Evaluation of Keishi-bukuryo-gan in a diabetic nephropathy model by comparison with aminoguanidine, butylated hydroxytoluene and captopril

桂枝茯苓丸の糖尿病性腎症に対する作用を,モデルラットを用い検討した。腎機能パラメーター,病理組織学的検討に加え,advanced glycation end products(AGEs)の蓄積,酸化ストレスに及ぼす影響を,アミノグアニジン(AGEs阻害薬),カプトプリル(アンジオテンシン変換酵素阻害薬),buthylated hydroxytoluene(BHT)(抗酸化剤)とで比較検討した。桂枝茯苓丸では腎機能(血清Cr,尿蛋白排泄量)と病理所見の有意な改善作用が認められ,糖尿病性腎症の進展を抑制することが実験的に明らかとなったが,このような腎保護作用はカプトプリルよりは弱く,アミノグアニジンと同程度であった。BHTには腎保護作用は認められなかった。腎組織中のAGEsの蓄積に対しては,桂枝茯苓丸,カプトプリル,BHTがいずれも有意に低下していたが,アミノグアニジンの作用よりは弱かった。腎組織中の脂質過酸化量はBHTで最も低下し,桂枝茯苓丸,カプトプリルでも有意に低下していた。一方,血中脂質過酸化に対しては,すべてにおいて有意な低下作用が認められたが,カプトプリルで最も強かった。このことから,桂枝茯苓丸はカプトプリルやアミノグアニジンとは異なった機序で糖尿病性腎症の進展を抑制している可能性が示された。 A study was done to investigate whether Keishi-bukuryo-gan can delay the progression of diabetic nephropathy in an experimentally induced diabetic nephropathy model. The efficacy of Keishi-bukuryo-gan against renal functional and structural changes and its influence on accumulation of advanced glycation end-products (AGEs) and oxidative stress were also examined by comparison with aminoguanidine (an AGEs inhibitor), butylated hydroxytoluene (BHT; an antioxidant) and captopril (an angiotensin converting enzyme inhibitor). Treatment with Keishi-bukuryo-gan for 10 weeks preserved renal function, as assessed in terms of proteinuria and serum creatinine, and prevented the morphological changes peculiar to diabetic nephropathy. However, its renoprotective activity was inferior to that of captopril and comparable to that of aminoguanidine. BHT lacked any of these effects. On the other hand, renal AGEs accumulation and oxidative stress were significantly enhanced in rats with untreated diabetic nephropathy compared with normal rats. Keishi-bukuryo-gan, captopril and BHT showed significant reduction of AGEs levels, but not to the extent shown by aminoguanidine. Renal lipid peroxidation levels were significantly lowered in the groups given Keishi-bukuryo-gan and captopril, but not to the extent shown in the rats given BHT. The reduction of serum lipid peroxidation levels by captopril was stronger than that by BHT. The effects of Keishi-bukuryo-gan and aminoguanidine on serum lipid peroxidation levels were similar to those of BHT. These results suggest that the pharmaceutical characteristics of Keishi-bukuryo-gan may differ from those of the other three medicines examined

Revisiting Aire and tissue-restricted antigens at single-cell resolution

The thymus is a highly specialized organ that plays an indispensable role in the establishment of self-tolerance, a process characterized by the “education” of developing T-cells. To provide competent T-cells tolerant to self-antigens, medullary thymic epithelial cells (mTECs) orchestrate negative selection by ectopically expressing a wide range of genes, including various tissue-restricted antigens (TRAs). Notably, recent advancements in the high-throughput single-cell analysis have revealed remarkable heterogeneity in mTECs, giving us important clues for dissecting the mechanisms underlying TRA expression. We overview how recent single-cell studies have furthered our understanding of mTECs, with a focus on the role of Aire in inducing mTEC heterogeneity to encompass TRAs

PHENOTYPIC ANALYSIS OF MICE DEFICIENT FOR Ly6C1/Ly6C2

Ly6C comprises two homologous components of Ly6C1 and Ly6C2, and the expression of either of the Ly6C molecules defines unique functional subsets of monocytes. Ly6C is also expressed by other immune cell types, including Aire-expressing medullary thymic epithelial cells. Because the role of Ly6C expression in determining the functional subsets remains unclear, we generated mice deficient for both Ly6C1 and Ly6C2 with CRISPR-Cas9–mediated deletion. Mice deficient for Ly6C1/Ly6C2 showed no major alterations in the subsets and function of monocyte and other immune cells, including the cells involved in the dextran sulfate sodium salt–induced colitis model. By generating the mice deficient for Ly6C1 alone, we have also investigated the expression pattern of Ly6C1 and Ly6C2 in immune cells. Except for medullary thymic epithelial cells and CD4 single-positive T cells, immune cells predominantly expressed Ly6C2. Thus, despite the importance as a marker with a unique differential expression pattern, the Ly6C molecules have no major impact on determining the functional subsets and maintaining immune homeostasis

Rotation in the NGC 1333 IRAS 4C Outflow

We report molecular line observations of the NGC 1333 IRAS 4C outflow in the Perseus Molecular Cloud with the Atacama Large Millimeter/Submillimeter Array. The CCH and CS emission reveal an outflow cavity structure with clear signatures of rotation with respect to the outflow axis. The rotation is detected from about 120 au up to about 1400 au above the envelope/disk mid-plane. As the distance to the central source increases, the rotation velocity of the outflow decreases while the outflow radius increases, which gives a flat specific angular momentum distribution along the outflow. The mean specific angular momentum of the outflow is about 100 au km/s. Based on reasonable assumptions on the outward velocity of the outflow and the protostar mass, we estimate the range of outflow launching radii to be 5-15 au. Such a launching radius rules out that this outflow is launched as an X-wind, but rather, it is more consistent to be a slow disk wind launched from relatively large radii on the disk. The radius of the centrifugal barrier is roughly estimated, and the role of the centrifugal barrier in the outflow launching is discussed.Comment: Accepted to ApJ. 29 pages, 8 figure

Subarcsecond Analysis of Infalling-Rotating Envelope around the Class I Protostar IRAS 04365+2535

Sub-arcsecond images of the rotational line emission of CS and SO have been obtained toward the Class I protostar IRAS 04365$+$2535 in TMC-1A with ALMA. A compact component around the protostar is clearly detected in the CS and SO emission. The velocity structure of the compact component of CS reveals infalling-rotating motion conserving the angular momentum. It is well explained by a ballistic model of an infalling-rotating envelope with the radius of the centrifugal barrier (a half of the centrifugal radius) of 50 AU, although the distribution of the infalling gas is asymmetric around the protostar. The distribution of SO is mostly concentrated around the radius of the centrifugal barrier of the simple model. Thus a drastic change in chemical composition of the gas infalling onto the protostar is found to occur at a 50 AU scale probably due to accretion shocks, demonstrating that the infalling material is significantly processed before being delivered into the disk.Comment: 15 March 2016, ApJ, accepte

Progress of Artificial Intelligence and Molecular Pathology

A pathological diagnosis that incorporates a molecular biology technique into a conventional pathological diagnosis based on morphology is called a molecular pathological diagnosis. Immunostaining, which detects proteins derived from oncogenes and tumor suppressor genes with specific antibodies, and FISH, which uses a fluorescently labeled nucleic acid probe to examine the amplification of a target gene, are already in clinical practice. In recent years, the application of genome analysis using a next-generation sequencer to pathological diagnosis has become available, and cancer genomic medicine has been rapidly expanding and evolving. In addition, new technologies such as liquid biopsy technology that detects proteins, DNA, microRNA, methylated DNA, etc. from samples that are less invasive at the time of collection, such as blood, are being incorporated into pathological diagnosis. The application of artificial intelligence（AI）is being studied around the world to reflect the diagnosis. This article introduces the application of rapid mass spectrometry（PESI-MS）to liquid biopsy and the development of diagnostic aids for urine cytology using AI

Verification of the Impact of Blood Glucose Level on Liver Carcinogenesis and the Efficacy of a Dietary Intervention in a Spontaneous Metabolic Syndrome Model

Metabolic syndrome (MS) is a risk factor for type 2 diabetes mellitus, vascular inflammation, atherosclerosis, and renal, liver, and heart diseases. Non-alcoholic steatohepatitis (NASH) is a progressive representative liver disease and may lead to the irreversible calamities of cirrhosis and hepatocellular carcinoma. Metabolic disorders such as hyperglycemia have been broadly reported to be related to hepatocarcinogenesis in NASH; however, direct evidence of a link between hyperglycemia and carcinogenesis is still lacking. Tsumura Suzuki Obese Diabetic (TSOD) mice spontaneously develop metabolic syndrome, including obesity, insulin resistance, and NASH-like liver phenotype, and eventually develop hepatocellular carcinomas. TSOD mice provide a spontaneous human MS-like model, even with significant individual variations. In this study, we monitored mice in terms of their changes in blood glucose levels, body weights, and pancreatic and liver lesions over time. As a result, liver carcinogenesis was delayed in non-hyperglycemic TSOD mice compared to hyperglycemic mice. Moreover, at the termination point of 40 weeks, liver tumors appeared in 18 of 24 (75%) hyperglycemic TSOD mice; in contrast, they only appeared in 5 of 24 (20.8%) non-hyperglycemic mice. Next, we investigated three kinds of oligosaccharide that could lower blood glucose levels in hyperglycemic TSOD mice. We monitored the levels of blood and urinary glucose and assessed pancreatic lesions among the experimental groups. As expected, significantly lower levels of blood and urinary glucose and smaller deletions of Langerhans cells were found in TSOD mice fed with milk-derived oligosaccharides (galactooligosaccharides and lactosucrose). At the age of 24 weeks, mild steatohepatitis was found in the liver but there was no evidence of liver carcinogenesis. Steatosis in the liver was alleviated in the milk-derived oligosaccharide-administered group. Taken together, suppressing the increase in blood glucose level from a young age prevented susceptible individuals from diabetes and the onset of NAFLD/NASH, as well as carcinogenesis. Milk-derived oligosaccharides showed a lowering effect on blood glucose levels, which may be expected to prevent liver carcinogenesis

Vertical Structure of the Transition Zone from Infalling Rotating Envelope to Disk in the Class 0 Protostar, IRAS04368+2557

We have resolved for the first time the radial and vertical structure of the almost edge-on envelope/disk system of the low-mass Class 0 protostar L1527. For that, we have used ALMA observations with a spatial resolution of 0.25$^{\prime\prime}$$\times$0.13$^{\prime\prime}$ and 0.37$^{\prime\prime}$$\times$0.23$^{\prime\prime}$ at 0.8 mm and 1.2 mm, respectively. The L1527 dust continuum emission has a deconvolved size of 78 au $\times$ 21 au, and shows a flared disk-like structure. A thin infalling-rotating envelope is seen in the CCH emission outward of about 150 au, and its thickness is increased by a factor of 2 inward of it. This radius lies between the centrifugal radius (200 au) and the centrifugal barrier of the infalling-rotating envelope (100 au). The gas stagnates in front of the centrifugal barrier and moves toward vertical directions. SO emission is concentrated around and inside the centrifugal barrier. The rotation speed of the SO emitting gas is found to be decelerated around the centrifugal barrier. A part of the angular momentum could be extracted by the gas which moves away from the mid-plane around the centrifugal barrier. If this is the case, the centrifugal barrier would be related to the launching mechanism of low velocity outflows, such as disk winds

Chemical survey toward young stellar objects in the Perseus molecular cloud complex

Chemical diversity of the gas in low-mass protostellar cores is widely recognized. In order to explore its origin, a survey of chemical composition toward 36 Class 0/I protostars in the Perseus molecular cloud complex, which are selected in an unbiased way under certain physical conditions, has been conducted with IRAM 30 m and NRO 45 m telescope. Multiple lines of C2H, c-C3H2 and CH3OH have been observed to characterize the chemical composition averaged over a 1000 au scale around the protostar. The derived beam-averaged column densities show significant chemical diversity among the sources, where the column density ratios of C2H/CH3OH are spread out by 2 orders of magnitude. From previous studies, the hot corino sources have abundant CH3OH but deficient C2H, their C2H/CH3OH column density ratios being relatively low. In contrast, the warm-carbon-chain chemistry (WCCC) sources are found to reveal the high C2H/CH3OH column density ratios. We find that the majority of the sources have intermediate characters between these two distinct chemistry types. A possible trend is seen between the C2H/CH3OH ratio and the distance of the source from the edge of a molecular cloud. The sources located near cloud edges or in isolated clouds tend to have a high C2H/CH3OH ratio. On the other hand, the sources having a low C2H/CH3OH ratio tend to be located in inner regions of the molecular cloud complex. This result gives an important clue to an understanding of the origin of the chemical diversity of protostellar cores in terms of environmental effects.Comment: Accepted for publication in ApJ

2002年以前日本人胃のHIP

Gastric hamartomatous inverted polyp （g-HIP） is rare gastric elevated lesion forming endophytic growth pattern which etiology remains unknown. G-HIP is said to be associated with gastric cancer and gastritis. We systematically reviewed Japanese g-HIP’s clinicopathological features reported before２００２. Japanese g-HIP amount to２０lesions,１８patients ; ７（３８．９％）were males and １１（６１．１％）were females. The mean age of patients was ６０．２ years old. The mean size of the lesions was２１．７millimeter. No of the polyp shape was Yamada type IV７, Yamada type I/flat elevation ６, Yamada type III ４ and Yamada II ３, respectively. The site of the lesions was Body１１, Cardia３, Fornix３and Antrum１, respectively. In１２described cases, accompanied lesion was Gastritis, Carcinoma, GCP, Hyperplastic polyp, GIST and remnant stomach due to ulcer. Of the submucosal shaped（Yamada type I/flat elevation）g-HIP,５０％ has GCP and６２．５％ has gastric cancer. The common feature of g-HIP was pyloric gland-like mucous gland proliferation and cystic dilatation in the H. pylori era of Japan