Department Of Zoology

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2D Nanomaterials in Diagnostics and Therapy of Cardiovascular Diseases
(CRC Press, 2022-09-26T00:00:00) Yadav, Pooja; Beura, Samir K.; Panigrahi, Abhishek R.; Chatterjee, Abhinaba; Yadav, Jyoti; Singh, Sunil K.
[No abstract available]
Advantages of mesenchymal stem cell over the other stem cells
(Elsevier GmbH, 2023-05-09T00:00:00) Gopalarethinam, Janani; Nair, Aswathy P.; Iyer, Mahalaxmi; Vellingiri, Balachandar; Subramaniam, Mohana Devi
A stem cell is a particular group of cells that has the extraordinary potential to convert within the body into particular cell types. They are used to regenerate tissues and cells in the body that have been damaged or destroyed by the disease. Stem cells come in three different varieties: adult stem cells, embryonic stem cells and induced pluripotent stem cells (iPSCs). Embryonic stem cells have a high chance of immune rejection and also have ethical dilemmas and iPSCs have genetic instability. Adult stem cells are difficult to analyze and extract for research since they are frequently insufficient in native tissues. However, mesenchymal stem cells (MSC) one of the categories of adult stem cells are stromal cells with a variety of potentials that can differentiate into a wide range of cell types. MSCs can be transplanted into a variety of people without worrying about rejection because they have demonstrated the ability to prevent an adverse reaction from the immune system. These transplants have powerful anti-inflammatory and immunosuppressive effects and greatly enhance the body's inherent healing capacity. While MSCs do not offer treatment for illnesses, the idea behind them is to enable the body to recover sufficiently for a protracted reduction in symptoms. In many cases, this is sufficient to significantly enhance the patient's well-being. Inspite of several advantages some potential long-term concerns connected to MSC therapy are maldifferentiation, immunosuppression and cancerous tumor growth. In this review, we will compare the mesenchymal stem cells with other stem cells with respect to the source of origin, their properties and therapeutic applications, and discuss the MSC's disadvantages. � 2023 Elsevier GmbH
Ampelopsin targets in cellular processes of cancer: Recent trends and advances
(Elsevier Inc., 2022-07-27T00:00:00) Tuli, Hardeep Singh; Sak, Katrin; Garg, Vivek Kumar; Kumar, Ajay; Adhikary, Shubham; Kaur, Ginpreet; Parashar, Nidarshana Chaturvedi; Parashar, Gaurav; Mukherjee, Tapan Kumar; Sharma, Uttam; Jain, Aklank; Mohapatra, Ranjan K.; Dhama, Kuldeep; Kumar, Manoj; Singh, Tejveer
Cancer is being considered as a serious threat to human health globally due to limited availability and efficacy of therapeutics. In addition, existing chemotherapeutic drugs possess a diverse range of toxic side effects. Therefore, more research is welcomed to investigate the chemo-preventive action of plant-based metabolites. Ampelopsin (dihydromyricetin) is one among the biologically active plant-based chemicals with promising anti-cancer actions. It modulates the expression of various cellular molecules that are involved in cancer progressions. For instance, ampelopsin enhances the expression of apoptosis inducing proteins. It regulates the expression of angiogenic and metastatic proteins to inhibit tumor growth. Expression of inflammatory markers has also been found to be suppressed by ampelopsin in cancer cells. The present review article describes various anti-tumor cellular targets of ampelopsin at a single podium which will help the researchers to understand mechanistic insight of this phytochemical. � 2022 The Authors
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.
APE1 modulates cellular responses to organophosphate pesticide-induced oxidative damage in non-small cell lung carcinoma A549 cells
(Springer New York LLC, 2018) Thakur, Shweta; Dhiman, Monisha; Mantha, Anil K.
Monocrotophos (MCP) and chlorpyrifos (CP) are widely used organophosphate pesticides (OPPs), speculated to be linked with human pathologies including cancer. Owing to the fact that lung cells are most vulnerable to the environmental toxins, the development and progression of lung cancer can be caused by the exposure of OPPs. The present study investigates the oxidative DNA damage response evoked by MCP and CP in human non-small cell lung carcinoma A549 cells. A549 cells were exposed to MCP and CP; cytotoxicity and reactive oxygen species (ROS) generation were measured to select the non-toxic dose. In order to establish whether MCP and CP can initiate the DNA repair and cell survival signalling pathways in A549 cells, qRT-PCR and Western blotting techniques were used to investigate the mRNA and protein expression levels of DNA base excision repair (BER)-pathway enzymes and transcription factors (TFs) involved in cell survival mechanisms. A significant increase in cell viability and ROS generation was observed when exposed to low and moderate doses of MCP and CP at different time points (24, 48 and 72?h) studied. A549 cells displayed a dose-dependent accumulation of apurinic/apyrimidinic (AP) sites after 24?h exposure to MCP advocating for the activation of AP endonuclease-mediated DNA BER-pathway. Cellular responses to MCP- and CP-induced oxidative stress resulted in an imbalance in the mRNA and protein expression of BER-pathway enzymes, viz. PARP1, OGG1, APE1, XRCC1, DNA pol ? and DNA ligase III ? at different time points. The treatment of OPPs resulted in the upregulation of TFs, viz. Nrf2, c-jun, phospho-c-jun and inducible nitric oxide synthase. Immunofluorescent confocal imaging of A549 cells indicated that MCP and CP induces the translocation of APE1 within the cytoplasm at an early 6?h time point, whereas it promotes nuclear localization after 24?h of treatment, which suggests that APE1 subcellular distribution is dynamically regulated in response to OPP-induced oxidative stress. Furthermore, nuclear colocalization of APE1 and the TF c-jun was observed in response to the treatment of CP and MCP for different time points in A549 cells. Therefore, in this study we demonstrate that MCP- and CP-induced oxidative stress alters APE1-dependent BER-pathway and also mediates cell survival signalling mechanisms via APE1 regulation, thereby promoting lung cancer cell survival and proliferation. ? 2017, Springer Science+Business Media, LLC.
APE1/Ref-1 as an emerging therapeutic target for various human diseases: Phytochemical modulation of its functions
(Nature Publishing Group, 2014) Thakur, Shweta; Sarkar, Bibekananda; Cholia, Ravi P.; Gautam, Nandini; Dhiman, Monisha; Mantha, Anil K.
Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme involved in the base excision repair (BER) pathway, which repairs oxidative base damage caused by endogenous and exogenous agents. APE1 acts as a reductive activator of many transcription factors (TFs) and has also been named redox effector factor 1, Ref-1. For example, APE1 activates activator protein-1, nuclear factor kappa B, hypoxia-inducible factor 1a, paired box gene 8, signal transducer activator of transcription 3 and p53, which are involved in apoptosis, inflammation, angiogenesis and survival pathways. APE1/Ref-1 maintains cellular homeostasis (redox) via the activation of TFs that regulate various physiological processes and that crosstalk with redox balancing agents (for example, thioredoxin, catalase and superoxide dismutase) by controlling levels of reactive oxygen and nitrogen species. The efficiency of APE1/Ref-1's function(s) depends on pairwise interaction with participant protein(s), the functions regulated by APE1/Ref-1 include the BER pathway, TFs, energy metabolism, cytoskeletal elements and stress-dependent responses. Thus, APE1/Ref-1 acts as a 'hub-protein' that controls pathways that are important for cell survival. In this review, we will discuss APE1/Ref-1's versatile nature in various human etiologies, including neurodegeneration, cancer, cardiovascular and other diseases that have been linked with alterations in the expression, subcellular localization and activities of APE/Ref-1. APE1/Ref-1 can be targeted for therapeutic intervention using natural plant products that modulate the expression and functions of APE1/Ref-1. In addition, studies focusing on translational applications based on APE1/Ref-1-mediated therapeutic interventions are discussed. ? 2014 KSBMB.
APE1: A Molecule of Focus with Neuroprotective and Anti-Cancer Properties
(OMICS Publishing Group, 2013) Mantha, Anil K.
Apurinic/Apyrimidinic endonuclease (APE1) is a multi-functional, central enzyme of base excision repair (BER) pathway that takes care of oxidized base damage (AP sites and strand breaks) caused by both endogenous and exogenous oxidative DNA damaging agents. In repair function, APE1 exhibits majorly abasic (AP) endonuclease activity and stable interaction(s) with BER-pathway participant proteins. Second function of APE1 is redox activation of various transcription factors (TFs e.g., c-jun, NF-kB, p53 and HIF1α) and also named as redox effector factor 1(Ref-1). In redox function, APE1 reductively activates TFs involved in regulation of gene expression for cell survival mechanisms through stable pair-wise interaction(s). Recent studies have indicated that APE1 also possesses other distinct functions such as RNA metabolism, riboendonuclease activity and protein-protein interaction for maintaining cellular homeostasis. Altered APE1 expression has been reported in various cancers and neurodegenerative diseases. Taken together such findings advocates the necessity to delineate the underlying molecular mechanism(s) for understanding its role in various biological functions, that could be translated to its application in therapeutics against human diseases like cancer, neurodegenerative diseases and other pathologies such as cardiovascular diseases.
Application of curcumin nanoformulations to target folic acid receptor in cancer: Recent trends and advances
(Academic Press Inc., 2023-06-20T00:00:00) Hussain, Arif; Kumar, Ajay; Uttam, Vivek; Sharma, Uttam; Sak, Katrin; Saini, Reena V.; Saini, Adesh K.; Haque, Shafiul; Tuli, Hardeep Singh; Jain, Aklank; Sethi, Gautam
Curcumin, derived from turmeric, has a strong anticancer potential known for millennia. The development of this phytochemical as a medicine has been hampered by several significant deficiencies, including its poor water solubility and low bioavailability. This review article discusses possibilities to overcome these bottlenecks by focusing on this natural polyphenol's nanoformulation. Moreover, preparation of curcumin conjugates containing folates as ligands for folic acid receptors can add a new important dimension in this field, allowing specific targeting of cancer cells, considering the significantly higher expression of these receptors in malignant tissues compared to normal cells. It is highly expected that simultaneous improvement of different aspects of curcumin in fighting against such a complex and multifaceted disease like cancer. Therefore, we can better comprehend cancer biology by developing a mechanistic understanding of curcumin, which will also inspire the scientific community to develop new pharmacological models, and exploration of emerging directions to revitalize application of natural products in cancer therapy. � 2023 Elsevier Inc.
Artificial intelligence in heavy metals detection: Methodological and ethical challenges
(Elsevier B.V., 2023-07-02T00:00:00) Yadav, Nidhi; Maurya, Brij Mohan; Chettri, Dewan; Pooja; Pulwani, Chirag; Jajula, Mahesh; kanda, Savleen Singh; babu, Harysh Winster Suresh; Elangovan, Ajay; Velusamy, Parthasarathy; Iyer, Mahalaxmi; Vellingiri, Balachandar
Heavy metals (HMs) are metallic substances. They enter biotic and abiotic systems through natural and human activities. These HMs have an impact on the atmosphere, soil, and groundwater, and they also affect all living things, especially humans, when they enter the food chain. Therefore, monitoring and removing HMs from the environment and humans are crucial for maintaining HMs-based toxicity. The detection of HMs from environmental and human samples has been performed by techniques such as atomic adsorption spectrometry (AAS) and inductively coupled plasma mass spectrometry (ICP-MS). With the advancement of AI-based technology, HMs are now detected and removed from the environment and human systems. This review discusses the impact of HMs on the environment and human health, their detection and removal techniques, and the integration of recent advancements in AI-based technology for the detection and removal of HMs from environmental and human samples. � 2023 The Author(s)
Assessment of Antioxidant Potential of Dietary Components
(Elsevier, 2017) Kumar, Shashank; Chaitanya, Rapalli Krishna; Preedy, Victor R.
Antioxidants neutralize or mitigate the harmful effects of free radicals. Such antioxidants may be classed as either enzymatic or nonenzymatic. Some components in the diet act as important antioxidants as they may have direct antioxidant activity or are a component of antioxidant systems. Free radical-mediated stress arises when body fails to ameliorate the excess generation of free radicals. In such circumstances the need for supplementary or other dietary antioxidants arises. As a consequence, it is necessary to assay antioxidants status in subjects or antioxidant potential of novel dietary components. Several techniques have been developed to measure the antioxidant potential of dietary components. We describe antioxidants in general, then various platforms using spectroscopic, chromatographic, electrochemical, and photochemical methods. The following in assays and protocols are reviewed: hydrogen atom transfer, oxygen radical absorbance capacity, diphenyl-1-picrylhydrazyl radical scavenging, trolox equivalent antioxidant capacity, ferric-reducing antioxidant power, total radical-trapping antioxidant parameter, metal-chelating capacity, hydroxyl radical antioxidant capacity, diene conjugates, thiobarbituric acid reactive substances, hexanal, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid, phycoerythrin, bleomycin-iron, copper-1,10-phenanthroline complex, peroxynitrite, lipid-soluble antioxidants, beta-carotene bleaching, hydroxyl radical scavenging, superoxide anion radical scavenging capacity, ferrous oxidation-xylenol orange, ferric thiocyanate, nonenzymatic in vivo and enzymatic in vivo assays. ? 2018 Elsevier Inc. All rights reserved.
Assessment of tRNAThr and tRNAGln Variants and Mitochondrial Functionality in Parkinson�s Disease (PD) Patients of Tamil Nadu Population
(Springer, 2023-10-17T00:00:00) Venkatesan, Dhivya; Iyer, Mahalaxmi; Raj, Neethu; Gopalakrishnan, Abilash Valsala; Narayanasamy, Arul; Kumar, Nachimuthu Senthil; Vellingiri, Balachandar
Parkinson�s disease (PD) is speculated with genetic and environmental factors. At molecular level, the mitochondrial impact is stated to be one of the causative reasons for PD. In this study, we investigated the mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels along with mitochondrial tRNA alterations among three age categories of PD. By determining the genetic and organellar functionality using molecular techniques, the ROS levels were reported to be high with decreased MMP and ATP in the late-onset age group than in other two age categories. Likewise, the tRNA significancy in tRNAThr and tRNAGln was noticed with C4335T and G15927A mutations in late-onset and early-onset PD groups respectively. Therefore, from the findings, ageing has shown a disruption in tRNA metabolism leading to critical functioning of ATP synthesis and MMP, causing oxidative stress in PD patients. These physiological outcomes show that ageing has a keen role in the divergence of mitochondrial function, thereby proving a correlation with ageing and maintenance of mitochondrial homeostasis in PD. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Association of IRGM gene promoter polymorphisms with hepatitis B virus infection
(John Wiley and Sons Inc, 2022-06-04T00:00:00) Sharma, Ambika; Duseja, Ajay; Parkash, Jyoti; Changotra, Harish
Background: In response to intracellular pathogens, the autophagy gene IRGM plays an essential role in the innate immune response. Various identified IRGM gene risk loci are associated with several diseases but, so far, no study is available that shows the association of IRGM with hepatitis B virus (HBV) infection. Methods: We genotyped promoter variants (rs4958842, rs4958843, and rs4958846) of IRGM in HBV infected patients (551) and healthy controls (247) for their role in HBV infection. The genotyping was performed by applying methods developed in our laboratory and various biochemical parameters were assessed applying commercially available kits. Results: Data analysis has shown that the mutant allele A of rs4958842 plays a role in the protection from HBV infection in various genetic models that includes allelic, co-dominant and dominant models with the respective statistical data: allelic (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.48�0.78; p = 0.0003), co-dominant (OR = 0.52; 95% CI = 0.38�0.71; p = 0.0008) and dominant (OR = 0.51; 95% CI = 0.38�0.70, p = 0.0004). In chronic hepatitis B (CHB), protective association was observed in the allelic (OR = 0.48; 95% CI = 0.35�0.65, p = 0.0004), co-dominant (OR = 0.38; 95% CI = 0.26�0.54, p = 0.0004) and dominant (OR = 0.38; 95% CI = 0.26�0.54, p = 0.0002) models. Mutant allele C of rs49598843 was associated with the risk of CHB in co-dominant (OR = 1.52; 95% CI = 1.07�2.16, p = 0.04) and dominant (OR = 1.41; 95% CI = 1.00�2.00, p = 0.04) models. The mutant allele C of rs4958846 decreased the risk of HBV infection in allelic (OR = 0.74; 95% CI = 0.59�0.92, p = 0.01), dominant (OR = 0.72; 95% CI = 0.53�0.98, p = 0.05), homozygous (OR = 0.42; 95% CI = 0.24�0.74, p = 0.01) and recessive (OR = 0.42; 95% CI = 0.24�0.74, p = 0.0004) models. However, in the asymptomatic group, it was associated with the increased chance of HBV infection. Haplotypes, ATT (OR = 0.47; 95% CI = 0.33�0.68, p = 0.001) and GTC (OR = 0.68; 95% CI = 0.51�0.92, p = 0.01) protect, whereas GTT (OR = 2.01; 95% CI = 1.55�2.60, p < 0.0001) predisposes the individuals to HBV infection. All of these p�values mentioned here were obtained after performing Bonferroni correction. Conclusions: In conclusion, our findings revealed that mutant allele A of rs4958842, mutant allele C of rs4958843 and rs4958846 were associated with hepatitis B virus infection in the North Indian population. � 2022 John Wiley & Sons Ltd.
ATG5: A central autophagy regulator implicated in various human diseases
(John Wiley and Sons Ltd, 2022-09-05T00:00:00) Changotra, Harish; Kaur, Sargeet; Yadav, Suresh Singh; Gupta, Girdhari Lal; Parkash, Jyoti; Duseja, Ajay
Autophagy, an intracellular conserved degradative process, plays a central role in the renewal/recycling of a cell to maintain the homeostasis of nutrients and energy within the cell. ATG5, a key component of autophagy, regulates the formation of the autophagosome, a hallmark of autophagy. ATG5 binds with ATG12 and ATG16L1 resulting in E3 like ligase complex, which is necessary for autophagosome expansion. Available data suggest that ATG5 is indispensable for autophagy and has an imperative role in several essential biological processes. Moreover, ATG5 has also been demonstrated to possess autophagy-independent functions that magnify its significance and therapeutic potential. ATG5 interacts with various molecules for the execution of different processes implicated during physiological and pathological conditions. Furthermore, ATG5 genetic variants are associated with various ailments. This review discusses various autophagy-dependent and autophagy-independent roles of ATG5, highlights its various deleterious genetic variants reported until now, and various studies supporting it as a potential drug target. � 2022 John Wiley & Sons Ltd.
Autoinducer N-(3-oxododecanoyl)-L-homoserine lactone induces calcium and reactive oxygen species-mediated mitochondrial damage and apoptosis in blood platelets
(Academic Press, 2021-02-23T00:00:00) Yadav, Vivek Kumar; Singh, Pradeep Kumar; Sharma, Deepmala; Pandey, Himanshu; Singh, Sunil Kumar; Agarwal, Vishnu
Acylated homoserine lactones (AHL) such as N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12 HSL) and N-butyryl-L-homoserine lactone (C4 HSL) are the most common autoinducer molecules in Pseudomonas aeruginosa. These AHL molecules not only regulate the expression of virulence factors but also have been shown to interfere with the host cell and modulate its functions. Recently, we reported that 3-oxo-C12 HSL but not C4 HSL causes cytosolic Ca2+ rise and ROS production in platelets. In this study, we examined the potential of AHLs to induce apoptosis in the human blood platelet. Our result showed that 3-oxo-C12 HSL but not C4 HSL causes phosphatidylserine (PS) exposure, mitochondrial dysfunction (mitochondrial transmembrane potential loss, and mitochondrial permeability transition pore (mPTP) formation). Besides, 3-oxo-C12 HSL also inhibited thrombin-induced platelet aggregation and clot retraction. The pretreatment of an intracellular calcium chelator BAPTA-AM or ROS inhibitor (DPI) significantly attenuated the 3-oxo-C12 HSL induced apoptotic characters such as PS exposure and mitochondrial dysfunctions. These data, including our previous findings, confirmed that 3-oxo-C12 HSL induced intracellular Ca2+ mediated ROS production results in the activation and subsequent induction of apoptotic features in platelets. Our results demonstrated that the 3-oxo-C12 HSL modulates the functions of platelets that may cause severe thrombotic complications in P. aeruginosa infected individuals. � 2021 Elsevier Ltd
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.
Bioactive peptides for boosting stem cell culture platform: Methods and applications
(Elsevier Masson s.r.l., 2023-02-09T00:00:00) Abdal Dayem, Ahmed; Lee, Soo Bin; Lim, Kyung Min; Kim, Aram; Shin, Hyun Jin; Vellingiri, Balachandar; Kim, Young Bong; Cho, Ssang-Goo
Peptides, short protein fragments, can emulate the functions of their full-length native counterparts. Peptides are considered potent recombinant protein alternatives due to their specificity, high stability, low production cost, and ability to be easily tailored and immobilized. Stem cell proliferation and differentiation processes are orchestrated by an intricate interaction between numerous growth factors and proteins and their target receptors and ligands. Various growth factors, functional proteins, and cellular matrix-derived peptides efficiently enhance stem cell adhesion, proliferation, and directed differentiation. For that, peptides can be immobilized on a culture plate or conjugated to scaffolds, such as hydrogels or synthetic matrices. In this review, we assess the applications of a variety of peptides in stem cell adhesion, culture, organoid assembly, proliferation, and differentiation, describing the shortcomings of recombinant proteins and their full-length counterparts. Furthermore, we discuss the challenges of peptide applications in stem cell culture and materials design, as well as provide a brief outlook on future directions to advance peptide applications in boosting stem cell quality and scalability for clinical applications in tissue regeneration. � 2023 The Authors
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.
Biodegradable nanoparticulate co-delivery of flavonoid and doxorubicin: Mechanistic exploration and evaluation of anticancer effect in vitro and in vivo
(Elsevier Ltd, 2021-07-30T00:00:00) Khan, Iliyas; Sarkar, Bibekananda; Joshi, Gaurav; Nakhate, Kartik T.; Ajazuddin; Mantha, Anil K.; Kumar, Raj; Kaul, Ankur; Chaturvedi, Shubhra; Mishra, Anil K.; Gupta, Umesh
The proposed study involves delivering drug/bioactive using a single nanoplatform based on poly lactic-co-glycolic acid (PLGA) for better efficacy, synergistic effect, and reduced toxicity. PLGA was conjugated to doxorubicin (D1), and this conjugate was used for encapsulation of naringenin (D2) to develop naringenin loaded PLGA-doxorubicin nanoparticles (PDNG). The PDNG NPs were 165.4 � 4.27 nm in size, having 0.112 � 0.035 PDI, with -10.1 � 2.74 zeta potential. The surface morphology was confirmed through transmission electron microscopy (TEM) and atomic force microscopy (AFM). The in vitro studies revealed that PDNG NPs exhibited selective anticancer potential in breast cancer cells, and induced apoptosis with S-phase inhibition via an increase in intrinsic reactive oxygen species (ROS) and altering the mitochondrial potential. The results also signified the efficient uptake of nanoparticles encapsulated drugs by cells besides elevating the caspase level suggesting programmed cell death induction upon treatment. In vivo studies results revealed better half-life (27.35 � 1.58 and 11.98 � 1.21 h for doxorubicin and naringenin) with higher plasma drug concentration. In vivo biodistribution study was also in accordance with the in vitro studies and in line with the in vivo pharmacokinetic. In vivo tumor regression assay portrayed that the formulation PDNG halts the tumor growth and lessen the tumor volume with the stable bodyweight of the mice. Conclusively, the dual delivery approach was beneficial and highly effective against tumor-induced mice. � 2021 The Author(s)
Bioremediation: A favorable perspective to eliminate heavy metals from polluted soil
(Elsevier, 2022-09-30T00:00:00) Kaur, Sukhchain; Midha, Tushar; Verma, Harkomal; Muduli, Rasmi Ranjan; Dutta, Oyindril; Saini, Omprakash; Prakash, Richa; Sharma, Sandeep; Mantha, Anil K.; Dhiman, Monisha
The heavy metal contamination in the environment causes serious risk and long-term lethal effects to all living organisms due to their ability to show toxicity at low concentrations. The bio-magnification of heavy metals in the food chain is a matter of concern for public health. The persistent exposure to heavy metals such as mercury (Hg), lead (Pb), cadmium (Cd), arsenic (As), and uranium (U) cause several pathologic conditions in humans by interfering with normal cellular processes. Due to the non-biodegradable nature of these pollutants, they get accumulated for a long time in the soil. The removal of these pollutants by conventional methods is not satisfactory due to the high cost and generation of huge quantities of waste products. Hence, the use of micro-organisms is the most successful approach to remediate heavy metals from the environment due to their efficacy and financial viability. Numerous microorganisms have been employed to diminish the toxic effects of heavy metals. The combination of microorganisms and plants as a bioremediation strategy is another efficient method for heavy metal bioremediation. The chapter will summarize the heavy metal exploitation with a focus on Cd, As, Pb, and Chromium (Cr). It will also describe the various bioremediation techniques which are being used in the removal of these heavy metals from soil. � 2023 Elsevier Inc. All rights reserved.
Biosensors for breast cancer diagnosis: A review of bioreceptors, biotransducers and signal amplification strategies
(Elsevier Ltd, 2017) Mittal, Sunil; Kaur, Hardeep; Gautam, Nandini; Mantha, Anil K.
Breast cancer is highly prevalent in females and accounts for second highest number of deaths, worldwide. Cumbersome, expensive and time consuming detection techniques presently available for detection of breast cancer potentiates the need for development of novel, specific and ultrasensitive devices. Biosensors are the promising and selective detection devices which hold immense potential as point of care (POC) tools. Present review comprehensively scrutinizes various breast cancer biosensors developed so far and their technical evaluation with respect to efficiency and potency of selected bioreceptors and biotransducers. Use of glycoproteins, DNA biomarkers, micro-RNA, circulatory tumor cells (CTC) and some potential biomarkers are introduced briefly. The review also discusses various strategies used in signal amplification such as nanomaterials, redox mediators, p19 protein, duplex specific nucleases (DSN) and redox cycling. ? 2016 Elsevier B.V.