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41.
Sarika Gunjan Sunil Kumar Singh Tanuj Sharma Hemlata Dwivedi Bhavana Singh Chauhan Mohammad Imran Siddiqi Renu Tripathi 《Apoptosis : an international journal on programmed cell death》2016,21(9):955-964
Recent studies pioneer the existence of a novel programmed cell death pathway in malaria parasite plasmodium and suggest that it could be helpful in developing new targeted anti-malarial therapies. Considering this fact, we evaluated the underlying action mechanism of this pathway in mefloquine (MQ) treated parasite. Since cysteine proteases play a key role in apoptosis hence we performed preliminary computational simulations to determine binding affinity of MQ with metacaspase protein model. Binding pocket identified using computational studies, was docked with MQ to identify it’s potential to bind with the predicted protein model. We further determined apoptotic markers such as mitochondrial dysregulation, activation of cysteine proteases and in situ DNA fragmentation in MQ treated/untreated parasites by cell based assay. Our results showed low mitochondrial membrane potential, enhanced activity of cysteine protease and increased number of fragmented DNA in treated parasites compared to untreated ones. We next tested the involvement of oxidative stress in MQ mediated cell death and found significant increase in reactive oxygen species generation after 24 h of treatment. Therefore we conclude that apart from hemozoin inhibition, MQ is competent to induce apoptosis in plasmodium by activating metacaspase and ROS production. 相似文献
42.
Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library. 总被引:16,自引:0,他引:16
F S Wong J Karttunen C Dumont L Wen I Visintin I M Pilip N Shastri E G Pamer C A Janeway 《Nature medicine》1999,5(9):1026-1031
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed at an early age by an immune process that involves both CD4 and CD8 T lymphocytes. The identification of autoantigens in diabetes is very important for the design of antigen-specific immunotherapy. By screening a pancreatic islet cDNA library, we have identified the autoantigen recognized by highly pathogenic CD8 T cells in the non-obese diabetic mouse, one of the best animal models for human diabetes. This is the first identification, to our knowledge, of a CD8 T-cell epitope in an autoimmune disease. The peptide recognized by the cells is in the same region of the insulin B chain as the epitope recognized by previously isolated pathogenic CD4 T cells. This has very important implications for the potential use of insulin in preventative therapy. 相似文献
43.
Jurre Y. Siegers Vijaykrishna Dhanasekaran Ruopeng Xie Yi-Mo Deng Sarika Patel Vanra Ieng Jean Moselen Heidi Peck Ammar Aziz Borann Sarr Savuth Chin Seng Heng Asheena Khalakdina Michael Kinzer Darapheak Chau Philomena Raftery Veasna Duong Ly Sovann Ian G. Barr Erik A. Karlsson 《Journal of virology》2021,95(24)
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Yu Tao Sarika Chaudhari Parisa Yazdizadeh Shotorbani Yanfeng Ding Zhenglan Chen Ramesh Kasetti Gulab Zode Rong Ma 《The Journal of biological chemistry》2022,298(6)
Podocyte injury induced by hyperglycemia is the main cause of kidney dysfunction in diabetic nephropathy. However, the underlying mechanism is unclear. Store-operated Ca2+ entry (SOCE) regulates a diversity of cellular processes in a variety of cell types. Calpain, a Ca2+-dependent cysteine protease, was recently shown to be involved in podocyte injury. In the present study, we sought to determine whether increased SOCE contributed to high glucose (HG)–induced podocyte injury through activation of the calpain pathway. In cultured human podocytes, whole-cell patch clamp indicated the presence of functional store-operated Ca2+ channels, which are composed of Orai1 proteins and mediate SOCE. Western blots showed that HG treatment increased the protein abundance of Orai1 in a dose-dependent manner. Consistently, calcium imaging experiments revealed that SOCE was significantly enhanced in podocytes following HG treatment. Furthermore, HG treatment caused overt podocyte F-actin disorganization as well as a significant decrease in nephrin protein abundance, both of which are indications of podocyte injury. These podocyte injury responses were significantly blunted by both pharmacological inhibition of Orai1 using the small molecule inhibitor BTP2 or by genetic deletion of Orai1 using CRISPR-Cas9 lentivirus. Moreover, activation of SOCE by thapsigargin, an inhibitor of Ca2+ pump on the endoplasmic/sarcoplasmic reticulum membrane, significantly increased the activity of calpain, which was inhibited by BTP2. Finally, the calpain-1/calpain-2 inhibitor calpeptin significantly blunted the nephrin protein reduction induced by HG treatment. Taken together, our results suggest that enhanced signaling via an Orai1/SOCE/Calpain axis contributes to HG-induced podocyte injury. 相似文献
48.
Background: Many factors have been implicated in the etiology of cerebral venous sinus thrombosis (CVT). These include head injury, cancer, infections (sepsis, sinusitis, and mastoiditis), coagulopathies, pregnancy, systemic lupus erythematosus, and dehydration.Case summary: We present the case of a patient who received long-term estrogen therapy for ~15 years after feminizing genitoplasty. The patient experienced a CVT with an excellent clinical outcome. A similar case has not been reported in the literature.Conclusion: Because CVT may be associated with morbidity, mortality, and risks from the complications and treatments of the condition, further research is needed to clarify the factors that may contribute to the long-term risk of CVT in patients receiving long-term estrogen therapy after feminizing genitoplasty. 相似文献
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Context: Nickel oxide (NiO) nanoparticles (NPs) with appropriate surface chemistry have been widely used for their potential new applications in biomedical industry. Increased usage of these NPs enhances the chance of exposure of personnel involved in the work place.Objective: This study was designed to assess the ability of NiO NPs to cause biochemical alterations post-acute oral exposure in female Wistar rats.Materials and methods: Rats were administered with 125, 250, and 500?mg/kg doses of NiO NPs for haematological, biochemical, and histopathological studies. Biodistribution patterns of NiO NPs in female Wistar rats were also monitored.Results: NiO NPs caused significant (p?0.01) inhibition of RBC and brain AchE of treated rats at the high dose. Activation of the hepatotoxicity marker enzymes, aminotransferases, was recorded in serum and liver, whereas inhibition was observed in kidney. The activity of antioxidant enzymes was also altered by NiO NPs in a dose-dependent manner and found to be significant at the high dose of exposure.Conclusions: This study revealed that exposure to nanosized NiO particles at acute doses may cause adverse changes in animal biochemical profiles. Further, the in vivo studies on toxicity evaluation help in biomonitoring of the potential contaminants. 相似文献
50.
Supriya Purru Sarika Sahu Saurabh Rai A. R. Rao K. V. Bhat 《Physiology and Molecular Biology of Plants》2018,24(5):929-937
Molecular breeding in sesame is still at infancy due to limited number of microsatellite markers available and the low level of polymorphism exhibited by them. Therefore, whole genome sequencing was used for development of microsatellite markers so as to ensure availability of substantial number of polymorphic markers for use in marker assisted breeding programs. Whole genome sequencing of sesame variety ‘Swetha’ was done using Illumina paired-end sequencing and Roche 454 shotgun sequencing technologies (GCA_000975565.1 in GenBank). ‘GinMicrosatDb’, a genome-wide microsatellite marker database has been developed using the whole genome sequence data of sesame variety ‘Swetha’. The database consists of microsatellites localized on both linkage groups and scaffolds with their genomic co-ordinates. It provides five sets of forward and reverse primers for each of the microsatellite loci along with the flanking sequences, primer GC content, product size and melting temperature etc. The distribution of microsatellites can be viewed and selected through a genome browser as well as through a physical map. The newly identified microsatellite markers are expected to help sesame breeders in developing marker tags for traits of economic importance thereby bringing about greater efficiency in marker-assisted selection programs. 相似文献