Publications by authors named "Amit Singh"

727 Publications

Global Transcriptome Characterization and Assembly of the Thermophilic Ascomycete .

Genes (Basel) 2021 Sep 29;12(10). Epub 2021 Sep 29.

Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany.

A correct genome annotation is fundamental for research in the field of molecular and structural biology. The annotation of the reference genome of has been reported previously, but it is essentially limited to open reading frames (ORFs) of protein coding genes and contains only a few noncoding transcripts. In this study, we identified and annotated full-length transcripts of by deep RNA sequencing. We annotated 7044 coding genes and 4567 noncoding genes. Astonishingly, 23% of the coding genes are alternatively spliced. We identified 679 novel coding genes as well as 2878 novel noncoding genes and corrected the structural organization of more than 50% of the previously annotated genes. Furthermore, we substantially extended the Gene Ontology (GO) and Enzyme Commission (EC) lists, which provide comprehensive search tools for potential industrial applications and basic research. The identified novel transcripts and improved annotation will help to understand the gene regulatory landscape in The analysis pipeline developed here can be used to build transcriptome assemblies and identify coding and noncoding RNAs of other species.
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http://dx.doi.org/10.3390/genes12101549DOI Listing
September 2021

Dual-channel Neural Network for Atrial Fibrillation Detection from a Single Lead ECG Wave.

IEEE J Biomed Health Inform 2021 Oct 19;PP. Epub 2021 Oct 19.

With the dramatic progress of wearable devices, continuous collection of single lead ECG wave is able to be implemented in a comfortable fashion. Data mining on single lead ECG wave is therefore attracting increasing attention, where atrial fibrillation (AF) detection is a hot topic. In this paper, we propose a dual-channel neural network for AF detection from a single lead ECG wave. Two primary phases are included, the data preprocessing part followed by a dual-channel neural network. A two-stage denoising procedure is developed for data preprocessing, so as to tackle the high noise and disturbance which generally resides in the ECG wave collected by wearable devices. Then the time-frequency spectrum and Poincare plot of the denoised ECG signal are imported into the developed dual-channel neural network for feature extraction and AF detection. On the 2017 PhysioNet/CinC Challenge database, the F1 values were 0.83, 0.90, and 0.75 for AF rhythm and normal rhythm, and other rhythm, respectively. The results well validate the effectiveness of the proposed method for AF detection from a single lead ECG wave, and also indicate its performance advantages over some state-of-the-art counterparts.
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http://dx.doi.org/10.1109/JBHI.2021.3120890DOI Listing
October 2021

Identifying the natural compound Catechin from tropical mangrove plants as a potential lead candidate against 3CL from SARS-CoV-2: An integrated approach.

J Biomol Struct Dyn 2021 Oct 13:1-20. Epub 2021 Oct 13.

Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P., India.

SARS-CoV-2, a member of beta coronaviruses, is a single-stranded, positive-sense RNA virus responsible for the COVID-19 pandemic. With global fatalities of the pandemic exceeding 4.57 million, it becomes crucial to identify effective therapeutics against the virus. A protease, 3CL, is responsible for the proteolysis of viral polypeptides into functional proteins, which is essential for viral pathogenesis. This indispensable activity of 3CL makes it an attractive target for inhibition studies. The current study aimed to identify potential lead molecules against 3CL of SARS-CoV-2 using a manually curated in-house library of antiviral compounds from mangrove plants. This study employed the structure-based virtual screening technique to evaluate an in-house library of antiviral compounds against 3CL of SARS-CoV-2. The library was comprised of thirty-three experimentally proven antiviral molecules extracted from different species of tropical mangrove plants. The molecules in the library were virtually screened using AutoDock Vina, and subsequently, the top five promising 3CL-ligand complexes along with 3CL-N3 (control molecule) complex were subjected to MD simulations to comprehend their dynamic behaviour and structural stabilities. Finally, the MM/PBSA approach was used to calculate the binding free energies of 3CLpro complexes. Among all the studied compounds, Catechin achieved the most significant binding free energy (-40.3 ± 3.1 kcal/mol), and was closest to the control molecule (-42.8 ± 5.1 kcal/mol), and its complex with 3CL exhibited the highest structural stability. Through extensive computational investigations, we propose Catechin as a potential therapeutic agent against SARS-CoV-2. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1988710DOI Listing
October 2021

Effectiveness of community-based health education and home support program to reduce blood pressure among patients with uncontrolled hypertension in Nepal: A cluster-randomized trial.

PLoS One 2021 12;16(10):e0258406. Epub 2021 Oct 12.

Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.

Background: Hypertension is a major global public health problem. Elevated blood pressure can cause cardiovascular and kidney diseases. We assessed the effectiveness of health education sessions and home support programs in reducing blood pressure among patients with uncontrolled hypertension in a suburban community of Nepal.

Methods: We conducted a community-based, open-level, parallel-group, cluster randomized controlled trial in Birendranagar municipality of Surkhet, Nepal. We randomly assigned four clusters (wards) into intervention and control arms. We provided four health education sessions, frequent home and usual care for intervention groups over six months. The participants of the control arm received only usual care from health facilities. The primary outcome of this study was the proportion of controlled systolic blood pressure (SBP). The analysis included all participants who completed follow-up at six months.

Results: 125 participants were assigned to either the intervention (n = 63) or the control (n = 62) group. Of them, 60 participants in each group completed six months follow-up. The proportion of controlled SBP was significantly higher among the intervention participants compared to the control (58.3% vs. 40%). Odds ratio of this was 2.1 with 95% CI: 1.01-4.35 (p = 0.046) and that of controlled diastolic blood pressure (DBP) was 1.31 (0.63-2.72) (p = 0.600). The mean change (follow-up minus baseline) in SBP was significantly higher in the intervention than in the usual care (-18.7 mmHg vs. -11.2 mmHg, p = 0.041). Such mean change of DBP was also higher in the intervention (-10.95 mmHg vs. -5.53 mmHg, p = 0.065). The knowledge score on hypertension improved by 2.38 (SD 2.4) in the intervention arm, which was significantly different from that of the control group, 0.13 (1.8) (p<0.001).

Conclusions: Multiple health education sessions complemented by frequent household visits by health volunteers can effectively improve knowledge on hypertension and reduce blood pressure among uncontrolled hypertensive patients at the community level in Nepal.

Trial Registration: ClinicalTrial.gov: NCT02981251.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258406PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509872PMC
October 2021

COVID-19 and Psychotic Symptoms: the View from Psychiatric Immunology.

Curr Behav Neurosci Rep 2021 Oct 4:1-7. Epub 2021 Oct 4.

Department of Psychiatry, King George's Medical University, Lucknow, U.P India.

Purpose Of Review: To explore the immunological underpinnings of psychosis in the COVID-19 patients.

Recent Findings: COVID-19 pandemic led to a surge in psychiatric morbidities, including psychosis. Various putative biological and psychosocial changes have been implicated in COVID-19-related psychosis. COVID-19 is a proinflammatory state. Alterations in immunological processes both as a direct consequence of infection or secondary to the hyperimmune response heuristically explain the etiopathogenesis of psychosis in the affected individual. The uses of immunosuppressant and immunomodulatory drugs may be the other moderators of a psychotic presentation in COVID-19 patients. Evidence to substantiate this hypothesis is still lacking however, which further studies should address. Because of its management implications, a better understanding of the involved immunological mechanisms becomes extremely important.

Summary: Evidence suggests a putative role of immunological alterations in the pathogenesis of COVID-19-related psychosis. The immunological abnormalities are primarily attributed to the pathophysiology of COVID-19 infection, medications used, and stress.
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http://dx.doi.org/10.1007/s40473-021-00235-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487803PMC
October 2021

Recurrent proteinuria with graft dysfunction: a diagnostic and clinical conundrum.

Transpl Int 2021 Sep 27. Epub 2021 Sep 27.

Department of Nephrology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India.

The index case is a 45-year old male with unknown cause for native kidney disease, who received a kidney from his wife. Antithymocyte globulin (ATG) was used for induction, and tacrolimus, mycophenolate mofetil and prednisolone were prescribed for maintenance. His baseline serum creatinine was 0.9 mg/dl. Two years after the transplant, the patient developed 3+ proteinuria on routine urinalysis with stable graft function. His 24-hour urinary protein was 2.3 grams, serum albumin was 3.0 g/dl, and the total cholesterol was 251 mg/dl. The tacrolimus C0 levels were maintained between 6-8 ng/ml range. Allograft biopsy revealed diffuse thickening of glomerular basement membranes, with the immunofluorescence showing 2+ granular positivity along the loops for IgG and C3.
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http://dx.doi.org/10.1111/tri.14124DOI Listing
September 2021

Skin Diseases and their Treatment Strategies in Sub-Saharan African Regions.

Infect Disord Drug Targets 2021 Sep 27. Epub 2021 Sep 27.

Faculty of Pharmacy, AIMST University, Kedah-08100. Malaysia.

Background: In the rural areas of sub-Saharan African regions, skin diseases are so common. Due to which the population of the sub-Saharan region suffers from different types of skin disorders. In these regions, many treatment options are not available for the treatment of skin disease.

Aim: The current study aims to discuss various skin diseases and their treatment strategies specifically in sub-Saharan African regions.

Method: Extensive literature survey was carried out by using scopus, science direct, elsevier, google scholar and bentham science databases.

Result And Discussion: It was demonstrated from the literature surveys that different effective techniques are used in the management of skin disease. In the result, it was shown that the condition of the disease is at a dangerous level which must be controlled.

Conclusion: It is concluded from the manuscript that the skin disorder in the sub-Saharan region is at a very dangerous level. The research must be done to develop a better understanding of the disease and its treatment.
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http://dx.doi.org/10.2174/1871526521666210927120334DOI Listing
September 2021

Dhat syndrome: Systematic review of epidemiology, nosology, clinical features, and management strategies.

Asian J Psychiatr 2021 Sep 20;65:102863. Epub 2021 Sep 20.

Department of Psychiatry, Faculty of Medicine, University of Peradeniya, Sri Lanka. Electronic address:

Background: Dhat syndrome is a culture-bound syndrome prevailing in the Indian subcontinent, first described in the 1960s. Over time, newer studies are exploring various aspects of Dhat syndrome, including its epidemiology, nosology, clinical features, and management predominantly in South Asia. We aimed to review the epidemiology, nosology, clinical presentation, and management of Dhat syndrome over the last six decades through a systematic review of studies.

Methods: We searched PubMed and Scopus using the following search terms - "Dhat syndrome," "Semen loss syndrome," "Semen loss anxiety" together with the Boolean operator OR. We collected the articles from inception till March 2021. We included articles in the English language published in peer-reviewed journals.

Results: A total of 89 articles were included in the analysis. Most of the articles were published in the last decade (2011-2020). Most of the publications were cross-sectional studies and of unsatisfactory quality. Most of the studies lack representativeness of the population; hence the generalizability of the findings was poor. Most of the articles discussed phenomenology (64%), overview (52.8%), and cultural basis of Dhat syndrome. The comorbidities associated with Dhat syndrome were discussed in 37.1% of the articles. The nosological status of Dhat syndrome and management of Dhat syndrome was discussed in 18% of publications each; whereas, the outcome of Dhat syndrome was discussed in 5.6% of articles.

Conclusion: Though Dhat syndrome is a commonly diagnosed entity in the South Asian population, the research on Dhat syndrome is sparse and of poor quality.
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http://dx.doi.org/10.1016/j.ajp.2021.102863DOI Listing
September 2021

Impact of a relationship-centered care communication curriculum on pediatric residents' practice, perspectives, and opportunities to evelop expertise.

Patient Educ Couns 2021 Sep 9. Epub 2021 Sep 9.

Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. Electronic address:

Objectives: To investigate the impacts of a Relationship-Centered Care (RCC) communication curriculum with coaching on pediatric residents 1) self-reported use of RCC strategies and perspectives, and 2) opportunities to develop adaptive expertise.

Methods: Residents (n = 77) completed a 4 h RCC training and shared resultant RCC goals with Coaches (n = 15). Data included resident surveys and reflections immediately post-training, and resident and coach surveys 6-months later. Reported use of RCC strategies were compared over time with paired t-tests. Qualitative data were analyzed using open coding guided by sensitizing principles from the RCC framework and adaptive expertise.

Results: Pediatric residents reported significant increases (p < 0.001) in use of 4/9 RCC strategies after 6 months: eliciting all concerns, chunking information, checking for understanding, and teach-back. Resident reflections highlighted shifts in perspective around RCC. Training combined with coaching provided opportunities for residents to develop adaptive expertise through adapting and innovating across settings and contexts.

Conclusion: Residents had significant increases in reported use of key RCC strategies after a training combined with coaching and demonstrated opportunities to develop adaptive expertise.

Practice Implications: Residency programs should include RCC training with an emphasis on the new and challenging strategies and provide opportunities to practice and receive coaching.
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http://dx.doi.org/10.1016/j.pec.2021.08.014DOI Listing
September 2021

Antimicrobial activity of synthetic antimicrobial peptides loaded in poly-Ɛ-caprolactone nanoparticles against mycobacteria and their functional synergy with rifampicin.

Int J Pharm 2021 Oct 14;608:121097. Epub 2021 Sep 14.

Experimental Animal Facility, ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282004, India. Electronic address:

Tuberculosis (TB) treatment has become a challenge because of the natural presence of multilayered cell wall rich in lipids which restrict antibiotic permeability within the bacteria. The development of mutations conferring resistance has aggravated the situation. Consequently, maximum pharmaceutical efforts are required to improve the treatment, and antimicrobial peptides (AMPs) with antimycobacterial activity can be exploited as a new treatment strategy against TB. The synergistic interaction between conventional antibiotics and AMPs has broadened its application landscape. To overcome peptide instability and bioavailability issues, encapsulation of these bioactive in biocompatible polymers was adopted. In this study, the effect of synthetic AMPs HHC-8 [KIWWWWRKR] and MM-10 [MLLKKLLKKM] encapsulated in poly (ε-caprolactone) nanoparticles (PCL-NPs) was evaluated against mycobacteria using REMA (Resazurin Microtiter Assay Plate) technique. PCL encapsulation allowed us to load the required amount of peptides, i.e. HHC-8 and MM-10, with an efficiency of ∼ 18.9 ± 5.24 and ∼ 21.1 ± 6.19 % respectively, and sphere size was around 376.5 ± 14.9 nm and 289.87 ± 17.98 nm for PCL-HHC-8-NPs and PCL-MM-10-NPs, respectively. Minimal degradation and sustained release of peptides from nanoparticles improved antimicrobial activity, decreasing the MIC from 75 µg/ml to 18.75 µg/ml against M. smegmatis and from 75 µg/ml to 9 µg/ml against M. tuberculosis, respectively. The combinatorial MIC assays of encapsulated AMP with rifampicin antibiotics against M. smegmatis showed synergism between AMP-PCL-NPs and antibiotics with fractional inhibitory concentrations (FICs) around ∼ 0.09. The combinations of AMP NPs also demonstrated synergy against the mycobacteria. Our findings suggest that enhanced efficacy is due to protection offered by AMPs encapsulation resulting in augmentation of membrane permeation by AMPs and enhanced accumulation of antibiotics within mycobacteria resulting in synergy. The study findings might assist in the preclinical development of AMP for the fight against TB.
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http://dx.doi.org/10.1016/j.ijpharm.2021.121097DOI Listing
October 2021

Study protocol for yoga-based lifestyle intervention for healthy ageing phenotype in the older adults (yHAP): a two-armed, waitlist randomised controlled trial with multiple primary outcomes.

BMJ Open 2021 Sep 16;11(9):e051209. Epub 2021 Sep 16.

Swami Vivekananda Yoga Anusandhana Samsthana, Bengaluru, Karnataka, India.

Introduction: The conceptualisation of healthy ageing phenotype (HAP) and the availability of a tentative panel for HAP biomarkers raise the need to test the efficacy of potential interventions to promote health in older adults. This study protocol reports the methodology for a 24-week programme to explore the holistic influence of the yoga-based intervention on the (bio)markers of HAP.

Methods And Analysis: The study is a two-armed, randomised waitlist controlled trial with blinded outcome assessors and multiple primary outcomes. We aim to recruit 250 subjects, aged 60-80 years from the residential communities and old age clubs in Bangalore city, India, who will undergo randomisation into intervention or control arms (1:1). The intervention will include a yoga-based programme tailored for the older adults, 1 hour per day for 6 days a week, spread for 24 weeks. Data would be collected at the baseline and post-intervention, the 24th week. The multiple primary outcomes of the study are the (bio)markers of HAP: glycated haemoglobin, low-density lipoprotein cholesterol (LDL-C), systolic blood pressure, and forced expiratory volume in 1 s for physiological and metabolic health; Digit Symbol Substitution Test, Trail Making Tests A and B for cognition; hand grip strength and gait speed for physical capability; loneliness for social well-being and WHO Quality of Life Instrument-Short Form for quality of life. The secondary outcomes include inflammatory markers, tumour necrosis factor-alpha receptor II, C reactive protein, interleukin 6 and serum Klotho levels. Analyses will be by intention-to-treat and the holistic impact of yoga on HAP will be assessed using global statistical test.

Ethics And Dissemination: The study is approved by the Institutional Ethics Committee of Swami Vivekananda Yoga Anusandhana Samsthana University, Bangalore (ID: RES/IEC-SVYASA/143/2019). Written informed consent will be obtained from each participant prior to inclusion. Results will be available through research articles and conferences.

Trial Registration Number: CTRI/2021/02/031373.
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http://dx.doi.org/10.1136/bmjopen-2021-051209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449966PMC
September 2021

Median Duration of Hospital Stay after Early Removal of Foley's Catheter among Patients Undergoing Transurethral Resection of Prostate: A Descriptive Cross-sectional Study.

JNMA J Nepal Med Assoc 2021 Jul 30;59(239):688-691. Epub 2021 Jul 30.

Department of Surgery, National Medical College, Birgunj, Nepal.

Introduction: Transurethral resection of the prostate requires a catheter in situ post-surgery. Early removal of catheter can reduce the length of hospital stay reducing the healthcare cost. It can also reduce the risk of infection due to prolonged catheterization. Our aim was to determine the median duration of hospital stay after early foley's removal after transurethral resection of prostate among patients in a tertiary care hospital.

Methods: A descriptive cross-sectional study was done in a tertiary care hospital from July 2019 to December 2020 and ethical clearance was obtained from the institutional review committee. Foley's catheter were removed on the first post-operative day, who met the criteria of catheter removal. Convenience sampling was done. After foley's removal patients were observed for spontaneous voiding. Patients with complications like hematuria, clot retention, urinary retention were recatherized. The data were expressed in mean with standard deviation, median with interquartile range and frequency and percentage as applicable using Statistical Package for the Social Sciences version 16.

Results: Out of the 150 participants included in the study, the median duration of hospital stay after the early removal of foley's catheter was 3 days (interquartile range 2-4 days). A total of 20 (13.3%) patients underwent recatherization. Nine (6%) patients had to be recatheterized due to clot retention, and 11 (7.3%) were due to urinary retention.

Conclusions: This study showed that the median duration of hospital stay after early removal of foley's catheter among patients undergoing transurethral resection of the prostate was similar to studies done in national/international settings.
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http://dx.doi.org/10.31729/jnma.6384DOI Listing
July 2021

Bacteriological Profile of Urine in Patients with Different Types of Kidney Stones in a Tertiary Care Hospital: A Descriptive Cross-sectional Study.

JNMA J Nepal Med Assoc 2020 Nov 22;58(231):871-874. Epub 2020 Nov 22.

Department of General Surgery, Kathmandu University School of Medical Sciences Dhulikhel Hospital, Dhulikhel, Kavre, Nepal.

Introduction: The association of bacteriology in the pathogenesis of urolithiasis is a known and fact. The urinary tract stones being the most common problem that brings the patient to the surgical outpatient department; it is important to know the relation between the types of stone and the organism isolated from the urine for better management of the patient. The aim of this study was to find out the urine bacteriological profile of patients with kidney stones.

Methods: This is a descriptive cross-sectional study done over 18 months in a tertiary care hospital in Nepal. Ethical clearance was taken from the Institutional Review Committee (No: 03/16). Preoperative urine cultures were done routinely in all the patients who agreed to take participate in the study. The biochemical stone analysis was done. Urinary microbial floras and stone composition were noted. Data entry and analysis was done using Statistical Package for the Social Sciences version 25.0.

Results: Among 107 patients, kidney stones were more common in males and most of the patients were in their 2nd to 4th decade. Female patients 45 (42.05%) had more predilections towards the urinary tract infection. Among 15 (14.01%) positive cultures, Escherichia coli 10 (67%) was the most common organism isolated followed by Klebsiella; 4 (27%), and Pseudomonas; 1 (6%).

Conclusions: Thus, we would like to state that Escherichia coli, though being a non-urease producing organism, is a major organism isolated in the preoperative culture of urine in a patient with kidney stones.
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http://dx.doi.org/10.31729/jnma.5226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775010PMC
November 2020

A prospective observational safety study on ChAdOx1 nCoV-19 corona virus vaccine (recombinant) use in healthcare workers- first results from India.

EClinicalMedicine 2021 Aug 23;38:101038. Epub 2021 Jul 23.

Department of Geriatric Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India.

Background: We provide the first post-approval safety analysis of COVISHIELD in health care workers (HCWs) in northern India.

Methods: This continuing prospective observational study (February 2021 to May 2022) enrolled participants ≥18 years receiving COVISHIELD vaccination. Primary outcome was safety and reactogenicity. Categories (FDA toxicity grading) and outcomes of adverse events following immunization (AEFIs) were recorded, causality assessment performed, and risk factors analysed.

Findings: We present the results of an interim analysis of 804 participants. AEFIs following first dose were reported in 321 (40%; systemic involvement in 248). Among 730 participants who completed a 7-day follow-up post second dose, AEFIs occurred in 115 (15.7%; systemic in 99). Majority of AEFIs were mild-moderate and resolved spontaneously. Serious AEFIs, leading to hospitalization was noticed in 1 (0.1%) participant with suspicion of immunization stress related response (ISRR). AEFIs of grade 3 severity (FDA) were recorded in 4 participants (0.5%). No deaths were recorded. Regression analysis showed increased risk of AEFIs in younger individuals, a two times higher odds in females, those with hypertension or with history of allergy; and three times higher odds in individuals with hypothyroidism.

Interpretation: COVISHIELD carries an overall favourable safety profile with AEFI rates much less than reported for other adenoviral vaccines. Females, those with hypertension, individuals with history of allergy and hypothyroidism may need watchful vaccine administration. This being an interim analysis and based on healthcare workers who may not reflect the general population demographics, larger inclusive studies are warranted for confirming the findings.

Funding: No funding support.
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http://dx.doi.org/10.1016/j.eclinm.2021.101038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413251PMC
August 2021

Role of Texting as a Source of Cognitive Burden in a Pediatric Cardiovascular ICU.

Hosp Pediatr 2021 Oct 8;11(10):e253-e257. Epub 2021 Sep 8.

Division of Pediatric Cardiology

Objectives: To characterize frontline provider perception of clinical text messaging and quantify clinical texting data in a pediatric cardiovascular ICU (CICU).

Methods: This is a mixed-methods, retrospective single center study. A survey of frontline CICU providers (pediatric fellows, nurse practitioners, and physician assistants) was conducted to assess attitudes characterizing text messaging on cognitive burden. Text messaging data were abstracted and quantified between January 29, 2020, and April 18, 2020, and the patterns of text messages were analyzed per shift and by provider.

Results: The survey was completed by 33 of 39 providers (85%). Out of responders, 78% indicated that clinical text messaging frequently or very frequently disrupts critical thinking and workflow. They also felt that the burden of messages was worse during the night shift. Through abstraction, 31 926 text messages were identified. A median of 15 (interquartile range: 12-19) messages per hour were received. A median of 5 messages were received per hour per provider during the day shift and 6 during the night shift. From the entire study period, there were total 2 hours of high-frequency texting (≥15 texts per hour) during the day shift and 68 hours during the night shift.

Conclusion: In our study, providers in the CICU received a large number of texts with a disproportionate burden during the night shift. Text messages are a potential source of cognitive overload for providers. Optimization of text messaging may be needed to mitigate cognitive burden for frontline providers.
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http://dx.doi.org/10.1542/hpeds.2021-005869DOI Listing
October 2021

Effects of supplemental xylanase and xylooligosaccharides on production performance and gut health variables of broiler chickens.

J Anim Sci Biotechnol 2021 Sep 6;12(1):98. Epub 2021 Sep 6.

Department of Human Nutrition, Food and Animal Sciences, University of Hawaii at Manoa, Honolulu, HI, 96822, USA.

Background: This study evaluated the effects of supplemental xylanase and xylooligosaccharides (XOS) in a corn-soybean meal (SBM)-based diet on growth performance and intestinal health of broilers. A total of 288 day-old chicks (Cobb 500) were allocated to 36 floor pens (8 birds/pen) equally in 9 dietary treatments in a 3 × 3 factorial arrangement. The treatments were combinations of 3 levels of xylanase (0, 0.005% and 0.01% Econase XT) and 3 levels of prebiotics (0, 0.005% and 0.01% XOS) added to basal mash diets formulated in three phases (starter, d 0-14; grower, d 15-28; finisher, d 29-42). The feed intake and body weights were recorded weekly. On d 42, ileal sections were collected for histomorphometric and gene expression analysis, and cecal content was collected for determining short-chain fatty acids (SCFA) and microbiota.

Results: Xylanase linearly (P < 0.01) increased the average daily gain (ADG) in both the finisher and total period and the final body weight gain (FBWG, 2940 & 2932 vs. 2760 g) of broilers. XOS did not significantly increase either ADG or FBWG (P > 0.05). Supplemental xylanase and XOS did not affect average daily feed intake and feed conversion ratio (P > 0.05). Xylanase and XOS did not change villus height (VH) or crypt depth (CD) ratio (P > 0.05). However, xylanase exhibited a trend (P = 0.097) on VH:CD ratio. The inclusion of 0.01% XOS without xylanase increased the level of IL-10 (a marker of anti-inflammatory cytokine) and IL-4 (a T-cell differentiation cytokine) genes compared with control (P < 0.05). The acetate production was increased by xylanase (P < 0.01) and XOS (P < 0.05) without an additive effect. Xylanase increased total SCFA (P < 0.01) while XOS had a tendency to increase (P = 0.052). Alpha and beta diversity of microbiota among treatments were not different (P > 0.05). However, the mean proportion of family Ruminococcaceae was increased by the supplemental 0.01% xylanase (P < 0.01).

Conclusion: It can be concluded that XOS can enhance cecal fermentation, while xylanase can increase the body weight gain along with the fermentation metabolites in the ceca of broilers fed the corn-SBM-based diet but the effects may not always translate into an improved mucosal absorptive capacity and a better feed efficiency.
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http://dx.doi.org/10.1186/s40104-021-00617-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419990PMC
September 2021

Aptamer-based diagnostic and therapeutic approaches in animals: Current potential and challenges.

Saudi J Biol Sci 2021 Sep 20;28(9):5081-5093. Epub 2021 May 20.

Gene Manipulation Laboratory, Department of Biotechnology and Medical Engineering, National Institute of Technology Rourkela, Odisha, India.

Fast and precise diagnosis of infectious and non-infectious animal diseases and their targeted treatments are of utmost importance for their clinical management. The existing biochemical, serological and molecular methods of disease diagnosis need improvement in their specificity, sensitivity and cost and, are generally not amenable for being used as points-of-care (POC) device. Further, with dramatic changes in environment and farm management practices, one should also arm ourselves and prepare for emerging and re-emerging animal diseases such as cancer, prion diseases, COVID-19, influenza etc. Aptamer - oligonucleotide or short peptides that can specifically bind to target molecules - have increasingly become popular in developing biosensors for sensitive detection of analytes, pathogens (bacteria, virus, fungus, prions), drug residues, toxins and, cancerous cells. They have also been proven successful in the cellular delivery of drugs and targeted therapy of infectious diseases and physiological disorders. However, the in vivo application of aptamer-mediated biosensing and therapy in animals has been limited. This paper reviews the existing reports on the application of aptamer-based biosensors and targeted therapy in animals. It also dissects the various modifications to aptamers that were found to be successful in application of the aptamers in diagnostics and therapeutics. Finally, it also highlights major challenges and future directions in the application of aptamers in the field of veterinary medicine.
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http://dx.doi.org/10.1016/j.sjbs.2021.05.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381015PMC
September 2021

Prevalence and Risk Factors for Oral Potentially Malignant Disorders in Indian Population.

J Pharm Bioallied Sci 2021 Jun 5;13(Suppl 1):S398-S401. Epub 2021 Jun 5.

Department of Oral Pathology Private Practitioner, Patna, Bihar, India.

Background: The present study was conducted to assess risk factors and prevalence of potentially malignant disorders (PMDs) among Indian population.

Materials And Methods: 1280 Indian population of both genders were enrolled. Habits such as smoking bidi, cigarette, consumption of tobacco such as in the form of zarda, chaini khaini, pan masala, arecanut, and alcohol were recorded. Risk factors and prevalence rate of disorders were recorded.

Results: There were 750 (58.6%) males and 530 (41.4%) females. Speckled leukoplakia was seen among 470 (36.7%), oral lichen planus (OLP) in 246 (19.2%), oral submucous fibrosis (OSMF) in 274 (21.4%), erythroplakia in 120 (9.3%), and oral squamous cell carcinoma (OSCC) in 107 (8.3%) participants. Maximum cases of speckled leukoplakia (162) was seen in the age group of 31-40 years, OLP (99) in 41-50 years, OSMF (95) in 31-40 years, erythroplakia (48) in 21-30 years, OSCC (44) in 41-50 years.

Conclusion: Risks factors associated with PMDs were found to be tobacco and arecanut. There was higher prevalence of leukoplakia. Age group of 31-40 years had higher cases and most common site was buccal mucosa and vestibule.
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http://dx.doi.org/10.4103/jpbs.JPBS_751_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375802PMC
June 2021

Phylogenetics of Sarcocystis fusiformis isolates based on 18S rRNA and cox 1 genes.

Microb Pathog 2021 Oct 17;159:105144. Epub 2021 Aug 17.

Department of Parasitology, U. P. Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go Anusandhan Sansthan (DUVASU), Mathura, 281001, India.

Sarcocystosis is a significant meat borne coccidian disease with immense zoonotic potential. Sarcocystis fusiformis is the most prevalent Sarcocystis spp. affecting buffaloes across the globe. Most of the molecular characterization works on S. fusiformis are from Egypt and there is no record of such work from India. In the present study, 21 isolates of S. fusiformis from Northern India were characterized for 18S rRNA (MF595821-MF595841) and cox 1 (MF423105-MF423119 and MH899162-MH899167) genes. S. fusiformis was seen as a monophyletic sister group to S. cafferi on the phylogenetic tree comprising of different Sarcocystis spp. Both genes placed S. fusiformis close to those Sarcocystis spp. which have felids as definitive hosts in comparison to those with canids as definitive host. A total of 15 and 7 haplotypes were noticed for both the genes, respectively. The studied Indian isolates showed 99.1-100.0% and 99.2-100.0% nucleotide homologies within themselves for both the respective gene loci. Over all, cox 1 gene was found to be better in delineating the evolutionary phylogenetics in comparison to 18S rRNA gene. The findings are important from evolutionary point of view.
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http://dx.doi.org/10.1016/j.micpath.2021.105144DOI Listing
October 2021

Mycobacterium tuberculosis SufR responds to nitric oxide via its 4Fe-4S cluster and regulates Fe-S cluster biogenesis for persistence in mice.

Redox Biol 2021 10 2;46:102062. Epub 2021 Jul 2.

Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, 560012, India; Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India. Electronic address:

The persistence of Mycobacterium tuberculosis (Mtb) is a major problem in managing tuberculosis (TB). Host-generated nitric oxide (NO) is perceived as one of the signals by Mtb to reprogram metabolism and respiration for persistence. However, the mechanisms involved in NO sensing and reorganizing Mtb's physiology are not fully understood. Since NO damages iron-sulfur (Fe-S) clusters of essential enzymes, the mechanism(s) involved in regulating Fe-S cluster biogenesis could help Mtb persist in host tissues. Here, we show that a transcription factor SufR (Rv1460) senses NO via its 4Fe-4S cluster and promotes persistence of Mtb by mobilizing the Fe-S cluster biogenesis system; suf operon (Rv1460-Rv1466). Analysis of anaerobically purified SufR by UV-visible spectroscopy, circular dichroism, and iron-sulfide estimation confirms the presence of a 4Fe-4S cluster. Atmospheric O and HO gradually degrade the 4Fe-4S cluster of SufR. Furthermore, electron paramagnetic resonance (EPR) analysis demonstrates that NO directly targets SufR 4Fe-4S cluster by forming a protein-bound dinitrosyl-iron-dithiol complex. DNase I footprinting, gel-shift, and in vitro transcription assays confirm that SufR directly regulates the expression of the suf operon in response to NO. Consistent with this, RNA-sequencing of MtbΔsufR demonstrates deregulation of the suf operon under NO stress. Strikingly, NO inflicted irreversible damage upon Fe-S clusters to exhaust respiratory and redox buffering capacity of MtbΔsufR. Lastly, MtbΔsufR failed to recover from a NO-induced non-growing state and displayed persistence defect inside immune-activated macrophages and murine lungs in a NO-dependent manner. Data suggest that SufR is a sensor of NO that supports persistence by reprogramming Fe-S cluster metabolism and bioenergetics.
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http://dx.doi.org/10.1016/j.redox.2021.102062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371249PMC
October 2021

Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples.

EBioMedicine 2021 Aug 12;70:103525. Epub 2021 Aug 12.

Microbiology & Cell Biology Department, Indian Institute of Science, Bengaluru, India; Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India. Electronic address:

Background: While our battle with the COVID-19 pandemic continues, a multitude of Omics data have been generated from patient samples in various studies. Translation of these data into clinical interventions against COVID-19 remains to be accomplished. Exploring host response to COVID-19 in the upper respiratory tract can unveil prognostic markers and therapeutic targets.

Methods: We conducted a meta-analysis of published transcriptome and proteome profiles of respiratory samples of COVID-19 patients to shortlist high confidence upregulated host factors. Subsequently, mRNA overexpression of selected genes was validated in nasal swabs from a cohort of COVID-19 positive/negative, symptomatic/asymptomatic individuals. Guided by this analysis, we sought to check for potential drug targets. An FDA-approved drug, Auranofin, was tested against SARS-CoV-2 replication in cell culture and Syrian hamster challenge model.

Findings: The meta-analysis and validation in the COVID-19 cohort revealed S100 family genes (S100A6, S100A8, S100A9, and S100P) as prognostic markers of severe COVID-19. Furthermore, Thioredoxin (TXN) was found to be consistently upregulated. Auranofin, which targets Thioredoxin reductase, was found to mitigate SARS-CoV-2 replication in vitro. Furthermore, oral administration of Auranofin in Syrian hamsters in therapeutic as well as prophylactic regimen reduced viral replication, IL-6 production, and inflammation in the lungs.

Interpretation: Elevated mRNA level of S100s in the nasal swabs indicate severe COVID-19 disease, and FDA-approved drug Auranofin mitigated SARS-CoV-2 replication in preclinical hamster model.

Funding: This study was supported by the DBT-IISc partnership program (DBT (IED/4/2020-MED/DBT)), the Infosys Young Investigator award (YI/2019/1106), DBT-BIRAC grant (BT/CS0007/CS/02/20) and the DBT-Wellcome Trust India Alliance Intermediate Fellowship (IA/I/18/1/503613) to ST lab.
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http://dx.doi.org/10.1016/j.ebiom.2021.103525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358265PMC
August 2021

Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples.

EBioMedicine 2021 Aug 12;70:103525. Epub 2021 Aug 12.

Microbiology & Cell Biology Department, Indian Institute of Science, Bengaluru, India; Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India. Electronic address:

Background: While our battle with the COVID-19 pandemic continues, a multitude of Omics data have been generated from patient samples in various studies. Translation of these data into clinical interventions against COVID-19 remains to be accomplished. Exploring host response to COVID-19 in the upper respiratory tract can unveil prognostic markers and therapeutic targets.

Methods: We conducted a meta-analysis of published transcriptome and proteome profiles of respiratory samples of COVID-19 patients to shortlist high confidence upregulated host factors. Subsequently, mRNA overexpression of selected genes was validated in nasal swabs from a cohort of COVID-19 positive/negative, symptomatic/asymptomatic individuals. Guided by this analysis, we sought to check for potential drug targets. An FDA-approved drug, Auranofin, was tested against SARS-CoV-2 replication in cell culture and Syrian hamster challenge model.

Findings: The meta-analysis and validation in the COVID-19 cohort revealed S100 family genes (S100A6, S100A8, S100A9, and S100P) as prognostic markers of severe COVID-19. Furthermore, Thioredoxin (TXN) was found to be consistently upregulated. Auranofin, which targets Thioredoxin reductase, was found to mitigate SARS-CoV-2 replication in vitro. Furthermore, oral administration of Auranofin in Syrian hamsters in therapeutic as well as prophylactic regimen reduced viral replication, IL-6 production, and inflammation in the lungs.

Interpretation: Elevated mRNA level of S100s in the nasal swabs indicate severe COVID-19 disease, and FDA-approved drug Auranofin mitigated SARS-CoV-2 replication in preclinical hamster model.

Funding: This study was supported by the DBT-IISc partnership program (DBT (IED/4/2020-MED/DBT)), the Infosys Young Investigator award (YI/2019/1106), DBT-BIRAC grant (BT/CS0007/CS/02/20) and the DBT-Wellcome Trust India Alliance Intermediate Fellowship (IA/I/18/1/503613) to ST lab.
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http://dx.doi.org/10.1016/j.ebiom.2021.103525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358265PMC
August 2021

Increased frequency of Th17 cells and IL-17 levels are associated with low bone mineral density in postmenopausal women.

Sci Rep 2021 08 9;11(1):16155. Epub 2021 Aug 9.

Molecular Immunodiagnostics Division, ICMR-National Institute for Research in Reproductive Health, Mumbai, India.

Osteoporosis is one of the chronic and often neglected bone diseases in aging postmenopausal women that affect the quality of life. Studies on ovariectomized mice models indicated the reciprocal role of Th17 cells and Treg cells in the aetiology of osteoporosis. While Th17 cells promote osteoclastogenesis, Treg cells exhibit anti-osteoclastogenic activity. This exploratory study aimed to determine the difference in the frequency of these T-cell subtypes in pre-and postmenopausal women and to examine their association with BMD. In our study, the frequency of Treg cells, analyzed by flow cytometry, did not differ between pre-and postmenopausal women. However, plasma levels of IL-10 along with IL-10CD4T cells were higher in post- compared to premenopausal women. The frequency of Th17 cells was higher in postmenopausal women irrespective of their BMD, however, only postmenopausal women with low BMD had elevated IL-17 levels and their T-scores were associated with Th17 frequency. Collectively, the results suggest that estrogen insufficiency in postmenopausal women may lead to increased Th17 cell frequency and elevated IL-17 levels which are associated with low BMD. This study highlights, Th17 cells and IL-17 as key players in the pathogenesis of osteoporosis and they can be the potential targets for immunotherapy in the treatment of osteoporosis.
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http://dx.doi.org/10.1038/s41598-021-95640-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352954PMC
August 2021

Effectiveness of Yoga Lifestyle on Lipid Metabolism in a Vulnerable Population-A Community Based Multicenter Randomized Controlled Trial.

Medicines (Basel) 2021 Jul 13;8(7). Epub 2021 Jul 13.

Swami Vivekananda Yoga Anusandhana Samsthana (S-VYASA), Bengaluru 560105, India.

Dyslipidemia poses a high risk for cardiovascular disease and stroke in Type 2 diabetes (T2DM). There are no studies on the impact of a validated integrated yoga lifestyle protocol on lipid profiles in a high-risk diabetes population. Here, we report the results of lipid profile values of 11,254 (yoga 5932 and control 5322) adults (20-70 years) of both genders with high risk (≥60 on Indian diabetes risk score) for diabetes from a nationwide rural and urban community-based two group (yoga and conventional management) cluster randomized controlled trial. The yoga group practiced a validated integrated yoga lifestyle protocol (DYP) in nine day camps followed by daily one-hour practice. Biochemical profiling included glycated hemoglobin and lipid profiles before and after three months. There was a significant difference between groups ( < 0.001 ANCOVA) with improved serum total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein in the yoga group compared to the control group. Further, the regulatory effect of yoga was noted with a significant decrease or increase in those with high or low values of lipids, respectively, with marginal or no change in those within the normal range. Yoga lifestyle improves and regulates (lowered if high, increased if low) the blood lipid levels in both genders of prediabetic and diabetic individuals in both rural and urban Indian communities.
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http://dx.doi.org/10.3390/medicines8070037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303653PMC
July 2021

Unbiased automated quantitation of ROS signals in live retinal neurons of using Fiji/ImageJ.

Biotechniques 2021 Aug 5;71(2):416-424. Epub 2021 Aug 5.

Department of Biology, University of Dayton, Dayton, OH 45469, USA.

Numerous imaging modules are utilized to study changes that occur during cellular processes. Besides qualitative (immunohistochemical) or semiquantitative (Western blot) approaches, direct quantitation method(s) for detecting and analyzing signal intensities for disease(s) biomarkers are lacking. Thus, there is a need to develop method(s) to quantitate specific signals and eliminate noise during live tissue imaging. An increase in reactive oxygen species (ROS) such as superoxide (O) radicals results in oxidative damage of biomolecules, which leads to oxidative stress. This can be detected by dihydroethidium staining in live tissue(s), which does not rely on fixation and helps prevent stress on tissues. However, the signal-to-noise ratio is reduced in live tissue staining. We employ the eye model of Alzheimer's disease as a proof of concept to quantitate ROS in live tissue by adapting an unbiased method. The method presented here has a potential application for other live tissue fluorescent images.
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http://dx.doi.org/10.2144/btn-2021-0006DOI Listing
August 2021

Genome-wide association mapping reveals key genomic regions for physiological and yield-related traits under salinity stress in wheat (Triticum aestivum L.).

Genomics 2021 Sep 19;113(5):3198-3215. Epub 2021 Jul 19.

ICAR-National Bureau of Plant Genetic Resources, Pusa Campus, New Delhi 110012, India.

A genome-wide association study (GWAS) was conducted using six different multi-locus GWAS models and 35K SNP array to demarcate genomic regions underlying reproductive stage salinity tolerance. Marker-trait association analysis was performed for salt tolerance indices (STI) of 11 morpho-physiological traits, and the actual concentrations of Na and K, and the Na/K ratio in flag leaf. A total of 293 significantly associated quantitative trait nucleotides (QTNs) for 14 morpho-physiological traits were identified. Of these 293 QTNs, 12 major QTNs with R ≥ 10.0% were detected in three or more GWAS models. Novel major QTNs were identified for plant height, number of effective tillers, biomass, grain yield, thousand grain weight, Na and K content, and the Na/K ratio in flag leaf. Moreover, 48 candidate genes were identified from the associated genomic regions. The QTNs identified in this study could potentially be targeted for improving salinity tolerance in wheat.
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http://dx.doi.org/10.1016/j.ygeno.2021.07.014DOI Listing
September 2021

brain abscess: a sinister aetiology.

Postgrad Med J 2021 Jul 21. Epub 2021 Jul 21.

Neurology, Fortis Hospital Mohali, Mohali, Punjab, India

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http://dx.doi.org/10.1136/postgradmedj-2021-140656DOI Listing
July 2021

Glycolysis downregulation is a hallmark of HIV-1 latency and sensitizes infected cells to oxidative stress.

EMBO Mol Med 2021 08 20;13(8):e13901. Epub 2021 Jul 20.

Department of Infectious Diseases, Italian Institute of Health, Rome, Italy.

HIV-1 infects lymphoid and myeloid cells, which can harbor a latent proviral reservoir responsible for maintaining lifelong infection. Glycolytic metabolism has been identified as a determinant of susceptibility to HIV-1 infection, but its role in the development and maintenance of HIV-1 latency has not been elucidated. By combining transcriptomic, proteomic, and metabolomic analyses, we here show that transition to latent HIV-1 infection downregulates glycolysis, while viral reactivation by conventional stimuli reverts this effect. Decreased glycolytic output in latently infected cells is associated with downregulation of NAD /NADH. Consequently, infected cells rely on the parallel pentose phosphate pathway and its main product, NADPH, fueling antioxidant pathways maintaining HIV-1 latency. Of note, blocking NADPH downstream effectors, thioredoxin and glutathione, favors HIV-1 reactivation from latency in lymphoid and myeloid cellular models. This provides a "shock and kill effect" decreasing proviral DNA in cells from people living with HIV/AIDS. Overall, our data show that downmodulation of glycolysis is a metabolic signature of HIV-1 latency that can be exploited to target latently infected cells with eradication strategies.
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http://dx.doi.org/10.15252/emmm.202013901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350904PMC
August 2021

Exploring the Mystery of Angiotensin-Converting Enzyme II (ACE2) in the Battle against SARS-CoV-2.

J Renin Angiotensin Aldosterone Syst 2021 4;2021:9939929. Epub 2021 Jun 4.

CCRF, All India Institute of Medical Sciences, New Delhi 110029, India.

COVID-19 is the newly born pandemic caused by the SARS-CoV-2 virus, which is the recently emerged betacoronavirus that crosses the species barrier. It predominantly infects pneumocytes of the respiratory tract, but due to the presence of angiotensin-converting enzyme II (ACE2) on other cells like surface enterocytes of the upper esophagus and colon, these are also considered as the primary sites of infection. ACE2 receptor served as a cellular entry point for SARS-CoV-2. The expression of the ACE2 receptors is regulated by several factors such as age, tobacco smoking, inflammatory signaling, ACE inhibitors, angiotensin receptor blockers, and comorbidities (chronic obstructive pulmonary disease (COPD), tuberculosis, cerebrovascular disease, coronary heart disease, hypertension, and diabetes). Therefore, scientists are trying to explore the in-depth knowledge of ACE2 and considered it as a potential indirect target for COVID-19 therapeutics. In this focused review, we discussed in detail ACE2 expressions and regulation by different factors in the primary or vulnerable sites of SARS-CoV-2 infections. Clinical trials of rhACE2 in COVID-19 patients are ongoing, and if the outcome of the trials proves positive, it will be a breakthrough for the management of COVID-19. Finally, we suggest that targeting the ACE2 (a master regulator) in a balanced way could serve as a potential option against the management of COVID-19.
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http://dx.doi.org/10.1155/2021/9939929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265022PMC
July 2021

Leucoefdin a potential inhibitor against SARS CoV-2 M.

J Biomol Struct Dyn 2021 Aug 17;39(12):4427-4432. Epub 2020 Jun 17.

School of Biochemical Engineering, Indian Institute of Technology (BHU), Varanasi, India.

Leucoefdin an important constituent of various fruits such as banana, raspberry, etc. was explored to target M protease of SARS Co-V 2. Ligand was found to bind at active site of M with large negative binding energies in molecular docking and simulation study. The docking results showed that Leucoefdin interacted with the M by forming hydrogen bonds, at Leu 141, His163, His 164, and Glu 166. Other non-bonded interactions were seen at Met49, Pro52, Tyr54, Phe140, Leu141, Cys145 and Met165. Results of Leucoefdin was in coherence with the recently reported M protease-inhibitor complex. It even displayed better binding energies (kcal/mol) in HTVS (-6.28), SP (-7.28), XP (-9.29) and MMGBSA (-44.71) as compared to the reference ligand [HTVS (-4.87), SP (-6.79), XP (-5.75) and MMGBSA (-47.76)]. Leucoefdin-M complex on molecular dynamic simulation showed initial fluctuations in RMSD plot for a certain period and attained equilibrium which remained stable during entire simulation for 150 ns. RMSF of protein showed less secondary structure fluctuations and a greater number of H-bond formation with Leucoefdin during 150 ns simulation. Post simulation MMGBSA analysis showed binding energy of -45.98 Kcal/mol. These findings indicated the potential of Leucoefdin as lead compound in R&D for drug discovery and development against SARS CoV-2.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1777903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309301PMC
August 2021
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