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51.
52.
Daniel J. Bolus Gobinath Shanmugam Madhusudhanan Narasimhan Namakkal S. Rajasekaran 《Cell stress & chaperones》2018,23(3):399-410
Heat-related illness and injury are becoming a growing safety concern for the farmers, construction workers, miners, firefighters, manufacturing workers, and other outdoor workforces who are exposed to heat stress in their routine lives. A primary response by a cell to an acute heat shock (HS) exposure is the induction of heat-shock proteins (HSPs), which chaperone and facilitate cellular protein folding and remodeling processes. While acute HS is well studied, the effect of repeated bouts of hyperthermia and the sustained production of HSPs in the myoblast-myotube model system of C2C12 cells are poorly characterized. In C2C12 myoblasts, we found that robust HS (43 °C, dose/time) significantly decreased the proliferation by 50% as early as on day 1 and maintained at the same level on days 2 and 3 of HS. This was accompanied by an accumulation of cells at G2 phase with reduced cell number in G1 phase indicating cell cycle arrest. FACS analysis indicates that there was no apparent change in apoptosis (markers) and cell death upon repeated HS. Immunoblot analysis and qPCR demonstrated a significant increase in the baseline expression of HSP25, 70, and 90 (among others) in cells after a single HS (43 °C) for 60 min as a typical HS response. Importantly, the repeated HS for 60 min each on days 2 and 3 maintained the elevated levels of HSPs compared to the control cells. Further, the continuous HS exposure resulted in significant inhibition of the differentiation of C2C12 myocytes to myotubes and only 1/10th of the cells underwent differentiation in HS relative to control. This was associated with significantly higher levels of HSPs and reduced expression of myogenin and Myh2 (P < 0.05), the genes involved in the differentiation process. Finally, the cell migration (scratch) assay indicated that the wound closure was significantly delayed in HS cells relative to the control cells. Overall, these results suggest that a repeated HS may perturb the active process of proliferation, motility, and differentiation processes in an in vitro murine myoblast-myotube model. 相似文献
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Muthiah Subramanian Sachin Yalagudri Daljeet Kaur Saggu Vickram Vignesh Rangaswamy Calambur Narasimhan 《Indian pacing and electrophysiology journal》2021,21(3):169-173
A 40 year old man with frequent PVCs with two different morphologies was referred for catheter ablation. Although initial mapping in the RVOT revealed fragmented potentials 20ms earlier than PVC2 onset with a good pace map score, ablation at this site was unsuccessful. Subsequent mapping in the LCC/NCC junction revealed that local ventricular activation preceded QRS onset by 30 and 28 ms for PVC1 and PVC2, respectively. Altering the pacing output at this site produced QRS morphologies similar to PVC1(low output,6mA) and PVC2(high output,15mA) with better pace map scores compared to RVOT. During high-output pacing, there was an increase in stim-QRS latency with decremental conduction. Ablation at this site was successful and suppressed both PVCs. 相似文献
55.
Danilo ML Prado Fabiana B Benatti Ana L de Sá-Pinto Ana P Hayashi Bruno Gualano Rosa MR Pereira Adriana ME Sallum Eloisa Bonfá Clovis A Silva Hamilton Roschel 《Arthritis research & therapy》2013,15(2):R46
Introduction
Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.Methods
Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO2, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise).Results
The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO2 (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.Conclusion
A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.Trial registration
NCT01515163. 相似文献56.
57.
Joao H. F. Pedra Sukanya Narasimhan Dubravko Rendić Kathleen DePonte Lesley Bell‐Sakyi Iain B. H. Wilson Erol Fikrig 《Cellular microbiology》2010,12(9):1222-1234
Fucosylated structures participate in a wide range of pathological processes in eukaryotes and prokaryotes. The impact of fucose on microbial pathogenesis, however, has been less appreciated in arthropods of medical relevance. Thus, we used the tick‐borne bacterium Anaplasma phagocytophilum– the agent of human granulocytic anaplasmosis to understand these processes. Here we show that A. phagocytophilum uses α1,3‐fucose to colonize ticks. We demonstrate that A. phagocytophilum modulates the expression of α1,3‐fucosyltransferases and gene silencing significantly reduces colonization of tick cells. Acquisition but not transmission of A. phagocytophilum was affected when α1,3‐fucosyltransferases were silenced during tick feeding. Our results uncover a novel mechanism of pathogen colonization in arthropods. Decoding mechanisms of pathogen invasion in ticks might expedite the development of new strategies to interfere with the life cycle of A. phagocytophilum. 相似文献
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W L Cody C Cai A M Doherty J J Edmunds J X He L S Narasimhan J S Plummer S T Rapundalo J R Rubin C A Van Huis Y St-Denis P D Winocour M A Siddiqui 《Bioorganic & medicinal chemistry letters》1999,9(17):2497-2502
Utilizing X-ray crystallography and molecular modeling, highly potent and selective peptidomimetic thrombin inhibitors have been designed containing a rigid piperazinedione template. The synthesis and biological activity of these compounds will be described. 相似文献
60.
W L Cody C E Augelli-Szafran K A Berryman C Cai A M Doherty J J Edmunds J X He L S Narasimhan J Penvose-Yi J S Plummer S T Rapundalo J R Rubin C A Van Huis L Leblond P D Winocour M A Siddiqui 《Bioorganic & medicinal chemistry letters》1999,9(17):2503-2508
Potent and selective thrombin inhibitors have been prepared with a piperazinedione template and L-amino acids. Likewise, incorporation of D-amino acids led to potent inhibitors with a novel mode of binding. Herein, the structure activity relationships and structural aspects of these compounds will be described. 相似文献