), light-intensity PA (LPA; 1.6-2.9 METs), and moderate-to-vigorous PA (MVPA; ≥3.0 METs) were assessed. Lacunes, cerebral microbleeds, enlarged perivascular spaces, and white matter hyperintensities were evaluated using brain magnetic resonance imaging. The total SVD score (range, 0-4) was calculated, and participants were categorized into either mild (score 0-1) or moderate-to-severe (score 2-4) groups. To estimate the odds of having moderate-to-severe SVD associated with a hypothetical reallocation of 10 min of sedentary time to either LPA or MVPA, multiple logistic regression analysis using an isotemporal substitution model was performed. Of the 66 participants, 29 (43.9%) had moderate-to-severe SVD. A hypothetical reallocation of 10 min from sedentary time to MVPA was associated with lower odds of moderate-to-severe SVD (odds ratio, 0.78; 95% confidence interval, 0.61-1.00; p = 0.047). LPA exhibited no significant association. Engaging in MVPA is associated with lower SVD severity in older adults with type 2 diabetes. Show less

Solid-predominant lung adenocarcinoma (SPA), which is one of the high-risk subtypes with poor prognosis and unsatisfactory response to chemotherapy and targeted therapy in lung adenocarcinoma, remains molecular profile unclarified. Weighted correlation network analysis (WGCNA) was used for data mining, especially for studying biological networks based on pairwise correlations between variables. This study aimed to identify disease-related protein co-expression networks associated with early-stage SPA. We assessed cancerous cells laser-microdissected from formalin-fixed paraffin-embedded (FFPE) tissues of a SPA group ( Among the forty WGCNA network modules identified, two network modules were found to be associated significantly with the SPA subtype. Canonical enriched pathways were highly associated with cellular growth, proliferation, and immune response. Upregulated HLA class I molecules HLA-G and HLA-B implicated high mutation burden and T cell activation in the SPA subtype. Upstream analysis implicated the involvement of highly activated oncogenic regulators, MYC, MLXIPL, MYCN, the redox master regulator NFE2L2, and the highly inhibited LARP1, leading to oncogenic IRES-dependent translation, and also regulators of the adaptive immune response, including highly activated IFNG, TCRD, CD3-TCR, CD8A, CD8B, CD3, CD80/CD86, and highly inhibited LILRB2. Interestingly, the immune checkpoint molecule HLA-G, which is the counterpart of LILRB2, was highly expressed characteristically in the SPA subtype and might be associated with antitumor immunity. Our findings provide a disease molecular profile based on protein co-expression networks identified for the high-risk solid predominant adenocarcinoma, which will help develop future therapeutic strategies. Show less

No therapeutic targets have been identified for lung squamous cell cancer (SqCC) which is the second most prevalent lung cancer because its molecular profiles remain unclear. This study aimed to unveil disease-related protein networks by proteomic and bioinformatic assessment of laser-microdissected cancerous cells from seven SqCCs compared with eight representative lung adenocarcinomas. We identified three network modules significant to lung SqCC using weighted gene co-expression network analysis. One module was intrinsically annotated to keratinization and cell proliferation of SqCC, accompanied by hypoxia-induced aerobic glycolysis, in which key regulators were activated (HIF1A, ROCK2, EFNA1-5) and highly suppressed (KMT2D). The other two modules were significant for translational initiation, nonsense-mediated mRNA decay, inhibited cell death, and interestingly, eIF2 signaling, in which key regulators, MYC and MLXIPL, were highly activated. Another key regulator LARP1, the master regulator in cap-dependent translation, was highly suppressed although upregulations were observed for hub proteins including EIF3F and LARP1 targeted ribosomal proteins, among which PS25 is the key ribosomal protein in IRES-dependent translation. Our results suggest an underlying progression mechanism largely caused by switching to the cap-independent, IRES-dependent translation of mRNA subsets encoding oncogenic proteins. Our findings may help to develop therapeutic strategies to improve patient outcomes. Show less