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  1. Quantitative Structure-Activity Relationship (QSAR) Studies for the Inhibition of MAOs
    Ramesh M, Muthuraman A
    Comb Chem High Throughput Screen, 2020;23(9):887-897.
    PMID: 32208114 DOI: 10.2174/1386207323666200324173231
    Monoamine oxidases are the crucial drug targets for the treatment of neurodegenerative disorders like depression, Parkinson's disease, and Alzheimer's disease. The enzymes catalyze the oxidative deamination of several monoamine containing neurotransmitters, i.e. serotonin (5-HT), melatonin, epinephrine, norepinephrine, phenylethylamine, benzylamine, dopamine, tyramine, etc. The oxidative reaction of monoamine oxidases results in the production of hydrogen peroxide that leads to the neurodegeneration process. Therefore, the inhibition of monoamine oxidases has shown a profound effect against neurodegenerative diseases. At present, the design and development of newer lead molecules for the inhibition of monoamine oxidases are under intensive research in the field of medicinal chemistry. Recently, the advancement in QSAR methodologies has shown considerable interest in the development of monoamine oxidase inhibitors. The present review describes the development of QSAR methodologies, and their role in the design of newer monoamine oxidase inhibitors. It will assist the medicinal chemist in the identification of selective and potent monoamine oxidase inhibitors from various chemical scaffolds.
  2. Computer-Aided Drug Discovery (CADD) Approaches for the Management of Neuropathic Pain
    Ramesh M, Muthuraman A
    Curr Top Med Chem, 2021;21(32):2856-2868.
    PMID: 34809547 DOI: 10.2174/1568026621666211122161932
    Neuropathic pain occurs due to physical damage, injury, or dysfunction of neuronal fibers. The pathophysiology of neuropathic pain is too complex. Therefore, an accurate and reliable prediction of the appropriate hits/ligands for the treatment of neuropathic pain is a challenging process. However, computer-aided drug discovery approaches contributed significantly to discovering newer hits/ligands for the treatment of neuropathic pain. The computational approaches like homology modeling, induced-fit molecular docking, structure-activity relationships, metadynamics, and virtual screening were cited in the literature for the identification of potential hit molecules against neuropathic pain. These hit molecules act as inducible nitric oxide synthase inhibitors, FLAT antagonists, TRPA1 modulators, voltage-gated sodium channel binder, cannabinoid receptor-2 agonists, sigma-1 receptor antagonists, etc. Sigma-1 receptor is a distinct type of opioid receptor and several patents were obtained for sigma-1 receptor antagonists for the treatment of neuropathic pain. These molecules were found to have a profound role in the management of neuropathic pain. The present review describes the validated therapeutic targets, potential chemical scaffolds, and crucial protein-ligand interactions for the management of neuropathic pain based on the recently reported computational methodologies of the present and past decades. The study can help the researcher to discover newer drugs/drug-like molecules against neuropathic pain.
  3. Fulltext Efficacy of rajayoga meditation on positive thinking: an index for self-satisfaction and happiness in life
    Ramesh MG, Sathian B, Sinu E, Kiranmai SR
    J Clin Diagn Res, 2013 Oct;7(10):2265-2267.
    PMID: 24298493 DOI: 10.7860/JCDR/2013/5889.3488
    OBJECTIVES: Psychological studies have shown that brief period of mindfulness meditation significantly improves critical cognitive skills. But, there are no studies which have assessed the effects of Brahma Kumaris Rajayoga Meditation (BKRM) practice on positive thinking and happiness in life. The present study was designed to test the hypothesis is BKRM enhances positive thinking and that essential to attain higher levels of self-satisfaction and happiness in life.

    MATERIAL AND METHODS: This study is a cross sectional comparative study which was done between Rajayoga meditators and non-meditators. This study was conducted at BKRM Centres at Manipal and Udupi in Karnataka, India. Fifty subjects were selected for this study, which included those practising BKRM in their normal routine life (n=25) and non-meditators (n=25) who were aged 42.95+/15.29 years. Self-reported Oxford happiness questionnaire (OHQ) was administered to all subjects and their happiness scores and status were assessed and compared. Items related to self-satisfaction in life were selected from the OHQ and compared between meditators and non-meditators. Participants completed self-reported OHQ, from which data of happiness status and self-satisfaction in relation to meditation duration and frequency were analyzed by descriptive statistics and test of hypothesis.

    RESULTS: Mean happiness scores of BKRM were significantly higher (p<0.001) in meditators as compared to those in non-meditators. The number of meditators experiencing happiness status were significantly higher (p<0.05) in comparison with non-meditators. Additionally, meditators scored significantly higher on self-satisfaction items (p<0.001) as compared to non-meditators. There was no correlation between age and years of meditation practice with happiness score and self-satisfaction score.

    CONCLUSION: BKRM helps in significantly increasing self-satisfaction and happiness in life by enhancing positive thinking. Irrespective of age and years of short-term or long-term meditation practice, enhanced positive thinking increases self-satisfaction and happiness in life.

  4. Fulltext Distribution of isopod parasites in commercially important marine fishes of the Miri coast, East Malaysia
    Anand Kumar A, Rameshkumar G, Ravichandran S, Nagarajan R, Prabakaran K, Ramesh M
    J Parasit Dis, 2017 Mar;41(1):55-61.
    PMID: 28316388 DOI: 10.1007/s12639-016-0749-6
    Isopods occur very commonly as parasites in food fishes. Parasitic isopods are typically marine and usually inhabit the warmer seas. They are blood-feeding; several species settle in the buccal cavity of fish, others live in the gill chamber or on the body surface including the fins. Isopods can cause morbidity and mortality in captive fish populations. The infestation usually pressure atrophy often accompanies the presence of larger parasites. The present study was aimed at collecting information on the neglected group of isopod parasites of the marine fishes from the Miri coastal environment, East Malaysia. A very little information available regarding the distribution of isopod parasites of Malaysian coastal environment. In the present study, nine isopod parasites were  oberved from ten marine fish species. The maximum number of parasites were observed in the months of June and October, 2013. Maximum prevalence was observed in October (50 %) and the minimum was observed in June (7.14 %). The parasitic infestation may lead to an economic loss in commercial fish species.
  5. A review of natural polysaccharides for drug delivery applications: Special focus on cellulose, starch and glycogen
    Gopinath V, Saravanan S, Al-Maleki AR, Ramesh M, Vadivelu J
    Biomed Pharmacother, 2018 Nov;107:96-108.
    PMID: 30086465 DOI: 10.1016/j.biopha.2018.07.136
    Natural polysaccharides are renewable with a high degree of biocompatibility, biodegradability, and ability to mimic the natural extracellular matrix (ECM) microenvironment. Comprehensive investigations of polysaccharides are essential for our fundamental understanding of exploiting its potential as bio-composite, nano-conjugate and in pharmaceutical sectors. Polysaccharides are considered to be superior to other polymers, for its ease in tailoring, bio-compatibility, bio-activity, homogeneity and bio-adhesive properties. The main focus of this review is to spotlight the new advancements and challenges concerned with surface modification, binding domains, biological interaction with the conjugate including stability, polydispersity, and biodegradability. In this review, we have limited our survey to three essential polysaccharides including cellulose, starch, and glycogen that are sourced from plants, microbes, and animals respectively are reviewed. We also present the polysaccharides which have been extensively modified with the various types of conjugates for combating last-ditch pharmaceutical challenges.
  6. Physiological and Pathophysiological Role of Cysteine Metabolism in Human Metabolic Syndrome
    Muthuraman A, Ramesh M, Shaikh SA, Aswinprakash S, Jagadeesh D
    Drug Metab Lett, 2021;14(3):177-192.
    PMID: 34895129 DOI: 10.2174/1872312814666211210111820
    Cysteine is one of the major intermediate products of cellular amino-acid metabolism. It is a semi-essential amino acid for protein synthesis. Besides, it is also employed in the regulation of major endogenous anti-oxidant molecule i.e., reduced glutathione (GSH). Further, it is a precursor of multiple sulfur-containing molecules like hydrogen sulfide, lanthionine, taurine, coenzyme A and biotin. It is also one of the key molecules for post-translational modifications of various cellular proteins. In physiological conditions, it is employed in the sulfhydration process and plays a key role in the physiology modification of the inflammatory process in various organs, including the neurological system. The catabolism of cysteine is regulated by cysteine dioxygenase enzyme activity. The dysregulated conditions of cysteine and cysteine-associated hydrogen sulfide metabolism are widely employed in the acceleration of the neurodegenerative process. Moreover, the upregulation of cysteine and hydrogen sulfide synthesis occurs via the reverse trans-sulfuration process. This process helps to manage the worsening of a pathological condition of a cellular system. Moreover, it is also employed in the accumulation of homocysteine contents. Further, both cysteine and homocysteine molecules are widely accepted as biomarkers for various types of diseases. Therefore, the targets involved in the regulation of cysteine have been considered as valid targets to treat various disorders like cardiac disease, ischemic stroke, diabetes, cancer, and renal dysfunction.
  7. Fulltext The effect of fluorosis on human teeth under light microscopy: A cross-sectional study
    Ramesh M, Narasimhan M, Krishnan R, Aruna RM, Kuruvilla S
    J Oral Maxillofac Pathol, 2017 Sep-Dec;21(3):345-350.
    PMID: 29391706 DOI: 10.4103/jomfp.JOMFP_247_16
    Background: Fluoride is needed for the normal development of bone and teeth; in high levels, it affects developing teeth and bone. Dental fluorosis (DF) is caused by ingestion of excess fluoride mainly through drinking water.

    Aim: The present study aims to observe and understand the histological changes of fluorosed teeth under light microscope (LM).

    Materials and Methods: Teeth which were indicated for extractions for orthodontic or periodontal problems were selected. Thirty extracted teeth were selected with varying degrees of DF based on modified Dean's fluorosis index. Ground sections of these teeth were prepared and the sections were studied under binocular LM. Photomicrographs were taken under high power objective using 15 megapixels Nikon camera.

    Results and Conclusion: Qualitative histologic changes in different grades of fluorosed teeth were evaluated in enamel, dentin, cementum and between their junctions. Fluoride interacts with enamel in both mineral phases and organic macromolecules by strong ionic and hydrogen bonds resulting in incomplete crystal growth at prism peripheries. This presents as hypomineralization of enamel and dentin, increased interglobular dentin, increased secondary curvatures and changes in cementum such as diffuse cementodentinal junction and increased thickness of Tomes' granular layer. Changes in the structure of the teeth with Dean's index below 2 and teeth with Dean's index of 2 and above were compared using Chi-square test. P value was found to be highly significant being 0.00047. Many of the features of dental fluorosis seen in the present study under light microscope are comparable to those results studied under specialized microscopes.
  8. Comparative Evaluation of Dental and Skeletal Fluorosis in an Endemic Fluorosed District, Salem, Tamil Nadu
    Ramesh M, Malathi N, Ramesh K, Aruna RM, Kuruvilla S
    J Pharm Bioallied Sci, 2017 Nov;9(Suppl 1):S88-S91.
    PMID: 29284943 DOI: 10.4103/jpbs.JPBS_77_17
    Background: High levels of fluoride in the drinking water, especially ground water, results in skeletal fluorosis which involves the bone and major joints. This study was conducted to assess the prevalence of skeletal fluorosis to compare with dental fluorosis in an endemically fluorosed population in the District of Salem, Tamil Nadu.

    Materials and Methods: Institutional ethical clearance was obtained. A total of 206 patients who reported to the Department of Hematology for blood investigations were the participants in this study. Age, sex, place, weight, height, dental fluorosis, and skeletal complaints were noted down. Body mass index was calculated, and statistical analysis was performed.

    Results: Dental fluorosis was present in 63.1% and absent in 36.9% of the samples reported. Skeletal fluorosis was present in 24.8% and was absent in 75.2%. A large number of the patients had knee pain and difficulty in bending. Chi-square test was used for statistical analysis. Skeletal fluorosis and age were compared and P value was 0.00 and was significant. Dental fluorosis and skeletal fluorosis were compared and P value was found to be 0.000 and significant.

    Discussion and Conclusion: There is a need to take measures to prevent dental and skeletal fluorosis among the residents of Salem district. Calcium balance should be maintained, and fluoride intake should be minimized to reduce the symptoms. The government should provide water with low fluoride level for drinking and cooking. Once the symptoms develop, treatment largely remains symptomatic, using analgesics and physiotherapy.

  9. Fulltext The prevalence of dental fluorosis and its associated factors in Salem district
    Ramesh M, Narasimhan M, Krishnan R, Chalakkal P, Aruna RM, Kuruvilah S
    Contemp Clin Dent, 2016 6 17;7(2):203-8.
    PMID: 27307668 DOI: 10.4103/0976-237X.183061
    CONTEXT: There are various regions in India that have high levels of fluoride in drinking water sources. Many people residing in such places suffer from dental fluorosis (DF).

    AIMS: To evaluate the prevalence of DF in children residing in Salem and also to find any correlation between DF and other related factors.

    MATERIALS AND METHODS: One school from each block of Salem (total 21 blocks) was selected for the study. A single examiner had evaluated untreated caries, lesions, and DF (for permanent anterior teeth and molars) using the Dean's fluorosis index, in all children. Water fluoride level determination at each school was done using the Tamil Nadu Water Fluoridation and Drainage Board field kit. Other factors that may have contributed to DF were assessed using a questionnaire, which was provided to each student. The data obtained were statistically analyzed using the SPSS software version 11.5.

    STATISTICAL ANALYSIS: Chi-square test was used for statistical analysis.

    RESULTS: DF was present in 56.9% of the children examined. It was mostly seen in 9 years old (72%) and male (59%) children. A positive correlation was found between the occurrence of DF and the duration of residence in a place with high water fluoride content, consumption of borewell water (64%), the parts per million of fluoride in drinking water, consumption of black tea (59%). However, no correlation was found between DF, dental caries, consumption of milk, or consumption of foods cooked in aluminum vessels.

    CONCLUSION: There was a correlation between DF and factors such as male gender, bore well water consumption, black tea consumption and the duration of residence in a place with high water fluoride content.

  10. Current Perspectives of Healthy Mitochondrial Function for Healthy Neurons
    Arunachalam M, Ramesh M, Thiagarajan V, Singla SK, Mudhol S, Muthukumar SP
    Curr Drug Targets, 2021;22(14):1688-1703.
    PMID: 33618645 DOI: 10.2174/1389450122666210222163528
    The neuron is high-energy utilizing tissue. The rate of neuronal cell respiration is higher than in other cells. Cellular respiration occurs with mitochondria. The healthy production and functions of mitochondria play a key role in the maintenance of healthy neurons. In pathological conditions such as neurodegenerative diseases, healthy mitochondria help to alleviate pathological events in neuronal cells. Conversely, mitochondrial dysfunction promotes the acceleration of the neurodegenerative process. Furthermore, glial-derived mitochondria contribute to multiple roles in the regulation of healthy neuron functions. It also supports releasing of the neurotransmitters; generation of the impulses, regulation of the membrane potential and molecular dynamics; controlling of the axonal transport; controlling of the mitochondrial fission and fusion functions in the peripheral as well as the central nervous system. Moreover, it plays a key role in the regeneration process of neuronal cells. Therefore, healthy mitochondria can provide a healthy environment for neuronal cell function and can treat neurodegenerative disorders. In this review, we explore the current view of healthy mitochondria and their role in healthy neuronal functions.
  11. Fulltext In Silico and In Vitro Methods in the Characterization of Beta-Carotene as Pharmaceutical Material via Acetylcholine Esterase Inhibitory Actions
    Muthuraman A, Ramesh M, Mustaffa F, Nadeem A, Nishat S, Paramakrishnan N, et al.
    Molecules, 2023 May 26;28(11).
    PMID: 37298835 DOI: 10.3390/molecules28114358
    Molecular docking is widely used in the assessment of the therapeutic potential of pharmaceutical agents. The binding properties of beta-carotene (BC) to acetylcholine esterase (AChE) proteins were characterized using the molecular docking method. The mechanism of AChE inhibition was assessed by an experimental in vitro kinetic study. In addition, the role of BC action was tested by the zebrafish embryo toxicity test (ZFET). The results of the docking ability of BC to AChE showed significant ligand binding mode. The kinetic parameter, i.e., the low AICc value shown as the compound was the competitive type of inhibition of AChE. Further, BC also showed mild toxicity at a higher dose (2200 mg/L) in ZFET assessment with changes in biomarkers. The LC50 value of BC is 1811.94 mg/L. Acetylcholine esterase (AChE) plays a pivotal role in the hydrolysis of acetylcholine, which leads to the development of cognitive dysfunction. BC possesses the regulation of acetylcholine esterase (AChE) and acid phosphatase (AP) activity to prevent neurovascular dysfunction. Therefore, the characterization of BC could be used as a pharmaceutical agent for the treatment of cholinergic neurotoxicity-associated neurovascular disorders such as developmental toxicity, vascular dementia, and Alzheimer's disease due to its AChE and AP inhibitory actions.
  12. The impact of ocean acidification and cadmium toxicity in the marine crab Scylla serrata: Biological indices and oxidative stress responses
    Thangal SH, Nandhinipriya R, Vasuki C, Gayathri V, Anandhan K, Yogeshwaran A, et al.
    Chemosphere, 2023 Oct 17.
    PMID: 37858766 DOI: 10.1016/j.chemosphere.2023.140447
    Ocean acidification (OA) and heavy metals pollution in marine environments are potentially threatening marine life. The interactive effect of OA and heavy metals could be more vulnerable to marine organisms than individual exposures. In the current study, the effect of OA on the toxicity of cadmium (Cd) in the crab Scylla serrata was evaluated. Crab instars (0.07 cm length and 0.1 g weight) were subjected to pH 8.2, 7.8, 7.6, 7.4, 7.2, and 7.0 with and without 0.01 mg l-1 of Cd for 60 days. We notice a significant decrease in growth, molting, protein, carbohydrate, amino acid, lipid, alkaline phosphatase, and haemocytes of crabs under OA + Cd compared to OA treatment. In contrast, the growth, protein, amino acid, and haemocyte levels were significantly affected by OA, Cd, and its interactions (OA + Cd). However, superoxide dismutase, catalase, lipid peroxidation, glutamic oxaloacetate transaminase, glutamic pyruvate transaminase, and accumulation of Cd in crabs were considerably elevated in OA + Cd treatments compared to OA alone treatments. The present investigation showed that the effect of Cd toxicity might be raised under OA on S. serrata. Our study demonstrated that ocean acidification significantly affects the biological indices and oxidative stress responses of S. serrata exposed to Cd toxicity.
  13. Fulltext Induction of Caspase-Mediated Apoptosis in HepG2 Liver Carcinoma Cells Using Mutagen-Antioxidant Conjugated Self-Assembled Novel Carbazole Nanoparticles and In Silico Modeling Studies
    Anand K, Abdul NS, Ghazi T, Ramesh M, Gupta G, Tambuwala MM, et al.
    ACS Omega, 2021 Jan 12;6(1):265-277.
    PMID: 33458478 DOI: 10.1021/acsomega.0c04461
    In this study, novel self-assembled carbazole-thiooctanoic acid nanoparticles (CTNs) were synthesized from amino carbazole (a mutagen) and thiooctanoic acid (an antioxidant). The nanoparticles were characterized using hyperspectral techniques. Then, the antiproliferative potential of CTNs was determined in HepG2 liver carcinoma cells. This study employed a solvent-antisolvent interaction method to synthesize a spherical CTN of size less than 50 nm. Moreover, CT was subsequently capped to gold nanoparticles (AuNPs) in the additional comparative studies. The CT derivative was synthesized from carbazole and lipoic acid by the amide bond formation reaction using a coupling agent. Furthermore, it was characterized using infrared (IR), 1H nuclear magnetic resonance, dynamic light scattering (DLS), and transmission electron microscopy techniques. The CT-capped gold nanoparticles (CTAuNPs) were prepared from CT, chloroauric acid, and NaBH4. The CTAuNPs were characterized using ultraviolet-visible, high-resolution TEM, DLS, and Fourier transform IR techniques. The cytotoxicity and apoptosis-inducing ability of both nanoparticles were determined in HepG2 cells. The results demonstrate that CTNs exhibit antiproliferative activity in the cancerous HepG2 cells. Moreover, molecular docking and molecular dynamics studies were conducted to explore the therapeutic potential of CT against human EGFR suppressor protein to gain more insights into the binding mode of the CT, which may show a significant role in anticancer therapy.
  14. A review on titanium oxide nanoparticles modified metal-organic frameworks for effective CO2 conversion and efficient wastewater remediation
    Zango ZU, Khoo KS, Garba A, Garba ZN, Danmallam UN, Aldaghri O, et al.
    Environ Res, 2024 Apr 30;252(Pt 3):119024.
    PMID: 38692419 DOI: 10.1016/j.envres.2024.119024
    Environmental pollution has been increasing since last decade due to increasing industrialisation and urbanisation. Various kinds ofenvironmental pollutants including carbon dioxide (CO2), dyes, pharmaceuticals, phenols, heavy metals along with many organic and inorganic species have been discovered in the various environmental compartments which possess harmful impacts tox human health, wildlife, and ecosystems. Thus, various efforts have been made through regulations, technological advancements, and public awareness campaigns to reduce the impact of the pollution. However, finding suitable alternatives to mitigate their impacts remained a challenge. Metal-organic frameworks (MOFs) are one of the advanced materials with unique features such as high porosity and stability which exhibit versatile applications in environmental remediation. Their composites with titanium oxide nanoparticles (TiO2) have been discovered to offer potential feature such as light harvesting capacity and catalytic activity. The composite integration and properties have been confirmed through characterization using surface area analysis, scanning electron/transmission electron microscopy, atomic force microscopy, fourier transformed infrared spectroscopy, X-ray diffraction analysis, X-ray photoelectron spectroscopy, thermogravimetric analysis, and others. Thus, this work rigorously discussed potential applications of the MOF@TiO2 nanomaterials for the CO2 capture and effective utilization in methanol, ethanol, acetone, acetaldehyde, and other useful products that served as fuel to various industrial processes. Additionally, the work highlights the effective performance of the materials towards photocatalytic degradation of both organic and inorganic pollutants with indepth mechanistic insights. The article will offer significant contribution for the development of sustainable and efficient technologies for the environmental monitoring and pollution mitigation.
  15. Systemic Solutions for Addressing Non-Communicable Diseases in Low- and Middle-Income Countries
    Ganju A, Goulart AC, Ray A, Majumdar A, Jeffers BW, Llamosa G, et al.
    J Multidiscip Healthc, 2020;13:693-707.
    PMID: 32801732 DOI: 10.2147/JMDH.S252300
    Non-communicable diseases (NCDs) have been on the rise in low- and middle-income countries (LMICs) over the last few decades and represent a significant healthcare concern. Over 85% of "premature" deaths worldwide due to NCDs occur in the LMICs. NCDs are an economic burden on these countries, increasing their healthcare expenditure. However, targeting NCDs in LMICs is challenging due to evolving health systems and an emphasis on acute illness. The major issues include limitations with universal health coverage, regulations, funding, distribution and availability of the healthcare workforce, and availability of health data. Experts from across the health sector in LMICs formed a Think Tank to understand and examine the issues, and to offer potential opportunities that may address the rising burden of NCDs in these countries. This review presents the evidence and posits pragmatic solutions to combat NCDs.
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