Browsing by Author "Singh, Surya P."

Now showing 1 - 7 of 7
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    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) Singh, Saumitra S.; Rai, Sachchida N.; Birla, Hareram; Zahra, Walia; Kumar, Gaurav; Gedda, Mallikarjuna R.; Tiwari, Neeraj; Patnaik, Ranjana; Singh, Rakesh K.; Singh, Surya P.
    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.
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    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) Waiker, Digambar Kumar; Verma, Akash; Akhilesh, None; Gajendra, T.A.; Singh, Namrata; Roy, Anima; Dilnashin, Hagera; Tiwari, Vinod; Trigun, Surendra Kumar; Singh, Surya P.; Krishnamurthy, Sairam; Lama, Prem; Davisson, Vincent Jo; Shrivastava, Sushant Kumar
    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), ?-secretase-1 (hBACE-1), and amyloid ? (A?) 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 A? 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 ?M 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 ?M concentrations. In both the scopolamine- and A?-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-?) 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 A?, amyloid precursor protein (APP)/A?, 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 A? levels, which was comparable to donepezil-treated group. Compounds 5d and 5f represent new lead candidates for developing AD therapeutics. � 2023 American Chemical Society.
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    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) Thakur, Keshav; Goud, Emmagouni Sharath Kumar; Jawa, Yashika; Keswani, Chetan; Onteru, Suneel; Singh, Dheer; Singh, Surya P.; Roy, Partha; Tyagi, Rakesh K.
    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.
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    Economic Shock and Agri-Sector: Post-COVID-19 Scenario in India
    (Springer Nature, 2021) Dilnashin, Hagera; Birla, Hareram; Rajput, Vishnu D.; Keswani, Chetan; Singh, Surya P.; Minkina, Tatiana M.; Mandzhieva, Saglara S.
    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.
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    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) Agrawal, Himanshu; Thakur, Keshav; Mitra, Shreyasi; Mitra, Debarghya; Keswani, Chetan; Sircar, Debabrata; Onteru, Suneel; Singh, Dheer; Singh, Surya P.; Tyagi, Rakesh K.; Roy, Partha
    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.
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    Global footprints of organochlorine pesticides: a pan-global survey
    (Springer Science and Business Media B.V., 2022) Keswani, Chetan; Dilnashin, Hagera; Birla, Hareram; Roy, Partha; Tyagi, Rakesh K.; Singh, Dheer; Rajput, Vishnu D.; Minkina, Tatiana; Singh, Surya P.
    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.
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    Silver Nanoparticles Synthesized Using Carica papaya Leaf Extract (AgNPs-PLE) Causes Cell Cycle Arrest and Apoptosis in Human Prostate (DU145) Cancer Cells
    (Humana Press Inc., 2021) Singh, Surya P.; Mishra, Abhijeet; Shyanti, Ritis K.; Singh, Rana P.; Acharya, Arbind
    Treatment of cancer has been limited by the poor efficacy and toxicity profiles of available drugs. There is a growing demand to develop alternative approaches to combat cancer such as use of nano-formulation-based drugs. Here, we report biosynthesis and characterization of silver nanoparticles (AgNPs) with papaya leaf extract (PLE) and its anti-cancer properties against different human cancer cells. Purified nanoparticles were characterized by standard techniques, such as TEM, STM, SEM, EDS, XRD, and FTIR. Furthermore, cytotoxic activity of AgNPs-PLE was carried out against different human cancer cells and non-tumorigenic human keratinocytes cells. AgNPs-PLE when compared with AgNPs-citric acid or PLE showed better efficacy against cancer cells and was also relatively less toxic to normal cells. Treatment of DU145 cells with AgNPs-PLE (0.5�5.0�?g/ml) for 24�48�h lowered total cell number by 24�36% (P < 0.05). Inhibition of cell growth was linked with arrest of cell cycle at G2/M phase at 24�h, while G1 and G2/M phase arrests at 48�h. ROS production was observed at earlier time points in presence of AgNPs-PLE, suggesting its role behind apoptosis in DU145 cells. Induction of apoptosis (57%) was revealed by AO/EB staining in DU145 cells along with induction of Bax, cleaved caspase-3, and cleaved PARP proteins. G1-S phase cell cycle check point marker, cyclin D1 was down-regulated along with an increase in cip1/p21 and kip1/p27 tumor suppressor proteins by AgNPs-PLE. These findings suggest the anti-cancer properties of AgNPs-PLE. � 2020, Springer Science+Business Media, LLC, part of Springer Nature.