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Innate immune cells play important roles in tissue injury and repair following acute myocardial infarction (MI). Although reprogramming of macrophage metabolism has been observed during inflammation and resolution phases, the mechanistic link to macrophage phenotype is not fully understood. In this study, we found that myeloid-specific deletion (mKO) of mitochondrial complex I protein, encoded by Ndufs4, reproduced the proinflammatory metabolic profile in macrophages and exaggerated the response to LPS. Moreover, mKO mice showed increased mortality, poor scar formation, and worsened cardiac function 30 days after MI. We observed a greater inflammatory response in mKO mice on day 1 followed by increased cell death of infiltrating macrophages and blunted transition to the reparative phase during post-MI days 3-7. Efferocytosis was impaired in mKO macrophages, leading to lower expression of antiinflammatory cytokines and tissue repair factors, which suppressed the proliferation and activation of myofibroblasts in the infarcted area. Mitochondria-targeted ROS scavenging rescued these impairments, improved myofibroblast function in vivo, and reduced post-MI mortality in mKO mice. Together these results reveal a critical role of mitochondria in inflammation resolution and tissue repair via modulation of efferocytosis and crosstalk with fibroblasts. These findings have potential significance for post-MI recovery as well as for other inflammatory conditions. [ABSTRACT FROM AUTHOR]

Multi-temporal satellite images are available at very high revisit frequency, allowing the characterization of land-cover transitions and trajectories in greater detail. However, most change detection methods aim to capture a snapshot of land cover, for instance on an annual scale, which do not describe changes that occurred between the annual time points. In this study, we present a sub-annual change detection (SCD) approach to detect change dates from dense satellite time series. SCD estimates change dates by analyzing differences between two consecutive annual segments in two steps. To validate the proposed method, SCD was applied to real and simulated time series of MODIS 16-day NDVI from 2000 to 2012 for MODIS tile h11v05 and a sub-area in southeast Ohio, USA. The results show that SCD can successfully detect from dense time series the dates of changes representing land-cover transitions among various vegetated land covers. In addition, SCD can achieve comparable accuracy on the date of abrupt land-cover changes for the real time series tested in the study area when compared with the trend and seasonal changes identified by a Breaks for Additive Seasonal and Trend (BFAST) method. Future effort will be given to apply the proposed approach to various remotely sensed time series for other areas with extreme climates. [ABSTRACT FROM AUTHOR]

Bacterial flagellin is critical to mediate NLRC4 inflammasome-dependent caspase-1 activation. However, Shigella flexneri, a nonflagellated bacterium, and a flagellin (fliC) knockout strain of Pseudomonas aeruginosa are known to activate NLRC4 in bone marrow-derived macrophages. Furthermore, the flagellin-deficient fliC strain of P. aeruginosa was used in a mouse model of peritonitis to show the requirement of NLRC4. In a model of pulmonary P. aeruginosa infection, flagellin was shown to be essential for the induction of NLRC4-dependent caspase-1 activation. Moreover, in all P. aeruginosa studies, IL-Iβ production was attenuated in NLRC4-/- mice; however, the role of IL-1β in NLRC4-mediated innate immunity in the lungs against a nonflagellated bacterium was not explored. In this article, we report that NLRC4 is important for host survival and bacterial clearance, as well as neutrophil-mediated inflammation in the lungs following Klebsiella pneumoniae infection. NLRC4 is essential for K. pneumoniae-induced production of IL-1β, IL-17A, and neutrophil chemoattractants (keratinocyte cell-derived chemokines, MIP-2, and LPS-induced CXC chemokines) in the lungs. NLRC4 signaling in hematopoietic cells contributes to K. pneumoniaeinduced lung inflammation. Furthermore, exogenous IL-1β, but not IL-18 or IL-17A, partially rescued survival, neutrophil accumulation, and cytokine/chemokine expression in the lungs of NLRC4-/- mice following infectious challenge. Furthermore, IL-lRl-/- mice displayed a decrease in neutrophilic inflammation in the lungs postinfection. Taken together, these findings provide novel insights into the role of NLRC4 in host defense against K. pneumoniae infection. [ABSTRACT FROM AUTHOR]

Objective(s): Our previous study has showed that human amniotic mesenchymal stem cells (hAMSCs) transplantation improves neurological recovery after traumatic spinal cord injury (TSCI) in rats. However, less is known about the effects of exosomes derived from hAMSCs for TSCI. Here, we investigated whether hAMSCs-derived exosomes improve neurological recovery in TSCI rats and the underlying mechanisms. Materials and Methods: A rat traumatic spinal cord injury (TSCI) mode was established using a weight drop device. At 2 hr after TSCI, rats were administered either hAMSCs-derived exosomes or phosphate buffered saline via the tail vein. Locomotor recovery was evaluated by an open-field locomotor rating scale and gridwalk task. Spinal cord water content, hematoxylin and eosin (H&E) staining, Evans blue (EB) dye extravasation, immunofluorescence staining, and enzyme-linked immunosorbent were performed to elucidate the underlying mechanism. Results: hAMSCs-derived exosomes significantly reduced the numbers of ED1+ macrophages/ microglia and caspase-3+cells and decreased the levels of reactive oxygen species, myeloperoxidase activity and inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6 and interleukin-1β. In addition, hAMSCs-derived exosomes significantly attenuated spinal cord water content and Evans blue extravasation, and enhanced angiogenesis and axonal regeneration. Finally, hAMSCs-derived exosomes also significantly reduced the lesion volume, inhibited astrogliosis, and improved functional recovery. Conclusion: Taken together, these findings demonstrate that hAMSCs-derived exosomes have favourable effects on rats after acute TSCI, and that they may serve as an alternative cell-free therapeutic approach for treating acute TSCI. [ABSTRACT FROM AUTHOR]

Brassica rapa L., an edible and medical vegetable, has been traditionally used in Uyghur folk medicine to treat coughs and asthma in the Xinjiang Uygur Autonomous Region, China. In this study, we prepared an n-butanol subfraction of B. rapa L. (BRBS) and investigated the anti-tumor effect on A549 lung adenocarcinoma cells. The proliferation of A549 cells was significantly inhibited by BRBS treatment in a dose- and time-dependent manner. BRBS significantly induced cell cycle arrest and apoptosis in A549 cells through increased reactive oxygen species (ROS) production and mitochondrial dysfunction characterized by a reduction in mitochondrial membrane potential and the release of cytochrome c, which promoted caspase-3 and poly(ADP-ribose) polymerase processing. Moreover, BRBS significantly suppressed the migration of A549 cells in vitro. These results suggest that BRBS inhibited A549 cell proliferation through increased ROS production and the mitochondria-dependent apoptosis pathway. Consequently, BRBS might be a potential candidate for the treatment of lung cancer. [ABSTRACT FROM AUTHOR]

Glycyrrhiza uralensis is a Chinese herbal medicine with various bioactivities. Three fractions (GUPS-I, GUPS-II and GUPS-III) of G. uralensis polysaccharides (GUPS) were obtained with molecular weights of 1.06, 29.1, and 14.9 kDa, respectively. The monosaccharide compositions of GUPS-II and GUPS-III were similar, while that of GUPS-I was distinctively different. The results of scanning electron microscopy, FT-IR, and NMR suggested that GUPS-II and GUPS-III were flaky with a smooth surface and contained α- and β-glycosidic linkages, while GUPS-I was granulated and contained only ff-glycosidic linkages. Moreover, GUPS-II and GUPS-III exhibited better bioactivities on the maturation and cytokine production of dendritic cells (DCs) in vitro than that of GUPS-I. An in vivo experiment showed that only GUPS-II significantly enhanced the maturation of DCs. These results indicate that GUPS-II has the potential to be used in combination with cancer immunotherapy to enhance the therapeutic effect. [ABSTRACT FROM AUTHOR]

Schwannoma is a kind of slow-growing and rare neoplasm which poses diagnostic challenges owing to its clinical silence at the presentation period. Here, a schwannoma tumor was studied by multiphoton microscopy (MPM). Results indicate that MPM is capable of identifying a schwannoma tumor without the need for labels. Based on the two-photon excited fluorescence signals from cells and blood vessels and second harmonic generation signals from collagens, several significant features for the identification of schwannoma were visualized, including the Antoni A region, Antoni B region, pericellular collagen pattern, hyalinized vessels and hyalinized stroma. These conclusions highlight the potential of MPM taken as a diagnostic method for label-free identification of schwannoma tumors by these histopathologic characteristics. [ABSTRACT FROM AUTHOR]

Consistency of pituitary adenomas is an important variable in the surgical resection of these lesions. Preoperative evaluation of tumor consistency will be useful in guiding the operative approach. In this study, multiphoton microscopy (MPM) was used to evaluate the consistency of pituitary adenomas by combining qualitative and quantitative approaches. Three types of pituitary adenomas with different consistencies were first observed through the MPM imaging system to provide the cellular micro-structural details from fresh and unstained tissue samples. The morphologies of cell and collagen were clearly discerned by the endogenous second harmonic generation (SHG) signal from collagen and two-photon excited fluorescence (TPEF) signal from nicotinamide adenine dinucleotide and flavin adenine dinucleotide. Furthermore, RSHG/TPEF (the ratio of the maximum SHG signal over the maximum TPEF signal) and collagen content were calculated as quantitative parameters, which would provide an objective standard for evaluation of the tumor consistency. With the development of multiphoton endoscopy for in vivo imaging, MPM would provide the accurate estimation of the adenoma consistency and help neurosurgeons select appropriate surgical methods during surgery. [ABSTRACT FROM AUTHOR]