Cellular Interplay between Cardiomyocytes and Nonmyocytes in Cardiac Remodeling

Cardiac hypertrophy entails complex structural remodeling involving rearrangement of muscle fibers, interstitial fibrosis, accumulation of extracellular matrix, and angiogenesis. Many of the processes underlying cardiac remodeling have features in common with chronic inflammatory processes. During these processes, nonmyocytes, such as endothelial cells, fibroblasts, and immune cells, residing in or infiltrating into the myocardial interstitium play active roles. This paper mainly addresses the functional roles of nonmyocytes during cardiac remodeling. In particular, we focus on the communication between cardiomyocytes and nonmyocytes through direct cell-cell interactions and autocrine/paracrine-mediated pathways

A comparison theorem for eigenvalues of the covariant Laplacian

AbstractWe present comparison theorems for the eigenvalues of the covariant Laplacian acting on the sections of vector bundle with the structure group U(N)

Administration of PDE4 Inhibitors Suppressed the Pannus-Like Inflammation by Inhibition of Cytokine Production by Macrophages and Synovial Fibroblast Proliferation

A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA). Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4) inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA) were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1β, TNF-α, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-α and IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation

血中ヘモグロビン濃度及び血中乳酸濃度に対する鉄摂取の影響

ヘモグロビン（Hb）の構成要素である鉄は、ヒトにとって不可欠な栄養素である。Hb は全身に酸素を供給する役割を担っており、鉄の摂取不足は、結果として筋肉への酸素供給の不足を引き起こす。一方、長距離走者のトレーニング効果を評価する生理的指標として血中乳酸濃度が主に用いられているが、鉄の摂取状況と安静時血中乳酸濃度の関係はほとんど明らかとなってない。そこで本研究では鉄欠乏、あるいは鉄過剰食を２週間与えた発育期ラットを用いて、Hb 濃度及び血中乳酸濃度に対する鉄摂取の影響を検討した。鉄欠乏群の体重変化は対照群と比し、小さくなる傾向がみられた。実験最終日の肝臓重量は有意（p＜０.０５）に低下し、腎臓、精巣も低下傾向を示した。一方、心臓重量は有意（p＜０.０１）に増加し、心肥大が認められた。欠乏群の Hb 濃度は経日的に減少し、実験最終日には貧血状態を示した。また、血中乳酸濃度は対照群に比較して約２.５倍の上昇が認められた。逆に、過剰群では Hb 濃度は６日目より著しく上昇し、血中乳酸濃度は低下傾向を示した。以上より、長距離走者における鉄の摂取不足は血中乳酸濃度の上昇をきたすため、身体持久力の低下を引き起こす可能性が大きく、身体能力を維持する上で日常の食生活における十分な鉄の摂取が不可欠であることが示唆された

Caspase-11 contributes to site-1 protease cleavage and SREBP1 activation in the inflammatory response of macrophages

Sterol regulatory element-binding proteins (SREBPs) are key transcription factors that control fatty acid and cholesterol metabolism. As the major SREBP isoform in macrophages, SREBP1a is also required for inflammatory and phagocytotic functions. However, it is insufficiently understood how SREBP1a is activated by the innate immune response in macrophages. Here, we show that mouse caspase-11 is a novel inflammatory activator of SREBP1a in macrophages. Upon LPS treatment, caspase-11 was found to promote the processing of site-1 protease (S1P), an enzyme that mediates the cleavage and activation of SREBP1. We also determined that caspase-11 directly associates with S1P and cleaves it at a specific site. Furthermore, deletion of the Casp4 gene, which encodes caspase-11, impaired the activation of S1P and SREBP1 as well as altered the expression of genes regulated by SREBP1 in macrophages. These results demonstrate that the caspase-11/S1P pathway activates SREBP1 in response to LPS, thus regulating subsequent macrophage activation

The Most-cited Articles in Dentistry Up to 2017

Introduction: Citation analysis is a suitable way to help us to identify research trends within a specific topic. The purpose of this study was to identify the 100 most cited articles in the field of dentistry published over the past 67 years. Methods: A comprehensive list of the most cited articles in dentistry was compiled using ISI Web of Science. The characteristics including number of citations, authors and journals were analyzed. Results: The database resulted in 3,831 articles with 100 or more citations published between 1950 and 2017. Most of these articles had been published by the Journal of Clinical Periodontology, followed by the Journal of Periodontology, and Journal of Dental Research. Sokransky SS followed by Lindhe J, Nyman S, and Genco RJ had the most number of citations. Conclusion: The most cited articles in the field of dentistry allows for advances in this field and also provide useful information for direct future studies and patient care

Bipolar localization of putative photoreceptor protein for phototaxis in thermophilic cyanobacterium Synechococcus elongatus

Funding Information: This work was supported in part by Grants-in-Aid for scientific research from the Ministry of Education, Science, Sports and Culture, Japan (no. 11640653 to K.M.).We identified an open reading frame from a database of the entire genome of Synechococcus elongatus, the product of which was very similar to pixJ1, which was proposed as photoreceptor gene for phototaxis in Synechocystis sp. PCC6803 [Yoshihara et al. (2000) Plant Cell Physiol. 41: 1299]. The mRNA of S. elongatus pixJ (SepixJ) was expressed in vivo as a part of the product of an operon. SePixJ was detected exclusively in the membrane fraction after cell fractionation. Immunogold labeling of SePixJ in ultra-thin sections indicated that it existed only in both ends of the rod-shaped cell; probably bound with the cytoplasmic membrane.publishersversionPeer reviewe

Two Ck1δ transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock.

Fustin, J.-M., Kojima, R., Itoh, K., Chang, H.-Y., Shiqi, Y., Zhuang, B., . . . Okamura, H. (2018). Two Ck1δ transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock. Proceedings of the National Academy of Sciences of the United States of America, 115(23), 5980-5985. doi:10.1073/pnas.172137111