Publications by authors named "Sandeep Singh"

464 Publications

Comparative study of bioinformatic tools for the identification of chimeric RNAs from RNA Sequencing.

Authors:
Sandeep Singh Hui Li

RNA Biol 2021 Jun 18:1-13. Epub 2021 Jun 18.

Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, USA.

Chimeric RNAs are gaining more and more attention as they have broad implications in both cancer and normal physiology. To date, over 40 chimeric RNA prediction methods have been developed to facilitate their identification from RNA sequencing data. However, a limited number of studies have been conducted to compare the performance of these tools; additionally, previous studies have become outdated as more software tools have been developed within the last three years. In this study, we benchmarked 16 chimeric RNA prediction software, including seven top performers in previous benchmarking studies, and nine that were recently developed. We used two simulated and two real RNA-Seq datasets, compared the 16 tools for their sensitivity, positive prediction value (PPV), F-measure, and also documented the computational requirements (time and memory). We noticed that none of the tools are inclusive, and their performance varies depending on the dataset and objects. To increase the detection of true positive events, we also evaluated the pair-wise combination of these methods to suggest the best combination for sensitivity and F-measure. In addition, we compared the performance of the tools for the identification of three classes (read-through, inter-chromosomal and intra-others) of chimeric RNAs. Finally, we performed TOPSIS analyses and ranked the weighted performance of the 16 tools.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1080/15476286.2021.1940047DOI Listing
June 2021

Ameliorative Role of Nutraceuticals on Neurodegenerative Diseases Using the as a Discovery Model to Define Bioefficacy.

Authors:
Ranjana Himalian Sandeep Kumar Singh Mahendra Pratap Singh

J Am Coll Nutr 2021 Jun 14:1-29. Epub 2021 Jun 14.

School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India.

Neurodegeneration is the destruction of neurons, and once the neurons degenerate they can't revive. This is one of the most concerned health conditions among aged population, more than ∼70% of the elderly people are suffering from neurodegeneration. Among all of the neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease (PD) and Poly-glutamine disease (Poly-Q) are the major one and affecting most of the people around the world and posing excessive burden on the society. In order to understand this disease in non-human animal models it is pertinent to examine in model organism and various animal model are being used for such diseases like rat, mice and non-vertebrate model like Drosophila. is one of the best animal proven by several eminent scientist and had received several Nobel prizes for uncovering mechanism of human related genes and highly efficient model for studying neurodegenerative diseases due to its great affinity with human disease-related genes. Another factor is also employed to act as therapeutic or preventive method that is nutraceuticals. Nutraceuticals are functional natural compounds with antioxidant properties and had extensively showed the neuroprotective effect in different organisms. These nutraceuticals having antioxidant properties act through scavenging free radicals or by increasing endogenous cellular antioxidant defense molecules. For the best benefit, we are trying to utilize these nutraceuticals, which will have no or negligible side effects. In this review, we are dealing with various types of such nutraceuticals which have potent value in the prevention and curing of the diseases related to neurodegeneration.HighlightsNeurodegeneration is the silently progressing disease which shows its symptoms when it is well rooted.Many chemical drugs (almost all) have only symptomatic relief with side effects.Potent mechanism of neurodegeneration and improvement effect by nutraceuticals is proposed.Based on the Indian Cuisine scientists are trying to find the medicine from the food or food components having antioxidant properties.The best model to study the neurodegenerative diseases is .Many nutraceuticals having antioxidant properties have been studied and attenuated various diseases are discussed.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1080/07315724.2021.1904305DOI Listing
June 2021

Discontinuation of Antihypertensive Medications on the Outcome of Hospitalized Patients With Severe Acute Respiratory Syndrome-Coronavirus 2.

Authors:
Sandeep Singh Annette K Offringa-Hup Susan J J Logtenberg Paul D Van der Linden Wilbert M T Janssen Hubertina Klein Femke Waanders Suat Simsek Cornelis P C de Jager Paul Smits Machteld van der Feltz Gerrit Jan Beumer Christine Widrich Martijn Nap Sara-Joan Pinto-Sietsma

Hypertension 2021 07 9;78(1):165-173. Epub 2021 Jun 9.

From the Department of Clinical Epidemiology, Biostatistics and Bioinformatics (S.S., S.-J.P.-S.), Amsterdam UMC, Academic Medical Center Amsterdam, the Netherlands.

[Figure: see text].
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189257PMC
July 2021

A Case of Systemic Toxicity Related to Intravesical Bacillus Calmette-Guerin for the Treatment of Bladder Cancer.

Authors:
Sachin Gupta Balraj Singh Harshil Bhatt Sandeep Singh Sorab Gupta

Cureus 2021 May 29;13(5):e15321. Epub 2021 May 29.

Department of Hematology and Oncology, Bronx Lebanon Hospital, New York, USA.

Intravesical administration of Bacillus Calmette-Guerin (BCG) has been utilized for the treatment of superficial bladder cancer for the past several decades. Though this treatment is well tolerated in general, both local and systematic side effects have been reported. We present a case of a patient who presented with systemic symptoms of fever with chills associated with leucopenia, thrombocytopenia, abnormal liver function tests (LFTs), and splenomegaly a few weeks after an episode of traumatic instillation of intravesical BCG. Though the mycobacterial cultures were negative, he was started on an anti-mycobacterial regimen empirically to which he responded and ultimately fully recovered.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.7759/cureus.15321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164525PMC
May 2021

Optimization of FFF Process Parameters by Naked Mole-Rat Algorithms with Enhanced Exploration and Exploitation Capabilities.

Authors:
Jasgurpreet Singh Chohan Nitin Mittal Raman Kumar Sandeep Singh Shubham Sharma Shashi Prakash Dwivedi Ambuj Saxena Somnath Chattopadhyaya Rushdan A Ilyas Chi Hieu Le Szymon Wojciechowski

Polymers (Basel) 2021 May 23;13(11). Epub 2021 May 23.

Faculty of Mechanical Engineering and Management, Poznan University of Technology, 60-965 Poznan, Poland.

Fused filament fabrication (FFF) has numerous process parameters that influence the mechanical strength of parts. Hence, many optimization studies are performed using conventional tools and algorithms. Although studies have also been performed using advanced algorithms, limited research has been reported in which variants of the naked mole-rat algorithm (NMRA) are implemented for solving the optimization issues of manufacturing processes. This study was performed to scrutinize optimum parameters and their levels to attain maximum impact strength, flexural strength and tensile strength based on five different FFF process parameters. The algorithm yielded better results than other studies and successfully achieved a maximum response, which may be helpful to enhance the mechanical strength of FFF parts. The study opens a plethora of research prospects for implementing NMRA in manufacturing. Moreover, the findings may help identify critical parametric levels for the fabrication of customized products at the commercial level and help to attain the objectives of Industry 4.0.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.3390/polym13111702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196965PMC
May 2021

Biotite as a geoindicator of rare earth element contamination in Gomati River Basin, Ganga Alluvial Plain, northern India.

Authors:
Priyanka Singh Jitendra Kumar Yadav Dharmendra Kumar Jigyasu Sandeep Singh Narendra Kumar Indra Bir Singh Munendra Singh

Environ Monit Assess 2021 May 27;193(6):361. Epub 2021 May 27.

Department of Geology, University of Lucknow, Lucknow, 226007, India.

Rare earth elements (REE) are emerging as modern high-technology-related novel micro-contaminants in freshwater aquatic systems and are therefore attracting global attention due to their potential human health risks. The Gomati River (a tributary of the Ganga River) sediments were analyzed for REE concentrations to establish REE contamination and to identify biotite mica mineral as a geoindicator. Chondrite-normalized REE pattern of the river sediments and biotite mica mineral were similar and depict a strong light REE (LREE) enrichment and relatively flatter heavy REE (HREE). The maximum total REE (∑REE) concentration increased from 323 µg/g in 2012 to 673 µg/g in 2019. In the ∑REE, LREE contribution was > 80%, because of anthropogenic inputs, mainly petroleum-cracking catalysts and other high-technology-based products. The XRD analysis and the geochemical signature of the Gomati River sediments reveal the meaningful existence of biotite mica mineral. A distinct downstream REE enrichment pattern was identified in biotite from the mica-rich bedload sediments. The scanning electron microscopy-energy dispersive X-ray (SEM-EDX) mapping images of biotite also revealed the precipitation of Lanthanum, at the weathered edges, during the early stage of mineral weathering. Biotite mica was identified as a geoindicator for the assessment of REE contamination in the Gomati River and the Hindon River Basin of the Ganga Alluvial Plain. Future research is needed for the application of biotite mica mineral as a geoindicator that can help the environmental scientists to contribute more effectively to the interdisciplinary efforts in River Science.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1007/s10661-021-09105-yDOI Listing
May 2021

18-F Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography of a Large Inflammatory-Hepatocellular Adenoma.

Authors:
Meghana Prabhu Averilicia Passah Vanjul Kansotia Sandeep Singh

Indian J Nucl Med 2021 Jan-Mar;36(1):95-96. Epub 2021 Mar 4.

Department of Nuclear Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.

We report a case of an 81-year-old male evaluated for a liver space-occupying lesion. US-guided biopsy and immunohistochemistry were suggestive of hepatocellular adenoma (HCA)-inflammatory (with telangiectasia). Serial 18-F fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography scans revealed a heterogeneously enhancing hypermetabolic mass in the right lobe of the liver, remaining stable for a span of 3 years. This case highlights that benign rare tumors of the liver such as HCA can be intensely FDG avid and that uptake cannot conclude its malignant transformation.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.4103/ijnm.IJNM_87_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130690PMC
March 2021

Multiple House Occupancy is Associated with Mortality in Hospitalised Patients with Covid-19.

Authors:
Eilidh Bruce Ben Carter Terence J Quinn Alessia Verduri Oliver Pearson Arturo Vilches-Moraga Angeline Price Aine McGovern Louis Evans Kathryn McCarthy Jonathan Hewitt Susan Moug Phyo K Myint Behalf Of Cope Study Team Alice Einarsson Anna Fleck Carly Bisset Ross Alexander Giovanni Guaraldi Caroline Murphy Joanna Kelly Roxanna Short Philip Braude Tarik El Jichi Mutasem Sandeep Singh Dolcie Paxton Will Harris James Hesford Mark Holloway Emma Mitchell

Eur J Public Health 2021 May 17. Epub 2021 May 17.

Institute of Applied Health Science, University of Aberdeen, Aberdeen Scotland.

Background: In response to the COVID-19 pandemic, many countries mandated staying at home to reduce transmission. This study examined the association between living arrangements (house occupancy numbers) and outcomes in COVID-19.

Methods: Study population was drawn from the COPE Study, a multicentre cohort study. House occupancy was defined as: living alone; living with one other person; living with multiple other people; or living in a nursing/residential home. Outcomes were time from admission to mortality and discharge (Cox regression), and Day-28 mortality (logistic regression), analyses were adjusted for key comorbidities and covariates including admission: age; sex, smoking; heart failure; admission CRP; COPD; eGFR, frailty and others.

Results: 1584 patients were included from 13 hospitals across UK and Italy: 676 (42.7%) were female, 907 (57.3%) were male, median age was 74 years (range: 19-101). At 28 days, 502 (31.7%) had died. Median admission CRP was 67, 82, 79.5 and 83mg/L for those living alone, with someone else, in a house of multiple occupancy and in a nursing/residential home, respectively. Compared to living alone, living with anyone was associated with increased mortality: within a couple (aHR 1.39, 95%CI 1.09-1.77, p = 0.007); living in a house of multiple occupancy (aHR=1.67, 95%CI 1.17-2.38, p = 0.005); and living in a residential home (aHR=1.36, 95%CI 1.03-1.80, p = 0.031).

Conclusion: For patients hospitalised with COVID-19, those living with one or more people had an increased association with mortality, they also exhibited higher CRP indicating increased disease severity suggesting they delayed seeking care.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1093/eurpub/ckab085DOI Listing
May 2021

A comprehensive review of environmental fate and degradation of fipronil and its toxic metabolites.

Authors:
Ngangbam Sarat Singh Ranju Sharma Sandeep Kumar Singh Dileep Kumar Singh

Environ Res 2021 Aug 11;199:111316. Epub 2021 May 11.

Pesticide Toxicology and Soil Microbial Ecology Lab, Department of Zoology, University of Delhi, Delhi, 110007, India.

The use of pesticides to increase crop production has become one of the inevitable components of modern agriculture. Fipronil, a phenylpyrazoles insecticide, is one of the most widely used, systemic, broad-spectrum insecticides. Owing to its unique mode of action and selective toxicity, it was once regarded as safer alternatives to more toxic and persistent organochlorine insecticides. However, with the increased use, many studies have reported the toxicity of fipronil and its metabolites in various non-target organisms during the last two decades. Currently, it is regarded as one of the most persistent and lipophilic insecticides in the market. In the environment, fipronil can undergo oxidation, reduction, hydrolysis, or photolysis to form fipronil sulfone, fipronil sulfide, fipronil amide, or fipronil desulfinyl respectively. These metabolites except fipronil amide are more or less toxic and persistent than fipronil and have been reported from diverse environmental samples. Recently many studies have focused on the degradation and removal of fipronil residues from the environment. However, a comprehensive review summarizing and combining these recent findings is lacking. In the present review, we evaluate, summarize, and combine important findings from recent degradation studies of fipronil and its metabolites. An attempt has been made to elucidate the possible mechanism and pathways of degradation of fipronil and its toxic metabolites.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.envres.2021.111316DOI Listing
August 2021

"The pharmacological profile of SGLT2 inhibitors: Focus on mechanistic aspects and pharmacogenomics".

Authors:
Prabhsimran Kaur Bidwan Sekhar Behera Sandeep Singh Anjana Munshi

Eur J Pharmacol 2021 Aug 11;904:174169. Epub 2021 May 11.

Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, 151401, India. Electronic address:

Diabetes, characterized by high glucose levels, has been listed to be one of the world's major causes of death. Around 1.6 million deaths are attributed to this disease each year. Persistent hyperglycemic conditions in diabetic patients affect various organs of the body leading to diabetic complications and worsen the disease condition. Current treatment strategies for diabetes include biguanides, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, insulin and its analogs, DPP-4(dipeptidyl peptidase-4) and GLP-1 (glucagon-like peptide) analogs. However, many side effects contributing to the devastation of the disease are associated with them. Sodium glucose co-transporter-2 (SGLT2) inhibition has been reported to be new insulin-independent approach to diabetes therapy. It blocks glucose uptake in the kidneys by inhibiting SGLT2 transporters, thereby promoting glycosuria. Dapagliflozin, empagliflozin and canagliflozin are the most widely used SGLT2 inhibitors. They are effective in controlling blood glucose and HbA1c levels with few side effects including hypoglycemia or weight gain which makes them preferable to other anti-diabetic drugs. However, treatment is found to be associated with inter-individual drug response to SGLT2 inhibitors and adverse drug reactions which are also affected by genetic variations. There have been very few pharmacogenetics trials of these drugs. This review discusses the various SGLT2 inhibitors, their pharmacokinetics, pharmacodynamics and genetic variation influencing the inter-individual drug response.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.ejphar.2021.174169DOI Listing
August 2021

Alarmingly Increased Public Interest in "Chest Pain" During the COVID-19 Pandemic: Insights From Google Trends Analysis.

Authors:
Hee Kong Fong Sandeep Singh Jilmil S Raina Vikram B Itare Violeta Spasova Rupak Desai

Cureus 2021 Apr 4;13(4):e14292. Epub 2021 Apr 4.

Cardiology, Atlanta Veterans Affairs Medical Center, Decatur, USA.

Background The coronavirus disease 2019 (COVID-19) pandemic has been linked to a myriad of cardiac symptoms and disorders. Reports also suggest decreased hospital visits by patients with known cardiovascular disorders. Methodology To better elucidate the public interest in the information regarding "chest pain" during the COVID-19 pandemic, we conducted a Google Trends analysis from March 2019 to March 2021 to compare the internet searches between pre-COVID era and during the pandemic with country-wise [the United States (US) versus the United Kingdom (UK) versus India] variation. Results We observed a significantly rising public interest in "chest pain" internet searches during the peak COVID-19 pandemic. Rising trends were most prominent in the UK, followed by USA and India. Our analysis noted a spike in the trend of "chest pain" search in early March in the UK and USA, whereas in March and June 2020 for India. This shows an important temporal association between the surge of COVID-19 cases and the search for "chest pain" online. Conclusion Google Trends analyses indicate rising public interest in chest pain during the pandemic months and the possible association between COVID-19 and chest pain. These findings warrant further research, especially with increasing reports suggesting contradictory reports of decreased hospital visits by patients with known cardiovascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.7759/cureus.14292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099001PMC
April 2021

Promising drug discovery strategies for sirtuin modulators: what lessons have we learnt?

Authors:
Geetika Garg Abhishek Kumar Singh Sandeep Singh Syed Ibrahim Rizvi

Expert Opin Drug Discov 2021 Apr 21:1-13. Epub 2021 Apr 21.

Department of Biochemistry, University of Allahabad, Allahabad, India.

Introduction: Sirtuins, NAD-dependent protein deacetylases, require NAD for enzymatic activity. Recent research has indicated that sirtuins have a key role in the regulation of gene expression, the cell cycle, apoptosis, neurodegeneration and several age-related diseases. In mammals, there are seven sirtuin isoforms (SIRT-1-7) that catalyze specific lysine substrate deacetylation.

Areas Covered: This review explains the current information on the structure, function and importance of sirtuin modulators. It also explores the possible therapeutic applications of sirtuin modulators and related small molecules in the context of various diseases.

Expert Opinion: Sirtuin's modulators open a new area of research for targeting pathological conditions. Sirtuin modulators, through their targeted function, may provide a possible tool for the amelioration of various diseases. However, the search of activators/inhibitors for sirtuins needs further research. The structural elucidation of sirtuins will create an understanding for the development of isoform-specific selective modulators. This could be a useful tool to determine the functions of individual sirtuins as potential therapeutic agents.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1080/17460441.2021.1915980DOI Listing
April 2021

Utility of Caudal Angulation for Venous Access under Fluoroscopic Guidance during Cardiovascular Implantable Electronic Device Implantation.

Authors:
Siddharthan Deepti Dhara Singh Nirmal Ghati Manish Shaw Nitish Naik Sandeep Singh

Cardiology 2021 Apr 13:1-5. Epub 2021 Apr 13.

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

Background: Axillary venous access is preferred for CIED implantation. The procedure is usually performed under fluoroscopic guidance in anteroposterior (A-P) view. However, there is a lack of perception of depth in this view with a fear of creating complications. Caudal fluoroscopy (adding 30°-35° caudal angulation to A-P projection) has been proposed to circumvent this problem.

Objective: The aim of this study was to elucidate the advantages of caudal fluoroscopy using fluoroscopic images, contrast venograms, and CT angiography images of axillary vein.

Methods: The fluoroscopic images and contrast venograms obtained in the A-P view were compared with caudal fluoroscopy in patients undergoing CIED implantation at our centre. Also, the CT angiography images of axillary vein were reconstructed to understand the relative anatomy of the vein and the underlying lung parenchyma, simulating these 2 projections.

Results: The CT angiography images, contrast venograms, and fluoroscopic images confirmed that caudal fluoroscopy allows better visualization of the vein in relation to the lung parenchyma and rib cage. Analysis of fluoroscopic images revealed that the bend of the first rib formed a conical prominence in caudal fluoroscopy. This served as an important bony landmark for successful venous access, which was usually obtained while the needle was being directed towards this prominence in caudal fluoroscopy.

Conclusions: The proposed advantages of caudal fluoroscopy for CIED implantation have been elucidated by analysis of CT angiography images, contrast venograms, and fluoroscopic images.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1159/000515360DOI Listing
April 2021

Design and Synthesis of Non-Covalent Imidazo[1,2-]quinoxaline-Based Inhibitors of EGFR and Their Anti-Cancer Assessment.

Authors:
Manvendra Kumar Gaurav Joshi Sahil Arora Tashvinder Singh Sajal Biswas Nisha Sharma Zahid Rafiq Bhat Kulbhushan Tikoo Sandeep Singh Raj Kumar

Molecules 2021 Mar 9;26(5). Epub 2021 Mar 9.

Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, School of Health Sciences, Central University of Punjab, Bathinda 151401, Punjab, India.

A series of 30 non-covalent imidazo[1,2-]quinoxaline-based inhibitors of epidermal growth factor receptor (EGFR) were designed and synthesized. EGFR inhibitory assessment (against wild type) data of compounds revealed , , , and as potent EGFR inhibitors with IC values of 211.22, 222.21, 193.18, 223.32 and 221.53 nM, respectively, which were comparable to erlotinib (221.03 nM), a positive control. Furthermore, compounds exhibited excellent antiproliferative activity when tested against cancer cell lines harboring EGFR; A549, a non-small cell lung cancer (NSCLC), HCT-116 (colon), MDA-MB-231 (breast) and gefitinib-resistant NSCLC cell line H1975 harboring EGFR. In particular, compound demonstrated significant inhibitory potential against gefitinib-resistant H1975 cells (IC = 3.65 μM) as compared to gefitinib (IC > 20 μM). Moreover, molecular docking disclosed the binding mode of the to the domain of EGFR (wild type and mutant type), indicating the basis of inhibition. Furthermore, its effects on redox modulation, mitochondrial membrane potential, cell cycle analysis and cell death mode in A549 lung cancer cells were also reported.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.3390/molecules26051490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967119PMC
March 2021

Variation in the analytical figure of merit for in situ Hf isotopic measurements by LA-MC-ICPMS in zircon standards at variable spatial resolutions.

Authors:
Saurabh Singhal Sandeep Singh Dharmendra Singh

J Mass Spectrom 2021 Mar 1;56(5):e4715. Epub 2021 Mar 1.

Department of Electronics and Communication Engineering, Indian Institute of Technology Roorkee, Roorkee, 247667, India.

Lu-Hf isotopic systematics is a powerful tool and gained importance as a geochemical tracer in geosciences. A multi-collector inductively coupled plasma mass spectrometer coupled with a laser ablation system has been used to perform zircon hafnium (Hf) isotopic analysis, and protocol is established for measurement of Hf isotopes. Toward this, two zircon standards, Z91500 and Plesovice, have been used for Hf isotopic measurements at four different spot sizes (50, 40, 25, and 20 μm). The isotopic data for ≥25 μm have an excellent agreement with published data, but for 20 μm, the results are erroneous and irrelevant to geological application. It has been observed that Hf beam intensity has a linear relation to the volume of the target (RM) ablated. Hf/ Hf ratio and ɛHf for both standards are comparable with the published recommended values. The present study indicates that Lu/ Hf ratio for Z91500 is more homogeneous than Plesovice zircon. The Hf/ Hf isotopic ratio for 50 and 25 μm shows an excellent agreement with the previously reported data. However, for 40-μm spot size, a slightly higher but negative offset of -123 and -105 ppm in Hf/ Hf ratio have been observed for Plesovice and 91500, respectively.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1002/jms.4715DOI Listing
March 2021

Alarming trends in the frequency of malignant hypertension among admissions with a known cannabis use disorder.

Authors:
Hee Kong Fong Muhammad Uzair Lodhi Venkata Neelima Kothapudi Sandeep Singh Rupak Desai

Int J Cardiol Heart Vasc 2021 Apr 21;33:100729. Epub 2021 Feb 21.

Division of Cardiology, Atlanta VA Medical Center, Decatur, GA, USA.

View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.ijcha.2021.100729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905181PMC
April 2021

An elaborative NMR based plasma metabolomics study revealed metabolic derangements in patients with mild cognitive impairment: a study on north Indian population.

Authors:
Umesh Kumar Abhai Kumar Smita Singh Payal Arya Sandeep Kumar Singh Rameshwar Nath Chaurasia Anup Singh Dinesh Kumar

Metab Brain Dis 2021 06 2;36(5):957-968. Epub 2021 Mar 2.

Centre of Biomedical Research (CBMR), SGPGIMS Campus, Raibareli Road, Lucknow, Uttar Pradesh, 226014, India.

Mild cognitive impairment (MCI) is transition phase between cognitive decline and dementia. The current study aims to investigate altered metabolic pattern in plasma of MCI for potential biomarkers. MCI (N = 50) and healthy controls (HC, N = 50) age group 55-75 years were screened based on Mini Mental State Examination Test (MMSE) and diffusion tensor imaging (DTI imaging). The MMSE score of MCI was significantly lower (25.74 ± 1.83) compared to healthy control subjects (29 ± 1). The MCI patients exhibit significant changes in white matter integrity in the right frontal lobe, right temporal lobe, left frontal lobe, forcep major, fornix, corpus callosum. Further, the plasma samples of twenty seven MCI patients (N = 27) and twenty HC subjects (N = 20; having no significant differences in any demographics) were analyzed using H NMR based metabolomics approach. Consistent with many previous reports, the levels of several plasma metabolites were found to be elevated in MCI patients compared to healthy controls. Further univariate and multivariate ROC curve analyses provided three plasma metabolites as a diagnostic panel of biomarker for MCI; which are lysine, glycine, and glutamine. Overall, the results of this study will help to improve the diagnostic and prognostic strategies of MCI in addition to improving our understanding about disease pathogenesis. We believe that the over-nutritional metabolic phenotype of MCI needs to be targeted for developing future dietary interventions so that the progression of MCI can be limited. Metabolic derangements associated with Mild Cognitive Impairment.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1007/s11011-021-00700-zDOI Listing
June 2021

The role of LR-TIMAP/PP1c complex in the occurrence and development of no-reflow.

Authors:
Xiaoyu Quan Xiucheng Liu Xichun Qin Yuzhuo Wang Teng Sun Zhimin Li Lidong Zhu Jiali Chen Yeqing Zhou Sandeep Singh Hongyan Dong Zhongming Zhang Hao Zhang

EBioMedicine 2021 Mar 24;65:103251. Epub 2021 Feb 24.

Thoracic Surgery Laboratory, the First College of Clinical Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221006, China; Department of Thoracic Surgery, Affifiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou, Jiangsu 221006, China. Electronic address:

Background: The presence of no-reflow can increase the risk of major adverse cardiac events and is widely regarded as an important sign of serious prognosis. Previous studies show that laminin receptor (LR) is closely related to the morphology and function of microvessels. However, whether LR is involved in the occurrence and development of no-reflow is still unknown.

Methods: In vivo, positron emission tomography (PET) perfusion imaging was performed to detect the effects of intramyocardial gene (LR-AAV and LR-siRNA-AAV) delivery treatment on the degree of no-reflow. In vitro, LC-MS/MS analysis was conducted to identify the LR phosphorylation sites of human cardiac microvascular endothelial cells (HCMECs) treated with oxygen-glucose deprivation (OGD) for 4 h. Western blot analyses were used to evaluate the phosphorylation levels of LR at residues Tyr47 (phospho-Tyr47-LR/pY47-LR) and Thr125 (phospho-Thr125-LR/pT125-LR) and their effects on the phosphorylation of VE-cadherin residue Ser665 (phospho-Ser665-VE-cad).

Findings: LR over-expression, LR (phosphonull) and LR (phosphonull) treatments were found to reduce the level of phospho-Ser665-VE-cad, and subsequently maintain adherent junctions and endothelial barrier integrity in hypoxic environments. Mechanistically, TIMAP/PP1c can combine with LR on the cell membrane to form a novel LR-TIMAP/PP1c complex. The level of pY47-LR determined the stability of LR-TIMAP/PP1c complex. The binding of TIMAP/PP1c on LR activated the protein phosphatase activity of PP1c and regulated the level of pT125-LR.

Interpretation: This study demonstrates that low level of phospho-LR reduces no-reflow area through stabilizing the LR-TIMAP/PP1c complex and promoting the stability of adherens junctions, and may help identify new therapeutic targets for the treatment of no-reflow.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.ebiom.2021.103251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921471PMC
March 2021

Work from home culture and acute cardiovascular events: A bidirectional conundrum yet to be resolved!

Authors:
Sonali Sachdeva Rupak Desai Sandeep Singh Gautam Kumar Rajesh Sachdeva

Int J Cardiol 2021 06 22;333:250. Epub 2021 Feb 22.

Division of Cardiology, Atlanta VA Medical Center, Decatur, GA, USA; Division of Cardiology, Medical College of Georgia, Augusta, GA, USA; Division of Cardiology, Morehouse School of Medicine, Atlanta, GA, USA.

View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.ijcard.2021.02.051DOI Listing
June 2021

Compromising situation of India's bio-medical waste incineration units during pandemic outbreak of COVID-19: Associated environmental-health impacts and mitigation measures.

Authors:
Parteek Singh Thind Arjun Sareen Dapinder Deep Singh Sandeep Singh Siby John

Environ Pollut 2021 May 8;276:116621. Epub 2021 Feb 8.

Department of Civil Engineering, Punjab Engineering College, Chandigarh, 160012, India. Electronic address:

COVID-19 induced pandemic situations have put the bio-medical waste (BMW) management system, of the world, to test. Sudden influx, of COVID-infected patients, in health-care facilities, has increased the generation of yellow category BMW (Y-BMW) and put substantial burden on the BMW-incineration units of India. This study presents the compromising situation of the BMW-incineration units of India, in the wake of COVID-19 pandemic, from 21st March 2020 to 31st August 2020. This analysis revealed that on an average each COVID-infected patient in India generates approximately 3.41 kg/d of BMW and average proportion of Y-BMW in it is 50.44%. Further, it was observed that on 13th July 2020, the total Y-BMW, generated by both the normal and COVID-infected patients, fully utilized the BMW-incineration capacity of India. Also, it was made evident that, during the study period, BMW-incineration emitted several pollutants and their concentration was in the order: NO > CO > SO > PM > HCl > Cd > Pb > Hg > PCBs > Ni > Cr > Be > As. Subsequently, life time cancer risk assessment depicted that with hazard quotient >10, Cd may induce carcinogenic health impacts on both the adults and children of India. Therefore, to mitigate the environmental-health impacts associated with the incineration of BMW, evaluation of various options, viz., alternative technologies, substitution of raw materials and separate treatment of specific wastes, was also done. It is expected that the findings of this study may encourage the global auditory comprising scientific community and authorities to adopt alternate BMW-management strategies during the pandemic.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.envpol.2021.116621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869633PMC
May 2021

Response to the comments on 'Minimally invasive organ-preserving approaches in the management of mesh erosion after laparoscopic ventral mesh rectopexy'.

Authors:
Keshara Ratnatunga Roel Bolckmans Sandeep Singh Chris Cunningham

Colorectal Dis 2021 Apr 17;23(4):1001. Epub 2021 Feb 17.

Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1111/codi.15551DOI Listing
April 2021

Impact of COVID-19 on acute coronary syndrome-related hospitalizations: A pooled analysis.

Authors:
Sandeep Singh Hee Kong Fong Rupak Desai Aeilko H Zwinderman

Int J Cardiol Heart Vasc 2021 Feb 16;32:100718. Epub 2021 Jan 16.

Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Center, AMC, Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.ijcha.2021.100718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836359PMC
February 2021

Proteotoxicity: A Fatal Consequence of Environmental Pollutants-Induced Impairments in Protein Clearance Machinery.

Authors:
Shweta Devi Jong-Joo Kim Anand Prakash Singh Surendra Kumar Ashish Kant Dubey Sandeep Kumar Singh Ravi Shankar Singh Vijay Kumar

J Pers Med 2021 Jan 25;11(2). Epub 2021 Jan 25.

Department of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Korea.

A tightly regulated protein quality control (PQC) system maintains a healthy balance between correctly folded and misfolded protein species. This PQC system work with the help of a complex network comprised of molecular chaperones and proteostasis. Any intruder, especially environmental pollutants, disrupt the PQC network and lead to PQCs disruption, thus generating damaged and infectious protein. These misfolded/unfolded proteins are linked to several diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and cataracts. Numerous studies on proteins misfolding and disruption of PQCs by environmental pollutants highlight the necessity of detailed knowledge. This review represents the PQCs network and environmental pollutants' impact on the PQC network, especially through the protein clearance system.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.3390/jpm11020069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912547PMC
January 2021

Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders.

Authors:
Shweta Devi Vijay Kumar Sandeep Kumar Singh Ashish Kant Dubey Jong-Joo Kim

Biomedicines 2021 Jan 20;9(2). Epub 2021 Jan 20.

Department of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Korea.

Neurodegenerative disorders, such as Parkinson's disease (PD), Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), are the most concerning disorders due to the lack of effective therapy and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and endoplasmic reticulum (ER)-stress, which combats with stress conditions. Environmental stress/toxicity weakened the cellular stress response which results in cell damage. Small molecules, such as flavonoids, could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways, such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the potential role of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.3390/biomedicines9020099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909525PMC
January 2021

CaFu MOF as an efficient adsorbent for simultaneous removal of imidacloprid pesticide and cadmium ions from wastewater.

Authors:
Sandeep Singh Sandeep Kaushal Jasmeen Kaur Gurmeet Kaur Susheel Kumar Mittal Prit Pal Singh

Chemosphere 2021 Jun 13;272:129648. Epub 2021 Jan 13.

Department of Chemistry, Sri Guru Granth Sahib World University, Fatehgarh Sahib, Punjab, India. Electronic address:

Heavy metal ions and pesticides are the noteworthy toxic substances which must be removed from contaminated water for safeguarding public health. The higher levels of these substances in natural water may adversely affect the human health, climate and the eco-framework. The adsorptive removal of hazardous constituents employing metal organic frameworks has drawn considerable attention of researchers during the last decade. From this point of view, single crystal of calcium fumarate [Ca(CHO) (HO)(CHOH)] has been developed and analyzed by single crystal X-ray crystallography which confirmed the formation of 3-D metal organic frameworks (MOFs). The synthesized MOFs was employed for simultaneous adsorptive removal of imidacloprid, a high consumption pesticide, and highly toxic Cd (II) from aqua ecosystem. The effect of variation in experimental conditions such as solution pH, adsorbent dosage, contact time, initial concentration and temperature on adsorption was systematically evaluated. Both the imidacloprid and Cd(II) exhibited maximum adsorption at pH 6.5 and 7.8, respectively. The equilibrium empirical data was fitted into Langmuir, Freundlich and Temkin isotherms. The adsorption capacity of CaFu MOFs was observed to be 467.23 and 781.2 mg g for imidacloprid and cadmium ions, respectively. The adsorbed pollutants were desorbed from the adsorbent using dilute HCl, and the material was reused for five adsorption-desorption cycles without any appreciable loss of adsorption capacity. Therefore, the 3-D CaFu MOFs could be utilized as a novel material for adsorptive removal of imidacloprid pesticide as well as Cd (II) from wastewater.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.chemosphere.2021.129648DOI Listing
June 2021

Necrotizing fasciitis, causative agents and management: a five-year retrospective study in two tertiary care hospitals in Central Malaysia.

Authors:
Sanjiv Rampal Sandra Maniam Poh Ying Lim Rubenandran Ramachandran Eng Kee Tan Mohd Asyraf Hafizuddin Ab Halim Zulfahrizzat Shamsudin Sandeep Singh Sarawan Singh Pravind Narayanan Vasantha Kumari Neela

Int Orthop 2021 Jun 23;45(6):1399-1405. Epub 2021 Jan 23.

Department of Medical Microbiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.

Purpose: Necrotizing fasciitis (NF) is a rapidly progressive inflammatory infection of the fascia, with secondary necrosis of the subcutaneous tissues. The severity of the disease depends on the virulence of the organism and host immunity. There is a paucity of reports on the prevalence of NF causing pathogens and management.

Methods: Retrospective data of patients treated for NF were collected from two tertiary care hospitals in Central Malaysia between January 2014 and December 2018.

Results: A total of 469 NF patients were identified. More than half of the NF patients were males (n = 278; 59.28%). The highest number of cases was found among age groups between 30 and 79, with mean age of 56.17. The majority of the NF cases (n = 402; 85.72%) were monomicrobial. Streptococcus spp. (n = 89; 18.98%), Pseudomonas aeruginosa (n = 63; 13.44%) and Staphylococcus spp. (n = 61; 13.01%) were identified as the top three microorganisms isolated. Among the 469 NF cases, 173 (36.8%) were amputated or dead while 296 (63.1%) recovered. Proteus spp. (n = 19; 12.93%), Klebsiella pneumoniae (n = 18; 12.24%) and Escherichia coli (n = 14; 9.52%) were associated with all types of amputations. The most common antibiotic prescribed was unasyn (n = 284; 60.56%), followed by clindamycin (n = 56; 11.94%) and ceftazidime (n = 41; 8.74%). A total of 239 (61.8%) recovered while 148 (38.2%) were either amputated or dead when managed with the unasyn, clindamycin or ceftazidime.

Conclusion: This study represents the largest NF cases series in Malaysia highlighting the causative agents and management.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1007/s00264-020-04905-2DOI Listing
June 2021

Anticancer potential of some imidazole and fused imidazole derivatives: exploring the mechanism epidermal growth factor receptor (EGFR) inhibition.

Authors:
Sourav Kalra Gaurav Joshi Manvendra Kumar Sahil Arora Harsimrat Kaur Sandeep Singh Anjana Munshi Raj Kumar

RSC Med Chem 2020 Aug 8;11(8):923-939. Epub 2020 Jul 8.

Department of Pharmaceutical Sciences and Natural Products , School of Basic and Applied Sciences , Central University of Punjab , Bathinda , 151001 , India . Email:

Imidazole-based epidermal growth factor receptor (EGFR) inhibitors were computationally designed and synthesized. All the compounds were assessed for their anti-proliferative activity against five cancer cell lines, , MDA-MB-231 (breast), T47D (breast) and MCF-7 (breast), A549 (lung) and HT-29 (colorectal). Compounds and emerged as better anticancer molecules with no toxicity towards normal cells. and inhibited EGFR enzymatic activity with IC values of 617.33 ± 0.04 nM and 710 ± 0.05 nM, respectively. In order to further improve the potency, we explored an unoccupied area of the ATP binding domain of EGFR and analysed an interaction model of and -EGFR complexes that guided and allowed substitution of the 4-fluorophenyl ring ( and ) with 4-(4-methylpiperazinyl)-3-nitrophenyl at the N-9 position, resulting in compound with a better binding score and potent EGFR inhibitory activity (IC: 236.38 ± 0.04 nM), which was comparable to the positive control erlotinib (239.91 ± 0.05 nM). exhibited a great improvement in anticancer potency with inhibition of cell growth of all cancer cell lines at very low micromolar concentrations (IC = 1.98 to 4.07 μM). Further investigation revealed that also induced an increase in ROS levels in cancer cells in a mitochondrial-independent manner and halted the cell cycle at the sub-G phase.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1039/d0md00146eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497068PMC
August 2020

A 64-Year-Old Man with Low Back Pain Due to Clostridium perfringens Lumbar Discitis.

Authors:
Harshil Bhatt Sandeep Singh

Am J Case Rep 2021 Jan 22;22:e928014. Epub 2021 Jan 22.

Department of Medicine, Indiana University School of Medicine, South Bend, IN, USA.

BACKGROUND Lumbar discitis caused by Clostridium perfringens is extremely rare. There have only been 7 published cases of confirmed discitis caused by Clostridium perfringens. We write this report to underscore this unusual relationship by discussing an additional case and providing a review of the previously published cases so clinicians can adequately evaluate and treat patients presenting with discitis. CASE REPORT A 64-year-old morbidly obese man presented with an acute onset of worsening back pain and generalized weakness after incurring physical trauma related to falling. Additionally, he also developed fever and chills before the presentation. Based on the clinical presentation and elevated serum levels of inflammatory markers, magnetic resonance imaging was ordered, which showed L5-S1 discitis with extension of infection into the epidural space. Fluoroscopy-guided aspiration of the L5-S1 epidural space facilitated the detection of Clostridium perfringens as the involved pathogen. Based on the antibiotic susceptibility report, the patient was treated with intravenous ampicillin for 8 weeks, after which his symptoms resolved. CONCLUSIONS Diagnosis of discitis can be very challenging due to its ambiguous clinical presentation, especially in the elderly population due to the presence of underlying degenerative changes. Even though Clostridium perfringens remains a rare cause of lumbar discitis, it should be considered as a pathogen capable of causing infection of the vertebrae and intervertebral discs, thus allowing clinicians to make necessary diagnostic evaluations to provide appropriate targeted treatment to patients presenting with discitis.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.12659/AJCR.928014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836320PMC
January 2021

Evidence of Coronavirus (CoV) Pathogenesis and Emerging Pathogen SARS-CoV-2 in the Nervous System: A Review on Neurological Impairments and Manifestations.

Authors:
Niraj Kumar Jha Shreesh Ojha Saurabh Kumar Jha Harish Dureja Sachin Kumar Singh Shakti D Shukla Dinesh Kumar Chellappan Gaurav Gupta Shanu Bhardwaj Neeraj Kumar Madhan Jeyaraman Rashmi Jain Sathish Muthu Rohan Kar Dhruv Kumar Vineet Kumar Goswami Janne Ruokolainen Kavindra Kumar Kesari Sandeep Kumar Singh Kamal Dua

J Mol Neurosci 2021 Jan 19. Epub 2021 Jan 19.

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute (HMRI), University of Newcastle, New Lambton Heights, Newcastle, NSW, 2305, Australia.

The coronavirus disease 2019 (COVID-19) pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1007/s12031-020-01767-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814864PMC
January 2021

Elucidation of plasma protein binding, blood partitioning, permeability, CYP phenotyping and CYP inhibition studies of Withanone using validated UPLC method: An active constituent of neuroprotective herb Ashwagandha.

Authors:
Sandeep K Singh Guru R Valicherla Anil K Bikkasani Srikanth H Cheruvu Zakir Hossain Isha Taneja Hafsa Ahmad Kanumuri S R Raju Neelam S Sangwan Shio K Singh Anil K Dwivedi Mohammad Wahajuddin Jiaur R Gayen

J Ethnopharmacol 2021 Apr 16;270:113819. Epub 2021 Jan 16.

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

Ethnopharmacological Relevance: Withanone (WN), an active constituent of Withania somnifera commonly called Ashwagandha has remarkable pharmacological responses along with neurological activities. However, for a better understanding of the pharmacokinetic and pharmacodynamic behavior of WN, a comprehensive in-vitro ADME (absorption, distribution, metabolism, and excretion) studies are necessary.

Aim Of The Study: A precise, accurate, and sensitive reverse-phase ultra-performance liquid chromatographic method of WN was developed and validated in rat plasma for the first time. The developed method was successfully applied to the in-vitro ADME investigation of WN.

Material And Methods: The passive permeability of WN was assayed using PAMPA plates and the plasma protein binding (PPB) was performed using the equilibrium dialysis method. Pooled liver microsomes of rat (RLM) and human (HLM) were used for the microsomal stability, CYP phenotyping, and inhibition studies. CYP phenotyping was evaluated using the specific inhibitors. CYP inhibition study was performed using specific probe substrates along with WN or specific inhibitors.

Results: WN was found to be stable in the simulated gastric and intestinal environment and has a high passive permeability at pH 4.0 and 7.0 in PAMPA assay. The PPB of WN at 5 and 20 μg/mL concentrations were found to be high i.e. 82.01 ± 1.44 and 88.02 ± 1.15%, respectively. The in vitro half-life of WN in RLM and HLM was found to be 59.63 ± 2.50 and 68.42 ± 2.19 min, respectively. CYP phenotyping results showed that WN was extensively metabolized by CYP 3A4 and1A2 enzymes in RLM and HLM. However, the results of CYP Inhibition studies showed that none of the CYP isoenzymes were potentially inhibited by WN in RLM and HLM.

Conclusion: The in vitro results of pH-dependent stability, plasma stability, permeability, PPB, blood partitioning, microsomal stability, CYP phenotyping, and CYP inhibition studies demonstrated that WN could be a better phytochemical for neurological disorders.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.jep.2021.113819DOI Listing
April 2021