Browsing by Author "Surya P. Singh"

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1800 MHz mobile phone irradiation induced oxidative and nitrosative stress leads to p53 dependent Bax mediated testicular apoptosis in mice, Mus musculus
(Wiley-Liss Inc., 2018) Saba Shahin; Surya P. Singh; Chandra M. Chaturvedi
Present study was carried out to investigate the effect of long-term mobile phone radiation exposure in different operative modes (Dialing, Receiving, and Stand-by) on immature male mice. Three-week old male mice were exposed to mobile phone (1800 MHz) radiation for 3 hr/day for 120 days in different operative modes. To check the changes/alteration in testicular histoarchitecture and serum testosterone level, HE staining and ELISA was performed respectively. Further, we have checked the redox status (ROS, NO, MDA level, and antioxidant enzymes: SOD, CAT, and GPx) by biochemical estimation, alteration in the expression of pro-apoptotic proteins (p53 and Bax), active executioner caspase-3, full length/uncleaved PARP-1 (DNA repair enzyme), anti-apoptotic proteins (Bcl-2 and Bcl-xL) in testes by immunofluorescence and cytosolic cytochrome-c by Western blot. Decreased seminiferous tubule diameter, sperm count, and viability along with increased germ cells apoptosis and decreased serum testosterone level, was observed in the testes of all the mobile phone exposed mice compared with control. We also observed that, mobile phone radiation exposure in all the three different operative modes alters the testicular redox status via increasing ROS, NO, and MDA level, and decreasing antioxidant enzymes levels leading to enhanced apoptosis of testicular cells by increasing the expression of pro-apoptotic and apoptotic proteins along with decreasing the expression of anti-apoptotic protein. On the basis of results, it is conclude that long-term mobile phone radiation exposure induced oxidative stress leads to apoptosis of testicular cells and thus impairs testicular function. © 2018 Wiley Periodicals, Inc.
Anticancer Attributes of Silibinin: Chemo- and Radiosensitization of Cancer
(Elsevier, 2017) Arpit Dheeraj; Dhanir Tailor; Surya P. Singh; Rana P. Singh
Silymarin, a flavolignan from dried fruit of the milk thistle (Silybum marianum) plant, is used as an ancient medicinal plant for protection against various liver disorders. The role of silymarin and its active constituents, mainly silibinin, has been extensively explored and established in the chemopreventive efficacy against different cancers including prostate, lung, stomach, colon, skin, pancreas, and bladder cancer. Its efficacy is accomplished through growth inhibition; cell-cycle arrest through modulation of cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors; induction of apoptotic cell death; modulation of mitogenic and survival signaling involving MAPK, Akt, EGFR, STAT, NF-κB, and TGF-beta; inhibition of angiogenesis through downregulation of VEGF, iNOS, eNOS, CD31, and HIF-1alpha; reversal of epithelial-mesenchymal transition; and inhibition of invasion and migration. Silibinin, a major constituent of silymarin, has been proved as potential inhibitor of tumor progression and metastasis in preclinical animal models. Silibinin has strong potential as a chemosensitizer and has shown improved efficacy of several chemotherapeutic agents in the treatment and management of cancer with reduced toxicity. The development of resistance to these conventional therapies through induction of prosurvival and mitogenic signaling is reversed by silibinin when combined with chemo- and radiotherapies even at very low doses. Overall, silibinin targets multistep of the carcinogenesis process and improves the therapeutic effects of chemotherapeutic and radiation treatment regimens against cancer with reduced side effects. © 2018 Elsevier Inc. All rights reserved.
Biocontrol technology: Eco-friendly approaches for sustainable agriculture
(Elsevier, 2018) Ratul M. Ram; Chetan Keswani; Kartikay Bisen; Ruchi Tripathi; Surya P. Singh; Harikesh B. Singh
Recent advances in structural and functional genomics are having penetrating impact on human and environmental health. As a potential alternative of hazardous chemical pesticides, agriculturally important microorganisms have gained popularity throughout the globe. There are various naturally occurring soil microbes that aggressively attack and destroy soil and seed-borne plant pathogens, hence referred as biocontrol agents that comprise members from bacterial, fungal, and viral genera. These biocontrol agents exhibit multiple beneficial characters such as plant growth promotion activity by secretion of various plant growth promoting hormones and by mobilization of many essential inorganic macro- and micronutrients, therefore commonly referred as biofertilizers. In addition to this, biocontrol efficacy in rhizospheric region imparts strong antagonistic potential against an array of plant pathogens by secretion of various antimicrobial secondary metabolites and hydrolytic enzymes (protease, pectinase, chitinase, lipase, etc.). The biocontrol activity is exercised directly by destruction of soil-borne pathogens or indirectly by inducing plant-mediated resistance responses. Role of biocontrol agents such as Trichoderma sp., Pseudomonas fluorescens, Beauveria bassiana, and Bacillus sp. for sustainable crop production has been investigated by multi-omics approach including functional genomics, transcriptomics, proteomics, metabolomics, and secretomics. Omics-based approaches have unraveled efficient application of genetic modifications for development of various target-specific formulations. This chapter focuses on the recent biotechnological advances in biocontrol of plant pathogens for sustainable agriculture. © 2019 Elsevier Inc. All rights reserved.
Chronic nonmodulated microwave radiations in mice produce anxiety-like and depressionlike behaviours and calcium- and NO-related biochemical changes in the brain
(Korean Society for Neurodegenerative Disease, 2016) Manoj Kumar; Surya P. Singh; Chandra M. Chaturvedi
The present study was aimed to investigate behavioural and biochemical effects of chronic exposure of amplitude modulated and non-modulated microwave radiation on laboratory mice. Chronic microwave exposures were executed with 2.45 GHz of either modulated (power density, 0.029 mW/cm2; specific absorption rate, 0.019 W/Kg with sinusoidal modulation of 400 Hz) or nonmodulated continuous sinusoidal wave (power density, 0.033 mW/cm2; specific absorption rate, 0.023 W/Kg) for 2 hrs daily for 1 month. Mice subjected to non-modulated microwave exposure had significantly increased acetylcholinesterase activity and increased intracellular calcium and nitric oxide levels in the cerebral cortex and hippocampus, and also had increased glucose and corticosterone levels in blood compared to control mice. These non-modulated microwave-exposed mice exhibited anxiety-like and depression-like behaviours. In contrast, mice exposed to modulated microwave for the same period did not show such changes in concomitant biochemical and behavioural analyses. These results suggest that chronic non-modulated microwave, but not modulated microwave, radiation may cause anxiety-like and depression-like behaviours and calcium- and NO-related biochemical changes in the brain. © Experimental Neurobiology 2017.
Commentary: Metformin reverses TRAP1 mutation-associated alterations in mitochondrial function in parkinson’s disease
(Frontiers Media S.A., 2018) Sachchida N. Rai; Saumitra S. Singh; Hareram Birla; Walia Zahra; Aaina S. Rathore; Payal Singh; Surya P. Singh
[No abstract available]
Commentary: Mild endoplasmic reticulum stress ameliorates lpopolysaccharide-induced neuroinflammation and cognitive impairment via regulation of microglial polarization
(Frontiers Media S.A., 2018) Sachchida N. Rai; Walia Zahra; Hareram Birla; Saumitra S. Singh; Surya P. Singh
[No abstract available]
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 Biological Evaluation of Piperazine and N-Benzylpiperidine Hybrids of 5-Phenyl-1,3,4-oxadiazol-2-thiol as Potential Multitargeted Ligands for Alzheimer’s Disease Therapy
(American Chemical Society, 2023) Digambar Kumar Waiker; Akash Verma; None Akhilesh; T.A. Gajendra; Namrata Singh; Anima Roy; Hagera Dilnashin; Vinod Tiwari; Surendra Kumar Trigun; Surya P. Singh; Sairam Krishnamurthy; Prem Lama; Vincent Jo Davisson; Sushant Kumar Shrivastava
Our present work demonstrates the successful design and synthesis of a new class of compounds based upon a multitargeted directed ligand design approach to discover new agents for use in Alzheimer’s disease (AD). All the compounds were tested for their in vitro inhibitory potential against human acetylcholinesterase (hAChE), human butylcholinesterase (hBChE), β-secretase-1 (hBACE-1), and amyloid β (Aβ) aggregation. Compounds 5d and 5f have shown hAChE and hBACE-1 inhibition comparable to donepezil, while hBChE inhibition was comparable to rivastigmine. Compounds 5d and 5f also demonstrated a significant reduction in the formation of Aβ aggregates through the thioflavin T assay and confocal, atomic force, and scanning electron microscopy studies and significantly displaced the total propidium iodide, that is, 54 and 51% at 50 μM concentrations, respectively. Compounds 5d and 5f were devoid of neurotoxic liabilities against RA/BDNF (RA = retinoic acid; BDNF = brain-derived neurotrophic factor)-differentiated SH-SY5Y neuroblastoma cell lines at 10-80 μM concentrations. In both the scopolamine- and Aβ-induced mouse models for AD, compounds 5d and 5f demonstrated significant restoration of learning and memory behaviors. A series of ex vivo studies of hippocampal and cortex brain homogenates showed that 5d and 5f elicit decreases in AChE, malondialdehyde, and nitric oxide levels, an increase in glutathione level, and reduced levels of pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) mRNA. The histopathological examination of mice revealed normal neuronal appearance in the hippocampal and cortex regions of the brain. Western blot analysis of the same tissue indicated a reduction in Aβ, amyloid precursor protein (APP)/Aβ, BACE-1, and tau protein levels, which were non-significant compared to the sham group. The immunohistochemical analysis also showed significantly lower expression of BACE-1 and Aβ levels, which was comparable to donepezil-treated group. Compounds 5d and 5f represent new lead candidates for developing AD therapeutics. © 2023 American Chemical Society.
Detection of endocrine and metabolism disrupting xenobiotics in milk-derived fat samples by fluorescent protein-tagged nuclear receptors and live cell imaging
(Taylor and Francis Ltd., 2023) Keshav Thakur; Emmagouni Sharath Kumar Goud; Yashika Jawa; Chetan Keswani; Suneel Onteru; Dheer Singh; Surya P. Singh; Partha Roy; Rakesh K. Tyagi
Nuclear receptors (NRs) are ligand-modulated transcription factors that regulate multiple physiological functions in our body. Many NRs in their unliganded state are localized in the cytoplasm. The ligand-inducible nuclear translocation of NRs provides a valuable tool for studying the NR-ligand interactions and their downstream effects. The translocation response of NRs can be studied irrespective of the nature of the interacting ligand (agonist, antagonist, or a small molecule modulator). These nuclear translocation studies offer an advantage over promoter-reporter-based transcription assays where transcription response is observed only with the activating hormones or agonistic ligands. Globally, milk serves as a major dietary source. However, suspected presence of endocrine/metabolism-disrupting chemicals like bisphenols, parabens, organochlorine pesticides, carbamates, non-steroidal anti-inflammatory drugs, chloramphenicol, brominated flame retardants, etc. has been reported. Considering that these chemicals may impart serious developmental and metabolism-related health concerns, it is essential to develop assays suitable for the detection of xenobiotics present at differing levels in milk. Since milk samples cannot be used directly on cultured cells or for microscopy, a combination of screening strategies has been developed herein based on the revelation that i) lipophilic NR ligands can be successfully retrieved in milk-fat; ii) milk-fat treatment of cells is compatible with live-cell imaging studies; and finally, iii) treatment of cells with xenobiotics-spiked and normal milk derived fat provides a visual and quantifiable response of NR translocation in living cells. Utilizing a milk-fat extraction method and Green Fluorescent Protein (GFP) tagged NRs expressed in cultured mammalian cells, followed by an assessment of NR response proved to be an effective approach for screening xenobiotics present in milk samples.Highlights Diverse endocrine and metabolism-disrupting chemicals are suspected to contaminate milk. Nuclear receptors serve as ‘xenosensors’ for assessing the presence of xenobiotics in milk. Nuclear import of steroid receptors with (ant)agonist can be examined in live cells. Lipophilic xenobiotics are extracted and observed enriched in milk-fat fraction. A comprehensive cell-based protocol aids in the detection of xenobiotics in milk. © 2022 Informa UK Limited, trading as Taylor & Francis Group.
Economic Shock and Agri-Sector: Post-COVID-19 Scenario in India
(Springer Nature, 2021) Hagera Dilnashin; Hareram Birla; Vishnu D. Rajput; Chetan Keswani; Surya P. Singh; Tatiana M. Minkina; Saglara S. Mandzhieva
The COVID-19 pandemic had a devastating impact on the human health and global economy. The food and agriculture sectors have also felt these effects. In many countries, the measures taken to curb the spread of the virus were initiated to hinder the supply of agricultural products to markets and consumers inside and outside the borders. How this impacts the food safety, nutrition, and the livelihoods of farmers, fishermen, and others working in the food supply chain depends mainly on short-, medium-, and long-term policy responses. Epidemics pose severe challenges to the food system in the short term, but they also offer an opportunity to face challenges and accelerate the transformation of the food and agricultural sectors to increase resilience. The aim of the review was to highlight the valuable insight on the impact of COVID-19 on the Indian agricultural system and rural economy, as well as potential strategies for post-pandemic recovery. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Effect of Bisphenol A on human health and its degradation by microorganisms: A review
(2014) Shikha Chouhan; Satyndra K. Yadav; Jay Prakash; Swati; Surya P. Singh
Bisphenol A (BPA), is an industrially important compound and is widely used for the production of polycarbonates and other plastics. Over the past few years, there have been many issues raised all over the world on the use of BPA. BPA is known to possess estrogenic activities; hence, it mimics the role of estrogen once it enters living systems. Thus, it has been placed in the category of compounds called endocrine disruptors. It can cause damage to reproductive organs, thyroid gland, and brain tissues at developmental stages, and most recently it has also been linked to cancer development in humans. Here, in this review, we aim to summarize the various effects of BPA on humans and animals, and at the same time we wish to throw some light on the emerging field of biodegradation of BPA in the natural environment. A few studies conducted recently have tried to isolate BPA-degrading microorganisms from various sites, like water bodies receiving wastes from industries, landfills, etc. In the present scenario, with huge controversies on the use of BPA, we emphasize on bridging the gap between studies, aiming at finding the damage caused by BPA, and the studies which aim at the safe removal of BPA from the environment, with the help of naturally occurring microbes. Once this gap is filled, we will be able to find a way which will allow the use of BPA in manufacturing plastics, without its accumulation in the environment. © 2013 Springer-Verlag Berlin Heidelberg and the University of Milan.
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.
Evaluation of (Anti)androgenic Activities of Environmental Xenobiotics in Milk Using a Human Liver Cell Line and Androgen Receptor-Based Promoter-Reporter Assay
(American Chemical Society, 2022) Himanshu Agrawal; Keshav Thakur; Shreyasi Mitra; Debarghya Mitra; Chetan Keswani; Debabrata Sircar; Suneel Onteru; Dheer Singh; Surya P. Singh; Rakesh K. Tyagi; Partha Roy
The recent reports on milk consumption and its associated risk with hormone related disorders necessitates the evaluation of dairy products for the presence of endocrine disrupting chemicals (EDCs) and ensure the safety of consumers. In view of this, we investigated the possible presence of (anti)androgenic contaminants in raw and commercialized milk samples. For this purpose, a novel HepARE-Luc cell line that stably expresses human androgen receptor (AR) and the androgen responsive luciferase reporter gene was generated and used in the present study. Treatment of this cell line with androgens and corresponding antiandrogen (flutamide) stimulated or inhibited expression of reporter luciferase, respectively. Real time polymerase chain reaction and immunostaining results exhibited transcription response and translocation of AR from the cytoplasm to the nucleus in response to androgen. Observations implied that a cell-based xenobiotic screening assay via AR response can be conducted for assessing the (anti)androgenic ligands present in food chain including milk. Therefore, the cell line was further used to screen the (anti)androgenic activity of a total of 40 milk fat samples procured as raw or commercial milk. Some of the raw and commercial milk fat samples distinctly showed antiandrogenic activities. Subsequently, some commonly used environmental chemicals were also evaluated for their (anti)androgenic activities. Initial observations with molecular docking studies of experimental compounds were performed to assess their interaction with AR ligand binding domain. Furthermore, (anti)androgenic activities of these compounds were confirmed by performing luciferase assay using the HepARE-Luc cell line. None of the test compounds showed androgenic activities rather some of them like Bisphenol A (BPA) and rifamycin showed antiandrogenic activities. In conclusion, our results provide a valuable information about the assessment of (anti)androgenic activities present in milk samples. Overall, it is proposed that a robust cell-based CALUX assay can be used to assess the (anti)androgenic activities present in milk which can be attributed to different environmental chemicals present therein. © 2022 American Chemical Society. All rights reserved.
Global footprints of organochlorine pesticides: a pan-global survey
(Springer Science and Business Media B.V., 2022) Chetan Keswani; Hagera Dilnashin; Hareram Birla; Partha Roy; Rakesh K. Tyagi; Dheer Singh; Vishnu D. Rajput; Tatiana Minkina; Surya P. Singh
Organochlorine pesticides (OCPs) are ubiquitous environmental contaminants widely used all over the world. These chlorinated hydrocarbons are toxic and often cause detrimental health effects because of their long shelf life and bioaccumulation in the adipose tissues of primates. OCP exposure to humans occurs through skin, inhalation and contaminated foods including milk and dairy products, whereas developing fetus and neonates are exposed through placental transfer and lactation, respectively. In 1960s, OCPs were banned in most developed countries, but because they are cheap and easily available, they are still widely used in most third world countries. The overuse or misuse of OCPs has been rising continuously which pose threats to environmental and human health. This review reports the comparative occurrence of OCPs in human and bovine milk samples around the globe and portrays the negative impacts encountered through the long history of OCP use. © 2021, The Author(s), under exclusive licence to Springer Nature B.V.
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.
Impact of the alkaloid colletotrichumine A on the pathogenicity of Colletotrichum capsici in Capsicum annum L
(Elsevier B.V., 2020) Manoj K. Chitara; Chetan Keswani; Kyriakos G. Varnava; Hareram Birla; Hagera Dilnashin; Surya P. Singh; Viji Sarojini; Jonathan Sperry; Harikesh B. Singh
Herein we report a study examining the effects of colletotrichumine A, an indole-pyrazine alkaloid isolated from the anthracnose pathogen Colletotrichum capsici, on chilli plants. A colletotrichumine A-pathogen combination was more toxic to the host than individual inoculations of colletotrichumine A or the pathogen. The colletotrichumine A-pathogen combination led to an increased activity of defense related enzymes viz. PPO and SOD, while levels of the lignification enzymes PAL and PO decreased. Higher levels of phenols including catechin and ferulic acid were also observed with the colletotrichumine A-pathogen combination compared to individual treatment. The likely role of colletotrichumine A during chilli anthracnose infection is supported by histochemical analysis of infected plants that showed increased cell death after infection. © 2020 Elsevier B.V.
Impaired estrogen feedback and infertility in female mice with pituitary-specific deletion of estrogen receptor alpha (ESR1)
(2009) Surya P. Singh; Andrew Wolfe; Yewade Ng; Sara A. DiVall; Colleen Buggs; Jon E. Levine; Fredric E. Wondisford; Sally Radovick
Mice lacking estrogen receptor alpha in the pituitary gonadotroph (PitEsr1KO) were generated to determine the physiologic role of pituitary estrogen signaling in the reproductive axis. PitEsr1KO female mice are subfertile or infertile and have elevated levels of serum luteinizing hormone (LH) and LH beta subunit gene expression, reflecting a lack of estrogen negative feedback effect on the gonadotroph. While serum LH values are elevated in PitEsr1KO mice, the degree of elevation is much less than that observed in ESR1-null mice, indicating that the hypothalamus must also have an important role in estrogen negative feedback. PitEsr1KO mice also demonstrate a defect in estrogen positive feedback, as surge LH values and estrous cyclicity are absent in these mice. Although sex steroid feedback in the reproductive axis is thought to involve discrete anatomic regions that mediate either a positive or negative estrogen effect, PitEsr1KO mice demonstrate novel evidence that localizes both estrogen positive feedback and estrogen negative feedback to the gonadotroph, which suggests that they may be mechanistically related. © 2009 by the Society for the Study of Reproduction, Inc.
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.
Mucuna pruriens protects against MPTP intoxicated neuroinflammation in Parkinson's disease through NF-κB/pAKT signaling pathways
(Frontiers Media S.A., 2017) Sachchida N. Rai; Hareram Birla; Saumitra S. Singh; Walia Zahra; Ravishankar R. Patil; Jyoti P. Jadhav; Mallikarjuna R. Gedda; Surya P. Singh
Till date, drugs that have been used to manage Parkinson's disease (PD) have only shown symptomatic relief with several adverse effects besides their inability to prevent neurodegeneration. Neuroinflammation plays an important role in the advancement of PD and can be targeted for its effective treatment. Researchers have suggested that herbal plants exhibiting the anti-inflammatory and anti-oxidant properties are therefore beneficial to human health. Conventionally, Mucuna pruriens (Mp) seeds are used for maintaining male virility in India. Reportedly, Mp is used as a rejuvenator drug having neuroprotective property. Our study aimed to investigate effects of aqueous extract of Mp (100 mg/kgbwt) on neuroinflammation, orally administered to mice intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as well as the molecular mechanism involved in the progression of PD. In this study, we have observed significant behavioral abnormalities beside decreased antioxidant defense in MPTP intoxicated mice. We have also observed significant increase in inflammatory parameters like Glial Fibrillary Acidic Protein, Inducible Nitric Oxide Synthase, Intercellular Cell Adhesion Molecule, and Tumor Necrosis Factor alpha in substantia nigra pars compacta (SNpc) of parkinsonian mice, while Mp treatment has notably reduced these inflammatory parameters. Mp also inhibited the MPTP induced activation of NF-κB and promoted pAkt1 activity which further prevented the apoptosis of the dopaminergic neurons. Moreover, Mp exhibited significant antioxidant defense by inhibiting the lipid peroxidation and nitrite level, and by improving catalase activity and enhancing GSH level in nigrostriatal region of mouse brain. Mp also recovered the behavioral abnormalities in MPTP treated mice. Additionally, Mp treatment considerably increased the immunoreactivity of Tyrosine Hydroxylase and Dopamine Transporter in SNpc of parkinsonian mice. Our high performance liquid chromatography analysis of the Mp seed extract have shown L-DOPA, gallic acid, phytic acid, quercetin, and catechin equivalents as the major components which might cause neuroprotection in PD mice. Our result suggested that Mp extract treatment containing L-DOPA and a mixture of rich novel phytochemicals significantly alleviates the MPTP induced neurotoxicity by NF-κB and pAkt pathway. The findings observed thereby indicate that Mp extract have suggestively ameliorated MPTP induced neuroinflammation, restored the biochemical and behavioral abnormalities in PD mouse and thus provided a scientific basis for its traditional claim. © 2017 Rai, Birla, Singh, Zahra, Patil, Jadhav, Gedda and Singh.