Despite the long-standing recognition that the immune response to acute myocardial injury contributes to adverse left ventricular (LV) remodeling, it has not been possible to effectively target this clinically. Using 2 different in vivo models of acute myocardial injury, we show that pirfenidone confers beneficial effects in the murine heart through an unexpected mechanism that depends on cardiac B lymphocytes. Naive hearts contained a large population of CD19+CD11b-CD23-CD21-IgD+IgMlo lymphocytes, and 2 smaller populations of CD19+CD11b+ B1a and B1b cells. In response to tissue injury, there was an increase in neutrophils, monocytes, macrophages, as well as an increase in CD19+ CD11b- B lymphocytes. Treatment with pirfenidone had no effect on the number of neutrophils, monocytes, or macrophages, but decreased CD19+CD11b- lymphocytes. B cell depletion abrogated the beneficial effects of pirfenidone. In vitro studies demonstrated that stimulation with lipopolysaccharide and extracts from necrotic cells activated CD19+ lymphocytes through a TIRAP-dependent pathway. Treatment with pirfenidone attenuated this activation of B cells. These findings reveal a previously unappreciated complexity of myocardial B lymphocytes within the inflammatory infiltrate triggered by cardiac injury and suggest that pirfenidone exerts beneficial effects in the heart through a unique mechanism that involves modulation of cardiac B lymphocytes.
In this paper, we present a comprehensive performance comparison of MPI implementations over InfiniBand, Myrinet and Quadrics. Our performance evaluation consists of two major parts. The first part consists of a set of MPI level micro-benchmarks that characterize different aspects of MPI implementations. The second part of the performance evaluation consists of application level benchmarks. We have used the NAS Parallel Benchmarks and the sweep3D benchmark. We not only present the overall performance results, but also relate application communication characteristics to the information we acquired from the micro-benchmarks. Our results show that the three MPI implementations all have their advantages and disadvantages. For our 8-node cluster, InfiniBand can offer significant performance improvements for a number of applications compared with Myrinet and Quadrics when using the PCI-X bus. Even with just the PCI bus, InfiniBand can still perform better if the applications are bandwidth-bound.
MiR‐329 has been proved to be a tumor suppressor gene in various malignancies, however, its role in osteosarcoma remains elusive. We found that miR‐329 is remarkably downregulated in osteosarcoma tissues and relates to advanced stages. MiR‐329 is able to inhibit osteosarcoma cell proliferation, promote apoptosis, and induce G0/G1 cell cycle arrest. In addition, miR‐329 also suppresses wound‐healing and migration ability of osteosarcoma cells and inhibits tumorigenicity in vivo. Rab10 was identified as a target of miR‐329 in osteosarcoma and mediates its biofunction. These findings may shed light to the understanding of tumor development in osteosarcoma.
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