Publications by authors named "Minakshi Sharma"

27 Publications

  • Page 1 of 1

Recent advancements in urea biosensors for biomedical applications.

IET Nanobiotechnol 2021 Jun 19;15(4):358-379. Epub 2021 May 19.

Department of Biomedical Engineering, Deenbandhu Chhotu Ram University of Science and Technology, Murthal, Sonepat, India.

The quick progress in health care technology as a recurrent measurement of biochemical factors such as blood components leads to advance development and growth in biosensor technology necessary for effectual patient concern. The review wok of authors present a concise information and brief discussion on the development made in the progress of potentiometric, field effect transistor, graphene, electrochemical, optical, polymeric, nanoparticles and nanocomposites based urea biosensors in the past two decades. The work of authors is also centred on different procedures/methods for detection of urea by using amperometric, potentiometric, conductometric and optical processes, where graphene, polymer etc. are utilised as an immobilised material for the fabrication of biosensors. Further, a comparative revision has been accomplished on various procedures of urea analysis using different materials-based biosensors, and it discloses that electrochemical and potentiometric biosensor is the most promise one among all, in terms of rapid response time, extensive shelf life and resourceful design.
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http://dx.doi.org/10.1049/nbt2.12050DOI Listing
June 2021

Promotion of Early Childhood Development Using mHealth: Learnings From an Implementation Experience in Haryana.

Indian Pediatr 2021 Nov;58 Suppl 1:S37-S41

Survival for Women and Children Foundation, Sector 16, Panchkula, Haryana.

Pregnancy and the early years of life (0-3 years) are of crucial importance for a child's survival, health, growth and development. Improving care for young children is now considered fundamental to achieving the Sustainable Development Goals by 2030. With support from WHO and Intervida (an international non-governmental organization), implementation on care for early childhood development was carried out by Survival for Women and Children Foundation in 100 villages in Haryana, India. In addition to the implementation of evidence-based interventions, mHealth (phone message (SMS) and phone call) was used as a complementary strategy. The intention was to promote self-care, increase coverage, and improve inter-sectoral collaboration. One message per day was developed (915 messages) and 1564630 SMS were sent to all beneficiaries and providers to facilitate interaction. Based on learnings, the consolidation of this approach into 46 core themes helped to refine interactions. Lot Quality Assurance Sampling was used for evaluation. SMS was received, read and practiced by the caregivers and the care providers in the intervention block, being substantially higher than in the control blocks. There was a remarkable improvement in under-nutrition and wasting; however, the reduction in stunting was modest in the intervention area as compared with two control blocks. This is attributed to implementation of all strategies in the project including the complementary approach of use of mHealth. The application of SMS and phone communication continues to have relevance, since people most in need are poor and require integrated package of services maximally during this crucial period for improving equity and coverage.
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November 2021

Emerging role of trimethylamine-N-oxide (TMAO) in colorectal cancer.

Appl Microbiol Biotechnol 2021 Oct 27;105(20):7651-7660. Epub 2021 Sep 27.

Special Centre for Nanoscience, Jawaharlal Nehru University, New Delhi, 110067, India.

Among gut microbiota-derived metabolites, trimethylamine-N-oxide (TMAO) is receiving increased attention due to its possible role in the carcinogenesis of colorectal cancer (CRC). In spite of numerous reports implicating TMAO with CRC, there is a lack of empirical mechanistic evidences to concretize the involvement of TMAO in the carcinogenesis of CRC. Possible mechanisms such as inflammation, oxidative stress, DNA damage, and protein misfolding by TMAO have been discussed in this review in the light of the latest advancements in the field. This review is an attempt to discuss the probable correlation between TMAO and CRC but this linkage can be concretized only once we get sufficient empirical evidences from the mechanistic studies. We believe, this review will augment the understanding of linking TMAO with CRC and will motivate researchers to move towards mechanistic study for reinforcing the idea of implicating TMAO with CRC causation. KEY POINTS: • TMAO is a gut bacterial metabolite which has been implicated in CRC in recent years. • The valid mechanistic approach of CRC causation by TMAO is unknown. • The article summarizes the possible mechanisms which need to be explored for validation.
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http://dx.doi.org/10.1007/s00253-021-11582-7DOI Listing
October 2021

Gut microbiota-derived metabolites in CRC progression and causation.

J Cancer Res Clin Oncol 2021 Nov 17;147(11):3141-3155. Epub 2021 Jul 17.

Gene Regulation Laboratory, National Institute of Immunology, New Delhi, 110067, India.

Background: Based on recent research reports, dysbiosis and improper concentrations of microbial metabolites in the gut may result into the carcinogenesis of colorectal cancer. Recent advancement also highlights the involvement of bacteria and their secreted metabolites in the cancer causation. Gut microbial metabolites are functional output of the host-microbiota interactions and produced by anaerobic fermentation of food components in the diet. They contribute to influence variety of biological mechanisms including inflammation, cell signaling, cell-cycle disruption which are majorly disrupted in carcinogenic activities.

Purpose: In this review, we intend to discuss recent updates and possible molecular mechanisms to provide the role of bacterial metabolites, gut bacteria and diet in the colorectal carcinogenesis. Recent evidences have proposed the role of bacteria, such as Fusobacterium nucleaturm, Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis and Clostridium septicum, in the carcinogenesis of CRC. Metagenomic study confirmed that these bacteria are in increased abundance in CRC patient as compared to healthy individuals and can cause inflammation and DNA damage which can lead to development of cancer. These bacteria produce metabolites, such as secondary bile salts from primary bile salts, hydrogen sulfide, trimethylamine-N-oxide (TMAO), which are likely to promote inflammation and subsequently cancer development.

Conclusion: Recent studies suggest that gut microbiota-derived metabolites have a role in CRC progression and causation and hence, could be implicated in CRC diagnosis, prognosis and therapy.
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http://dx.doi.org/10.1007/s00432-021-03729-wDOI Listing
November 2021

Bioprospecting beneficial endophytic bacterial communities associated with Rosmarinus officinalis for sustaining plant health and productivity.

World J Microbiol Biotechnol 2021 Jul 15;37(8):135. Epub 2021 Jul 15.

Department of Soil Science and Water Management, Dr YS Parmar University of Horticulture and Forestry, Nauni, Solan, India.

The present study aimed to isolate and identify root endophytic bacteria with multifunctional plant growth promoting (PGP) traits from medicinal plant Rosmarinus officinalis grown in the North-Western Himalayas. A total of 42 strains were isolated, exhibiting variable degrees of PGP traits, including phosphate solubilization (10-375 µg/mL), indole-3-acetic acid (6-66 µg/mL), siderophore (32.37%-301.48% SU) production and antifungal activity in terms of percent growth inhibition (% GI) against Fusarium oxysporum (44.44%-77.77% GI), Fusarium graminearum (48.88%-71.42% GI) and Rhizoctonia solani (44.44%-77.7% GI). The 16S rDNA sequencing results showed lineage of these strains to 15 genera viz., Aneurinibacillus, Bacillus, Beijerinckia, Cedecea, Ensifer, Enterobacter, Kosakonia, Lactobacillus, Lysobacter, Oxynema, Pseudomonas, Pantoea, Paenibacillus, Pseudoxanthomonas and Serratia. Out of 42 strains, 11 potential strains were selected for in vivo growth studies of R. officinalis. The results showed that the inoculation of Bacillus subtilis KU21, Pseudomonas aeruginosa SI12, and Cedecea lapagei KU14 significantly increased the physical growth parameters of plant over uninoculated control viz., number of lateral of branches (43.95%-46.39%), stem height (29.04%-38.57%), root length (32.31%-37.14%), shoot (34.76%-40.91%) and root biomass (62.89%-70.70%). Physiological characteristics such as total chlorophyll (30.41%-30.96%), phenol (14.43%-24.55%) and carotenoids (34.26%-39.87%) content, also showed a relative increase as compared to uninoculated control; furthermore, the macronutrients (NPK) contents of the plant as well as soil also showed an increase. The developed module may be recommended for sustainable production of R. officinalis in the North-Western Himalayan region without hampering the soil health and fertility.
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http://dx.doi.org/10.1007/s11274-021-03101-7DOI Listing
July 2021

Omics technologies for improved diagnosis and treatment of colorectal cancer: Technical advancement and major perspectives.

Biomed Pharmacother 2020 Nov 19;131:110648. Epub 2020 Oct 19.

Gene Regulation Laboratory, National Institute of Immunology, New Delhi 110067, India. Electronic address:

Colorectal cancer (CRC) ranks third among the most commonly occurring cancers worldwide, and it causes half a million deaths annually. Alongside mechanistic study for CRC detection and treatment by conventional techniques, new technologies have been developed to study CRC. These technologies include genomics, transcriptomics, proteomics, and metabolomics which elucidate DNA markers, RNA transcripts, protein and, metabolites produced inside the colon and rectum part of the gut. All these approaches form the omics arena, which presents a remarkable opportunity for the discovery of novel prognostic, diagnostic and therapeutic biomarkers and also delineate the underlying mechanism of CRC causation, which may further help in devising treatment strategies. This review also mentions the latest developments in metagenomics and culturomics as emerging evidence suggests that metagenomics of gut microbiota has profound implications in the causation, prognosis, and treatment of CRC. A majority of bacteria cannot be studied as they remain unculturable, so culturomics has also been strengthened to develop culture conditions suitable for the growth of unculturable bacteria and identify unknown bacteria. The overall purpose of this review is to succinctly evaluate the application of omics technologies in colorectal cancer research for improving the diagnosis and treatment strategies.
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http://dx.doi.org/10.1016/j.biopha.2020.110648DOI Listing
November 2020

Electrochemical sensing of cytochrome c using Graphene Oxide nanoparticles as platform.

Int J Biol Macromol 2020 Dec 1;165(Pt A):1455-1462. Epub 2020 Oct 1.

Department of Zoology, Maharshi Dayanand University, Rohtak, Haryana, India. Electronic address:

An improved cytochrome c (Cyt c) biosensor based on immobilization of cytochrome c oxidase (COx) on the surface of graphene oxide nanoparticles (GONPs) electrodeposited onto pencil graphite (PG) electrode. Characterization of graphene oxide nanoparticle was done by Transmission electron microscopy (TEM), Fourier transform infra-red spectroscopy (FTIR) and X-ray diffraction study (XRD). The working electrode (COx/GONPs/PG) was characterized at its different stages of fabrication by scanning electron microscopy (SEM) and FTIR. Fabrication of Cyt c biosensor was done by connecting COx/GONPs/PG as working electrode, Ag/AgCl as reference electrode and Pt as auxiliary electrode to potentiostat. The mechanism of detection of present biosensor was based on oxidation of Cyt c (reduced) to Cyt c (oxidized) by COx resulting in flow of electrons through GONPs to the PG electrode, hence current generated is proportional to the concentration of Cyt c. Present biosensor exhibited optimum potential at 0.49 V with optimum pH 7.5 and optimum temperature 35°C. Biosensor showed linearity within 40-180 ng/ml having 40 ng/ml limit of detection. The precision i.e. within and between-batch coefficients of variation (CVs) were found <0.04% and <0.21% respectively. The enzyme electrode lost 50% of its initial activity when operated for more than 6 months on weekly basis. It was applied for detection of Cyt c level in in apparently healthy and diseased human sera. The present biosensing method was co-related with standard colorimetric method and co-relation coefficient was found 0.99.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.09.203DOI Listing
December 2020

Strategies and perspectives to develop SARS-CoV-2 detection methods and diagnostics.

Biomed Pharmacother 2020 Sep 19;129:110446. Epub 2020 Jun 19.

Special Centre for Nanoscience, Jawaharlal Nehru University, New Delhi, 110067, India. Electronic address:

To develop diagnostics and detection methods, current research is focussed on targeting the detection of coronavirus based on its RNA. Besides the RNA target, research reports are coming to develop diagnostics by targeting structure and other parts of coronavirus. PCR based detection system is widely used and various improvements in the PCR based detection system can be seen in the recent research reports. This review will discuss multiple detection methods for coronavirus for developing appropriate, reliable, and fast alternative techniques. Considering the current scenario of COVID-19 diagnostics around the world and an urgent need for the development of reliable and cheap diagnostic, various techniques based on CRISPR technology, antibody, MIP, LAMP, microarray, etc. should be discussed and tried.
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http://dx.doi.org/10.1016/j.biopha.2020.110446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303646PMC
September 2020

The proofreading activity of Pfprex from Plasmodium falciparum can prevent mutagenesis of the apicoplast genome by oxidized nucleotides.

Sci Rep 2020 07 7;10(1):11157. Epub 2020 Jul 7.

Regional Centre for Biotechnology, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad, Haryana, 121001, India.

The DNA polymerase module of the Pfprex enzyme (PfpPol) is responsible for duplication of the genome of the apicoplast organelle in the malaria parasite. We show that PfpPol can misincorporate oxidized nucleotides such as 8oxodGTP opposite dA. This event gives rise to transversion mutations that are known to lead to adverse physiological outcomes. The apicoplast genome is particularly vulnerable to the harmful effects of 8oxodGTP due to very high AT content (~ 87%). We show that the proofreading activity of PfpPol has the unique ability to remove the oxidized nucleotide from the primer terminus. Due to this property, the proofreading domain of PfpPol is able to prevent mutagenesis of the AT-rich apicoplast genome and neutralize the deleterious genotoxic effects of ROS generated in the apicoplast due to normal metabolic processes. The proofreading activity of the Pfprex enzyme may, therefore, represent an attractive target for therapeutic intervention. Also, a survey of DNA repair pathways shows that the observed property of Pfprex constitutes a novel form of dynamic error correction wherein the repair of promutagenic damaged nucleotides is concomitant with DNA replication.
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http://dx.doi.org/10.1038/s41598-020-67853-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341739PMC
July 2020

Comparative accuracy of 1,3 beta-D glucan and galactomannan for diagnosis of invasive fungal infections in pediatric patients: a systematic review with meta-analysis.

Med Mycol 2021 Feb;59(2):139-148

Department of Medical Microbiology, Postgraduate institute of medical education and research (PGIMER), Chandigarh, 160012.

Invasive fungal infections (IFI) cause considerable morbidity and mortality in pediatric patients. Serum biomarkers such as 1,3-beta-D glucan (BDG) and galactomannan (GM) have been evaluated for the IFI diagnosis. However, most evidence regarding their utility is derived from studies in adult oncology patients. This systematic review aimed to compare the diagnostic accuracy of BDG and GM individually or in combination for diagnosing IFI in pediatric patients. PubMed, CINAHL, Embase, and Cochrane Library were searched until March 2019 for diagnostic studies evaluating both serum GM and BDG for diagnosing pediatric IFI. The pooled diagnostic odds ratio (DOR), specificity and sensitivity were computed. Receiver operating characteristics (ROC) curve and area under the curve (AUC) were used for summarizing overall assay performance. Six studies were included in the meta-analysis. The summary estimates of sensitivity, specificity, pooled DOR, AUC of the GM assay for proven or probable IFI were 0.74, 0.76, 13.25, and 0.845. The summary estimates of sensitivity, specificity, pooled DOR, AUC of the BDG assay were 0.70, 0.69, 4.3, and 0.722. The combined predictive ability of both tests was reported in two studies (sensitivity: 0.67, specificity: 0.877). Four studies were performed in hematology-oncology patients, while two were retrospective studies from pediatric intensive care units (ICUs). In the subgroup of hematology-oncology patients, DOR of BDG remained similar at 4.25 but increased to 40.28 for GM. We conclude that GM and BDG have a modest performance for identifying IFI in pediatric patients. GM has a better accuracy over BDG. Combining both improves the specificity at the cost of sensitivity.
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http://dx.doi.org/10.1093/mmy/myaa038DOI Listing
February 2021

Novel electrochemical sensing of galactose using GalOxNPs/CHIT modified pencil graphite electrode.

Carbohydr Res 2019 Sep 17;483:107749. Epub 2019 Jul 17.

Department of Zoology, Maharshi Dayanand University, Rohtak, 124001, Haryana, India. Electronic address:

For the construction of galactose biosensor, chitosan was electropolymerised onto the pencil graphite electrode. This chitosan modified pencil graphite electrode acts as good matrix for immobilization of enzyme nanoparticles of galactose oxidase. Development of this nanocomposite was further confirmed by Fourier transform infrared spectroscopy and scanning electron microscopy. The presence of chitosan makes the present galactose biosensor more efficient, reproducible and stable. The sensitivity was reported 7 × 10 mA/mM/cm with linear range from 0.05 to 25 mM and better detection limit of 0.05 mM. When the solution of galactose was spiked with 0.5 mM and 1 mM, the analytical recoveries were found 98.6% and 97.6%. A better storage stability was achieved (90days) when compared to earlier reported biosensors.
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http://dx.doi.org/10.1016/j.carres.2019.107749DOI Listing
September 2019

Cholesterol biosensors: A review.

Steroids 2019 03 10;143:6-17. Epub 2018 Dec 10.

Department of Biotechnology, Deen Bandhu Chhotu Ram University of Science and Technology, Murthal, Sonipat, India.

Cholesterol is the most important sterol synthesized by most of the human cells majorly in the liver. It is a necessary constituent of cell membranes, it acts as a precursor for the synthesis of steroid hormones, vitamin D, and bile acids. Cholesterol is transported in plasma primarily in the form of low-density lipoproteins (LDL), the principal route for its removal from tissues to the liver is in high-density lipoproteins (HDL), followed by excretion in the bile. Cholesterol level is less than 200 mg/dL in healthy persons. 200 and 239 mg/dL is considered borderline high and 240 mg/dL and above is considered a biomarker for cardiovascular diseases, heart attack, strokes, peripheral arterial disease, type 2 diabetes and high blood pressure. Several methods are available for detection of cholesterol, among them, most are burdensome, time-consuming, require sample pre-treatment, high-cost instrumental set-up, and experienced personnel to operate. Biosensing approach overcomes these disadvantages, as these are highly specific, fast, easy, cost-effective, and highly sensitive. The review describes the various cholesterol biosensors. Cholesterol biosensors work ideally within 1 to 300 s, in pH range, 7.0-8.6, temperature 25-37 °C and cholesterol concentration range, 0.000025-700 mM, the detection limits being in the range, 0.000002-4 mM, with working potential -0.05 to 0.65 V. These biosensors measured cholesterol level in fruit juices, beverages, sera and urine samples and reused up to 200 times over a period of 15 to 50 days, while stored dry at 4 °C (Table 1). Future perspective for further improvement and commercialization of cholesterol biosensors are discussed.
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http://dx.doi.org/10.1016/j.steroids.2018.12.003DOI Listing
March 2019

Improving quality of care during childbirth in primary health centres: a stepped-wedge cluster-randomised trial in India.

BMJ Glob Health 2018 8;3(5):e000907. Epub 2018 Oct 8.

Western Command Hospital, Panchkula, India.

Background: Low/middle-income countries need a large-scale improvement in the quality of care (QoC) around the time of childbirth in order to reduce high maternal, fetal and neonatal mortality. However, there is a paucity of scalable models.

Methods: We conducted a stepped-wedge cluster-randomised trial in 15 primary health centres (PHC) of the state of Haryana in India to test the effectiveness of a multipronged quality management strategy comprising capacity building of providers, periodic assessments of the PHCs to identify quality gaps and undertaking improvement activities for closure of the gaps. The 21-month duration of the study was divided into seven periods (steps) of 3  months each. Starting from the second period, a set of randomly selected three PHCs (cluster) crossed over to the intervention arm for rest of the period of the study. The primary outcomes included the number of women approaching the PHCs for childbirth and 12 directly observed essential practices related to the childbirth. Outcomes were adjusted with random effect for cluster (PHC) and fixed effect for 'months of intervention'.

Results: The intervention strategy led to increase in the number of women approaching PHCs for childbirth (26 vs 21 women per PHC-month, adjusted incidence rate ratio: 1.22; 95% CI 1.17 to 1.28). Of the 12 practices, 6 improved modestly, 2 remained near universal during both intervention and control periods, 3 did not change and 1 worsened. There was no evidence of change in mortality with a majority of deaths occurring either during referral transport or at the referral facilities.

Conclusion: A multipronged quality management strategy enhanced utilisation of services and modestly improved key practices around the time of childbirth in PHCs in India.

Trial Registration Number: CTRI/2016/05/006963.
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http://dx.doi.org/10.1136/bmjgh-2018-000907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195146PMC
October 2018

Cell-penetrating peptide and antibiotic combination therapy: a potential alternative to combat drug resistance in methicillin-resistant Staphylococcus aureus.

Appl Microbiol Biotechnol 2016 May 2;100(9):4073-83. Epub 2016 Feb 2.

Bioactive Screening Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, 160036, India.

The diverse pattern of resistance by methicillin-resistant Staphylococcus aureus (MRSA) is the major obstacle in the treatment of its infections. The key reason of resistance is the poor membrane permeability of drug molecules. Over the last decade, cell-penetrating peptides (CPPs) have emerged as efficient drug delivery vehicles and have been exploited to improve the intracellular delivery of numerous therapeutic molecules in preclinical studies. Therefore, to overcome the drug resistance, we have investigated for the first time the effects of two CPPs (P3 and P8) in combination with four antibiotics (viz. oxacillin, erythromycin, norfloxacin, and vancomycin) against MRSA strains. We found that both CPPs internalized into the MRSA efficiently at very low concentration (<10 μM) which was non-toxic to bacteria as well as mammalian cells and showed no significant hemolytic activity. However, the combinations of CPPs (≤10 μM) and antibiotics showed high toxicity against MRSA as compared to antibiotics alone. The significant finding is that P3 and P8 could lower the MICs against oxacillin, norfloxacin, and vancomycin to susceptible levels (generally <1 μg/mL) for almost all five clinical isolates. Further, the bacterial cell death was confirmed by scanning electron microscopy as well as propidium iodide uptake assay. Simultaneously, time-kill kinetics revealed the increased uptake of antibiotics. In summary, CPPs assist to restore the effectiveness of antibiotics at much lower concentration, eliminate the antibiotic toxicity, and represent the CPP-antibiotic combination therapy as a potential novel weapon to combat MRSA infections.
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http://dx.doi.org/10.1007/s00253-016-7329-7DOI Listing
May 2016

An in silico platform for predicting, screening and designing of antihypertensive peptides.

Sci Rep 2015 Jul 27;5:12512. Epub 2015 Jul 27.

Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh-160036, India.

High blood pressure or hypertension is an affliction that threatens millions of lives worldwide. Peptides from natural origin have been shown recently to be highly effective in lowering blood pressure. In the present study, we have framed a platform for predicting and designing novel antihypertensive peptides. Due to a large variation found in the length of antihypertensive peptides, we divided these peptides into four categories (i) Tiny peptides, (ii) small peptides, (iii) medium peptides and (iv) large peptides. First, we developed SVM based regression models for tiny peptides using chemical descriptors and achieved maximum correlation of 0.701 and 0.543 for dipeptides and tripeptides, respectively. Second, classification models were developed for small peptides and achieved maximum accuracy of 76.67%, 72.04% and 77.39% for tetrapeptide, pentapeptide and hexapeptides, respectively. Third, we have developed a model for medium peptides using amino acid composition and achieved maximum accuracy of 82.61%. Finally, we have developed a model for large peptides using amino acid composition and achieved maximum accuracy of 84.21%. Based on the above study, a web-based platform has been developed for locating antihypertensive peptides in a protein, screening of peptides and designing of antihypertensive peptides.
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http://dx.doi.org/10.1038/srep12512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515604PMC
July 2015

Identification and characterization of novel protein-derived arginine-rich cell-penetrating peptides.

Eur J Pharm Biopharm 2015 Jan 29;89:93-106. Epub 2014 Nov 29.

Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh, India. Electronic address:

Cell-penetrating peptides (CPPs) have proven their potential as an efficient delivery system due to their intrinsic ability to traverse biological membranes and transport various cargoes into the cells. In the present study, we have identified novel natural protein-derived CPPs using an integrated (in silico and experimental) approach. First, using bioinformatics approach, arginine-rich peptide segments were extracted from SwissProt proteins and their cell-penetrating properties were predicted. Finally, eight peptides were selected and their internalization was validated using experimental techniques. Laser scanning confocal microscopy and flow cytometry confirmed that seven out of eight peptides were internalized into live cells with varying efficiencies without significant cytotoxicity. Three peptides have shown higher internalization efficacy than TAT peptide, the most widely used CPP. Among these three peptides, one peptide (P8), derived from voltage-dependent L-type calcium channel subunit alpha-1D, was able to accumulate inside in a variety of cell types very efficiently through a rapid dose-dependent process. Further, experiments involving inhibition with various endocytic inhibitors along with co-localization studies indicate that the uptake mechanism of P8 is macropinocytosis, a fluid-phase endocytosis process. In addition, competitive inhibition with heparin revealed the involvement of cell-surface proteoglycans in P8 uptake. In summary, the present study provides evidence that an integrated in silico and experimental approach is an effective strategy for the identification of novel CPPs and CPPs identified in the present study have promising perspectives for future drug delivery applications.
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http://dx.doi.org/10.1016/j.ejpb.2014.11.020DOI Listing
January 2015

AHTPDB: a comprehensive platform for analysis and presentation of antihypertensive peptides.

Nucleic Acids Res 2015 Jan 11;43(Database issue):D956-62. Epub 2014 Nov 11.

Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh 160036, India

AHTPDB (http://crdd.osdd.net/raghava/ahtpdb/) is a manually curated database of experimentally validated antihypertensive peptides. Information pertaining to peptides with antihypertensive activity was collected from research articles and from various peptide repositories. These peptides were derived from 35 major sources that include milk, egg, fish, pork, chicken, soybean, etc. In AHTPDB, most of the peptides belong to a family of angiotensin-I converting enzyme inhibiting peptides. The current release of AHTPDB contains 5978 peptide entries among which 1694 are unique peptides. Each entry provides detailed information about a peptide like sequence, inhibitory concentration (IC50), toxicity/bitterness value, source, length, molecular mass and information related to purification of peptides. In addition, the database provides structural information of these peptides that includes predicted tertiary and secondary structures. A user-friendly web interface with various tools has been developed to retrieve and analyse the data. It is anticipated that AHTPDB will be a useful and unique resource for the researchers working in the field of antihypertensive peptides.
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http://dx.doi.org/10.1093/nar/gku1141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383949PMC
January 2015

Carbon-Mercaptooctadecane/Carboxylated Multi-walled Carbon Nanotubes Composite Based Genosensor for Detection of Bacterial Meningitis.

Indian J Microbiol 2014 Jun 27;54(2):170-7. Epub 2013 Oct 27.

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

Human brain bacterial meningitis is a life-threatening disease mainly caused by Neisseria meningitidis, lead to several complications including damage of brain or even death. The present available methods for diagnosis of meningitis have one or more limitations. A rmpM gene based genosensor was fabricated by immobilizing 5'-amino modified 19-mer single stranded DNA probe onto carbon-mercaptooctadecane/carboxylated multi-walled carbon nanotubes composite electrode and hybridized with 2.5-40 ng/6 μL of single stranded genomic DNA (ssG-DNA) of N. meningitidis from cerebrospinal fluid (CSF) of the suspected meningitis patients. The electrochemical response was measured by using cyclic voltammetry and differential pulse voltammetry (DPV) using 1 mM methylene blue as redox indicator in 30 min (including a response time of 1 min) at 25 °C. The sensitivity of the genosensor was 3.762 (μA/cm(2))/ng and limit of detection was 2 ng of ssG-DNA of N. meningitidis with DPV. The genosensor has specificity only to N. meningitidis and does not hybridize with the genomic DNA of any other possible pathogen in human CSF. The immobilization of the probe and hybridization of the ssG-DNA were characterized by using electrochemical impedance in presence of 5 mM potassium ferricyanide and scanning electron microscopy. The genosensor loses only 12 % of its original DPV current on storage at 4 °C for 6 months. Carbon composite based electrochemical array can be constructed to detect multiple bacterial meningitis suspected patient CSF samples during an outbreak of the disease.
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http://dx.doi.org/10.1007/s12088-013-0435-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188495PMC
June 2014

CancerPPD: a database of anticancer peptides and proteins.

Nucleic Acids Res 2015 Jan 30;43(Database issue):D837-43. Epub 2014 Sep 30.

Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh 160036, Punjab, India

CancerPPD (http://crdd.osdd.net/raghava/cancerppd/) is a repository of experimentally verified anticancer peptides (ACPs) and anticancer proteins. Data were manually collected from published research articles, patents and from other databases. The current release of CancerPPD consists of 3491 ACP and 121 anticancer protein entries. Each entry provides comprehensive information related to a peptide like its source of origin, nature of the peptide, anticancer activity, N- and C-terminal modifications, conformation, etc. Additionally, CancerPPD provides the information of around 249 types of cancer cell lines and 16 different assays used for testing the ACPs. In addition to natural peptides, CancerPPD contains peptides having non-natural, chemically modified residues and D-amino acids. Besides this primary information, CancerPPD stores predicted tertiary structures as well as peptide sequences in SMILES format. Tertiary structures of peptides were predicted using the state-of-art method, PEPstr and secondary structural states were assigned using DSSP. In order to assist users, a number of web-based tools have been integrated, these include keyword search, data browsing, sequence and structural similarity search. We believe that CancerPPD will be very useful in designing peptide-based anticancer therapeutics.
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http://dx.doi.org/10.1093/nar/gku892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384006PMC
January 2015

PCMdb: pancreatic cancer methylation database.

Sci Rep 2014 Feb 26;4:4197. Epub 2014 Feb 26.

Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh-160036, India.

Pancreatic cancer is the fifth most aggressive malignancy and urgently requires new biomarkers to facilitate early detection. For providing impetus to the biomarker discovery, we have developed Pancreatic Cancer Methylation Database (PCMDB, http://crdd.osdd.net/raghava/pcmdb/), a comprehensive resource dedicated to methylation of genes in pancreatic cancer. Data was collected and compiled manually from published literature. PCMdb has 65907 entries for methylation status of 4342 unique genes. In PCMdb, data was compiled for both cancer cell lines (53565 entries for 88 cell lines) and cancer tissues (12342 entries for 3078 tissue samples). Among these entries, 47.22% entries reported a high level of methylation for the corresponding genes while 10.87% entries reported low level of methylation. PCMdb covers five major subtypes of pancreatic cancer; however, most of the entries were compiled for adenocarcinomas (88.38%) and mucinous neoplasms (5.76%). A user-friendly interface has been developed for data browsing, searching and analysis. We anticipate that PCMdb will be helpful for pancreatic cancer biomarker discovery.
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http://dx.doi.org/10.1038/srep04197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3935225PMC
February 2014

Quick diagnosis of human brain meningitis using omp85 gene amplicon as a genetic marker.

Indian J Microbiol 2013 Jun 12;53(2):238-40. Epub 2013 Feb 12.

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

The usual diagnosis of life-threatening human brain bacterial meningitis are expensive, time consuming or non-confirmatory. A quick PCR based diagnosis of meningitis in cerebrospinal fluids (CSF) using specific primers of virulent Omp85 gene of Neisseria meningitidis can detect as low as 1.0 ng of genomic DNA (G-DNA) in 80 min for confirmation of bacterial meningitis caused by N. meningitidis infection. The 257 bp amplicon of Omp85 gene does not show homology with other suspected pathogens in CSF and can be used as a specific genetic marker for diagnosis of the disease.
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http://dx.doi.org/10.1007/s12088-013-0371-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626959PMC
June 2013

Celiac disease and chronic liver disease: is there a relationship?

Indian J Gastroenterol 2013 Nov 7;32(6):404-8. Epub 2013 Aug 7.

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India.

Celiac disease is a multisystem disease, and the liver is affected in a subset of patients. We herein present a case series of 25 patients with celiac disease who had evidence of cirrhosis of the liver. We retrospectively reviewed the case records of patients with celiac disease having concomitant cirrhosis. The diagnosis of celiac disease was made on the basis of the modified European Society of Pediatric Gastroenterology, Hepatology, and Nutrition criteria. Of 25 patients (nine males; mean age 28.8 ± 16.6 years) with celiac disease and cirrhosis, 17 patients presented predominantly with cirrhosis, while 8 presented primarily with celiac disease. Five patients had known cause of cirrhosis (autoimmune hepatitis, three; PBC, one; hepatic venous outflow tract obstruction, one); the remaining 20 were cryptogenic. Gluten-free diet led to improvement in diarrhea and anemia and to a better control of ascites and other features of liver failure. Some patients with cryptogenic cirrhosis have coexistent celiac disease, and they show response to gluten-free diet. Patients with cryptogenic cirrhosis should be screened for celiac disease.
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http://dx.doi.org/10.1007/s12664-013-0352-zDOI Listing
November 2013

Celiac disease: a disease with varied manifestations in adults and adolescents.

J Dig Dis 2013 Oct;14(10):518-25

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.

Objective: We aimed to determine the characteristics of patients with celiac disease and differences between those who presented during adolescence or adulthood.

Methods: We retrospectively reviewed the case records of 233 consecutive patients with celiac disease who were diagnosed at 12-18 years or >18 years of age. The diagnosis of celiac disease was made on the basis of the modified European Society of Pediatric Gastroenterology, Hepatology and Nutrition criteria.

Results: The diagnosis of celiac disease was made after 18 years of age in 153 (65.7%) patients. Median duration of symptoms at the diagnosis was 54 months (range 1 month to 29 years). In all, 103 (44.2%) patients with atypical manifestations were referred by other departments for evaluation. Chronic diarrhea (48.5%), short stature (27.0%) and chronic anemia (9.0%) were the common modes of presentation. Elevated level of aminotransaminase were present in 50 (24.3%) patients. Chronic diarrhea, hypocalcemia and hypoalbuminemia were present in significantly higher number of adult than adolescent patients. In all, 227 (97.4%) patients responded to a 6-month gluten-free diet and six non-responders were non-compliant.

Conclusions: More than 40% of the patients with celiac disease present to clinicians other than gastroenterologists or internists with atypical manifestations. A high index of suspicion is required for diagnosing its variant forms.
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http://dx.doi.org/10.1111/1751-2980.12078DOI Listing
October 2013

rmpM genosensor for detection of human brain bacterial meningitis in cerebrospinal fluid.

Appl Biochem Biotechnol 2013 Sep 4;171(1):198-208. Epub 2013 Jul 4.

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

Human brain bacterial meningitis is a life-threatening disease caused mainly by Neisseria meningitidis, lead to damage of the outer membrane covering (meninges) of brain or even death. The usual methods of diagnosis are either time-consuming or have some limitations. The specific rmpM (reduction-modifiable protein M) virulent gene based genosensor is more sensitive, specific, and can detect N. meningitidis directly from the patient cerebrospinal fluid in 30 min including 1-min response time. 5'-Thiol-labeled single-stranded DNA (ssDNA) probe was immobilized onto screen-printed gold electrode (SPGE) and hybridized with denatured (95 °C) single-stranded genomic DNA (ssG-DNA) for 10 min at 25 °C. The electrochemical response was measured by cyclic voltammetry, differential pulse voltammetry (DPV) and electrochemical impedance using redox indicators. The sensitivity of the genosensor was 9.5087 (μA/cm(2))/ng with DPV and limit of detection was 3 ng/6 μL ssG-DNA. The immobilization of the ssDNA probe and hybridization with ssG-DNA from N. meningitidis was characterized by atomic force microscopy and Fourier transform infrared spectroscopy. The rmpM genosensor was stable for 6 months at 4 °C with 10 % loss in initial DPV current. The advantage of rmpM genosensor is to detect bacterial meningitis simultaneously in multiple patients using SPGE array during an outbreak of the disease.
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http://dx.doi.org/10.1007/s12010-013-0339-3DOI Listing
September 2013

Omp85 genosensor for detection of human brain bacterial meningitis.

Biotechnol Lett 2013 Jun 8;35(6):929-35. Epub 2013 Mar 8.

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

The 5'-thiolated DNA probe based on specific virulence gene, Omp85, was immobilized onto a screen-printed gold electrode followed by hybridization with 6-100 ng/6 μl (5.9 × 10(5)-9.3 × 10(6 )c.f.u.) of Neisseria meningitidis single stranded genomic DNA (ssG-DNA) for 10 min at 25 °C from the cerebrospinal fluid (CSF) of a meningitis patient. The Omp85 genosensor can detect as little as 6 ng ssG-DNA in 6 μl CSF of a human brain meningitis patient in 30 min including a response time of 1 min by cyclic voltammetry, differential pulse voltammetry (DPV) and electrochemical impedance. The sensitivity of the genosensor electrode was 2.6(μA/cm(2))/ng using DPV with regression coefficient (R(2)) 0.954. The genosensor was characterized using Fourier transform infrared spectroscopy and atomic force microscopy. Omp85 genosensor was stable for 12 months at 4 °C with 12 % loss in DPV current.
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http://dx.doi.org/10.1007/s10529-013-1161-2DOI Listing
June 2013

Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode.

Asian J Psychiatr 2013 Feb 12;6(1):29-34. Epub 2012 Jul 12.

Department of Psychiatry, Post Graduate Institute of Medical Sciences, Rohtak 124 001, Haryana, India.

Introduction: Role of l-5-hydroxytryptophan (l-5-HTP) in depression is relatively less studied but the literature has shown its robust role in depression. The present randomized double blind study was undertaken to assess the role of l-5-HTP as an antidepressant and to compare its antidepressant efficacy with fluoxetine in first depressive episode patients of Indian population.

Methods: A total of 70 patients of first depressive episode, all of whom were diagnosed with ICD-10 criteria, were recruited but only 60 patients completed the study and were randomly divided into two groups, receiving l-5-HTP and fluoxetine, respectively, for a period of 8weeks. All patients were administered Hamilton Rating Scale for Depression (HAM-D) to assess severity of depression at baseline, 2weeks, 4weeks and 8weeks. The efficacy of treatment was assessed by comparing HAM-D scores obtained at these examinations with the baseline examination; final evaluation of both efficacy and tolerance was assessed using the Clinical Global Impression (CGI) scale at the end of study.

Results: Both treatment groups showed significant and nearly equal reduction in HAM-D scores beginning at week two and continuing through week eight. Twenty-two patients (73.33%) in the l-5-HTP group and 24 patients (80%) in the fluoxetine group showed positive response at the end of the study.

Conclusion: l-5-HTP has definitely got antidepressant effect in patients of depression. Antidepressant effect was seen within 2weeks of treatment and was apparent in all degrees of depression. The therapeutic efficacy of l-5-HTP was considered as equal to that of fluoxetine.
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http://dx.doi.org/10.1016/j.ajp.2012.05.011DOI Listing
February 2013

Integrated management of childhood illness (IMCI) follow-up of basic health workers.

Indian J Pediatr 2005 Sep;72(9):735-9

Society for Women and Children's Health (SWACH), Panchkula, Haryana, India.

Objective: To assess the practice of skills learnt by basic health workers for 4 - 8 weeks and one year after IMCI training, and to identify the gaps in practices due to various constraints.

Methods: The Anganwadi Workers (AWWS) and the supervisory staff were given 5 days IMCI training using WHO package. The supervisors gave follow up visits to AWWs using standardized follow up forms adapted from WHO material. The supervisors gave follow up visit to the 1st batch of AWWs 1 year after training in IMCI and a second visit was given 4-8 weeks after the 1st visit. The 2nd batch of AWWs was followed up 4-8 weeks after training in IMCI.

Results: The performance on correct treatment of cases by AWWs weeks were trained 4-6 weeks prior to follow up was better than group followed up one year after the completion of training (81.8% and 47.9% respectively). At the same time, the performance on correct treatment showed significant improvement during the second follow up (47.9% and 83.8% respectively). Performance on counseling improved from 15.6% during 1st follow up to 52.1% during 2nd follow up visit. The average number of cases seen by AWWs increased from 6.6 in 1st follow up to 9.3 during second follow up of the same AWWs.

Conclusion: The basic health workers (AWWs) are capable of correct case management of sick children using the IMCI guidelines. The first follow up visit should not be delayed as delay leads to loss of skills. The health workers benefit from frequent and regular follow up by supervisors. Provision of requisite supplies is essential for practice of skills after training in IMCI by basic health worker.
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http://dx.doi.org/10.1007/BF02734143DOI Listing
September 2005
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