Publications by authors named "M V Padma Srivastava"

1,021 Publications

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Insights from a Pan India Sero-Epidemiological survey (Phenome-India Cohort) for SARS-CoV2.

Authors:
Salwa Naushin Viren Sardana Rajat Ujjainiya Nitin Bhatheja Rintu Kutum Akash Kumar Bhaskar Shalini Pradhan Satyartha Prakash Raju Khan Birendra Singh Rawat Karthik Bharadwaj Tallapaka Mahesh Anumalla Giriraj Ratan Chandak Amit Lahiri Susanta Kar Shrikant Ramesh Mulay Madhav Nilakanth Mugale Mrigank Srivastava Shaziya Khan Anjali Srivastava Bhawana Tomar Murugan Veerapandian Ganesh Venkatachalam Selvamani Raja Vijayakumar Ajay Agarwal Dinesh Gupta Prakash M Halami Muthukumar Serva Peddha Gopinath M Sundaram Ravindra P Veeranna Anirban Pal Vinay Kumar Agarwal Anil Ku Maurya Ranvijay Kumar Singh Ashok Kumar Raman Suresh Kumar Anandasadagopan Parimala Karuppanan Subramanian Venkatesan Harish Kumar Sardana Anamika Kothari Rishabh Jain Anupama Thakur Devendra Singh Parihar Anas Saifi Jasleen Kaur Virendra Kumar Avinash Mishra Iranna Gogeri Geethavani Rayasam Praveen Singh Rahul Chakraborty Gaura Chaturvedi Pinreddy Karunakar Rohit Yadav Sunanda Singhmar Dayanidhi Singh Sharmistha Sarkar Purbasha Bhattacharya Sundaram Acharya Vandana Singh Shweta Verma Drishti Soni Surabhi Seth Sakshi Vashisht Sarita Thakran Firdaus Fatima Akash Pratap Singh Akanksha Sharma Babita Sharma Manikandan Subramanian Yogendra S Padwad Vipin Hallan Vikram Patial Damanpreet Singh Narendra Vijay Tripude Partha Chakrabarti Sujay Krishna Maity Dipyaman Ganguly Jit Sarkar Sistla Ramakrishna Balthu Narender Kumar Kiran A Kumar Sumit G Gandhi Piyush Singh Jamwal Rekha Chouhan Vijay Lakshmi Jamwal Nitika Kapoor Debashish Ghosh Ghanshyam Thakkar Umakanta Subudhi Pradip Sen Saumya Ray Chaudhury Rashmi Kumar Pawan Gupta Amit Tuli Deepak Sharma Rajesh P Ringe Amarnarayan D Mahesh Kulkarni Dhansekaran Shanmugam Mahesh S Dharne Sayed G Dastager Rakesh Joshi Amita P Patil Sachin N Mahajan Abujunaid Habib Khan Vasudev Wagh Rakesh Kumar Yadav Ajinkya Khilari Mayuri Bhadange Arvindkumar H Chaurasiya Shabda E Kulsange Krishna Khairnar Shilpa Paranjape Jatin Kalita Narahari G Sastry Tridip Phukan Prasenjit Manna Wahengbam Romi Pankaj Bharali Dibyajyoti Ozah Ravi Kumar Sahu Elapavalooru Vssk Babu Rajeev Sukumaran Aiswarya R Nair Prajeesh Kooloth Valappil Anoop Puthiyamadam Adarsh Velayudhanpillai Kalpana Chodankar Samir Damare Yennapu Madhavi Ved Varun Aggarwal Sumit Dahiya Anurag Agrawal Debasis Dash Shantanu Sengupta

Elife 2021 Apr 20;10. Epub 2021 Apr 20.

Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.

To understand the spread of SARS-CoV2, in August and September 2020, the Council of Scientific and Industrial Research (India), conducted a sero-survey across its constituent laboratories and centers across India. Of 10,427 volunteers, 1058 (10.14%) tested positive for SARS CoV2 anti-nucleocapsid (anti-NC) antibodies; 95% of which had surrogate neutralization activity. Three-fourth of these recalled no symptoms. Repeat serology tests at 3 (n=607) and 6 (n=175) months showed stable anti-NC antibodies but declining neutralization activity. Local sero-positivity was higher in densely populated cities and was inversely correlated with a 30 day change in regional test positivity rates (TPR). Regional seropositivity above 10% was associated with declining TPR. Personal factors associated with higher odds of sero-positivity were high-exposure work (Odds Ratio, 95% CI, p value; 2∙23, 1∙92-2∙59, <0.0001), use of public transport (1∙79, 1∙43-2∙24, <0.0001), not smoking (1∙52, 1∙16-1∙99, 0∙0257), non-vegetarian diet (1∙67, 1∙41-1∙99, <0.0001), and B blood group (1∙36,1∙15-1∙61, 0∙001).
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http://dx.doi.org/10.7554/eLife.66537DOI Listing
April 2021

Inhibition of the DNA damage response to activate immune responses toward tumors.

FEBS J 2021 04 2. Epub 2021 Apr 2.

TIFR Centre for Interdisciplinary Sciences, Tata Institute of Fundamental Research (TIFR) Hyderabad, India.

Cancer immunotherapy represents a very encouraging mode of treatment for cancer where one's immune system is utilized to eliminate tumor cells. Wayne et al. explore inhibition of DNA damage response (DDR) pathways with small molecule inhibitors as a means to prime cells with immune response. These findings suggest that a one-size-fits-all approach cannot be used when harnessing immune response via DDR inhibitors and genotoxic agents, which are required ultimately for the success of immunotherapy.
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http://dx.doi.org/10.1111/febs.15836DOI Listing
April 2021

Transcriptomics of Long-Term Meditation Practice: Evidence for Prevention or Reversal of Stress Effects Harmful to Health.

Medicina (Kaunas) 2021 Mar 1;57(3). Epub 2021 Mar 1.

Department of Physiology and Health, Maharishi International University, Fairfield, IA 52556, USA.

Stress can overload adaptive mechanisms, leading to epigenetic effects harmful to health. Research on the reversal of these effects is in its infancy. Early results suggest some meditation techniques have health benefits that grow with repeated practice. This study focused on possible transcriptomic effects of 38 years of twice-daily Transcendental Meditation (TM) practice. First, using Illumina BeadChip microarray technology, differences in global gene expression in peripheral blood mononuclear cells (PBMCs) were sought between healthy practitioners and tightly matched controls ( = 12, age 65). Second, these microarray results were verified on a subset of genes using quantitative polymerase chain reaction (qPCR) and were validated using qPCR in larger TM and control groups ( = 45, age 63). Bioinformatics investigation employed Ingenuity Pathway Analysis (IPA), DAVID, Genomatix, and R packages. The 200 genes and loci found to meet strict criteria for differential expression in the microarray experiment showed contrasting patterns of expression that distinguished the two groups. Differential expression relating to immune function and energy efficiency were most apparent. In the TM group, relative to the control, all 49 genes associated with inflammation were downregulated, while genes associated with antiviral and antibody components of the defense response were upregulated. The largest expression differences were shown by six genes related to erythrocyte function that appeared to reflect a condition of lower energy efficiency in the control group. Results supporting these gene expression differences were obtained with qPCR-measured expression both in the well-matched microarray groups and in the larger, less well-matched groups. These findings are consistent with predictions based on results from earlier randomized trials of meditation and may provide evidence for stress-related molecular mechanisms underlying reductions in anxiety, post-traumatic stress disorder (PTSD), cardiovascular disease (CVD), and other chronic disorders and diseases.
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http://dx.doi.org/10.3390/medicina57030218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001870PMC
March 2021

Comparison of Quality of Life and Bone Mass Density among Postmenopausal Women: A Cross-sectional Study.

J Midlife Health 2020 Oct-Dec;11(4):224-230. Epub 2021 Jan 21.

Department of Physical Medicine and Rehabilitation, King George's Medical University, Lucknow, Uttar Pradesh, India.

Background: Postmenopausal women are at highest risk of developing osteoporosis, since their bone mineral density is reduced due to decrease in estrogen level. Various other physiological, emotional, and psychological changes jeopardize the health of these vulnerable females in total and reduce their quality of life (QoL).

Aims And Objectives: To compare the QoL and bone mass density (BMD) among normal BMD, osteopenic, and osteoporotic postmenopausal women.

Setting And Design: A cross-sectional observational study was conducted in the outpatient department of physical medicine and rehabilitation at a tertiary care center of northern India from August 2019 to February 2020.

Materials And Methods: Baseline sociodemographic characteristics of all postmenopausal women were collected using a quantitative tool. Assessment of QoL was done by pretested and validated QUALEFFO-41 scale. For all the women, a bone mineral densitometry test was performed on the L1-L4 lumbar spine, femoral neck, and forearm by the dual-energy X-ray absorptiometry method.

Statistical Analysis: One-way ANOVA test was used to compare the mean BMD values across the three groups. Determination of predictive factors for QoL was performed using stepwise logistic regression analysis.

Results: Significant differences were noted for the mean values of the three domains, i.e., pain, physical, and social function ( < 0.01). Women with osteoporosis had significantly higher pain scores as compared to others. Among those with osteoporosis, the pain scores have significantly increased gradually as age increases.

Conclusion: Postmenopausal women with osteopenia and osteoporosis have poor QoL as compared to those with normal BMD.
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http://dx.doi.org/10.4103/jmh.JMH_107_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978055PMC
January 2021

Terminally Differentiated CD4 T Cells Promote Myocardial Inflammaging.

Front Immunol 2021 19;12:584538. Epub 2021 Feb 19.

Comprehensive Heart Failure Centre, University Hospital Würzburg, Würzburg, Germany.

The cardiovascular and immune systems undergo profound and intertwined alterations with aging. Recent studies have reported that an accumulation of memory and terminally differentiated T cells in elderly subjects can fuel myocardial aging and boost the progression of heart diseases. Nevertheless, it remains unclear whether the immunological senescence profile is sufficient to cause age-related cardiac deterioration or merely acts as an amplifier of previous tissue-intrinsic damage. Herein, we sought to decompose the causality in this cardio-immune crosstalk by studying young mice harboring a senescent-like expanded CD4 T cell compartment. Thus, immunodeficient NSG-DR1 mice expressing HLA-DRB1*01:01 were transplanted with human CD4 T cells purified from matching donors that rapidly engrafted and expanded in the recipients without causing xenograft reactions. In the donor subjects, the CD4 T cell compartment was primarily composed of naïve cells defined as CCR7CD45RO. However, when transplanted into young lymphocyte-deficient mice, CD4 T cells underwent homeostatic expansion, upregulated expression of PD-1 receptor and strongly shifted towards effector/memory (CCR7 CD45RO) and terminally-differentiated phenotypes (CCR7CD45RO), as typically seen in elderly. Differentiated CD4 T cells also infiltrated the myocardium of recipient mice at comparable levels to what is observed during physiological aging. In addition, young mice harboring an expanded CD4 T cell compartment showed increased numbers of infiltrating monocytes, macrophages and dendritic cells in the heart. Bulk mRNA sequencing analyses further confirmed that expanding T-cells promote myocardial inflammaging, marked by a distinct age-related transcriptomic signature. Altogether, these data indicate that exaggerated CD4 T-cell expansion and differentiation, a hallmark of the aging immune system, is sufficient to promote myocardial alterations compatible with inflammaging in juvenile healthy mice.
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http://dx.doi.org/10.3389/fimmu.2021.584538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935504PMC
February 2021

Feasibility of combining functional near-infrared spectroscopy with electroencephalography to identify chronic stroke responders to cerebellar transcranial direct current stimulation-a computational modeling and portable neuroimaging methodological study.

Cerebellum 2021 Mar 6. Epub 2021 Mar 6.

University at Buffalo, Buffalo, NY, 14260, USA.

Feasibility of portable neuroimaging of cerebellar transcranial direct current stimulation (ctDCS) effects on the cerebral cortex has not been investigated vis-à-vis cerebellar lobular electric field strength. We studied functional near-infrared spectroscopy (fNIRS) in conjunction with electroencephalography (EEG) to measure changes in the brain activation at the prefrontal cortex (PFC) and the sensorimotor cortex (SMC) following ctDCS as well as virtual reality-based balance training (VBaT) before and after ctDCS treatment in 12 hemiparetic chronic stroke survivors. We performed general linear modeling (GLM) that putatively associated the lobular electric field strength with the changes in the fNIRS-EEG measures at the ipsilesional and contra-lesional PFC and SMC. Here, fNIRS-EEG measures were found in the latent space from canonical correlation analysis (CCA) between the changes in total hemoglobin (tHb) concentrations (0.01-0.07Hz and 0.07-0.13Hz bands) and log10-transformed EEG bandpower within 1-45 Hz where significant (Wilks' lambda>0.95) canonical correlations were found only for the 0.07-0.13-Hz band. Also, the first principal component (97.5% variance accounted for) of the mean lobular electric field strength was a good predictor of the latent variables of oxy-hemoglobin (O2Hb) concentrations and log10-transformed EEG bandpower. GLM also provided insights into non-responders to ctDCS who also performed poorly in the VBaT due to ideomotor apraxia. Future studies should investigate fNIRS-EEG joint-imaging in a larger cohort to identify non-responders based on GLM fitting to the fNIRS-EEG data.
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http://dx.doi.org/10.1007/s12311-021-01249-4DOI Listing
March 2021

Immunization with Calreticulin Protein Generates Robust Antiparasitic Immunity and Offers Protection during Experimental Lymphatic Filariasis.

ACS Infect Dis 2021 04 5;7(4):790-799. Epub 2021 Mar 5.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

Lymphatic filariasis causes permanent and long-term disability worldwide. Lack of potent adulticidal drugs, the emergence of drug resistance, and the nonavailability of effective vaccines are the major drawbacks toward LF elimination. However, immunomodulatory proteins present in the parasite secretome are capable of providing good protection against LF and thus offer hope in designing new vaccines against LF. Here, we evaluated the immunogenicity and protective efficacy of calreticulin protein (BmCRT) using and approaches. Stimulation with recombinant BmCRT (rBmCRT) significantly upregulated Th1 cytokine production in mouse splenocytes, mesenteric lymph nodes (mLNs), and splenic and peritoneal macrophages (PMΦs). Heightened NO release, ROS generation, increased lymphocyte proliferation, and increased antigen uptake were also observed after rBmCRT exposure. Mice immunized with rBmCRT responded with increased Th1 and Th2 cytokine secretion and exhibited highly elevated titers of anti-BmCRT specific IgG at day 14 and day 28 postimmunization while splenocytes and mLNs from immunized mice showed a robust recall response on restimulation with rBmCRT. Infective larvae (L3) challenge and protection studies undertaken in , a permissive model for LF, showed that rBmCRT-immunized animals mounted a robust humoral immune response as evident by elevated levels of total IgG, IgG1, IgG2a, IgG2b, and IgG3 in their serum even 150 days after L3 challenge, which led to significantly reduced microfilariae and worm burden in infected animals. BmCRT is highly immunogenic and generates robust antiparasitic immunity in immunized animals and should therefore be explored further as a putative vaccine candidate against LF.
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http://dx.doi.org/10.1021/acsinfecdis.0c00565DOI Listing
April 2021

SUMO enables substrate selectivity by mitogen-activated protein kinases to regulate immunity in plants.

Proc Natl Acad Sci U S A 2021 Mar;118(10)

Department of Biosciences, Durham University, DH1 3LE Durham, United Kingdom;

The versatility of mitogen-activated protein kinases (MAPKs) in translating exogenous and endogenous stimuli into appropriate cellular responses depends on its substrate specificity. In animals, several mechanisms have been proposed about how MAPKs maintain specificity to regulate distinct functional pathways. However, little is known of mechanisms that enable substrate selectivity in plant MAPKs. Small ubiquitin-like modifier (SUMO), a posttranslational modification system, plays an important role in plant development and defense by rapid reprogramming of cellular events. In this study we identified a functional SUMO interaction motif (SIM) in MPK3 and MPK6 that reveals a mechanism for selective interaction of MPK3/6 with SUMO-conjugated WRKY33, during defense. We show that WRKY33 is rapidly SUMOylated in response to infection and flg22 elicitor treatment. SUMOylation mediates WRKY33 phosphorylation by MPKs and consequent transcription factor activity. Disruption of either WRKY33 SUMO or MPK3/6 SIM sites attenuates their interaction and inactivates WRKY33-mediated defense. However, MPK3/6 SIM mutants show normal interaction with a non-SUMOylated form of another transcription factor, SPEECHLESS, unraveling a role for SUMOylation in differential substrate selectivity by MPKs. We reveal that the SUMO proteases, SUMO PROTEASE RELATED TO FERTILITY1 (SPF1) and SPF2 control WRKY33 SUMOylation and demonstrate a role for these SUMO proteases in defense. Our data reveal a mechanism by which MPK3/6 prioritize molecular pathways by differentially selecting substrates using the SUMO-SIM module during defense responses.
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http://dx.doi.org/10.1073/pnas.2021351118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958252PMC
March 2021

CPAP adherence is associated with reduced risk for stroke among older adult Medicare beneficiaries with obstructive sleep apnea.

J Clin Sleep Med 2021 Feb 22. Epub 2021 Feb 22.

Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD.

Study Objectives: To examine the impact of adherence to continuous positive airway pressure (CPAP) therapy on risk for stroke among a nationally representative sample of older adults with obstructive sleep apnea (OSA).

Methods: We performed a retrospective cohort study among Medicare beneficiaries aged ≥65 years who were newly diagnosed with OSA and initiated CPAP (2009-2013). Monthly indicators of CPAP adherence included charges for machines, masks, or supplies and were summed over 25-month follow-up to create a CPAP adherence variable. Stroke was modelled as a function of CPAP adherence using generalized estimating equations.

Results: 5,757 beneficiaries met inclusion criteria and were included in the final sample. Of these, 407 (7%) experienced stroke. After adjusting for demographic and clinical characteristics, CPAP adherence was associated with reduced risk of stroke (hazard ratio 0.98; 95% confidence interval 0.96, 0.99) over 25 months, indicating a 2% reduction in risk of stroke for each month of CPAP adherence. When sensitivity analyses were performed to stratify results by time since first CPAP charge, the protective effect remained significant for the 12- and 6-month, but not 3-month, outcome models.

Conclusions: In this national analysis of older adult Medicare beneficiaries with OSA, CPAP adherence was associated with significantly reduced risk for stroke.
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http://dx.doi.org/10.5664/jcsm.9176DOI Listing
February 2021

Elucidation of Structural Determinants Delineates the Residues Playing Key Roles in Differential Dynamics and Selective Inhibition of Sirt1-3.

J Chem Inf Model 2021 Mar 19;61(3):1105-1124. Epub 2021 Feb 19.

Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana 121001, India.

Sirt1-3 are the most studied sirtuins, playing a key role in caloric-dependent epigenetic modifications. Since they are localized in distinct cellular compartments and act differently under various pathological conditions, selective inhibition would be a promising strategy to understand their biological function and to discover effective therapeutics. Here, sirtuin's inhibitor Ex527* is used as a probe to speculate the possible root cause of selective inhibition and differential structural dynamics of Sirt1-3. Comparative energetics and mutational studies revealed the criticality of residues I279 and I316 for the Sirt1 selectivity toward Ex527*. Furthermore, essential dynamics and residue network analysis revealed that the side-chain reorientation in residue F190 due to nonconserved residue Y191 played a major role in the formation of an extended selectivity pocket in Sirt2. These changes at the dynamical and residual level, which impact the internal wiring significantly, might help in rationally designing selective inhibitors against Sirt1-3.
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http://dx.doi.org/10.1021/acs.jcim.0c01193DOI Listing
March 2021

Neuronal inclusions resembling Negri bodies in the thalamus of a red kangaroo (Macropus rufus).

Aust Vet J 2021 Feb 8. Epub 2021 Feb 8.

Department of Primary Industries, Elizabeth Macarthur Agricultural Institute, Menangle, New South Wales, 2568, Australia.

Eosinophilic intracytoplasmic neuronal inclusions resembling Negri bodies, but not associated with lyssaviral infection, were detected in the ventrolateral thalamus of a young-adult, male red kangaroo (Macropus rufus). Similar neuronal inclusions, also with a regional distribution in the brain, have been reported as an incidental, possibly age-related finding in other animal species.
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http://dx.doi.org/10.1111/avj.13057DOI Listing
February 2021

Immunological characterization of chimeras of high specificity antigens from Mycobacterium tuberculosis H37Rv.

Tuberculosis (Edinb) 2021 Mar 28;127:102054. Epub 2021 Jan 28.

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

Tuberculosis remains a serious global health problem. BCG is the only prophylactic TB vaccine and it shows variable protective efficacy. Chimeric protein subunit vaccines hold great potential as stand-alone vaccines or heterologous BCG prime boosters. We have designed a protein chimera, PP31, by combining Mtb ESAT-6 family antigen Rv1198 and MoCo biosynthesis family antigen Rv3111. Further, PP31 was extended by addition of latency antigen Rv1813c to yield PP43. Immunization of BALB/c mice with PP31 or PP43 with FIA adjuvant elicited strong humoral immune response. Restimulation of splenocytes of the immunized mice lead to significant proliferation of lymphocytes, secretion of cytokines IFN-γ, TNF, IL-2 of the Th1 class, IL-17A of the Th17 class, and IL-6. PP31 and PP43 also induced intracellular cytokine expression (IFN-γ, TNF, and IL-2) from both CD4-CD44 and CD8-CD44 T-cells. Antigen-specific IFN-γ/IL-2 double positive CD4 T-cells were significantly higher in case of PP43 than PP31-immunized mice and control group. PP43 showed protection equivalent to heat-inactivated BCG in response to challenge of the immunized mice with Mtb H37Ra. Based on its immunogenicity and protective efficacy, PP43 appears to be a potential candidate for further development as a subunit vaccine against TB.
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http://dx.doi.org/10.1016/j.tube.2021.102054DOI Listing
March 2021

Efficacy of Low-Frequency Repetitive Transcranial Magnetic Stimulation in Ischemic Stroke: A Double-Blind Randomized Controlled Trial.

Arch Rehabil Res Clin Transl 2020 Mar 11;2(1):100039. Epub 2020 Jan 11.

Department of Neurology, All India Institutes of Medical Sciences, New Delhi.

Objective: To investigate the role of low-frequency repetitive transcranial magnetic stimulation (rTMS) along with conventional physiotherapy in the functional recovery of patients with subacute ischemic stroke.

Design: Double-blind, parallel group, randomized controlled trial.

Setting: The outpatient department of a tertiary hospital participants: first ever ischemic stroke patients (N=96) in the previous 15 days were recruited and were randomized after a run-in period of 75±7 days into real rTMS (n=47) and sham rTMS (n=49) groups.

Intervention: Conventional physical therapy was given to both the groups for 90±7 days postrecruitment. Total 10 sessions of low-frequency rTMS on contralesional premotor cortex was administered to real rTMS group (n=47) over a period of 2 weeks followed by physiotherapy regime for 45-50 minutes.

Main Outcome Measures: The primary efficacy outcomes were change in modified Barthel Index (mBI) score (pre- to postscore) and proportion of participants with mBI score more than 90, measured at 90±7 days postrecruitment. The secondary outcomes were change in Fugl-Meyer Assessment-upper extremity, Fugl-Meyer Assessment-lower extremity, Hamilton Depression Scale, modified Rankin Scale, and National Institute of Health and Stroke Scale (pre- to post-rTMS) scores at 90±7 days post recruitment.

Results: Modified intention to treat analysis showed a significant increase in the mBI score from pre- to post-rTMS in real rTMS group (4.96±4.06) versus sham rTMS group (2.65±3.25). There was no significant difference in proportion of patients with mBI>90 (55% vs 59%; =.86) at 3 months between the groups.

Conclusion: In patients with subacute ischemic stroke, 1-Hz low-frequency rTMS on contralesional premotor cortex along with conventional physical therapy resulted in significant change in mBI score.
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http://dx.doi.org/10.1016/j.arrct.2020.100039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853333PMC
March 2020

Biohydrogen production using kitchen waste as the potential substrate: A sustainable approach.

Chemosphere 2021 May 4;271:129537. Epub 2021 Jan 4.

Biorefining and Advanced Materials Research Center, Scotland's Rural College (SRUC), Kings Buildings, West Mains Road, Edinburgh, EH9 3JG, UK; Center for Safe and Improved Food, Scotland's Rural College (SRUC), Kings Buildings, West Mains Road, Edinburgh, EH9 3JG, UK. Electronic address:

This review explores the sustainable feasibility of kitchen wastes to implement as an effective substrate for biohydrogen production through dark fermentation. Being organic in nature, kitchen wastes are enomerous source of nutrients and carbohydrate, which are produced in huge quantity in our daily life, and therefore can be potentially used for biohydrogen production through microbial technique. The review discussed in detail about the impact of kitchen waste, its availability and sustainability on the biohydrogen production process along with future scope at industrial scale for the production of sustainable and renewable energy. In addition, recent advances, and their possibility to enhance the fermentative biohydrogen production using kitchen waste have been covered. Emphasis is also made on the application of nanomaterials to increase the yield of biohydrogen production and to make the entire process more economical and sustainable while using kitchen wastes as substrate for the microbial fermentation. Finally, advantages, limitations and future prospects of the process of biohydrogen production using kitchen wastes as potential substrate have been discussed.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129537DOI Listing
May 2021

Transcriptome-wide high-throughput mapping of protein-RNA occupancy profiles using POP-seq.

Sci Rep 2021 Jan 13;11(1):1175. Epub 2021 Jan 13.

Department of BioHealth Informatics, School of Informatics and Computing, Indiana University Purdue University, Informatics and Communications Technology Complex, IT475H, 535 West Michigan Street, Indianapolis, IN, 46202, USA.

Interaction between proteins and RNA is critical for post-transcriptional regulatory processes. Existing high throughput methods based on crosslinking of the protein-RNA complexes and poly-A pull down are reported to contribute to biases and are not readily amenable for identifying interaction sites on non poly-A RNAs. We present Protein Occupancy Profile-Sequencing (POP-seq), a phase separation based method in three versions, one of which does not require crosslinking, thus providing unbiased protein occupancy profiles on whole cell transcriptome without the requirement of poly-A pulldown. Our study demonstrates that ~ 68% of the total POP-seq peaks exhibited an overlap with publicly available protein-RNA interaction profiles of 97 RNA binding proteins (RBPs) in K562 cells. We show that POP-seq variants consistently capture protein-RNA interaction sites across a broad range of genes including on transcripts encoding for transcription factors (TFs), RNA-Binding Proteins (RBPs) and long non-coding RNAs (lncRNAs). POP-seq identified peaks exhibited a significant enrichment (p value < 2.2e-16) for GWAS SNPs, phenotypic, clinically relevant germline as well as somatic variants reported in cancer genomes, suggesting the prevalence of uncharacterized genomic variation in protein occupied sites on RNA. We demonstrate that the abundance of POP-seq peaks increases with an increase in expression of lncRNAs, suggesting that highly expressed lncRNA are likely to act as sponges for RBPs, contributing to the rewiring of protein-RNA interaction network in cancer cells. Overall, our data supports POP-seq as a robust and cost-effective method that could be applied to primary tissues for mapping global protein occupancies.
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http://dx.doi.org/10.1038/s41598-020-80846-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806670PMC
January 2021

Acidic Calcium-Independent Phospholipase A2 Regulates Eosinophil-Mediated Pathology during Filarial Manifestation of Tropical Pulmonary Eosinophilia.

J Immunol 2021 Feb 13;206(4):722-736. Epub 2021 Jan 13.

Molecular Parasitology and Immunology Division, Council of Scientific and Industrial Research-Central Drug Research Institute, Lucknow 226031, India; and

Eosinophils mediate pathological manifestations during tropical pulmonary eosinophilia (TPE), a potentially fatal complication of lymphatic filariasis, by mechanisms that are incompletely understood. Using two-dimensional gel electrophoresis, mass spectrometry, flow cytometry, and pharmacological and functional studies, we identified acidic calcium-independent phospholipase A2 (aiPLA2) as the master regulator of TPE pathogenesis. FACS-sorted lung eosinophils from TPE mice exhibited aiPLA2-dependent activation characterized by heavy calcium influx, F-actin polymerization, increased degranulation, and heightened reactive oxygen species generation. Interestingly, aiPLA2 also promoted alternative activation in lung macrophages and regulated the release of inflammatory intermediates from them. Treatment of TPE mice with MJ33, a nontoxic pharmacological inhibitor of aiPLA2, lowered eosinophil counts in the bronchoalveolar lavage fluid, reduced eosinophil peroxidase and β-hexosaminidase activity, increased airway width, improved lung endothelial barrier, and lowered the production of inflammatory lipid intermediates, which significantly improved the pathological condition of the lungs. Importantly, ex vivo reconstitution of arachidonic acid to eosinophils from MJ33-treated TPE mice increased eosinophil degranulation and inflammatory lipid intermediates underlining the pivotal role of aiPLA2 in arachidonic acid metabolism. Mechanistically, phosphorylation of JNK-1 regulated phospholipase activity of aiPLA2, whereas IgG cross-linking mediated pathological activation of eosinophils. Taken together, ours is the first study, to our knowledge, to report hitherto undocumented role of aiPLA2 in regulating TPE pathogenesis.
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http://dx.doi.org/10.4049/jimmunol.2000604DOI Listing
February 2021

Interplay among Structural Stability, Plasticity, and Energetics Determined by Conformational Attuning of Flexible Loops in PD-1.

J Chem Inf Model 2021 Jan 12;61(1):358-384. Epub 2021 Jan 12.

NCR Biotech Science Cluster, Translational Health Science and Technology Institute (THSTI), 3rd Milestone, Faridabad-Gurugram Expressway, Faridabad, Haryana 121001, India.

The dynamics and plasticity of the PD-1/PD-L1 axis are the bottlenecks for the discovery of small-molecule antagonists to perturb this interaction interface significantly. Understanding the process of this protein-protein interaction (PPI) is of fundamental biological interest in structure-based drug designing. Food and Drug Administration (FDA)-approved anti-PD-1 monoclonal antibodies (mAbs) are the first-in-class with distinct binding modes to access this axis clinically; however, their mechanistic aspects remain elusive. Here, we have unveiled the interactive interfaces with PD-L1 and mAbs to investigate the native plasticity of PD-1 at global (structural and dynamical) and local (residue side-chain orientations) levels. We found that the structural stability and coordinated C movements are increased in the presence of PD-1's binding partners. The rigorous analysis of these PPIs using computational biophysical approaches revealed PD-1's intrinsic plasticity, its concerted loops' movement (BC, FG, and CC'), distal side-chain motions, and the thermodynamic landscape, which are perturbed remarkably from its unbound to bound states. Based on intra-/inter-residues' contact networks and energetics, the have been identified that were found to be essential to arrest the dynamical motions of PD-1 significantly for the rational design of therapeutic agents by mimicking the mAbs mechanism.
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http://dx.doi.org/10.1021/acs.jcim.0c01080DOI Listing
January 2021

Case Report: Isolated Central Nervous System Melioidosis from a Non-Endemic Area.

Am J Trop Med Hyg 2021 Jan 11. Epub 2021 Jan 11.

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

Central nervous system (CNS) melioidosis is a rare neurological infectious disease which carries a high mortality. We describe a previously healthy middle-aged female, who presented to us with left-sided hemiparesis and was on antitubercular therapy from a previous presumed diagnosis of CNS tuberculoma. Non-characteristic imaging picture, multiple negative body fluid cultures, and positive Cerebrospinal fluid galactomannan led to a further delay in diagnosis. Gram stain of the tissue obtained from brain biopsy revealed Gram-negative rods in "safety pin" appearance. By picking up the colonies that appeared on blood agar and MacConkey agar, the identification of the clinical isolates was performed using VITEK matrix (BioMerieux)-assisted laser desorption ionization time-of-flight mass spectrometry (VITEK MALDI TOF MS database version 3.2) which revealed . After the institution of appropriate treatment, she survived but with significant morbidity. A high index of suspicion should be kept for such previously healthy individuals belonging to non-endemic areas, where presentation is suspicious of an infective etiology, but not improving despite appropriate therapy. This may help in early recognition and institution of recommended treatment so that mortality can be avoided.
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http://dx.doi.org/10.4269/ajtmh.20-1166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045644PMC
January 2021

Characterization of transcripts emanating from enhancer Eβ of the murine TCRβ locus.

FEBS Open Bio 2021 Apr 16;11(4):1014-1028. Epub 2021 Mar 16.

Epigenetics Research Laboratory, National Institute of Immunology, New Delhi, India.

Enhancers are well established as critical regulators of gene expression, but the mechanisms underlying the molecular basis of their specificity and activity are only partly understood. One of the most exciting recent observations is the discovery of enhancer RNA (eRNA), a class of noncoding RNAs derived from enhancer regions. Transcription of developmentally regulated enhancers has been observed to be associated with their active state. The nature of transcripts (eRNA) and their functional attributes are diverse and context dependent. The majority of eRNA are nonpolyadenylated and present in low abundance owing to their low stability, and may represent transcriptional noise. However, some eRNAs have been reported to be reasonably long and stable, are enriched in nuclei, exhibit tissue-specific expression and may contribute to enhancer function. Transcription of enhancers has been postulated to mediate enhancer function through either the act of transcription or via the transcribed RNA per se and is a useful feature to be analysed to understand mechanisms underlying enhancer activity. Enhancer Eβ at the murine TCRβ locus has been reported to exhibit enhanced occupancy of RNA polymerase II in developing thymocytes. Here, we investigated the transcriptional potential of Eβ in developing thymocytes and detected overlapping bidirectional transcripts at Eβ ranging between 0.7 and 1.7 kb. These noncoding transcripts are capped, polyadenylated, nuclear and expressed specifically in thymocytes. Delineation of these characteristics is important to further investigate their functional roles in mediating enhancer activity.
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http://dx.doi.org/10.1002/2211-5463.13079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016127PMC
April 2021

Identification and characterization of in vitro and in vivo fidarestat metabolites: Toxicity and efficacy evaluation of metabolites.

J Mass Spectrom 2021 Feb;56(2):e4694

Analytical Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.

The progression of diabetic complications can be prevented by inhibition of aldose reductase and fidarestat considered to be highly potent. To date, metabolites of the fidarestat, toxicity, and efficacy are unknown. Therefore, the present study on characterization of hitherto unknown in vitro and in vivo metabolites of fidarestat using liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) is undertaken. In vitro and in vivo metabolites of fidarestat have been identified and characterized by using LC/ESI/MS/MS and accurate mass measurements. To identify in vivo metabolites, plasma, urine, and feces samples were collected after oral administration of fidarestat to Sprague-Dawley rats, whereas for in vitro metabolites, fidarestat was incubated in human S9 fraction, human liver microsomes, and rat liver microsomes. Furthermore, in silico toxicity and efficacy of the identified metabolites were evaluated. Eighteen metabolites have been identified. The main in vitro phase I metabolites of fidarestat are oxidative deamination, oxidative deamination and hydroxylation, reductive defluroniation, and trihydroxylation. Phase II metabolites are methylation, acetylation, glycosylation, cysteamination, and glucuronidation. Docking studies suggest that oxidative deaminated metabolite has better docking energy and conformation that keeps consensus with fidarestat whereas the rest of the metabolites do not give satisfactory results. Aldose reductase activity has been determined for oxidative deaminated metabolite (F-1), and it shows an IC50 value of 0.44 μM. The major metabolite, oxidative deaminated, did not show any cytotoxicity in H9C2, HEK, HEPG2, and Panc1 cell lines. However, in silico toxicity, the predication result showed toxicity in skin irritation and ocular irritancy SEV/MOD versus MLD/NON (v5.1) model for fidarestat and its all metabolites. In drug discovery and development research, it is distinctly the case that the potential for pharmacologically active metabolites must be considered. Thus, the active metabolites of fidarestat may have an advantage as drug candidates as many drugs were initially observed as metabolites.
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http://dx.doi.org/10.1002/jms.4694DOI Listing
February 2021

Effect of Periodic Water Clusters on AISI 304 Welded Surfaces.

Materials (Basel) 2021 Jan 4;14(1). Epub 2021 Jan 4.

Faculty of Manufacturing Technologies, Technical University of Kosice, Prešov, Bayerova 1, 080 01 Presov, Slovakia.

This study compared the effect of the interaction time of periodic water clusters on the surface integrity of AISI 304 tungsten inert gas (TIG) welded joints at different excitation frequencies, as the effect of the technological parameters of pulsating water jet (PWJ) on the mechanical properties of TIG welded joints are under-researched. The TIG welded joints were subjected to different frequencies (20 and 40 kHz) and traverse speeds (1-4 mm/s) at a water pressure of 40 MPa and a standoff distance of 70 mm. The effect of the interaction of the pulsating jet on the material and the enhancement in its mechanical properties were compared through residual stress measurements, surface roughness, and sub-surface microhardness. A maximum enhancement in the residual stress values of up to 480 MPa was observed in the heat-affected zone, along with a maximum roughness of 6.03 µm and a maximum hardness of 551 HV using a frequency of 40 kHz. The improvement in the surface characteristics of the welded joints shows the potential of utilizing pulsed water jet technology with an appropriate selection of process parameters in the treatment of welded structures.
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http://dx.doi.org/10.3390/ma14010210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795861PMC
January 2021

APX005M, a CD40 agonist antibody with unique epitope specificity and Fc receptor binding profile for optimal therapeutic application.

Cancer Immunol Immunother 2021 Jan 3. Epub 2021 Jan 3.

Apexigen, Inc, 75 Shoreway Road, Suite C, San Carlos, CA, 94070, USA.

Targeting CD40 with agonist antibodies is a promising approach to cancer immunotherapy. CD40 acts as a master regulator of immunity by mobilizing multiple arms of the immune system to initiate highly effective CD8 + T-cell-mediated responses against foreign pathogens and tumors. The clinical development of CD40 agonist antibodies requires careful optimization of the antibody to maximize therapeutic efficacy while minimizing adverse effects. Both epitope specificity and isotype are critical for CD40 agonist antibody mechanism of action and potency. We developed a novel antibody, APX005M, which binds with high affinity to the CD40 ligand-binding site on CD40 and is optimized for selective interaction with Fcγ receptors to enhance agonistic potency while limiting less desirable Fc-effector functions like antibody-dependent cellular cytotoxicity of CD40-expressing immune cells. APX005M is a highly potent inducer of innate and adaptive immune effector responses and represents a promising CD40 agonist antibody for induction of an effective anti-tumor immune response with a favorable safety profile.
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http://dx.doi.org/10.1007/s00262-020-02814-2DOI Listing
January 2021

Standoff Distance in Ultrasonic Pulsating Water Jet.

Materials (Basel) 2020 Dec 27;14(1). Epub 2020 Dec 27.

Faculty of Manufacturing Technologies, Technical University of Kosice, Prešov, Bayerova 1, 080 01 Presov, Slovakia.

The water hammer effect is the basis of technologies which is artificially responsible for the decay of continuous jets. A recently developed technique enhances the pressure fluctuations using an acoustic chamber, leading to enhanced erosion effects for various water volume flow rates. The optimum standoff distance for an ultrasonic enhanced water jet is not appropriately estimated using an inclined trajectory. The objective of this study is to comprehend the true nature of the interaction of the standoff distance following the stair trajectory and traverse speed of the nozzle on the erosion depth. Additionally, it also critically compares the new method (staircase trajectory) that obeys the variation in frequency of the impingements for defined volume flow rates with the inclined trajectory. In this study, at constant pressure ( = 70 MPa), the role of impingement distribution with the variation of traverse speed ( = 5-35 mm/s) along the centerline of the footprint was investigated. The maximum erosion depth corresponding to each traverse speed is observed at approximately same standoff distance (65 ± 5 mm) and decreases with the increment in traverse speed (= 1042 and 47 µm at = 5 and 35 mm/s, respectively). The results are attributed to the variation in the number of impingements per unit length. The surface and morphology analysis of the cross-section using SEM manifested the presence of erosion characteristics (micro-cracks, cavities, voids, and upheaved surface). By varying the water cluster, different impingement densities can be achieved that are suitable for technological operations such as surface peening, material disintegration, or surface roughening.
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http://dx.doi.org/10.3390/ma14010088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795501PMC
December 2020

Ion transfer channel network formed by flower and rod shape crystals of hair hydrolysate in poly(vinyl alcohol) matrix and its application as anion exchange membrane in fuel cells.

J Colloid Interface Sci 2021 Apr 9;587:214-228. Epub 2020 Dec 9.

Department of Chemical Engineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India. Electronic address:

Ion transfer phenomena occurring in nature are known to be most efficient. Many efforts have been made to mimic such phenomena, especially in the area of energy transfer. Proteins consisting of various amino acids are known to be the fundamental materials behind these phenomena. In the current study, an effort was made to extract proteinaceous material from human hair bio-waste by a green chemical-free thermal hydrolysis process. A simple heat treatment of the human hairs in presence of water led to the formation of a water soluble material, which was called hair hydrolysate (HH), contains 70 wt% proteinaceous material. It was utilized for the fabrication of poly(vinyl alcohol) (PVA) matrix-based anion exchange membrane (AEM). Presence of 27 wt% charged amino acids and 19 wt% polarizable amino acids in the HH provided effective charge transfer sites. 7 wt% arginine present in the HH, having continuous delocalized net positive charge helped the membrane to be stable in highly alkaline conditions, which was confirmed by an indirect analysis of alkaline stability. Formation of rod and flower shaped crystal morphology by the HH in glutaraldehyde crosslinked PVA matrix, created a continuous channel network at higher loadings, which provided a simple path for ion transfer, achieving OH conductivity of 7.46 mS/cm at 70 °C. Swelling of the PVA matrix was minimized by annealing of the HH loaded sample, which resulted in reduction of ionic conductivity to 6.16 mS/cm (at 70 °C). At the same time, improvement in the properties like increase in thermal, mechanical and thermo-mechanical stability, reduction in water uptake, %swelling and methanol permeability was observed. The selectivity of the membrane was increased to almost a decimal place. Thus, the HH obtained from simple green thermal hydrolysis of human hair bio-waste is a cheap material, which is found to be suitable as ion conductive material for alkaline fuel cells.
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http://dx.doi.org/10.1016/j.jcis.2020.12.012DOI Listing
April 2021

An Insight into the Factors Influencing Specificity of the SUMO System in Plants.

Plants (Basel) 2020 Dec 17;9(12). Epub 2020 Dec 17.

Department of Biosciences, Durham University, Stockton Road, Durham DH1 3LE, UK.

Due to their sessile nature, plants are constantly subjected to various environmental stresses such as drought, salinity, and pathogen infections. Post-translational modifications (PTMs), like SUMOylation, play a vital role in the regulation of plant responses to their environment. The process of SUMOylation typically involves an enzymatic cascade containing the activation, (E1), conjugation (E2), and ligation (E3) of SUMO to a target protein. Additionally, it also requires a class of SUMO proteases that generate mature SUMO from its precursor and cleave it off the target protein, a process termed deSUMOylation. It is now clear that SUMOylation in plants is key to a plethora of adaptive responses. How this is achieved with an extremely limited set of machinery components is still unclear. One possibility is that novel SUMO components are yet to be discovered. However, current knowledge indicates that only a small set of enzymes seem to be responsible for the modification of a large number of SUMO substrates. It is yet unknown where the specificity lies within the SUMO system. Although this seems to be a crucial question in the field of SUMOylation studies, not much is known about the factors that provide specificity. In this review, we highlight the role of the localisation of SUMO components as an important factor that can play a vital role in contributing to the specificity within the process. This will introduce a new facet to our understanding of the mechanisms underlying such a dynamic process.
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http://dx.doi.org/10.3390/plants9121788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767294PMC
December 2020

An Acquired Neuro-Nephrology Syndrome.

J Clin Rheumatol 2020 Dec 14. Epub 2020 Dec 14.

From the Departments of Neurology.

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http://dx.doi.org/10.1097/RHU.0000000000001663DOI Listing
December 2020

Treatment With Mifepristone Allows a Patient With End-stage Pancreatic Cancer in Hospice on a Morphine Drip to Restore a Decent Quality of Life.

Anticancer Res 2020 Dec 7;40(12):6997-7001. Epub 2020 Dec 7.

Division of Gynecologic Oncology, Cooper Medical School of Rowan University, Camden, NJ, U.S.A.

Background: There is evidence that a unique immunomodulatory protein, known as the progesterone induced blocking factor (PIBF), is utilized by a large variety of cancers to escape immune surveillance. Mifepristone, a progesterone receptor antagonist/modulator, anecdotally, has been found to increase both length and quality of life in many different types of advanced cancers.

Case Report: Though there was one previous case of pancreatic cancer that showed a significant reduction in pain for the one month she took mifepristone before changing to an experimental drug, the case presented here provided much greater evidence that this drug can markedly improve both length and quality of life, in at least some patients, with very advanced pancreatic cancer.

Conclusion: It is hoped that this case report will influence others to prescribe mifepristone off-label and hopefully substantiate this finding of marked palliative benefit in the majority of a larger series of patients.
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http://dx.doi.org/10.21873/anticanres.14724DOI Listing
December 2020

Prospects of nanomaterials-enabled biosensors for COVID-19 detection.

Sci Total Environ 2021 Feb 16;754:142363. Epub 2020 Sep 16.

Nano-Bioelectronics Laboratory, Department of Biotechnology, Delhi Technological University, Main Bawana Road, Delhi 110042, India. Electronic address:

We are currently facing the COVID-19 pandemic which is the consequence of severe acute respiratory syndrome coronavirus (SARS-CoV-2). Since no specific vaccines or drugs have been developed till date for the treatment of SARS-CoV-2 infection, early diagnosis is essential to further combat this pandemic. In this context, the reliable, rapid, and low-cost technique for SARS-CoV-2 diagnosis is the foremost priority. At present reverse transcription polymerase chain reaction (RT-PCR) is the reference technique presently being used for the detection of SARS-CoV-2 infection. However, in a number of cases, false results have been noticed in COVID-19 diagnosis. To develop advanced techniques, researchers are continuously working and in the series of constant efforts, nanomaterials-enabled biosensing approaches can be a hope to offer novel techniques that may perhaps meet the current demand of fast and early diagnosis of COVID-19 cases. This paper provides an overview of the COVID-19 pandemic and nanomaterials-enabled biosensing approaches that have been recently reported for the diagnosis of SARS-CoV-2. Though limited studies on the development of nanomaterials enabled biosensing techniques for the diagnosis of SARS-CoV-2 have been reported, this review summarizes nanomaterials mediated improved biosensing strategies and the possible mechanisms that may be responsible for the diagnosis of the COVID-19 disease. It is reviewed that nanomaterials e.g. gold nanostructures, lanthanide-doped polysterene nanoparticles (NPs), graphene and iron oxide NPs can be potentially used to develop advanced techniques offered by colorimetric, amperometric, impedimetric, fluorescence, and optomagnetic based biosensing of SARS-CoV-2. Finally, critical issues that are likely to accelerate the development of nanomaterials-enabled biosensing for SARS-CoV-2 infection have been discussed in detail. This review may serve as a guide for the development of advanced techniques for nanomaterials enabled biosensing to fulfill the present demand of low-cost, rapid and early diagnosis of COVID-19 infection.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492839PMC
February 2021