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51.
52.
Cindy Y. Kok Sindhu Igoor Renuka Rao Shinya Tsurusaki Tracy Titus Lauren M. MacLean Megha Kadian Rhys Skelton James J. H. Chong Eddy Kizana 《The journal of gene medicine》2024,26(3):e3681
Doxorubicin is a commonly used anti-cancer drug used in treating a variety of malignancies. However, a major adverse effect is cardiotoxicity, which is dose dependent and can be either acute or chronic. Doxorubicin causes injury by DNA damage, the formation of free reactive oxygen radicals and induction of apoptosis. Our aim is to induce expression of the multidrug resistance-associated protein 1 (MRP1) in cardiomyocytes derived from human iPS cells (hiPSC-CM), to determine whether this will allow cells to effectively remove doxorubicin and confer cardioprotection. We generated a lentivirus vector encoding MRP1 (LV.MRP1) and validated its function in HEK293T cells and stem cell-derived cardiomyocytes (hiPSC-CM) by quantitative PCR and western blot analysis. The activity of the overexpressed MRP1 was also tested, by quantifying the amount of fluorescent dye exported from the cell by the transporter. We demonstrated reduced dye sequestration in cells overexpressing MRP1. Finally, we demonstrated that hiPSC-CM transduced with LV.MRP1 were protected against doxorubicin injury. In conclusion, we have shown that we can successfully overexpress MRP1 protein in hiPSC-CM, with functional transporter activity leading to protection against doxorubicin-induced toxicity. 相似文献
53.
Mohammad Abass Ahanger Nisha Singh Tomar Megha Tittal Surendra Argal R. M. Agarwal 《Physiology and Molecular Biology of Plants》2017,23(4):731-744
Plants are confronted with a variety of environmenmtal stresses resulting in enhanced production of ROS. Plants require a threshold level of ROS for vital functions and any change in their concentration alters the entire physiology of plant. Delicate balance of ROS is maintained by an efficient functioning of intriguing indigenous defence system called antioxidant system comprising enzymatic and non enzymatic components. Down regulation of antioxidant system leads to ROS induced oxidative stress causing damage to important cellular structures and hence anomalies in metabolism. Proper mineral nutrition, in addition to other agricultural practices, forms an important part for growth and hence the yield. Potassium (K) is a key macro-element regulating growth and development through alterations in physiological and biochemical attributes. K has been reported to result into accumulation of osmolytes and augmentation of antioxidant components in the plants exposed to water and salt stress. In the present review an effort has been made to revisit the old findings and the current advances in research regarding the role of optimal, suboptimal and deficient K soil status on growth under normal and stressful conditions. Effect of K deficiency and sufficiency is discussed and the information about the K mediated antioxidant regulation and plant response is highlighted. 相似文献
54.
D. Nathan Jackson Bailey Davis Sandra M. Tirado Megha Duggal Jessica K. van Frankenhuyzen Deanna Deaville M. A. K. Wijesinghe Michael Tessaro J. T. Trevors 《Antonie van Leeuwenhoek》2009,96(4):377-394
Culture-based isolation and enumeration of bacterial human pathogens from environmental and human food samples has significant
limitations. Many pathogens enter a viable but non-culturable (VBNC) state in response to stress, and cannot be detected via
culturing methods. Favourable growth conditions with a source of energy and an ideal stoichiometric ratio of carbon to inorganic
elements can reverse this VBNC state. This review will focus on the bacterium Campylobacter jejuni which is a leading cause of food borne illness in the developed world. C. jejuni can enter a VBNC state in response to extremes in: pH, moisture content, temperature, nutrient content and salinity. Once
in a VBNC state, the organism must maintain an energy balance from substrate oxidation through respiration to grow, divide
and remain viable. The goal of this review is a greater understanding of how abiotic stress and thermodynamics influence the
viability of C. jejuni. 相似文献
55.
Krishan Kumar Megha Tharad Swetha Ganapathy Geeta Ram Azeet Narayan Jameel Ahmad Khan Rana Pratap Anamika Ghosh Sachin Kumar Samuchiwal Sushil Kumar Kuhulika Bhalla Deepti Gupta Krishnamurthy Natarajan Yogendra Singh Anand Ranganathan 《PloS one》2009,4(11)
Background
The secretory proteins of Mycobacterium tuberculosis (M. tuberculosis) have been known to be involved in the virulence, pathogenesis as well as proliferation of the pathogen. Among this set, many proteins have been hypothesized to play a critical role at the genesis of the onset of infection, the primary site of which is invariably the human lung.Methodology/Principal Findings
During our efforts to isolate potential binding partners of key secretory proteins of M. tuberculosis from a human lung protein library, we isolated peptides that strongly bound the virulence determinant protein Esat6. All peptides were less than fifty amino acids in length and the binding was confirmed by in vivo as well as in vitro studies. Curiously, we found all three binders to be unusually rich in phenylalanine, with one of the three peptides a short fragment of the human cytochrome c oxidase-3 (Cox-3). The most accessible of the three binders, named Hcl1, was shown also to bind to the Mycobacterium smegmatis (M. smegmatis) Esat6 homologue. Expression of hcl1 in M. tuberculosis H37Rv led to considerable reduction in growth. Microarray analysis showed that Hcl1 affects a host of key cellular pathways in M. tuberculosis. In a macrophage infection model, the sets expressing hcl1 were shown to clear off M. tuberculosis in much greater numbers than those infected macrophages wherein the M. tuberculosis was not expressing the peptide. Transmission electron microscopy studies of hcl1 expressing M. tuberculosis showed prominent expulsion of cellular material into the matrix, hinting at cell wall damage.Conclusions/Significance
While the debilitating effects of Hcl1 on M. tuberculosis are unrelated and not because of the peptide''s binding to Esat6–as the latter is not an essential protein of M. tuberculosis–nonetheless, further studies with this peptide, as well as a closer inspection of the microarray data may shed important light on the suitability of such small phenylalanine-rich peptides as potential drug-like molecules against this pathogen. 相似文献56.
57.
Blood samples of malaria patients (n = 30), selected based on the severity of parasitemia, were divided into low (LP), medium (MP) and high (HP) parasitemia, which represent increasing levels of the disease severity. Healthy subjects (n = 10) without any history of disease were selected as a control group. By processing of erythrocytes images their contours were obtained and from these the shape parameters area, perimeter and form factor were obtained. The gray level intensity was determined by scanning of erythrocyte along its largest diameter. A comparison of these with that of normal cells showed a significant change in shape parameters. The gray level intensity decreases with the increase of severity of the disease. The changes in shape parameters directly and gray level intensity variation inversely are correlated with the increase in parasite density due to the disease. 相似文献
58.
Larrubia JR Benito-Martínez S Miquel J Calvino M Sanz-de-Villalobos E González-Praetorius A Albertos S García-Garzón S Lokhande M Parra-Cid T 《Cellular immunology》2011,269(2):104-114
PD-1 molecule promotes anergy and IL-7 receptor (CD127) induces an anti-apoptotic effect on T cells. Correlation between PD-1/CD127 phenotype and hepatitis C virus (HCV)-specific CD8+ cell reactivity in resolved infection (RI) after treatment and persistent HCV-infection (PI) was analysed. Directly ex vivo, PD-1 and CD127 expression on HCV-specific CD8+ cells displayed a positive and negative correlation, respectively with viraemia. Proliferation after stimulation on PD-1−/CD127+ cells from RI cases was preserved, while it was impaired on PD-1+/CD127− cells from PI patients. PD1+/CD127+ population was observed in PI, and these maintained expansion ability but they did not target the virus. Frequency of PI cases with HCV-specific CD8+ cell proliferation increased after anti-PD-L1 and anti-apoptotic treatment. Bim expression on HCV-specific CD8+ cells from PI patients was enhanced. In conclusion, during chronic HCV infection non-reactive HCV-specific CD8+ cells targeting the virus are PD-1+/CD127−/Bim+ and, blocking apoptosis and PD-1/PD-L1 pathway on them enhances in vitro reactivity. 相似文献
59.
This study describes the changes in biochemical composition of follicular fluid during reproductive acyclicity in buffalo. A total of 73 pairs of ovaries collected from 26 reproductively acyclic and 47 reproductively cyclic buffaloes were used in the investigation. Ovarian follicles were classified into small (5.0-6.9 mm), medium (7.0-9.9 mm) and large (≥10.0 mm) sized categories depending upon their diameter. Follicular fluid was aspirated, processed and assayed for glucose, cholesterol, total protein, acid phosphatase and alkaline phosphatase. Glucose concentration was lesser in reproductively acyclic compared to cyclic buffaloes (19.3 ± 2.59 mg/dl compared to 32.6 ± 2.60 mg/dl; P<0.05), mainly due to difference in concentration between small sized follicles (12.4 ± 2.59 mg/dl compared to 28.0 ± 3.32 mg/dl; P<0.05). Cholesterol concentration was also lesser in reproductively acyclic compared to cyclic buffaloes (32.2 ± 2.14 mg/dl compared to 35.5 ± 2.16 mg/dl; P<0.05) and this was related to the lesser concentration found in large follicles (13.8 ± 3.45 mg/dl compared to 37.2 ± 4.10mg/dl; P<0.001). Total protein and acid phosphatase levels were not affected by either the reproductive cyclicity status or the follicular size (4.9 ± 1.07 g/dl to 6.0 ± 0.28 g/dl and 1.2 ± 0.17 U/dl to 2.5 ± 1.22 U/dl, respectively). An increased alkaline phosphatase activity was, however, observed in reproductively acyclic compared to cyclic buffaloes (27.5 ± 3.08 U/dl compared to 14.0 ± 1.09 U/dl; P<0.0001). In conclusion, results of the present study indicate an alteration in the biochemical composition of follicular fluid during reproductive acyclicity in buffalo. The findings provide further support to the notion that poor nutrition is an important factor triggering reproductive acyclicity in buffalo. 相似文献
60.
The heterocystous nitrogen-fixing cyanobacterium, Anabaena sp. strain PCC7120 displayed two superoxide dismutase (SOD) activities, namely FeSOD and MnSOD. Prolonged exposure of Anabaena PCC7120 cells to methyl viologen mediated oxidative stress resulted in loss of both SOD activities and induced cell lysis. The two SOD proteins were individually overexpressed constitutively in Anabaena PCC7120, by genetic manipulation. Under nitrogen-fixing conditions, overexpression of MnSOD (sodA) enhanced oxidative stress tolerance, while FeSOD (sodB) overexpression was detrimental. Under nitrogen supplemented conditions, overexpression of either SOD protein, especially FeSOD, conferred significant tolerance against oxidative stress. The results demonstrate a nitrogen status-dependent protective role of individual superoxide dismutases in Anabaena PCC7120 during oxidative stress. 相似文献