Publications by authors named "Rajendra Prasad"

671 Publications

Pharmacotherapy of schizophrenia: immunological aspects and potential role of immunotherapy.

Expert Rev Neurother 2021 Oct 15. Epub 2021 Oct 15.

Department of Pharmacology, Government Medical College & Hospital, Chandigarh, India.

Introduction: Schizophrenia is a complex disorder owing to diversity in clinical phenotypes, overlapping symptoms and heterogeneous clinical presentation. Even after decades of research, the exact causative mechanisms of schizophrenia are not completely known. Recent evidence indicates the role of immune dysfunction in schizophrenia pathogenesis as observed from alteration in immune cells, increased activity of complement cascade and development of autoantibodies against neurotransmitter receptors. Immunotherapy involving immunosuppressants and cytokine-targeting drugs have shown promising results in several clinical studies and it demands further research in this area.

Areas Covered: Here, the authors review the immunopathogenesis of schizophrenia, limitations of conventional and atypical antipsychotic drugs and the potential role and limitations of immunotherapeutic drugs in schizophrenia management.

Expert Opinion: Schizophrenia is a complex disorder and poses a challenge to the currently available treatment approaches. Nearly 30 % schizophrenia patients exhibit minimal response towards conventional and atypical antipsychotic drugs. Immune system dysfunction plays an important part of schizophrenia pathophysiology and existing monoclonal antibody (mAb) drugs targeting specific components of the immune system are being repositioned in schizophrenia. The authors call upon public and private funders to facilitate urgent and rigorous research efforts in exploring potential role of immunotherapy in schizophrenia.
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http://dx.doi.org/10.1080/14737175.2021.1994857DOI Listing
October 2021

Overexpression of an oxidoreductase YghA confers tolerance against furfural in ethanologenic strain SSK42.

Appl Environ Microbiol 2021 Sep 29:AEM0185521. Epub 2021 Sep 29.

Microbial Engineering Group, International Center for Genetic Engineering and Biotechnology, New Delhi, India.

Furfural is a common furan inhibitor formed due to dehydration of pentose sugar like xylose and acts as an inhibitor of microbial metabolism. Overexpression of NADH specific FucO and deletion of NADPH specific YqhD had been a successful strategy in the past in conferring tolerance against furfural in , which highlight the importance of oxidoreductases in conferring tolerance against furfural. In a screen consisting of various oxidoreductases, dehydrogenases, and reductases, we identified gene as an overexpression target to confer tolerance against furfural. YghA preferably used NADH as a cofactor and had apparent value of 0.03 mM against furfural. In presence of 1 g L furfural and 10% xylose (wt/vol), overexpression in an ethanologenic strain SSK42 resulted in a 5.3-fold increase in ethanol titers as compared to the control strain with an efficiency of ∼97%. YghA also exhibited activity against the lesser toxic inhibitor 5-hydroxymethyl furfural that is formed due to dehydration of hexose sugars and thus is a formidable target for overexpression in ethanologenic strain for fermentation of sugars in biomass hydrolysate. Lignocellulosic biomass represents an inexhaustible source of carbon for second-generation biofuels. Thermo-acidic pretreatment of biomass is performed to loosen the lignocellulosic fibers and make the carbon bioavailable for microbial metabolism. The pretreatment process also results in the formation of inhibitors that inhibit microbial metabolism and increase production costs. Furfural is a potent furan inhibitor that increases the toxicity of other inhibitors present in the hydrolysate. Thus it is desirable to engineer furfural tolerance in for efficient fermentation of hydrolysate sugars.
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http://dx.doi.org/10.1128/AEM.01855-21DOI Listing
September 2021

Synthesis and crystal structure of 1-hy-droxy-8-methyl-9-carbazole-2-carbaldehyde.

Acta Crystallogr E Crystallogr Commun 2021 Sep 16;77(Pt 9):867-870. Epub 2021 Jul 16.

Department of Chemistry, Purdue University, West Lafayette, IN 47907-2084, USA.

Two crystallographically independent mol-ecules are present in the asymmetric unit of the title compound, CHNO, with virtually identical geometries. The carbazole units are planar. The hy-droxy group at position 1, carbaldehyde group at position 2, and methyl group at position 8 (with the exception of two H atoms) are coplanar with the attached benzene rings. The dihedral angle between the two benzene rings is 2.20 (9)° in mol-ecule and 2.01 (9)° in mol-ecule . The pyrrole ring makes dihedral angles of 0.82 (10) and 1.40 (10)° [0.84 (10) and 1.18 (10)° in mol-ecule ] with the (-CH)-substituted and (-OH and -CHO) substituted benzene rings, respectively. The mol-ecular structure is stabilized by the intra-molecular O-H⋯O hydrogen bonds, while the crystal structure features N-H⋯O and C-H⋯O hydrogen bonds. A range of π-π contacts further stabilizes the crystal structure.
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http://dx.doi.org/10.1107/S2056989021007210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423023PMC
September 2021

Synergistic action of silicon nanoparticles and indole acetic acid in alleviation of chromium (Cr) toxicity in Oryza sativa seedlings.

J Biotechnol 2021 Sep 14. Epub 2021 Sep 14.

Department of Biotechnology, Motilal Nehru National Institute of Technology Allahabad, Prayagraj-211004 (UP) India. Electronic address:

The present study investigates ameliorative effect of silicon nanoparticles (SiNPs) and indole acetic acid (IAA) alone and in combination against hexavalent chromium (Cr) toxicity in rice seedlings. The results of the study revealed protective effects of SiNPs and IAA against Cr toxicity. The 100μM of Cr imposed toxic effects in rice seedlings at morphological, physiological and biochemical levels which coincided with increased level of intracellular Cr and declined level of endogenous nitric oxide (NO). The Cr enhanced levels of superoxide radicals (SOR) (59.51% and 50.1% in shoot and root, respectively) and HO (19.5% and 23.69% in shoot and root, respectively). However, when SiNPs and IAA were applied to plants under Cr stress, they enhanced tolerance and defence mechanisms as manifested in terms of increased biomass, endogenous NO, photosynthetic pigments, and antioxidants level (ascorbate-glutathione cycle). It was also noticed that Cr arrested cell cycle at G2/M phase whereas growth was restored as compared to control when SiNPs and IAA were supplemented. Thus, the hypothesis that combined application of SiNPs and IAA will be effective in alleviating Cr toxicity is validated from the results of this study. Moreover, in SiNPs and IAA-mediated mitigation of Cr toxicity, endogenous NO has a positive role. The importance of the study will be that the combination of SiNPs and IAA can be utilized against heavy metal stress and even when supplied alone, they will enhance the crop productivity parameters with and without stress conditions.
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http://dx.doi.org/10.1016/j.jbiotec.2021.09.005DOI Listing
September 2021

Exogenous addition of silicon alleviates metsulfuron methyl induced stress in wheat seedlings.

Plant Physiol Biochem 2021 Oct 5;167:705-712. Epub 2021 Aug 5.

Department of Biotechnology, Motilal Nehru National Institute of Technology Allahabad, Prayagraj, 211004, UP, India. Electronic address:

Uncontrolled application of herbicides in the agricultural field poses a severe risk to crops by affecting their yields. Therefore, methods are required to reduce the toxic effects of herbicides in plants. Studies indicate that silicon (Si) provides tolerance and enhances defence mechanism of the plant against abiotic stress. But its role in alleviating Metsulfuron methyl (Meth) herbicide induced toxicity in wheat seedlings is still not known. This study highlighted the potential of exogenous addition of Si in the alleviation of toxic effect of Meth herbicide in wheat seedlings. The exposure of wheat seedlings to Meth herbicide reduced the growth, photosynthetic pigments, antioxidant enzyme activity and nitric oxide (NO) content. Further, Meth herbicide also increased cell death and decreased cell viability in root tips. However, addition of Si reversed Meth-induced these alterations. Moreover, Si also activates antioxidant system which helps in scavenging of free radicals generated under Meth herbicide stress in wheat seedlings. Application of Si to Meth treated wheat seedlings also up-regulated silicon transporter gene Lsi1 (silicon influx transporter) and some of the antioxidant enzyme genes. All together, the data indicate that Si has capability of alleviating Meth herbicide stress in wheat seedlings but it appears that endogenous NO has a positive role in this endeavour of Si.
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http://dx.doi.org/10.1016/j.plaphy.2021.07.031DOI Listing
October 2021

Potential molecular mechanisms of zinc- and copper-mediated antiviral activity on COVID-19.

Nutr Res 2021 08 13;92:109-128. Epub 2021 Jun 13.

Department of Biochemistry, M.M. Institute of Medical Sciences and Research (MMIMSR), Maharishi Markandeshwar University (MMU), Mullana, Ambala, Haryana, India. Electronic address:

Novel coronavirus disease 2019 (COVID-19) has spread across the globe; and surprisingly, no potentially protective or therapeutic antiviral molecules are available to treat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, zinc (Zn) and copper (Cu) have been shown to exert protective effects due to their antioxidant, anti-inflammatory, and antiviral properties. Therefore, it is hypothesized that supplementation with Zn and Cu alone or as an adjuvant may be beneficial with promising efficacy and a favorable safety profile to mitigate symptoms, as well as halt progression of the severe form of SARS-CoV-2 infection. The objective of this review is to discuss the proposed underlying molecular mechanisms and their implications for combating SARS-CoV-2 infection in response to Zn and Cu administration. Several clinical trials have also included the use of Zn as an adjuvant therapy with dietary regimens/antiviral drugs against COVID-19 infection. Overall, this review summarizes that nutritional intervention with Zn and Cu may offer an alternative treatment strategy by eliciting their virucidal effects through several fundamental molecular cascades, such as, modulation of immune responses, redox signaling, autophagy, and obstruction of viral entry and genome replication during SARS-CoV-2 infection.
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http://dx.doi.org/10.1016/j.nutres.2021.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200255PMC
August 2021

Phytochemicals reverse P-glycoprotein mediated multidrug resistance via signal transduction pathways.

Biomed Pharmacother 2021 Jul 9;139:111632. Epub 2021 May 9.

Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608002, Tamil Nadu, India. Electronic address:

P-glycoprotein, encoded by ATP-binding cassette transporters B1 gene (ABCB1), renders multidrug resistance (MDR) during cancer chemotherapy. Several synthetic small molecule inhibitors affect P-glycoprotein (P-gp) transport function in MDR tumor cells. However, inhibition of P-gp transport function adversely accumulates chemotherapeutic drugs in non-target normal tissues. Moreover, most small-molecule P-gp inhibitors failed in the clinical trials due to the low therapeutic window at the maximum tolerated dose. Therefore, downregulation of ABCB1-gene expression (P-gp) in tumor tissues seems to be a novel approach rather than inhibiting its transport function for the reversal of multidrug resistance (MDR). Several plant-derived phytochemicals modulate various signal transduction pathways and inhibit translocation of transcription factors, thereby reverses P-gp mediated MDR in tumor cells. Therefore, phytochemicals may be considered an alternative to synthetic small molecule P-gp inhibitors for the reversal of MDR in cancer cells. This review discussed the role of natural phytochemicals that modulate ABCB1 expression through various signal transduction pathways in MDR cancer cells. Therefore, modulating the cell signaling pathways by phytochemicals might play crucial roles in modulating ABCB1 gene expression and the reversal of MDR.
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http://dx.doi.org/10.1016/j.biopha.2021.111632DOI Listing
July 2021

Prevalence of Y chromosome microdeletion in north Indian infertile males with spermatogenesis defect.

J Genet 2021 ;100

Department of Biochemistry, All India Institute of Medical Science, Bathinda 151 001, India.

Deletion of specific genes present in the long arm of Y chromosome has been identified as the most common genetic cause of defective spermatogenesis. Studies have shown that frequency of Y chromosome microdeletion varies in different geographical location and is related to genetic and environmental influence preponderance. Therefore, the present study was carried out to identify the frequency of Y chromosome microdeletion in the northern region of India and to define subgroup of infertile patients who are critically under more risk of having microdeletion. A total of 292 north Indian infertile males with nonobstructive azoospermia and oligozoospermia were selected for screening the Y chromosome microdeletion. Healthy fertile males (=100) were also enrolled as control subjects. Frequency of Y chromosome microdeletion in north Indian infertile males was found to be about 8.5%, with azoospermia factor (AZFc) region as the most susceptible region for microdeletion. Comparatively microdeletion is more common in patients with nonobstructive azoospermia than oligozoospermia (9.2% versus 7.1%). Statistical analysis also revealed that patients with hormonal FSH level between 20 and 40 mIU/mL have more chances of harbouring microdeletion. Hence, the present study highlights the importance of screening AZFc region among infertile patients with very high serum FSH value.
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September 2021

New Perspectives in Underlying Molecular Defects Based Cystic Fibrosis Therapeutics.

Authors:
Rajendra Prasad

Indian J Clin Biochem 2021 Jul 15;36(3):255-256. Epub 2021 Jun 15.

Department of Biochemistry, MM Institute of Medical Science and Research, MM (Deemed To Be University), Mullana, Ambala, Haryana 133207 India.

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http://dx.doi.org/10.1007/s12291-021-00988-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215001PMC
July 2021

Perspectives on formaldehyde dysregulation: Mitochondrial DNA damage and repair in mammalian cells.

DNA Repair (Amst) 2021 09 11;105:103134. Epub 2021 May 11.

Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. Electronic address:

Maintaining genome stability involves coordination between different subcellular compartments providing cells with DNA repair systems that safeguard against environmental and endogenous stresses. Organisms produce the chemically reactive molecule formaldehyde as a component of one-carbon metabolism, and cells maintain systems to regulate endogenous levels of formaldehyde under physiological conditions, preventing genotoxicity, among other adverse effects. Dysregulation of formaldehyde is associated with several diseases, including cancer and neurodegenerative disorders. In the present review, we discuss the complex topic of endogenous formaldehyde metabolism and summarize advances in research on fo dysregulation, along with future research perspectives.
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http://dx.doi.org/10.1016/j.dnarep.2021.103134DOI Listing
September 2021

Experience of establishing and coordinating a nationwide network for bidirectional intussusception surveillance in India: lessons for multisite research studies.

BMJ Open 2021 05 28;11(5):e046827. Epub 2021 May 28.

The INCLEN Trust International, New Delhi, Delhi, India

Objectives: To document and share the process of establishing the nationally representative multisite surveillance network for intussusception in India, coordination, data management and lessons learnt from the implementation.

Design: This study combined both retrospective and prospective surveillance approaches.

Setting: 19 tertiary care institutions were selected in India considering the geographic representation and public and private mix PARTICIPANTS: All children under-2 years of age with intussusception PRIMARY AND SECONDARY OUTCOME MEASURES: The experience of site selection, regulatory approvals, data collection, quality assurance and network coordination were documented.

Results: The site selection process involved systematic and objective four steps including shortlisting of potential institutions, information seeking and telephonic interaction, site visits and site selection using objective criteria. Out of over 400 hospitals screened across India, 40 potential institutions were shortlisted and information was sought by questionnaire and interaction with investigators. Out of these, 25 institutes were visited and 19 sites were finally selected to participate in the study. The multistep selection process allowed filtering and identification of sites with adequate capacity and motivated investigators. The retrospective surveillance documented 1588 cases (range: 14-652 cases/site) and prospective surveillance recruited 621 cases (range: 5-191 cases/site). The multilayer quality assurance measures monitored and ensured protocol adherence, complete record retrieval and data completeness. The key challenges experienced included time taken for obtaining regulatory and ethical approvals, which delayed completion of the study. Ten sites continued with another multisite vaccine safety surveillance study.

Conclusion: The experience and results of this systematic and objective site selection method in India are promising. The systematic multistep site selection and data quality assurance methods presented here are feasible and practical. The lessons from the establishment and coordination of this surveillance network can be useful in planning, selecting the sites and conducting multisite and surveillance studies in India and developing countries.
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http://dx.doi.org/10.1136/bmjopen-2020-046827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166592PMC
May 2021

Association of meteorological parameters with intussusception in children aged under 2 years: results from a multisite bidirectional surveillance over 7 years in India.

BMJ Open 2021 05 25;11(5):e043687. Epub 2021 May 25.

The INCLEN Trust International, New Delhi, India

Objectives: The study aimed to document the association between intussusception in Indian children and meteorological parameters and examine regional variations.

Design: A bidirectional (retrospective and prospective) surveillance between July 2010 and September 2017.

Setting: At 20 hospitals in India, retrospective case record review during July 2010 and March 2016 and prospective surveillance during April 2016 and September 2017 were performed.

Participants: 2161 children aged 2-24 months with first intussusception episode were included.

Interventions: The monthly mean meteorological parameters (temperature, sunshine, rainfall, humidity and wind speed) for the study sites were collected.

Methods: The association between monthly intussusception cases and meteorological parameters was examined at pooled, regional and site levels using Pearson () and Spearman's rank-order () correlation, factorial analysis of variance, and Poisson regression or negative binomial regression analyses.

Results: The intussusception cases were highest in summer and lowest in autumn seasons. Pearson correlation analysis showed that temperature (=0.056; p<0.05), wind speed (=0.134; p<0.01) and humidity (=0.075; p<0.01) were associated with monthly intussusception cases. Spearman's rank-order correlation analysis found that temperature (=0.049; p<0.05), wind speed (=0.096; p<0.01) and sunshine (=0.051; p<0.05) were associated with monthly intussusception cases. Poisson regression analysis resulted that monthly intussusception case was associated with rising temperature (North region, p<0.01 and East region, p<0.05), sunshine (North region, p<0.01), humidity (East region, p<0.01) and wind speed (East region, p<0.01). Factorial analysis of variance revealed a significant seasonal difference in intussusception cases for pooled level (p<0.05), 2-6 months age group (p<0.05) and North region (p<0.01). Significant differences in intussusception cases between summer and autumn seasons were observed for pooled (p<0.01), children aged 2-6 months (p<0.05) and 7-12 months (p<0.05).

Conclusions: Significant correlations between intussusception cases and temperature, humidity, and wind speed were observed at pooled and regional level in India. A peak in summer months was noted, which may be used for prediction, early detection and referral for appropriate management of intussusception.
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http://dx.doi.org/10.1136/bmjopen-2020-043687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154980PMC
May 2021

Functional and Comparative Analysis of Centromeres Reveals Clade-Specific Genome Rearrangements in and a Chromosome Number Change in Related Species.

mBio 2021 05 11;12(3). Epub 2021 May 11.

Molecular Mycology Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India

The thermotolerant multidrug-resistant ascomycete rapidly emerged since 2009 causing systemic infections worldwide and simultaneously evolved in different geographical zones. The molecular events that orchestrated this sudden emergence of the killer fungus remain mostly elusive. Here, we identify centromeres in and related species, using a combined approach of chromatin immunoprecipitation and comparative genomic analyses. We find that and multiple other species in the clade shared a conserved small regional GC-poor centromere landscape lacking pericentromeres or repeats. Further, a centromere inactivation event led to karyotypic alterations in this species complex. Interspecies genome analysis identified several structural chromosomal changes around centromeres. In addition, centromeres are found to be rapidly evolving loci among the different geographical clades of the same species of Finally, we reveal an evolutionary trajectory of the unique karyotype associated with clade 2 that consists of the drug-susceptible isolates of , the killer fungus, emerged as different geographical clades, exhibiting multidrug resistance and high karyotype plasticity. Chromosomal rearrangements are known to play key roles in the emergence of new species, virulence, and drug resistance in pathogenic fungi. Centromeres, the genomic loci where microtubules attach to separate the sister chromatids during cell division, are known to be hot spots of breaks and downstream rearrangements. We identified the centromeres in and related species to study their involvement in the evolution and karyotype diversity reported in We report conserved centromere features in 10 related species and trace the events that occurred at the centromeres during evolution. We reveal a centromere inactivation-mediated chromosome number change in these closely related species. We also observe that one of the geographical clades, the East Asian clade, evolved along a unique trajectory, compared to the other clades and related species.
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http://dx.doi.org/10.1128/mBio.00905-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262905PMC
May 2021

SARS-CoV-2: Pathogenesis, Molecular Targets and Experimental Models.

Front Pharmacol 2021 22;12:638334. Epub 2021 Apr 22.

Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, India.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recent pandemic outbreak threatening human beings worldwide. This novel coronavirus disease-19 (COVID-19) infection causes severe morbidity and mortality and rapidly spreading across the countries. Therefore, there is an urgent need for basic fundamental research to understand the pathogenesis and druggable molecular targets of SARS-CoV-2. Recent sequencing data of the viral genome and X-ray crystallographic data of the viral proteins illustrate potential molecular targets that need to be investigated for structure-based drug design. Further, the SARS-CoV-2 viral pathogen isolated from clinical samples needs to be cultivated and titrated. All of these scenarios demand suitable laboratory experimental models. The experimental models should mimic the viral life cycle as it happens in the human lung epithelial cells. Recently, researchers employing primary human lung epithelial cells, intestinal epithelial cells, experimental cell lines like Vero cells, CaCo-2 cells, HEK-293, H1299, Calu-3 for understanding viral titer values. The human iPSC-derived lung organoids, small intestinal organoids, and blood vessel organoids increase interest among researchers to understand SARS-CoV-2 biology and treatment outcome. The SARS-CoV-2 enters the human lung epithelial cells using viral Spike (S1) protein and human angiotensin-converting enzyme 2 (ACE-2) receptor. The laboratory mouse show poor ACE-2 expression and thereby inefficient SARS-CoV-2 infection. Therefore, there was an urgent need to develop transgenic hACE-2 mouse models to understand antiviral agents' therapeutic outcomes. This review highlighted the viral pathogenesis, potential druggable molecular targets, and suitable experimental models for basic fundamental research.
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http://dx.doi.org/10.3389/fphar.2021.638334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100521PMC
April 2021

ABC-finder: A containerized web server for the identification and topology prediction of ABC proteins.

Biochim Biophys Acta Biomembr 2021 Aug 3;1863(8):183640. Epub 2021 May 3.

Amity Institute of Biotechnology and Amity Institute of Integrative Sciences and Health, Amity University Haryana, Gurugram, India. Electronic address:

In view of the multiple clinical and physiological implications of ABC transporter proteins, there is a considerable interest among researchers to characterize them functionally. However, such characterizations are based on the premise that ABC proteins are accurately identified in the proteome of an organism, and their topology is correctly predicted. With this objective, we have developed ABC-finder, i.e., a Docker-based package for the identification of ABC proteins in all organisms, and visualization of the topology of ABC proteins using a web browser. ABC-finder is built and deployed in a Linux container, making it scalable for many concurrent users on our servers and enabling users to download and run it locally. Overall, ABC-finder is a convenient, portable, and platform-independent tool for the identification and topology prediction of ABC proteins. ABC-finder is accessible at http://abc-finder.osdd.jnu.ac.in.
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http://dx.doi.org/10.1016/j.bbamem.2021.183640DOI Listing
August 2021

An Integrated Approach of the Potential Underlying Molecular Mechanistic Paradigms of SARS-CoV-2-Mediated Coagulopathy.

Indian J Clin Biochem 2021 Apr 15:1-17. Epub 2021 Apr 15.

Department of Biochemistry, Maharishi Markandeshwar Institute of Medical Sciences and Research (MMIMSR), Maharishi Markandeshwar University (MMU), Mullana, Ambala, Haryana, India.

Coronavirus disease 2019 (Covid-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic disease which has affected more than 6.2 million people globally, with numbers mounting considerably daily. However, till date, no specific treatment modalities are available for Covid-19 and also not much information is known about this disease. Recent studies have revealed that SARS-CoV-2 infection is associated with the generation of thrombosis and coagulopathy. Fundamentally, it has been believed that a diverse array of signalling pathways might be responsible for the activation of coagulation cascade during SARS-CoV-2 infection. Henceforth, a detailed understanding of these probable underlying molecular mechanistic pathways causing thrombosis in Covid-19 disease deserves an urgent exploration. Therefore, in this review, the hypothetical crosstalk between distinct signalling pathways including apoptosis, inflammation, hypoxia and angiogenesis attributable for the commencement of thrombotic events during SARS-CoV-2 infection has been addressed which might further unravel promising therapeutic targets in Covid-19 disease.
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http://dx.doi.org/10.1007/s12291-021-00972-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047580PMC
April 2021

Nanotechnology synergized immunoengineering for cancer.

Eur J Pharm Biopharm 2021 Jun 24;163:72-101. Epub 2021 Mar 24.

Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA. Electronic address:

Novel strategies modulating the immune system yielded enhanced anticancer responses and improved cancer survival. Nevertheless, the success rate of immunotherapy in cancer treatment has been below expectation(s) due to unpredictable efficacy and off-target effects from systemic dosing of immunotherapeutic(s). As a result, there is an unmet clinical need for improving conventional immunotherapy. Nanotechnology offers several new strategies, multimodality, and multiplex biological targeting advantage to overcome many of these challenges. These efforts enable programming the pharmacodynamics, pharmacokinetics, and delivery of immunomodulatory agents/co-delivery of compounds to prime at the tumor sites for improved therapeutic benefits. This review provides an overview of the design and clinical principles of biomaterials driven nanotechnology and their potential use in personalized nanomedicines, vaccines, localized tumor modulation, and delivery strategies for cancer immunotherapy. In this review, we also summarize the latest highlights and recent advances in combinatorial therapies availed in the treatment of cold and complicated tumors. It also presents key steps and parameters implemented for clinical success. Finally, we analyse, discuss, and provide clinical perspectives on the integrated opportunities of nanotechnology and immunology to achieve synergistic and durable responses in cancer treatment.
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http://dx.doi.org/10.1016/j.ejpb.2021.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170847PMC
June 2021

Assessment of prescribability and switchability by using multiple bioequivalence assessment approaches.

Drug Metab Lett 2021 Mar 19. Epub 2021 Mar 19.

Department of Chemistry, School of Advanced Sciences, VIT University, Vellore, Tamilnadu 632014. India.

Background: In the drug development process, an assessment of bioequivalence is an integral part. For the evaluation of generics against the comparator, average bioequivalence approach is the gold standard method. In the recent past, there were many discussions on whether we have the adequate tool to evaluate generics and thereby drug interchangeability (prescribability and switchability) issue is addressed as average bioequivalence approach just considers population mean. Hence, the alternative approaches like population bioequivalence and individual bioequivalence assessment approaches arise as different variances like inter/ intra-subject variance and subject-by-formulation variance along with population mean are considered.

Objectives: Methoxsalen, in combination with long-wave UVA radiation, is used in the symptomatic management certain psoriasis. The study was aimed to establish the bioequivalence (BE) of a newly developed methoxsalen capsule (MTX test) with that of a reference methoxsalen capsule (MTX reference) using multiple BE methods (i.e., average [ABE], population [PBE], and individual [IBE]) by utilizing a new LC-MS/MS method.

Methods: This is an open-label, randomized, balanced, two-treatment, three-period, three-sequence, crossover, single-dose (20 mg, 2 × 10 mg capsules), comparative, oral BE study conducted in 52 healthy, adult males under fasting conditions. Along with various pharmacokinetic (PK) parameters ABE, PBE, and IBE were also determined in the single study.

Results: A non-compartmental model best described the concentration-time data of both MTX test and reference. Both the formulations demonstrated nearly similar values of BE parameters (i.e., AUCo-t, AUC0-∞, Cmax, Tmax, and t1/2). For MTX test, the observed Cmax, AUC0-t, and AUC0-∞ were 125.16±81.53 ng/mL, 313.73±260.86 ng h/mL, and 321.25±271.85 ng h/mL, respectively. For MTX reference, the values were 127.63±71.60 ng/mL, 329.11±252.91 ng h/mL, and 335.48±264.54 ng h/mL, respectively. The bioanalytical method was validated over the concentration range 0.100-100.00ng/mL and the coefficient of determination (r2) was ≥ 0.9991. The sensitivity of the method was 0.100 ng/mL with the accuracy and precision values of 115% and 10.54%, respectively.

Conclusion: A single dose of MTX test met the ABE criteria of 80.00% -125.00% for Cmax, AUCo-t, and AUC0-∞, against MTX reference. The study outcome by PBE and IBE approaches proved that MTX Test was bio-inequivalent to MTX reference. Using multiple BE assessment methods in a single BE study is a novel approach and may overcome shortcomings of conventional bioequivalence assessment methods.
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http://dx.doi.org/10.2174/1872312814666210319124659DOI Listing
March 2021

Cytokine signaling pathway in cystic fibrosis: expression of SOCS and STATs genes in different clinical phenotypes of the disease.

Mol Cell Biochem 2021 Jul 19;476(7):2869-2876. Epub 2021 Mar 19.

Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

This was an observational cross-sectional study which was done to assess the expression profile of STATs and SOCS genes in cystic fibrosis. The mRNA was isolated from peripheral blood mononuclear cells of CF patients in exacerbation, colonization and post exacerbation phases of the disease. The relative gene expression level for SOCS 1, -3, -5 and STAT 1, -3,-4,-6 genes was quantified by Real-time PCR. The levels of IL-6 were also measured in the serum by ELISA. The expression of the Th1 pathway associated genes (SOCS1, SOCS5, STAT4 and STAT1) was downregulated while the expression of Th2/Th17 pathway genes (SOCS3, STAT3, STAT6) was upregulated in both exacerbation and colonization phases as compared to healthy controls. The serum levels of IL-6 were also elevated in both the disease groups. After antibiotic treatment, the expression of SOCS5 and STAT4 was increased while the expression of rest of the genes showed downregulation which shows a shift in immune response from Th2/Th17 to Th1. Our results suggest that infection alters the cytokine signaling pathway through modulation of STATs and SOCS genes which is not able to regulate the overstimulation of cytokine signaling further leading to chronic inflammation in CF.
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http://dx.doi.org/10.1007/s11010-021-04051-2DOI Listing
July 2021

Multiple roles of ABC transporters in yeast.

Fungal Genet Biol 2021 05 4;150:103550. Epub 2021 Mar 4.

Amity Institute of Integrative Science and Health, Amity Institute of Biotechnology, Amity University Gurgaon, 122413 Haryana, India. Electronic address:

The ATP binding cassette (ABC) transporters, first discovered as high-affinity nutrient importers in bacteria, rose to prominence when their ability to confer multidrug resistance (MDR) to cancer cells was realized. The most characterized human permeability glycoprotein (P-gp) is a dominant exporter of anti-cancer drugs and its overexpression is directly linked to MDR. The overexpression of drug efflux pumps belonging to the ABC superfamily is also a frequent cause of resistance to antifungals. Fungi has a battery of ABC proteins, but in variable numbers and at different subcellular locations. These proteins perform many critical functions, from serving as gatekeepers for xenobiotic cleansing to translocating various structurally unrelated cargoes, including lipids, fatty acids, ions, peptides, sterols, metabolites and toxins. Their emerging additional roles in cellular physiology and virulence call for attention to analyze and re-examine their divergent functions in yeast. In brief, this review traces the history of ABC transporters in yeast and discusses their typical physiological functions that go beyond their well-known role as antifungal drug efflux pumps.
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http://dx.doi.org/10.1016/j.fgb.2021.103550DOI Listing
May 2021

Apigenin prevents gamma radiation-induced gastrointestinal damages by modulating inflammatory and apoptotic signalling mediators.

Nat Prod Res 2021 Mar 5:1-5. Epub 2021 Mar 5.

Department of Biotechnology, Thiruvalluvar University, Vellore, Tamil Nadu, India.

The objective of this study was to evaluate the protective effect of apigenin against radiation-induced gastrointestinal (GI) damages in whole-body irradiated (WBI) Swiss albino mice. Swiss albino mice were pre-treated with apigenin (15 mg/kg body wt.) intraperitoneally for six consecutive days, and on the seventh day, the mice were exposed to 7 Gy WBI. Histological findings revealed a deterioration of the crypt-villus architecture in the 7 Gy irradiated mice intestine. Conversely, apigenin pre-treatment ameliorated radiation-induced intestinal damages and restored intestinal crypt-villus architecture. Besides, apigenin modulates 7 Gy radiation-induced apoptotic markers (p53, p21, Bax, caspase-3, -9) expression in the GI tissue of WBI mice. Furthermore, apigenin prevented radiation-induced activation of NF-kB expression in the GI tissue. Therefore, the present results indicate apigenin's radioprotective effect through modulating NF-kB mediated apoptotic signalling in the WBI intestinal tissue.
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http://dx.doi.org/10.1080/14786419.2021.1893316DOI Listing
March 2021

An Unusual Case of Anterior Abdominal wall Dialysate Leak Diagnosed with Tc99m-Sulfur Colloid Single-Photon Emission Computed Tomography/Computed Tomography Peritoneal Scintigraphy.

Indian J Nucl Med 2020 Oct-Dec;35(4):370-371. Epub 2020 Oct 21.

Department of Urology, Princess Esra Hospital, Hyderabad, Telangana, India.

Peritoneal dialysis (PD) was commonly used renal replacement therapy for treating end-stage renal failure patients leading to various infectious and mechanical complications. We present a case of a 50-year-old female patient who presented with reduced dialysate return and abdominal wall edema following continuous ambulatory PD. Peritoneal scintigraphy done on suspicion of dialysate leak shows tracer accumulation in the anterior abdominal wall below the insertion of the peritoneal catheter.
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http://dx.doi.org/10.4103/ijnm.IJNM_89_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905276PMC
October 2020

Synthesis and characterization of an injectable microparticles integrated hydrogel composite biomaterial: In-vivo biocompatibility and inflammatory arthritis treatment.

Colloids Surf B Biointerfaces 2021 May 2;201:111597. Epub 2021 Feb 2.

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay (IIT Bombay), Mumbai, India. Electronic address:

Polymeric hydrogels and microparticles have been widely used for localized drug delivery applications for the treatment of arthritis. Nonetheless, owing to initial burst drug release, non-specific biodistribution and low retention time at the target site in body, these polymeric drug delivery systems have been found with low in-vivo performance. Hence, the above limitations need to be resolved by designing a smart novel drug delivery system which is the current need in biomedicine. Herein, a novel localized injectable thermoresponsive microparticles embedded hydrogel composite drug delivery system has been developed for the treatment of inflammatory arthritis. In the current study, methotrexate (MTX) loaded alginate microparticles (MTX-Microparticles) are embedded into thermoreversible hydrogel matrix (MTX-MPs-H) prepared by physical blending of sodium hyaluronate and methylcellulose (SHMC). Microparticles-hydrogel composite system exhibited appropriate in-vitro thermoreversibility (sol at 4 °C and gel at 37 °C), biocompatibility (>80 %), hemocompatibility, and controlled drug release profile. The in-vivo biocompatibility studies for 10 days revealed that composite system is non-toxic in nature. The developed MTX-MPs-H composite drug delivery system effectively decreased the swelling/ inflammation of the arthritis affected paw in wistar rats in comparison to only alginate microparticles and pure MTX up to 30 days.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111597DOI Listing
May 2021

Retraction Note: Flavonoids modulate multidrug resistance through wnt signaling in P-glycoprotein overexpressing cell lines.

BMC Cancer 2021 Feb 11;21(1):151. Epub 2021 Feb 11.

Bioinformatics Infrastructure Facility (BIF), University of Madras, Guindy Campus, Chennai, Tamil Nadu, India.

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http://dx.doi.org/10.1186/s12885-021-07827-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877022PMC
February 2021

Copper and Zinc Status in Psoriasis: Correlation with Severity.

Indian J Clin Biochem 2021 Jan 1;36(1):120-123. Epub 2020 Jan 1.

Department of Biochemistry, MMIMSR, Mullana, Ambala, India.

Psoriasis is a common and an inflammatory skin disease. Trace elements play an important role in the skin metabolism such as keratinisation and melanin formation as well as immunological and inflammatory reactions. Henceforth, the present study was aimed to evaluate the essential metals with special reference to Cu and Zn. In this study, 72 psoriatic patients and 50 controls were enrolled. On the basis of PASI score psoriatic group comprising of 48 mild and 24 severe psoriatic patients were grouped. The serum trace elements analysis in the subjects revealed that serum Cu levels and Cu/Zn ratio was significantly higher in the psoriatic patients as compared to controls. Interestingly, severity of the psoriasis was well correlated with the serum Cu levels. Taking together, all these findings suggest that Cu may be a major culprit in the pathogenesis as well as in the severity of the disease.
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http://dx.doi.org/10.1007/s12291-019-00870-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817745PMC
January 2021

Directed Mutational Strategies Reveal Drug Binding and Transport by the MDR Transporters of .

J Fungi (Basel) 2021 Jan 20;7(2). Epub 2021 Jan 20.

Amity Institute of Biotechnology, Amity University Haryana, Gurgaon 122413, India.

Multidrug resistance (MDR) transporters belonging to either the ATP-Binding Cassette (ABC) or Major Facilitator Superfamily (MFS) groups are major determinants of clinical drug resistance in fungi. The overproduction of these proteins enables the extrusion of incoming drugs at rates that prevent lethal effects. The promiscuity of these proteins is intriguing because they export a wide range of structurally unrelated molecules. Research in the last two decades has used multiple approaches to dissect the molecular basis of the polyspecificity of multidrug transporters. With large numbers of drug transporters potentially involved in clinical drug resistance in pathogenic yeasts, this review focuses on the drug transporters of the important pathogen . This organism harbors many such proteins, several of which have been shown to actively export antifungal drugs. Of these, the ABC protein Cdr1 and the MFS protein Mdr1 are the two most prominent and have thus been subjected to intense site-directed mutagenesis and suppressor genetics-based analysis. Numerous results point to a common theme underlying the strategy of promiscuity adopted by both Cdr1 and Mdr1. This review summarizes the body of research that has provided insight into how multidrug transporters function and deliver their remarkable polyspecificity.
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http://dx.doi.org/10.3390/jof7020068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908972PMC
January 2021

Establishment of primary chicken embryo myoblast cell culture, antigenic epitopes prediction and production of anti activin receptor type IIB polyclonal antibody in chicken.

Anim Biotechnol 2021 Jan 24:1-14. Epub 2021 Jan 24.

Division of Animal Genetics and Breeding, Indian Veterinary Research Institute, Izatnagar, India.

The detection of activin receptor typeIIB ( protein, a prominent negative muscle growth regulator has paramount value in augmenting growth traits through molecular breeding schemes in chicken. The study was formulated to establish primary chicken embryo myoblast culture (CEM) using 9th and 18th day chick embryos and to develop antibodies for immunodetection of protein. The physicochemical and structural attributes of the sequence were evaluated to identify substantial antigenic regions. The sequence was transfected into CEM and expressed protein was injected subcutaneously into rats to produce hyperimmune serum. The average propensity of protein sequence for beta turns, surface accessibility, chain flexibility, antigenicity, hydrophilicity and linear epitopes was 0.978, 1.000, 0.991, 1.038, 1.258 and 0.512, respectively. The 9th day CEM exhibited confluency (80-90%) earlier than the 18th day. The expression of myogenic regulatory factors in 9th day myoblasts was higher than the 18th day by 7.28, 5.16, 6.28 and 6.93 folds for , MRF4, and , respectively. The mRNA was downregulated by 2.54 folds on the 9th day compared to the 18th day myoblasts and protein varied significantly between 9th and 18th day myoblasts. The CEM culture can be harnessed unequivocally to investigate molecular mechanisms underlying muscle growth besides raising antibodies.
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http://dx.doi.org/10.1080/10495398.2020.1870483DOI Listing
January 2021

ABCG: a new fold of ABC exporters and a whole new bag of riddles!

Adv Protein Chem Struct Biol 2021 4;123:163-191. Epub 2020 Dec 4.

Amity Institute of Biotechnology, Amity University Haryana, Gurgaon, Haryana, India; Amity Institute of Integrative Sciences and Health, Amity University Haryana, Gurgaon, Haryana, India.

ATP-binding cassette (ABC) superfamily comprises membrane transporters that power the active transport of substrates across biological membranes. These proteins harness the energy of nucleotide binding and hydrolysis to fuel substrate translocation via an alternating-access mechanism. The primary structural blueprint is relatively conserved in all ABC transporters. A transport-competent ABC transporter is essentially made up of two nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). While the NBDs are conserved in their primary sequence and form at their interface two nucleotide-binding sites (NBSs) for ATP binding and hydrolysis, the TMDs are variable among different families and form the translocation channel. Transporters catalyzing the efflux of substrates from the cells are called exporters. In humans, they range from A to G subfamilies, with the B, C and G subfamilies being involved in chemoresistance. The recently elucidated structures of ABCG5/G8 followed by those of ABCG2 highlighted a novel structural fold that triggered extensive research. Notably, suppressor genetics in the orthologous yeast Pleiotropic Drug Resistance (PDR) subfamily proteins have pointed to a crosstalk between TMDs and NBDs modulating substrate export. Considering the structural information provided by their neighbors from the G subfamily, these studies provide mechanistic keys and posit a functional role for the non-hydrolytic NBS found in several ABC exporters. The present chapter provides an overview of structural and functional aspects of ABCG proteins with a special emphasis on the yeast PDR systems.
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http://dx.doi.org/10.1016/bs.apcsb.2020.09.006DOI Listing
April 2021

High energy implementation of coil-target scheme for guided re-acceleration of laser-driven protons.

Sci Rep 2021 Jan 12;11(1):699. Epub 2021 Jan 12.

School of Mathematics and Physics, Queen's University Belfast, Belfast, BT71NN, UK.

Developing compact ion accelerators using intense lasers is a very active area of research, motivated by a strong applicative potential in science, industry and healthcare. However, proposed applications in medical therapy, as well as in nuclear and particle physics demand a strict control of ion energy, as well as of the angular and spectral distribution of ion beam, beyond the intrinsic limitations of the several acceleration mechanisms explored so far. Here we report on the production of highly collimated ([Formula: see text] half angle divergence), high-charge (10s of pC) and quasi-monoenergetic proton beams up to [Formula: see text] 50 MeV, using a recently developed method based on helical coil targetry. In this concept, ions accelerated from a laser-irradiated foil are post-accelerated and conditioned in a helical structure positioned at the rear of the foil. The pencil beam of protons was produced by guided post-acceleration at a rate of [Formula: see text] 2 GeV/m, without sacrificing the excellent beam emittance of the laser-driven proton beams. 3D particle tracing simulations indicate the possibility of sustaining high acceleration gradients over extended helical coil lengths, thus maximising the gain from such miniature accelerating modules.
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http://dx.doi.org/10.1038/s41598-020-77997-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804017PMC
January 2021

An effective assessment of cluster tendency through sampling based multi-viewpoints visual method.

J Ambient Intell Humaniz Comput 2021 Jan 4:1-14. Epub 2021 Jan 4.

Department of CSE, Koneru Lakshmaiah Education Foundation, Guntur, Andhra Pradesh India.

Social networks are the rich sources to people for sharing the knowledge on health-related issues. Nowadays, Twitter is one of the great significant social platforms to the people for a discussion on topics. Analyzing the clusters for the tweets concerning terms is a complex process due to the sparsity problem. Topic models are useful or avoiding this problem with derivations of topic clusters. Finding pre-cluster tendency is the major problem in many clustering methods. Existing methods, such as visual access tendency (VAT), cosine-based VAT (cVAT), multi viewpoints-based cosine similarity VAT (MVS-VAT) majorly used to access the prior information about clusters tendency problem. Solution of cluster tendency indicates the tractable number of clusters. The MVS-VAT enables the cluster tendency for the tweet documents effectively than other visual methods. However, it takes a higher number of viewpoints, thus requiring more computational time for the clustering of tweets data. Therefore, sampling-based visual methods are proposed to overcome the computational problem. Several standard health keywords are used for the extraction of health tweets to illustrate the effectiveness of proposed work in the experimental study.
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http://dx.doi.org/10.1007/s12652-020-02710-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779163PMC
January 2021
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