Publications by authors named "Ankita Sharma"

88 Publications

Acute Kidney Injury in Hospitalized Children with COVID19.

J Trop Pediatr 2021 05;67(2)

Department of Paediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi 110001, India.

Background: Acute kidney injury (AKI) has been recognized as a significant risk factor for mortality among adults with severe acute respiratory syndrome coronavirus infection.

Aim: The aim of this study is to assess the prevalence and risk factors for AKI and mortality in children with coronavirus disease 2019 (COVID19) from a resource-limited setting.

Methods: Cross-sectional analysis of laboratory confirmed COVID19 children admitted from 1 March to 30 November 2020 in a tertiary care hospital in New Delhi, India was done. Clinical features and associated comorbidities of COVID19 were noted. Baseline serum creatinine (height-independent Hoste's equation) and peak serum creatinine were used for staging of AKI by the 2012 Kidney Disease Improving Global Outcomes serum creatinine criteria. Univariate analysis and Kaplan-Meier survival analysis were used to compare the overall outcome in the AKI vs. the non-AKI group.

Results: A total of 64 810 children between 1 month and 18 years visited the hospital; 3412 were tested for suspected COVID19, 295 tested positive and 105 (54% boys) were hospitalized. Twenty-four hospitalized children (22.8%) developed AKI; 8 in Stage 1 (33.3%), 7 in Stage 2 (29.2%) and 9 in Stage 3 (37.5%) respectively. Overall, three patients received KRT. Highest reported mortality was (66.6%) in AKI Stage 3. Risk factors for AKI included associated sepsis (OR 95% CI, 1.22-9.43, p < 0.01), nephrotic syndrome (OR 95% CI, 1.13-115.5, p < 0.01), vasopressor support (OR 3.59, 95% CI, 1.37-9.40, p value< 0.007), shock at presentation (OR 2.98, 95% CI, 1.16-7.60, p value 0.01) and mechanical ventilation (OR 2.64, 95% CI, 1.04-6.71, p value< 0.03). Mortality (25.71%) was higher in the AKI group (OR 95% CI, 1.14-8.35, p < 0.023) with shock (OR 45.92; 95% CI, 3.44-612.0, p value <0.004) and ventilation (OR 46.24; 95% CI, 1.6-1333.0 p value< 0.02) as significant risk factors for mortality.

Conclusion: AKI is an important modifiable risk factor for mortality in children with COVID19 in a resource-limited setting. Our study supports the strengthening of kidney replacement therapy and its timely initiation to reduce the progression of AKI and thus mortality in children.
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http://dx.doi.org/10.1093/tropej/fmab037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195178PMC
May 2021

Genome-wide analysis of RING-type E3 ligase family identifies potential candidates regulating high amylose starch biosynthesis in wheat (Triticum aestivum L.).

Sci Rep 2021 Jun 1;11(1):11461. Epub 2021 Jun 1.

Agri-Food Biotechnology Division, National Agri-Food Biotechnology Institute, Mohali, 140306, Punjab, India.

In ubiquitin-mediated post-translational modifications, RING finger families are emerged as important E3 ligases in regulating biological processes. Amylose and amylopectin are two major constituents of starch in wheat seed endosperm. Studies have been found the beneficial effects of high amylose or resistant starch on health. The ubiquitin-mediated post-translational regulation of key enzymes for amylose/amylopectin biosynthesis (GBSSI and SBEII) is still unknown. In this study, the genome-wide analysis identified 1272 RING domains in 1255 proteins in wheat, which is not reported earlier. The identified RING domains classified into four groups-RING-H2, RING-HC, RING-v, RING-G, based on the amino acid residues (Cys, His) at metal ligand positions and the number of residues between them with the predominance of RING-H2 type. A total of 1238 RING protein genes were found to be distributed across all 21 wheat chromosomes. Among them, 1080 RING protein genes were identified to show whole genome/segmental duplication within the hexaploid wheat genome. In silico expression analysis using transcriptome data revealed 698 RING protein genes, having a possible role in seed development. Based on differential gene expression and correlation analysis of 36 RING protein genes in diverse (high and low) amylose mutants and parent, 10 potential RING protein genes found to be involved in high amylose biosynthesis and significantly associated with two starch biosynthesis genes; GBSSI and SBEIIa. Characterization of mutant lines using next-generation sequencing method identified unique mutations in 698 RING protein genes. This study signifies the putative role of RING-type E3 ligases in amylose biosynthesis and this information will be helpful for further functional validation and its role in other biological processes in wheat.
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http://dx.doi.org/10.1038/s41598-021-90685-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169666PMC
June 2021

A novel regulatory element regulates human in CTCF-dependent manner.

Mol Cell Biol 2021 Jun 1:MCB0038220. Epub 2021 Jun 1.

Centre of Excellence in Epigenetics, Department of Biology, Indian Institute of Science Education and Research, Pune, India.

The long non-coding RNA XIST is the master regulator for the process of X chromosome inactivation (XCI) in mammalian females. Here we report the existence of a hitherto uncharacterized regulatory element (cRE) within the first exon of human , which determines the transcriptional status of during the initiation and maintenance phases of XCI. In the initiation phase, pluripotency factors bind to this cRE and keep repressed. In the maintenance phase of XCI, the cRE is enriched for CTCF which activates transcription. By employing a CRISPR-dCas9-KRAB based interference strategy, we demonstrate that binding of CTCF to the newly identified cRE is critical for regulating in a YY1-dependent manner. Collectively, our study uncovers the combinatorial effect of multiple transcriptional regulators influencing expression during the initiation and maintenance phases of XCI.
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http://dx.doi.org/10.1128/MCB.00382-20DOI Listing
June 2021

Ferroptosis: A potential therapeutic target for neurodegenerative diseases.

J Biochem Mol Toxicol 2021 May 28:e22830. Epub 2021 May 28.

Department of Biotechnology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Raebareli, Lucknow, India.

Ferroptosis is a newly identified regulated form of cell death, which is thought to play a major role in neurodegenerative diseases. In this review, we discuss recent studies elucidating the molecular mechanisms involved in the regulation and execution of ferroptotic cell death and also its role in the brain. Ferroptosis is regulated mainly via iron homeostasis, glutathione metabolism, and lipid peroxidation. Ferroptotic cell death and pro-ferroptotic factors are correlated with the etiopathogenesis of Parkinson's disease (PD) and Alzheimer's disease (AD). Ferroptosis and etiological factors act synergistically in PD and AD pathogenesis. Furthermore, several preclinical and clinical studies targeting ferroptosis in PD and AD have also shown positive results. Evidence of ferroptosis in the brain thus gives new insights into understanding neurodegenerative diseases. Ferroptosis studies in the brain are still in their infancy, but the existing pieces of evidence suggest a strong correlation between ferroptotic cell death and neurodegenerative diseases. Thus, ferroptosis might be a promising target for treating neurodegenerative diseases.
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http://dx.doi.org/10.1002/jbt.22830DOI Listing
May 2021

Positive and Negative Regulation of Ferroptosis and Its Role in Maintaining Metabolic and Redox Homeostasis.

Oxid Med Cell Longev 2021 28;2021:9074206. Epub 2021 Apr 28.

Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research-Raebareli, Bijnor-Sisendi Road, Post Office Mati, Lucknow 226002, India.

Ferroptosis is a recently recognized regulated form of cell death characterized by accumulation of lipid-based reactive oxygen species (ROS), particularly lipid hydroperoxides and loss of activity of the lipid repair enzyme glutathione peroxidase 4 (GPX4). This iron-dependent form of cell death is morphologically, biochemically, and also genetically discrete from other regulated cell death processes, which include autophagy, apoptosis, necrosis, and necroptosis. Ferroptosis is defined by three hallmarks, defined as the loss of lipid peroxide repair capacity by GPX4, the bioavailability of redox-active iron, and oxidation of polyunsaturated fatty acid- (PUFA-) containing phospholipids. Experimentally, it can be induced by many compounds (e.g., erastin, Ras-selective lethal small-molecule 3, and buthionine sulfoximine) and also can be pharmacologically inhibited by iron chelators (e.g., deferoxamine and deferoxamine mesylate) and lipid peroxidation inhibitors (e.g., ferrostatin and liproxstatin). The sensitivity of a cell towards ferroptotic cell death is tightly associated with the metabolism of amino acid, iron, and polyunsaturated fatty acid metabolism, and also with the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis sensitivity is also governed by many regulatory proteins, which also link ferroptosis to the function of key tumour suppressor pathways. In this review, we highlight the discovery of ferroptosis, the mechanism of ferroptosis regulation, and its association with other cellular metabolic processes.
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http://dx.doi.org/10.1155/2021/9074206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102094PMC
April 2021

Anaesthesia management for Winchester syndrome.

Indian J Anaesth 2021 Feb 10;65(2):165-167. Epub 2021 Feb 10.

Department of Anaesthesia and Critical Care, Level III IFH Hospital, Goma, Democratic Republic of the Congo.

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http://dx.doi.org/10.4103/ija.IJA_984_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983827PMC
February 2021

Berbamine induced activation of the SIRT1/LKB1/AMPK signaling axis attenuates the development of hepatic steatosis in high-fat diet-induced NAFLD rats.

Food Funct 2021 Jan 7;12(2):892-909. Epub 2021 Jan 7.

Herbal Research Laboratory, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Post Box No. 80, Mahatma Gandhi Marg, Lucknow-226001, India.

Non-alcoholic fatty liver disease (NAFLD), a chronic metabolic disorder is concomitant with oxidative stress and inflammation. This study aimed to assess the effects of berbamine (BBM), a natural bisbenzylisoquinoline alkaloid with manifold biological activities and pharmacological effects on lipid, cholesterol and glucose metabolism in a rat model of NAFLD, and to explicate the potential mechanisms underlying its activity. BBM administration alleviated the increase in the body weight and liver index of HFD rats. The aberrations in liver function, serum parameters, and microscopic changes in the liver structure of HFD fed rats were significantly improved upon BBM administration. BBM also significantly attenuated oxidative damage and inhibited triglyceride and cholesterol synthesis. The SIRT1 deacetylase activity was also enhanced by BBM through liver kinase B1 and activated AMP-activated protein kinase. Activation of the SIRT1/LKB1/AMPK pathway prevented the downstream target ACC (acetyl-CoA carboxylase) and elevation in the expression of FAS (fatty acid synthase) and SCD1 (steroyl CoA desaturase). BBM also modulated the expression of PPARs maintaining the fatty acid homeostasis regulation. The assessment of berbamine induced ultrastructural changes by TEM analysis and the expression of autophagic markers LC3a/b, Beclin 1 and p62 revealed the induction of autophagy to alleviate fatty liver conditions. These results show novel findings that BBM induced protection against hepatic lipid metabolic disorders is achieved by regulating the SIRT1/LKB1/AMPK pathway, and thus it emerges as an effective phyoconstituent for the management of NAFLD.
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http://dx.doi.org/10.1039/d0fo02501aDOI Listing
January 2021

Crocetin promotes clearance of amyloid-β by inducing autophagy via the STK11/LKB1-mediated AMPK pathway.

Autophagy 2021 Jan 19:1-20. Epub 2021 Jan 19.

Division of PK-PD-Toxicology and Formulation, CSIR-Indian Institute of Integrative Medicine, Jammu, India.

Alzheimer disease (AD) is usually accompanied by two prominent pathological features, cerebral accumulation of amyloid-β (Aβ) plaques and presence of MAPT/tau neurofibrillary tangles. Dysregulated clearance of Aβ largely contributes to its accumulation and plaque formation in the brain. Macroautophagy/autophagy is a lysosomal degradative process, which plays an important role in the clearance of Aβ. Failure of autophagic clearance of Aβ is currently acknowledged as a contributing factor to increased accumulation of Aβ in AD brains. In this study, we have identified crocetin, a pharmacologically active constituent from the flower stigmas of , as a potential inducer of autophagy in AD. In the cellular model, crocetin induced autophagy in N9 microglial and primary neuron cells through STK11/LKB1 (serine/threonine kinase 11)-mediated AMP-activated protein kinase (AMPK) pathway activation. Autophagy induction by crocetin significantly increased Aβ clearance in N9 cells. Moreover, crocetin crossed the blood-brain barrier and induced autophagy in the brains' hippocampi of wild-type male C57BL/6 mice. Further studies in transgenic male 5XFAD mice, as a model of AD, revealed that one-month treatment with crocetin significantly reduced Aβ levels and neuroinflammation in the mice brains and improved memory function by inducing autophagy that was mediated by AMPK pathway activation. Our findings support further development of crocetin as a pharmacological inducer of autophagy to prevent, slow down progression, and/or treat AD.
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http://dx.doi.org/10.1080/15548627.2021.1872187DOI Listing
January 2021

Evaluation of indirect pulp capping using pozzolan-based cement (ENDOCEM-Zr®) and mineral trioxide aggregate - A randomized controlled trial.

J Conserv Dent 2020 Mar-Apr;23(2):152-157. Epub 2020 Nov 5.

Department of Oral Pathology and Microbiology, Manipal College of Dental Sciences, Affiliated to Manipal Academy of Higher Education, Mangalore, Karnataka, India.

Background: Pulp capping should always be considered as the primary treatment of choice for teeth without irreversible pulpitis in lesions approaching dental pulp. The predictability of vital pulp therapy has improved with the introduction of newer bioceramic materials.

Aim: The purpose of this randomized controlled trial was to compare the outcomes of mineral trioxide aggregate (MTA) (Angelus, Londrina, Brazil) and a pozzolan-based cement (ENDOCEM-Zr [Maruchi, Wonju, Korea]) as an indirect pulp capping (IPC) material.

Materials And Methods: IPC was performed in forty patients who were randomly divided into ENDOCEM-Zr and MTA groups. The outcome was assessed using clinical and radiographic tests at different time intervals. The prognostic factors on the outcome of IPC were also evaluated.

Results And Conclusions: The success rate of ENDOCEM-Zr and MTA groups was 94.7% and 89.4%, respectively. The results were not statistically significant. Binary logical regression showed that the age of the patient and the status of the pulp before treatment were deciding variables for the outcome of the study. Therefore, it was concluded from the study that the evaluated pozzolan-based cement could be used as an alternative to MTA because of its faster setting time and lower discoloration potential. In addition, pulp capping should be performed with caution in individuals above 40 years and in teeth with reversible pulpitis.
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http://dx.doi.org/10.4103/JCD.JCD_367_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720766PMC
November 2020

Plasma Proteome Profiling of Coronary Artery Disease Patients: Downregulation of Transthyretin-An Important Event.

Mediators Inflamm 2020 10;2020:3429541. Epub 2020 Nov 10.

Council of Industrial Research (CSIR)-Institute of Genomics and Integrative Biology, Mall Road, Delhi University Campus, 110007, Delhi, India.

Coronary artery disease (CAD) is a prevalent chronic inflammatory cardiac disorder. An early diagnosis is likely to help in the prevention and proper management of this disease. As the study of proteomics provides the potential markers for detection of a disease, in the present investigation, attempt has been made to identify disease-associated differential proteins involved in CAD pathogenesis. For this study, a total of 200 selected CAD patients were considered, who were recruited for percutaneous coronary intervention (PCI) treatment. The proteomic analysis was performed using two-dimensional gel electrophoresis (2-DE) and MALDI-TOF MS/MS. Samples were also subjected to Western blot analysis, enzyme-linked immunosorbent assay (ELISA), peripheral blood mononuclear cells isolation immunofluorescence (IF) analysis, analytical screening by fluorescence-activated cell sorting (FACS), and in silico analysis. The representative data were shown as mean ± SD of at least three experiments. A total of 19 proteins were identified. Among them, the most abundant five proteins (serotransferrin, talin-1, alpha-2HS glycoprotein, transthyretin (TTR), fibrinogen- chain) were found to have altered level in CAD. Serotransferrin, talin-1, alpha-2HS glycoprotein, and transthyretin (TTR) were found to have lower level, whereas fibrinogen- chain was found to have higher level in CAD plasma compared to healthy, confirmed by Western blot analysis. TTR, an important acute phase transport protein, was validated low level in 200 CAD patients who confirmed to undergo PCI treatment. Further, in silico and in vitro studies of TTR indicated a downexpression of CAD in plasma as compared to the plasma of healthy individuals. Lower level of plasma TTR was determined to be an important risk marker in the atherosclerotic-approved CAD patients. We suggest that the TTR lower level predicts disease severity and hence may serve as an important marker tool for CAD screening. However, further large-scale studies are required to determine the clinical significance of TTR.
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http://dx.doi.org/10.1155/2020/3429541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707994PMC
November 2020

Effect of serum vitamin D, calcium, and phosphorus on mandibular residual ridge resorption in completely edentulous participants: A clinical study.

J Prosthet Dent 2020 Nov 17. Epub 2020 Nov 17.

Post-Graduate student, Department of Prosthodontics, D.A.P.M.R.V. Dental College, Bangalore, Karnataka, India.

Statement Of Problem: Published data regarding association between edentulous mandibular residual ridge resorption and nutritional status of geriatric patients is limited.

Purpose: The purpose of this clinical study was to evaluate the degree of mandibular residual ridge resorption in completely edentulous participants and to investigate the role of dietary nutrients in the resorption process.

Material And Methods: Three hundred (55% men and 45% women; aged between 35 and 85 years) completely edentulous participants with specific inclusion and exclusion criteria were enrolled for the study. A standardized panoramic radiograph was made, measurements were made digitally, and the amount of resorption was calculated using the Wical and Swoope method. The blood plasma levels of vitamin D3 were analyzed by using the direct competitive chemiluminescence immunoassay (CLIA) method, whereas the total calcium and phosphorus were determined by using spectrophotometer method. Statistical data of serum nutrient levels (calcium, phosphorus, and vitamin D3), age, sex, and residual ridge resorption were subjected to the Mann-Whitney U test, the Spearman correlation test, and a stepwise multiple linear regression analysis (α=.05).

Results: Calcium (P=.003) and phosphorus (P<.001) levels were significantly increased in the female participants as compared with the male participants. Vitamin D3 levels were similar in all the participants. Moreover, metabolic levels of calcium (rho=-0.09), phosphorus (rho=-0.10), and vitamin D3 (rho=-0.02) were found to be reduced with increasing age. However, male participants had increased mandibular residual ridge resorption (P<.001) with positive correlation (rho=0.06) when compared with female participants. Mandibular ridge resorption was increased with a decrease in levels of serum nutrients.

Conclusions: Increased levels of mandibular residual ridge resorption were observed in participants with decreased levels of systemic biochemical parameters, including calcium, phosphorus, and vitamin D3. Moreover, male participants showed increased residual ridge resorption when compared with female participants, who showed a significantly higher level of serum nutrient levels. Serum nutrient levels decreased, whereas mandibular residual ridge resorption increased with age.
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http://dx.doi.org/10.1016/j.prosdent.2020.07.019DOI Listing
November 2020

Functional analysis of bovine interleukin-10 receptor alpha in response to Mycobacterium avium subsp. paratuberculosis lysate using CRISPR/Cas9.

BMC Genet 2020 11 2;21(1):121. Epub 2020 Nov 2.

Animal and Bioscience Research Department, Animal and Grassland Research and Innovation Centre, Teagasc, Grange, Co. Meath, Ireland.

Background: The interleukin-10 receptor alpha (IL10RA) gene codes for the alpha chain of the IL-10 receptor which binds the cytokine IL-10. IL-10 is an anti-inflammatory cytokine with immunoregulatory function during the pathogenesis of many inflammatory disorders in livestock, including Johne's disease (JD). JD is a chronic enteritis in cattle caused by Mycobacterium avium subsp. paratuberculosis (MAP) and is responsible for significant economic losses to the dairy industry. Several candidate genes including IL10RA have been found to be associated with JD. The aim of this study was to better understand the functional significance of IL10RA in the context of immune stimulation with MAP cell wall lysate.

Results: An IL10RA knock out (KO) bovine mammary epithelial cell (MAC-T) line was generated using the CRISPR/cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9) gene editing system. These IL10RA KO cells were stimulated with the immune stimulant MAP lysate +/- IL-10, or with LPS as a positive control. In comparison to unedited cells, relative quantification of immune-related genes after stimulation revealed that knocking out IL10RA resulted in upregulation of pro-inflammatory cytokine gene expression (TNFA, IL1A, IL1B and IL6) and downregulation of suppressor of cytokine signaling 3 (SOCS3), a negative regulator of pro-inflammatory cytokine signaling. At the protein level knocking out IL10RA also resulted in upregulation of inflammatory cytokines - TNF-α and IL-6 and chemokines - IL-8, CCL2 and CCL4, relative to unedited cells.

Conclusions: The findings of this study illustrate the broad and significant effects of knocking out the IL10RA gene in enhancing pro-inflammatory cytokine expression and further support the immunoregulatory role of IL10RA in eliciting an anti-inflammatory response as well as its potential functional involvement during the immune response associated with JD.
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http://dx.doi.org/10.1186/s12863-020-00925-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607837PMC
November 2020

Identification of Ovine Serum miRNAs Following Bacterial Lipopolysaccharide Challenge.

Int J Mol Sci 2020 Oct 25;21(21). Epub 2020 Oct 25.

Department of Animal Biosciences, University of Guelph, Guelph, ON N1G 2W1, Canada.

Host-pathogen interactions are complex and influenced by host genetic and epigenetic modifications. Recently, the significance of microRNAs (miRNAs) in pathogenic infection and the regulation of immune response has been highlighted. However, information on miRNAs' role in the course of inflammation is still very limited in small ruminants. The present study was intended to identify changes in the expression of circulatory miRNAs post-lipopolysaccharide (LPS)-challenge. In this study, young ewes ( = 18) were challenged with LPS (400 ng/kg ) and blood samples were collected for serum miRNA isolation at two-time points; prior to challenge (T0), and 4 h (T4) post-challenge, reflecting the peak cortisol response. A total of 91 miRNAs were profiled, including 84 miRNAs on a commercial ovine miRNA-PCR array, and seven individual miRNAs. Forty five miRNAs were differentially expressed (DE) with 35 being up-regulated (Fold regulation, FR > 2) and 10 being down-regulated (FR < 1, < 0.05) at T4. Among the up-regulated miRNAs, 14 were significantly ( < 0.05) induced, including oar-miRs: 369-3p, 495-3p, 376a-3p, 543-3p, 668-3p, 329a-3p, 655-3p, 411a-5p, and 154a-3p, which were located on ovine chromosome 18 forming four miRNA clusters within 10 kb. The elevated miRNAs belonged to different functional classes, playing roles in activating the hypothalamic-pituitary-adrenal axis; increasing cell survival and differentiation; and inducing inflammatory responses and targeted PI3K-Akt and MAPK signaling and chemokine signaling pathways. In summary, these results reveal the dynamic nature of ovine serum miRNAs during LPS-induced stress and highlight the potential role of identified miRNA-clusters on chromosome 18 to understand the regulation of the acute-phase response. Some of these identified circulating miRNAs may also serve as stress biomarkers for livestock in the future.
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http://dx.doi.org/10.3390/ijms21217920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663744PMC
October 2020

Natural Products in Mitigation of SARS CoV Infections.

Curr Med Chem 2020 Oct 27. Epub 2020 Oct 27.

Medicinal Chemistry Division, CSIR- Indian Institute of Integrative Medicine, Canal Road, Jammu 180001. India.

The severe acute respiratory syndrome (SARS) is a critical respiratory disease caused by coronaviruses (CoV). The available antiviral agents or host-specific anti-inflammatory therapies are the principal treatment modalities, with drugrepurposing as the most viable approach to timely tackle the CoV pandemic. Though these approaches are successful to some extent in reducing the mortality rate, however, it is too far to see a complete escape from the current CoV-2 pandemic. Plants are the primary source of diet, dietary supplements, botanical drugs, and natural products (NPs). It has been well accepted and proved via several scientific studies that plant-based therapies play a vital role in protecting against such infections. The faulty immune system (compromised innate immunity or aberrant immune activation) decides the severity of the respiratory distress in CoV-2 infected patients. Natural products intervene at various stages of the virus replication cycle, including inhibition of virus entry into the host cells, inhibition of serine/ cysteine proteases, RNA-dependent RNA polymerase (RdRp) or helicase. Besides, several natural products or plant-based dietary ingredients have a unique ability to strengthen the immune system or alleviate the hyper-inflammatory condition. Many plant-based formulations, dietary supplements, and NPs are being investigated in clinical trials in CoV-2 patients, and few have already shown positive results. The review has unearthed several NP leads for medicinal chemistry programs as well as some having direct opportunity of repurposing in SARS CoV infections.
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http://dx.doi.org/10.2174/0929867327666201027153940DOI Listing
October 2020

Comparative Evaluation of Mechanical and Microleakage Properties of Cention-N, Composite, and Glass Ionomer Cement Restorative Materials.

J Contemp Dent Pract 2020 Jun 1;21(6):691-695. Epub 2020 Jun 1.

Department of Conservative Dentistry and Endodontics, Maharshi Markandeshwar College of Dental Sciences and Research, Mullana, Ambala, Haryana, India.

Aim: The longevity of restorative materials depends on the resistance to masticatory forces. The present study was undertaken to evaluate the mechanical and microleakage properties of Cention-N with glass ionomer cement (GIC) and composite restorative materials.

Materials And Methods: A total of 45 specimen blocks were prepared with 15 samples of each type of restorative material, namely Cention-N, GIC, and hybrid composite. Samples were subjected to load at crosshead speed of 0.75 ± 0.25 mm/min till the fracture of sample. Class V cavities were prepared on the buccal surface of orthodontically extracted premolars followed by restoration of each test material. All the surfaces of the tooth were coated with clear nail varnish except 1 mm around the margins of the restorations. These samples were immersed in 0.5% basic fuchsine dye and longitudinally sectioned and observed under stereomicroscope to check microleakage. The obtained data were statistically evaluated.

Results: We found the highest mean compressive and flexural strength for hybrid composite followed by Cention-N and least for GIC which is statistically significant ( < 0.001).

Conclusion: Mean microleakage was least for Cention-N. Cention-N is a newer restorative material having higher mechanical properties with lesser microleakage.

Clinical Significance: Cention-N is a newer restorative material having promising properties. This material can be used as an alternative restorative material.
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June 2020

Incidence and prevalence of giant cell arteritis and polymyalgia rheumatica: A systematic literature review.

Semin Arthritis Rheum 2020 10 14;50(5):1040-1048. Epub 2020 Jul 14.

Rheumatology, Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden; Department of Rheumatology, Skåne University Hospital, Jan Waldenströms gata 1B, 205 02, Malmö, Sweden. Electronic address:

Background: Giant cell arteritis (GCA; sometimes referred to as temporal arteritis) and polymyalgia rheumatica (PMR) are common and interrelated inflammatory conditions that almost exclusively affect adults older than 50 years. There is a need for updated information on the epidemiology of these diseases.

Objective: This systematic literature review (SLR) aims to summarize current evidence regarding the global incidence and prevalence of GCA and PMR.

Methodology: A systematic search of PubMed and Google Scholar databases from their inception dates to July 30, 2019 for relevant publications was performed. Studies that reported incidence and/or prevalence estimates for GCA and/or PMR were identified. When there were multiple studies of the same population, the most recent estimates were used. Details on source populations and case validation were systematically reviewed. Results were tabulated per region in the world.

Results: Screening by 2 authors resulted in 2643 abstracts, of which 77 articles met the inclusion criteria. There were more studies on GCA compared to PMR, and more on incidence than on prevalence. Wide variations were found in study design and populations studied. Studies that included a thorough case validation tended to give lower estimates, in particular for PMR. The highest incidence per 100 000 aged ≥50 years of GCA was observed in studies from Scandinavia and the UK (14.6 to 43.6), and in Minnesota, USA (19.8 per 100 000). Corresponding estimates for Southern Europe were lower (1.1 to 11.1). Limited evidence indicates that GCA and PMR is less common in non-Caucasian populations. Prevalence estimates for PMR were ≥ 3 times higher than that of GCA in Caucasians.

Conclusion: This SLR provides up to date estimates of the occurrence of GCA and PMR in different populations around the world. The incidence of GCA is higher in populations of Northern European ancestry. Data on the epidemiology of PMR are more limited, with greater variation in incidence and prevalence estimates.
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http://dx.doi.org/10.1016/j.semarthrit.2020.07.005DOI Listing
October 2020

Reactivity of allyl methyl sulphide, the in-vitro metabolite of garlic, with some amino acids and with phospholipid involved in viral infections.

J Biomol Struct Dyn 2020 Aug 24:1-7. Epub 2020 Aug 24.

CSIR-Indian Institute of Petroleum, Dehradun, India.

Garlic, as well as several natural food ingredients such as basil, ginger, turmeric, cinnamon, clove, pepper etc., has long been traditionally used as routine anti-viral and anti-bacterial remedy. Allyl methyl sulfide (AMS) is reportedly a persistent main active metabolite component of allicin after garlic ingestion accounting for at least 90% of the allicin consumed. Several studies have reported the presence of AMS in organs such as lung, kidney etc. and body fluids such as mucous, and blood-plasma. Glycoproteins of enveloped viruses are actively involved in viral pathogenesis. N-acetylneuraminic acid (sialic acid) and N-Acetylglucosamine, are some of the vital amino acids involved in several viral infections using glycoproteins via glycosylation. Simulations studies based on First-principles density functional theory show that these amino acids attach with AMS, and the reactions are thermodynamically spontaneous (ΔG and ΔS negative are at 310.15 K as well as lower and higher temperatures). Further, phospholipid phosphatidylethanolamine (a component of some viral envelops) also attaches readily with AMS and the reaction is spontaneous. AMS molecules attachment with viral phospholipids and amino-acids involved in viral infection would denature the virus and prevent its attachment to the host cell.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1811154DOI Listing
August 2020

A Comparative Study of the Diagnostic and Prognostic Utility of Soluble Urokinase-type Plasminogen Activator Receptor and Procalcitonin in Patients with Sepsis and Systemic Inflammation Response Syndrome.

Indian J Crit Care Med 2020 Apr;24(4):245-251

Department of Research, Sir Ganga Ram Hospital, New Delhi, India.

Introduction: Differentiation between sepsis and systemic inflammation response syndrome (SIRS) remains a diagnostic challenge for clinicians as both may have similar clinical presentation. A quick and accurate diagnostic tool that can discriminate between these two conditions would aid in appropriate therapeutic decision-making. This prospective study was conducted to evaluate the diagnostic and prognostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) and procalcitonin (PCT) in sepsis and SIRS patients.

Materials And Methods: Eighty-eight patients were enrolled, of which 29 were SIRS and 59 were sepsis patients. The levels of suPAR and PCT were measured on the day of admission (day 1), day 3, and day 7.

Results: The levels of suPAR and PCT were significantly higher ( = 0.05 and < 0.001, respectively) in sepsis group as compared to the SIRS group. The soluble urokinase-type plasminogen activator receptor was a better diagnostic tool in predicting sepsis over PCT [area under curve (AUC) 0.89 vs 0.82] on day 1. The best cutoff for suPAR was 5.58 pg/mL [96% sensitivity and 90% negative predictive value (NPV)] and the best cut-off for PCT was 1.96 ng/mL (93.1% sensitivity and 80% NPV). However, PCT had better prognostic trends ( = 0.006) to identify nonsurvivors in sepsis group.

Conclusion: Our findings suggest that both suPAR and PCT can be used as potential test tools to differentiate between SIRS and sepsis. Procalcitonin showed significant prognostic trends to identify nonsurvivors. The soluble urokinase-type plasminogen activator receptor showed better diagnostic potential than PCT on day 1.

Clinical Significance: Both suPAR and PCT can be used as surrogate biomarkers to distinguish sepsis from SIRS. Procalcitonin showing a significant prognostic trend to identify nonsurvivors can help the clinicians to take relevant clinical decisions. Also, the use of biomarkers like PCT and suPAR could reduce the inappropriate use of antibiotics in noninfective SIRS.

How To Cite This Article: Sharma A, Ray S, Mamidipalli R, Kakar A, Chugh P, Jain R, A Comparative Study of the Diagnostic and Prognostic Utility of Soluble Urokinase-type Plasminogen Activator Receptor and Procalcitonin in Patients with Sepsis and Systemic Inflammation Response Syndrome. Indian J Crit Care Med 2020;24(4):245-251.
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http://dx.doi.org/10.5005/jp-journals-10071-23385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297249PMC
April 2020

Preoperative Noninvasive Cardiac Testing in Older Adults with Hip Fracture: A Multi-Site Study.

J Am Geriatr Soc 2020 08 11;68(8):1690-1697. Epub 2020 Jun 11.

Department of Medicine, Northwell Health System, Manhasset, New York, USA.

Background/objectives: For older adults with acute hip fracture, use of preoperative noninvasive cardiac testing may lead to delays in surgery, thereby contributing to worse outcomes. Our study objective was to evaluate the preoperative use of pharmacologic stress testing and transthoracic echocardiogram (TTE) in older adults hospitalized with hip fracture.

Design: Retrospective chart review.

Setting: Seven hospitals (three tertiary, four community) within a large health system.

Participants: Patients, aged 65 years and older, hospitalized with hip fracture (n = 1,079; mean age = 84.2 years; 75% female; 82% white; 36% married).

Measurements: Data were extracted from electronic medical records. The study evaluated associations between patient factors as well as clinical outcomes (time to surgery [TTS], length of stay [LOS], and in-hospital mortality) and the use of preoperative noninvasive cardiac testing (pharmacologic stress tests or TTE). Descriptive statistics were calculated. Cox regression was performed for both TTS and LOS (evaluated as time-dependent variable); logistic regression was used for in-hospital mortality.

Results: Although 34.3% (n = 370) had a preoperative TTE, .7% (n = 8) underwent a nuclear stress test and none had a dobutamine stress echocardiogram. Median TTS was 1.1 days (IQR [interquartile range] = .8-1.8 days), median LOS was 5.3 days (IQR = 4.2-7.2 days), and in-hospital mortality was 3% (n = 32). Patients admitted to the medical service had 3.5 times greater odds of undergoing a TTE compared with those on the orthopedic service (P < .001). Community hospitals had almost three times greater odds of preoperative TTE than tertiary centers (P < .001). In multivariable analysis, preoperative TTE was significantly associated with increased TTS (P < .001). No difference in mortality was found between patients with and without a preoperative TTE.

Conclusion: This study highlights the high rate of TTE in preoperative assessment of older adults with acute hip fracture. Given the association between TTE and longer TTS, further studies must clarify the role of preoperative TTE in this population. J Am Geriatr Soc 68:1690-1697, 2020.
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http://dx.doi.org/10.1111/jgs.16555DOI Listing
August 2020

Berbamine induced AMPK activation regulates mTOR/SREBP-1c axis and Nrf2/ARE pathway to allay lipid accumulation and oxidative stress in steatotic HepG2 cells.

Eur J Pharmacol 2020 Sep 8;882:173244. Epub 2020 Jun 8.

Herbal Research Laboratory, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan 31, Post Box No. 80, Mahatma Gandhi Marg, Lucknow, 226001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India. Electronic address:

Non-alcoholic fatty liver disease is emanating as a global cataclysm. This study was designed to investigate the antioxidative, anti-inflammatory and fat metabolism-regulating potential of berbamine (BBM), a natural bis-benzylisoquinoline alkaloid. BBM attenuated intracellular lipid accumulation in oleic-acid exposed HepG2 cells (0.5 mM) by inhibiting fatty acid uptake, lipogenesis, and promoting fatty acid β-oxidation by activating AMP-activated kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR)-α. Berbamine (5 μM) induced AMPK activation (P < 0.001) via LKB1 (Ser-428) and elevated AMP:ATP ratio (P < 0.001). AMPK activation negatively regulated mTOR and also constrained the nuclear translocation of SREBP-1c and inhibited the lipogenic proteins, stearoyl-CoA desaturase-1 (SCD-1) and fatty acid synthase (FAS) (P < 0.001). BBM stimulated nuclear translocation of redox-sensitive nuclear factor erythroid-2-related factor-2 (Nrf2) and increased hepatic expression of Nrf2 responsive enzymes, HO-1 and Nqo-1. BBM treatment reduced the oxidative burst and pro-inflammatory responses by significantly enhancing hepatic antioxidant defenses [SOD (P < 0.001), catalase (P < 0.001) and cellular glutathione (P < 0.01)] and diminishing NF-κB regulated pro-inflammatory cytokines (TNF-α, and IL-6) levels respectively. TEM analysis confirmed the disruption of mitochondrial structure and reduction in mitochondrial size (50.97%, P < 0.001) in steatotic HepG2 cells which was significantly prevented by 5 μM BBM treatment (71.84% as compared to control, P < 0.01). Pre-treatment of Compound C (AMPK inhibitor, 25 μM) greatly repressed the anti-steatotic properties exhibited by BBM confirming the involvement of AMPK signaling pathway. In summary, the results manifest that BBM reduces intracellular lipid accumulation via AMPK/mTOR/SREBP-1c axis mediated regulation of lipid metabolism and upsurged nuclear stability of Nrf2 by promoting AMPK/Nrf2 association to ameliorate oxidative stress/proinflammatory response.
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http://dx.doi.org/10.1016/j.ejphar.2020.173244DOI Listing
September 2020

Identification and characterization of long non-coding RNAs regulating resistant starch biosynthesis in bread wheat (Triticum aestivum L.).

Genomics 2020 09 22;112(5):3065-3074. Epub 2020 May 22.

Agri-Food Biotechnology Division, National Agri-Food Biotechnology Institute, Mohali, 140306, Punjab, India. Electronic address:

Resistant starch (RS) also known as healthy starch has shown several health benefits. Enhancing the RS through genetic modification approaches has huge commercial importance. Regulatory RNA like long non-coding RNA (lncRNA) plays an important role in gene regulation. In this study, we mined 63 transcriptome datasets of wheat belonging to 35 genotypes representing two seed developmental stages. Contrasting expression of a subset of lncRNAs in RS mutant lines compared to parent wheat variety 'C 306' signifies their probable role in RS biosynthesis. Further, lncRNA- TCONS_00130663 showed strong positive correlation (r = 1) with LYPL gene and strong negative correlation with SBEIIb (r = -0.94). We found TCONS_00130663 as positive regulator of LYPL gene through interaction with miR1128. Based on relative expression, in silico interaction and DSC analysis we hypothesize the dual role of TCONS_00130663 in RS type 2 and type 5. The study provides a useful resource for functional mechanism of lncRNAs.
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http://dx.doi.org/10.1016/j.ygeno.2020.05.014DOI Listing
September 2020

Activation of autophagic flux via LKB1/AMPK/mTOR axis against xenoestrogen Bisphenol-A exposure in primary rat hepatocytes.

Food Chem Toxicol 2020 Jul 17;141:111314. Epub 2020 Apr 17.

Herbal Research Laboratory, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), 31, Vishvigyan Bhawan, Mahatma Gandhi Marg, Lucknow, 226001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India. Electronic address:

Bisphenol-A, an endocrine disruptive chemical widely used to manufacture polycarbonate plastics and epoxy resins, acts via multiple mechanisms that perturb cellular and molecular functions. BPA has the potential to induce hepatotoxicity via generation of ROS and oxidative stress. However, the mechanism of BPA induced oxidative stress and autophagy is still ambiguous at molecular and cellular levels. This study aims to elucidate the impact of BPA exposure (50 and 100 μM) in primary rat hepatocytes. AMP kinase, an intracellular energy sensor and key regulator in cellular signaling were found to be activated during BPA exposure. The increased AMP/ATP ratio and subsequent phosphorylation by its upstream mediator Liver Kinase B1 (LKB1) activates AMPK. BPA down-regulated AMPK downstream molecule i.e. mammalian target of rapamycin (mTOR) by inhibiting its phosphorylation, eventually enhances expression of autophagic markers LC3B, Beclin-1 while lowers p62. Results also revealed that BPA induces mitophagy by promoting accumulation of PINK1 and translocation of Parkin to damaged mitochondria culminating in decreased mitochondrial mass. Ultra-structural changes also confirmed mitochondrial disintegration, enhanced autophagic induction as evident from autophagosome formation. Findings confirm that BPA caused oxidative stress which eventually triggered LKB1/AMPK mediated autophagy and maintains cellular energy balance by mitophagic removal of unhealthy mitochondria in primary rat hepatocytes.
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http://dx.doi.org/10.1016/j.fct.2020.111314DOI Listing
July 2020

Spatio-temporal distribution of micronutrients in rice grains and its regulation.

Crit Rev Biotechnol 2020 Jun 23;40(4):490-507. Epub 2020 Mar 23.

Department of Agri-Biotechnology, National Agri-Food Biotechnology Institute (NABI), Mohali, India.

Rice has been a staple food for more than half of the global population. Different parts of rice grains contain different amounts of macro- and micro-nutrients. Polished white rice, which is the main form of rice consumption, mainly contains starch, however, the bran and germ, which are removed during polishing, contain large amounts of micronutrients and bioactive compounds. To engineer nutritionally superior rice varieties, it is imperative to understand the spatial and temporal distribution of different nutrients in different parts of the rice grain. Keeping this in mind, in this review, we have performed a comprehensive literature review to put together all the recent findings regarding the spatio-temporal distribution of all the important micronutrients in different cell-layers/tissues of developing seeds and mature seed grains. Furthermore, we have overviewed the underlying cell-layer specific possible regulatory mechanism responsible for the loading/partitioning for each of the micronutrients into specific tissue types. Most of the nutrient filling occurs between 7 and 18 days after fertilization (DAF) through the dorsal vascular bundle and the aleurone layer. During the last few years, spatio-temporal distribution of various minerals and the role of their transporters has been studied in great detail. However, with regard to vitamins and other bioactive compounds, such studies are still very limited. Distribution of minerals in the grain is mainly regulated by the distribution of their ligands and transporters, whereas the accumulation of various vitamins is mainly metabolic enzyme activity. Collective knowledge discussed here in this niche area would help to design new studies to improve the micronutrient content located in the inner part of the seed.
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http://dx.doi.org/10.1080/07388551.2020.1742647DOI Listing
June 2020

Sickle cell disease presenting in the third trimester of pregnancy: Delayed detection heralding a public health problem?

Indian J Public Health 2020 Jan-Mar;64(1):93-95

Director Professor, Department of Pathology, Lady Hardinge Medical College, New Delhi, India.

We report the case of a 22-year-old primigravida detected as having sickle cell disease (SCD), initially presenting in the third trimester (30 week) of pregnancy. The patient came to our center with a complaint of severe lower limb pain. The peripheral smear showed marked anisopoikilocytosis, numerous leptocytes, sickle cells, and target cells. High-performance liquid chromatography corroborated the diagnosis of SCD, showing a significant peak in the sickle window. The patient was conservatively managed and delivered a healthy baby through normal vaginal delivery. Delayed presentation of SCD in the third trimester of pregnancy is unusual. This report aims to bring attention to the possible causes of such a lag in detection. We also suggest measures to refine the antenatal healthcare screening at multiple levels, with regard to the detection of sickle cell hemoglobinopathy.
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http://dx.doi.org/10.4103/ijph.IJPH_223_19DOI Listing
December 2020

Heat stress modulates differential response in skin fibroblast cells of native cattle (Bos indicus) and riverine buffaloes (Bubalus bubalis).

Biosci Rep 2020 02;40(2)

Animal Biotechnology Division, ICAR-National Bureau of Animal Genetic Resources, Karnal 132001, Haryana, India.

Heat stress in hot climates is a major cause that negatively affects dairy animals, leading to substantial economic loss. The present study was aimed to analyze the effect of heat stress on cellular and molecular levels in dermal fibroblast of cattle and buffaloes. Primary fibroblast culture was established using ear pinna tissue samples of cattle (Bos indicus) and riverine buffaloes (Bubalus Bubalis). The cells were exposed to thermal stress at 42°C for 1 h and subsequently allowed to recover and harvest at 37°C at different time points (0, 2, 4, 8, 16, and 24 h) along with control samples. Different cellular parameters viz., apoptosis, proliferation, mitochondrial membrane potential (ΔΨm), oxidative stress, along with expression pattern of heat responsive genes and miRNAs were determined. Cell viability and proliferation rate of heat-stressed fibroblasts decreased significantly (P < 0.05) albeit to a different extent in both species. The cell cytotoxicity, apoptosis, production of reactive oxygen species, and ΔΨm increased more significantly (P < 0.01) in heat stressed fibroblasts of buffalo than cattle. The pattern of heat shock proteins, inflammation/immune genes, and heat responsive miRNA showed differences in induction of their expression level in buffalo and native cattle fibroblasts. Conclusively, finding indicates that heat stress induces more profound impact on buffalo fibroblasts than native cattle fibroblasts. The differential response of cellular parameters, HSP genes, and miRNA expression could be due to better adaptive capacity of skin fibroblast of Bos indicus cattle in comparison with riverine buffaloes.
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http://dx.doi.org/10.1042/BSR20191544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012655PMC
February 2020

Effect of Natural Phenolics on Pharmacokinetic Modulation of Bedaquiline in Rat to Assess the Likelihood of Potential Food-Drug Interaction.

J Agric Food Chem 2020 Feb 24;68(5):1257-1265. Epub 2020 Jan 24.

PK-PD, Toxicology and Formulation Division , CSIR-Indian Institute of Integrative Medicine , Jammu 180001 , India.

Bedaquiline (TMC-207) is a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB). Moreover, there is a present and growing concern for natural-product-mediated drug interaction, as these are inadvertently taken by patients as a dietary supplement, food additive, and medicine. In the present study, we investigated the impact of 20 plant-based natural products, typically phenolics, on in vivo oral bedaquiline pharmacokinetics, as previous studies are lacking. Three natural phenolics were identified that can significantly enhance the oral exposure of bedaquiline upon coadministration. We further investigated the possible role of all of the phytochemicals on in vitro -glycoprotein (-gp) induction and inhibition and CYP3A4 inhibition in a single platform as bedaquiline is the substrate for both -gp and CYP3A4. In conclusion, curcumin, CC-I (3',5-dihydroxyflavone-7--β-d-galacturonide-4'--β-d-glucopyranoside), and 6-gingerol should not be coadministered with bedaquiline to avoid untoward drug interactions and, subsequently, its dose-dependent adverse effects.
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http://dx.doi.org/10.1021/acs.jafc.9b06529DOI Listing
February 2020

Evaluation of Milk Colostrum Derived Lactoferrin of Sahiwal () and Karan Fries (Cross-Bred) Cows for Its Anti-Cancerous Potential.

Int J Mol Sci 2019 Dec 14;20(24). Epub 2019 Dec 14.

ICAR-National Bureau of Animal Genetic Resources, Karnal 132001, India.

Lactoferrin (Lf) is an iron-binding glycoprotein protein known to have immune-modulatory role and recently, its anticancerous effect against different cancer cell types was emphasized. In the present investigation, a comparative evaluation of anticancer potential of colostrum-derived lactoferrin from Indian native zebu cow (Sahiwal, SAC), crossbred (Karan Fries, KFC) and commercially available (C-Lf) lactoferrin from exotic cow using cellular models was made. A protocol was standardized successfully to purify Lf protein from colostrum of both breeds using HPLC and purity was confirmed by LC-MS. A standardized dose of 750 µg/mL Lf was used to treat two cell types MDA-MB-231 and MCF-7 with Lf from three different sources; SAC-Lf, KFC-Lf and C-Lf for 48 h and 72 h. Different cellular parameters including cytotoxicity, viability, apoptosis and cell proliferation were determined. Comparatively, Lf from commercial source (C-Lf) had maximum effect in both cell types followed by SAC-Lf and KFC-Lf. Further, transcriptional changes in genes associated with apoptosis ( and ), tumor progression (, , and ) and survival () were evaluated in Lf treatment. The overall results strongly emphasized to the fact that Lf purified from cow colostrum has the capacity to inhibit the in vitro growth of cancerous cell lines albeit to a varied extent.
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http://dx.doi.org/10.3390/ijms20246318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940737PMC
December 2019

Evaluation of Anti-inflammatory Effects of Choerospondias axillaris Fruit's Methanolic Extract in Synoviocytes and CIA Rat Model.

Curr Pharm Biotechnol 2020 ;21(7):596-604

CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.

Background: Rheumatoid Arthritis (RA) is an autoimmune, systemic disease mainly affecting joints. Presently, there is no specific treatment/ drug available for curing RA except few supportive medicines. Therefore, the focus has been shifted to medicinal plants for the treatment of such diseases. Choerospondias axillaris commonly known as Lupsi/Lapsi and has been reported to have several properties for the treatment of various diseases.

Objective: The present study has been conducted to explore the anti-inflammatory effects of Choerospondias axillaris fruit extract on Synoviocytes (FLS) and Collagen-Induced Arthritis (CIA) rat model.

Methods: Methanolic extract of the Choerospondias axillaris fruit was used for determining phytochemical, antioxidant and anti-inflammatory properties. Antioxidant activity of Choerospondias axillaris fruit was determined by free radicals scavenging assays and bioactive compounds were identified via LC-MS/MS analysis. Anti-inflammatory effect was investigated in RA and Osteo Arthritis (OA) primary cells and also in Collagen Induced Arthritis (CIA) rat models. Further, the medicinal properties of anti-inflammatory bioactive compounds were supported by docking studies.

Results: In-vitro and in-vivo studies showed significant decrease in the levels of inflammatory cytokines. Docking analysis revealed that quercetin inhibits TNF-α having -9.1 kcal/mol binding energy and 10.13 μM inhibitory constant. Quercetin also inhibits IL-6 having -6.6 kcal/mol binding energy and 21.9 μM inhibitory constant.

Conclusion: Observed results suggest that the underutilized fruit Choerospondias axillaris can be used to reduce the inflammation of inflammatory diseases like RA.
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http://dx.doi.org/10.2174/1389201021666191210114127DOI Listing
August 2020

Entrenching role of cell cycle checkpoints and autophagy for maintenance of genomic integrity.

DNA Repair (Amst) 2020 02 13;86:102748. Epub 2019 Nov 13.

Herbal Research Laboratory, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), 31, Vishvigyan Bhawan, Mahatma Gandhi Marg, Lucknow, 226001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India. Electronic address:

Genomic integrity of the cell is crucial for the successful transmission of genetic information to the offspring and its survival. Persistent DNA damage induced by endogenous and exogenous agents leads to various metabolic manifestations. To combat this, eukaryotes have developed complex DNA damage response (DDR) pathway which senses the DNA damage and activates an arsenal of enzymes for the repair of damaged DNA. The active pathways for DNA repair are nucleotide excision repair (NER), base excision repair (BER) and mismatch repair (MMR) for single-strand break repair whereas homologous recombination (HR) and non-homologous end-joining (NHEJ) for double-strand break repair. OGG1 is a DNA glycosylase which initiates BER while Mre11-Rad50-Nbs1 (MRN) protein complex is the primary responder to DSBs which gets localized to damage sites. DNA damage response is meticulously executed by three related kinases: ATM, ATR, and DNA-PK. ATM- and ATR-dependent phosphorylation of p53, Chk1, and Chk2 regulate the G1/S, intra-S, or G2/M checkpoints of the cell cycle, respectively. Autophagy is an evolutionarily conserved process that plays a pivotal role in the regulation of DNA repair and maintains the cellular homeostasis. Genotoxic stress-induced altered autophagy occurs in a P53 dependent manner which is also the master regulator of genotoxic stress. A plethora of proteins involved in autophagy is regulated by p53 which involve DRAM, DAPK, and AMPK. As evident, the mtDNA is more prone to damage than nuclear DNA because of its close proximity to the site of ROS generation. Depending on the extent of damage either the repair mechanism or mitophagy gets triggered. SIRT1 is the master regulator which directs the stress response to mitophagy. Nix, a LC3 adapter also participates in Parkin mediated mitophagy. This review highlights the intricate crosstalks between DNA damage and cell cycle checkpoints activation. The DNA damage mediated regulation of autophagy and mitophagy is also reviewed in detail.
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http://dx.doi.org/10.1016/j.dnarep.2019.102748DOI Listing
February 2020

Characterizing binding sites of heat responsive microRNAs and their expression pattern in heat stressed PBMCs of native cattle, exotic cattle and riverine buffaloes.

Mol Biol Rep 2019 Dec 22;46(6):6513-6524. Epub 2019 Oct 22.

ICAR-National Bureau of Animal Genetic Resources, Karnal, Haryana, India.

It is generally believed that due to evolutionary differences and adaptation to tropical conditions, Indian native cattle has superior heat tolerant ability than Bos taurus cattle. In the present study, 3'-UTR of two most important heat responsive genes i.e., heat shock protein 70.1 (HSP70.1) and heat shock factor- 1 (HSF-1) were sequence characterized in different breeds of Indian native cattle to identify the variations and miRNA binding sites. In addition, the impact of heat stress was assessed in a total of 57 PBMCs samples of native Sahiwal cows (Bos indicus), exotic Holstein cows (Bos taurus) and Murrah buffaloes (Bubalus bubalis) using various cellular parameters like cell viability, cytotoxicity and apoptosis. Further, expression profile of 12 heat responsive miRNAs were also evaluated in unstressed and stressed PBMCs to understand post transcriptional changes in native cows, exotic cows and Murrah buffaloes. The sequence data showed 3'-UTR of HSP70.1 gene of Indian cattle to be exactly similar to Bos taurus with no miRNA binding site. Whereas, sequencing of 3'-UTR of HSF-1 gene revealed 3 SNPs at positions G1762T; C1811T and C1983T with 7 well conserved miRNA binding sites. The impact of heat stress on various cellular parameters in terms of cell viability, cytotoxicity and apoptosis was highest in PBMCs of Holstein cows followed by Murrah buffaloes and Sahiwal cows. Further, in contrast to Holstein Frisian cows and Murrah buffaloes, the expression pattern of 12 heat responsive miRNAs, in heat stressed PBMCs of Sahiwal cows were quite distinct. There was a significant (p < 0.05) induction in expression of most of the miRNAs after heat stress in PBMCs of Sahiwal cows followed by a rapid decline. The distinct cellular response and pattern of miRNA expression across cattle types and buffaloes might be influencing their PBMCs tolerance level to heat stress.
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http://dx.doi.org/10.1007/s11033-019-05097-8DOI Listing
December 2019