Department Of Zoology

Permanent URI for this communityhttps://kr.cup.edu.in/handle/32116/62

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Start date: 2013End date: 2020

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    ORGANOPHOSPHATE PESTICIDES PESTER Aβ- INDUCED GENOTOXIC RESPONSES IN CULTURED NEURONAL CELLS: APE1/Ref-1 MEDIATED INTERVENTION
    (Central University of Punjab, 2018) Sarkar, Bibekananda; Mantha, Anil K. and Mittal, Sunil
    Amyloid beta ( ) peptide deposition is the primary cause of neurodegeneration in reasons deposition, but the actual cause is not apparent. Several reports point towards the role of pesticides in the AD pathogenesis, especially organophosphate pesticides (OPPs) that also act as acetylcholinesterase inhibitors (AChEIs) and are reported to be neurotoxic in nature at sub-lethal doses. Monocrotophos (MCP) and Chlorpyrifos (CP) are the most widely used OPPs with highest production and consumption throughout the world. - induced oxidative stress associated with the neurodegeneration in AD has been assessed -35) peptide. Natural compounds like curcumin have been well documented for their ameliorating powers against various neurodegenerative disease models. The cell survival assay showed that MCP and CP kill the neuronal cells in both dose- and time-dependently. Nitro blue tetrazolium (NBT) based assay for determination of intracellular reactive oxygen species (ROS) demonstrated that MCP and CP produce significant oxidative stress in IMR-32 and SH-SY -35) increased oxidative stress in IMR-32 and SH-SY5Y cells, whereas curcumin reduced ROS levels significantly (p
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    A BIOCHEMICAL STUDY TO EVALUATE THE ROLE OF APURINIC/APYRIMIDINIC ENDONUCLEASE 1 (APE1) IN LUNG CANCER PROGRESSION
    (Central University of Punjab, 2018) Thakur, Shweta; Mantha, Anil K. and Dhiman, Monisha
    Globally, lung cancer has the highest incidence and mortality rate. Environmental factors such as chlorpyrifos (CP) and monocrotophos (MCP), widely used organophosphate pesticides (OPPs), and are reported to be involved in the process of lung carcinogenesis. Present study attempts to investigate the genotoxic potential of CP and MCP, and investigates the oxidative DNA base damage response evoked by CP and MCP in non-small cell lung carcinoma (NSCLC) A549 and NCI-H1299 cells. A549 and NCI-H1299 cells were exposed to a range of concentration of CP and MCP at different time points; cell viability and reactive oxygen species (ROS) generation were measured to select the non-toxic dose. In order to establish whether CP and MCP treatment can initiate the DNA repair and cell survival signalling pathways in A549 cells, semi-quantitative RTPCR, qRT-PCR and Western blotting techniques were used to investigate the mRNA and protein expression levels of DNA base excision repair (BER)-pathway enzymes, transcription factors (TFs) involved in pro-survival mechanisms and apoptosis-related factors. Significant increase in ROS generation was observed when cells were exposed to low and moderate doses of CP and MCP. A549 cells displayed a dose-dependent accumulation of DNA damage apurinic/apyrimidinic (AP) sites after MCP treatment. Cellular responses to CP and MCP-induced oxidative stress resulted in alterations in the mRNA and protein expression of BER-pathway enzymes viz. PARP1, APE1, XRCC1, DNA pol β and DNA ligase III α at different time points, which indicates imbalanced BER-pathway. OPPs treatment resulted in alterations in TFs viz. Nrf2, c-jun, phospho-c-jun (p-c-jun); inducible nitric oxide synthase (NOS2) and PCNA, which may lead to cell proliferation and promotion of carcinogenic events. Possible protein-protein interactions of BER-pathway’s key enzyme APE1 were also analyzed using STRING database, and intrinsically disordered (ID) regions of APE1 and TFs AP- v 1, NF-ĸB and Nrf2 were determined using PONDR analysis. PONDR prediction score and presence of ID regions in N-terminal segment of APE1, middle and Cterminal segments of AP-1, NF-ĸB and Nrf2 advocates for the possible direct protein-protein interactions, to be required for redox-regulatory function of APE1. Altered subcellular localization of APE1 and colocalization between APE1 and cjun; APE1 and p-c-jun; and APE1 and NF-ĸB were analyzed in A549 cells and; between APE1 and c-jun and, APE1 and Nrf2 were analyzed in NCI-H1299 cells following CP and MCP exposure using immunofluorescent confocal laser scanning microscopy. The present study results indicate that CP and MCP induces translocation of APE1 within the cytoplasm at an early time point of 6 hr; whereas it promotes nuclear localization at 24 hr, which suggests that APE1 subcellular localization is dynamically regulated in response to the oxidative stress. Furthermore, nuclear colocalization of APE1 and TF c-jun, APE1 and NF-ĸB and, APE1 and Nrf2 was also observed in response to CP and MCP treatment in A549 and NCI-H1299 cells, which indicates for the APE1-mediated redox regulation of TFs c-jun, NF-ĸB and Nrf2. However, no significant nuclear colocalization was observed for APE1 and p-c-jun indicating the role of phosphorylation on c-jun on Ser63 (p-c-jun) to act as a “switch off” form from the redox complex after the regulation. Immunoprecipitation (IP) was also performed to identify the interacting protein partners of APE1 under the influence of CP and MCP exposure; result indicated that MCP could moderately induce the interaction between APE1 and Nrf2, and APE1 and c-jun. Therefore, the present study suggest that CP and MCP-induced oxidative stress alters BER-pathway and mediates cell-survival signalling mechanisms via APE1 regulation thereby promoting lung cancer cell survival and proliferation.
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    Molecular mechanisms of action of epigallocatechin gallate in cancer: Recent trends and advancement
    (Academic Press, 2020) Aggarwal, V; Tuli, H.S; Tania, M; Srivastava, S; Ritzer, E.E; Pandey, A; Aggarwal, D; Barwal, T.S; Jain, A; Kaur, G; Sak, K; Varol, M; Bishayee, A.
    Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is an ester of epigallocatechin and gallic acid. EGCG, abundantly found in tea, is a polyphenolic flavonoid that has the potential to affect human health and disease. EGCG interacts with various recognized cellular targets and inhibits cancer cell proliferation by inducing apoptosis and cell cycle arrest. In addition, scientific evidence has illustrated the promising role of EGCG in inhibiting tumor cell metastasis and angiogenesis. It has also been found that EGCG may reverse drug resistance of cancer cells and could be a promising candidate for synergism studies. The prospective importance of EGCG in cancer treatment is owed to its natural origin, safety, and low cost which presents it as an attractive target for further development of novel cancer therapeutics. A major challenge with EGCG is its low bioavailability which is being targeted for improvement by encapsulating EGCG in nano-sized vehicles for further delivery. However, there are major limitations of the studies on EGCG, including study design, experimental bias, and inconsistent results and reproducibility among different study cohorts. Additionally, it is important to identify specific EGCG pharmacological targets in the tumor-specific signaling pathways for development of novel combined therapeutic treatments with EGCG. The present review highlights the ongoing development to identify cellular and molecular targets of EGCG in cancer. Furthermore, the role of nanotechnology-mediated EGCG combinations and delivery systems will also be discussed. � 2020 Elsevier Ltd
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    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 Authors
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    Molecular mechanisms of action of genistein in cancer: Recent advances
    (Frontiers Media S.A., 2019) Tuli H.S.; Tuorkey M.J.; Thakral F.; Sak K.; Kumar M.; Sharma A.K.; Sharma U.; Jain A.; Aggarwal V.; Bishayee A.
    Background: Genistein is one among the several other known isoflavones that is found in different soybeans and soy products. The chemical name of genistein is 4?,5,7-trihydroxyisoflavone. Genistein has drawn attention of scientific community because of its potential beneficial effects on human grave diseases, such as cancer. Mechanistic insight of genistein reveals its potential for apoptotic induction, cell cycle arrest, as well as antiangiogenic, antimetastatic, and anti-inflammatory effects. Objective: The purpose of this review is to unravel and analyze various molecular mechanisms of genistein in diverse cancer models. Data sources: English language literature was searched using various databases, such as PubMed, ScienceDirect, EBOSCOhost, Scopus, Web of Science, and Cochrane Library. Key words used in various combinations included genistein, cancer, anticancer, molecular mechanisms prevention, treatment, in vivo, in vitro, and clinical studies. Study selection: Study selection was carried out strictly in accordance with the statement of Preferred Reporting Items for Systematic Reviews and Meta-analyses. Data extraction: Four authors independently carried out the extraction of articles. Data synthesis: One hundred one papers were found suitable for use in this review. Conclusion: This review covers various molecular interactions of genistein with various cellular targets in cancer models. It will help the scientific community understand genistein and cancer biology and will provoke them to design novel therapeutic strategies.
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    Crosstalk between platelet and bacteria: A therapeutic prospect
    (Bentham Science Publishers, 2019) Yadav V.K.; Singh P.K.; Agarwal V.; Singh S.K.
    Platelets are typically recognized for their roles in the maintenance of hemostasis and vascular wall repair to reduce blood loss. Beyond hemostasis, platelets also play a critical role in pathophysiological conditions like atherosclerosis, stroke, thrombosis, and infections. During infection, platelets interact directly and indirectly with bacteria through a wide range of cellular and molecular mechanisms. Platelet surface receptors such as GPIb?, Fc?RIIA, GPIIbIIIa, and TLRs, etc. facilitate direct interaction with bacterial cells. Besides, the indirect interaction between platelet and bacteria involves host plasma proteins such as von Willebrand Factor (vWF), fibronectin, IgG, and fibrinogen. Bacterial cells induce platelet activation, aggregation, and thrombus formation in the microvasculature. The activated platelets induce the Neutrophil Extracellular Traps (NETs) formation, which further contribute to thrombosis. Thus, platelets are extensively anticipated as vital immune modulator cells during infection, which may further lead to cardiovascular complications. In this review, we cover the interaction mechanisms between platelets and bacteria that may lead to the development of thrombotic disorders. Platelet receptors and other host molecules involved in such interactions can be used to develop new therapeutic strategies to combat against infection-induced cardiovascular complications. In addition, we highlight other receptor and enzyme targets that may further reduce infection-induced platelet activation and various pathological conditions.
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    RNA-Seq analysis and de novo transcriptome assembly of Cry toxin susceptible and tolerant Achaea janata larvae
    (NLM (Medline), 2019) Dhania N.K.; Chauhan V.K.; Chaitanya R.K.; Dutta-Gupta A.
    Larvae of most lepidopteran insect species are known to be voracious feeders and important agricultural pests throughout the world. Achaea janata larvae cause serious damage to Ricinus communis (Castor) in India resulting in significant economic losses. Microbial insecticides based on crystalline (Cry) toxins of Bacillus thuringiensis (Bt) have been effective against the pest. Excessive and indiscriminate use of Bt-based biopesticides could be counter-productive and allow susceptible larvae to eventually develop resistance. Further, lack of adequate genome and transcriptome information for the pest limit our ability to determine the molecular mechanisms of altered physiological responses in Bt-exposed susceptible and tolerant insect strains. In order to facilitate biological, biochemical and molecular research of the pest species that would enable more efficient biocontrol, we report the midgut de novo transcriptome assembly and clustering of susceptible Cry toxin-exposed and Cry toxin tolerant Achaea janata larvae with appropriate age-matched and starvation controls.
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    Role of reactive oxygen species in cancer progression: Molecular mechanisms and recent advancements
    (MDPI AG, 2019) Aggarwal V.; Tuli H.S.; Varol A.; Thakral F.; Yerer M.B.; Sak K.; Varol M.; Jain A.; Khan M.A.; Sethi G.
    Reactive oxygen species (ROS) play a pivotal role in biological processes and continuous ROS production in normal cells is controlled by the appropriate regulation between the silver lining of low and high ROS concentration mediated effects. Interestingly, ROS also dynamically influences the tumor microenvironment and is known to initiate cancer angiogenesis, metastasis, and survival at different concentrations. At moderate concentration, ROS activates the cancer cell survival signaling cascade involving mitogen-activated protein kinase/extracellular signal-regulated protein kinases 1/2 (MAPK/ERK1/2), p38, c-Jun N-terminal kinase (JNK), and phosphoinositide-3-kinase/ protein kinase B (PI3K/Akt), which in turn activate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B), matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF). At high concentrations, ROS can cause cancer cell apoptosis. Hence, it critically depends upon the ROS levels, to either augment tumorigenesis or lead to apoptosis. The major issue is targeting the dual actions of ROS effectively with respect to the concentration bias, which needs to be monitored carefully to impede tumor angiogenesis and metastasis for ROS to serve as potential therapeutic targets exogenously/endogenously. Overall, additional research is required to comprehend the potential of ROS as an effective anti-tumor modality and therapeutic target for treating malignancies.
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    Nanosilica: Recent Progress in Synthesis, Functionalization, Biocompatibility, and Biomedical Applications
    (American Chemical Society, 2019) Singh P.; Srivastava S.; Singh S.K.
    Silica nanoparticles (Si-NPs) are widely explored in biomedical applications due to their high surface area, excellent biocompatibility, and tunable pore size. The silica surface can be readily functionalized for wide range of applications such as cellular imaging, biosensing, and targeted drug delivery. This comprehensive review discusses different synthesis methodologies of Si-NPs and their surface functionalization with various functional groups. Nanosilica functionalization methods are discussed in detail, emphasizing their suitability for targeted drug delivery, cancer therapy, bioimaging, and biosensing. The toxicity assessment of nanosilica is also critically reviewed to get a clear focus before employing them for nanomedicine.
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    CHAPTER 9: Nanomaterial-Blood Interactions: A Biomedical Perspective
    (Royal Society of Chemistry, 2019) Singh, Priti; Singh, Sunil Kumar
    Within the short span of a decade, nanotechnology has gained tremendous recognition in diagnostic and therapeutic applications owing to its unique physiochemical properties. Whenever nanomaterials (NMs) are intravenously injected inside the biological system, NMs encounter the complex physiological environment of blood. Blood is a connective tissue consisting of blood cells, plasma proteins and lipoproteins, and a coagulation system that maintains the haemostasis of the body. NMs can interact with blood constituents and trigger patho-physiological events such as complement activation and thrombosis. Therefore, in this chapter, the roles of blood constituents in a biological system and interactions between NMs and blood components is critically reviewed. The shape, size, functionalisation and surface charge of NMs may be deciding factors for their adverse toxic effects. A critical analysis of nanomaterial-blood interactions will help with designing engineered NMs and manipulating their properties for impeccable applications in nanomedicine. © The Royal Society of Chemistry 2019.