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181.
182.
Sujatha Venkataraman Irina Alimova Rong Fan Peter Harris Nicholas Foreman Rajeev Vibhakar 《PloS one》2010,5(6)
Background
MicroRNAs (miRNAs) are a class of short non-coding RNAs that regulate cell homeostasis by inhibiting translation or degrading mRNA of target genes, and thereby can act as tumor suppressor genes or oncogenes. The role of microRNAs in medulloblastoma has only recently been addressed. We hypothesized that microRNAs differentially expressed during normal CNS development might be abnormally regulated in medulloblastoma and are functionally important for medulloblastoma cell growth.Methodology and Principal Findings
We examined the expression of microRNAs in medulloblastoma and then investigated the functional role of one specific one, miR-128a, in regulating medulloblastoma cell growth. We found that many microRNAs associated with normal neuronal differentiation are significantly down regulated in medulloblastoma. One of these, miR-128a, inhibits growth of medulloblastoma cells by targeting the Bmi-1 oncogene. In addition, miR-128a alters the intracellular redox state of the tumor cells and promotes cellular senescence.Conclusions and Significance
Here we report the novel regulation of reactive oxygen species (ROS) by microRNA 128a via the specific inhibition of the Bmi-1 oncogene. We demonstrate that miR-128a has growth suppressive activity in medulloblastoma and that this activity is partially mediated by targeting Bmi-1. This data has implications for the modulation of redox states in cancer stem cells, which are thought to be resistant to therapy due to their low ROS states. 相似文献183.
Kadapakkam Nandabalan Sangeetha Sundaresan Sujatha Velusamy Shanmuganathan Muthusamy Singaravel Anand Nirmal Nithya Devadasan Velmurugan Arun Balakrishnan Baddireddi Subhadra Lakshmi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2010
Background
The present study focuses on identifying and developing an anti-diabetic molecule from plant sources that would effectively combat insulin resistance through proper channeling of glucose metabolism involving glucose transport and storage.Methods
Insulin-stimulated glucose uptake formed the basis for isolation of a bioactive molecule through column chromatography followed by its characterization using NMR and mass spectroscopic analysis. Mechanism of glucose transport and storage was evaluated based on the expression profiling of signaling molecules involved in the process.Results
The study reports (i) the isolation of a bioactive compound 3β-taraxerol from the ethyl acetate extract (EAE) of the leaves of Mangifera indica (ii) the bioactive compound exhibited insulin-stimulated glucose uptake through translocation and activation of the glucose transporter (GLUT4) in an IRTK and PI3K dependent fashion. (iii) the fate of glucose following insulin-stimulated glucose uptake was ascertained through glycogen synthesis assay that involved the activation of PKB and suppression of GSK3β.General significance
This study demonstrates the dual activity of 3β-taraxerol and the ethyl acetate extract of Mangifera indica as a glucose transport activator and stimulator of glycogen synthesis. 3β-taraxerol can be validated as a potent candidate for managing the hyperglycemic state. 相似文献184.
Deep Prakash Akhil MS Buddidhathi Radhika Radhika Venkatesan Sreekanth H Chalasani Varsha Singh 《The EMBO journal》2021,40(13)
Animals possess conserved mechanisms to detect pathogens and to improve survival in their presence by altering their own behavior and physiology. Here, we utilize Caenorhabditis elegans as a model host to ask whether bacterial volatiles constitute microbe‐associated molecular patterns. Using gas chromatography–mass spectrometry, we identify six prominent volatiles released by the bacterium Pseudomonas aeruginosa. We show that a specific volatile, 1‐undecene, activates nematode odor sensory neurons inducing both flight and fight responses in worms. Using behavioral assays, we show that worms are repelled by 1‐undecene and that this aversion response is driven by the detection of this volatile through AWB odor sensory neurons. Furthermore, we find that 1‐undecene odor can induce immune effectors specific to P. aeruginosa via AWB neurons and that brief pre‐exposure of worms to the odor enhances their survival upon subsequent bacterial infection. These results show that 1‐undecene derived from P. aeruginosa serves as a pathogen‐associated molecular pattern for the induction of protective responses in C. elegans. 相似文献
185.
Vipin S. Rana Sonam Popli Gunjan K. Saurav Karuna Yadav Ankit Kumar Sujatha Sunil Narendra Kumar Om P. Singh Krishnamurthy Natarajan Raman Rajagopal 《Cellular microbiology》2020,22(7)
Dengue virus (DENV) comprises of four serotypes (DENV‐1 to ‐4) and is medically one of the most important arboviruses (arthropod‐borne virus). DENV infection is a major human health burden and is transmitted between humans by the insect vector, Aedes aegypti. Ae. aegypti ingests DENV while feeding on infected humans, which traverses through its gut, haemolymph and salivary glands of the mosquito before being injected into a healthy human. During this process of transmission, DENV must interact with many proteins of the insect vector, which are important for its successful transmission. Our study focused on the identification and characterisation of interacting protein partners in Ae. aegypti to DENV. Since domain III (DIII) of envelope protein (E) is exposed on the virion surface and is involved in virus entry into various cells, we performed phage display library screening against domain III of the envelope protein (EDIII) of DENV‐2. A peptide sequence showing similarity to lachesin protein was found interacting with EDIII. The lachesin protein was cloned, heterologously expressed, purified and used for in vitro interaction studies. Lachesin protein interacted with EDIII and also with DENV. Further, lachesin protein was localised in neuronal cells of different organs of Ae. aegypti by confocal microscopy. Blocking of lachesin protein in Ae. aegypti with anti‐lachesin antibody resulted in a significant reduction in DENV replication. 相似文献
186.
Single visit endodontics offers many advantages over multi visit treatment. Therefore, it is of interest to assess the preference of single visit over multiple visit root canals. We used 86,000 patient records and selected 9017 records matching the inclusion criteria for the analysis using statistical tools (Chi square test at p value <0.05). Data shows that people between 26 to 45 years are often affected with dental caries. Available data is biased towards multi visits rather than single visit regardless number of canals. 相似文献
187.
Wojciech G. Lesniak Amar Jyoti Manoj K. Mishra Nicolette Louissaint Roberto Romero Diane C. Chugani Sujatha Kannan Rangaramanujam M. Kannan 《Analytical biochemistry》2013
An imbalance in tryptophan (TRP) metabolites is associated with several neurological and inflammatory disorders. Therefore, analytical methods allowing for simultaneous quantification of TRP and its major metabolites would be highly desirable, and may be valuable as potential biomarkers. We have developed a HPLC method for concurrent quantitative determination of tryptophan, serotonin, 5-hydroxyindoleacetic acid, kynurenine, and kynurenic acid in tissue and fluids. The method utilizes the intrinsic spectroscopic properties of TRP and its metabolites that enable UV absorbance and fluorescence detection by HPLC, without additional labeling. The origin of the peaks related to analytes of interest was confirmed by UV–Vis spectral patterns using a PDA detector and mass spectrometry. The developed methods were validated in rabbit fetal brain and amniotic fluid at gestational day 29. Results are in excellent agreement with those reported in the literature for the same regions. This method allows for rapid quantification of tryptophan and four of its major metabolites concurrently. A change in the relative ratios of these metabolites can provide important insights in predicting the presence and progression of neuroinflammation in disorders such as cerebral palsy, autism, multiple sclerosis, Alzheimer disease, and schizophrenia. 相似文献
188.
Venkateshwar Rao Gummadi Sujatha Rajagopalan Chung-Yeng Looi Mohammadjavad Paydar Girish Aggunda Renukappa Bharathi Raja Ainan Narasimha Rao Krishnamurthy Sunil Kumar Panigrahi Kumari Mahasweta Sangeetha Raghuramachandran Manoj Rajappa Anuradha Ramanathan Anirudha Lakshminarasimhan Murali Ramachandra Pooi-Fong Wong Mohammad Rais Mustafa Srinivas Nanduri Subramanya Hosahalli 《Bioorganic & medicinal chemistry letters》2013,23(17):4911-4918
We have identified a novel 7-azaindole series of anaplastic lymphoma kinase (ALK) inhibitors. Compounds 7b, 7m and 7n demonstrate excellent potencies in biochemical and cellular assays. X-ray crystal structure of one of the compounds (7k) revealed a unique binding mode with the benzyl group occupying the back pocket, explaining its potency towards ALK and selectivity over tested kinases particularly Aurora-A. This binding mode is in contrast to that of known ALK inhibitors such as Crizotinib and NVP-TAE684 which occupy the ribose binding pocket, close to DFG motif. 相似文献
189.
Changes in the levels of antiapoptotic protein B-cell lymphoma 2 (Bcl-2) protein has been reported in murine and human tuberculosis.
We investigated the role of mitogen-activated protein kinase pathways in the production of Bcl-2 protein in THP-1 human monocytes
infected with Mycobacterium tuberculosis H37Rv and H37Ra. Analysis of phosphorylation profiles of mitogen-activated protein kinase kinase-1, extracellular-signal
regulated kinase 1/2, mitogen-activated protein kinase kinase 3/6, and p38 mitogen-activated protein kinase; B-cell lymphoma
2 kinetics; and tumor necrosis factor-α (TNF-α) secretion levels showed variation between the two strains. Mycobacterium tuberculosis H37Rv induced higher Bcl-2 and lower TNF-α levels, whereas H37Ra the reverse. The strains also differed in their usage of
CD14 and human leukocyte antigen-DR receptors in mediating extracellular-signal regulated kinase 1/2 and p38 mitogen-activated
protein kinase activation. Mycobacterium tuberculosis H37Rv- and H37Ra-induced Bcl-2 production was reduced by specific inhibitors of mitogen-activated protein kinase kinase-1
(PD98059) and p38 (SB203580), but increased by nuclear factor κB (NF-κB) inhibitor (BAY 11-7082). TNF-α production by both
strains was reduced in the presence of specific inhibitors of mitogen-activated protein kinase kinase-1 (PD98059), p38 (SB203580),
and NF-κB (BAY 11-7082). Furthermore, inhibition of NF-κB was accompanied by an increase in strain-induced extracellular-signal
regulated kinase 1/2 phosphorylation. Collectively, these results indicate for the first time that the production of Bcl-2
and TNF-α by M. tuberculosis H37Rv/H37Ra-infected THP-1 human monocytes is mediated through mitogen-activated protein kinases and NF-κB. 相似文献
190.
Muralidharan S Hanley PJ Liu E Chakraborty R Bollard C Shpall E Rooney C Savoldo B Rodgers J Dotti G 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(10):5221-5232
The canonical Wnt/β-catenin signaling pathway plays an important role in thymocyte development and T cell migration, but little is known about its role in naive-to-effector differentiation in human peripheral T cells. We show that activation of Wnt/β-catenin signaling arrests human peripheral blood and cord blood T lymphocytes in the naive stage and blocks their transition into functional T effector cells. Wnt signaling was induced in polyclonally activated human T cells by treatment either with the glycogen synthase kinase 3β inhibitor TWS119 or the physiological Wnt agonist Wnt-3a, and these T cells preserved a naive CD45RA(+)CD62L(+) phenotype compared with control-activated T cells that progressed to a CD45RO(+)CD62L(-) effector phenotype, and this occurred in a TWS119 dose-dependent manner. TWS119-induced Wnt signaling reduced T cell expansion, as a result of a block in cell division, and impaired acquisition of T cell effector function, measured by degranulation and IFN-γ production in response to T cell activation. The block in T cell division may be attributed to the reduced IL-2Rα expression in TWS119-treated T cells that lowers their capacity to use autocrine IL-2 for expansion. Collectively, our data suggest that Wnt/β-catenin signaling is a negative regulator of naive-to-effector T cell differentiation in human T lymphocytes. The arrest in T cell differentiation induced by Wnt signaling might have relevant clinical applications such as to preserve the naive T cell compartment in Ag-specific T cells generated ex vivo for adoptive T cell immunotherapy. 相似文献