Department Of Zoology
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Item Cancer Susceptibility Candidate 9 (CASC9): A Novel Targetable Long Noncoding RNA in Cancer Treatment(Neoplasia Press, Inc., 2020) Sharma, U; Barwal, T.S; Acharya, V; Tamang, S; Vasquez, K.M; Jain, A.Based on epidemiological data provided by the World Health Organization (2018), cancer is the second most prevalent cause of death worldwide. Several factors are thought to contribute to the high mortality rate in cancer patients, including less-than-optimal diagnostic and therapeutic strategies. Thus, there is an urgent need to identify accurate biomarkers with diagnostic, prognostic, and potential therapeutic applications. In this regard, long noncoding RNAs (lncRNAs) hold immense potential due to their regulatory roles in cancer development and associated cancer hallmarks. Recently, CASC9 transcripts have attracted significant attention due to their altered expression during the pathogenesis of cancer and their apparent contributions to various cancer-associated phenotypes involving a broad spectrum of molecular mechanisms. Here, we have provided an in-depth review describing the known functions of the lncRNA CASC9 in cancer development and progression. - 2020 The AuthorsItem Molecular mechanisms of action of tocotrienols in cancer: Recent trends and advancements(MDPI AG, 2019) Aggarwal, V; Kashyap, D; Sak, K; Tuli, H.S; Jain, Aklank; Chaudhary, A; Garg, V.K; Sethi, G; Yerer, M.B.Tocotrienols, found in several natural sources such as rice bran, annatto seeds, and palm oil have been reported to exert various beneficial health promoting properties especially against chronic diseases, including cancer. The incidence of cancer is rapidly increasing around the world not only because of continual aging and growth in global population, but also due to the adaptation of Western lifestyle behaviours, including intake of high fat diets and low physical activity. Tocotrienols can suppress the growth of different malignancies, including those of breast, lung, ovary, prostate, liver, brain, colon, myeloma, and pancreas. These findings, together with the reported safety profile of tocotrienols in healthy human volunteers, encourage further studies on the potential application of these compounds in cancer prevention and treatment. In the current article, detailed information about the potential molecular mechanisms of actions of tocotrienols in different cancer models has been presented and the possible effects of these vitamin E analogues on various important cancer hallmarks, i.e., cellular proliferation, apoptosis, angiogenesis, metastasis, and inflammation have been briefly analyzed. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.Item Midgut de novo transcriptome analysis and gene expression profiling of Achaea janata larvae exposed with Bacillus thuringiensis (Bt)-based biopesticide formulation(Elsevier, 2019) Dhania, N.K; Chauhan, V.K; Chaitanya, R.K; Dutta-Gupta, A.India is the major producer and exporter of castor oil in the world. Castor semilooper, Achaea janata is one of the main castor crop pests, which causes serious economic loss of crop, hence management and control of the pest are important. Currently, Bacillus thuringiensis (Bt) based biopesticides are being used for their control. However, the insects are known to develop resistance not only against chemical pesticides but also to Bt based biopesticides. In the present study, de novo transcriptome analysis was conducted to monitor the expression pattern of larval midgut genes in Achaea janata exposed to sublethal dose of Bt formulation. A total of 34,612 and 41,109 transcripts were identified in control and toxin-exposed larval midgut samples out of which 18,836 in control and 21,046 in toxin-exposed samples are annotated. Microarray data analysis employed to monitor the gene expression upon Cry toxin exposure revealed that 375 genes were upregulated and 579 genes were downregulated during all the time points (12–60 h) of toxin exposure. The differentially expressed transcripts include i.e. Cry toxin receptors, gut proteases, arylphorin, REPATs, detoxification enzymes and aquaporins. Validation of microarray data was performed by real-time quantitative PCR using few randomly selected genes and the results obtained were in corroboration. This is the first study on transcriptome data from the castor semilooper and the results would provide valuable resources for the characterization of Bt toxin response in the pest. © 2019Item Mechanism underlying N-(3-oxo-dodecanoyl)-L-homoserine lactone mediated intracellular calcium mobilization in human platelets(Academic Press, 2019) Yadav, V.K; Singh, P.K; Sharma, D; Singh, Sunil Kumar; Agarwal,V.Acyl-homoserine lactones (AHLs), are the key autoinducer molecules that mediate Pseudomonas aeruginosa associated quorum sensing. P. aeruginosa produces two types of AHLs; N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12 HSL) and N-butyryl-L-homoserine lactone (C4 HSL). AHLs are not only regulating the virulence gene of bacteria but also influence the host cell functions by interkingdom signaling. In this study, we explored the mechanism of AHLs induced calcium mobilization in human platelets. We found that 3-oxo-C12 HSL but not C4 HSL induces intracellular calcium release. 3-oxo-C12 HSL induced calcium mobilization was majorly contributed from the dense tubular system (DTS). Furthermore, 3-oxo-C12 HSL also stimulates the store-operated Ca2+ entry (SOCE) in platelet. Intracellular calcium rise was significantly lowered in rotenone, and bafilomycin pre-treated platelets suggesting partial involvement of mitochondria and acidic vacuoles. The significant effect of 3-oxo-C12 HSL on calcium mobilization can alter the platelet functions that might results in thrombotic disorders in individuals infected with P. aeruginosa. © 2019Item Pseudomonas aeruginosa quorum sensing molecule N-3-oxo-dodecanoyl-Lhomoserine lactone activates human platelets through intracellular calciummediated ROS generation(Elsevier, 2018) Yadav, V. K.; Singh, P. K.; Kalia, M.; Sharma, D.; Singh, S. K.; Agarwal, V.Pseudomonas aeruginosa, an opportunistic pathogen release N-3-oxo-dodecanoyl-l-homoserine lactone (3-oxo-C12HSL) and N-butyryl-l-homoserine lactone (C4-HSL) quorum sensing (QS) molecules to regulate various virulence factors responsible for infection in the host. 3-oxo-C12 HSL not only regulates the bacterial gene expression but also modulates the host cell system. Thus, it is pertinent to evaluate the effect of these QS molecules on blood platelets which is responsible for the maintenance of hemostasis and thrombus formation. Here, in the present study, we showed that 3-oxo-C12 HSL activates platelets in a dose-dependent manner and induces intracellular calcium-mediated reactive oxygen species (ROS) release, whereas no such effect was observed with C4-HSL. 3-oxo-C12 HSL stimulated ROS release was mediated by NADPH oxidase. Results confirmed the involvement of phospholipase C (PLC) and IP3 receptor behind intracellular calcium-mediated ROS generation. The impact of 3-oxo-C12 HSL on platelet activation suggests that it could interfere and alter the normal function of platelet in individuals infected with P. aeruginosa.Item Hormones of hypothalamus and ageing(Springer, 2018) Kaur, Gurcharan; Parkash, JyotiHypothalamus being the master regulator of the vertebrate endocrine system undergoes many adjustments/alterations which body makes during the course of aging. Moreover, the endocrinological basis of aging in male and female organisms is very complex, with multiple hormones along the hypothalamic-pituitary (HP) axis interacting with each other via different feedback loops to maintain homeodynamic state. Also the sensitivity of the hypothalamus to the external stimuli decreases with age mainly due to its lack of sensitivity towards the feedback system The endocrine system is although severely affected by aging but all the organ systems are not affected at the same time or in the same way. During aging cellular protein synthesis machinery as well as immune functions are diminished and gradually physiological functions decline. There is also an increase in fat mass, a loss of muscle mass and strength, and a decrease in bone mineral density profile that contribute to declining health status with increasing age. The hallmarks of aging such as Genomic instability, Telomere attrition, Epigenetic alterations, Loss of proteostasis, Dysregulated Nutrient Sensing, Mitochondrial dysfunction, Altered intracellular communication, Cellular senescence etc. are well reported in literature. In this chapter we have compiled information and discussed various hormonal changes that occur with age in hypothalamus and pituitary gland and how these two master regulators gradually lose their sensitivity with the increasing age.Item Anticancer activity of dihydropyrazolo[1,5-c]quinazolines against rat C6 glioma cells via inhibition of topoisomerase II.(Wiley, 2018) Kaur, G; Cholia, RP; Joshi, G; Amrutkar, SM; Kalra, S; Mantha, Anil K.; Banerjee, UC; Kumar, R.The design and synthesis of dihydropyrazolo[1,5‐c]quinazolines (1a–h) as human topoisomerase II (TopoII) catalytic inhibitors are reported. The compounds were investigated for their antiproliferative activity against the C6 rat glial cell line. Two compounds, 1b and 1h, were found to be potent cytotoxic agents against glioma cells and exerted selective TopoII inhibitory activity. Furthermore, the compounds induced alterations in reactive oxygen species levels as measured by DCFDA assay and were found to induce cell cycle arrest at the G1 phase at lower concentrations and profound apoptosis at higher concentrations. The interaction of selected investigational molecules with TopoII was further corroborated by molecular modeling.Item Synthesis, biological evaluation and molecular modeling studies of phenyl-/benzhydrylpiperazine derivatives as potential MAO inhibitors.(Elsevier, 2018) Kumar, Bhupinder; Sheetal; Mantha, Anil K.; Kumar, VinodMonoamine oxidase inhibitors (MAOIs) are potential drug candidates for the treatment of various neurological disorders like Parkinson's disease, Alzheimer's disease and depression. In the present study, two series of 4-substituted phenylpiperazine and 1-benzhydrylpiperazine (1-21) derivatives were synthesized and screened for their MAO-A and MAO-B inhibitory activity using Amplex Red assay. Most of the synthesized compounds were found selective for MAO-B isoform except compounds 3, 7, 8, 9 and 13 (MAO-A selective) while compound 11 was non-selective. In the current series, compound 12 showed most potent MAO-B inhibitor activity with IC50 value of 80 nM and compound 7 was found to be most potent MAO-A inhibitor with IC50 value of 120 nM and both the compounds were found reversible inhibitors. Compound 8 was found most selective MAO-A inhibitor while compound 20 was found most selective inhibitor for MAO-B isoform. In the cytotoxicity evaluation, all the compounds were found non-toxic to SH-SY5Y and IMR-32 cells at 25 µM concentration. In the ROS studies, compound 8 (MAO-A inhibitor) reduced the ROS level by 51.2% while compound 13 reduced the ROS level by 61.81%. In the molecular dynamic simulation studies for 30 ns, compound 12 was found quite stable in the active cavity of MAO-B. Thus, it can be concluded that phenyl- and 1-benzhydrylpiperazine derivatives are promising MAO inhibitors and can act as a lead to design potent, and selective MAO inhibitors for the treatment of various neurological disorders.Item Bio-analytical applications of nicking endonucleases assisted signal-amplification strategies for detection of cancer biomarkers -DNA methyl transferase and microRNA.(Elsevier, 2019) Mittal, S; Thakur, S; Mantha, A. K.; Kaur, H.The low concentrations of cancer biomarkers in the blood have limited the utility of quantitative bioassays developed for the purpose. The advent of nicking endonucleases (NEases) as signal amplification tools have greatly enhanced the detection efficiency and provided a multi-optional platform to design target specific detection methods. The present review focuses on the prominent features of NEases, modified DNA probes (such as hairpin (HP) probes, molecular beacons, and G- quadruplex) that mediate cyclic cascade and role of helper enzymes. Application of NEase assisted signal amplification (NESA) has been discussed for diagnosis of two prominent cancer biomarkers viz. DNA methyl transferase (Dam MTase) and microRNA (miRNA). NESA mediated techniques such as rolling circle amplification (RCA), strand displacement amplification (SDA) and isothermal exponential amplification (EXPAR), have been compared in light of their future applications in clinical diagnosis. Significance of nanomaterials to achieve further amplification and NESA assays for simultaneous detection of miRNAs has also been conversed. It is anticipated that the information gained from the analyses of the prospects and limitations of NESA-based assays will be useful towards understanding the applications, and improvement of efficient isothermal exponential amplification strategies for highly sensitive and selective detection of cancer biomarkers.Item Oxidative stress responses to sub-lethal dose of Cry toxin in the larvae of castor semilooper, Achaea janata(Central University of Punjab, 2018) Singh, Kanika; Chaitanya,R.K.Development of synthetic insecticides to reduce the level of infestation led to deleterious effects on environment and human health. This lead to the development of ecofriendly pest management alternatives including Bacillus thuringensis (Bt). Bt produce Crystal (Cry), Cytotoxic (Cyt) and Vegetative (Vip) proteins with insecticidal activity against different orders of lepidoptera. Of late, pest resistance against Bt is reported in countries.The reduced toxicity of Bt formulation from degradation by UV light, wash-off by rain, drying, temperature, and soil acidity as well as its chemistry. Further, insects sense pesticides through odorant receptors and move away quickly, there is always a possibility of a population of larvae to get exposed to sub-lethal doses of toxin which might exhibit variable effects and escape mortality and eventually generate resistance. Sub-lethal dose lead to the generation of oxidative stress in the insect and eventually scavenged by anti-oxidant enzymes. These stress responses would enhance our understanding of adaptations for survival and resistance development. The current study is an attempt to monitor the antioxidative responses at the transcriptional level upon sub-lethal exposure of Cry toxin in the larvae of an polyphagous pest castor semilooper, Achaea janata. prevalent in the Indian subcontinent.