Browsing by Author "Neeraj Tiwari"

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2-Mercaptoquinoline Analogues: A Potent Antileishmanial Agent
(Wiley-Blackwell, 2018) Suvajit Koley; Neeraj Tiwari; Neelabh; Rakesh Kumar Singh; Maya Shankar Singh
Leishmaniases are endemic in various countries and parasite is developing resistance against available drugs. Thus, development of new drugs against Leishmania is an open area of investigation for synthetic organic chemist. In order to meet this challenge, a series of 2-mercaptoquinoline derivatives have been synthesized and docked into the active site of Trypanothione reductase (TryR) enzyme required for redox balance of parasite. These were screened on promastigote and intracellular amastigote stages of L. donovani and found to show high levels of antileishmanial activity together with no cytotoxicity. Some of the synthesized compounds tested here, exhibited very steady and promising leishmanicidal activity against both promastigotes & intracellular amastigotes form, and the observations have been superbly supported by the docking results. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
A modified western blot protocol for enhanced sensitivity in the detection of a tissue protein
(Bentham Science Publishers, 2020) Sachchida Nand Rai; Mallikarjuna Rao Gedda; Walia Zahra; Hareram Birla; Saumitra Sen Singh; Payal Singh; Neeraj Tiwari; Rakesh K. Singh; Surya Pratap Singh
Western blots (WB) are designed to investigate protein levels and their patterns of modification in homogenized tissue samples. Although, Western blots are quantifiable, unlike immunohistochemistry, cellular integrity is lost. The availability of antibodies against the protein and their patterns of modification of interest form the basis of both Western blots and Immunohistochemistry. Antibodies can also be directed not only against proteins but against chemical modifications of the proteins too, such as phosphorylation and glycosylation of specific amino acid residues. In Western blotting, the proteins in the sample are denatured, size-separated on a denaturing acrylamide gel, and transferred to a nylon membrane. Antibody paratopes can then bind to the antigenic epitope in the protein present on the nylon membrane. Thus, with the help of a chemiluminescent assay system that darkens X-ray films, the resulting antibody-antigen complex can be visualized. Because of the ubiquitous and relatively inexpensive availability of WB equipment, the quality of WB in publications and following analysis and investigation of the data can be variable, possibly resulting in forged conclusions. This may be because of the poor laboratory technique and/or lack of understanding of the significant steps involved in WB and what quality control procedures should be followed to ensure effective data generation. The present book chapter focuses on providing a detailed description and critique of WB procedures and technicalities, from sample collection through preparation, blotting, and detection, to examination of the data collected. We aim to provide the reader with the improved expertise to decisively carry out, assess, and troubleshoot the WB process, in order to produce reproducible and reliable blots. © 2020, Bentham eBooks imprint. All rights reserved.
Biochemical characterization of plant secondary metabolites
(Elsevier, 2024) Kakarla Ramakrishna; G. Chakravarthi; Sachchidanand Rai; Payal Singh; Sameer Mishra; Divisha Mishra; Vaanya Mishra; Aditi Vikram; Neeraj Tiwari
Plants are an integral part of human health. Plants secrete primary metabolites, which form secondary metabolites. These primary and secondary metabolites are used in nutraceuticals, pharmaceuticals, dyes, etc. A variety of phytochemicals such as alkaloids, phenols, glycosides, terpenes, lipids, oils, saponins, and carbohydrates are identified and some of them are preclinically and clinically validated. There is an increased interest in finding novel and potential molecules from plant sources to cure human illness. Hence, this chapter provides an understanding of secondary metabolites isolation, structural characterization (qualitative, quantitative, and dereplication), and biochemical characterization using in silico, in vitro, ex vivo, and in vivo tests for pharmacological and toxicological assessments. © 2024 Elsevier Inc. All rights reserved.
Corrigendum: Effect of chlorogenic acid supplementation in MPTP-intoxicated mouse(Front Pharmacol., (2018), 6, (9757), 10.3389/fphar.2018.00757)
(Frontiers Media S.A., 2023) Saumitra S. Singh; Sachchida N. Rai; Hareram Birla; Walia Zahra; Gaurav Kumar; Mallikarjuna R. Gedda; Neeraj Tiwari; Ranjana Patnaik; Rakesh K. Singh; Surya P. Singh
In the published article, there was an error in Figure 8 as published. The figure panels in Figure 8 were erroneously duplicated. The corrected Figure 8 and its caption appear below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. © 2023 Singh, Rai, Birla, Zahra, Kumar, Gedda, Tiwari, Patnaik, Singh and Singh.
Corrigendum: Identification and characterization of miRNAs in response to leishmania donovani infection: Delineation of their roles in macrophage dysfunction [Front. Microbiol., 8, (2017) (314)] doi: 10.3389/fmicb.2017.00314
(Frontiers Media S.A., 2017) Neeraj Tiwari; Vinod Kumar; Mallikarjuna Rao Gedda; Ashish K. Singh; Vijay K. Singh; Surya P. Singh; Rakesh K. Singh
It has come to our attention that Dr. Sreenivas Gannavaram does not meet criteria necessary to be listed as an author, as specified by Frontiers; therefore, he has been removed from the authors' list and mentioned Acknowledgments instead. The updated Author Contributions statement and Acknowledgments are below. The authors apologize for this error and state that it does not change the scientific conclusions of the article in any way. The original article has been updated. © 2017 Tiwari, Kumar, Gedda, Singh, Singh, Singh and Singh.
Design, Synthesis and Pharmacological Evaluation of Noscapine Glycoconjugates
(Wiley-Blackwell, 2019) Kunj B Mishra; Neeraj Tiwari; Priyanka Bose; Rajan Singh; Arun K Rawat; Sumit K. Singh; Ram C. Mishra; Rakesh K Singh; Vinod K. Tiwari
The present work is directed to design a series of molecules which are hybrids of two non-toxic biocompatible chemical architectures, noscapine and carbohydrates. Fourteen, 7-O-noscapine analogues have been synthesized out of which one of the analogue is 7-O-propargylated derivative and others are in its glycoconjugate form with triazole bridging achieved via Click reaction, where dinuclear copper(I) thiodiacetate complex [(PPh 3 ) 2 Cu(μ-tda)Cu(PPh 3 ) 2 ].6H 2 O has been emerged as an excellent catalyst for the noscapine-glyco Click-coupling. All the developed noscapine glycoconjugates have been investigated for anticancer activity using HeLa cell line and anti-leishmanial activity against Leishmania donovani. Result indicates that five of the developed noscapine glycoconjugates (5 a, 5 b, 5 c, 5 e and 5 l) showed significant anti-proliferative activity. On the other hand, four of them (5 b, 5 c, 5 e, and 5 l) showed significant anti-leishmanial activity. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Effect of chlorogenic acid supplementation in MPTP-intoxicated mouse
(Frontiers Media S.A., 2018) Saumitra S. Singh; Sachchida N. Rai; Hareram Birla; Walia Zahra; Gaurav Kumar; Mallikarjuna R. Gedda; Neeraj Tiwari; Ranjana Patnaik; Rakesh K. Singh; Surya P. Singh
Oxidative stress and neuroinflammation play a key role in dopaminergic (DA) neuronal degeneration, which results in the hindrance of normal ongoing biological processes in the case of Parkinson's disease. As shown in several studies, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, different behavioral parameters have suggested motor impairment and damage of antioxidant defence. Thus, some specific biological molecules found in medicinal plants can be used to inhibit the DA neuronal degeneration through their antioxidant and anti-inflammatory activities. With this objective, we studied chlorogenic acid (CGA), a naturally occurring polyphenolic compound, for its antioxidant and anti-inflammatory properties in MPTP-intoxicated mice. We observed significant reoccurrence of motor coordination and antioxidant defence on CGA supplementation, which has been in contrast with MPTP-injected mice. Moreover, in the case of CGA-treated mice, the enhanced expression of tyrosine hydroxylase (TH) within the nigrostriatal region has supported its beneficial effect. The activation of glial cells and oxidative stress levels were also estimated using inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) immunoreactivity within substantia nigra (SN) and striatum of MPTP-injected mice. Administration of CGA has prevented the neuroinflammation in SN by regulating the nuclear factor-κB expression in the MPTP-induced group. The significant release of certain pro-inflammatory mediators such as tumor necrosis factor-α and interleukin (IL)-1β has also been inhibited by CGA with the enhanced expression of anti-inflammatory cytokine IL-10. Moreover, reduced GFAP staining within the nigrostriatal region has supported the fact that CGA has significantly helped in the attenuation of astrocyte activation. Hence, our study has shown that CGA supplementation shows its therapeutic ability by reducing the oxidative stress and neuroinflammation in MPTP-intoxicated mice. © 2018 Singh, Rai, Birla, Zahra, Kumar, Gedda, Tiwari, Patnaik, Singh and Singh.
Effect of functionalities on the crystal structures of new zinc(II) dithiocarbamates: A combined anti-leishmanial and thermal decomposition study
(Royal Society of Chemistry, 2017) Krishna K. Manar; Chote L. Yadav; Neeraj Tiwari; Rakesh K. Singh; Akhilesh Kumar; Michael G. B. Drew; Nanhai Singh
New homoleptic zinc(ii) dithiocarbamates, [Zn(L)2] (L = N-ferrocenyl-N-methyl dithiocarbamate (L1) 1, (N-(benzo[d][1,3]dioxol-5-ylmethyl)-N-furfuryl) dithiocarbamate (L2) 2, N-(benzo[d][1,3]dioxol-5-ylmethyl)-(N-benzyl) dithiocarbamate (L3) 3, N-(benzo[d][1,3]dioxol-5-ylmethyl)-(N-methyl) dithiocarbamate (L4) 4, N-ethylmorpholine-(N-4-methoxyphenylmethyl) dithiocarbamate (L5) 5 and N-(benzo[d][1,4]dioxol-6-ylmethyl)-(N-benzylmethyl) dithiocarbamate (L6) 6, have been synthesized and characterized by elemental analyses and spectroscopy (IR, UV-vis, 1H and 13C{1H} NMR). X-ray crystallography revealed different dimeric structures for (1 and 2) and (3, 4, and 5) adopting distorted tetrahedral and TBP/SP coordination geometries, respectively, in which the dithiocarbamate ligands are bonded to the metal centers both in terminal S,S-chelating and μ2,κ2S,S-bridging and μ2,κ2-S,S-chelating-bridging arrangements. 6 is a mononuclear complex showing a distorted tetrahedral geometry. The supramolecular frameworks in these complexes have been sustained by C-H⋯S, C-H⋯O, C-H⋯π, π⋯π, C-H⋯π (ZnCS2, chelate) and H⋯H interactions. The anti-leishmanial activities of the complexes have been screened; 4 and 6 showed potential anti-promastigote and anti-amastigote activities with IC50 values of 0.66 ± 0.22, 1.48 ± 0.10 μg mL-1 and IC50 2.98 ± 0.30, 2.51 ± 0.10 μg mL-1, respectively. Cytotoxicity assays on both complexes showed toxicity on promastigotes but lower toxicity against the RAW 264.7 cell line at different concentrations. All the complexes show luminescence characteristics in CH2Cl2 solution at room temperature arising from the metal perturbed intra-ligand charge transfer (ILCT) states. Their TG analyses show single step decomposition with formation of binary ZnS and ternary FeZn2S3 materials which have been examined by PXRD, SEM and EDAX. © 2017 The Royal Society of Chemistry.
Exploring the Paradox of COVID-19 in Neurological Complications with Emphasis on Parkinson's and Alzheimer's Disease
(Hindawi Limited, 2022) Sachchida Nand Rai; Neeraj Tiwari; Payal Singh; Anurag Kumar Singh; Divya Mishra; Mohd. Imran; Snigdha Singh; Etrat Hooshmandi; Emanuel Vamanu; Santosh K. Singh; Mohan P. Singh
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a human coronavirus (HCoV) that has created a pandemic situation worldwide as COVID-19. This virus can invade human cells via angiotensin-converting enzyme 2 (ACE2) receptor-based mechanisms, affecting the human respiratory tract. However, several reports of neurological symptoms suggest a neuroinvasive development of coronavirus. SARS-CoV-2 can damage the brain via several routes, along with direct neural cell infection with the coronavirus. The chronic inflammatory reactions surge the brain with proinflammatory elements, damaging the neural cells, causing brain ischemia associated with other health issues. SARS-CoV-2 exhibited neuropsychiatric and neurological manifestations, including cognitive impairment, depression, dizziness, delirium, and disturbed sleep. These symptoms show nervous tissue damage that enhances the occurrence of neurodegenerative disorders and aids dementia. SARS-CoV-2 has been seen in brain necropsy and isolated from the cerebrospinal fluid of COVID-19 patients. The associated inflammatory reaction in some COVID-19 patients has increased proinflammatory cytokines, which have been investigated as a prognostic factor. Therefore, the immunogenic changes observed in Parkinson's and Alzheimer's patients include their pathogenetic role. Inflammatory events have been an important pathophysiological feature of neurodegenerative diseases (NDs) such as Parkinson's and Alzheimer's. The neuroinflammation observed in AD has exacerbated the Aβ burden and tau hyperphosphorylation. The resident microglia and other immune cells are responsible for the enhanced burden of Aβ and subsequently mediate tau phosphorylation and ultimately disease progression. Similarly, neuroinflammation also plays a key role in the progression of PD. Several studies have demonstrated an interplay between neuroinflammation and pathogenic mechanisms of PD. The dynamic proinflammation stage guides the accumulation of α-synuclein and neurodegenerative progression. Besides, few viruses may have a role as stimulators and generate a cross-autoimmune response for α-synuclein. Hence, neurological complications in patients suffering from COVID-19 cannot be ruled out. In this review article, our primary focus is on discussing the neuroinvasive effect of the SARS-CoV-2 virus, its impact on the blood-brain barrier, and ultimately its impact on the people affected with neurodegenerative disorders such as Parkinson's and Alzheimer's. © 2022 Sachchida Nand Rai et al.
Identification and characterization of miRNAs in response to Leishmania donovani infection: Delineation of their roles in macrophage dysfunction
(Frontiers Media S.A., 2017) Neeraj Tiwari; Vinod Kumar; Mallikarjuna Rao Gedda; Ashish K. Singh; Vijay K. Singh; Sreenivas Gannavaram; Surya P. Singh; Rakesh K. Singh
The outcome of Leishmania infection depends on parasite abilities to evade host immune response and its survival in hostile environment of host macrophages. Despite a wealth of gained crucial information, parasite strategies by which it dampens host macrophage functions remain poorly understood. Micro RNAs (miRNAs) are evolutionarily conserved class of endogenous 22-nucleotide small non-coding RNA gene products, described to participate in the regulation of almost every cellular process investigated so far. In this study, we identified 940 miRNAs in Leishmania donovani infected macrophages by de novo sequencing out of which levels of 85 miRNAs were found to be consistently modified by parasite infection. Herein, we report the functional characteristics of 10 miRNAs i.e., mir-3620, mir-6385, mir-6973a, mir-6996, mir-328, mir-8113, mir-3473f, mir-763, mir-6540, and mir-1264 that were differentially but constantly regulated in infected macrophages for their role in regulation of macrophage effector functions. The target gene prediction and biological interaction analysis revealed involvement of these miRNAs in various biological processes such as apoptosis inhibition, phagocytosis, drug response, and T cell phenotypic transitions. These findings could contribute for the better understanding of macrophages dysfunction and leishmanial pathogenesis. Further, the identified miRNAs could also be used as biomarker/s in diagnosis, prognosis, and therapeutics of Leishmania infection. © 2017 Tiwari, Kumar, Gedda, Singh, Singh, Gannavaram, Singh and Singh.
Immunohistochemistry as an important technique in experimental and clinical practices
(Bentham Science Publishers, 2020) Hareram Birla; Sachchida Nand Rai; Saumitra Sen Singh; Walia Zahra; Neeraj Tiwari; Aijaz A. Naik; Anamika Misra; Shikha Bharati; Surya Pratap Singh
Immunohistochemistry (IHC) is a well-known technique in the field of biological and medical sciences. This technique is based on the principle of antigenantibody interaction and is used for identification of cellular or tissue constituents, i.e., an antigen by using a specific antibody. The binding of an antibody to an antigen is confirmed either by labelled primary antibody itself or by using secondary labelling method such as fluorescence labelled antibody. Such interactions give information about the cellular process occurring inside the cell. In last few years, huge amount of data have been generated using IHC. Furthermore, adequate knowledge of this technique is required for the optimum result and its reproducibility. The detailed information about the tissue section, antigen retrieval (AR), increased sensitivity of the detection systems and proper standardization are the key points for this technique. This protocol will address overview of the technique, tissue preparation, microtome, antigen retrieval, antibodies and antigen fixation, detection methods, background reduction and trouble shootings. © 2020, Bentham eBooks imprint. All rights reserved.
Leishmania donovani infection activates Toll-like receptor 2, 4 expressions and Transforming growth factor-beta mediated apoptosis in renal tissues
(Elsevier Editora Ltda, 2017) Vinod Kumar; Neeraj Tiwari; Mallikarjuna Rao Gedda; Rizwanul Haque; Rakesh K. Singh
The present study was aimed to identify the underlying mechanisms of improper renal function in Leishmania donovani infection that causes VL. Mice (BALB/c) were infected with L. donovani and different parameters for proteinuria were assessed. The levels of superoxide anion (O2−), hydrogen peroxide (H2O2), lipid peroxidation (MDA), inflammatory cytokines, and toll-like receptor (TLR) 2 and 4 expression were found significantly elevated at 60th day in these animals and declined at 90th day post infection. However, TGF-β and caspase 3 activities were higher at 90th day in comparison to 60th day post infection. These findings suggested that exacerbated inflammatory conditions correlate with abnormal renal functions in L. donovani infection, which is further augmented by activated TLRs expressions by circulating leishmanial antigens. Further, the increased levels of TGF-β and caspase 3 at 90th day suggested TGF-β mediated apoptotic cell death of renal and other cells during later stages of disease that may eventually result in release of host and parasitic factors in urine during visceral leishmaniasis. © 2017 Sociedade Brasileira de Infectologia
Leishmania donovani infection induce differential miRNA expression in CD4+ T cells
(Nature Research, 2020) Vinod Kumar; Sushmita Das; Ajay Kumar; Neeraj Tiwari; Ashish Kumar; Kumar Abhishek; Abhishek Mandal; Manjay Kumar; Taj Shafi; Tanvir Bamra; Rakesh Kumar Singh; Saravanan Vijayakumar; Abhik Sen; Pradeep Das
Visceral leishmaniasis is characterized by mixed production of Th1/2 cytokines and the disease is established by an enhanced level of Th2 cytokine. CD4+ T cells are main cell type which produces Th1/2 cytokine in the host upon Leishmania infection. However, the regulatory mechanism for Th1/2 production is not well understood. In this study, we co-cultured mice CD4+ T cells with Leishmania donovani infected and uninfected macrophage for the identification of dysregulated miRNAs in CD4+ T cells by next-generation sequencing. Here, we identified 604 and 613 known miRNAs in CD4+ T cells in control and infected samples respectively and a total of only 503 miRNAs were common in both groups. The expression analysis revealed that 112 miRNAs were up and 96 were down-regulated in infected groups, compared to uninfected control. Nineteen up-regulated and 17 down-regulated miRNAs were statistically significant (p < 0.05), which were validated by qPCR. Further, using insilco approach, we identified the gene targets of significant miRNAs on the basis of CD4+ T cell biology. Eleven up-regulated miRNAs and 9 down-regulated miRNAs were associated with the cellular immune responses and Th1/2 dichotomy upon Leishmania donovani infection. The up-regulated miRNAs targeted transcription factors that promote differentiation of CD4+ T cells towards Th1 phenotype. While down-regulated miRNAs targeted the transcription factors that facilitate differentiation of CD4+ T cells towards Th2 populations. The GO and pathway enrichment analysis also showed that the identified miRNAs target the pathway and genes related to CD4+ T cell biology which plays important role in Leishmania donovani infection. © 2020, The Author(s).
Leishmaniasis control: Limitations of current drugs and prospects of natural products
(Elsevier, 2019) Neeraj Tiwari; Arun Kumar; Ashish K. Singh; Surabhi Bajpai; Anand K. Agrahari; Dhiraj Kishore; Vinod K. Tiwari; Rakesh K. Singh
Leishmaniases are endemic in 98 countries and a serious threat to approximately 310 million people living in endemic regions of affected countries. Out of 53 described species of Leishmania parasites, 20 are known to cause human pathogenesis and may produce three discreet clinical manifestations, that is, cutaneous (CL), mucocutaneous (MCL), and visceral (VL) leishmaniasis that differ in their immunopathologies and degree of morbidity and mortality. It is estimated that approximately 0.7-1.2 million new CL and 0.2-0.4 million of new VL cases occur each year in disease endemic countries. The current treatment options comprise only three drugs, viz. pentavalent antimonials, amphotericin B (and its liposomal formulation, AmBisome), and miltefosine that also produce severe side effects. These drugs do not produce a sterile cure, leaving behind a possible and potent source of parasitic reservoirs for further disease transmission along with the emergence of drug-resistant parasites. The limited drug regimen, coupled with the unavailability of a licensed vaccine, necessitates the development of a true antileishmanial drug to combat increasing incidences of leishmaniasis. In this chapter, we summarize a wide range of compounds isolated from various natural sources that are worth screening to develop a true antileishmanial drug along with a short discussion on the limitations of current drugs. © 2019 Elsevier Inc. All rights reserved.
Limitations of current therapeutic options, possible drug targets and scope of natural products in control of leishmaniasis
(Bentham Science Publishers, 2018) Neeraj Tiwari; Mallikarjuna Rao Gedda; Vinod K. Tiwari; Surya P. Singh; Rakesh K. Singh
Soon after the identification of Leishmania parasite as a causative agent, the pentavalent antimony compounds have been the mainstay to treat all forms of leishmaniasis. Due to growing inci-dences of antimony resistant parasites and unavailability of true antileishmanial compounds, few drugs like pentamidine (antimicrobial), amphotericin B (antifungal) or miltefosine (antitumor) are currently being used but these are associated with serious side effects. Unfortunately, the emergence of ampho-tericin B and miltefosine resistant parasites in clinical settings has further questioned their sustained use in leishmanial control. Moreover, the parameters of protective immunity are not well understood in leishmanial pathogenesis therefore, a vaccine candidate, either prophylactic or preventive, is still an unrealized goal. In addition, the emergence of insecticide resistance sand flies in disease endemic re-gions also stance a big threat for the current elimination strategies. Therefore, in lieu of the limited drug regimen and unavailability of a vaccine, the necessity of a true antileishmanial agent is always there. Although, leishmanial infections have been neglected for many decades but recent studies have identified potential drug targets that could be targeted to control the growth of parasites. In recent past many compounds derived from natural sources have also been shown to possess excellent antiparasitic potential; however, most of these studies are limited to primary evaluation and only a few have reached to clinical levels. In this review, we discuss the limitations of current drug regimen, explore possible drug targets of Leishmania species and summarize wide range of compounds isolated from various natural sources that are worth screening as antileishmanial drug candidates. © 2018 Bentham Science Publishers.
Phytochemicals and Gut Health
(Elsevier, 2025) Sachchida Nand Rai; Neeraj Tiwari; Sucheta Khubber
Shivangi Gupta, Romil Sharma, ... Sachchida Nand Rai © 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies..
Solute carrier protein family 11 member 1 (Slc11a1) activation efficiently inhibits Leishmania donovani survival in host macrophages
(Springer India, 2017) Nisha Singh; Mallikarjuna Rao Gedda; Neeraj Tiwari; Suya P. Singh; Surabhi Bajpai; Rakesh K. Singh
Visceral leishmaniasis (kala-azar), a life threatening disease caused by L. donovani, is a latent threat to more than 147 million people living in disease endemic South East Asia region of the Indian subcontinent. The therapeutic option to control leishmanial infections are very limited, and at present comprise only two drugs, an antifungal amphotericin B and an antitumor miltefosine, which are also highly vulnerable for parasitic resistance. Therefore, identification and development of alternate control measures is an exigent requirement to control leishmanial infections. In this study, we report that functionally induced expression of solute carrier protein family 11 member 1 (Slc11a1), a transmembrane divalent cationic transporter recruited on the surface of phagolysosomes after phagocytosis of parasites, effectively inhibits Leishmania donovani growth in host macrophages. Further, the increased Slc11a1 functionality also resulted in increased production of NOx, TNF-α and IL-12 by activated macrophages. The findings of this study signify the importance of interplay between Slc11a1 expression and macrophages activation that can be effectively used to control of Leishmania growth and survival. © 2016, Indian Society for Parasitology.
Synthesis, crystal structures and properties of new homoleptic Ni(II)/Pd(II) β-oxodithioester chelates
(Elsevier B.V., 2018) Chote L. Yadav; Krishna K. Manar; Manoj K. Yadav; Neeraj Tiwari; Rakesh K. Singh; Michael G.B. Drew; Nanhai Singh
Six new cis-chelate complexes, [M(L)2] (L = methyl-3-hydroxy-3-(furyl)-2-propenedithioate L1, M = Ni(II) 1, Pd(II) 4; methyl-3-hydroxy-3-(thiophenyl)-2-propenedithioate L2, M = Ni(II) 2, Pd(II) 5 and methyl-3-hydroxy-3-(phenyl)-2-propenedithioate L3, M = Ni(II) 3, Pd(II) 6 have been prepared and characterized by elemental analyses, spectroscopy (IR, UV–Vis., 1H and 13C{1H} NMR). The structures of 2–6 have been revealed by X-ray crystallography. In all the crystal structures, the metal has four-coordinate slightly distorted square planar geometry with a cis-configuration of the ligands. Anti-leishmanial properties of the complexes have been studied; 2, 3 and 6 showed potential anti-promastigote and anti-amastigote activities with IC50 values of 1.70 ± 0.50, 1.62 ± 0.19, 9.20 ± 2.16 μg/mL and IC50 2.50 ± 0.10, 2.05 ± 0.40, 12.84 ± 3.46 μg/mL respectively. Cytotoxicity assays on these complexes showed toxicity on the promastigotes but less toxicity against RAW 264.7 cell lines at different concentrations. Palladium complexes 4, 5 and 6 show luminescent characteristics in CH2Cl2 solution at room temperature. Complexes 1–6 are weakly conducting (σrt = 10−4-10−6 S cm−1, Ea = 0.19–1.13 eV) but show semiconducting behavior in the solid phase. © 2018 Elsevier B.V.
Therapeutic Potential of Vital Transcription Factors in Alzheimer’s and Parkinson’s Disease With Particular Emphasis on Transcription Factor EB Mediated Autophagy
(Frontiers Media S.A., 2021) Sachchida Nand Rai; Neeraj Tiwari; Payal Singh; Divya Mishra; Anurag Kumar Singh; Etrat Hooshmandi; Emanuel Vamanu; Mohan P. Singh
Autophagy is an important cellular self-digestion and recycling pathway that helps in maintaining cellular homeostasis. Dysregulation at various steps of the autophagic and endolysosomal pathway has been reported in several neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington disease (HD) and is cited as a critically important feature for central nervous system (CNS) proteostasis. Recently, another molecular target, namely transcription factor EB (TFEB) has been explored globally to treat neurodegenerative disorders. This TFEB, is a key regulator of autophagy and lysosomal biogenesis pathway. Multiple research studies suggested therapeutic potential by targeting TFEB to treat human diseases involving autophagy-lysosomal dysfunction, especially neurodegenerative disorders. A common observation involving all neurodegenerative disorders is their poor efficacy in clearing and recycle toxic aggregated proteins and damaged cellular organelles due to impairment in the autophagy pathway. This dysfunction in autophagy characterized by the accumulation of toxic protein aggregates leads to a progressive loss in structural integrity/functionality of neurons and may even result in neuronal death. In recent years TFEB, a key regulator of autophagy and lysosomal biogenesis, has received considerable attention. It has emerged as a potential therapeutic target in numerous neurodegenerative disorders like AD and PD. In various neurobiology studies involving animal models, TFEB has been found to ameliorate neurotoxicity and rescue neurodegeneration. Since TFEB is a master transcriptional regulator of autophagy and lysosomal biogenesis pathway and plays a crucial role in defining autophagy activation. Studies have been done to understand the mechanisms for TFEB dysfunction, which may yield insights into how TFEB might be targeted and used for the therapeutic strategy to develop a treatment process with extensive application to neurodegenerative disorders. In this review, we explore the role of different transcription factor-based targeted therapy by some natural compounds for AD and PD with special emphasis on TFEB. Copyright © 2021 Rai, Tiwari, Singh, Mishra, Singh, Hooshmandi, Vamanu and Singh.
Tinospora cordifolia Suppresses Neuroinflammation in Parkinsonian Mouse Model
(Humana Press Inc., 2019) Hareram Birla; Sachchida Nand Rai; Saumitra Sen Singh; Walia Zahra; Arun Rawat; Neeraj Tiwari; Rakesh K. Singh; Abhishek Pathak; Surya Pratap Singh
Parkinson’s disease (PD), a neurodegenerative central nervous system disorder, is characterised by progressive loss of nigrostriatal neurons in basal ganglia. Previous studies regarding PD have suggested the role of oxidative stress along with neuroinflammation in neurodegeneration. Accordingly, our study explore the anti-inflammatory activity of Tinospora cordifolia aqueous extract (TCAE) in 1-methyl-4-phenyl-1,2,3,6-tetra hydropyridine (MPTP)-intoxicated Parkinsonian mouse model. MPTP-intoxicated mice showed significant behavioral and biochemical abnormalities which were effectively reversed by TCAE. It is evident that TCAE inhibits the MPTP-intoxicated Nuclear factor-κB (NF-κB) activation and its associated pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) from immunohistochemistry and Western blot analysis. In MPTP-intoxicated mice, microglial and astroglial-specific inflammatory markers, ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP), respectively were increased while were significantly reduced in TCAE treatment. Expression of pro-inflammatory cytokine genes, TNF-α, Interleukin-12 (IL-12) and Interleukin-1β (IL-1β) were found to be upregulated in MPTP-intoxicated mice, whereas TCAE treatment restored their levels. Additionally, anti-inflammatory factor Interleukin-10 (IL-10) gene was found to be downregulated in MPTP-intoxicated mice which were significantly restored by TCAE treatment. Tyrosine hydroxylase (TH) expression was reduced in MPTP-intoxicated mice, while its expression was significantly increased in TCAE-treated group. Our result strongly suggests that T. cordifolia protects dopaminergic neurons by suppressing neuroinflammation in MPTP-induced Parkinsonian mouse model. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.