164 results on '"Singh TG"'
Search Results
2. In silico docking studies of Yucca gloriosa L. phytoconstituents with TNF-α, IL-6 and IL-13 receptor against Asthma
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Gupta, S, Grewal, AS, Deswal, G, Singh, S, Vishwas, S, Badavath, V, Dua, K, Thakur, P, and Singh, TG
- Abstract
Yucca gloriosa L. has been comprehensively assessed in vitro and in vivo for its action against asthma. Y. gloriosa L. is a rich source of phenolic compounds such as gloriosaols A-E and yuccaols A-E, which exhibit potent antioxidant activity. Gloriosaols A-E and yuccaols A-E are structurally related to corticosteroids. The current study describes the in silico docking of some important anti-asthmatic phytoconstituents from the plant Y. gloriosa L. with molecular targets of asthma. Toward the recognition of the binding methods of these pharmacologically dynamic components, molecular modelling studies were carried out with target proteins, i.e., interleukin (IL)-6 (1N26), IL-13 (3LB6) and TNF-α (2AZ5), using in silico molecular docking. The components demonstrated encouraging binding interactions with the amino acid residues at the active sites of these proteins, authenticating their verified efficiency as anti-asthmatic agents. The current research, in addition, provides insight into the possible herbal drug-receptor interaction and synthetic drug montelukast sodium receptor interaction, for the possible management of asthma.
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- 2023
3. Journey of Rosmarinic Acid as Biomedicine to Nano-Biomedicine for Treating Cancer: Current Strategies and Future Perspectives
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Chaitanya, MVNL, Ramanunny, AK, Babu, MR, Gulati, M, Vishwas, S, Singh, TG, Chellappan, DK, Adams, J, Dua, K, and Singh, SK
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1115 Pharmacology and Pharmaceutical Sciences - Abstract
Rosmarinic acid (RA) is a polyphenolic metabolite found in various culinary, dietary sources, and medicinal plants like Coleus scutellarioides (Linn) Benth., Lavandula angustifolia Linn., Mellisa officinalis Linn., Origanum vulgare Linn., Rosmarinus officinalis Linn., Zataria multiflora Boiss. and Zhumeria majdae Rech. F. Apart from its dietary and therapeutic values, RA is an important anticancer phytochemical owing to its multi-targeting anticancer mechanism. These properties provide a scope for RA’s therapeutic uses beyond its traditional use as a dietary source. However, its oral bioavailability is limited due to its poor solubility and permeability. This impedes its efficacy in treating cancer. Indeed, in recent years, tremendous efforts have been put towards the development of nanoformulations of RA for treating cancer. However, this research is in its initial stage as bringing a nanoparticle into the market itself is associated with many issues such as stability, toxicity, and scale-up issues. Considering these pitfalls during formulation development and overcoming them would surely provide a new face to RA as a nanomedicine to treat cancer. A literature search was conducted to systematically review the various biological sources, extraction techniques, and anticancer mechanisms through which RA showed multiple therapeutic effects. Various nanocarriers of RA pertaining to its anticancer activity are also discussed in this review.
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- 2022
4. Plant-based drug delivery systems in respiratory diseases
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Mehta, M, Sharma, P, Kaur, S, Dhanjal, DS, Singh, B, Vyas, M, Gupta, G, Chellappan, DK, Nammi, S, Singh, TG, Dua, K, Satija, S, Dua, K, Hansbro, P, Wadhwa, R, Haghi, M, Pont, L, and Williams, K
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- 2020
5. Development of a novel HPTLC fingerprint method for simultaneous estimation of berberine and rutin in medicinal plants and their pharmaceutical preparations followed by its application in antioxidant assay
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Satija, S, Tambuwala, MM, Pabreja, K, Bakshi, HA, Chellappan, DK, Aljabali, AA, Nammi, S, Singh, TG, Dureja, H, Gupta, G, Dua, K, Mehta, M, and Garg, M
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0301 Analytical Chemistry ,Analytical Chemistry - Abstract
The present study was designed to develop and validate a high-performance thin-layer chromatography (HPTLC) system for the simultaneous quantitative determination of berberine and rutin in Tinospora cordifolia extract and their pharmaceutical preparations. Chromatographic development was done using a blend of n-hexane, ethyl acetate, glacial acetic acid and methanol (10:1.1:1.1:2.5, v/v) as the mobile phase. Detection was completed densitometrically at 254 nm. The R estimation of berberine and rutin was observed to be 0.67 ± 0.02 and 0.47 ± 0.02, respectively. The developed HPTLC method was validated according to ICH guidelines; the method was specific, linear and accurate and can be used to determine berberine and rutin in marketed herbal preparations. The Tinospora cordifolia plant extract was further evaluated for antioxidant activity using HPTLC, and berberine was found to be more active than rutin during DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity. The method was found simple, rapid, accurate, specific and robust for the analysis of berberine and rutin in crude drug using the same method. [Figure not available: see fulltext.] F
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- 2020
6. Evolving significance of kinase inhibitors in the management of Alzheimer's disease.
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Ansari MM, Sahu SK, Singh TG, Singh SRJ, and Kaur P
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- Humans, Animals, tau Proteins metabolism, tau Proteins antagonists & inhibitors, Protein Kinases metabolism, Signal Transduction drug effects, Amyloid beta-Peptides metabolism, Amyloid beta-Peptides antagonists & inhibitors, Phosphorylation drug effects, Alzheimer Disease drug therapy, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors pharmacology
- Abstract
Alzheimer's disease is a neurodegenerative problem with progressive loss of memory and other cognitive function disorders resulting in the imbalance of neurotransmitter activity and signaling progression, which poses the need of the potential therapeutic target to improve the intracellular signaling cascade brought by kinases. Protein kinase plays a significant and multifaceted role in the treatment of Alzheimer's disease, by targeting pathological mechanisms like tau hyperphosphorylation, neuroinflammation, amyloid-beta production and synaptic dysfunction. In this review, we thoroughly explore the essential protein kinases involved in Alzheimer's disease, detailing their physiological roles, regulatory impacts, and the newest inhibitors and compounds that are progressing into clinical trials. All the findings of studies exhibited the promising role of kinase inhibitors in the management of Alzheimer's disease. However, it still poses the need of addressing current challenges and opportunities involved with this disorder for the future perspective of kinase inhibitors in the management of Alzheimer's disease. Further study includes the development of biomarkers, combination therapy, and next-generation kinase inhibitors with increased potency and selectivity for its future prospects., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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7. Elucidating the molecular symphony: unweaving the transcriptional & epigenetic pathways underlying neuroplasticity in opioid dependence and withdrawal.
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Wani SN, Grewal AK, Khan H, and Singh TG
- Abstract
The persistent use of opioids leads to profound changes in neuroplasticity of the brain, contributing to the emergence and persistence of addiction. However, chronic opioid use disrupts the delicate balance of the reward system in the brain, leading to neuroadaptations that underlie addiction. Chronic cocaine usage leads to synchronized alterations in gene expression, causing modifications in the Nucleus Accumbens (NAc), a vital part of the reward system of the brain. These modifications assist in the development of maladaptive behaviors that resemble addiction. Neuroplasticity in the context of addiction involves changes in synaptic connectivity, neuronal morphology, and molecular signaling pathways. Drug-evoked neuroplasticity in opioid addiction and withdrawal represents a complicated interaction between environmental, genetic, and epigenetic factors. Identifying specific transcriptional and epigenetic targets that can be modulated to restore normal neuroplasticity without disrupting essential physiological processes is a critical consideration. The discussion in this article focuses on the transcriptional aspects of drug-evoked neuroplasticity, emphasizing the role of key transcription factors, including cAMP response element-binding protein (CREB), ΔFosB, NF-kB, Myocyte-enhancing factor 2 (MEF2), Methyl-CpG binding protein 2 (MeCP2), E2F3a, and FOXO3a. These factors regulate gene expression and lead to the neuroadaptive changes observed in addiction and withdrawal. Epigenetic regulation, which involves modifying gene accessibility by controlling these structures, has been identified as a critical component of addiction development. By unraveling these complex molecular processes, this study provides valuable insights that may pave the way for future therapeutic interventions targeting the mechanisms underlying addiction and withdrawal., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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8. Pervasive expostulation of p53 gene promoting the precipitation of neurogenic convulsions: A journey in therapeutic advancements.
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Gupta V, Singh S, and Singh TG
- Abstract
Epilepsy, a neurological disorder characterized by prolonged and excessive seizures, has been linked to elevated levels of the tumor suppressor gene p53, which contributes to neuronal dysfunction. This review explores the molecular mechanisms of p53 in epilepsy and discusses potential future therapeutic strategies. Research indicates that changes in p53 expression during neuronal apoptosis, neuroinflammation, and oxidative stress play a significant role in the pathogenesis of epilepsy. Elevated p53 disrupts glutamatergic neurotransmission and hyperactivates NMDA and AMPA receptors, leading to increased neuronal calcium influx, mitochondrial oxidative stress, and activation of apoptotic pathways mediated neuronal dysfunction, exacerbating epileptogenesis. The involvement of p53 in epilepsy suggests that targeting this protein could be beneficial in mitigating neuronal damage and preventing seizure recurrence. Pharmacological agents like pifithrin-α have shown promise in reducing p53-mediated apoptosis and seizure severity. Gene therapy approaches, such as viral vector-mediated delivery of wild-type p53 or RNA interference targeting mutant p53, have also been effective in restoring normal p53 function and reducing seizure susceptibility. Despite these advances, the heterogeneous nature of epilepsy and potential long-term side effects of p53 modulation present challenges. Future research should focus on elucidating the precise molecular mechanisms of p53 and developing personalized therapeutic strategies. Modulating p53 activity holds promise for reducing seizure susceptibility and improving the quality of life for individuals with epilepsy. The current review provides the understanding the intricate role of p53 in neuroinflammatory pathways, including JAK-STAT, JNK, NF-κB, Sonic Hedgehog, and Wnt, is crucial for developing targeted therapies., Competing Interests: Declaration of competing interest This is to bring to your kind notice that the manuscript originally written by Vrinda Gupta, Shareen Singh, Thakur Gurjeet Singh titled “Pervasive Expostulation of p53 Gene Promoting the Precipitation of Neurogenic Convulsions: A Journey in Therapeutic Advancements” is here with submitted for publication in European Journal of Pharmacology. It has not been published before, and it is not under consideration for publication in any other journal (s).We certify that we have obtained written permission for the use of text, tables, and/or illustrations from any copyrighted source(s), and we declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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9. Emerging targets in amyotrophic lateral sclerosis (ALS): The promise of ATP-binding cassette (ABC) transporter modulation.
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Mohan M, Mannan A, Nauriyal A, and Singh TG
- Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative primarily affecting motor neurons, leading to disability and neuronal death, and ATP-Binding Cassette (ABC) transporter due to their role in drug efflux and modulation of various cellular pathways contributes to the pathogenesis of ALS. In this article, we extensively investigated various molecular and mechanistic pathways linking ALS transporter to the pathogenesis of ALS; this involves inflammatory pathways such as Mitogen-Activated Protein Kinase (MAPK), Phosphatidylinositol-3-Kinase/Protein Kinase B (PI3K/Akt), Toll-Like Receptor (TLR), Glycogen Synthase Kinase 3β (GSK-3β), Nuclear Factor Kappa-B (NF-κB), and Cyclooxygenase (COX). Oxidative pathways such as Astrocytes, Glutamate, Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Sirtuin 1 (SIRT-1), Forkhead box protein O (FOXO), Extracellular signal-regulated kinase (ERK). Additionally, we delve into the role of autophagic pathways like TAR DNA-binding protein 43 (TDP-43), AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and lastly, the apoptotic pathways. Furthermore, by understanding these intricate interactions, we aim to develop novel therapeutic strategies targeting ABC transporters, improving drug delivery, and ultimately offering a promising avenue for treating ALS., Competing Interests: Declaration of Competing Interest There are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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10. Multiple Sclerosis: Pathogenesis Mechanism and Biomarkers.
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Arya A, Dhall M, Mittal V, Kaushik D, Mudgal P, Kumar T, Pandey M, Kadian R, Sharma P, Rani N, and Singh TG
- Abstract
Multiple sclerosis (MS) is an unceasing, demyelinating, idiopathic inflammatory, and neurodegenerative disease of the Central Nervous System (CNS.) The disease is characterized by the occurrence of neurological symptoms over a period of days to weeks, abide by partial or absolute diminutions of various durations. In this review, a concise outline on disease activity and progression of MS, pathogenesis with the special prominence on the biomarkers for the MS as therapeutic targets has been discussed by carrying out a comprehensive literature survey employing chief websites and search engines for investigation. Cortical inflammation, neurodegeneration, demyelination, axonal injury, axonal loss, oligodendrocytes, mitochondrial dysfunction, microglia activation, oxidative and nitrosative stress are the pathological hallmarks of the MS. CNS neurofilaments, chitinase and chitinase 3-like proteins, soluble circulating form (sCD163), Chemokine ligand 13 (CXCL13), immunoglobulin M, MicroRNA (miRNA) and messenger Ribonucleic Acid (mRNA), Glial fibrillary acidic protein (GFAP), serum osteopontin, 8-iso-prostaglandin F2α (8-iso-PGF2 α), apo-Lipoprotein E and myelinreactive T cells are some of the therapeutically valuable biomarkers for such multifarious disorder. MS is one of the chronic neurodegenerative diseases with undefined etiology. The study of the pathophysiology of the disease and the involvement of certain biomarkers can help identify new targets for therapeutic intercession, identify individuals at risk of developing the disease later in life, and allow more effective treatment of progressive diseases such as MS., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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11. Therapeutic potential of transient receptor potential (TRP) channels in psychiatric disorders.
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Sharma V, Sharma P, and Singh TG
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- Humans, Animals, Transient Receptor Potential Channels metabolism, Mental Disorders metabolism, Mental Disorders drug therapy
- Abstract
Psychiatric disorders such as Bipolar disorder, Anxiety, Major depressive disorder, Schizophrenia, Attention-deficit/hyperactivity disorder, as well as neurological disorders such as Migraine, are linked by the evidence of altered calcium homeostasis. The disturbance of intra-cellular calcium homeostasis disrupts the activity of numerous ion channels including transient receptor potential (TRP) channels. TRP channel families comprise non-selective calcium-permeable channels that have been implicated in variety of physiological processes in the brain, as well as in the pathogenesis of psychiatric disorders. Through a comprehensive review of current research and experimentation, this investigation elucidates the role of TRP channels in psychiatric disorders. Furthermore, this review discusses about the exploration of epigenetics and TRP channels in psychiatric disorders., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)
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- 2024
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12. Non-coding RNAs as key regulators of Gasdermin-D mediated pyroptosis in cancer therapy.
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Gupta G, Afzal M, Moglad E, Ali H, Singh TG, Kumbhar P, Disouza J, Almujri SS, Kazmi I, Alzarea SI, Hemalatha KP, Goh BH, Singh SK, and Dua K
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- Humans, Animals, Gene Expression Regulation, Neoplastic, Gasdermins, Pyroptosis physiology, Neoplasms pathology, Neoplasms genetics, Neoplasms metabolism, Neoplasms therapy, Phosphate-Binding Proteins metabolism, Phosphate-Binding Proteins genetics, RNA, Untranslated genetics, RNA, Untranslated metabolism, Intracellular Signaling Peptides and Proteins metabolism, Intracellular Signaling Peptides and Proteins genetics
- Abstract
Pyroptosis is an inflammatory programed cell death process that plays a crucial role in cancer therapeutic, while Gasdermin-D is a critical effector protein for pyroptosis execution. This review discusses the intricate interactions between Gasdermin-D and some non-coding RNAs (lncRNA, miRNA, siRNA) and their potential application in the regulation of pyroptosis as an anticancer therapy. Correspondingly, these ncRNAs significantly implicate in Gasdermin-D expression and function regarding the pyroptosis pathway. Functioning as competing endogenous RNAs (ceRNAs), these ncRNAs might regulate Gasdermin-D at the molecular level, underlying fatal cell death caused by cancer and tumor propagation. Therefore, these interactions appeal to therapeutics, offering new avenues for cancer treatment. It address this research gap by discussing the possible roles of ncRNAs as mediators of gasdermin-D regulation. It suggest therapeutic strategies based on the current research findings to ensure the interchange between the ideal pyroptosis and cancer cell death., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)
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- 2024
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13. Proportion of Patients in the United States Who Fill Their Nirmatrelvir/Ritonavir Prescriptions.
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Rudolph AE, Khan FL, Singh TG, Valluri SR, Puzniak LA, and McLaughlin JM
- Abstract
Introduction: Although real-world studies demonstrate that those prescribed nirmatrelvir/ritonavir (and particularly within 5 days of symptom onset) are less likely to experience severe COVID-19 outcomes, prior studies show that only a small fraction of patients with COVID-19 who are eligible for nirmatrelvir/ritonavir receive a prescription. Studies calculating the proportion of nirmatrelvir/ritonavir prescriptions filled and identifying individual- and pharmacy-level correlates of filling nirmatrelvir/ritonavir are lacking., Methods: This retrospective cohort study included individuals aged ≥ 12 years with a nirmatrelvir/ritonavir prescription ordered at a large national retail pharmacy (December 22, 2021-August 12, 2023). Those taking contraindicated medications were excluded. For those with only one nirmatrelvir/ritonavir prescription ordered, the outcome was whether the prescription was filled (yes/no). In a subanalysis of these individuals, the outcome was whether the prescription was filled within 5 days of symptom onset (yes/no). For those with multiple prescriptions ordered, the outcome was whether > 1 (vs. 0 or 1) prescriptions were filled. A log-binomial regression with generalized estimating equations was used to identify individual (clinical and demographic) and pharmacy-level (percentage of trade area that is non-Hispanic white, urbanicity, US Census region, and tract-level area deprivation index) correlates., Results: A total of 2,103,570 unique nirmatrelvir/ritonavir prescriptions were ordered for 1,985,990 individuals. Among the 95% of individuals prescribed only one nirmatrelvir/ritonavir course, 88% filled their prescription. Among those with > 1 prescription ordered, 77% (82,993/108,411) filled one and 13% (13,662/108,411) filled > 1. Patients ≥ 50 years of age and those with documented high-risk conditions were slightly more likely to fill prescriptions, regardless of whether one or multiple courses were ordered. Individuals with cancer, asthma, or taking corticosteroids or immunosuppressive medications were more likely to fill multiple prescriptions., Conclusions: Most patients filled their nirmatrelvir/ritonavir prescriptions. Interventions to improve uptake should focus on increasing patient and provider awareness, reducing nirmatrelvir/ritonavir prescribing disparities, and ensuring treatment initiation within 5 days., (© 2024. The Author(s).)
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- 2024
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14. Leukotriene signaling in neurodegeneration: implications for treatment strategies.
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Sharma V, Sharma P, and Singh TG
- Abstract
Leukotrienes (LTs) are a group of substances that cause inflammation. They are produced by the enzyme 5-lipoxygenase (5-LOX) from arachidonic acid. Cysteinyl LTs are a group of lipid molecules that have a prominent role in inflammatory signaling in the allergic diseases. Although they are traditionally known for their role in allergic disease, current advancements in bio-medical research have shed light on the involvement of these inflammatory mediators in diseases such as in the inflammation related to central nervous system (CNS) disorders. Among the CNS diseases, LTs, along with 5-LOX and their receptors, have been shown to be associated with multiple sclerosis (MS), Alzheimer's disease (AD), and Parkinson's disease (PD). Through a comprehensive review of current research and experimentation, this investigation provides an insight on the biosynthesis, receptors, and biological effects of LTs in the body. Furthermore, implications of leukotriene signaling in CNS and its intricate role in neurodegeneration are also studied. Through the revelation of these insights, our aim is to establish a foundation for the development of enhanced and focused therapeutic approaches in the continuous endeavor to combat neurodegeneration. Furthermore, the pharmacological inhibition of leukotriene signaling with selective inhibitors offers promising prospects for future interventions and treatments for neurodegenerative diseases., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2024
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15. Opiorphin: an endogenous human peptide with intriguing application in diverse range of pathologies.
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Tiwari C, Khan H, Grewal AK, Dhankhar S, Chauhan S, Dua K, Gupta G, and Singh TG
- Abstract
Mammalian zinc ectopeptidases have significant functions in deactivating neurological and hormonal peptide signals on the cell surface. The identification of Opiorphin, a physiological inhibitor of zinc ectopeptidases that inactivate enkephalin, has revealed its strong analgesic effects in both chemical and mechanical pain models. Opiorphin achieves this by increasing the transmission of endogenous opioids, which are dependent on the body's own opioid system. The function of opiorphin is closely linked to the rat sialorphin peptide, which inhibits pain perception by enhancing the activity of naturally occurring enkephalinergic pathways that depend on μ- and δ-opioid receptors. Opiorphin is highly intriguing in terms of its physiological implications within the endogenous opioidergic pathways, particularly in its ability to regulate mood-related states and pain perception. Opiorphin can induce antidepressant-like effects by influencing the levels of naturally occurring enkephalin, which are released in response to specific physical and/or psychological stimuli. This effect is achieved through the modulation of delta-opioid receptor-dependent pathways. Furthermore, research has demonstrated that opiorphin's impact on the cardiovascular system is facilitated by the renin-angiotensin system (RAS), sympathetic ganglia, and adrenal medulla, rather than the opioid system. Hence, opiorphin shows great potential as a solitary candidate for the treatment of several illnesses such as neurodegeneration, pain, and mood disorders., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2024
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16. Mechanistic insights on TLR-4 mediated inflammatory pathway in neurodegenerative diseases.
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Sharma V, Sharma P, and Singh TG
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- Humans, Animals, NF-kappa B metabolism, Inflammation metabolism, Inflammation drug therapy, Toll-Like Receptor 4 metabolism, Neurodegenerative Diseases metabolism, Neurodegenerative Diseases drug therapy, Signal Transduction
- Abstract
Neurodegenerative diseases (NDDs) pose a significant issue in healthcare, needing a thorough knowledge of their complex molecular mechanisms. A diverse set of cell signaling mediators and their interactions play critical roles in neuroinflammation. The release of pro-inflammatory mediators in response to neural dysfunction is detrimental to normal cell survival. Moreover, the important role of nuclear factor-κB (NF-κB) in the central nervous system through Toll-like receptor (TLR) activation has been well established. Therefore, through a comprehensive review of current research and experimentation, this investigation elucidates the interactions between novel pharmacological agents (TLR-4/NF-κB inhibitors) and neurodegeneration encompassing Alzheimer's, Parkinson's, Huntington's disease, amyotrophic lateral sclerosis and stroke. Insights garnered from this exploration underscore the potential of TLR-4 as a therapeutic target. Through the revelation of these insights, our aim is to establish a foundation for the development of enhanced and focused therapeutic approaches in the continuous endeavor to combat neurodegeneration. This review thus serves as a roadmap, guiding future research endeavors toward innovative strategies for combatting the complex interplay between TLR-4 signaling and NDDs., (© 2024. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)
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- 2024
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17. Unlocking new avenues for neuropsychiatric disease therapy: the emerging potential of Peroxisome proliferator-activated receptors as promising therapeutic targets.
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Dey AD, Mannan A, Dhiman S, and Singh TG
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- Humans, Animals, Molecular Targeted Therapy, Peroxisome Proliferator-Activated Receptors agonists, Peroxisome Proliferator-Activated Receptors metabolism, Mental Disorders drug therapy, Mental Disorders metabolism
- Abstract
Rationale: Peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate various physiological processes such as inflammation, lipid metabolism, and glucose homeostasis. Recent studies suggest that targeting PPARs could be beneficial in treating neuropsychiatric disorders by modulating neuronal function and signaling pathways in the brain. PPAR-α, PPAR-δ, and PPAR-γ have been found to play important roles in cognitive function, neuroinflammation, and neuroprotection. Dysregulation of PPARs has been associated with neuropsychiatric disorders like bipolar disorder, schizophrenia, major depression disorder, and autism spectrum disorder. The limitations and side effects of current treatments have prompted research to target PPARs as a promising novel therapeutic strategy. Preclinical and clinical studies have shown the potential of PPAR agonists and antagonists to improve symptoms associated with these disorders., Objective: This review aims to provide an overview of the current understanding of PPARs in neuropsychiatric disorders, their potential as therapeutic targets, and the challenges and future directions for developing PPAR-based therapies., Methods: An extensive literature review of various search engines like PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out with the keywords "PPAR, Neuropsychiatric disorders, Oxidative stress, Inflammation, Bipolar Disorder, Schizophrenia, Major depression disorder, Autism spectrum disorder, molecular pathway"., Result & Conclusion: Although PPARs present a hopeful direction for innovative therapeutic approaches in neuropsychiatric conditions, additional research is required to address obstacles and convert this potential into clinically viable and individualized treatments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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18. Enhancing drug bioavailability for Parkinson's disease: The promise of chitosan delivery mechanisms.
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Shaikh MAJ, Gupta G, Bagiyal P, Gupta S, Singh SK, Pillappan R, Chellappan DK, Prasher P, Jakhmola V, Singh TG, Dureja H, Singh SK, and Dua K
- Abstract
Parkinson's disease (PD) is a widely seen neurodegenerative condition recognized by misfolded α-synuclein (αSyn) protein, a prominent indicator for PD and other synucleinopathies. Motor symptoms like stiffness, akinesia, rest tremor, and postural instability coexist with nonmotor symptoms that differ from person to person in the development of PD. These symptoms arise from a progressive loss of synapses and neurons, leading to a widespread degenerative process in multiple organs. Implementing medical and surgical interventions, such as deep brain stimulation, has enhanced individuals' overall well-being and long-term survival with PD. It should be mentioned that these treatments cannot stop the condition from getting worse. The complicated structure of the brain and the existence of a semi-permeable barrier, commonly known as the BBB, have traditionally made medication delivery for the treatment of PD a challenging endeavor. The drug's low lipophilic nature, enormous size, and peculiarity for various ATP-dependent transport mechanisms hinder its ability to enter brain cells. This article delves at the potential of drug delivery systems based on chitosan (CS) to treat PD., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)
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- 2024
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19. Exploring Therapeutic Potential of Phytoconstituents as a Gut Microbiota Modulator in the Management of Neurological and Psychological Disorders.
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Chandel P, Thapa K, Kanojia N, Rani L, Singh TG, and Rohilla P
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- Humans, Animals, Gastrointestinal Microbiome drug effects, Mental Disorders drug therapy, Nervous System Diseases drug therapy, Nervous System Diseases microbiology, Phytochemicals pharmacology
- Abstract
The functioning of the brain and its impact on behavior, emotions, and cognition can be affected by both neurological and psychiatric disorders that impose a significant burden on global health. Phytochemicals are helpful in the treatment of several neurological and psychological disorders, including anxiety, depression, Huntington's disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD), and autism spectrum disorder (ASD), because they have symptomatic benefits with few adverse reactions. Changes in gut microbiota have been associated with many neurological and psychiatric conditions. This review focuses on the potential efficacy of phytochemicals such as flavonoids, terpenoids, and polyphenols in regulating gut flora and providing symptomatic relief for a range of neurological and psychological conditions. Evidence-based research has shown the medicinal potentials of these phytochemicals, but additional study is required to determine whether altering gut microbiota might slow the advancement of neurological and psychological problems., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)
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- 2024
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20. Therapeutic Implications and Regulations of Protein Post-translational Modifications in Parkinsons Disease.
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Mishra T, Singh S, and Singh TG
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- Humans, Animals, Protein Processing, Post-Translational drug effects, Parkinson Disease metabolism, Parkinson Disease drug therapy
- Abstract
Parkinsons disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss and alpha-synuclein aggregation. This comprehensive review examines the intricate role of post-translational modifications (PTMs) in PD pathogenesis, focusing on DNA methylation, histone modifications, phosphorylation, SUMOylation, and ubiquitination. Targeted PTM modulation, particularly in key proteins like Parkin, DJ1, and PINK1, emerges as a promising therapeutic strategy for mitigating dopaminergic degeneration in PD. Dysregulated PTMs significantly contribute to the accumulation of toxic protein aggregates and dopaminergic neuronal dysfunction observed in PD. Targeting PTMs, including epigenetic strategies, addressing aberrant phosphorylation events, and modulating SUMOylation processes, provides potential avenues for intervention. The ubiquitin-proteasome system, governed by enzymes like Parkin and Nedd4, offers potential targets for clearing misfolded proteins and developing disease-modifying interventions. Compounds like ginkgolic acid, SUMO E1 enzyme inhibitors, and natural compounds like Indole-3-carbinol illustrate the feasibility of modulating PTMs for therapeutic purposes in PD. This review underscores the therapeutic potential of PTM-targeted interventions in modulating PD-related pathways, emphasizing the need for further research in this promising area of Parkinsons disease therapeutics., (© 2024. The Author(s).)
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- 2024
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21. Molecular Mechanisms Underlying the Therapeutic Potential of Plant-Based α-Amylase Inhibitors for Hyperglycemic Control in Diabetes.
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Kaur A, Singh S, Mujwar S, and Singh TG
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Background: Diabetes mellitus (DM), arising from pancreatic β-cell dysfunction and disrupted alpha-amylase secretion, manifests as hyperglycemia. Synthetic inhibitors of alphaamylase like acarbose manage glucose but pose adverse effects, prompting interest in plantderived alternatives rich in antioxidants and anti-inflammatory properties., Objective: The current review investigates plant-based alpha-amylase inhibitors, exploring their potential therapeutic roles in managing DM. Focusing on their ability to modulate postprandial hyperglycemia by regulating alpha-amylase secretion, it assesses their efficacy, health benefits, and implications for diabetes treatment., Method: This review examines plant-derived alpha-amylase inhibitors as prospective diabetic mellitus treatments using PubMed, Google Scholar, and Scopus data., Results: Plant-derived inhibitors, including A. deliciosa, B. egyptiaca, and N. nucifera, exhibit anti-inflammatory and antioxidant properties, effectively reducing alpha-amylase levels in diabetic conditions. Such alpha-amylase inhibitors showed promising alternative treatment in managing diabetes with reduced adverse effects., Conclusion: The current literature concludes that plant-derived alpha-amylase inhibitors present viable therapeutic avenues for diabetes management by modulating alpha-amylase secretion by regulating inflammatory, oxidative stress, and apoptotic mechanisms involved in the pathogenesis of diabetes. Further investigation into their formulations and clinical efficacy may reveal their more comprehensive diabetes therapeutic significance, emphasizing their potential impact on glucose regulation and overall health.
., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)- Published
- 2024
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22. 5,7-dihydroxy-3',4',5'-trimethoxyflavone mitigates lead induced neurotoxicity in rats via its chelating, antioxidant, anti-inflammatory and monoaminergic properties.
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Singh V, Shri R, Sood P, Singh M, Singh TG, Singh R, Kumar A, and Ahmad SF
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- Animals, Male, Rats, Neuroprotective Agents pharmacology, Flavones pharmacology, Lead toxicity, Chelating Agents pharmacology, Rats, Wistar, Hippocampus drug effects, Hippocampus metabolism, Neurotoxicity Syndromes drug therapy, Neurotoxicity Syndromes prevention & control, Glutathione metabolism, Maze Learning drug effects, Antioxidants pharmacology, Anti-Inflammatory Agents pharmacology
- Abstract
Chronic exposure to lead (Pb) induces neurodegenerative changes in animals and humans. Drugs with strong antioxidant properties are effective against Pb-mediated neurotoxicity. In a prior study, we identified 5,7-dihydroxy-3',4',5'-trimethoxyflavone (TMF) from Ocimum basilicum L. leaves as a potent antioxidant and neuroprotective compound. This research explores TMF's neuroprotective effects against Pb-induced brain toxicity in rats to establish it as a therapeutic agent. Rats received lead acetate (100 mg/kg, orally, once daily) for 30 days to induce brain injury, followed by TMF treatment (5 and 10 mg/kg, oral, once daily) 30 min later. Cognitive and motor functions were assessed using Morris Water Maze and horizontal bar tests. Lead, monoamine oxidase (MAO) A and B enzymes, reduced glutathione (GSH), thiobarbituric acid reactive species (TBARS), Tumor necrosis factor-alpha (TNF-α), and IL-6 levels were measured in the hippocampus and cerebellum. Pb exposure impaired cognitive and motor functions, increased Pb, TBARS, TNF-α, and IL-6 levels, and compromised MAO A & B and GSH levels. TMF reversed Pb-induced memory and motor deficits and normalized biochemical anomalies. TMF's neuroprotective effects against lead involve chelating, antioxidant, anti-inflammatory, and monoaminergic properties, suggesting its potential as a treatment for metal-induced brain injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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23. ncRNAs and their impact on dopaminergic neurons: Autophagy pathways in Parkinson's disease.
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Thapa R, Moglad E, Afzal M, Gupta G, Bhat AA, Almalki WH, Kazmi I, Alzarea SI, Pant K, Ali H, Paudel KR, Dureja H, Singh TG, Singh SK, and Dua K
- Subjects
- Humans, Animals, Parkinson Disease genetics, Parkinson Disease metabolism, Parkinson Disease pathology, Autophagy physiology, Dopaminergic Neurons metabolism, Dopaminergic Neurons pathology, RNA, Untranslated genetics
- Abstract
Parkinson's Disease (PD) is a complex neurological illness that causes severe motor and non-motor symptoms due to a gradual loss of dopaminergic neurons in the substantia nigra. The aetiology of PD is influenced by a variety of genetic, environmental, and cellular variables. One important aspect of this pathophysiology is autophagy, a crucial cellular homeostasis process that breaks down and recycles cytoplasmic components. Recent advances in genomic technologies have unravelled a significant impact of ncRNAs on the regulation of autophagy pathways, thereby implicating their roles in PD onset and progression. They are members of a family of RNAs that include miRNAs, circRNA and lncRNAs that have been shown to play novel pleiotropic functions in the pathogenesis of PD by modulating the expression of genes linked to autophagic activities and dopaminergic neuron survival. This review aims to integrate the current genetic paradigms with the therapeutic prospect of autophagy-associated ncRNAs in PD. By synthesizing the findings of recent genetic studies, we underscore the importance of ncRNAs in the regulation of autophagy, how they are dysregulated in PD, and how they represent novel dimensions for therapeutic intervention. The therapeutic promise of targeting ncRNAs in PD is discussed, including the barriers that need to be overcome and future directions that must be embraced to funnel these ncRNA molecules for the treatment and management of PD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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24. Therapeutic Potential of Plant-Derived Compounds and Plant Extracts in Rheumatoid Arthritis-Comprehensive Review.
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Kciuk M, Garg A, Rohilla M, Chaudhary R, Dhankhar S, Dhiman S, Bansal S, Saini M, Singh TG, Chauhan S, Mujwar S, Gielecińska A, and Kontek R
- Abstract
Rheumatoid arthritis (RA) is a persistent autoimmune disorder that is characterized by joint inflammation, discomfort, and impairment. Despite the existence of several therapeutic approaches, their effectiveness is often restricted and may be linked to unfavorable side effects. Consequently, there has been growing interest in investigating naturally derived compounds as plausible therapeutic agents for RA disease. The objective of this review is to summarize the existing preclinical and clinical evidence regarding the efficacy of naturally extracted compounds and plant extracts in the treatment of RA, focusing on their anti-inflammatory, anti-oxidative, and immunomodulatory properties. Some of the problems with using natural chemicals are the uneven quality of commercially available preparations and the poor bioavailability of these compounds. Future investigations should focus on improving the formulations, conducting thorough clinical trials, and exploring different techniques to fully utilize the intrinsic potential of naturally derived chemicals in treating RA.
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- 2024
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25. Harnessing Bioprinting Technologies for Diabetic Wound Regeneration.
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Dhankhar S, Garg N, Chauhan S, Saini M, and Singh TG
- Abstract
A chronic metabolic condition, diabetes mellitus (DM), is becoming more common all over the globe. Diabetic complications include diabetic foot ulcers (DFUs). Between fifteen and twenty-five percent of people with diabetes will experience DFU at some point in their lives. Prolonged hospital stays and amputations are common outcomes of DFUs due to the absence of targeted therapy and appropriate wound dressings. Specialized DFU wound care is expected to be in high demand due to the anticipated increase in the prevalence of DM. Therefore, there is a strong need to enhance and create more effective wound dressings and therapies that are unique to DFU. Bioengineered tissues, individualised prostheses, and implants are just a few examples of how 3D bioprinting has revolutionised healthcare in the past decade. This review delves into the difficulties of wound management and explores how 3D bioprinting could improve existing treatment approaches and biomanufacturing composite 3D human skin substitutes as an alternative to skin grafting. To alleviate the healthcare burden caused by the rising incidence of DM, it will be crucial to co-develop 3D bioprinting technologies with new therapeutic techniques to address the unique pathophysiological problems of DFU in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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26. Unravelling the Microbiome's Role in Healing Diabetic Wounds.
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Dhankhar S, Garg N, Chauhan S, Saini M, Singh TG, and Singh R
- Abstract
The process of wound healing is intricate and requires close coordination; any disruption to this process can have catastrophic results. It is hypothesized that chronic wounds that do not heal or that cease healing entirely can be caused by a combination of host factors and bacteria that are present in a wound bed or wound bed environment. There is currently a lack of understanding regarding the role that the cutaneous microbiome plays in the healing process of wounds, despite the fact that methods that do not rely on culture have revealed the role that the gut microbiome plays in human health and illness. In order to keep the host immune system in check, protect the epithelial barrier function, and ward off harmful microbes, skin commensals play a crucial role. This review compiles the research on the effects of microbiome modifications on wound healing and tissue regeneration from both clinical and pre-clinical investigations on a variety of chronic skin wounds. It is now clear that human skin commensals, symbionts, and pathogens all play a part in the inflammatory response, which in turn suggests a number of ways to treat wounds that are infected and not healing. To fully understand the function of the human skin microbiome in both short-term and long-term wound healing, additional study is required to reconcile the conflicting and contentious results of previous investigations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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27. Mechanistic correlation of molecular pathways in obesity-mediated stroke pathogenesis.
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Khan H, Tiwari C, Kalra P, Vyas D, Grewal AK, and Singh TG
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- Humans, Animals, Adipose Tissue metabolism, Brain metabolism, Brain pathology, Brain physiopathology, Obesity metabolism, Obesity complications, Obesity physiopathology, Signal Transduction, Stroke metabolism, Stroke physiopathology
- Abstract
Obesity, a prominent risk factor for the development of heart attacks and several cardiovascular ailments. Obesity ranks as the second most significant avoidable contributor to mortality, whereas stroke stands as the second leading cause of death on a global scale. While changes in lifestyle have been demonstrated to have significant impacts on weight management, the long-term weight loss remains challenging, and the global prevalence of obesity continues to rise. The pathophysiology of obesity has been extensively studied during the last few decades, and an increasing number of signal transduction pathways have been linked to obesity preclinically. This review is focused on signaling pathways, and their respective functions in regulating the consumption of fatty food as well as accumulation of adipose tissue, and the resulting morphological and cognitive changes in the brain of individuals with obesity. We have also emphasized the recent progress in the mechanisms behind the emergence of obesity, as elucidated by both experimental and clinical investigations. The mounting understanding of signaling transduction may shed light on the future course of obesity research as we move into a new era of precision medicine., (© 2024. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)
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- 2024
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28. Exploring the Comprehensive Neuroprotective and Anticancer Potential of Afzelin.
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Kciuk M, Garg N, Dhankhar S, Saini M, Mujwar S, Devi S, Chauhan S, Singh TG, Singh R, Marciniak B, Gielecińska A, and Kontek R
- Abstract
Neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, and others) and cancer, seemingly disparate in their etiology and manifestation, exhibit intriguing associations in certain cellular and molecular processes. Both cancer and neurodegenerative diseases involve the deregulation of cellular processes such as apoptosis, proliferation, and DNA repair and pose a significant global health challenge. Afzelin (kaempferol 3-O-rhamnoside) is a flavonoid compound abundant in various plant sources. Afzelin exhibits a diverse range of biological activities, offering promising prospects for the treatment of diseases hallmarked by oxidative stress and deregulation of cell death pathways. Its protective potential against oxidative stress is also promising for alleviating the side effects of chemotherapy. This review explores the potential therapeutic implications of afzelin, including its capacity to mitigate oxidative stress, modulate inflammation, and promote cellular regeneration in neurodegenerative and cancer diseases.
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- 2024
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29. Exploring ncRNA-mediated regulation of EGFR signalling in glioblastoma: From mechanisms to therapeutics.
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Thapa R, Afzal M, Goyal A, Gupta G, Bhat AA, Almalki WH, Kazmi I, Alzarea SI, Shahwan M, Kukreti N, Ali H, Dureja H, Kumar P, Singh TG, Kuppusamy G, Singh SK, and Dua K
- Subjects
- Humans, ErbB Receptors metabolism, Signal Transduction, RNA, Untranslated genetics, Glioblastoma drug therapy, Glioblastoma genetics, Glioblastoma metabolism, MicroRNAs metabolism, Brain Neoplasms drug therapy, Brain Neoplasms genetics, Brain Neoplasms metabolism
- Abstract
Glioblastoma (GBM) is the most prevalent and deadly primary brain tumor type, with a discouragingly low survival rate and few effective treatments. An important function of the EGFR signalling pathway in the development of GBM is to affect tumor proliferation, persistence, and treatment resistance. Advances in molecular biology in the last several years have shown how important ncRNAs are for controlling a wide range of biological activities, including cancer progression and development. NcRNAs have become important post-transcriptional regulators of gene expression, and they may affect the EGFR pathway by either directly targeting EGFR or by modifying important transcription factors and downstream signalling molecules. The EGFR pathway is aberrantly activated in response to the dysregulation of certain ncRNAs, which has been linked to GBM carcinogenesis, treatment resistance, and unfavourable patient outcomes. We review the literature on miRNAs, circRNAs and lncRNAs that are implicated in the regulation of EGFR signalling in GBM, discussing their mechanisms of action, interactions with the signalling pathway, and implications for GBM therapy. Furthermore, we explore the potential of ncRNA-based strategies to overcome resistance to EGFR-targeted therapies, including the use of ncRNA mimics or inhibitors to modulate the activity of key regulators within the pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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30. Unveiling the Role of PAR 1: A Crucial Link with Inflammation in Diabetic Subjects with COVID-19.
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Singh R, Singh V, Ahmad MA, Pasricha C, Kumari P, Singh TG, Kaur R, Mujwar S, Wani TA, and Zargar S
- Abstract
Inflammation is a distinguished clinical manifestation of COVID-19 and type 2 diabetes mellitus (T2DM), often associated with inflammatory dysfunctions, insulin resistance, metabolic dysregulation, and other complications. The present study aims to test the hypothesis that serum concentrations of PAR-1 levels differ between COVID-19 diabetic patients (T2DM) and non-diabetic COVID-19 patients and determine their association with different biochemical parameters and inflammatory biomarkers. T2DM patients with COVID-19 (n = 50) with glycated hemoglobin (HbA1c) levels of (9.23 ± 1.66) and non-diabetic COVID-19 patients (n = 50) with HbA1c levels (4.39 ± 0.57) were recruited in this study. The serum PAR-1 levels (ELISA method) were determined in both groups and correlated with parameters such as age, BMI, inflammatory markers including CRP, interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), D-dimer, homocysteine, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Demographic variables such as BMI (29.21 ± 3.52 vs. controls 21.30 ± 2.11) and HbA1c (9.23 ± 1.66 vs. controls 4.39 ± 0.57) were found to be statistically elevated in COVID-19 T2DM patients compared to non-diabetic COVID-19 patients. The concentrations of several inflammatory biomarkers and PAR-1 were remarkably increased in the COVID-19 T2DM group when compared with the non-diabetic COVID-19 group. The univariate analysis revealed that increased serum PAR-1 estimations were positively correlated with enhanced HbA1c, BMI, inflammatory cytokines, D-dimer, homocysteine, and NT-proBNP. The findings in the current study suggest that increased levels of serum PAR-1 in the bloodstream could potentially serve as an independent biomarker of inflammation in COVID-19 patients with T2DM.
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- 2024
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31. Sirtuin dysregulation in Parkinson's disease: Implications of acetylation and deacetylation processes.
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Dhiman S, Mannan A, Taneja A, Mohan M, and Singh TG
- Subjects
- Humans, Acetylation, Protein Processing, Post-Translational, Dopaminergic Neurons metabolism, Parkinson Disease drug therapy, Sirtuins metabolism
- Abstract
Parkinson's disease (PD) is a progressive neurodegenerative condition that primarily affects motor function and is caused by a gradual decline of dopaminergic neurons in the brain's substantia pars compacta (Snpc) region. Multiple molecular pathways are involved in the pathogenesis, which results in impaired cellular functions and neuronal degeneration. However, the role of sirtuins, a type of NAD
+ -dependent deacetylase, in the pathogenesis of Parkinson's disease has recently been investigated. Sirtuins are essential for preserving cellular homeostasis because they control a number of biological processes, such as metabolism, apoptosis, and DNA repair. This review shed lights on the dysregulation of sirtuin activity in PD, highlighting the role that acetylation and deacetylation processes play in the development of the disease. Key regulators of protein acetylation, sirtuins have been found to be involved in the aberrant acetylation of vital substrates linked to PD pathology when their balance is out of balance. The hallmark characteristics of PD such as neuroinflammation, oxidative stress, and mitochondrial dysfunction have all been linked to the dysregulation of sirtuin expression and activity. Furthermore, we have also explored how the modulators of sirtuins can be a promising therapeutic intervention in the treatment of PD., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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32. Effectiveness of BNT162b2 BA.4/5 Bivalent mRNA Vaccine Against Symptomatic COVID-19 Among Immunocompetent Individuals Testing at a Large US Retail Pharmacy.
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Rudolph AE, Khan FL, Shah A, Singh TG, Wiemken TL, Puzniak LA, Jodar L, and McLaughlin JM
- Subjects
- Humans, Adolescent, Adult, Child, Preschool, BNT162 Vaccine, mRNA Vaccines, SARS-CoV-2 genetics, Vaccines, Combined, COVID-19 epidemiology, COVID-19 prevention & control, Pharmacy
- Abstract
Background: Data on the effectiveness of BA.4/5 bivalent vaccine stratified by age and prior infection are lacking., Methods: This test-negative study used data from individuals ≥5 years of age testing for SARS-CoV-2 with symptoms (15 September 2022 to 31 January 2023) at a large national retail pharmacy chain. The exposure was receipt of 2-4 wild-type doses and a BNT162b2 BA.4/5 bivalent vaccine (>2 months since last wild-type dose). The outcome was a positive SARS-CoV-2 test. Absolute (vs unvaccinated) and relative (vs 2-4 wild-type doses) vaccine effectiveness (VE) were calculated as (1 - adjusted odds ratio from logistic regression) × 100. VE was stratified by age and self-reported prior infection., Results: Overall, 307 885 SARS-CoV-2 tests were included (7916 aged 5-11, 16 329 aged 12-17, and 283 640 aged ≥18 years). SARS-CoV-2 positivity was 39%; 21% were unvaccinated, 70% received 2-4 wild-type doses with no bivalent vaccine, and 9% received a BNT162b2 BA.4/5 bivalent dose. At a median of 1-2 months after BNT162b2 BA.4/5 bivalent vaccination, depending on age group, absolute VE was 22%-60% and was significantly higher among those reporting prior infection (range, 55%-79%) than not (range, no protection to 50%). Relative VE was 31%-64%., Conclusions: BNT162b2 BA.4/5 bivalent showed early additional protection against Omicron-related symptomatic COVID-19, with hybrid immunity offering greater protection., Competing Interests: Potential conflicts of interest. A. E. R., F. L. K., T. L. W., L. A. P., L. J., and J. M. M. are employees and shareholders of Pfizer. A. S. and T. A. S. are employees and shareholders of Walgreens. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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33. Pesticides: An alarming detrimental to health and environment.
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Kaur R, Choudhary D, Bali S, Bandral SS, Singh V, Ahmad MA, Rani N, Singh TG, and Chandrasekaran B
- Subjects
- Humans, Ecosystem, Environmental Pollution, Crops, Agricultural, Pesticides analysis, Pyrethrins
- Abstract
Pesticides are chemical substances of natural or synthetic origin that are used to eradicate pests and insects. These are indispensable in the agricultural processes for better crop production. Pesticide use aims to promote crop yield and protect the crops from diseases and damage. Pesticides must be handled carefully and disposed of appropriately because they are dangerous to people and other species by default. Environmental pollution occurs when pesticide contamination spreads away from the intended plants. Older pesticides such as lindane and dichlorodiphenyltrichloroethane (DDT) may remain in water and soil for a longer time. These accumulate in various parts of the food chain and cause damage to the ecosystem. Biological techniques in the management of pest control such as importation, augmentation, and conservation, and the accompanying procedures are more efficient, less expensive, and ecologically sound than other ways. This review mainly focuses on the consequences on the targeted and non-targeted organisms including the health and well-being of humans by the use of pesticides and their toxicity. The side effects that occur when a pesticide's LD
50 exceeds the accepted limit through oral or skin penetration due to their binding to various receptors such as estrogen receptors, GABA, EGFR, and others. These pesticide classes include carbamates, pyrethroids, organochlorides, organophosphorus, and others. The current study seeks to highlight the urgent requirement for a novel agricultural concept that includes a major reduction in the use of chemical pesticides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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34. Opening avenues for treatment of neurodegenerative disease using post-biotics: Breakthroughs and bottlenecks in clinical translation.
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Bashir B, Alam S, Khandale N, Birla D, Vishwas S, Pandey NK, Gupta G, Paudel KR, Dureja H, Kumar P, Singh TG, Kuppusamy G, Zacconi FC, Pinto TJA, Dhanasekaran M, Gulati M, Dua K, and Singh SK
- Subjects
- Humans, Amyloid beta-Peptides metabolism, Substantia Nigra metabolism, Neuroprotection, Neurodegenerative Diseases therapy, Neurodegenerative Diseases metabolism, Parkinson Disease metabolism
- Abstract
Recent studies have indicated the significant involvement of the gut microbiome in both human physiology and pathology. Additionally, therapeutic interventions based on microbiome approaches have been employed to enhance overall health and address various diseases including aging and neurodegenerative disease (ND). Researchers have explored potential links between these areas, investigating the potential pathogenic or therapeutic effects of intestinal microbiota in diseases. This article provides a summary of established interactions between the gut microbiome and ND. Post-biotic is believed to mediate its neuroprotection by elevating the level of dopamine and reducing the level of α-synuclein in substantia nigra, protecting the loss of dopaminergic neurons, reducing the aggregation of NFT, reducing the deposition of amyloid β peptide plagues and ameliorating motor deficits. Moreover, mediates its neuroprotective activity by inhibiting the inflammatory response (decreasing the expression of TNFα, iNOS expression, free radical formation, overexpression of HIF-1α), apoptosis (i.e. active caspase-3, TNF-α, maintains the level of Bax/Bcl-2 ratio) and promoting BDNF secretion. It is also reported to have good antioxidant activity. This review offers an overview of the latest findings from both preclinical and clinical trials concerning the use of post-biotics in ND., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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35. Wnt signalling pathways as mediators of neuroprotective mechanisms: therapeutic implications in stroke.
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Sharma V, Sharma P, and Singh TG
- Subjects
- Humans, Glycogen Synthase Kinase 3 beta, Wnt Signaling Pathway, Brain, Phosphatidylinositol 3-Kinases, Stroke
- Abstract
A stroke is a complicated neurological illness that occurs when there is a disruption in the blood flow to the brain. This disruption results in the damage of neurons, which then leads to functional abnormalities. The Wnt signalling pathway, which is already well-known for its important function in development and tissue homeostasis, has recently been recognised as a critical factor in the pathophysiology of stroke. Recent studies have shown the Wnt pathway's roles in stroke-related events. The complex-interactions between the Wnt pathway and stroke emphasising the pathway's contributions to neuro-protection and synaptic plasticity. The Wnt pathway's influence on neuro-genesis and synaptic plasticity underscores its potential for driving stroke recovery and rehabilitation strategies. The current review discusses about the Wnt signalling pathway in brain pathophysiology and stroke with special emphasis on the various pathways involved in the positive and negative modulation of Wnt pathway namely Phosphoinositide 3-kinase (PI3-K), Glycogen synthase kinase-3β (GSK-3β), Mitogen-activated protein kinase (MAPK) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathway., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
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- 2024
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36. Targeting inflammatory signaling in obsessive compulsive disorder: a promising approach.
- Author
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Bhatt S, Anitha K, Chellappan DK, Mukherjee D, Shilpi S, Suttee A, Gupta G, Singh TG, and Dua K
- Subjects
- Animals, Humans, Signal Transduction, Brain metabolism, Cognition, Quality of Life, Obsessive-Compulsive Disorder diagnosis
- Abstract
Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder. Approximately, around 2% to 3% percent of the general population experience symptoms of OCD over the course of their lifetime. OCD can lead to economic burden, poor quality of life, and disability. The characteristic features exhibited generally in OCD are continuous intrusive thoughts and periodic ritualized behaviours. Variations in genes, pathological function of Cortico-Striato-Thalamo-Cortical (CSTC) circuits and dysregulation in the synaptic conduction have been the major factors involved in the pathological progression of OCD. However, the basic mechanisms still largely unknown. Current therapies for OCD largely target monoaminergic neurotransmitters (NTs) in specific dopaminergic and serotonergic circuits. However, such therapies have limited efficacy and tolerability. Drug resistance has been one of the important reasons reported to critically influence the effectiveness of the available drugs. Inflammation has been a crucial factor which is believed to have a significant importance in OCD progression. A significant number of proinflammatory cytokines have been reportedly amplified in patients with OCD. Mechanisms of drug treatment involve attenuation of the symptoms via modulation of inflammatory signalling pathways, modification in brain structure, and synaptic plasticity. Hence, targeting inflammatory signaling may be considered as a suitable approach in the treatment of OCD. The present review focuses mainly on the significant findings from the animal and human studies conducted in this area, that targets inflammatory signaling in neurological conditions. In addition, it also focusses on the therapeutic approaches that target OCD via modification of the inflammatory signaling pathways., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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37. Targeting cardiovascular risk factors with eugenol: an anti-inflammatory perspective.
- Author
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Devi S, Chauhan S, Mannan A, and Singh TG
- Subjects
- Animals, Humans, Eugenol pharmacology, Eugenol therapeutic use, Risk Factors, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents therapeutic use, Inflammation drug therapy, Heart Disease Risk Factors, Cardiovascular Diseases drug therapy, Oils, Volatile therapeutic use
- Abstract
Inflammation is a multifaceted biological reaction to a wide range of stimuli, and it has been linked to the onset and progression of chronic diseases such as heart disease, cancer, and diabetes. Inflammatory markers found in the blood, including C-reactive protein, serum amyloid A, fibrinogen, plasma viscosity, erythrocyte sedimentation rate, interleukin-6, and soluble adhesion molecules (like intercellular adhesion molecule-1 and vascular cell adhesion molecule-1), are risk factors for cardiovascular diseases such as coronary heart disease, stroke, and peripheral arterial disease. These markers play a crucial role in understanding and assessing cardiovascular health. Due to this complicated relationship between inflammation and cardiovascular disease, anti-inflammatory agents of natural origin have been the subject of many preclinical and clinical studies in recent years. Eugenol is a natural phenolic compound found in clove oil, nutmeg oil, cinnamon oil, and bay leaf oil, as well as other essential oils. Eugenol has been shown to have anti-inflammatory properties in many forms of experimental inflammation. It may scavenge free radicals, which contribute to inflammation and tissue damage. Various studies also suggest that eugenol can limit the production of inflammatory mediators such as prostaglandins, cytokines, and chemokines. Animal models of arthritis, colitis, and lung damage, as well as human clinical studies, have shown that eugenol has phenomenal anti-inflammatory properties. These properties suggest that eugenol may be able to reduce the risk of cardiovascular diseases., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2024
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38. Understanding mechanistic aspect of the therapeutic role of herbal agents on neuroplasticity in cerebral ischemic-reperfusion injury.
- Author
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Bangar A, Khan H, Kaur A, Dua K, and Singh TG
- Subjects
- Humans, Phosphatidylinositol 3-Kinases, Plant Extracts therapeutic use, Tissue Plasminogen Activator, Neuroprotective Agents pharmacology, Neuroprotective Agents therapeutic use, Reperfusion Injury metabolism, Stroke drug therapy
- Abstract
Ethnopharmacological Relevance: Stroke is one of the leading causes of death and disability. The only FDA-approved therapy for treating stroke is tissue plasminogen activator (tPA), exhibiting a short therapeutic window. Due to this reason, only a small number of patients can be benefitted in this critical period. In addition, the use of endovascular interventions may reverse vessel occlusion more effectively and thus help further improve outcomes in experimental stroke. During recovery of blood flow after ischemia, patients experience cognitive, behavioral, affective, emotional, and electrophysiological changes. Therefore, it became the need for an hour to discover a novel strategy for managing stroke. The drug discovery process has focused on developing herbal medicines with neuroprotective effects via modulating neuroplasticity., Aim of the Study: We gather and highlight the most essential traditional understanding of therapeutic plants and their efficacy in cerebral ischemia-reperfusion injury. In addition, we provide a concise summary and explanation of herbal drugs and their role in improving neuroplasticity. We review the pharmacological activity of polyherbal formulations produced from some of the most frequently referenced botanicals for the treatment of cerebral ischemia damage., Materials and Methods: A systematic literature review of bentham, scopus, pubmed, medline, and embase (elsevier) databases was carried out with the help of the keywords like neuroplasticity, herbal drugs, neural progenitor cells, neuroprotection, stem cells. The review was conducted using the above keywords to understand the therapeutic and mechanistic role of herbal neuroprotective agents on neuroplasticity in cerebral ischemic-reperfusion injury., Results: Neuroplasticity emerged as an alternative to improve recovery and management after cerebral ischemic reperfusion injury. Neuroplasticity is a physiological process throughout one's life in response to any stimuli and environment. Traditional herbal medicines have been established as an adjuvant to stroke therapy since they were used from ancient times and provided promising effects as an adjuvant to experimental stroke. The plants and phytochemicals such as Curcuma longa L., Moringa oliefera Lam, Panax ginseng C.A. Mey., and Rehmannia glutinosa (Gaertn.) DC., etc., have shown promising effects in improving neuroplasticity after experimental stroke. Such effects occur by modulation of various molecular signalling pathways, including PI3K/Akt, BDNF/CREB, JAK/STAT, HIF-1α/VEGF, etc. CONCLUSIONS: Here, we gave a perspective on plant species that have shown neuroprotective effects and can show promising results in promoting neuroplasticity with specific targets after cerebral ischemic reperfusion injury. In this review, we provide the complete detail of studies conducted on the role of herbal drugs in improving neuroplasticity and the signaling pathway involved in the recovery and management of experimental stroke., Competing Interests: Declaration of competing interest This is to bring to your kind notice that the manuscript originally written by Annu Bangar, Heena Khan, Amarjot Kaur, Kamal Dua, Thakur Gurjeet Singh*” titled “Understanding mechanistic aspect on therapeutic role of herbal agents on neuroplasticity in cerebral ischemic-reperfusion injury” is herewith submitted for publication in Journal of Ethnopharmacology. It has not been published before, and it is not under consideration for publication in any other journal (s). We certify that we have obtained written permission for the use of text, tables, and/or illustrations from any copyrighted source(s), and we declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2024
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39. In-silico Investigation of Ginseng Phytoconstituents as Novel Therapeutics Against MAO-A.
- Author
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Choudhary D, Kaur R, Rani N, Singh TG, and Kumar B
- Subjects
- Humans, Ligands, Computer Simulation, Monoamine Oxidase metabolism, Panax chemistry, Molecular Docking Simulation, Monoamine Oxidase Inhibitors pharmacology, Monoamine Oxidase Inhibitors chemistry, Phytochemicals pharmacology, Phytochemicals chemistry
- Abstract
Background: Ginseng ( Panax ginseng ) is a herb of medicinal and nutritional importance. Ginseng has been used since ancient times for the treatment of numerous ailments as it has many therapeutic properties. Several phytoconstituents are present in Panax ginseng that possess a variety of beneficial pharmacological properties., Objective: To explore the potential of phytoconstituents of Panax ginseng in the treatment of depression, a molecular modeling technique was utilized targeting monoamine oxidase-A (MAO-A)., Methods: A total of sixty-one phytoconstituents of ginseng were drawn with the help of ChemBioDraw Ultra 12.0 software and PDBs for MAO-A enzyme were retrieved from the RCSB PDB database. The prepared ligands were screened for MAO-A properties using the software Molegro Virtual Docker (MVD 2010.4.1.0). All the prepared ligands were evaluated for drug-likeliness properties using Swiss ADME., Results: Among the docking studies of 60 Ginseng phytochemicals including one standard, 15 phytoconstituents with the highest dock score and better binding interactions were selected further for absorption, distribution, metabolism and excretion (ADME) studies. Stachyose (-227.287, 17 interactions), Raffinose (-222.157, 14 interactions), and Ginsenoside Rg1 (-216.593, 10 interactions) were found to possess better interactions as compared to Clorgyline taken as a standard drug., Conclusion: Stachyose was found to be the most potent inhibitor of MAO-A enzyme under investigation and can be a potential lead molecule for the development of newer phytochemical-based treatment of depression., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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40. Pyrazoline Derivatives as Promising MAO-A Targeting Antidepressants: An Update.
- Author
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Choudhary D, Kaur R, Singh TG, and Kumar B
- Subjects
- Humans, Structure-Activity Relationship, Depression drug therapy, Molecular Structure, Animals, Monoamine Oxidase metabolism, Antidepressive Agents pharmacology, Antidepressive Agents chemistry, Antidepressive Agents chemical synthesis, Monoamine Oxidase Inhibitors pharmacology, Monoamine Oxidase Inhibitors chemistry, Monoamine Oxidase Inhibitors chemical synthesis, Pyrazoles chemistry, Pyrazoles pharmacology, Pyrazoles chemical synthesis
- Abstract
Depression is one of the key conditions addressed by the Mental Health Gap Action Programme (mhGAP) of WHO that can lead to self-harm and suicide. Depression is associated with low levels of neurotransmitters, which eventually play a key role in the progression and development of mental illness. The nitrogen-containing heterocyclic compounds exhibit the most prominent pharmacological profile as antidepressants. Pyrazoline, a dihydro derivative of pyrazole, is a well-known five-membered heterocyclic moiety that exhibits a broad spectrum of biological activities. Many researchers have reported pyrazoline scaffold-containing molecules as potential antidepressant agents with selectivity for monoamine oxidase enzyme (MAO) isoforms. Several studies indicated a better affinity of pyrazoline-based moiety as (monoamine oxidase inhibitors) MAOIs. In this review, we have focused on the recent advancements (2019-2023) in the development of pyrazoline-containing derivatives exhibiting promising inhibition of MAO-A enzyme to treat depression. This review provides structural insights on pyrazoline-based molecules along with their SAR analysis, in silico exploration of binding interactions between pyrazoline derivatives and MAO-A enzyme, and clinical trial status of various drug molecules against depression. The in-silico exploration of potent pyrazoline derivatives at the active site of the MAOA enzyme will provide further insights into the development of new potential MAO-A inhibitors for the treatment of depression., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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41. From Traditional Medicine to Advanced Therapeutics: The Renaissance of Phyto-nano Interventions in Psoriasis.
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Semele R, Grewal S, Jeengar MK, Singh TG, and Swami R
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- Humans, Medicine, Traditional methods, Phytochemicals therapeutic use, Phytochemicals pharmacology, Phytochemicals chemistry, Animals, Nanoparticles therapeutic use, Nanoparticles chemistry, Phytotherapy methods, Anti-Inflammatory Agents therapeutic use, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents administration & dosage, Drug Delivery Systems methods, Psoriasis drug therapy, Psoriasis immunology
- Abstract
Psoriasis is an autoimmune systemic chronic inflammatory disease that exhibits characteristic detrimental effects on the skin, often leading to infections or comorbid conditions. The multifaceted nature of psoriasis has made it very challenging to treat, especially with current chemotherapy options. Therefore, it is essential to consider phytoconstituents as novel alternatives. However, despite demonstrating higher anti-inflammatory, anti-psoriasis, and immunomodulatory potential, their clinical usage is hindered due to their poor physicochemical properties. To address these drawbacks, nanoparticulate drug delivery systems have been developed, helping to achieve better permeation of phytoconstituents through topical administration. This has breathed new life into traditional systems of medicine, particularly in the context of treating psoriasis. In this current review, we present a detailed, comprehensive, and up-to-date analysis of the literature, which will contribute to affirming the clinical role of phyto-nano interventions against psoriasis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2024
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42. Pharmacoeconomic Aspects of Diabetes Mellitus: Outcomes and Analysis of Health Benefits Approach.
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Baishnab S, Jaura RS, Sharma S, Garg H, and Singh TG
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- Humans, Economics, Pharmaceutical, Cost-Benefit Analysis, Hypoglycemic Agents therapeutic use, Hypoglycemic Agents economics, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 economics
- Abstract
Pharmacoeconomics is an important tool for investigating and restructuring healthcare policies. In India, recent statistical studies have shown that the number of diabetic patients is rapidly increasing in the rural, middle and upper-class settings. The aim of this review is to call attention towards the need to carry out pharmacoeconomic studies for diabetes mellitus and highlight the outcome of these studies on healthcare. A well-structured literature search from PubMed, Embase, Springer, ScienceDirect, and Cochrane was done. Studies that evaluated the cost-effectiveness of various anti-diabetic agents for type 2 diabetes were eligible for inclusion in the analysis and review. Two independent reviewers sequentially assessed the titles, abstracts, and full articles to select studies that met the predetermined inclusion and exclusion criteria for data abstraction. Any discrepancies between the reviewers were resolved through consensus. By employing search terms such as pharmacoeconomics, diabetes mellitus, cost-effective analysis, cost minimization analysis, cost-utility analysis, and cost-benefit analysis, a total of 194 papers were gathered. Out of these, 110 papers were selected as they aligned with the defined search criteria and underwent the removal of duplicate entries. This review outlined four basic pharmacoeconomic studies carried out on diabetes mellitus. It gave a direction that early detection, patient counseling, personalized medication, appropriate screening intervals, and early start of pharmacotherapy proved to be a cost-effective as well as health benefits approach., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2024
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43. Cross Talks between CNS and CVS Diseases: An Alliance to Annihilate.
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Chib S, Devi S, Chalotra R, Mittal N, Singh TG, Kumar P, and Singh R
- Subjects
- Humans, Cardiovascular Diseases, Quality of Life, Central Nervous System Diseases, Cerebrovascular Disorders etiology
- Abstract
Cardiovascular and neurological diseases cause substantial morbidity and mortality globally. Moreover, cardiovascular diseases are the leading cause of death globally. About 17.9 million people are affected by cardiovascular diseases and 6.8 million people die every year due to neurological diseases. The common neurologic manifestations of cardiovascular illness include stroke syndrome which is responsible for unconsciousness and several other morbidities significantly diminished the quality of life of patients. Therefore, it is prudent need to explore the mechanistic and molecular connection between cardiovascular disorders and neurological disorders. The present review emphasizes the association between cardiovascular and neurological diseases specifically Parkinson's disease, Alzheimer's disease, and Huntington's disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2024
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44. Corrigendum to "Discussing pathologic mechanisms of Diabetic retinopathy & therapeutic potentials of curcumin and β-glucogallin in the management of Diabetic retinopathy" Biomed. Pharmacother. 169 (2023) 115881.
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Rohilla M, Rishabh, Bansal S, Garg A, Dhiman S, Dhankhar S, Saini M, Chauhan S, Alsubaie N, Batiha GE, Albezrah NKA, and Singh TG
- Published
- 2024
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45. Glycosylation: A new signaling paradigm for the neurovascular diseases.
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Kaur D, Khan H, Grewal AK, and Singh TG
- Subjects
- Humans, Glycosylation, Blood-Brain Barrier metabolism, Neurons metabolism, Brain metabolism, Atherosclerosis metabolism
- Abstract
A wide range of life-threatening conditions with complicated pathogenesis involves neurovascular disorders encompassing Neurovascular unit (NVU) damage. The pathophysiology of NVU is characterized by several features including tissue hypoxia, stimulation of inflammatory and angiogenic processes, and the initiation of intricate molecular interactions, collectively leading to an elevation in blood-brain barrier permeability, atherosclerosis and ultimately, neurovascular diseases. The presence of compelling data about the significant involvement of the glycosylation in the development of diseases has sparked a discussion on whether the abnormal glycosylation may serve as a causal factor for neurovascular disorders, rather than being just recruited as a secondary player in regulating the critical events during the development processes like embryo growth and angiogenesis. An essential tool for both developing new anti-ischemic therapies and understanding the processes of ischemic brain damage is undertaking pre-clinical studies of neurovascular disorders. Together with the post-translational modification of proteins, the modulation of glycosylation and its enzymes implicates itself in several abnormal activities which are known to accelerate neuronal vasculopathy. Despite the failure of the majority of glycosylation-based preclinical and clinical studies over the past years, there is a significant probability to provide neuroprotection utilizing modern and advanced approaches to target abnormal glycosylation activity at embryonic stages as well. This article focuses on a variety of experimental evidence to postulate the interconnection between glycosylation and vascular disorders along with possible treatment options., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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46. Evolutionary Unmasking Resuscitative Therapeutics Potential of Centhaquin Citrate in Hypovolemic Shock.
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Singh R, Singh V, Kumari P, Aggarwal N, Oberoi M, Khan H, and Singh TG
- Subjects
- Animals, Humans, Piperazines therapeutic use, Resuscitation methods, Shock drug therapy
- Abstract
Hypovolemic shock (HS), a clinical condition of insufficient blood perfusion and oxygenation in body tissues, is associated with immense morbidity and mortality. Treatment approaches include fluid replacement and surgical repair of reversible causes of hemorrhage; however, they cause irreversible blood perfusion loss, systemic inflammation, multiple organ failure, and death. Centhaquin citrate (CC) is an innovative centrally acting cardiovascular active agent that is initially intended as an antihypertensive drug. However, due to its positive ionotropic effect, Centhaquin citrate is being tested clinically as a resuscitative agent for the management of hypovolemic shock It acts at the α2B-adrenergic receptor to produce venous constriction followed by an increase in venous return to the heart. These actions are assumed to be capable of resuscitative activity observed by centhaquin citrate, through an increase in cardiac output and tissue perfusion. Pharmacokinetics investigations in animals and humans have shown that centhaquin citrate is well tolerated and has insignificant side effects. Therefore, centhaquin citrate seems to be a promising entity and gaining the interest of researchers to develop it as a resuscitative agent in HS. The review gives insight into the development of centhaquin citrate as a resuscitative agent and provides insight into the associated mechanism of action and molecular signalling to foster future research on CC for its clinical use in HS., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2024
- Full Text
- View/download PDF
47. Discussing pathologic mechanisms of Diabetic retinopathy & therapeutic potentials of curcumin and β-glucogallin in the management of Diabetic retinopathy.
- Author
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Rohilla M, Rishabh, Bansal S, Garg A, Dhiman S, Dhankhar S, Saini M, Chauhan S, Alsubaie N, Batiha GE, Albezrah NKA, and Singh TG
- Subjects
- Animals, Humans, Retina pathology, Hydrolyzable Tannins therapeutic use, Diabetic Retinopathy metabolism, Curcumin pharmacology, Curcumin therapeutic use, Curcumin metabolism, Diabetes Mellitus metabolism
- Abstract
Diabetic retinopathy (DR) is a form of retinal microangiopathy that occurs as a result of long-term Diabetes mellitus (DM). Patients with Diabetes mellitus typically suffer from DR as a progression of the disease that may be due to initiation and dysregulation of pathways like the polyol, hexosamine, the AGE/RAGE, and the PKC pathway, which all have negative impacts on eye health and vision. In this review, various databases, including PubMed, Google Scholar, Web of Science, and Science Direct, were scoured for data relevant to the aforementioned title. The three most common therapies for DR today are retinal photocoagulation, anti-vascular endothelial growth factor (VEGF) therapy, and vitrectomy, however, there are a number of drawbacks and limits to these methods. So, it is of critical importance and profound interest to discover treatments that may successfully address the pathogenesis of DR. Curcumin and β-glucogallin are the two potent compounds of natural origin that are already being used in various nutraceutical formulations for several ailments. They have been shown potent antiapoptotic, anti-inflammatory, antioxidant, anticancer, and pro-vascular function benefits in animal experiments. Their parent plant species have been used for generations by practitioners of traditional herbal medicine for the treatment and prevention of various eye ailments. In this review, we will discuss about pathophysiology of Diabetic retinopathy and the therapeutic potentials of curcumin and β-glucogallin one of the principal compounds from Curcuma longa and Emblica officinalis in Diabetic retinopathy., Competing Interests: Declaration of Competing Interest The authors declares no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2023
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48. Therapeutic targeting of angiopoietins in tumor angiogenesis and cancer development.
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Thapa K, Khan H, Kaur G, Kumar P, and Singh TG
- Subjects
- Humans, Vascular Endothelial Growth Factor A metabolism, Receptor, TIE-2 metabolism, Neovascularization, Pathologic drug therapy, Neovascularization, Pathologic metabolism, Angiopoietin-2 metabolism, Angiopoietin-1, Tumor Microenvironment, Angiopoietins metabolism, Neoplasms drug therapy, Neoplasms blood supply
- Abstract
The formation and progression of tumors in humans are linked to the abnormal development of new blood vessels known as neo-angiogenesis. Angiogenesis is a broad word that encompasses endothelial cell migration, proliferation, tube formation, and intussusception, as well as peri-EC recruitment and extracellular matrix formation. Tumor angiogenesis is regulated by angiogenic factors, out of which some of the most potent angiogenic factors such as vascular endothelial growth factor and Angiopoietins (ANGs) in the body are produced by macrophages and other immune cells within the tumor microenvironment. ANGs have a distinct function in tumor angiogenesis and behavior. ANG1, ANG 2, ANG 3, and ANG 4 are the family members of ANG out of which ANG2 has been extensively investigated owing to its unique role in modifying angiogenesis and its tight association with tumor progression, growth, and invasion/metastasis, which makes it an excellent candidate for therapeutic intervention in human malignancies. ANG modulators have demonstrated encouraging outcomes in the treatment of tumor development, either alone or in conjunction with VEGF inhibitors. Future development of more ANG modulators targeting other ANGs is needed. The implication of ANG1, ANG3, and ANG4 as probable therapeutic targets for anti-angiogenesis treatment in tumor development should be also evaluated. The article has described the role of ANG in tumor angiogenesis as well as tumor growth and the treatment strategies modulating ANGs in tumor angiogenesis as demonstrated in clinical studies. The pharmacological modulation of ANGs and ANG-regulated pathways that are responsible for tumor angiogenesis and cancer development should be evaluated for the development of future molecular therapies., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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49. Mechanistic Implications of GSK and CREB Crosstalk in Ischemia Injury.
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Khan H, Bangar A, Grewal AK, and Singh TG
- Subjects
- Humans, Glycogen Synthase Kinase 3 metabolism, Calcium, Signal Transduction physiology, Ischemia, Glycogen Synthase Kinase 3 beta metabolism, Apoptosis, Reperfusion Injury metabolism, Brain Ischemia metabolism
- Abstract
Ischemia-reperfusion (IR) injury is a damage to an organ when the blood supply is less than the demand required for normal functioning, leading to exacerbation of cellular dysfunction and death. IR injury occurs in different organs like the kidney, liver, heart, brain, etc., and may not only involve the ischemic organ but also cause systemic damage to distant organs. Oxygen-glucose deprivation in cells causes oxidative stress, calcium overloading, inflammation, and apoptosis. CREB is an essential integrator of the body's various physiological systems, and it is widely accepted that dysfunction of CREB signaling is involved in many diseases, including ischemia-reperfusion injury. The activation of CREB can provide life to a cell and increase the cell's survival after ischemia. Hence, GSK/CREB signaling pathway can provide significant protection to cells of different organs after ischemia and emerges as a futuristic strategy for managing ischemia-reperfusion injury. Different signaling pathways such as MAPK/ERK, TLR4/MyD88, RISK, Nrf2, and NF-κB, get altered during IR injury by the modulation of GSK-3 and CREB (cyclic AMP response element (CRE)-binding protein). GSK-3 (protein kinase B) and CREB are the downstream targets for fulfilling the roles of various signaling pathways. Calcium overloading during ischemia increases the expression of calcium-calmodulin-dependent protein kinase (CaMK), which subsequently activates CREB-mediated transcription, thus promoting the survival of cells. Furthermore, this review highlights the crosstalk between GSK-3 and CREB, promoting survival and rendering the cells resistant to subsequent severe ischemia., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
50. Pharmacological modulation of Sonic Hedgehog signaling pathways in Angiogenesis: A mechanistic perspective.
- Author
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Mannan A, Dhiamn S, Garg N, and Singh TG
- Subjects
- Female, Humans, Vascular Endothelial Growth Factor A metabolism, Phosphatidylinositol 3-Kinases metabolism, Placenta Growth Factor, Signal Transduction physiology, Hedgehog Proteins metabolism, Neoplasms
- Abstract
The Sonic hedgehog (SHh) signaling pathway is an imperative operating network that helps in regulates the critical events during the development processes like multicellular embryo growth and patterning. Disruptions in SHh pathway regulation can have severe consequences, including congenital disabilities, stem cell renewal, tissue regeneration, and cancer/tumor growth. Activation of the SHh signal occurs when SHh binds to the receptor complex of Patch (Ptc)-mediated Smoothened (Smo) (Ptc-smo), initiating downstream signaling. This review explores how pharmacological modulation of the SHh pathway affects angiogenesis through canonical and non-canonical pathways. The canonical pathway for angiogenesis involves the activation of angiogenic cytokines such as fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), placental growth factor (PGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF), stromal cell-derived factor 1α, transforming growth factor-β1 (TGF-β1), and angiopoietins (Ang-1 and Ang-2), which facilitate the process of angiogenesis. The Non-canonical pathway includes indirect activation of certain pathways like iNOS/Netrin-1/PKC, RhoA/Rock, ERK/MAPK, PI3K/Akt, Wnt/β-catenin, Notch signaling pathway, and so on. This review will provide a better grasp of the mechanistic approach of SHh in mediating angiogenesis, which can aid in the suppression of certain cancer and tumor growths., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
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