Phospholipase A2 in skin biology : new insights from gene-manipulated mice and lipidomics

The skin represents one of the tissues that are most profoundly influenced by alterations in the quality of lipids (lipoquality). Lipids not only constitute cellular membranes, but also serve as bioactive lipid mediators and essential components of the skin barrier. Phospholipase A2 (PLA2) enzymes supply fatty acids and lysophospholipids from membrane phospholipids, thereby variably affecting cutaneous homeostasis. Accordingly, perturbation of particular PLA2-driven lipid pathways can be linked to various forms of skin disease. In this review article, we highlight the roles of several PLA2 subtypes in cutaneous pathophysiology, as revealed by transgenic/knockout studies in combination with comprehensive lipidomics. We focus mainly on secreted PLA2 group IIF (sPLA2-IIF), which is associated with epidermal hyperplasia through mobilization of a unique lipid metabolite. We also address the distinct roles of sPLA2-IIE in hair follicles and sPLA2-IID in lymphoid immune cells that secondarily affect cutaneous inflammation, and provide some insights into species differences in sPLA2s. Additionally, we briefly overview the patatin-like phospholipase PNPLA1, which belongs to the Ca2+-independent PLA2 (iPLA2) family, as a key regulator of skin barrier function through catalysis of a unique non-PLA2 reaction. These knowledges on lipid metabolism driven by various PLA2 subtypes will open novel opportunities for translated studies toward diagnosis and therapy of human skin diseases

Proteinuria screening for children

Proteinuria screening for children.BackgroundIn Japan, urine screenings are performed annually at school for proteinuria and hematuria, but the effectiveness of this practice has not been clarified.MethodsUrine screening at school was performed, and we investigated the prevalence of urine abnormalities and incidence and the causes of their diseases. Therefore, we studied effectiveness of the school-screening program.ResultsThe prevalence of urinary abnormalities was 0.52% among elementary school children and 0.75% among junior high school children. The incidence was 0.24% among elementary school children. The school-screening program is effective in early detection of glomerulonephritis, so the number of new end-stage renal disease (ESRD) patients starting treatment has been changing.DiscussionThe school-screening program is effective for early detection of glomerulonephritis. In case of generations who underwent the school-screening program, the age that one develops ESRD has been rising year by year, and the number of new ESRD patients starting treatment before 20 years old is lower in Japan than in America.ConclusionThe school-screening program in Japan represents a highly effective mass screening technique

Bayesian inference to identify crystalline structures for XRD

Crystalline phase structure is essential for understanding the performance and properties of a material. Therefore, this study identified and quantified the crystalline phase structure of a sample based on the diffraction pattern observed when the crystalline sample was irradiated with electromagnetic waves such as X-rays. Conventional analysis necessitates experienced and knowledgeable researchers to shorten the list from many candidate crystalline phase structures. However, the Conventional diffraction pattern analysis is highly analyst-dependent and not objective. Additionally, there is no established method for discussing the confidence intervals of the analysis results. Thus, this study aimed to establish a method for automatically inferring crystalline phase structures from diffraction patterns using Bayesian inference. Our method successfully identified true crystalline phase structures with a high probability from 50 candidate crystalline phase structures. Further, the mixing ratios of selected crystalline phase structures were estimated with a high degree of accuracy. This study provided reasonable results for well-crystallized samples that clearly identified the crystalline phase structures

Secreted Phospholipase PLA2G2D Contributes to Metabolic Health by Mobilizing ω3 Polyunsaturated Fatty Acids in WAT

Polyunsaturated fatty acids (PUFAs) confer health benefits by preventing inflammation and obesity and by increasing thermogenesis in brown and beige adipocytes. As well as being supplied exogenously as nutrients, PUFAs are largely stored in membrane glycerophospholipids and released by phospholipase A2s (PLA2s). However, the molecular identity of the PLA2 subtype(s) that supplies endogenous PUFAs for metabolic homeostasis remains unclear. Here we show that PLA2G2D, a secreted PLA2 isoform, is constitutively expressed in M2-type macrophages in white adipose tissue (WAT) and shows a reciprocal correlation with obesity. Studies using global and macrophage-specific Pla2g2d-deficient mice reveal that PLA2G2D increases energy expenditure and thermogenesis by facilitating adipocyte browning, thereby ameliorating diet-induced obesity, insulin resistance, and WAT inflammation. Mechanistically, PLA2G2D constitutively supplies a pool of PUFAs, ω3 in particular, in WAT. Thus, our present findings underscore the contribution of the macrophage-driven PLA2G2D-ω3 PUFA axis to metabolic health

Activation of the PGE2–EP2 pathway as a potential drug target for treating eosinophilic rhinosinusitis

Current treatments of eosinophilic chronic rhinosinusitis (ECRS) involve corticosteroids with various adverse effects and costly therapies such as dupilumab, highlighting the need for improved treatments. However, because of the lack of a proper mouse ECRS model that recapitulates human ECRS, molecular mechanisms underlying this disease are incompletely understood. ECRS is often associated with aspirin-induced asthma, suggesting that dysregulation of lipid mediators in the nasal mucosa may underlie ECRS pathology. We herein found that the expression of microsomal PGE synthase-1 (encoded by PTGES) was significantly lower in the nasal mucosa of ECRS patients than that of non-ECRS subjects. Histological, transcriptional, and lipidomics analyses of Ptges-deficient mice revealed that defective PGE2 biosynthesis facilitated eosinophil recruitment into the nasal mucosa, elevated expression of type-2 cytokines and chemokines, and increased pro-allergic and decreased anti-allergic lipid mediators following challenges with Aspergillus protease and ovalbumin. A nasal spray containing agonists for the PGE2 receptor EP2 or EP4, including omidenepag isopropyl that has been clinically used for treatment of glaucoma, markedly reduced intranasal eosinophil infiltration in Ptges-deficient mice. These results suggest that the present model using Ptges-deficient mice is more relevant to human ECRS than are previously reported models and that eosinophilic inflammation in the nasal mucosa can be efficiently blocked by activation of the PGE2-EP2 pathway. Furthermore, our findings suggest that drug repositioning of omidenepag isopropyl may be useful for treatment of patients with ECRS

On the Food Habits of the Dragonets, Genus Callionymus : I. Food Habits of Callionymus punctatus LANGSDORFF

ネズミゴチの食性を明らかにするために,瀬戸内海中部の小型底曳網漁獲物の中から採集したネズミゴチ46個体の消化管内容物を調査し,さらに瀬戸内海中部の仙酔島の砂場および藻場のベントスとそこで採集した23個体のネズミゴチの消化管内容物をそれぞれ調査して次のような結果を得た。 1) ネズミゴチの餌生物は甲殻類のCumacea, Ostracoda, カニ類, Amphipoda, Copepoda,エビ類, Anomura, オキアミ類, Branchiopoda, Mycidaceaと巻貝,二枚貝および多毛類であるが,調査したネズミゴチの半数以上の個体に捕食されていたCumacea, Ostracodaおよび巻貝が重要な餌生物である。 2) ネズミゴチの成魚の餌生物組成は雌雄の間で差異がなく,また体長110～129mmと130～164mmとの間についても差異がない。 3) 仙酔島の砂場のベントスの組成と藻場のベントスの組成とは著しく相違しているのに対し,砂場と藻場の両者において,それぞれのベントスとそこで採集したネズミゴチの消化管内容物の組成は極めてよく類似していた。すなわち個体数において,砂場ではウミホタルが卓越してベントスの53%を占め,ネズミゴチの消化管内容物の中では79%を占めた。次いで砂場では貝類が多数出現して,それはベントスの28%を占めたのに対し,消化管内容物では8%を占めた。藻場ではホトトギスガイが卓越してベントスの87%を占め,消化管内容物の中では59%を占めた。 4) 藻場に生息していたネズミゴチの消化管内容物の59%を占め,ネズミゴチの最も重要な餌生物の一つであるホトトギスガイは仙酔島の藻場に比較的多く出現したアサヒアナハゼ,クジメおよびアイナメには殆んど捕食されていなかった。しかし藻場のネズミゴチに殆んど捕食されていないGammarideaはこれら3種の魚類によってしばしば捕食されており,それらの最も重要な餌生物であることがわかった。したがってネズミゴチは藻場ではアサヒアナハゼ,クジメおよびアイナメと食物について競合関係がない。The dragonets, genus Callionymus, is very common and found frequently with other demersal fish in the catch of a small trawl in the Seto Inland Sea. In this study, the food habits of "Nezumigochi", Callionymus punctatus LANGSDORFF, have been investigated through analysis of their gut contents and benthos of their habitat, Sensui-shima in the central region of the Seto Inland Sea (Fig. 1). The material of 46 individuals were caught by a small trawl net. They ranged from 110 mm to 163 mm in standard length (Fig. 2). To compair the diet of this fish with the benthos of their habitat, 14 individuals in the sand area and 9 individuals in the Zostra zone were sampled by spear, the benthos of the area were also sampled by quardrat method (Fig. 4 ). The general conclusions reached in this study are as follows: 1) The food organisms occurred in the guts were crustacea, bivalvia, gastropod a, and poly-chaeta. The crustacea contained the following organisms: branchiopoda, ostracoda, copepoda, mysidacea, cumacea, amphipoda, euphausiacea, macurura, anomura, brachyuran and stomatopoda. The main food organisms were cumacea for 72 % of the 46 stomachs, gastropoda for 65 %and ostracoda for 61 %. On the contrary, euphausiacea, macurura and anomura seemed to be preied on only occasionally, and branchiopoda, mysidacea and stomatopoda still more rarely (Table 1). 2) The difference between the diet of the male and female adult could not be statistically determined (Fig. 3). The diets of the specimens of 110-129mm and those of 130-164 mm were very similar. 3) The benthos of the sand area and that of the Zostera zone were clearly different in composition. Namely, in the benthos of the sand area Cypridina hilgendorfii (ostracoda) occupied 53%, but in the benthos of the Zostera zone Musculus (Musculista) senhousia (bivalvia) 87%. The composition of the food organisms and benthos sampled in each habitat were very similar to each other (Table 3). In the sand area, Cypridina hilgendorfii occupied 53% of the benthos but 79% in the food organisms. In the Zostera zone, Musculus (Musculista) senhousia occupied 87% of the benthos, but 59% in the food organisms (Table 2). 4) Musculus (Musculista) senhousia, the main food organisms of C. punctatus in the Zostera zone, were rarely taken in by the common inhabitant of the Zostera zone around Sensui-shima: Pseudoblennius cottoides, Agrammus agrammus and Hexagrammos otakii. But gammaridae that occupied only 6% in the food organisms of C. punctatus in the Zostera zone were often eaten by these 3 species mentioned above (Fig. 5). Accordingly, it is considered that C. punctatus is not in competition with these 3 species for prey

Cost-Effectiveness of Total Colonoscopy in Screening of Colorectal Cancer in Japan

Introduction. In Japan, the cost-effectiveness of total colonoscopy (TCS) for primary screening of colorectal cancer (CRC) is unclear. We compared the cost of identifying a patient with CRC using two primary screening strategies: TCS (strategy 1) and the immunochemical fecal test (FIT) (strategy 2). Materials and Methods. We retrospectively analyzed the TCS screening database at our institution from February 2004 to August 2010 (strategy 1, n = 15,348) and the Japanese nationwide survey of CRC screening in 2008 (strategy 2, n = 5,267,443). Results. 112 and 6,838 CRC cases were detected in strategies 1 and 2, costing 2,124,000 JPY and 1,629,000 JPY, respectively. The rate of earlier-stage CRC was higher in strategy 1. Conclusions. The cost was higher using TCS as a primary screening procedure. However, the difference was not excessive, and considering the increased rate of detecting earlier CRC, the use of TCS as a primary screening tool may be cost-effective

Relationship between sleep duration and clustering of metabolic syndrome diagnostic components

Sayuri Katano1, Yasuyuki Nakamura1,2, Aki Nakamura1, Yoshitaka Murakami3, Taichiro Tanaka4, Toru Takebayashi5, Akira Okayama6, Katsuyuki Miura2, Tomonori Okamura7, Hirotsugu Ueshima2, for HIPOP-OHP Research Group1Cardiovascular Epidemiology, Kyoto Women's University, Kyoto, Japan; 2Department of Health Science, Shiga University of Medical Science, Otsu, Japan; 3Department of Medical Statistics, Shiga University of Medical Science, Otsu, Japan; 4Department of Health Sciences, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Japan; 5Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan; 6The First Institute of Health Service, Japan Anti-Tuberculosis Association, Tokyo, Japan; 7Department of Preventive Cardiology, National Cardiovascular Center, Suita, JapanObjective: To examine the relation between sleep duration and metabolic syndrome (MetS).Methods: We examined the baseline data from 4356 healthy workers (3556 men and 800 women) aged 19–69 years. The physical activity of each participant was classified according to the International Physical Activity Questionnaire (IPAQ). We defined four components of MetS diagnostic components in this study as follows: 1) high blood pressure (BP) systolic BP [SBP] ≥ 130 mmHg, or diastolic BP [DBP] ≥ 85 mmHg, or on medication; 2) dyslipidemia (high-density lipoprotein-cholesterol concentration ,40 mg/dL, or triglycerides concentration ≥150 mg/dL, or on medication; 3) impaired glucose tolerance (fasting blood sugar concentration ≥ 110 mg/dL, or if less than 8 hours after meals ≥ 140 mg/dL), or on medication; and 4) overweight (body mass index [BMI] ≥ 25 kg/m2), or obesity (BMI ≥ 30 kg/m2). There were 680 participants in the group, with sleep duration <6 hours (15.6%).Results: Those who had 0–4 MetS diagnostic components, including overweight, accounted for 2159, 1222, 674, 255, and 46 participants, respectively, in the Poisson distribution. Poisson regression analysis revealed that independent factors that contributed to the number of MetS diagnostic components were being male (regression coefficient b = 0.752, P < 0.001), age (b = 0.026, P < 0.001), IPAQ classification (b = -0.238, P = 0.034), and alcohol intake (mL/day) (b = 0.018, P < 0.001). Short sleep duration (<6 hours) was also related to the number of MetS (b = 0.162, P < 0.001). The results of analyses with obesity component showed a similar association.Conclusion: Short sleep duration was positively associated with the number of MetS diagnostic components independent of other lifestyle habits.Keyword: short sleep duration, MetS diagnostic components, obesit