School Of Basic And Applied Sciences

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    Untangle the mystery behind DS-associated AD � Is APP the main protagonist?
    (Elsevier Ireland Ltd, 2023-04-07T00:00:00) Elangovan, Ajay; Babu, Harysh Winster Suresh; Iyer, Mahalaxmi; Gopalakrishnan, Abilash Valsala; Vellingiri, Balachandar
    Amyloid precursor protein profusion in Trisomy 21, also called Down Syndrome (DS), is rooted in the genetic determination of Alzheimer's disease (AD). With the recent development in patient care, the life expectancy of DS patients has gradually increased, leading to the high prospect of AD development, consequently leading to the development of plaques of amyloid proteins and neurofibrillary tangles made of tau by the fourth decade of the patient leading to dementia. The altered gene expression resulted in cellular dysfunction due to impairment of autophagy, mitochondrial and lysosomal dysfunction, and copy number variation controlled by the additional genes in Trisomy 21. The cognitive impairment and mechanistic insights underlying DS-AD conditions have been reviewed in this article. Some recent findings regarding biomarkers and therapeutics of DS-AD conditions were highlighted in this review. � 2023 Elsevier B.V.
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    Concurrent Assessment of Oxidative Stress and MT-ATP6 Gene Profiling to Facilitate Diagnosis of Autism Spectrum Disorder (ASD) in Tamil Nadu Population
    (Springer, 2023-03-27T00:00:00) Vellingiri, Balachandar; Venkatesan, Dhivya; Iyer, Mahalaxmi; Mohan, Gomathi; Krishnan, Padmavathi; Sai Krishna, Krothapalli; Sangeetha, R.; Narayanasamy, Arul; Gopalakrishnan, Abilash Valsala; Kumar, Nachimuthu Senthil; Subramaniam, Mohana Devi
    Autism spectrum disorder (ASD) is a neurodevelopmental disability that causes social impairment, debilitated verbal or nonverbal conversation, and restricted/repeated behavior. Recent research reveals that mitochondrial dysfunction and oxidative stress might play a pivotal role in ASD condition. The goal of this case�control study was to investigate oxidative stress and related alterations in ASD patients. In addition, the impact of mitochondrial DNA (mtDNA) mutations, particularly MT-ATP6, and its link with oxidative stress in ASD was studied. We found that ASD patient�s plasma had lower superoxide dismutase (SOD) and higher catalase (CAT) activity, resulting in lower SOD/CAT ratio. MT-ATP6 mutation analysis revealed that four variations, 8865 G>A, 8684 C>T, 8697 G>A, and 8836 A>G, have a frequency of more than 10% with missense and synonymous (silent) mutations. It was observed that abnormalities in mitochondrial complexes (I, III, V) are more common in ASD, and it may have resulted in MT-ATP6 changes or vice versa. In conclusion, our findings authenticate that oxidative stress and genetics both have an equal and potential role behind ASD and we recommend to conduct more such concurrent research to understand their unique mechanism for better diagnosis and therapeutic for ASD. Graphical Abstract: [Figure not available: see fulltext.] � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Targeting mitochondria as a potential therapeutic strategy against chemoresistance in cancer
    (Elsevier Masson s.r.l., 2023-02-09T00:00:00) Mukherjee, Soumi; Bhatti, Gurjit Kaur; Chhabra, Ravindresh; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
    The importance of mitochondria is not only limited to energy generation but also in several physical and chemical processes critical for cell survival. Mitochondria play an essential role in cellular apoptosis, calcium ion transport and cellular metabolism. Mutation in the nuclear and mitochondrial genes, altered oncogenes/tumor suppressor genes, and deregulated signalling for cell viability are major reasons for cancer progression and chemoresistance. The development of drug resistance in cancer patients is a major challenge in cancer treatment as the resistant cells are often more aggressive. The drug resistant cells of numerous cancer types exhibit the deregulation of mitochondrial function. The increased biogenesis of mitochondria and its dynamic alteration contribute to developing resistance. Further, a small subpopulation of cancer stem cells in the heterogeneous tumor is primarily responsible for chemoresistance and has an attribute of mitochondrial dysfunction. This review highlights the critical role of mitochondrial dysfunction in chemoresistance in cancer cells through the processes of apoptosis, autophagy/mitophagy, and cancer stemness. Mitochondria-targeted therapeutic strategies might help reduce cancer progression and chemoresistance induced by various cancer drugs. � 2023
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    Glycyrrhiza glabra (Licorice) root extract attenuates doxorubicin-induced cardiotoxicity via alleviating oxidative stress and stabilising the cardiac health in H9c2 cardiomyocytes
    (Elsevier, 2020) Upadhyay, S; Mantha, A.K; Dhiman, Monisha
    Ethnopharmacological relevance: Doxorubicin (DOX) is an effective anti-neoplastic drug, however; it has downside effects on cardiac health and other vital organs. The herbal remedies used in day to day life may have a beneficial effect without disturbing the health of the vital organs. Glycyrrhiza glabra L. is a ligneous perennial shrub belonging to Leguminosae/Fabaceae/Papilionaceae family growing in Mediterranean region and Asia and widespread in Turkey, Italy, Spain, Russia, Syria, Iran, China, India and Israel. Commonly known as mulaithi in north India, G. glabra has glycyrrhizin, glycyrrhetic acid, isoliquiritin, isoflavones, etc., which have been reported for several pharmacological activities such as anti-demulcent, anti-ulcer, anti-cancer, anti-inflammatory and anti-diabetic. Aim of the study: The objective of the present study is to investigate the interaction between the molecular factors like PPAR-?/? and SIRT-1 during cardiac failure arbitrated by DOX under in vitro conditions and role of Glycyrrhiza glabra (Gg) root extract in alleviating these affects. Materials and methods: In the present study, we have examined the DOX induced responses in H9c2 cardiomyocytes and investigated the role of phytochemical Glycyrrhiza glabra in modulating these affects. MTT assay was done to evaluate the cell viability, Reactive Oxygen Species (ROS)/Reactive Nitrogen Species (RNS) levels, mitochondrial ROS, mitochondrial membrane potential was estimated using fluorescent probes. The oxidative stress in terms of protein carbonylation, lipid peroxidation and DNA damage was detected via spectrophotometric methods and immune-fluorescence imaging. The cardiac markers and interaction between SIRT-1 and PPAR-?/? was measured using Real-Time PCR, Western blotting and Co-immunoprecipitation based studies. Results: The Glycyrrhiza glabra (Gg) extracts maintained the membrane integrity and improved the lipid homeostasis and stabilized cytoskeletal element actin. Gg phytoextracts attenuated aggravated ROS level, repaired the antioxidant status and consequently, assisted in repairing the DNA damage and mitochondrial function. Further, the expression of hypertrophic markers in the DOX treated cardiomyocytes reconciled the expression factors both at the transcriptional and translational levels after Gg treatment. SIRT-1 mediated pathway and its downstream activator PPARs are significant in maintaining the cellular functions. It was observed that the Gg extract allows regaining the nuclear SIRT-1 and PPAR-? level which was otherwise reduced with DOX treatment in H9c2 cardiomyocytes. The co-immunoprecipitation (Co-IP) documented that SIRT-1 interacts with PPAR-? in the untreated control H9c2 cardiomyocytes whereas DOX treatment interferes and diminishes this interaction however the Gg treatment maintains this interaction. Knocking down SIRT-1 also downregulated expression of PPAR-? and PPAR-? in DOX treated cells and Gg treatment was able to enhance the expression of PPAR-? and PPAR-? in SIRT-1 knocked down cardiomyocytes. Conclusions: The antioxidant property of Gg defend the cardiac cells against the DOX induced toxicity via; 1) reducing the oxidative stress, 2) maintaining the mitochondrial functions, 3) regulating lipid homeostasis and cardiac metabolism through SIRT-1 pathway, and 4) conserving the cardiac hypertrophy and hence preserving the cardiomyocytes health. Therefore, Gg can be recommended as a healthy supplement with DOX towards cancer therapeutics associated cardiotoxicity. - 2020
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    Impact of mitochondrial transplantation on cancer cells
    (Central University of Punjab, 2014) Aggarwal, Alza; Bhardwaj, Pankaj
    Mitochondria, the powerhouse of the cell, are small granular or filamentous bodies associated significantly with cellular respiration and are the main sources of energy, due to which they are present in maximum number in the organs that require large amounts of energy for doing their function like muscle cells, neural cells, etc. In case of any dysfunction of mitochondria, these organs are most affected culminating in a number of serious multi organs diseases, irrespective of age such as neurogenic weakness with ataxia and retinitis pigmentosa (NARP), or Leigh syndrome (LS), Cancer, etc. Although mutations in mitochondrial genes are common in cancer cells, they do not inactivate mitochondrial energy metabolism, but rather alter the mitochondrial bioenergetics and biosynthetic state. Literature survey also revealed that owing to mitochondrial dysfunction the clinical trial of many anticancer drugs has failed in patients. This study is focused on the impact of mitochondrial transplantation on cancer cells and their drug sensitivity against four human cancer cell lines HCT116 (WT & P53mutated), HepG2 and MCF7. The normal cell's Mitochondria was transplanted into cancer cells and then evaluated the Impact of transplantation of mitochondria from healthy cells into cancer cell upon their growth, ROS production and their drug sensitivity. The results of this study revealed that the healthy mitochondria transplanted to cancer cells decrease carcinogenesis and have drug sensitivity. So, it may be used as futuristic cancer remedy.