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Article ; Online: A deeper understanding about the role of uranium toxicity in neurodegeneration.

Vellingiri, Balachandar

2023 Volume 233, Page(s) 116430

Abstract: Natural deposits and human-caused releases of uranium have led to its contamination in the nature. Toxic environmental contaminants such as uranium that harm cerebral processes specifically target the brain. Numerous experimental researches have shown ... ...

Abstract	Natural deposits and human-caused releases of uranium have led to its contamination in the nature. Toxic environmental contaminants such as uranium that harm cerebral processes specifically target the brain. Numerous experimental researches have shown that occupational and environmental uranium exposure can result in a wide range of health issues. According to the recent experimental research, uranium can enter the brain after exposure and cause neurobehavioral problems such as elevated motion related activity, disruption of the sleep-wake cycle, poor memory, and elevated anxiety. However, the exact mechanism behind the factor for neurotoxicity by uranium is still uncertain. This review primarily aims on a brief overview of uranium, its route of exposure to the central nervous system, and the likely mechanism of uranium in neurological diseases including oxidative stress, epigenetic modification, and neuronal inflammation has been described, which could present the probable state-of-the-art status of uranium in neurotoxicity. Finally, we offer some preventative strategies to workers who are exposed to uranium at work. In closing, this study highlights the knowledge of uranium's health dangers and underlying toxicological mechanisms is still in its infancy, and there is still more to learn about many contentious discoveries.
MeSH term(s)	Humans ; Uranium/toxicity ; Environmental Exposure ; Brain ; Neurotoxicity Syndromes/etiology ; Learning
Chemical Substances	Uranium (4OC371KSTK)
Language	English
Publishing date	2023-06-15
Publishing country	Netherlands
Document type	Review ; Journal Article
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2023.116430
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Article ; Online: Correction: Association of Biochemical Parameters and Screening for Mutations in the MCU Gene in Alzheimer's Disease Patients.

Venugopal, Anila / Iyer, Mahalaxmi / Narayanasamy, Arul / Ravimanickam, T / Gopalakrishnan, Abilash Valsala / Yadav, Mukesh Kumar / Kumar, Nachimuthu Senthil / Vellingiri, Balachandar

Molecular neurobiology

2024

Language	English
Publishing date	2024-01-22
Publishing country	United States
Document type	Published Erratum
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-024-03929-8
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Article: Epigenetic regulation of the nuclear genome associated with mitochondrial dysfunction in Leber's hereditary optic neuropathy (LHON).

Nair, Aswathy P / Selvakumar, Ambika / Gopalarethinam, Janani / Abishek Kumar, B / Vellingiri, Balachandar / Subramaniam, Mohana Devi

Human genome variation

2024 Volume 11, Issue 1, Page(s) 6

Abstract: Leber's hereditary optic neuropathy (LHON) is a mitochondrial hereditary disease in which visual loss affects complex 1 activity of the electron transport chain of mitochondria. It first manifests as painless dulling or blurry in one or even both eyes, ... ...

Abstract	Leber's hereditary optic neuropathy (LHON) is a mitochondrial hereditary disease in which visual loss affects complex 1 activity of the electron transport chain of mitochondria. It first manifests as painless dulling or blurry in one or even both eyes, and as it develops, sharpness and color perception are lost. In addition to primary mitochondrial DNA (mtDNA) mutations, there are also other environmental and epigenetic factors involved in the pathogenesis of LHON. One of the most common locations for deadly pathogenic mutations in humans is the human complex I accessory NDUFS4 subunit gene. The iron-sulfur clusters of the electron input domain were distorted in the absence of NDUFS4, which reduced complex I function and elevated the production of reactive oxygen species. Therefore, here, we studied the epigenetic alterations of NDUFS4 by focusing on histone activation and repressive markers. We isolated peripheral blood mononuclear cells (PBMCs) from LHON patients and healthy individuals and examined epigenetic modifications in ND4 mutant cells and control cells. Chromatin immunoprecipitation-qRT PCR (ChIP-qRT PCR) assays were performed to investigate the modifications of histones. In comparison to their controls, both LHON patients and ND4 mutant cells exhibited a significant enrichment in activation and repressive markers. This finding indicates that these modifications might mitigate the impact of LHON mutations on complex 1 and aid in elucidating the mechanism underlying the progression of LHON disease.
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Journal Article
ISSN	2054-345X
ISSN	2054-345X
DOI	10.1038/s41439-023-00258-5
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Article ; Online: Midbrain organoids for Parkinson's disease (PD) - A powerful tool to understand the disease pathogenesis.

Babu, Harysh Winster Suresh / Kumar, Sindduja Muthu / Kaur, Harsimrat / Iyer, Mahalaxmi / Vellingiri, Balachandar

Life sciences

2024 Volume 345, Page(s) 122610

Abstract: Brain Organiods (BOs) are a promising technique for researching disease progression in the human brain. These organoids, which are produced from human induced pluripotent stem cells (HiPSCs), can construct themselves into structured frameworks. In the ... ...

Abstract	Brain Organiods (BOs) are a promising technique for researching disease progression in the human brain. These organoids, which are produced from human induced pluripotent stem cells (HiPSCs), can construct themselves into structured frameworks. In the context of Parkinson's disease (PD), recent advancements have been made in the development of Midbrain organoids (MBOs) models that consider key pathophysiological mechanisms such as alpha-synuclein (α-Syn), Lewy bodies, dopamine loss, and microglia activation. However, there are limitations to the current use of BOs in disease modelling and drug discovery, such as the lack of vascularization, long-term differentiation, and absence of glial cells. To address these limitations, researchers have proposed the use of spinning bioreactors to improve oxygen and nutrient perfusion. Modelling PD utilising modern experimental in vitro models is a valuable tool for studying disease mechanisms and elucidating previously unknown features of PD. In this paper, we exclusively review the unique methods available for cultivating MBOs using a pumping system that mimics the circulatory system. This mechanism may aid in delivering the required amount of oxygen and nutrients to all areas of the organoids, preventing cell death, and allowing for long-term culture and using co-culturing techniques for developing glial cell in BOs. Furthermore, we emphasise some of the significant discoveries about the BOs and the potential challenges of using BOs will be discussed.
MeSH term(s)	Humans ; Parkinson Disease/metabolism ; Induced Pluripotent Stem Cells ; alpha-Synuclein/metabolism ; Mesencephalon/metabolism ; Mesencephalon/pathology ; Organoids/metabolism ; Oxygen/metabolism ; Dopaminergic Neurons/metabolism
Chemical Substances	alpha-Synuclein ; Oxygen (S88TT14065)
Language	English
Publishing date	2024-04-03
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2024.122610
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Article ; Online: Cloning, expression and in vitro validation of chimeric multi epitope vaccine candidate against visceral leishmaniasis infection.

Ojha, Rupal / Chand, Kailash / Vellingiri, Balachandar / Prajapati, Vijay Kumar

Life sciences

2023 Volume 323, Page(s) 121689

Abstract: Visceral Leishmaniasis or Kala-Azar is one of the most severe and deadly neglected tropical disease caused by the Leishmania parasite. A few number of vaccines are going through different phases in clinical trial but failing of these vaccines in ... ...

Abstract	Visceral Leishmaniasis or Kala-Azar is one of the most severe and deadly neglected tropical disease caused by the Leishmania parasite. A few number of vaccines are going through different phases in clinical trial but failing of these vaccines in successive phase trial or less efficacy, urge to develop highly immunogenic and cost-effective treatment to get rid of deadly VL. This study focuses on the development of more potent vaccine candidate against VL. The recombinant vaccine candidate LeiSp was expressed in Pichia pastoris, followed by purification and characterization. The purified protein was also tested for any post-translation modification, which favors being a potent immunogenic candidate. Further, the expression modulation of different pro-inflammatory and anti-inflammatory cytokines was evaluated in THP1 cell lines. A significant upregulation in the expression of pro-inflammatory cytokines while no significant changes were observed in the expression of anti-inflammatory cytokines. The impact of recombinant vaccine protein candidates in infected conditions were determined. Here, upon treatment with chimeric vaccine protein candidate, we observed a considerable recovery in the expression level of pro-inflammatory cytokines, which were downregulated upon infection alone. In addition to this, we found a significant decrease in the expression of anti-inflammatory cytokines, which were upregulated during infection alone. We further validated our findings in infected hPBMCs and observed similar expression modulation of pro-inflammatory and anti-inflammatory cytokines with and without treatment. Thus, the present study indicates that the chimeric LeiSp protein which was designed using bioinformatics approaches shows a potential inductive efficacy for pro-inflammatory cytokines in Leishmania-infected cells.
MeSH term(s)	Animals ; Mice ; Leishmaniasis, Visceral/prevention & control ; Epitopes ; Leishmaniasis Vaccines ; Leishmania ; Cytokines/metabolism ; Vaccines, Synthetic ; Recombinant Proteins/genetics ; Cloning, Molecular ; Mice, Inbred BALB C
Chemical Substances	Epitopes ; Leishmaniasis Vaccines ; Cytokines ; Vaccines, Synthetic ; Recombinant Proteins
Language	English
Publishing date	2023-04-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.121689
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Article ; Online: Highlighting novel genes associated with the classical Rett syndrome patient from India.

Mohan, Gomathi / Sarma, Ranjan Jyoti / Iyer, Mahalaxmi / Kumar, Nachimuthu Senthil / Vellingiri, Balachandar

Genes & diseases

2022 Volume 9, Issue 6, Page(s) 1394–1396

Language	English
Publishing date	2022-01-06
Publishing country	China
Document type	Journal Article
ZDB-ID	2821806-1
ISSN	2352-3042 ; 2352-3042
ISSN (online)	2352-3042
ISSN	2352-3042
DOI	10.1016/j.gendis.2021.12.002
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Article ; Online: The incidence of male breast cancer: from fiction to reality - correspondence.

Mukherjee, Anirban Goutam / Gopalakrishnan, Abilash Valsala / Jayaraj, Rama / Renu, Kaviyarasi / Dey, Abhijit / Vellingiri, Balachandar / Malik, Tabarak

International journal of surgery (London, England)

2023 Volume 109, Issue 9, Page(s) 2855–2858

MeSH term(s)	Humans ; Male ; Breast Neoplasms, Male/epidemiology ; Incidence
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2212038-5
ISSN	1743-9159 ; 1743-9191
ISSN (online)	1743-9159
ISSN	1743-9191
DOI	10.1097/JS9.0000000000000512
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Article ; Online: Artificial intelligence and machine learning algorithms in the detection of heavy metals in water and wastewater: Methodological and ethical challenges.

Maurya, Brij Mohan / Yadav, Nidhi / T, Amudha / J, Satheeshkumar / A, Sangeetha / V, Parthasarathy / Iyer, Mahalaxmi / Yadav, Mukesh Kumar / Vellingiri, Balachandar

Chemosphere

2024 Volume 353, Page(s) 141474

Abstract: Heavy metals (HMs) enter waterbodies through various means, which, when exceeding a threshold limit, cause toxic effects both on the environment and in humans upon entering their systems. Recent times have seen an increase in such HM influx incident ... ...

Abstract	Heavy metals (HMs) enter waterbodies through various means, which, when exceeding a threshold limit, cause toxic effects both on the environment and in humans upon entering their systems. Recent times have seen an increase in such HM influx incident rates. This requires an instant response in this regard to review the challenges in the available classical methods for HM detection and removal. As well as provide an opportunity to explore the applications of artificial intelligence (AI) and machine learning (ML) for the identification and further redemption of water and wastewater from the HMs. This review of research focuses on such applications in conjunction with the available in-silico models producing worldwide data for HM levels. Furthermore, the effect of HMs on various disease progressions has been provided, along with a brief account of prediction models analysing the health impact of HM intoxication. Also discussing the ethical and other challenges associated with the use of AI and ML in this field is the futuristic approach intended to follow, opening a wide scope of possibilities for improvement in wastewater treatment methodologies.
MeSH term(s)	Humans ; Artificial Intelligence ; Wastewater ; Water/analysis ; Algorithms ; Machine Learning ; Metals, Heavy/analysis
Chemical Substances	Wastewater ; Water (059QF0KO0R) ; Metals, Heavy
Language	English
Publishing date	2024-02-19
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	120089-6
ISSN	1879-1298 ; 0045-6535 ; 0366-7111
ISSN (online)	1879-1298
ISSN	0045-6535 ; 0366-7111
DOI	10.1016/j.chemosphere.2024.141474
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Article ; Online: Plausible Role of Mitochondrial DNA Copy Number in Neurodegeneration-a Need for Therapeutic Approach in Parkinson's Disease (PD).

Venkatesan, Dhivya / Iyer, Mahalaxmi / Narayanasamy, Arul / Gopalakrishnan, Abilash Valsala / Vellingiri, Balachandar

Molecular neurobiology

2023 Volume 60, Issue 12, Page(s) 6992–7008

Abstract: Parkinson's disease (PD) is an advancing age-associated progressive brain disorder which has various diverse factors, among them mitochondrial dysfunction involves in dopaminergic (DA) degeneration. Aging causes a rise in mitochondrial abnormalities ... ...

Abstract	Parkinson's disease (PD) is an advancing age-associated progressive brain disorder which has various diverse factors, among them mitochondrial dysfunction involves in dopaminergic (DA) degeneration. Aging causes a rise in mitochondrial abnormalities which leads to structural and functional modifications in neuronal activity and cell death in PD. This ends in deterioration of mitochondrial function, mitochondrial alterations, mitochondrial DNA copy number (mtDNA CN) and oxidative phosphorylation (OXPHOS) capacity. mtDNA levels or mtDNA CN in PD have reported that mtDNA depletion would be a predisposing factor in PD pathogenesis. To maintain the mtDNA levels, therapeutic approaches have been focused on mitochondrial biogenesis in PD. The depletion of mtDNA levels in PD can be influenced by autophagic dysregulation, apoptosis, neuroinflammation, oxidative stress, sirtuins, and calcium homeostasis. The current review describes the regulation of mtDNA levels and discusses the plausible molecular pathways in mtDNA CN depletion in PD pathogenesis. We conclude by suggesting further research on mtDNA depletion which might show a promising effect in predicting and diagnosing PD.
MeSH term(s)	Humans ; DNA, Mitochondrial/genetics ; DNA, Mitochondrial/metabolism ; Parkinson Disease/genetics ; Parkinson Disease/therapy ; Parkinson Disease/metabolism ; DNA Copy Number Variations/genetics ; Mitochondria/metabolism ; Neurons/metabolism
Chemical Substances	DNA, Mitochondrial
Language	English
Publishing date	2023-07-31
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-023-03500-x
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Article ; Online: Advantages of mesenchymal stem cell over the other stem cells.

Gopalarethinam, Janani / Nair, Aswathy P / Iyer, Mahalaxmi / Vellingiri, Balachandar / Subramaniam, Mohana Devi

Acta histochemica

2023 Volume 125, Issue 4, Page(s) 152041

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Adult ; Humans ; Mesenchymal Stem Cells ; Embryonic Stem Cells ; Induced Pluripotent Stem Cells/metabolism ; Signal Transduction ; Mesenchymal Stem Cell Transplantation/methods
Language	English
Publishing date	2023-05-09
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	77-2
ISSN	1618-0372 ; 0065-1281
ISSN (online)	1618-0372
ISSN	0065-1281
DOI	10.1016/j.acthis.2023.152041
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