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Chuan-Ming Xie Xiao-Yu Liu Kathy WY Sham Josie MY Lai Christopher HK Cheng 《Autophagy》2014,10(9):1495-1508
EEF2K (eukaryotic elongation factor-2 kinase), also known as Ca2+/calmodulin-dependent protein kinase III, functions in downregulating peptide chain elongation through inactivation of EEF2 (eukaryotic translation elongation factor 2). Currently, there is a limited amount of information on the promotion of autophagic survival by EEF2K in breast and glioblastoma cell lines. However, the precise role of EEF2K in carcinogenesis as well as the underlying mechanism involved is still poorly understood. In this study, contrary to the reported autophagy-promoting activity of EEF2K in certain cancer cells, EEF2K is shown to negatively regulate autophagy in human colon cancer cells as indicated by the increase of LC3-II levels, the accumulation of LC3 dots per cell, and the promotion of autophagic flux in EEF2K knockdown cells. EEF2K negatively regulates cell viability, clonogenicity, cell proliferation, and cell size in colon cancer cells. Autophagy induced by EEF2K silencing promotes cell survival and does not potentiate the anticancer efficacy of the AKT inhibitor MK-2206. In addition, autophagy induced by silencing of EEF2K is attributed to induction of protein synthesis and activation of the AMPK-ULK1 pathway, independent of the suppression of MTOR activity and ROS generation. Knockdown of AMPK or ULK1 significantly abrogates EEF2K silencing-induced increase of LC3-II levels, accumulation of LC3 dots per cell as well as cell proliferation in colon cancer cells. In conclusion, silencing of EEF2K promotes autophagic survival via activation of the AMPK-ULK1 pathway in colon cancer cells. This finding suggests that upregulation of EEF2K activity may constitute a novel approach for the treatment of human colon cancer. 相似文献
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SS Padala MA Kiresur A Ananthaneni VS Guduru HK Puneeth B Bhavana 《Biotechnic & histochemistry》2013,88(5):336-339
Toto bodies are eosinophilic structures that resemble the cells of the superficial cell layer of the oral epithelium. Toto bodies commonly are associated with inflammatory gingival and other mucosal lesions including pyogenic granuloma, irritational fibroma, epulis fissuratum, peripheral giant cell granuloma and inflammatory hyperplastic gingivitis. We evaluated staining characteristics of Toto bodies to establish their origin and to identify their significance in lesions. We investigated pyogenic granuloma, fibroma and leukoplakia with epithelium that exhibited Toto bodies after hematoxylin and eosin (staining. Sections were stained with Alcian blue, periodic acid-Schiff and Ayoub-Shklar stains to evaluate staining intensity and distribution. More Toto bodies were found in pyogenic granuloma than in fibroma and leukoplakia. PAS and Alcian blue staining exhibited mild intensity and did not establish the origin of Toto bodies. High staining intensity and diffuse distribution of stain was observed using Ayoub-Shklar staining, which indicated that Toto bodies originate from keratin. 相似文献
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Joyce M Ngoi Peter K Quashie Collins M Morang'a Joseph HK Bonney Dominic SY Amuzu Selassie Kumordjie Ivy A Asante Evelyn Y Bonney Miriam Eshun Linda Boatemaa Vanessa Magnusen Erasmus N Kotey Nicaise T Ndam Frederick Tei-Maya Augustina K Arjarquah Evangeline Obodai Isaac D Otchere Yaw Bediako Joe K Mutungi Lucas N Amenga-Etego John K Odoom Abraham K Anang George B Kyei Bright Adu William K Ampofo Gordon A Awandare 《Experimental biology and medicine (Maywood, N.J.)》2021,246(8):960
The confirmed case fatality rate for the coronavirus disease 2019 (COVID-19) in Ghana has dropped from a peak of 2% in March to be consistently below 1% since May 2020. Globally, case fatality rates have been linked to the strains/clades of circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within a specific country. Here we present 46 whole genomes of SARS-CoV-2 circulating in Ghana, from two separate sequencing batches: 15 isolates from the early epidemic (March 12–April 1 2020) and 31 from later time-points ( 25–27 May 2020). Sequencing was carried out on an Illumina MiSeq system following an amplicon-based enrichment for SARS-CoV-2 cDNA. After genome assembly and quality control processes, phylogenetic analysis showed that the first batch of 15 genomes clustered into five clades: 19A, 19B, 20A, 20B, and 20C, whereas the second batch of 31 genomes clustered to only three clades 19B, 20A, and 20B. The imported cases (6/46) mapped to circulating viruses in their countries of origin, namely, India, Hungary, Norway, the United Kingdom, and the United States of America. All genomes mapped to the original Wuhan strain with high similarity (99.5–99.8%). All imported strains mapped to the European superclade A, whereas 5/9 locally infected individuals harbored the B4 clade, from the East Asian superclade B. Ghana appears to have 19B and 20B as the two largest circulating clades based on our sequence analyses. In line with global reports, the D614G linked viruses seem to be predominating. Comparison of Ghanaian SARS-CoV-2 genomes with global genomes indicates that Ghanaian strains have not diverged significantly from circulating strains commonly imported into Africa. The low level of diversity in our genomes may indicate lower levels of transmission, even for D614G viruses, which is consistent with the relatively low levels of infection reported in Ghana. 相似文献
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Gráinne H Long Brian HK Chan Judith E Allen Andrew F Read Andrea L Graham 《BMC evolutionary biology》2008,8(1):128
Background
Explaining parasite virulence (harm to the host) represents a major challenge for evolutionary and biomedical scientists alike. Most theoretical models of virulence evolution assume that virulence arises as a direct consequence of host exploitation, the process whereby parasites convert host resources into transmission opportunities. However, infection-induced disease can be immune-mediated (immunopathology). Little is known about how immunopathology affects parasite fitness, or how it will affect the evolution of parasite virulence. Here we studied the effects of immunopathology on infection-induced host mortality rate and lifetime transmission potential – key components of parasite fitness – using the rodent malaria model, Plasmodium chabaudi chabaudi. 相似文献8.
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Intracellular calcium ([Ca2+]i) plays a pivotal role in neuronal ischemia. The aim of the present study was to investigate the routes of Ca2+ entry during non-excitotoxic oxygen and glucose deprivation (OGD) in acutely dissociated rat CA1 neurons. During OGD the fluo-3/fura red ratio reflecting [Ca2+]i increased rapidly and irreversibly. [Ca2+]i increased to the same degree in Ca2+ depleted medium, and also when both the ryanodine receptors (RyR) and the inositol 1,4,5-trisphosphate (IP3) receptors were blocked. When the endoplasmic reticulum (ER) Ca2+ stores were emptied with thapsigargin no increase in [Ca2+]i was observed independent of extracellular Ca2+. The OGD induced Ca2+ deregulation in isolated CA1 neurons is not prevented by removing Ca2+, or by blocking the IP3– or RyR receptors. However, when SERCA was blocked, no increase in [Ca2+]i was observed suggesting that SERCA dysfunction represents an important mechanism for ischemic Ca2+ overload. 相似文献
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Ajay K Mishra Amita Mishra HK Kehri Bechan Sharma Abhay K Pandey 《Annals of clinical microbiology and antimicrobials》2009,8(1):1-7