62 research outputs found
Silencing of ZRF1 impedes survival of estrogen receptor positive MCF-7 cells and potentiates the effect of curcumin
No full textThe role and clinical implication of ZRF1 in breast cancer are poorly understood. So this study is aimed to explore the role of ZRF1 in breast cancer progression. With this context, we first assessed its expression pattern in FFPE primary and metastasis breast tissue samples as well as from publicly available databases. Moreover, we also explored the survival status of patients from the publicly available database and interestingly discover that high expression of ZRF1 decreases the survival of estrogen-positive breast cancer patients more than estrogen-negative status patients. In the perspective of this, we evaluated the role ZRF1 in MCF-7 breast cancer cells and found that it's silencing by knockdown results in decreased cell proliferation as well as cell viability. Results also show that expression of ZRF1 is down regulated in the presence of estrogen-depleted conditions but independent of RAS/MEK as well as AKT axes. Moreover, the decrease in viability of MCF-7 cells was accompanied by induction of apoptosis and DNA damage, well-marked with upregulation of cleaved PARP and downregulation of BCL2 and H2AUbK119 levels. Furthermore, we also explored that knockdown of ZRF1 sensitises the effect of curcumin, observed with decrease in cell viability and dropping of IC50 value from 25 to 15 mu M. This investigation thus shed a new light on the role on ZRF1 in breast cancer cells and hence can be exploited to design better therapeutic intervention.NIT-Rourkela; DST, Government of Indi
Outfitting COVID-19: An Effective Therapeutic Approach
No full textUse of antisense oligonucleotides of the type 3'-(N)x-AAAUUUG-(N)x-5' against slippery sequence and polynucleotides against pseudoknots forming sequences of SARS-CoV-2 RNA would block the first translation of ORF1a and ORF1b and hence dwindle the virus replication. It is easy to synthesize and deliver the antisense oligonucleotides to the target by directly injecting the nano formulation into the blood
Involvement of Lipid Rafts in Growth Factor Receptors-Mediated Signaling for Cancer Metastasis
No full textCMIP5 model evaluation for extreme ocean wave height responses to ENSO
No full textThe El Niño-Southern Oscillation (ENSO) exerts significant influences on extreme significant wave height (SWH) but climate model capabilities in reproducing the observed ENSO impact on SWH have not been evaluated. This study assesses the performances of the Coupled Model Intercomparison Project phase 5 (CMIP5) models in term of extreme SWH responses to ENSO over the Indo-Pacific Ocean focusing on December-February (DJF). 18 CMIP5 models are evaluated using their historical simulations for 1950–2005 in view of the ERA-20C reanalysis. A non-stationary generalized extreme value (GEV) analysis is employed to fit DJF maxima of 6-hourly SWHs and obtain the extreme SWH response patterns to ENSO by incorporating Niño3.4 index as a covariate. Results show that CMIP5 models can on average capture the major observed mean and extreme SWH responses to ENSO, including the increased SWH over the northeastern North Pacific (NENP) and the decreased SWH over the Maritime Continent (MC) during El Niño. The inter-model relations between ENSO characteristics and SWH responses are further examined for the two hotspot regions (NENP and MC). It is found that ENSO intensity is a dominant factor determining simulated SWH over the NENP such that models with stronger ENSO simulate stronger SWH responses. In contrast, for the MC, the sea level pressure teleconnection pattern significantly affects the inter-model spread in SWH responses, also explaining the systematic underestimation of SWH responses over the region. Implication is that ENSO intensity and atmospheric teleconnection patterns need to be considered for better simulations and reliable predictions of extreme SWH variability. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.11Nsciescopu
Molecular marks for epigenetic identification of developmental and cancer stem cells
No full textAbstract
Epigenetic regulations of genes by reversible methylation of DNA (at the carbon-5 of cytosine) and numerous reversible modifications of histones play important roles in normal physiology and development, and epigenetic deregulations are associated with developmental disorders and various disease states, including cancer. Stem cells have the capacity to self-renew indefinitely. Similar to stem cells, some malignant cells have the capacity to divide indefinitely and are referred to as cancer stem cells. In recent times, direct correlation between epigenetic modifications and reprogramming of stem cell and cancer stem cell is emerging. Major discoveries were made with investigations on reprogramming gene products, also known as master regulators of totipotency and inducer of pluoripotency, namely, OCT4, NANOG, cMYC, SOX2, Klf4, and LIN28. The challenge to induce pluripotency is the insertion of four reprogramming genes (Oct4, Sox2, Klf4, and c-Myc) into the genome. There are always risks of silencing of these genes by epigenetic modifications in the host cells, particularly, when introduced through retroviral techniques. In this contribution, we will discuss some of the major discoveries on epigenetic modifications within the chromatin of various genes associated with cancer progression and cancer stem cells in comparison to normal development of stem cell. These modifications may be considered as molecular signatures for predicting disorders of development and for identifying disease states.</jats:p
Monomeric and dimeric oxidomolybdenum(V and VI) complexes, cytotoxicity, and DNA interaction studies: molybdenum assisted C═N bond cleavage of salophen ligands
No full textFour novel dimeric bis-μ-imido bridged metal–metal bonded oxidomolybdenum(V) complexes [MoV2O2L′21–4] (1–4) (where L′1–4 are rearranged ligands formed in situ from H2L1–4) and a new mononuclear dioxidomolybdenum(VI) complex [MoVIO2L5] (5) synthesized from salen type N2O2 ligands are reported. This rare series of imido- bridged complexes (1–4) have been furnished from rearranged H3L′1–4 ligands, containing an aromatic diimine (o-phenylenediamine) “linker”, where Mo assisted hydrolysis followed by −C═N bond cleavage of one of the arms of the ligand H2L1–4 took place. A monomeric molybdenum(V) intermediate species [MoVO(HL′1–4)(OEt)] (Id1–4) was generated in situ. The concomitant deprotonation and dimerization of two molybdenum(V) intermediate species (Id1–4) ultimately resulted in the formation of a bis-μ-imido bridge between the two molybdenum centers of [MoV2O2L′21–4] (1–4). The mechanism of formation of 1–4 has been discussed, and one of the rare intermediate monomeric molybdenum(V) species Id4 has been isolated in the solid state and characterized. The monomeric dioxidomolybdenum(VI) complex [MoVIO2L5] (5) was prepared from the ligand H2L5 where the aromatic “linker” was replaced by an aliphatic diimine (1,2-diaminopropane). All the ligands and complexes have been characterized by elemental analysis, IR, UV–vis spectroscopy, NMR, ESI- MS, and cyclic voltammetry, and the structural features of 1, 2, 4, and 5 have been solved by X-ray crystallography. The DNA binding and cleavage activity of 1–5 have been explored. The complexes interact with CT-DNA by the groove binding mode, and the binding constants range between 103 and 104 M–1. Fairly good photoinduced cleavage of pUC19 supercoiled plasmid DNA was exhibited by all the complexes, with 4 showing the most promising photoinduced DNA cleavage activity of ∼93%. Moreover, in vitro cytotoxic activity of all the complexes was evaluated by MTT assay, which reveals that the complexes induce cell death in MCF-7 (human breast adenocarcinoma) and HCT-15 (colon cancer) cell lines
Overexpression of OCT4 induced by modulation of histone marks plays crucial role in breast cancer progression
No full textEffect of chain length on the photophysical properties of pyrene-based molecules substituted with extended chains
No full textThe important role played by organic conjugated compounds in the ?elds of electronics and optoelectronics has led to a vast ?eld of research concerned with synthesizing various complex structures where π-π stacking plays a vital role. Pyrene-based molecules are examples of compounds which allow ef?cient charge transfer through π-π molecular stacking. Photophysical studies of such compounds have shown similar behavior as that of pyrene, even though they bear two additional conjugated rings and four long alkyl chains. Chain length may have played an effective role in in?uencing the π-π molecular stacking of such molecules. In continuation of our earlier work(Moustafa, R. M.; Degheili, J. A.; Patra, D.; Kaafarani, B. R. J. Phys. Chem. A 2008, 113, 1235-1243), we hereby synthesize and investigate the role of the chain lengths on the photophysical aspects of 2,11-di-tert-butyl-6,7,15,16- tetrakis(alkoxy-alkythio)quinoxaline-[2′,3′:9,10]phenanthro[4, 5-ab-c]phenazine, TQPP-[t-Bu]2-[XR]4(X O, S; R C nH2n+1). Various photophysical parameters such as Stokes shift, ?uorescence lifetime, ?uorescence quantum yield, and radiative and nonradiative rate constants are evaluated for TQPP-[t-Bu]2-[OR] 4 and TQPP-[t-Bu]2-[SR]4 in tetrahydrofuran. The variation of the Stokes shift, ?uorescence quantum yield, and lifetime are also correlated with the number of carbons in the alkyl chain R for TQPP-[t-Bu]2-[OR]4 and TQPP-[t-Bu]2-[SR] 4. © 2009 American Chemical Society.Anthony JE, 2008, ANGEW CHEM INT EDIT, V47, P452, DOI 10.1002-anie.200604045; Boden N, 1999, J MATER CHEM, V9, P2081, DOI 10.1039-a903005k; Chen MC, 2008, J MATER CHEM, V18, P1029, DOI 10.1039-b715746k; Chen ZH, 2006, ORG LETT, V8, P273, DOI 10.1021-ol0526468; Katsuhara M, 2005, SYNTHETIC MET, V149, P219, DOI 10.1016-j.synthmet.2005.01.005; Kumar S, 2006, CHEM SOC REV, V35, P83, DOI 10.1039-b506619k; Lakowicz J. R., 1999, PRINCIPLES FLUORESCE; Mitzi DB, 2004, J MATER CHEM, V14, P2355, DOI 10.1039-b403482a; MOUSTAFA RM, J PHYS CHEM A UNPUB; Naraso, 2005, J AM CHEM SOC, V127, P10142, DOI 10.1021-ja051755e; Oukachmih M, 2005, SOL ENERG MAT SOL C, V85, P535, DOI 10.1016-j.solmat.2004.05.012; Palilis LC, 2003, ORG ELECTRON, V4, P113, DOI 10.1016-j.orgel.2003.08.006; Parker C.A., 1968, PHOTOLUMINESCENCE SO; Petritsch K, 1999, SYNTHETIC MET, V102, P1776, DOI 10.1016-S0379-6779(98)01035-2; Ponomarenko SA, 2003, ADV FUNCT MATER, V13, P591, DOI 10.1002-adfm.200304363; Subuddhi U, 2006, PHOTOCH PHOTOBIO SCI, V5, P459, DOI 10.1039-b600009f; Sun YG, 2007, ADV MATER, V19, P1897, DOI 10.1002-adma.200602223; van de Craats AM, 1999, ADV MATER, V11, P1469, DOI 10.1002-(SICI)1521-4095(199912)11:171469::AID-ADMA14693.0.CO;2-K; WARIS R, 1988, APPL SPECTROSC, V42, P1525, DOI 10.1366-000370288442980513131
5-Aza-2′-deoxycytidine stress response and apoptosis in prostate cancer
No full textAbstract
While studying on epigenetic regulatory mechanisms (DNA methylation at C-5 of –CpG– cytosine and demethylation of methylated DNA) of certain genes (FAS, CLU, E-cadh, CD44, and Cav-1) associated with prostate cancer development and its better management, we noticed that the used in vivo dose of 5-aza-2′-deoxycytidine (5.0 to 10.0 nM, sufficient to inhibit DNA methyltransferase activity in vitro) helped in the transcription of various genes with known (steroid receptors, AR and ER; ER variants, CD44, CDH1, BRCA1, TGFβR1, MMP3, MMP9, and UPA) and unknown (DAZ and Y-chromosome specific) proteins and the respective cells remained healthy in culture. At a moderate dose (20 to 200 nM) of the inhibitor, cells remain growth arrested. Upon subsequent challenge with increased dose (0.5 to 5.0 μM) of the inhibitor, we observed that the cellular morphology was changing and led to death of the cells with progress of time. Analyses of DNA and anti-, pro-, and apoptotic factors of the affected cells revealed that the molecular events that went on are characteristics of programmed cell death (apoptosis).</jats:p
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