Lansoprazole inhibits the development of sessile serrated lesions by inducing G1 arrest via Skp2/p27 signaling pathway.

Background: Although the serrated-neoplasia pathway reportedly accounts for 15-30% of colorectal cancer (CRC), no studies on chemoprevention of sessile serrated lesions (SSLs) have been reported. We searched for effective compounds comprehensively from a large series of compounds by employing Connectivity Map (CMAP) analysis of SSL-specific gene expression profiles coupled with in vitro screening using SSL patient-derived organoids (PDOs), and validated their efficacy using a xenograft mouse model of SSL.

Methods: We generated SSL-specific gene signatures based on DNA microarray data, and applied them to CMAP analysis with 1309 FDA-approved compounds to select candidate compounds.

Urokinase-type plasminogen activator blockade ameliorates experimental colitis in mice.

Although several angiogenesis-related factors are reportedly involved in the pathogenesis of ulcerative colitis (UC), the mechanisms by which they contribute to disease are unclear. We first examined the expression of angiogenesis-related factors in inflamed colorectal tissue of UC patients using antibody array, and identified the 5 factors with highest expression, which included matrix metalloproteinase-8, urokinase-type plasminogen activator (uPA), angiostatin/plasminogen, hepatocyte growth factor and endoglin. Subsequent real-time PCR experiments using additional colorectal tissues revealed that uPA mRNA levels were significantly higher in inflamed tissues than in non-inflamed tissues, and significantly correlated with the severity of UC.

Resveratrol inhibits development of colorectal adenoma via suppression of LEF1; comprehensive analysis with connectivity map.

Although many chemopreventive studies on colorectal tumors have been reported, no effective and safe preventive agent is currently available. We searched for candidate preventive compounds against colorectal tumor comprehensively from United States Food and Drug Administration (FDA)-approved compounds by using connectivity map (CMAP) analysis coupled with in vitro screening with colorectal adenoma (CRA) patient-derived organoids (PDOs). We generated CRA-specific gene signatures based on the DNA microarray analysis of CRA and normal epithelial specimens, applied them to CMAP analysis with 1309 FDA-approved compounds, and identified 121 candidate compounds that should cancel the gene signatures.

TIMP1 promotes cell proliferation and invasion capability of right-sided colon cancers via the FAK/Akt signaling pathway.

Although right-sided colorectal cancer (CRC) shows a worse prognosis than left-sided CRC, the underlying mechanism remains unclear. We established patient-derived organoids (PDOs) from left- and right-sided CRCs and directly compared cell proliferation and invasion capability between them. We then analyzed the expression of numerous genes in signal transduction pathways to clarify the mechanism of the differential prognosis.

Dynamic Cloth Manipulation Considering Variable Stiffness and Material Change Using Deep Predictive Model With Parametric Bias.

Dynamic manipulation of flexible objects such as fabric, which is difficult to modelize, is one of the major challenges in robotics. With the development of deep learning, we are beginning to see results in simulations and some actual robots, but there are still many problems that have not yet been tackled. Humans can move their arms at high speed using their flexible bodies skillfully, and even when the material to be manipulated changes, they can manipulate the material after moving it several times and understanding its characteristics.

MiR-125b-5p Is Involved in Sorafenib Resistance through Ataxin-1-Mediated Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma.

The mechanism of resistance to sorafenib in hepatocellular carcinoma (HCC) remains unclear. We analyzed miRNA expression profiles in sorafenib-resistant HCC cell lines (PLC/PRF5-R1/R2) and parental cell lines (PLC/PRF5) to identify the miRNAs responsible for resistance. Drug sensitivity, migration/invasion capabilities, and epithelial-mesenchymal transition (EMT) properties were analyzed by biochemical methods.

Evaluation of SAMP8 Mice as a Model for Sleep-Wake and Rhythm Disturbances Associated with Alzheimer's Disease: Impact of Treatment with the Dual Orexin (Hypocretin) Receptor Antagonist Lemborexant.

Background: Many patients with Alzheimer's disease (AD) display circadian rhythm and sleep-wake disturbances. However, few mouse AD models exhibit these disturbances. Lemborexant, a dual orexin receptor antagonist, is under development for treating circadian rhythm disorders in dementia.

Long-chain monounsaturated fatty acids improve endothelial function with altering microbial flora.

Fish oil-derived long-chain monounsaturated fatty acids (LCMUFAs) with a carbon chain length longer than 18 units ameliorate cardiovascular risk in mice. In this study, we investigated whether LCMUFAs could improve endothelial functions in mice and humans. In a double-blind, randomized, placebo-controlled, parallel-group, multi-center study, healthy subjects were randomly assigned to either an LCMUFA oil (saury oil) or a control oil (olive and tuna oils) group.

S100P Expression via DNA Hypomethylation Promotes Cell Growth in the Sessile Serrated Adenoma/Polyp-Cancer Sequence.

Background/aims: Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor lesion of colon cancer. Although the relevance of DNA hypermethylation in the SSA/P-cancer sequence is well documented, the role of DNA hypomethylation is unknown. We investigated the biological relevance of DNA hypomethylation in the SSA/P-cancer sequence by using 3-dimensional organoids of SSA/P.

Effect of olive oil consumption on aging in a senescence-accelerated mice-prone 8 (SAMP8) model.

Background : Mediterranean diets have been linked to a reduced risk of cancer, vascular illnesses, Parkinson's and Alzheimer's disease. Olive oil is the primary fat source in the Mediterranean diet ; however, only a few studies have investigated the effect of olive oil on aging. In the present study, we aimed to determine whether consumption of olive oil significantly influences aging and memory in senescence-accelerated mouse-prone 8 (SAMP8).

MicroRNA-296-5p Promotes Cell Invasion and Drug Resistance by Targeting Bcl2-Related Ovarian Killer, Leading to a Poor Prognosis in Pancreatic Cancer.

Background/aims: Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive invasion, early metastasis, and resistance to chemotherapy, leading to a poor prognosis. To clarify the molecular mechanism of these malignant characteristics, we performed a genome-wide microRNA (miRNA) array analysis utilizing micro-cancer tissues from patients with unresectable PDAC (stage IV), obtained by endoscopic ultrasound-fine needle aspiration (EUS-FNA).

Methods: The expression profiles of 2,042 miRNAs were determined using micro-cancer tissues from 13 patients with unresectable PDAC obtained by EUS-FNA.

Exposure-response analysis of drug-induced QT interval prolongation in telemetered monkeys for translational prediction to human.

Introduction: The preclinical in vivo assay for QT prolongation is critical for predicting torsadogenic risk, but still difficult to extrapolate to humans. This study ran preclinical tests in cynomolgus monkeys on seven QT reference drugs containing the drugs used in the IQ-CSRC clinical trial and applied exposure-response (ER) analysis to the data to investigate the potential for translational information on the QT effect.

Methods: In each of six participating facilities in the J-ICET project, telemetered monkeys were monitored for 24 h following administration of vehicle or 3 doses of test drugs, and pharmacokinetic profiles at the same doses were evaluated separately.

Long-chain monounsaturated fatty acid-rich fish oil attenuates the development of atherosclerosis in mouse models.

Scope: Fish oil-derived long-chain monounsaturated fatty acids (LCMUFA) containing chain lengths longer than 18 were previously shown to improve cardiovascular disease risk factors in mice. However, it is not known if LCMUFA also exerts anti-atherogenic effects. The main objective of the present study was to investigate the effect of LCMUFA on the development of atherosclerosis in mouse models.

Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance.

Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains largely unknown. Here we showed that obesity-related adipocyte degeneration causes release of cell-free DNA (cfDNA), which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9 (TLR9), originally known as a sensor of exogenous DNA fragments. Fat-fed obese wild-type mice showed increased release of cfDNA, as determined by the concentrations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in plasma.

High-Dose α-Tocopherol Supplementation Does Not Induce Bone Loss in Normal Rats.

Oxidative stress affects bone turnover. Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans. The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies.

On experiences of i2b2 (Informatics for integrating biology and the bedside) database with Japanese clinical patients' data.

Informatics for Integrating Biology and the Bedside (i2b2) is a database system to facilitate sharing and reuse of clinical patients' data collected in individual hospitals. The i2b2 provides an ontology based object-oriented database system with highly simple and flexible database schema which enables us to integrate clinical patients' data from different laboratories and different hospitals. 392 patients' data including carcinoma and non-carcinoma specimens from cancer patients are transported from the Integrated Clinical Omics Database (iCOD) to the i2b2 database for a feasibility study to check applicability of i2b2 ontology and database schema on Japanese clinical patients' data.