Shape of Barrett's epithelium is associated with prevalence of erosive esophagitis

AIM:To test the hypothesis that the shape and length of Barrett‘s epithelium are associated with prevalence of erosive esophagitis.METHODS:A total study population comprised 869 patients who underwent endoscopy during a health checkup at our hospital.The presence and extent of Barrett‘s epithelium were diagnosed based on the Prague C & M Criteria.We originally classified cases of Barrett‘s epithelium into two types based on its shape,namely,flamelike and lotus-like Barrett‘s epithelium,and into two groups b...     

Notch-Hes1 pathway is required for the development of IL-17-producing γδ T cells

Unlike conventional T cells, which are exported from the thymus as naive cells and acquire effector functions upon antigen encounter in the periphery, a subset of γδ T cells differentiates into effectors that produce IL-17 within the fetal thymus. We demonstrate here that intrathymic development of the naturally occurring IL-17-producing γδ T cells is independent of STAT3 and partly dependent on RORγt. Comparative gene-expression analysis identified Hes1, one of the basic helix-loop-helix proteins involved in Notch signaling, as a factor specifically expressed in IL-17-producing γδ T cells. Hes1 is critically involved in the development of IL-17-producing γδ T cells, as evidenced by their severe decrease in the thymi of Hes1-deficient fetal mice. Delta-like 4 (Dll4)-expressing stromal cells support the development of IL-17-producing γδ T cells in vitro. In addition, conditional Hes1 ablation in peripheral γδ T cells decreases their IL-17 production but not their IFN-γ production. These results reveal a unique differentiation pathway of IL-17-producing γδ T cells.     

A questionnaire-based survey on the etiopathogenesis of chronic constipation during a medical check-up in Japan

The study group of the Japanese Society of Gastroenterology released evidence-based clinical practice guidelines for chronic constipation (CC) in 2017, and irritable bowel syndrome (IBS) was treated as one of the causes of CC. We examined the differences in characteristics between IBS and non-IBS subjects with CC who underwent a medical check-up in Japan. A total of 10,658 subjects participated in this study, and we focused on 467 subjects who fulfilled the diagnostic criteria of CC using a questionnaire survey. The number of IBS subjects was 21, and they had sleep disorders, were more symptomatic (e.g., abdominal pain, abdominal bloating/distension, feeling stressed, annoyance, lack of motivation, fatigue upon waking, and feeling depressed), and had more episodes of sensation of incomplete evacuation and anorectal obstruction/blockage during defecation than non-IBS subjects. Furthermore, stool frequency of IBS subjects was significantly different from non-IBS subjects. Multivariate ordinal logistic regression analysis revealed that the factors associated with a higher stool frequency were IBS [odds ratio (OR), 2.46; 95% confidence interval (CI), 1.00–6.05; p = 0.049], male sex (OR, 1.97; 95% CI, 1.20–3.23; p = 0.007), and regular exercise (OR, 1.80; 95% CI, 1.05–3.07; p = 0.033). These findings suggest that IBS has unique characteristics in subjects with CC.     

microRNA‐99a‐5p induces cellular senescence in gemcitabine‐resistant bladder cancer by targeting SMARCD1

Patients with advanced bladder cancer are generally treated with a combination of chemotherapeutics, including gemcitabine, but the effect is limited due to acquisition of drug resistance. Thus, in this study, we investigated the mechanism of gemcitabine resistance. First, gemcitabine‐resistant cells were established and resistance confirmed in vitro and in vivo. Small RNA sequencing analyses were performed to search for miRNAs involved in gemcitabine resistance. miR‐99a‐5p, selected as a candidate miRNA, was downregulated compared to its parental cells. In gain‐of‐function studies, miR‐99a‐5p inhibited cell viabilities and restored sensitivity to gemcitabine. RNA sequencing analysis was performed to find the target gene of miR‐99a‐5p. SMARCD1 was selected as a candidate gene. Dual‐luciferase reporter assays showed that miR‐99a‐5p directly regulated SMARCD1. Loss‐of‐function studies conducted with si‐RNAs revealed suppression of cell functions and restoration of gemcitabine sensitivity. miR‐99a‐5p overexpression and SMARCD1 knockdown also suppressed gemcitabine‐resistant cells in vivo. Furthermore, β‐galactosidase staining showed that miR‐99a‐5p induction and SMARCD1 suppression contributed to cellular senescence. In summary, tumor‐suppressive miR‐99a‐5p induced cellular senescence in gemcitabine‐resistant bladder cancer cells by targeting SMARCD1.     

Effect of <Emphasis Type="Italic">Kaempferia parviflora</Emphasis> extract on knee osteoarthritis

Knee osteoarthritis (OA) is becoming more prevalent worldwide due to increases in the numbers of elderly and obese patients. Currently, pharmaceutical medicines used for the treatment of OA are for symptomatic therapy and therefore new therapeutic agents are needed. Kaempferia parviflora (KP) is a plant growing naturally in Southeast Asia and has various pharmacological effects including an anti-inflammatory effect, but no effect on OA has yet been reported. We therefore conducted a search for the effects KP and the active components of KP extract (KPE) exert on OA as well as its mechanism of action. Results from a study of KPE using the monoiodoacetic acid rat OA model revealed that KPE reduced the pain threshold and severity of osteoarthritic cartilage lesions. The mechanism of action and active components were then investigated using IL-1β-treated human knee-derived chondrocytes. KPE, as well as 5,7-dimethoxyflavone and 5,7,4′-trimethoxyflavone, which are key constituents of KPE and highly absorbable into the body, reduced the expression of matrix metalloproteinases (MMPs), which are the main extracellular matrix enzymes that degrade collagen within cartilage. As mentioned above, KPE acted to suppress OA and 5,7-dimethoxyflavone and 5,7,4′-trimethoxyflavone were shown to be involved as part of KPE’s mechanism that inhibits MMPs.     

Development of amperometric arsine gas sensor using gold-modified diamond electrodes

Amperometric gas sensor of arsine was developed using gold-modified diamond electrodes as the working electrodes. The detection method was conducted in high concentration of H₂SO₄. The reaction was declared based on two oxidation steps, involving oxidation of As³⁻ to As⁰ at mild potential in strong acid, followed by electrochemical oxidation of As⁰ to As³⁺ at gold-based electrodes. Linear calibration curve was observed in the concentration range of 5–50 ppb (r² = 0.985) with detection limit of ∼4.43 ppb (S/N = 3). Current decreasing of measurement was found ∼5.5% for 5 measurements. However, better stability was observed after the 5th measurement, indicated that the sensor could be applied for long time measurement. Investigation to several possible interference gasses, i.e. SO₂, H₂S, NO, NO₂, CO, O₃ and H₂ indicated no significant interference of the gas to arsine measurements.     

Age-related differences in maximum voluntary lip-closing force and ability to control lip-closing force

ObjectivesDeterioration of lip function in the elderly is a form of oral hypofunction. It is important to understand age-related changes in lip function to improve oral health. This study aimed to quantitatively compare the maximum lip-closing force (LCF) and the ability to control LCF during voluntary lip-pursing movements between elderly and young adults and clarify the influence of aging on both measurements.MethodsUsing a multidirectional LCF measurement system, we measured six-directional maximum LCFs (upper, upper right, lower right, lower, lower left, upper right) of 20 healthy elderly men (69.6 ± 4.2 years) and 20 healthy young men (25.1 ± 3.8 years). The ability to control the LCF in each direction was assessed based on the accuracy rate. The directional LCF and the ability to control LCF were compared between the elderly and young adults.ResultsThe maximum directional LCF in the elderly adults was significantly smaller than that in the young adults in three directions from the lower lip; moreover, the accuracy rate of the elderly adults was significantly lower than that of young adults in five of the six directions.ConclusionsOur findings suggest that the influence of aging on the accuracy of LCF may be different from that on muscle strength. Hypofunction of the lips due to aging may result not only from decreased muscle strength but also from reduced LCF accuracy.