Morphine pretreatment reduces myocardial ischemiareperfusion injury in heart failure rats via GSK-3β/Cx43 signaling proteins and apoptosis-related gene, Bcl-2/Bax

Purpose: To investigate the effect of morphine preconditioning on myocardial ischemia reperfusion injury in heart failure rats, and the  mechanism(s) of action involvedMethods: Seventy-two healthy male Sprague-Dawley rats were assigned to 4 groups: sham, model, morphine-preconditioning and SB203580 inhibitor groups, each with 18 rats. The expressions of P-p38, p-glycogen synthetase kinase-3, and p-gap junction protein 43 in rat myocardial cells were assayed by Western blotting. The mRNA expression levels of Bcl-2 and Bax, and Bcl-2/Bax were determined using real-time fluorescence quantitative PCR.Results: The expression levels of P-p38, p-glycogen synthetase kinase-3, p-gap junction protein 43, Bcl-2 mRNA and Bcl-2/Bax were significantly higher in the pretreatment group than in the model group, while Bax mRNA was significantly lower (p < 0.05). Moreover, the mRNA expression levels of P-p38, pglycogen synthetase kinase-3, p-gap junction protein, Bcl-2, and Bcl-2/Bax in inhibitor-treated rats decreased significantly, when compared to the values for pretreatment rats; furthermore, Bax mRNA was markedly upregulated (p < 0.05).Conclusion: Morphine preconditioning significantly inhibits the expressions of GSK-3β and Cx43 signaling proteins, as well as apoptosis-related gene, Bcl-2 and Bax. In addition, it inhibits the apoptosis of rat cardiomyocytes, and reduces myocardial injury, after ischemia reperfusion, via activation of the p38 MARK signaling pathway. This provides a new strategy for clinical reduction of myocardial injury after ischemia-reperfusion. Keywords: Morphine, Pretreatment, GSK-3β/Cx43 signaling protein, Bcl-2/Bax, Heart failure, Ischemiareperfusion injur

Effect of dexmedetomidine post-treatment on oxidative stress and apoptosis induced by myocardial ischemiareperfusion injury in rats

Purpose: To study the effect of dexmedetomidine on myocardial ischemia-reperfusion injury (MI/RI)- induced imbalance on oxidant-prooxidant status and apoptotic changes in rats. Methods: Ninety (90) male Wistar rats were randomly divided into three groups – sham, model and post-treatment. In model rats, the anterior descending branch of the left coronary artery was ligated for 25 min, prior to their being subjected to reperfusion for 2 h. Rats in the post-treatment group were subjected to ligation at the anterior descending branch of the left coronary artery for 25 min, but they were intravenously injected with dexmedetomidine at a dose of 10 μg/kg prior to reperfusion. There was no ligation in the sham group. Malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were assayed. Lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) levels were also evaluated. Apoptosis was measured with TdT-mediated dUTP nick end labeling (TUNEL) assay. Results: Compared with the sham group, MDA level in the model group was significantly rose, while SOD and GSH-Px activities were markedly decreased (p < 0.05). Moreover, there were higher LDH and CK-MB activities in model rats than in the sham rats, but they were significantly lower in the posttreatment group than in the model group (p < 0.05). Apoptosis was higher in model rats than in sham operation rats, but was markedly decreased in post-treatment rats than in model rats (p < 0.05). Conclusion: Post-treatment with dexmedetomidine exerts myocardial protective effect via significant reduction in oxidative stress-induced myocardial injury and apoptosis. Keywords: Dexmedetomidine, Myocardial ischemia-reperfusion injury, Antioxidant status, Programmed cell deat

Mesenchymal Stem Cell-based Cytotherapy for Osteoarthritis Management: State of the Art

Osteoarthritis (OA), a principal and challenging disorder of articular cartilage, has been regarded as the most frequent and prevalent chronic disease of degenerative joints, which is caused by multiple factors including aging, trauma, overweight, joint deformity and congenital abnormality, together with the increase in life expectancy. In spite of considerable improvements that have been obtained by conducting multidisciplinary therapies such as surgical procedures and anti-inflammatory drugs, the pathogenesis and efficacy of OA with functional losses and degeneration are still elusively complicated for ascertainment. Mesenchymal stem/stromal cells (MSCs), also termed as multipotent mesenchymal progenitor/precursor cells, skeletal stem cells, or medicinal signaling cells, are heterogeneous cell populations with hematopoietic-supporting and immunomodulatory properties, together with multilineage differentiation property. For decades, investigators have illuminated the application of the advantaged and promising sources with/without remarkable biomaterials for the treatment of recurrent and refractory disorders including OA. In this chapter, we mainly concentrate on the current progress of MSC-based cytotherapy in both preclinical study and clinical practice as well as the promising prospective and critical challenges in the field, which will conformably benefit the administration of OA in future

Natural Killer Cells for Cancer Immunotherapy: Opportunities and Challenges

Natural killer (NK) cells are advantaged immune cells and play a pivotal role in both innate and adaptive immune responses. To date, autogenous and allogenic NK cells have been generated from a variety of origins, including perinatal blood (e.g., umbilical cord blood and placental blood), peripheral blood, and even stem cells (hematopoietic stem cells and pluripotent stem cells). NK cells function mainly via antibody-dependent cell-mediated cytotoxicity (ADCC), direct cytolytic effect, and paracrine effects (e.g., IFN-γ, GM-CSF, granzyme, and perforin). Distinguishing from the adaptive immunizing cells (e.g., T and B lymphocytes), NK cells, and chimeric antigen receptor-transduced NK (CAR-NK), cell-based cytotherapy is adequate to fulfill the biofunction of eliminating pathogenic infection, combating hematological malignancies and metastatic solid tumors, and delaying aging. In this chapter, we mainly focus on the state-of-the-art renewal of NK cell-based cytotherapy for cancer immunosurveillance and immunotherapy from the view of high-efficient in vitro preparation (e.g., candidate cell sources and ex vivo cultivation) and preclinical and clinical investigation. Furthermore, we also figure out the promising prospects and the concomitant challenges of NK cell-based remedies for cancer management in future, which will collectively benefit the development of NK cell-based cancer immunotherapy in future

The linkages with fires, vegetation composition and human activity in response to climate changes in the Chinese Loess Plateau during the Holocene

Holocene paleo-records of the Chinese Loess Plateau loess-soil profiles were used to reconstruct wildfire patterns and landscape evolution. We examine black carbon and charcoal influx, combined with the Magnetic susceptibility, delta C-13 values of soil organic matter, pollen counts and other paleo-environmental proxies to discuss interactions with biomass-climate during the Holocene. The history of fires from the charcoal and black carbon (BC, char and soot) influx at the two sites demonstrates a transition from climate-controlled low amplitude variations with peaks during the Early and Middle Holocene (11-3.1kyearsB.P.) to higher amplitude variability in fire occurrence decoupled from climate and tied to human activities during the Late Holocene (3.1-0kyearsB.P.). The difference in fire patterns was attributed to regional effective moisture and human land use over the entre Loess Plateau; meanwhile, fire activities observed during the Holocene are consistent with variations in vegetation composition inferred from delta C-13 values in soil organic matter, pollen counts, and paleoclimate proxies. Regional wildfires rarely occurred on the desert steppe dominated by a weedy C-3 taxon (Artemisia, Compositae, and Chenopodiaceae dominated)during the late glacial period. A limited biomass would not meet fire propagation in the extreme colder and drier environment of the Loess Plateau during those periods, though. As the climate became ameliorated during the early Holocene, there was an increasing biomass and a sufficient contribution do to high fuel accumulation from C-4 taxon (Gramineae). As the middle Holocene progressed toward warmer and wetter conditions, fire events were less frequent on the steppe and forest-steppe (e.g. expansion of trees C-3,C- Quercus, Corylus) of the Loess Plateau. Subsequently, the number of local and regional fire events have largely increased with the colder and drier climate conditions (e.g. expansion of C-3 weedy), which have been decoupling with intensive anthropogenic burning for farming since the past 3kyr. These data suggests that the regional fire patterns vary strongly along environmental gradients in the effective moisture and regional fuel availability as well as the spatial and temporal distributions of Neolithic burning practices over the Loess Plateau in response to the weakening East Asian monsoon during the Holocene

Vitexin attenuates smoke inhalation induced acute lung injury in rats by inhibiting oxidative stress via PKC β/p66Shc signaling pathway

Purpose: To investigate the protective effect of vitexin on smoke inhalation-induced acute lung injury (SI-ALI), and the underlying mechanism of action.Methods: The ALI rat model was established by inhalation of smoke in a closed smoke chamber. Survival rate, arterial blood gas analysis, wet-to-dry weight ratio of lung tissues, bronchoalveolar lavage fluid protein concentration, lung tissue histology, and oxidative stress and inflammation level were evaluated. Expressions of protein kinase C β (PKC β), p66Shc, and phosphorylated p66Shc were determined by western blot or quantitative reverse transcription-polymerase chain reaction.Results: Compared with smoke inhalation group, vitexin alleviated the decline in arterial partial pressure of oxygen (p < 0.05), reduced lung tissue exudation and pathological lung tissue damage, inhibited the expression of PKC β/p66Shc signaling pathway proteins, downregulated the level of oxidative stress and inflammation, and ultimately improved the survival rate in SI-ALI rats (p < 0.05).Conclusion: Vitexin attenuates SI-ALI in rats by alleviating oxidative stress via inhibition of PKC β/p66Shc signaling pathway. Thus, this compound is a potential agent for the treatment of SI-ALI

Activity Analysis, Summarization, and Visualization for Indoor Human Activity Monitoring

DOI 10.1109/TCSVT.2008.2005612In this work, we study how continuous video monitoring and intelligent video processing can be used in eldercare to assist the independent living of elders and to improve the efficiency of eldercare practice. More specifically, we develop an automated activity analysis and summarization for eldercare video monitoring. At the object level, we construct an advanced silhouette extraction, human detection and tracking algorithm for indoor environments. At the feature level, we develop an adaptive learning method to estimate the physical location and moving speed of a person from a single camera view without calibration. At the action level, we explore hierarchical decision tree and dimension reduction methods for human action recognition. We extract important ADL (activities of daily living) statistics for automated functional assessment. To test and evaluate the proposed algorithms and methods, we deploy the camera system in a real living environment for about a month and have collected more than 200 hours (in excess of 600 G bytes) of activity monitoring videos. Our extensive tests over these massive video datasets demonstrate that the proposed automated activity analysis system is very efficient.This work was supported in part by National Institute of Health under Grant 5R21AG026412