School Of Basic And Applied Sciences

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    Connecting the Link between Oxidative Stress, Dietary Antioxidants and Hypertension
    (CRC Press, 2023-06-12T00:00:00) Kaur, Sukhchain; Midha, Tushar; Dutta, Oyndril; Saini, Om Prakash; Muduli, Rasmi Ranjan; Mantha, Anil K.; Dhiman, Monisha
    Cardiovascular disorders such as hypertension, coronary heart disease (CHD), cerebrovascular disease, etc. accounts for millions of deaths per year and among these, hypertension (i.e. increased blood pressure) acts as a silent killer and is responsible for 7.5 billion deaths worldwide. Previously, abnormal functioning of the Renin Angiotensin Aldosterone System (RAAS) was considered as a risk factor for hypertension but in recent times, oxidative stress is a key factor in exaggerating the disease progression. In hypertension, oxidative stress damages the biomolecules, decreases the NO availability and endothelial functioning. The use of external antioxidants as therapeutic agents is an excellent approach in the treatment of hypertension. These antioxidants can reverse the deleterious effects of oxidative stress and recover normal cellular homeostasis. The book chapter is focused on the various natural antioxidants and their role as anti-hypertensive agents. � 2024 selection and editorial matter, Victor R. Preedy, Vinood B. Patel, and Rajkumar Rajendram.
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    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.
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    Herbal Remedies for Improving Cancer Treatment Through Modulation of Redox Balance
    (Springer Singapore, 2022-09-28T00:00:00) Kaur, Sukhchain; Verma, Harkomal; Kaur, Sharanjot; Singh, Subham; Mantha, Anil K.; Dhiman, Monisha
    The redox modulation induced by oxidative stress is one of the major cause of the metabolic and inflammatory disorders including cancer. The reactive oxygen species (ROS) produced by various sources in the cell shift the redox homeostasis of cells towards more oxidizing or acidic environment. This shift results in the alterations of normal physiologic functioning of biomolecules as well as causes damage to these biomolecules (proteins, lipids, and DNA/RNA). The excessive ROS and redox modulation are the key factors that support growth, progression, and survival of cancer cells. ROS-induced redox modulation further activates pro-tumorigenic cellular pathways for e.g., PI3K/AKT, HIF-1, and MAPK signaling pathways as well as hinders epigenetic signaling. Increasing evidences demonstrate that long-term side effects of anti-cancer chemotherapy are major concern of medical sciences although modern treatments are quite effective. The combination of various herbal formulations with anti-cancer therapy shows improvement in treatment effectiveness in cancer patients. Bioactive compounds present in herbal formulations possess antioxidant and anti-cancer properties that help in the regulation of redox status of cancer cells. The synergetic effects of herbal remedies along with conventional treatment are proven as novel therapeutics in cancer progression management. Clinical studies have shown that broad range of herbs and bioactive compounds from various plants having antioxidant, anti-inflammatory properties can suppress the carcinogenesis. In this chapter we will discuss the role of various plants such as Glycyrrhiza glabra, Picrorhiza kurroa, Tinospora cordifolia, Curcuma longa, Ocimum sanctum, Viola odorata, and bioactive compound ferulic acid found in various cereals. The chapter will also focus on various mechanisms involved in the modulation of chemo-toxicity and improvement of efficacy of conventional anti-cancer therapies by these plants. � Springer Nature Singapore Pte Ltd. 2022.
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    Methods to Detect Nitric Oxide and Reactive Nitrogen Species in Biological Sample
    (Humana Press Inc., 2022-01-19T00:00:00) Kaur, Sharanjot; Gupta, Kunj Bihari; Kumar, Sandeep; Upadhyay, Shishir; Mantha, Anil Kumar; Dhiman, Monisha
    Oxidative stress has been implicated in various human diseases, including cancer, mainly through the generation of reactive nitrogen species (RNS), such as nitric oxide (NO), nitrite, nitroxyl, s-nitrosothiols, and reactive oxygen species (ROS) such as peroxides, superoxide, and hydroxyl radicals. NO being the main player among RNS induced altered cellular molecules and metabolisms, thus making it important to understand and detect the generation of NO in biological samples. There are many methods for direct and indirect detection of NO; out of these most commonly used are spectrophotometric-based Griess assay and fluorescence probe-based assays. In this chapter, we summarize these routinely used methods to detect NO and various challenges associated with these methods. � 2022, Springer Science+Business Media, LLC, part of Springer Nature.
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    Mitigation of Gliadin-Induced Inflammation and Cellular Damage by Curcumin in Human Intestinal Cell Lines
    (Springer, 2021-01-04T00:00:00) Gupta, Kunj Bihari; Mantha, Anil K.; Dhiman, Monisha
    Wheat is a major diet from many years; apart from its nutritious value, the wheat protein gliadin is responsible for many inflammatory diseases like celiac disease (CD), and non-celiac gluten sensitivity (NCGS). In this study, the gliadin-induced inflammation and associated cellular damage along with the protective role of curcumin was evaluated using human intestinal cell lines (HCT-116 and HT-29) as a model. Cells were cultured and exposed to 160 ?g/ml of gliadin, 100 ?M H2O2, and 10 ?M curcumin (3 h pretreatment) followed by the assessment of inflammation. Spectrophotometric methods, real-time-PCR, ELISA, Western blotting, and confocal microscopy techniques were used to assess inflammatory markers such as advanced oxidation protein products (AOPPs) level, activity of myeloperoxidase (MPO) and NADPH oxidase (NOX), cytokines, and cell damage markers. The results show that gliadin increases the AOPPs level and the activity of MPO and NOX expression. It enhances inflammation by increasing expression of pro-inflammatory cytokines, altered expression of anti-inflammatory, and regulatory cytokines. It exacerbates the cellular damage by increasing MMP-2 and 9 and decreasing integrin ? and ? expression. Gliadin promotes disease pathogenesis by inducing the inflammation and cellular damage which further alter the cellular homeostasis. The pretreatment of curcumin counteracts the adverse effect of gliadin and protect the cells via diminishing the inflammation and help the cell to regain the cellular morphology suggesting phytochemical-based remedial interventions against wheat allergies. � 2021, Springer Science+Business Media, LLC, part of Springer Nature.
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    A short review: Doxorubicin and its effect on cardiac proteins
    (Wiley-Liss Inc., 2020-12-26T00:00:00) Upadhyay, Shishir; Gupta, Kunj Bihari; Mantha, Anil Kumar; Dhiman, Monisha
    Doxorubicin (DOX) is a boon for cancer-suffering patients. However, the undesirable effect�on health on vital organs, especially the heart, is a�limiting factor, resulting in an increased number of patients with cardiac dysfunction. The present review focuses on the contractile machinery and associated factors, which get affected due to DOX toxicity in chemo-patients for which they are kept under life-long investigation for cardiac function. DOX-induced oxidative stress disrupts the integrity of cardiac contractile muscle proteins that alter�the rhythmic mechanism and oxygen consumption rate of the heart. DOX is an oxidant and it is further discussed that oxidative stress prompts the damage of contractile components and associated factors, which include Ca2+ load through Ca2+ ATPase, SERCA, ryanodine receptor-2, phospholamban, and calsequestrin, which ultimately results in left ventricular ejection and dilation. Based on data and evidence, the associated proteins can be considered as clinical markers to develop medications for patients. Even with the advancement of various diagnosing tools and modified drugs to mitigate DOX-induced cardiotoxicity, the risk could not be surmounted�with survivors of cancer. � 2020 Wiley Periodicals LLC
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    Understanding the multifaceted role of miRNAs in Alzheimer�s disease pathology
    (Springer, 2023-07-28T00:00:00) Kaur, Sharanjot; Verma, Harkomal; Kaur, Sukhchain; Gangwar, Prabhakar; Yadav, Anuradha; Yadav, Bharti; Rao, Rashmi; Dhiman, Monisha; Mantha, Anil Kumar
    Small non-coding RNAs (miRNAs) regulate gene expression by binding to mRNA and mediating its degradation or inhibiting translation. Since miRNAs can regulate the expression of several genes, they have multiple roles to play in biological processes and human diseases. The majority of miRNAs are known to be expressed in the brain and are involved in synaptic functions, thus marking their presence and role in major neurodegenerative disorders, including Alzheimer�s disease (AD). In AD, amyloid beta (A?) plaques and neurofibrillary tangles (NFTs) are known to be the major hallmarks. The clearance of A? and tau is known to be associated with miRNA dysregulation. In addition, the ?-site APP cleaving enzyme (BACE 1), which cleaves APP to form A?, is also found to be regulated by miRNAs, thus directly affecting A? accumulation. Growing evidences suggest that neuroinflammation can be an initial event in AD pathology, and miRNAs have been linked with the regulation of neuroinflammation. Inflammatory disorders have also been associated with AD pathology, and exosomes associated with miRNAs are known to regulate brain inflammation, suggesting for the role of systemic miRNAs in AD pathology. Several miRNAs have been related in AD, years before the clinical symptoms appear, most of which are associated with regulating the cell cycle, immune system, stress responses, cellular senescence, nerve growth factor (NGF)�signaling, and synaptic regulation. Phytochemicals, especially polyphenols, alter the expression of various miRNAs by binding to miRNAs or binding to the transcriptional activators of miRNAs, thus control/alter various metabolic pathways. Awing to the sundry biological processes being regulated by miRNAs in the brain and regulation of expression of miRNAs via phytochemicals, miRNAs and the regulatory bioactive phytochemicals can serve as therapeutic agents in the treatment and management of AD. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Gliadin induced oxidative stress and altered cellular responses in human intestinal cells: An in-vitro study to understand the cross-talk between the transcription factor Nrf-2 and multifunctional APE1 enzyme
    (John Wiley and Sons Inc, 2022-05-09T00:00:00) Gupta, Kunj Bihari; Dhiman, Monisha; Mantha, Anil Kumar
    The present study examined the wheat protein gliadin-induced oxidative and nitrosative stress and its downstream responses in human intestinal HCT-116 and HT-29 cells. The beneficial role of dietary phytochemical curcumin and role of multifunctional enzyme Apurinic/aprymidinic endonuclease 1 (APE1) a major player involved in the base excision repair (BER)-pathway in gliadin intolerant intestinal HCT-116 and HT-29 cell lines were evaluated as an in vitro model study. The cultured cells were exposed to gliadin protein, H2O2, and curcumin followed by the assessment of oxidative stress and the consequences were measured using spectrophotometric, PCR, flow cytometer, Western blotting, confocal microscopy, and other methods. Results demonstrate that a 3 h pretreatment of curcumin, followed by the treatment of gliadin protein for 24 h time period protected both the HCT-116 and HT-29 cells via: (i) decreasing the ROS/RNS, restoring the mitochondrial transmembrane potential; (ii) re-establishing the cellular antioxidant defense system (superoxide dismutase, catalase, and GSH); (iii) enhancing the functions of APE1 viz. endonuclease activity and redox activation of transcription factor Nrf-2, the later binds with the antioxidant response elements (ARE) and activates downstream targets involved in cell survival. The cross-talk between APE1 and Nrf-2 was also established using immunofluorescence imaging and co-immunoprecipitation assays. In conclusion, gliadin protein induces oxidative/nitrosative stress, mitochondrial dysfunction and it damages cellular biomolecules in the intestinal cells. Hence it can be attributed to the tissue damage and disease pathogenesis in wheat intolerance-associated intestinal diseases. The gliadin-induced stress and its consequences are significantly reduced by the pretreatment of curcumin via BER-pathway and ARE-pathway; which is evident through the interaction between these two essential proteins. Hence suggesting for the intervention of curcumin and other natural dietary phytochemicals-based disease management and treatment of gliadin intolerance associated intestinal diseases like celiac disease. � 2022 Wiley Periodicals LLC.
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    Correlative study on heavy metal-induced oxidative stress and hypertension among the rural population of Malwa Region of Punjab, India
    (Springer Science and Business Media Deutschland GmbH, 2022-07-26T00:00:00) Kaur, Sukhchain; Garg, Neha; Rubal, Rubal; Dhiman, Monisha
    Heavy metal-induced toxicity contributes to the progression of various metabolic disorders and possible mechanisms involved in disease progression are not well established. In this study, the correlation of heavy metal exposure and hypertension have been demonstrated. The results showed that in hypertensive subjects, the lipid profiles (triglycerides, LDL-C, HDL-C, and total cholesterol) and cardiac markers (CK-MB and LDH) were altered abruptly. As a consequence of heavy- induced oxidative stress, the oxidants (TBARS and protein carbonyls) and antioxidants (SOD, GSH, and TAC) were significantly increased and decreased, respectively in hypertension�subjects. The concentrations of heavy metals (Pb, Cd, and As) exceeded the permissible limits in hypertensive subjects. The Nrf-2 genotyping indicated that heavy metals may induce mutations at molecular level. The results of correlation analysis revealed that�the heavy metals interact with cellular components and interfere with metabolic processes which then�results in disturbed lipid profile, enhanced oxidative stress, and reduced antioxidant status. The current study systematically estimated the association of hair and nail heavy metal concentrations with hypertension among the population residing in the Malwa region of Punjab. The proposed study highlighted that heavy metals act as a silent risk factor in the hypertension progression in the population of Malwa region. Future studies are required to confirm current findings and further scrutinize the effect of heavy metals exposure in early adulthood, early, and late mid-life to develop metabolic complications such as hypertension. � 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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    Methods to Assess Oxidative DNA Base Damage Repair of Apurinic/Apyrimidinic (AP) Sites Using Radioactive and Nonradioactive Oligonucleotide-Based Assays
    (NLM (Medline), 2022-01-19T00:00:00) Gupta, Kunj Bihari; Kaur, Sharanjot; Dhiman, Monisha; Mantha, Anil Kumar
    Reactive oxygen species (ROS) overproduction results in oxidative stress leading to genomic instability via the generation of small base lesions in the genome, and this unrepaired DNA base damage leads to various cellular consequences. The oxidative stress-mediated DNA base damage is involved in various human disorders like cancer, cardiovascular, ocular, and neurodegenerative diseases. Base excision repair (BER) pathway, one of the DNA repair pathways, is majorly involved in the repair of oxidative DNA base lesions, which utilizes a different set of enzymes, including endonuclease viz Apurinic/apyrimidinic endonuclease 1 (APE1). APE1 is a well-known multifunctional enzyme with DNA repair, REDOX regulatory, and protein-protein interaction/cross-talk functions associated with the cell survival mechanisms. APE1 acts as an important player in both normal and cancerous cell survival; thus, evaluating its endonuclease activity in the biological samples provide useful readout of the DNA repair capacity/ability, which can be used to tune for the development of therapeutic candidates via either stimulating or blocking its DNA repair function in normal vs. cancer cells, respectively. This chapter enlists two methods used for the determination of APE1's endonuclease activity by oligonucleotide-based radioactive P32-labeled and nonradioactive fluorescence dyes using the cell extracts and recombinant APE1 protein. � 2022. Springer Science+Business Media, LLC, part of Springer Nature.