Publications by authors named "Ankit Gupta"

184 Publications

Successful Multimodality Management of Atypical Teratoid/Rhabdoid Tumour of the Lower Dorsal Spine with Spinal Drop Metastasis: Illustrated Review.

Pediatr Neurosurg 2021 24;56(2):184-196. Epub 2021 Mar 24.

Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India.

Introduction: Spinal atypical teratoid/rhabdoid tumour (AT/RT) is exquisitely rare and constitutes 2% of all AT/RTs.

Case Presentation: A 6-year-old boy presented with low backache for the last 5 months. MRI of the spine showed a 1.5 × 1.5 × 4.7 cm intradural extramedullary mass extending from D10 to D12, causing compression of the conus medullaris. With a preoperative diagnosis of ependymoma, a gross total resection (GTR) of tumour was performed. Post-operative histopathology showed AT/RT. The tumour cells were immunopositive for cytokeratin, epithelial membrane antigen, smooth muscle actin, and p53 and immunonegative for MIC2, desmin, glial fibrillary acidic protein, and INI1. Post-operative neuraxis MRI revealed post-operative changes (D10-D12) with a 9 mm enhancing lesion at L5-S1 junction suggesting drop metastasis. There was no lesion in brain. Cerebrospinal fluid cytology did not show any malignant cell. The metastatic work-up was normal. He received 3 cycles of chemotherapy with ICE regimen (ifosfamide, carboplatin, and etoposide). Subsequently, he received craniospinal irradiation (CSI)-36 Gy/20 fractions/4 weeks followed by focal boost to primary tumour bed and spinal drop metastasis-14.4 Gy/8 fractions/1.5 weeks. Thereafter, he received 3 more cycles of ICE regimen. End-of-treatment MRI spine showed post-op changes (D10-D12) and 38.9% reduction of the L5-S1 lesion suggesting partial response. Six monthly spinal MRI showed serial reduction of the metastatic lesion leading to complete response (CR) 1 year after completion of treatment. On last follow-up (30 months from the initial diagnosis), he was neurologically intact and in CR.

Conclusion: Multimodality management comprising GTR of tumour, CSI followed by focal boost, and multiagent chemotherapy (ICE) can lead to successful outcome in patients with this rare and aggressive spinal tumour.
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http://dx.doi.org/10.1159/000513936DOI Listing
March 2021

Spinal cord involvement in COVID-19: A review.

J Spinal Cord Med 2021 Mar 11:1-15. Epub 2021 Mar 11.

Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Context: Recent literature points towards myelitis, like encephalitis, as a common central nervous system complication of COVID-19. This review elaborates on disorders of the spinal cord caused by the SARS-CoV-2 virus.

Objectives: To review the published data about SARS-CoV-2-associated spinal cord disorders and assess their clinical, neuroimaging, treatment, and prognostic aspects.

Methods: The PubMed and Google Scholar databases were searched for published cases using the search items "COVID-19 OR SARS-CoV-2 AND myelitis", "COVID-19 OR SARS-CoV-2 AND myelopathy", and "COVID-19 OR SARS-CoV-2 AND spinal cord".

Results: Thirty-three isolated cases were included in the present review, of which 14 were aged 60 years and above (range: 3-70 years). Eighteen patients had lung abnormalities on chest imaging. Eight patients had developed either an areflexic paraparesis or quadriparesis. In 17 patients, neuroimaging demonstrated longitudinally extensive transverse myelitis, while 3 cases showed neuroimaging changes in the spinal cord as a part of acute disseminated encephalomyelitis syndrome. Cerebrospinal fluid (CSF) examinations revealed inflammatory changes in 18 patients. However, the SARS-CoV-2 virus in the CSF was discovered in 2 patients. In 2 patients, anti-SARS-CoV-2 antibodies were demonstrated in the CSF. Following treatment, 13 patients were able to walk.

Conclusions: A variety of COVID-19-related spinal cord manifestations, such as acute transverse myelitis, acute necrotizing myelitis, SARS-CoV-2 myelitis, acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorder, hypoxic myelopathy, MOG antibody-associated myelitis, spinal cord infarction, and spinal epidural abscess, have been reported. The possible mechanisms of this involvement being direct invasion, cytokine storm, coagulopathy, and an autoimmune response. However, response to treatment has been generally unsatisfactory, with many patients having residual weakness necessitating long-term rehabilitation.
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http://dx.doi.org/10.1080/10790268.2021.1888022DOI Listing
March 2021

A Hi-C data-integrated model elucidates E. coli chromosome's multiscale organization at various replication stages.

Nucleic Acids Res 2021 04;49(6):3077-3091

Tata Institute of Fundamental Research, Centre for Interdisciplinary Sciences, Hyderabad 500046, India.

The chromosome of Escherichia coli is riddled with multi-faceted complexity. The emergence of chromosome conformation capture techniques are providing newer ways to explore chromosome organization. Here we combine a beads-on-a-spring polymer-based framework with recently reported Hi-C data for E. coli chromosome, in rich growth condition, to develop a comprehensive model of its chromosome at 5 kb resolution. The investigation focuses on a range of diverse chromosome architectures of E. coli at various replication states corresponding to a collection of cells, individually present in different stages of cell cycle. The Hi-C data-integrated model captures the self-organization of E. coli chromosome into multiple macrodomains within a ring-like architecture. The model demonstrates that the position of oriC is dependent on architecture and replication state of chromosomes. The distance profiles extracted from the model reconcile fluorescence microscopy and DNA-recombination assay experiments. Investigations into writhe of the chromosome model reveal that it adopts helix-like conformation with no net chirality, earlier hypothesized in experiments. A genome-wide radius of gyration map captures multiple chromosomal interaction domains and identifies the precise locations of rrn operons in the chromosome. We show that a model devoid of Hi-C encoded information would fail to recapitulate most genomic features unique to E. coli.
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http://dx.doi.org/10.1093/nar/gkab094DOI Listing
April 2021

Vivid Visual Hallucinations in Visually Impaired: Charles Bonnet Syndrome - An Analog to "Phantom-Limb Phenomenon".

Ann Indian Acad Neurol 2020 Sep-Oct;23(5):734-735. Epub 2020 Jun 5.

Department of Neurology and, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

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http://dx.doi.org/10.4103/aian.AIAN_40_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887482PMC
June 2020

A hidden integral structure endows absolute concentration robust systems with resilience to dynamical concentration disturbances.

J R Soc Interface 2020 10 28;17(171):20200437. Epub 2020 Oct 28.

Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26 4058 Basel, Switzerland.

Biochemical systems that express certain chemical species of interest at the same level at any positive steady state are called 'absolute concentration robust' (ACR). These species behave in a stable, predictable way, in the sense that their expression is robust with respect to sudden changes in the species concentration, provided that the system reaches a (potentially new) positive steady state. Such a property has been proven to be of importance in certain gene regulatory networks and signaling systems. In the present paper, we mathematically prove that a well-known class of ACR systems studied by Shinar and Feinberg in 2010 hides an internal integral structure. This structure confers these systems with a higher degree of robustness than was previously known. In particular, disturbances much more general than sudden changes in the species concentrations can be rejected, and robust perfect adaptation is achieved. Significantly, we show that these properties are maintained when the system is interconnected with other chemical reaction networks. This key feature enables the design of insulator devices that are able to buffer the loading effect from downstream systems-a crucial requirement for modular circuit design in synthetic biology. We further note that while the best performance of the insulators are achieved when these act at a faster timescale than the upstream module (as typically required), it is not necessary for them to act on a faster timescale than the downstream module in our construction.
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http://dx.doi.org/10.1098/rsif.2020.0437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653391PMC
October 2020

Impact assessment of clean cookstove intervention in Gujarat, India: a potential case for corporate social responsibility (CSR) funding.

Environ Sci Pollut Res Int 2021 Mar 22;28(10):12740-12752. Epub 2020 Oct 22.

Energy and Resource Management Division, CSIR-National Environmental Engineering Research Institute (NEERI), Nagpur, Maharashtra, 440020, India.

Exposure to indoor air pollutants released from traditional cookstoves in rural Indian households is a matter of great concern. While there are various studies over several decades focused towards intervention strategies for reducing air pollutants, limited literature exists towards the identification of appropriate methodology for feasible intervention, adoption and usage of improved cookstoves (ICS). In the present study, PM and CO microenvironment concentrations are estimated in households using traditional and improved cookstove (NEERDHUR). The reduction in PM and CO microenvironment concentrations after the introduction of ICS was found to be 89-94% and 35-57%, respectively. Information-education-communication (IEC) activity was used as a tool to increase the adoption and usage rate in the ICS using households. The cost-benefit analysis was also performed to check the benefits of ICS use, and the benefit-cost ratio was found to be 3 to 4 times. Findings of the study suggest that, although the ICS intervention could significantly improve the indoor air quality, however, it fails to comply with the permissible safe limits; further focus on greener fuels and ventilation characteristics is suggested. The outcomes from the study can help decision-makers, corporate social responsibility fund mobilizers and policymakers for effective policy advocacy to design efforts by promoting clean cooking interventions and linking and mapping these with national missions and flagship programs.
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http://dx.doi.org/10.1007/s11356-020-11011-8DOI Listing
March 2021

Effect of different irrigating solutions with surfactants on the microhardness and smear layer removal of root canal dentin: An study.

J Conserv Dent 2019 Sep-Oct;22(5):454-458. Epub 2020 Aug 4.

Department of Conservative Dentistry and Endodontics National Dental College and Hospital Derabassi, Punjab, India.

Aim: The present study was undertaken to check the effect of the different irrigating solutions with surfactants, i.e., sodium hypochlorite-(Naocl)-Extra, chlorhexidine (CHX)-Ultra, ethylenediaminetetraacetic acid (EDTA), QMix, and BioPure MTAD on the microhardness and smear layer removal of root canal dentin.

Materials And Methods: A total of 120 straight rooted lower premolars were collected and were randomly divided into 2 equal groups of 60 each ( = 60). The microhardness of the samples was evaluated by Vickers hardness tester and the removal of smear layer by scanning electron microscope after irrigation of the samples with the tested solutions.

Results: CHX-Ultra showed the least microhardness reduction, and EDTA showed the maximum microhardness reduction in all the tested groups. BioPure MTAD showed the maximum removal of smear layer in the apical third, and CHX-Ultra showed the minimal smear layer removal in the apical third.

Conclusion: During smear layer removal, irrigating solutions cause alterations in the chemical composition of dentin, which may decrease the microhardness of the root dentin causing erosion and affecting the clinical performance of the endodontically treated teeth. Irrigating solution with maximum smear layer removal with minimum changes in microhardness should be used.
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http://dx.doi.org/10.4103/JCD.JCD_487_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537743PMC
August 2020

COVID-19 Creating another problem? Sustainable solution for PPE disposal through LCA approach.

Environ Dev Sustain 2020 Oct 9:1-15. Epub 2020 Oct 9.

CSIR-National Environmental Engineering Research Institute, CSIR-NEERI, Nagpur, Maharashtra 440 020 India.

Amid COVID-19, there have been rampant increase in the use of Personal Protective Equipment (PPE) kits by frontline health and sanitation communities, to reduce the likelihoods of infections. The used PPE kits, potentially being infectious, pose a threat to human health, terrestrial, and marine ecosystems, if not scientifically handled and disposed. However, with stressed resources on treatment facilities and lack of training to the health and sanitation workers, it becomes vital to vet different options for PPE kits disposal, to promote environmentally sound management of waste. Given the various technology options available for treatment and disposal of COVID-19 patients waste, Life Cycle Assessment, i.e., cradle to grave analysis of PPE provides essential guidance in identifying the environmentally sound alternatives. In the present work, Life Cycle Assessment of PPE kits has been performed using GaBi version 8.7 under two disposal scenarios, namely landfill and incineration (both centralized and decentralized) for six environmental impact categories covering overall impacts on both terrestrial and marine ecosystems, which includes Global Warming Potential (GWP), Human Toxicity Potential (HTP), Eutrophication Potential (EP), Acidification Potential (AP), Freshwater Aquatic Ecotoxicity Potential (FAETP) and Photochemical Ozone Depletion Potential (POCP). Considering the inventories of PPE kits, disposal of PPE bodysuit has the maximum impact, followed by gloves and goggles, in terms of GWP. The use of metal strips in face-mask has shown the most significant HTP impact. The incineration process (centralized-3816 kg CO2 eq. and decentralized-3813 kg CO2 eq.) showed high GWP but significantly reduced impact w.r.t. AP, EP, FAETP, POCP and HTP, when compared to disposal in a landfill, resulting in the high overall impact of landfill disposal compared to incineration. The decentralized incineration has emerged as environmentally sound management option compared to centralized incinerator among all the impact categories, also the environmental impact by transportation is significant (2.76 kg CO2 eq.) and cannot be neglected for long-distance transportation. Present findings can help the regulatory authority to delineate action steps for safe disposal of PPE kits.
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http://dx.doi.org/10.1007/s10668-020-01033-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546389PMC
October 2020

Phosphorylation of Rhoptry Protein RhopH3 Is Critical for Host Cell Invasion by the Malaria Parasite.

mBio 2020 10 6;11(5). Epub 2020 Oct 6.

Eukaryotic Gene Expression Laboratory, National Institute of Immunology, New Delhi, India

Merozoites formed after asexual division of the malaria parasite invade the host red blood cells (RBCs), which is critical for initiating malaria infection. The process of invasion involves specialized organelles like micronemes and rhoptries that discharge key proteins involved in interaction with host RBC receptors. RhopH complex comprises at least three proteins, which include RhopH3. RhopH3 is critical for the process of red blood cell (RBC) invasion as well as intraerythrocytic development of human malaria parasite It is phosphorylated at serine 804 (S804) in the parasite; however, it is unclear if phosphorylation regulates its function. To address this, a CRISPR-CAS9-based approach was used to mutate S804 to alanine (A) in Using this phosphomutant (R3_S804A) of RhopH3, we demonstrate that the phosphorylation of S804 is critical for host RBC invasion by the parasite but not for its intraerythrocytic development. Importantly, the phosphorylation of RhopH3 regulates its localization to the rhoptries and discharge from the parasite, which is critical for RBC invasion. We also identified CDPK1 (PfCDPK1) as a possible candidate kinase for RhopH3-S804 phosphorylation and found that it regulates RhopH3 secretion from the parasite. These findings provide novel insights into the role of phosphorylation in rhoptry release and invasion, which is poorly understood. Host cell invasion by the malaria parasite is critical for establishing infection in human host and is dependent on discharge of key ligands from organelles like rhoptry and microneme, and these ligands interact with host RBC receptors. In the present study, we demonstrate that phosphorylation of a key rhoptry protein, RhopH3, is critical for host invasion. Phosphorylation regulates its localization to rhoptries and discharge from the parasite.
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http://dx.doi.org/10.1128/mBio.00166-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542355PMC
October 2020

Synthesis and Study of Some 17a-aza-D-homo Steroids as 5α-Reductase Inhibitors.

Curr Drug Discov Technol 2020 Sep 22. Epub 2020 Sep 22.

University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014. India.

Background And Objective: Tremendous advances have been made in the development of new pharmacotherapuetic agents and less invasive techniques to help men with lower urinary tract symptoms. The use of 5α-reductase inhibitor (5-ARI) is restricted to the patients with large prostate volumes, whose symptoms are refractory to antiandrogens or α- adrenergic blockers Out of the various synthesized5-reductase inhibitors with different substituents on steroidal nucleus, esters have been found to exhibited high anti-androgenic activity.

Methods: In our attempt to find new, safer and potent 5-ARI and our continued interest in azasteorids, esters of 17a-Aza-Dhomo-5-androsten-3β-ol with synergistic effect were synthesized and characterized using different analytical techniques. The compounds were evaluated for their 5α-reductase inhibitory activity in-vivo by their effect on serum androgen level by ELISA assay procedure. The interaction with receptors was studied using advanced docking programme to predict the correlation of the synthesized compounds with actual biological activity.

Results: The target compounds (6-12) showed increased anti-androgenic activity as compared to finasteride and control, which imply that the target compounds are effective in inhibiting 5α-reductase. Particularly, compound 6 showing highest inhibitory activity and greater affinity for 5-AR receptor with highest dock score. Results of these studies when compared with Finasteride showed increased solubility and dissolution of target compound 6.

Conclusion: Compound6 showed immense potential with improved efficacy and better bioavailability, thus makes it a suitable candidate for further studies and optimal formulation.
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http://dx.doi.org/10.2174/1570163817666200922120406DOI Listing
September 2020

Neuromuscular presentations in patients with COVID-19.

Neurol Sci 2020 Nov 15;41(11):3039-3056. Epub 2020 Sep 15.

Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, UP, 226014, India.

COVID-19 is caused by the coronavirus SARS-CoV-2 that has an affinity for neural tissue. There are reports of encephalitis, encephalopathy, cranial neuropathy, Guillain-Barrè syndrome, and myositis/rhabdomyolysis in patients with COVID-19. In this review, we focused on the neuromuscular manifestations of SARS-CoV-2 infection. We analyzed all published reports on SARS-CoV-2-related peripheral nerve, neuromuscular junction, muscle, and cranial nerve disorders. Olfactory and gustatory dysfunction is now accepted as an early manifestation of COVID-19 infection. Inflammation, edema, and axonal damage of olfactory bulb have been shown in autopsy of patients who died of COVID-19. Olfactory pathway is suggested as a portal of entry of SARS-CoV-2 in the brain. Similar to involvement of olfactory bulb, isolated oculomotor, trochlear and facial nerve has been described. Increasing reports Guillain-Barrè syndrome secondary to COVID-19 are being published. Unlike typical GBS, most of COVID-19-related GBS were elderly, had concomitant pneumonia or ARDS, more prevalent demyelinating neuropathy, and relatively poor outcome. Myalgia is described among the common symptoms of COVID-19 after fever, cough, and sore throat. Duration of myalgia may be related to the severity of COVID-19 disease. Few patients had muscle weakness and elevated creatine kinase along with elevated levels of acute-phase reactants. All these patients with myositis/rhabdomyolysis had severe respiratory complications related to COVID-19. A handful of patients with myasthenia gravis showed exacerbation of their disease after acquiring COVID-19 disease. Most of these patients recovered with either intravenous immunoglobulins or steroids.
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http://dx.doi.org/10.1007/s10072-020-04708-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491599PMC
November 2020

PfKsgA1 functions as a transcription initiation factor and interacts with the N-terminal region of the mitochondrial RNA polymerase of Plasmodium falciparum.

Int J Parasitol 2021 Jan 5;51(1):23-37. Epub 2020 Sep 5.

Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:

The small mitochondrial genome (mtDNA) of the malaria parasite is known to transcribe its genes polycistonically, although promoter element(s) have not yet been identified. An unusually large Plasmodium falciparum candidate mitochondrial phage-like RNA polymerase (PfmtRNAP) with an extended N-terminal region is encoded by the parasite nuclear genome. Using specific antibodies against the enzyme, we established that PfmtRNAP was targeted exclusively to the mitochondrion and interacted with mtDNA. Phylogenetic analysis showed that it is part of a separate apicomplexan clade. A search for PfmtRNAP-associated transcription initiation factors using sequence homology and in silico protein-protein interaction network analysis identified PfKsgA1. PfKsgA1 is a dual cytosol- and mitochondrion-targeted protein that functions as a small subunit rRNA dimethyltransferase in ribosome biogenesis. Chromatin immunoprecipitation showed that PfKsgA1 interacts with mtDNA, and in vivo crosslinking and pull-down experiments confirmed PfmtRNAP-PfKsgA1 interaction. The ability of PfKsgA1 to serve as a transcription initiation factor was demonstrated by complementation of yeast mitochondrial transcription factor Mtf1 function in Rpo41-driven in vitro transcription. Pull-down experiments using PfKsgA1 and PfmtRNAP domains indicated that the N-terminal region of PfmtRNAP interacts primarily with the PfKsgA1 C-terminal domain with some contacts being made with the linker and N-terminal domain of PfKsgA1. In the absence of full-length recombinant PfmtRNAP, solution structures of yeast mitochondrial RNA polymerase Rpo41 complexes with Mtf1 or PfKsgA1 were determined by small-angle X-ray scattering. Protein interaction interfaces thus identified matched with those reported earlier for Rpo41-Mtf1 interaction and overlaid with the PfmtRNAP-interfacing region identified experimentally for PfKsgA1. Our results indicate that in addition to a role in mitochondrial ribosome biogenesis, PfKsgA1 has an independent function as a transcription initiation factor for PfmtRNAP.
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http://dx.doi.org/10.1016/j.ijpara.2020.07.010DOI Listing
January 2021

Valuation of air pollution externalities: comparative assessment of economic damage and emission reduction under COVID-19 lockdown.

Air Qual Atmos Health 2020 Jun 10:1-12. Epub 2020 Jun 10.

CSIR-National Environmental Engineering Research Institute (CSIR-NEERI), Nehru Marg, Nagpur, Maharashtra India.

Air pollution (AP) is one of the major causes of health risks as it leads to widespread morbidity and mortality each year. Its environmental impacts include acid rains, reduced visibility, but more importantly and significantly, it affects human health. The price tag of not managing AP is seen in the rise of chronic obstructive pulmonary disease (COPD), cardiovascular disease, and respiratory ailments like asthma and chronic bronchitis. But as the world battles the corona pandemic, COVID-19 lockdown has abruptly halted human activity, leading to a significant reduction in AP levels. The effect of this reduction is captured by reduced cases of morbidity and mortality associated with air pollution. The current study aims to monetarily quantify the decline in health impacts due to reduced AP levels under lockdown scenario, as against business as usual, for four cities-Delhi, London, Paris, and Wuhan. The exposure assessment with respect to pollutants like particulate matter (PM and PM), NO, and SO are evaluated. Value of statistical life (VSL), cost of illness (CoI), and per capita income (PCI) for disability-adjusted life years (DALY) are used to monetize the health impacts for the year 2019 and 2020, considering the respective period of COVID-19 lockdown of four cities. The preventive benefits related to reduced AP due to lockdown is evaluated in comparison to economic damage sustained by these four cities. This helps in understanding the magnitude of actual damage and brings out a more holistic picture of the damages related to lockdown.
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http://dx.doi.org/10.1007/s11869-020-00845-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286556PMC
June 2020

Air pollution aggravating COVID-19 lethality? Exploration in Asian cities using statistical models.

Environ Dev Sustain 2020 Jul 15:1-10. Epub 2020 Jul 15.

CSIR-National Environmental Engineering Research Institute (NEERI), Nagpur, Maharashtra 440020 India.

The present work estimates the increased risk of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 by establishing the linkage between the mortality rate in the infected cases and the air pollution, specifically Particulate Matters (PM) with aerodynamic diameters ≤ 10 µm and ≤ 2.5 µm. Data related to nine Asian cities are analyzed using statistical approaches, including the analysis of variance and regression model. The present work suggests that there exists a positive correlation between the level of air pollution of a region and the lethality related to COVID-19, indicating air pollution to be an elemental and concealed factor in aggravating the global burden of deaths related to COVID-19. Past exposures to high level of PM over a long period, is found to significantly correlate with present COVID-19 mortality per unit reported cases ( < 0.05) compared to PM, with non-significant correlation ( = 0.118). The finding of the study can help government agencies, health ministries and policymakers globally to take proactive steps by promoting immunity-boosting supplements and appropriate masks to reduce the risks associated with COVID-19 in highly polluted areas.
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http://dx.doi.org/10.1007/s10668-020-00878-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362608PMC
July 2020

Understanding COVID-19 transmission through Bayesian probabilistic modeling and GIS-based Voronoi approach: a policy perspective.

Environ Dev Sustain 2020 Jul 8:1-19. Epub 2020 Jul 8.

CSIR-National Environmental Engineering Research Institute (CSIR-NEERI), Nehru Marg, Nagpur, Maharashtra India.

Originating from Wuhan, China, COVID-19 is spreading rapidly throughout the world. The transmission rate is reported to be high for this novel strain of coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as compared to its predecessors. Major strategies in terms of clinical trials of medicines and vaccines, social distancing, use of personal protective equipment (PPE), and so on are being implemented in order to control the spread. The current study concentrates on lockdown and social distancing policy followed by the Indian Government and evaluates its effectiveness using Bayesian probability model (BPM). The change point analysis (CPA) done through the above approach suggests that the states which implemented the lockdown before the exponential rise of cases are able to control the spread of the disease in a much better and efficient way. The analysis has been done for states of Maharashtra, Gujarat, Madhya Pradesh, Rajasthan, Tamil Nadu, West Bengal, Uttar Pradesh, and Delhi as union territory. The highest value of Δ (delta) is reported for Gujarat and Madhya Pradesh with a value of 9.6 weeks, while the lowest value is 4.7, evidently for Maharashtra which is the worst affected. All of the states indicate a significant correlation ( < 0.05, tstat > tcritical) for Δ, i.e., the difference in the time period of CPA and lockdown with cases per population (CPP) and cases per unit area (CPUA), while weak correlation ( < 0.1 and tstat < tcritical) is exhibited by delta and cases per unit population density (CPD). For both CPP and CPUA, tstat > tcritical indicating a significant correlation, while Pearson's correlation indicates the direction to be negative. Further analysis in terms of identification of high-risk areas has been studied from the Voronoi approach of GIS based on the inputs from BPM. All the states follow the above pattern of high population, high case scenario, and the boundaries of risk zones can be identified by Thiessen polygon (TP) constructed therein. The findings of the study help draw strategic and policy-driven response for India, toward tackling COVID-19 pandemic.
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http://dx.doi.org/10.1007/s10668-020-00849-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340861PMC
July 2020

Understanding air and water borne transmission and survival of coronavirus: Insights and way forward for SARS-CoV-2.

Sci Total Environ 2020 Dec 4;749:141486. Epub 2020 Aug 4.

CSIR-National Environmental Engineering Research Institute (NEERI), Nagpur, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-NEERI, Nagpur, India. Electronic address:

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in unprecedented disease burden, healthcare costs, and economic impacts worldwide. Despite several measures, SARS-CoV-2 has been extremely impactful due to its extraordinary infection potential mainly through coronavirus-borne saliva respiratory and droplet nuclei of an infected person and its considerable stability on surfaces. Although the disease has affected over 180 countries, its extent and control are significantly different across the globe, making it a strong case for exploration of its behavior and dependence across various environmental pathways and its interactions with the virus. This has spurred efforts to characterize the coronavirus and understand the factors impacting its transmission and survival such as aerosols, air quality, meteorology, chemical compositions and characteristics of particles and surfaces, which are directly or indirectly associated with coronaviruses infection spread. Nonetheless, many peer-reviewed articles have studied these aspects but mostly in isolation; a complete array of coronavirus survival and transmission from an infected individual through air- and water-borne channels and its subsequent intractions with environmental factors, surfaces, particulates and chemicals is not comprehensively explored. Particulate matter (PM) is omnipresent with variable concentrations, structures and composition, while most of the surfaces are also covered by PM of different characteristics. Learning from the earlier coronavirus studies, including SARS and MERS, an attempt has been made to understand the survival of SARS-CoV-2 outside of the host body and discuss the probable air and water-borne transmission routes and its interactions with the outside environment. The present work 1) Helps appreciate the role of PM, its chemical constituents and surface characteristics and 2) Further identifies gaps in this field and suggests possible domains to work upon for better understanding of transmission and survival of this novel coronavirus.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402210PMC
December 2020

Phytosterol supplements do not inhibit dipeptidyl peptidase-4.

Diabetes Metab Syndr 2020 Sep - Oct;14(5):1475-1478. Epub 2020 Jul 15.

School of Pharmacy and Pharmacology, University of Tasmania, Hobart, TAS, 7005, Australia.

Background And Aims: Several commercially available phytosterol supplements are promoted for their cholesterol-lowering effects. However, limited information is available about their potential anti-hyperglycaemic effects. This study aimed to evaluate the dipeptidyl peptidase-4 (DPP-4) inhibitory effects of phytosterol supplements in silico and in vitro to determine their potential for anti-diabetic activity.

Methods: Docking studies were carried out in silico to evaluate the potential for interactions between three major phytosterol compounds (stigmasterol, β-sitosterol, campesterol) and the DPP-4 enzyme, the enzyme that is inhibited by the anti-diabetic gliptins. Gas chromatography-tandem mass spectrometry (GC-MS/MS) was used to analyse three different supplements for phytosterol content. DPP-4 inhibitory activity was tested in vitro for these phytosterol supplements and two major phytosterol standards.

Results: In silico calculations predicted free binding energies for DPP-4 with the phytosterols to be: stigmasterol -8.78 kcal/mol; β-sitosterol -8.70 kcal/mol; campesterol -8.40 kcal/mol. These binding energies indicated a potential for significant DPP-4 inhibition. However, these results were not supported by the in vitro studies. Stigmasterol and β-sitosterol had an IC > 50 mg/ml (maximum tested concentration) and the Thompson's Cholesterol Manager® and Mega Strength Beta Sitosterol® supplements gave an IC > 100 mg/ml (maximum tested concentration). Blackmores Cholesterol Health® gave an IC value of 40 mg/ml which was attributed to β-carotene content.

Conclusions: Phytosterol supplements do not appear to offer any anti-diabetic activity potential via pathways that involve the inhibition of DPP-4.
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http://dx.doi.org/10.1016/j.dsx.2020.07.019DOI Listing
July 2020

The probability distribution of the ancestral population size conditioned on the reconstructed phylogenetic tree with occurrence data.

J Theor Biol 2021 01 30;509:110400. Epub 2020 Jul 30.

Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland. Electronic address:

We consider a homogeneous birth-death process with three different sampling schemes. First, individuals can be sampled through time and included in a reconstructed phylogenetic tree. Second, they can be sampled through time and only recorded as a point 'occurrence' along a timeline. Third, extant individuals can be sampled and included in the reconstructed phylogenetic tree with a fixed probability. We further consider that sampled individuals can be removed or not from the process, upon sampling, with fixed probability. We derive the probability distribution of the population size at any time in the past conditional on the joint observation of a reconstructed phylogenetic tree and a record of occurrences not included in the tree. We also provide an algorithm to simulate ancestral population size trajectories given the observation of a reconstructed phylogenetic tree and occurrences. This distribution can be readily used to draw inferences about the ancestral population size in the field of epidemiology and macroevolution. In epidemiology, these results will allow data from epidemiological case count studies to be used in conjunction with molecular sequencing data (yielding reconstructed phylogenetic trees) to coherently estimate prevalence through time. In macroevolution, it will foster the joint examination of the fossil record and extant taxa to reconstruct past biodiversity.
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http://dx.doi.org/10.1016/j.jtbi.2020.110400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733867PMC
January 2021

Ipsilesional Torsional Nystagmus in Midbrain Infarction: A Rare Entity of Localizing Value.

Ann Indian Acad Neurol 2020 May-Jun;23(3):378-379. Epub 2020 May 9.

Department of Neurology, Lady Hardinge Medical College, New Delhi, India.

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http://dx.doi.org/10.4103/aian.AIAN_646_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313563PMC
May 2020

Vaccine Potential of a Recombinant Bivalent Fusion Protein LcrV-HSP70 Against Plague and Yersiniosis.

Front Immunol 2020 12;11:988. Epub 2020 Jun 12.

Microbiology Division, Defence Research and Development Establishment, Gwalior, India.

To counteract the deadly pathogens, i.e., , and , we prepared a recombinant DNA construct encoding the bivalent fusion protein LcrV-HSP70. The gene of and domain II DNA fragment of were amplified by PCR. The amplicon was first ligated in the pET vector using NcoI and BamHI restriction sites. Just downstream to the gene, the domain II was ligated using BamHI and Hind III restriction sites. The in-frame and the orientation of cloned lcrV-hsp70 were checked by restriction analysis and nucleotide sequencing. The recombinant bivalent fusion protein LcrV-HSP70 was expressed in and purified by affinity chromatography. The vaccine potential of LcrV-HSP70 fusion protein was evaluated in formulation with alum. BALB/c mice were vaccinated, and the humoral and cellular immune responses were studied. The fusion protein LcrV-HSP70 induced a strong and significant humoral immune response in comparison to control animals. We also observed a significant difference in the expression levels of IFN-γ and TNF-α in LcrV-HSP70-immunized mice in comparison to control, HSP70, and LcrV groups. To test the protective efficacy of the LcrV-HSP70 fusion protein against plague and Yersiniosis, the vaccinated mice were challenged with , and separately. The bivalent fusion protein LcrV-HSP70 imparted 100% protection against the plague. In the case of Yersiniosis, on day 2 post challenge, there was a significant reduction in the number of CFU of and in the blood (CFU/ml) and the spleen (CFU/g) of vaccinated animals in comparison to the LcrV, HSP70, and control group animals.
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http://dx.doi.org/10.3389/fimmu.2020.00988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303293PMC
March 2021

Author Correction: Arginyltransferase knockdown attenuates cardiac hypertrophy and fibrosis through TAK1-JNK1/2 pathway.

Sci Rep 2020 Jun 25;10(1):10662. Epub 2020 Jun 25.

Drug Discovery Research Centre, Translational Health Science and Technology Institute, Faridabad, Haryana, India.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-67556-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314792PMC
June 2020

Encephalopathy in patients with COVID-19: A review.

J Med Virol 2021 01 11;93(1):206-222. Epub 2020 Jul 11.

Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

Encephalopathy and encephalitis are major and devastating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus-associated central nervous system complications. Hypoxic/metabolic changes produced by intense inflammatory response against the virus triggers cytokine storm and subsequently acute respiratory distress syndrome and multiple organ failure. Hypoxic/metabolic changes result in encephalopathy. The presence of comorbidities predisposes to hypoxic/metabolic changes responsible for encephalopathy. Altered consciousness, ranging from mild confusion, delirium, to deep coma, is hallmark clinical features. Cortical and subcortical T2/FLAIR signal changes are common neuroimaging abnormalities. In a few isolated case reports of SARS-CoV-2 encephalitis, the virus has been demonstrated in cerebrospinal fluid. The presence of anosmia and ageusia can help in differentiation from other encephalopathies. We analyzed published reports on coronavirus disease 2019-associated encephalopathy. Encephalopathy is common in older patients, the majority are more than 50 years of age. The patients having encephalopathy/encephalitis are either severely or critically ill. Many patients were already on mechanical ventilation. Lung abnormalities are noted in almost all of the patients, presenting with encephalopathy. Encephalopathy is always preceded by commoner clinical features, like, fever, cough, dyspnoea, and headache. In majority, patients are already in the intensive care unit, when encephalopathy develops.
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http://dx.doi.org/10.1002/jmv.26207DOI Listing
January 2021

Morphologically designed micro porous zeolite-geopolymers as cool coating materials.

J Hazard Mater 2020 Nov 26;398:123022. Epub 2020 May 26.

CSIR-National Environmental Engineering Research Institute (CSIR-NEERI), Nehru Marg, Nagpur 440 020, India. Electronic address:

Functionally modified fly ash zeolite-geopolymeric material was developed as cooling coatings for structural application. The tailored precursor of cool coating materials was obtained through modified grain behavior of zeolite with variable pour morphology and mechanical activation of fly ash followed by geopolymerization with alkaline activator. The modified zeolite was found to possess unique heat management properties through disorderly connected pores. The solar temperature profile showed a temperature variance of 4-6 °C for solar radiation. The samples showed a high solar reflective index (SRI) due to absorbance and less heat retention followed by cooling behavior in the sunshine.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123022DOI Listing
November 2020

Study of electromagnetic shielding effectiveness of metal oxide polymer composite in their bulk and layered forms.

Environ Sci Pollut Res Int 2021 Jan 2;28(4):3880-3887. Epub 2020 Jun 2.

VGU Jaipur, Jaipur, India.

In this paper, we present the studies on electromagnetic interference (EMI) shielding effectiveness (SE) of KCrO-PMMA composites developed by two different methods: one in bulk form of thickness 1.2 mm and another by stacking twelve layers of thin films each of thickness 100 μm. The EMI SE of stacked twelve layers of 1.2-mm-thick composite films has been achieved until 23.2 dB in the frequency range 8.0-12.0 GHz. This is remarkably higher than the 17 dB achieved for the bulk composites of 1.2 mm thickness. The characteristic EMI SE graphs obtained using Agilent E82B Vector Network Analyzer in the X band frequency range have been depicted, and the shielding mechanism in these composites has been analyzed. It is found that the SE in this frequency range is dominated by absorption. The study suggests these composites to be a potentially promising material for EMI shielding purpose.
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http://dx.doi.org/10.1007/s11356-020-09322-xDOI Listing
January 2021

Is COVID-19-related Guillain-Barré syndrome different?

Brain Behav Immun 2020 07 20;87:177-178. Epub 2020 May 20.

Department of Neurology, King George Medical University, Lucknow, UP, India.

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http://dx.doi.org/10.1016/j.bbi.2020.05.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239011PMC
July 2020

Impact of Postoperative Infarcts in Determining Outcome after Clipping of Anterior Communicating Artery Aneurysms.

Neurol India 2020 Jan-Feb;68(1):132-140

Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Background: Development of cerebral infarcts following clipping of ruptured intracranial aneurysm is one of the major determinants of functional outcome in patients with subarachnoid hemorrhage (SAH). The aim of this study is to evaluate the factors affecting development of postoperative infarcts, its incidence, pattern, and functional outcome.

Material And Methods: This study includes 118 patients of spontaneous SAH because of ruptured anterior communicating artery aneurysm, who underwent clipping. Relevant points in history, preoperative and intraoperative findings, and postoperative outcome are evaluated.

Results: 29 of 118 (24.5%) patients developed postoperative radiological infarcts. Approximately 37.9%, 17.2%, and 3.4% patients developed isolated infarcts, respectively, in anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) territory. About 20.7% patients developed infarcts in deep perforator territory. Nine of 29 (31.3%) patients developed multiple-vessel territory infarcts. Patients with poor preoperative neurologic status, prior history of seizure, and history of intraoperative rupture had higher chances of development of infarcts. Development of infarct was irrespective of temporary clipping (TC), duration of clipping, and elective versus rescue clipping. Development of infarcts adversely affected the outcome in significant proportions. Among patients with infarcts, unilateral ACA territory infarcts showed best prognosis, whereas all patients with multiple territory infarcts and PCA territory infarcts died. Age or sex of the patients did not affect the functional outcome. Timing of development of infarcts has no influence on functional recovery.

Conclusion: Development of symptomatic infarct is the sole important predictor of functional outcome. A crowded neurovascular neighborhood and complex variations in local angioarchitecture make anterior communication (ACOM) territory predisposed to operative insults. Elective TC and aggressive management of cerebral vasospasm are recommended to prevent development of infarcts.
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http://dx.doi.org/10.4103/0028-3886.279675DOI Listing
December 2020

Complex nutrient channel phenotypes despite Mendelian inheritance in a Plasmodium falciparum genetic cross.

PLoS Pathog 2020 02 18;16(2):e1008363. Epub 2020 Feb 18.

Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.

Malaria parasites activate a broad-selectivity ion channel on their host erythrocyte membrane to obtain essential nutrients from the bloodstream. This conserved channel, known as the plasmodial surface anion channel (PSAC), has been linked to parasite clag3 genes in P. falciparum, but epigenetic switching between the two copies of this gene hinders clear understanding of how the encoded protein determines PSAC activity. Here, we used linkage analysis in a P. falciparum cross where one parent carries a single clag3 gene to overcome the effects of switching and confirm a primary role of the clag3 product with high confidence. Despite Mendelian inheritance, CLAG3 conditional knockdown revealed remarkably preserved nutrient and solute uptake. Even more surprisingly, transport remained sensitive to a CLAG3 isoform-specific inhibitor despite quantitative knockdown, indicating that low doses of the CLAG3 transgene are sufficient to confer block. We then produced a complete CLAG3 knockout line and found it exhibits an incomplete loss of transport activity, in contrast to rhoph2 and rhoph3, two PSAC-associated genes that cannot be disrupted because nutrient uptake is abolished in their absence. Although the CLAG3 knockout did not incur a fitness cost under standard nutrient-rich culture conditions, this parasite could not be propagated in a modified medium that more closely resembles human plasma. These studies implicate oligomerization of CLAG paralogs encoded by various chromosomes in channel formation. They also reveal that CLAG3 is dispensable under standard in vitro conditions but required for propagation under physiological conditions.
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http://dx.doi.org/10.1371/journal.ppat.1008363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048409PMC
February 2020

YihA GTPases localize to the apicoplast and mitochondrion of the malaria parasite and interact with LSU of organellar ribosomes.

Mol Biochem Parasitol 2020 03 11;236:111265. Epub 2020 Feb 11.

Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, 226031, India. Electronic address:

The YihA TRAFAC GTPases are critical for late-stage assembly of the ribosomal large subunit (LSU). In order to explore biogenesis of the reduced organellar ribosomes of the malaria parasite, we identified three nuclear-encoded homologs of YihA in Plasmodium falciparum. PfYihA1 targeted to the parasite apicoplast, PfYihA2 to the mitochondrion, and PfYihA3 was found in both the apicoplast and cytosol. The three PfYihA, expressed as recombinant proteins, were active GTPases and interacted with surrogate E. coli ribosomes in a nucleotide-independent manner. In vivo complexation of PfYihA with parasite organellar and/or cytosolic LSU was confirmed by co-immunoprecipitation using specific antibodies. Mitochondrial PfYihA2 carries a large C-ter extension with a strongly positively charged stretch. We hypothesise that this is important in compensating for the absence of helices of the central protuberance in the fragmented rRNA of Plasmodium mitoribosomes and may provide additional contact sites to aid in complex assembly. Combined with previous reports, our results indicate that P. falciparum mitochondria are likely to assemble ribosomes with the aid of PfEngA, PfObg1 and PfYihA2 GTPases while apicoplast ribosomes might use PfYihA1 and 3 in combination with other factors.
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http://dx.doi.org/10.1016/j.molbiopara.2020.111265DOI Listing
March 2020

Arginyltransferase knockdown attenuates cardiac hypertrophy and fibrosis through TAK1-JNK1/2 pathway.

Sci Rep 2020 01 17;10(1):598. Epub 2020 Jan 17.

Drug Discovery Research Centre, Translational Health Science and Technology Institute, Faridabad, Haryana, India.

Myocardial hypertrophy, an inflammatory condition of cardiac muscles is a maladaptive response of the heart to biomechanical stress, hemodynamic or neurohormonal stimuli. Previous studies indicated that knockout of Arginyltransferase (ATE1) gene in mice and embryos leads to contractile dysfunction, defective cardiovascular development, and impaired angiogenesis. Here we found that in adult rat model, downregulation of ATE1 mitigates cardiac hypertrophic, cardiac fibrosis as well as apoptosis responses in the presence of cardiac stress i.e. renal artery ligation. On contrary, in wild type cells responding to renal artery ligation, there is an increase of cellular ATE1 protein level. Further, we have shown the cardioprotective role of ATE1 silencing is mediated by the interruption of TAK1 activity-dependent JNK1/2 signaling pathway. We propose that ATE1 knockdown in presence of cardiac stress performs a cardioprotective action and the inhibition of its activity may provide a novel approach for the treatment of cardiac hypertrophy.
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http://dx.doi.org/10.1038/s41598-019-57379-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969214PMC
January 2020

Turning Foes to Friends: Knocking Down Diabetes Associated SGLT2 Transporters and Sustaining Life.

Curr Diabetes Rev 2020 ;16(7):716-732

Department of Pharmaceutical Chemistry, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.

Background: The discovery of Sodium-Glucose co-transporter-2 (SGLT2) inhibitors had rewritten the treatment of diabetes mellitus with an impressive fall in the incidence of death and associated complications.

Introduction: The SGLT2 inhibitors by inhibiting the SGLT2 in the proximal nephron, helps in reducing the reabsorption of approximately 90% of the filtered glucose and increased urinary glucose excretion (UGE).

Methods: The literature related to SGLT2 inhibitors has been thoroughly explored from various available public domains and reviewed extensively for this article. Detailed and updated information related to SGLT2 inhibitors with a major focus on the recently approved Ertuglifolzin is structured in this review.

Result: The present review is an effort to understand the management of diabetes mellitus over the past few decades with a special focus on the role of SGLT2 receptor in the causes of therapeutic and preventive strategies for diabetes mellitus. Pragmatic placement of the currently available Canagliflozin, Dapagliflozin, and Empagliflozin as oral antidiabetic agents has been done. Well accommodated stereochemistry and a high docking score of Ertugliflozin in ligand-receptor simulation studies attribute to its high potency.

Conclusion: This review highlights the unique mechanism of SGLT2 Inhibitors coupled with pleiotropic benefits on weight and blood pressure, which make it an attractive choice of therapy to diabetic patients, not controlled by other medications.
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http://dx.doi.org/10.2174/1573399816666200117155016DOI Listing
September 2020