Publications by authors named "Namita Singh"

80 Publications

Functional disruption of transferrin expression alters reproductive physiology in Anopheles culicifacies.

PLoS One 2022 4;17(3):e0264523. Epub 2022 Mar 4.

Laboratory of Host-Parasite Interaction Studies, ICMR-National Institute of Malaria Research, Dwarka, New Delhi, India.

Background: Iron metabolism is crucial to maintain optimal physiological homeostasis of every organism and any alteration of the iron concentration (i.e. deficit or excess) can have adverse consequences. Transferrins are glycoproteins that play important role in iron transportation and have been widely characterized in vertebrates and insects, but poorly studied in blood-feeding mosquitoes.

Results: We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. culicifacies. A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. Structure modelling prediction confirms the presence of an iron-binding site at the N-terminal lobe of the transferrin. Our spatial and temporal expression analysis under altered pathophysiological conditions showed that AcTrf1a is abundantly expressed in the fat-body, ovary, and its response is significantly altered (enhanced) after blood meal uptake, and exogenous bacterial challenge. Additionally, non-heme iron supplementation of FeCl3 at 1 mM concentration not only augmented the AcTrf1a transcript expression in fat-body but also enhanced the reproductive fecundity of gravid adult female mosquitoes. RNAi-mediated knockdown of AcTrf1a causes a significant reduction in fecundity, confirming the important role of transferrin in oocyte maturation.

Conclusion: All together our results advocate that detailed characterization of newly identified AcTrf1a transcript may help to select it as a unique target to impair the mosquito reproductive outcome.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0264523PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8896695PMC
April 2022

A comparative evaluation of microleakage and dentin shear bond strength of three restorative materials.

Biomater Investig Dent 2022 10;9(1):1-9. Epub 2022 Feb 10.

Department of Pedodontics and Preventive Dentistry, Christian Dental College, Ludhiana, CMC, Ludhiana, India.

Aim: To evaluate the microleakage and dentin shear bond strength of two glass containing restorative materials, Zirconomer and Cention N, and to compare them with a conventional glass ionomer cement (GIC) (GC Fuji II).

Materials And Methods: Zirconomer (Shofu) and GC Fuji II (GC Corp.) are self-curing GICs whereas Cention N (IvoclarVivadent) also offers a self-curing option as well as the option of light-curing using an adhesive. For evaluating microleakage, standardized class V cavities were prepared on the buccal surface of 30 premolars. The cavities were restored with one of the three restorative materials ( = 10) according to manufacturers' instructions, Cention N being used with an adhesive (Te-EconomBond, IvoclarVivadent) and in the light-curing mode. After restoration and thermocycling, the microleakage assessment was made under a stereomicroscope at 40x magnification following immersing of the teeth in 0.5% methylene blue dye and buccolingual sectioning. For evaluating dentin shear bond strength, the occlusal surface of the 30 premolars was ground flat, and cylinders of the three restorative materials ( = 10) were bonded to the occlusal surface according to manufacturers' instructions, Cention N being used with an adhesive (Te-EconomBond, IvoclarVivadent) and in the light-curing mode. Following 24-h storage at 100% humidity, the dentin shear bond strength was measured and the fracture mode was determined under a stereomicroscope at 10× magnification. Data were statistically analyzed using Mann-Whitney and Scheffé tests ( = .05).

Results: Cention N displayed significantly less microleakage than did Zirconomer and GC Fuji II at occlusal as well as the gingival margins. Dentin shear bond strength varied significantly between 5.15 and 9.89 MPa with Cention N showing the highest bond strength and GC Fuji II the lowest.

Conclusion: In this evaluation, Cention N consistently performed better than the conventional GIC (GC Fuji II) as well as Zirconomer.
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http://dx.doi.org/10.1080/26415275.2022.2033623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8843194PMC
February 2022

Etiology and management of Alzheimer's disease: Potential role of gut microbiota modulation with probiotics supplementation.

J Food Biochem 2022 01 19;46(1):e14043. Epub 2021 Dec 19.

Dairy Microbiology Division, ICAR-National Dairy Research Institute, Karnal, India.

Alzheimer's disease (AD) is the leading type of dementia in aging people and is a progressive condition that causes neurodegeneration, resulting in confusion, memory loss, and deterioration of mental functions. AD happens because of abnormal twisting of the microtubule tau protein in neurons into a tangled neurofibrillary structure. Different factors responsible for AD pathogenesis include heavy metals, aging, cardiovascular disease, and environmental and genetic factors. Market available drugs for AD have several side effects that include hepato-toxicity, accelerated cognitive decline, worsened neuropsychiatric symptoms, and triggered suicidal ideation. Therefore, an emerging alternative therapeutic approach is probiotics, which can improve AD by modulating the gut-brain axis. Probiotics modulate different neurochemical pathways by regulating the signalling pathways associated with inflammation, histone deacetylation, and microglial cell activation and maturation. In addition, probiotics-derived metabolites (i.e., short-chain fatty acid, neurotransmitters, and antioxidants) have shown ameliorative effects against AD. Probiotics also modulate gut microbiota, with a beneficial impact on neural signalling and cognitive activity, which can attenuate AD progression. Therefore, the current review describes the etiology and mechanism of AD progression as well as various treatment options with a focus on the use of probiotics. PRACTICAL APPLICATIONS: In an aging population, dementia concerns are quite prevalent globally. AD is one of the most commonly occurring cognition disorders, which is linked to diminished brain functions. Scientific evidence supports the findings that probiotics and gut microbiota can regulate/modulate brain functions, one of the finest strategies to alleviate such disorders through the gut-brain axis. Thus, gut microbiota modulation, especially through probiotic supplementation, could become an effective solution to ameliorate AD.
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http://dx.doi.org/10.1111/jfbc.14043DOI Listing
January 2022

Emission inventory for road transport in India in 2020: framework and post facto policy impact assessment.

Environ Sci Pollut Res Int 2022 Mar 6;29(14):20844-20863. Epub 2021 Nov 6.

Interdisciplinary Programme in Climate Studies, Indian Institute of Technology Bombay, Mumbai, 400076, India.

India's growing population and economic development lead to an increase in transport emissions. Quantification of emission at frequent intervals is required to assess the emission levels and impact of implemented control policies. Implemented policies affect the fleet configuration over time. Therefore, in the present paper, an age-wise emission analysis framework is developed for the road transport sector with updated fleet characteristics corresponding to the vehicles' age. The results show that fuel consumption is estimated to be 92 (87-95) Mt, and total CO, CO, PM, and NOx vehicle emissions are estimated to be 274 (265-292) Tg, 4463 (3253-6676) Gg, 164 (119-250) Gg, and 2378 (2191-3045) Gg, respectively for the reference year 2020. The study contributes by developing an inventory for the fleet of 2020, which is used as a benchmark to compare past emission inventory, evaluate control policies, estimate state-wise vehicle emission inventories, and identify significant emitters in the fleet. Sensitivity analysis indicates the considerable variation in total emissions resulting from different age-mix of vehicles. Among the investigated policies, advancement in emission norms followed by fuel efficiency improvement in vehicles led to a substantial reduction in gaseous pollutants. Based on the inventory results, suitable policies are suggested for India's future fleet, and the need for country-level fleet characteristics data is recommended.
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http://dx.doi.org/10.1007/s11356-021-17238-3DOI Listing
March 2022

Differences in Nutrient Intake with Homemade versus Chef-Prepared Specific Carbohydrate Diet Therapy in Inflammatory Bowel Disease: Insights into Dietary Research.

Pediatr Gastroenterol Hepatol Nutr 2021 Sep 8;24(5):432-442. Epub 2021 Sep 8.

Division of Gastroenterology, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.

Purpose: The aim of this study was to evaluate the nutrient content consumed by children and adolescents on home-prepared versus chef-prepared specific carbohydrate diets (SCD) as therapy for inflammatory bowel disease (IBD).

Methods: Dietary intake of two cohorts with active IBD initiating the SCD over 12 weeks was assessed. The home-prepared cohort received detailed guidance from dietitians on implementation of the SCD. The chef in the other cohort was knowledgeable in the SCD and prepared meals from a fixed set of recipes. Data from 3-day diet diaries at 4 different time points were collected. US Recommended Daily Allowances (RDA) were calculated for macronutrients, vitamins, and minerals.

Results: Eight participants on the homemade SCD and 5 participants on the chef-prepared SCD were included in analysis. Mean % RDA for energy intake was 115% and 87% for homemade and chef-prepared groups (<0.01). Mean % RDA for protein intake was 337% for homemade SCD and 216% for chef-prepared SCD (<0.01). The homemade SCD group had higher mean % RDA values for vitamin A and iron, while the chef-prepared SCD group had higher intake of vitamins B1, B2, D, phosphorus and zinc (<0.01 for all).

Conclusion: The SCD implemented homemade versus chef-prepared can result in significantly different intake of nutrients and this may influence efficacy of this dietary therapy. Meal preparation dynamics and the motivation of families who pursue dietary treatment may play an important role on the foods consumed and the outcomes on dietary therapy with the SCD.
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http://dx.doi.org/10.5223/pghn.2021.24.5.432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443856PMC
September 2021

Biocompatibility and biodegradability of metal organic frameworks for biomedical applications.

J Mater Chem B 2021 08;9(30):5925-5934

Smart Hybrid Materials (SHMs) Laboratory, Advanced Membranes and Porous Materials Center, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia.

Metal organic frameworks (MOFs) are a unique class of smart hybrid materials that have recently attracted significant interest for catalysis, separation and biomedical applications. Different strategies have been developed to overcome the limitations of MOFs for bio-applications in order to produce a system with high biocompatibility and biodegradability. In this review, we outline the chemical and physical factors that dictate the biocompatibility and biodegradability characteristics of MOFs including the nature of the metal ions and organic ligands, size, surface properties and colloidal stability. This review includes the in vitro biodegradation and in vivo biodistribution studies of MOFs to better understand their pharmacokinetics, organ toxicity and immune response. Such studies can guide the design of future bio-friendly systems that bring us closer to safely translating these platforms into the pharmaceutical consumer market.
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http://dx.doi.org/10.1039/d1tb01044aDOI Listing
August 2021

Hemocyte RNA-Seq analysis of Indian malarial vectors Anopheles stephensi and Anopheles culicifacies: From similarities to differences.

Gene 2021 Sep 2;798:145810. Epub 2021 Jul 2.

Laboratory of Host-Parasite Interaction Studies, ICMR-National Institute of Malaria, Research, Dwarka, New Delhi 110077, India. Electronic address:

Anopheles stephensi and Anopheles culicifacies are dominant malarial vectors in urban and rural India, respectively. Both species carry significant biological differences in their behavioral adaptation and immunity, but the genetic basis of these variations are still poorly understood. Here, we uncovered the genetic differences of immune blood cells, that influence several immune-physiological responses. We generated, analyzed and compared the hemocyte RNA-Seq database of both mosquitoes. A total of 5,837,223,769 assembled bases collapsed into 7,595 and 3,791 transcripts, originating from hemocytes of laboratory-reared 3-4 days old naïve (sugar-fed) mosquitoes, Anopheles stephensi and Anopheles culicifacies respectively. Comparative GO annotation analysis revealed that both mosquito hemocytes encode similar proteins. Furthermore, while An. stephensi hemocytes showed a higher percentage of immune transcripts encoding APHAG (Autophagy), IMD (Immune deficiency pathway), PRDX (Peroxiredoxin), SCR (Scavenger receptor), IAP (Inhibitor of apoptosis), GALE (galactoside binding lectins), BGBPs (1,3 beta D glucan binding proteins), CASPs (caspases) and SRRP (Small RNA regulatory pathway), An. culicifacies hemocytes yielded a relatively higher percentage of transcripts encoding CLIP (Clip domain serine protease), FREP (Fibrinogen related proteins), PPO (Prophenol oxidase), SRPN (Serpines), ML (Myeloid differentiation 2-related lipid recognition protein), Toll path and TEP (Thioester protein), family proteins. However, a detailed comparative Interproscan analysis showed An. stephensi mosquito hemocytes encode proteins with increased repeat numbers as compared to An. culicifacies. Notably, we observed an abundance of transcripts showing significant variability of encoded proteins with repeats such as LRR (Leucine rich repeat), WD40 (W-D dipeptide), Ankyrin, Annexin, Tetratricopeptide and Mitochondrial substrate carrier repeat-containing family proteins, which may have a direct influence on species-specific immune-physiological responses. Summarily, our deep sequencing analysis unraveled that An. stephensi evolved with an expansion of repeat sequences in hemocyte proteins as compared to An. culicifacies, possibly providing an advantage for better adaptation to diverse environments.
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http://dx.doi.org/10.1016/j.gene.2021.145810DOI Listing
September 2021

The use of thiazide diuretics for the treatment of hypertension in patients with advanced chronic kidney disease.

Cardiol Rev 2021 Jun 29. Epub 2021 Jun 29.

University of New Mexico Hospitals 2211 Lomas Blvd Albuquerque, NM 87160 Phone: 505.272.3100 Fax: 505.925.4445 Email: University of New Mexico Health Sciences Center 1 University of New Mexico, MSC04-2785, Albuquerque, NM, 87131 University of New Mexico Health Sciences Center 1 University of New Mexico, MSC04-2785, Albuquerque, NM, 87131 University of New Mexico Health Sciences Center 1 University of New Mexico, MSC04-2785, Albuquerque, NM, 87131.

The use of thiazide diuretics for the treatment of hypertension in patients with advance chronic kidney disease Thiazides have been recommended as the first-line for the treatment of hypertension, yet their use has been discouraged in advanced chronic kidney disease (CKD), as they are suggested to be ineffective in advanced CKD. Recent data suggest that thiazide diuretics may be beneficial blood pressure control in addition to natriuresis in existing CKD. This review discusses the commercially available thiazides with a focus on thiazide pharmacology, most common adverse effects, clinical uses of thiazide diuretic, and the evidence for efficacy of thiazide use in advanced CKD.
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http://dx.doi.org/10.1097/CRD.0000000000000404DOI Listing
June 2021

A comparative evaluation of penetration depth and surface microhardness of Resin Infiltrant, CPP-ACPF and Novamin on enamel demineralization after banding: an study.

Biomater Investig Dent 2021 Jun 11;8(1):64-71. Epub 2021 Jun 11.

Department of Orthodontics and Dento-facial Orthopaedics, Christian Dental College, Ludhiana, Punjab.

Background: The field of dentistry has been revolutionized by various concepts. Minimal invasive dentistry is the preferred treatment approach in the present era; therefore, various techniques have been advocated to arrest caries lesions at an early stage on the grounds of better understanding of the dynamic nature of dental caries. Thus, study was conducted to compare and evaluate the penetration depth and enamel microhardness of Resin Infiltrant, CPP-ACPF and Novamin on artificial demineralized enamel surface after orthodontic banding.

Material And Methods: Eighty extracted sound premolars were banded. The bands were cemented with type 1 GIC and further divided into - Group I: Resin Infiltrant, Group II: CCP-ACPF, Group III: Novamin and Group IV: Control. The samples were incubated for 30 days and then thermocycled. A window of 4 mm × 4 mm was prepared on the buccal surface of samples and artificially demineralized for 4 weeks. A single application was made for Resin Infiltrant, while Novamin and CCP-ACPF were applied twice daily. These samples were otherwise immersed in artificial saliva, and this was protocol was observed for 14 days. For the evaluation of penetration depth, 10 samples from each group were bucco-lingually sectioned and immersed in methylene blue dye solution for 24 h and then evaluated under stereomicroscope. For the enamel surface microhardness, remaining 10 samples from each group were embedded in acrylic resin with outer buccal surface exposed and were tested by a using digital Micro-Vickers hardness tester.

Results: All groups showed a significant difference in the depth of dye penetration and surface microhardness compared to the control group. As compared to the other tested groups, Resin Infiltrant exhibited the highest significant reduction in demineralization and increased microhardness. Novamin had a deeper penetration and increase in microhardness as compared to CCP-ACPF.

Conclusion: Resin Infiltrant exhibited the highest potential to impede caries and constitutes a competent aerosol free micro-invasive strategy for combating non cavitated lesions approaching the outer layer dentine which are too advanced for remineralizing agents but do not necessarily require any drilling of tooth.
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http://dx.doi.org/10.1080/26415275.2021.1919119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204967PMC
June 2021

assembled ZIF superstructures an emulsion-free soft-templating approach.

Chem Sci 2020 Sep 22;11(41):11280-11284. Epub 2020 Sep 22.

Smart Hybrid Materials (SHMs) Laboratory, Advanced Membranes and Porous Materials Center, King Abdullah University of Science and Technology (KAUST) Thuwal 23955-6900 Kingdom of Saudi Arabia

Assembling well-defined MOF superstructures remains challenging as it requires easily removable hard templates or readily available immiscible solutions for an emulsion-based soft-template approach. In this work, a single-step emulsion-free soft templating approach is reported to spontaneously prepare hollow ZIF-8 and ZIF-67 colloidosomes with no further purification. These superstructures can load different enzymes regardless of the size and charge with a high encapsulation efficiency of 99%. We envisage that this work will expand the repertoires of MOF superstructures by the judicious selection of precursors and the reaction medium.
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http://dx.doi.org/10.1039/d0sc04513fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162773PMC
September 2020

Patulin in food: A mycotoxin concern for human health and its management strategies.

Toxicon 2021 Jul 29;198:12-23. Epub 2021 Apr 29.

Applied Microbiology Lab., Department of Forestry, North Eastern Regional Institute of Science and Technology, Nirjuli, 791109, Arunachal Pradesh, India. Electronic address:

The mycotoxin patulin is primarily produced as a secondary metabolite by numerous fungal species and predominantly by Aspergillus, Byssochlamys, and Penicillium species. It is generally associated with fungal infected food materials. Penicillium expansum is considered the only fungal species liable for patulin contamination in pome fruits, especially in apples and apple-based products. This toxin in food poses serious health concerns and economic threat, which has aroused the need to adopt effective detection and mitigation strategies. Understanding its origin sources and biosynthetic mechanism stands essential for efficiently designing a management strategy against this fungal contamination. This review aims to present an updated outline of the sources of patulin occurrence in different foods and their biosynthetic mechanisms. It further provides information regarding the detrimental effects of patulin on human and agriculture as well as its effective detection, management, and control strategies.
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http://dx.doi.org/10.1016/j.toxicon.2021.04.027DOI Listing
July 2021

Are the Protective Effects of SGLT2 Inhibitors a "Class-Effect" or Are There Differences between Agents?

Kidney360 2021 May 5;2(5):881-885. Epub 2021 Feb 5.

Division of Nephrology, University of New Mexico School of Medicine, University of New Mexico, Albuquerque, New Mexico.

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http://dx.doi.org/10.34067/KID.0000622021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791337PMC
May 2021

Spices and herbs: Potential antiviral preventives and immunity boosters during COVID-19.

Phytother Res 2021 Jan 29. Epub 2021 Jan 29.

Dairy Microbiology Division, National Dairy Research Institute, ICAR, Karnal, India.

A severe acute respiratory syndrome is an unusual type of contagious pneumonia that is caused by SARS coronavirus. At present, the whole world is trying to combat this coronavirus disease and scientific communities are putting rigorous efforts to develop vaccines. However, there are only a few specific medical treatments for SARS-CoV-2. Apart from other public health measures taken to prevent this virus, we can boost our immunity with natural products. In this article, we have highlighted the potential of common spices and herbs as antiviral agents and immunity boosters. A questionnaire-based online survey has been conducted on home remedies during COVID-19 among a wide range of peoples (n-531) of different age groups (13-68 years) from various countries. According to the survey, 71.8% of people are taking kadha for combating infection and boosting immunity. Most people (86.1%) think that there is no side effect of kadha while 13.9% think vice versa. A total of 93.6% of people think that spices are helpful in curing coronavirus or other viral infection as well as boosting immunity. Most people are using tulsi drops, vitamin C, and chyawanprash for boosting their immunity. Therefore, we conclude from the survey and available literature that spices and herbs play a significant role against viral infections.
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http://dx.doi.org/10.1002/ptr.7019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013177PMC
January 2021

Role of p38 mitogen-activated protein kinase signalling in virus replication and potential for developing broad spectrum antiviral drugs.

Rev Med Virol 2021 09 15;31(5):1-16. Epub 2021 Jan 15.

National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, Haryana, India.

Mitogen-activated protein kinases (MAPKs) play a key role in complex cellular processes such as proliferation, development, differentiation, transformation and apoptosis. Mammals express at least four distinctly regulated groups of MAPKs which include extracellular signal-related kinases (ERK)-1/2, p38 proteins, Jun amino-terminal kinases (JNK1/2/3) and ERK5. p38 MAPK is activated by a wide range of cellular stresses and modulates activity of several downstream kinases and transcription factors which are involved in regulating cytoskeleton remodeling, cell cycle modulation, inflammation, antiviral response and apoptosis. In viral infections, activation of cell signalling pathways is part of the cellular defense mechanism with the basic aim of inducing an antiviral state. However, viruses can exploit enhanced cell signalling activities to support various stages of their replication cycles. Kinase activity can be inhibited by small molecule chemical inhibitors, so one strategy to develop antiviral drugs is to target these cellular signalling pathways. In this review, we provide an overview on the current understanding of various cellular and viral events regulated by the p38 signalling pathway, with a special emphasis on targeting these events for antiviral drug development which might identify candidates with broad spectrum activity.
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http://dx.doi.org/10.1002/rmv.2217DOI Listing
September 2021

Transcriptome Analysis Identified Coordinated Control of Key Pathways Regulating Cellular Physiology and Metabolism upon Infection Resulting in Reduced Aflatoxin Production in Groundnut.

J Fungi (Basel) 2020 Dec 16;6(4). Epub 2020 Dec 16.

Center of Excellence in Genomics & Systems Biology (CEGSB), International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), Hyderabad 502324, India.

Aflatoxin-affected groundnut or peanut presents a major global health issue to both commercial and subsistence farming. Therefore, understanding the genetic and molecular mechanisms associated with resistance to aflatoxin production during host-pathogen interactions is crucial for breeding groundnut cultivars with minimal level of aflatoxin contamination. Here, we performed gene expression profiling to better understand the mechanisms involved in reduction and prevention of aflatoxin contamination resulting from infection in groundnut seeds. RNA sequencing (RNA-Seq) of 16 samples from different time points during infection (24 h, 48 h, 72 h and the 7th day after inoculation) in U 4-7-5 (resistant) and JL 24 (susceptible) genotypes yielded 840.5 million raw reads with an average of 52.5 million reads per sample. A total of 1779 unique differentially expressed genes (DEGs) were identified. Furthermore, comprehensive analysis revealed several pathways, such as disease resistance, hormone biosynthetic signaling, flavonoid biosynthesis, reactive oxygen species (ROS) detoxifying, cell wall metabolism and catabolizing and seed germination. We also detected several highly upregulated transcription factors, such as ARF, DBB, MYB, NAC and C2H2 in the resistant genotype in comparison to the susceptible genotype after inoculation. Moreover, RNA-Seq analysis suggested the occurrence of coordinated control of key pathways controlling cellular physiology and metabolism upon infection, resulting in reduced aflatoxin production.
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http://dx.doi.org/10.3390/jof6040370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767264PMC
December 2020

The Specific Carbohydrate Diet and Diet Modification as Induction Therapy for Pediatric Crohn's Disease: A Randomized Diet Controlled Trial.

Nutrients 2020 Dec 6;12(12). Epub 2020 Dec 6.

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.

Background: Crohn's disease (CD) is a chronic inflammatory intestinal disorder associated with intestinal dysbiosis. Diet modulates the intestinal microbiome and therefore has a therapeutic potential. The aim of this study is to determine the potential efficacy of three versions of the specific carbohydrate diet (SCD) in active Crohn's Disease.

Methods: 18 patients with mild/moderate CD (PCDAI 15-45) aged 7 to 18 years were enrolled. Patients were randomized to either SCD, modified SCD(MSCD) or whole foods (WF) diet. Patients were evaluated at baseline, 2, 4, 8 and 12 weeks. PCDAI, inflammatory labs and multi-omics evaluations were assessed.

Results: Mean age was 14.3 ± 2.9 years. At week 12, all participants (n = 10) who completed the study achieved clinical remission. The C-reactive protein decreased from 1.3 ± 0.7 at enrollment to 0.9 ± 0.5 at 12 weeks in the SCD group. In the MSCD group, the CRP decreased from 1.6 ± 1.1 at enrollment to 0.7 ± 0.1 at 12 weeks. In the WF group, the CRP decreased from 3.9 ± 4.3 at enrollment to 1.6 ± 1.3 at 12 weeks. In addition, the microbiome composition shifted in all patients across the study period. While the nature of the changes was largely patient specific, the predicted metabolic mode of the organisms increasing and decreasing in activity was consistent across patients.

Conclusions: This study emphasizes the impact of diet in CD. Each diet had a positive effect on symptoms and inflammatory burden; the more exclusionary diets were associated with a better resolution of inflammation.
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http://dx.doi.org/10.3390/nu12123749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762109PMC
December 2020

Transitional care units: How successful in increasing home dialysis?

Authors:
Namita Singh

Semin Dial 2021 01 10;34(1):3-4. Epub 2020 Aug 10.

Nephrology Associates of Utah, Salt Lake City, UT, USA.

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http://dx.doi.org/10.1111/sdi.12910DOI Listing
January 2021

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper on the Evaluation and Management for Patients With Very Early-onset Inflammatory Bowel Disease.

J Pediatr Gastroenterol Nutr 2020 03;70(3):389-403

Division of Gastroenterology, Hepatology, and Nutrition.

The rate of pediatric inflammatory bowel disease (IBD) has been increasing over the last decade and this increase has occurred most rapidly in the youngest children diagnosed <6 years, known as very early-onset inflammatory bowel disease (VEO-IBD). These children can present with more extensive and severe disease than older children and adults. The contribution of host genetics in this population is underscored by the young age of onset and the distinct, aggressive phenotype. In fact, monogenic defects, often involving primary immunodeficiency genes, have been identified in children with VEO-IBD and have led to targeted and life-saving therapy. This position paper will discuss the phenotype of VEO-IBD and outline the approach and evaluation for these children and what factors should trigger concern for an underlying immunodeficiency. We will then review the immunological assays and genetic studies that can facilitate the identification of the underlying diagnosis in patients with VEO-IBD and how this evaluation may lead to directed therapies. The position paper will also aid the pediatric gastroenterologist in recognizing when a patient should be referred to a center specializing in the care of these patients. These guidelines are intended for pediatricians, allied health professionals caring for children, pediatric gastroenterologists, pediatric pathologists, and immunologists.
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http://dx.doi.org/10.1097/MPG.0000000000002567DOI Listing
March 2020

Does tumour necrosis factor alpha-induced cyclooxygenase-2 expression lead to spontaneous abortion in Chlamydia trachomatis-infected women.

Microb Pathog 2020 Jan 24;142:103994. Epub 2020 Jan 24.

Microbiology Laboratory, National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, 110 029, India. Electronic address:

Cytokines might be involved in spontaneous abortion by triggering inflammatory mediators (Cyclooxygenases (Cox)) leading to spontaneous abortion in Chlamydia trachomatis (Ct)-infected women. Study aimed to quantitate the expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-8) and Cox-2 in endometrial curettage tissue (ECT) of Spontaneous Aborters (SA). SA (n = 135) and 120 age-matched controls were enrolled from SJH, New Delhi, India. PCR was performed for detection of Ct MOMP gene (537 bp) in ECT. mRNA expression of pro-inflammatory cytokines and Cox-2 was assessed by real-time qPCR. Data was statistically evaluated. 14.8% SA were diagnosed as Ct-positive. Elevated expression of TNF-α, IFN-γ, IL-8 and Cox-2 was observed in Ct-infected SA. Ct-positive recurrent aborters showed significantly higher cytokine expression. Significant positive correlation was found between expression of Cox-2 and TNF-α in infected SA. Data suggested an increased expression of Th-1 cytokines, particularly TNF-α that induced Cox-2 expression in ECT, leading to spontaneous abortion in Ct-infected pregnant women.
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http://dx.doi.org/10.1016/j.micpath.2020.103994DOI Listing
January 2020

Purification, characterization and antibacterial spectrum of a compound produced by Bacillus cereus MTCC 10072.

Arch Microbiol 2019 Nov 6;201(9):1195-1205. Epub 2019 Jun 6.

Department of Agronomy, CCS Haryana Agricultural University, Hisar, Haryana, 125001, India.

Awareness of the consumer has increased the demand of safe and chemical-free foods, and consequently it has increased the demand of antibacterial bioactive compounds. In the present study, antibacterial compound produced by a local bacterial isolate NSD MTCC 10072, showing antagonistic activity against six human pathogens, was isolated, partially purified and characterized. Maximum production of antibacterial compound was observed between 51 and 60 h after seeding. The antibacterial activity of the compound was found to be thermostable up to 80 °C for 60 min and its efficacy was very good between pH 4 and 12. Minimum inhibitory concentration (25.84 µg/µl) of the antibacterial compound was observed against Streptococcus aureus NICM 2901. GC-MS analysis of the bacterium secreted chemical compound (CHNO) was used to identify the antimicrobial compound as Pyrrolo(1,2-a) pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl). In Silico studies showed that the antimicrobial compound is non-toxic, non-irritating and followed Lipinski-type properties which suggested that the compound could be used as potential drug against different human pathogens.
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http://dx.doi.org/10.1007/s00203-019-01685-1DOI Listing
November 2019

Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Children.

Clin Gastroenterol Hepatol 2020 03 19;18(3):612-619.e1. Epub 2019 Apr 19.

Medical College of Wisconsin, Milwaukee, Wisconsin.

Background & Aims: Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI.

Methods: We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMT at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT.

Results: Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39-5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26-4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05-4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04-1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations.

Conclusions: Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients-factors associated with success differ from those of adult patients.
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http://dx.doi.org/10.1016/j.cgh.2019.04.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549313PMC
March 2020

Promoter hypermethylation of SOX11 promotes the progression of cervical cancer in vitro and in vivo.

Oncol Rep 2019 Apr 1;41(4):2351-2360. Epub 2019 Feb 1.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.

The development of cervical cancer (CC) is a multi‑gene, multi‑step carcinogenic process that involves complex genetic and epigenetic mechanisms. SRY‑related HMG‑box gene 11 (SOX11) is a member of the SOX family of transcription factors with an emerging crucial role in the development of various tumor types. To elucidate the function of SOX11 in cervical carcinogenesis, the expression level of SOX11 during the development of human CC was analyzed by immunohistochemistry and western blot analysis. Additionally, the methylation status of the SOX11 was examined using bisulfite sequencing and methylation‑specific polymerase chain reaction. The SOX11 expression and promoter methylation in human CC cell lines were also determined. The effect of SOX11 expression restoration after 5‑aza‑2'‑deoxycytidine (5‑Aza‑dC) treatment on the CC cell proliferation ability was evaluated in CC cell lines. SOX11 was highly expressed in normal cervix (NC) and precancerous low‑grade squamous intraepithelial lesions, but weakly expressed or virtually absent in precancerous high‑grade squamous intraepithelial lesions and CC, which is consistent with the result of the western blot analysis. Hypermethylation of the SOX11 promoter was detected in CC, which was significantly higher than that in NC samples at each CpG site. The expression level of SOX11 in the CC cell lines was downregulated compared with the positive control, Tera‑1human teratoma cell line. Upon 5‑Aza‑dC treatment, SOX11 expression was significantly upregulated in the CC cell lines at the mRNA and protein levels, and cell proliferation was inhibited. The results indicated that the downregulation of SOX11 in CC is due to the hypermethylation of the SOX11 promoter region. Thus, SOX11 methylation may have a role in the growth of CC cells and cervical carcinogenesis.
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http://dx.doi.org/10.3892/or.2019.6993DOI Listing
April 2019

Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt Regulatory T Cells and Exacerbate Colitis in Mice.

Immunity 2019 01;50(1):212-224.e4

Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

Microbiota are thought to influence the development and progression of inflammatory bowel disease (IBD), but determining generalizable effects of microbiota on IBD etiology requires larger-scale functional analyses. We colonized germ-free mice with intestinal microbiotas from 30 healthy and IBD donors and determined the homeostatic intestinal T cell response to each microbiota. Compared to microbiotas from healthy donors, transfer of IBD microbiotas into germ-free mice increased numbers of intestinal Th17 cells and Th2 cells and decreased numbers of RORγt Treg cells. Colonization with IBD microbiotas exacerbated disease in a model where colitis is induced upon transfer of naive T cells into Rag1 mice. The proportions of Th17 and RORγt Treg cells induced by each microbiota were predictive of human disease status and accounted for disease severity in the Rag1 colitis model. Thus, an impact on intestinal Th17 and RORγt Treg cell compartments emerges as a unifying feature of IBD microbiotas, suggesting a general mechanism for microbial contribution to IBD pathogenesis.
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http://dx.doi.org/10.1016/j.immuni.2018.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512335PMC
January 2019

Cytokine-induced expression of nitric oxide synthases in infected spontaneous aborters.

J Matern Fetal Neonatal Med 2019 Nov 2;32(21):3511-3519. Epub 2018 May 2.

a Microbiology Laboratory , National Institute of Pathology (ICMR), Safdarjung Hospital Campus , New Delhi , India.

The aim of study was to evaluate expression of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) in (CT)-infected spontaneous aborters (SA). Endometrial curettage tissue was collected from 140 SA (sporadic SA- 70; recurrent SA- 70) (Group I) and 140 age-matched controls (Group II) from Department of Obstetrics and Gynecology, Safdarjung Hospital, New Delhi, India. Polymerase chain reaction was performed for diagnosis of CT. The expression of iNOS/ eNOS/ IFN-γ/ TNF-α was assessed by real-time polymerase chain reaction (PCR). 15.7% SA were CT-positive (Group I); none in controls. Sporadic spontaneous aborters (SSA) ( = 8/70), recurrent spontaneous aborters (RSA) ( = 14/70) diagnosed as CT-positive (Group-I). Significant upregulation of iNOS/ eNOS was found in CT-positive SSA/RSA compared with CT-negative SSA/RSA and healthy controls. TNF-α and IFN-γ were expressed in CT-positive SSA/RSA compared with negative SSA/controls. iNOS showed a significant strong positive correlation with TNF-α and IFN-γ in CT-infected SA. eNOS showed a significant positive correlation with TNF-α and no correlation with IFN-γ in CT-infected SA. TNF-α was positively correlated with IFN-γ. Significantly high expression of iNOS/ eNOS and proinflammatory cytokines affected pregnancy in CT-infected RSA, thereby implying that there occurs cytokine-induced expression of nitric oxide synthase (NOS).
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http://dx.doi.org/10.1080/14767058.2018.1465914DOI Listing
November 2019

Tailored Rabbit Antithymocyte Globulin Induction Dosing for Kidney Transplantation.

Transplant Direct 2018 Feb 2;4(2):e343. Epub 2018 Feb 2.

Division of Nephrology and Transplantation, Maine Medical Center, Portland, ME.

Background: Rabbit antithymocyte globulin (rATG) is the most widely used kidney transplant induction immunotherapy in the United States. It was recently Food and Drug Administration approved for this indication with typical dose recommendations of 1.5 mg/kg for up to 7 days given via a central line.

Methods: We theorized that reduced rATG dosing when compared with conventional dosing (6-10.5 mg/kg) is safe and effective, leading to development of a risk-stratified treatment protocol. Five-year data from a retrospective cohort of 224 adult kidney transplants (2008-2013) with follow-up through 2015 is presented. Cumulative rATG doses of 3 mg/kg were administered peripherally to nonsensitized living donor recipients, 4.5 mg/kg to nonsensitized deceased donor recipients. A subset of higher immunologic risk recipients (defined as history of prior transplant, panel reactive antibody greater than 20%, or flow cytometry crossmatch positivity) received 6 mg/kg.

Results: There were no differences in patient or graft survival between the 3 groups. One-year rejection rates in the first 2 groups were 8.3% and 8.8%, respectively, comparable to contemporaneous rates reported to the Scientific Registry of Transplant Recipients. Dose tailoring permitted substantial cost savings estimated at US $1 091 502. Mean length of stay fell by almost 3 days as the protocol was refined. There were no episodes of phlebitis. Infection rates were comparable with those reported to the Scientific Registry of Transplant Recipients.

Conclusions: The novel findings of the current study include peripheral administration, reduced dosing, favorable safety, excellent allograft outcomes, and clear associative data regarding reduced costs and length of stay.
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http://dx.doi.org/10.1097/TXD.0000000000000765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811272PMC
February 2018

QASI: A collaboration for implementation of an independent quality assessment programme in India.

Afr J Lab Med 2016 12;5(2):442. Epub 2016 Oct 12.

National HIV & Retrovirology Laboratories, Public Health Agency of Canada, JC Wilt Infectious Diseases Research Centre, Winnipeg, Canada.

Objective: The HIV pandemic remains a significant global health concern. Accurate determination of CD4+ T-cells in patient samples relies on reliable CD4 enumeration. The Quality Assessment and Standardization programme for Immunological measures relevant to HIV/AIDS (QASI) programme of the Public Health Agency of Canada provides clinical laboratories from resource-limited countries with a mechanism to evaluate the quality of CD4 testing and develop the implementation of an independent national External Quality Assessment (EQA) programme. This study describes how QASI helped develop the capacity for managing a sustainable national CD4 EQA programme in India.

Design: Supported by the Public Health Agency of Canada and Clinton Foundation HIV/AIDS Initiative, QASI engaged with the National AIDS Control Organization and the Indian National AIDS Research Institute to assist in technology transfer in preparation for the implementation/management of an independent CD4 EQA programme. Technology transfer training was provided to support corrective actions and to improve the quality of CD4 testing. Inter-laboratory variation of EQA surveys between pre- and post-skill development was compared.

Results: Prior to training, coefficient of variation values were 14.7% (mid-level CD4 count controls) and 39.0% (low-level). Following training, variation was reduced to 10.3% for mid-level controls and 20.0% for low-level controls.

Conclusion: This training assisted the National AIDS Control Organization and the Indian National AIDS Research Institute in identifying the information necessary for management of an EQA programme, and developed the foundation for India to provide corrective actions for sites with challenges in achieving reliable results for CD4 enumeration. This led to a demonstrable improvement in CD4 testing quality and illustrates how country-specific training significantly improved CD4 enumeration performance for better clinical management of HIV care in India.
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http://dx.doi.org/10.4102/ajlm.v5i2.442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433822PMC
October 2016

T2DiACoD: A Gene Atlas of Type 2 Diabetes Mellitus Associated Complex Disorders.

Sci Rep 2017 07 31;7(1):6892. Epub 2017 Jul 31.

G N Ramachandran Knowledge of Centre, Council of Scientific and Industrial Research - Institute of Genomics and Integrative Biology (CSIR-IGIB), Room No. 130, Mathura Road, New Delhi, 110025, India.

We performed integrative analysis of genes associated with type 2 Diabetes Mellitus (T2DM) associated complications by automated text mining with manual curation and also gene expression analysis from Gene Expression Omnibus. They were analysed for pathogenic or protective role, trends, interaction with risk factors, Gene Ontology enrichment and tissue wise differential expression. The database T2DiACoD houses 650 genes, and 34 microRNAs associated with T2DM complications. Seven genes AGER, TNFRSF11B, CRK, PON1, ADIPOQ, CRP and NOS3 are associated with all 5 complications. Several genes are studied in multiple years in all complications with high proportion in cardiovascular (75.8%) and atherosclerosis (51.3%). T2DM Patients' skeletal muscle tissues showed high fold change in differentially expressed genes. Among the differentially expressed genes, VEGFA is associated with several complications of T2DM. A few genes ACE2, ADCYAP1, HDAC4, NCF1, NFE2L2, OSM, SMAD1, TGFB1, BDNF, SYVN1, TXNIP, CD36, CYP2J2, NLRP3 with details of protective role are catalogued. Obesity is clearly a dominant risk factor interacting with the genes of T2DM complications followed by inflammation, diet and stress to variable extents. This information emerging from the integrative approach used in this work could benefit further therapeutic approaches. The T2DiACoD is available at www.http://t2diacod.igib.res.in/ .
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http://dx.doi.org/10.1038/s41598-017-07238-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5537262PMC
July 2017

Differential expression of circulating Th1/ Th2/ Th17 cytokines in serum of Chlamydia trachomatis-infected women undergoing incomplete spontaneous abortion.

Microb Pathog 2017 Sep 23;110:152-158. Epub 2017 Jun 23.

Microbiology Laboratory, National Institute of Pathology (ICMR), Sriramachari Bhawan, Safdarjung Hospital Campus, Post Box No. 4909, New Delhi, 110 029, India. Electronic address:

The study aimed to elucidate role of Th1/Th2/Th17 cytokines in the immunopathogenesis of spontaneous abortion in Chlamydia trachomatis (Ct)-positive first-trimester aborters. Endometrial curettage tissue and serum were collected from 145 aborters (spontaneous abortion (SA) group, n = 85; recurrent miscarriage (RM) group, n = 60) and 120 controls attending Department of Obstetrics & Gynecology at Safdarjung hospital, New Delhi (India). Polymerase chain reaction was used to detect Ct plasmid/MOMP, while commercial cytometric bead array kit was utilized to estimate circulating serum cytokines. 13.7% aborters were Ct-positive, however, none was found to be infected among controls. IFN-γ, TNF-α, IL-2, IL-6 and IL-17A cytokines were significantly increased in SA group/RM group (Ct-infected) versus controls. IL-4 showed no difference between groups, while IL-10 was significantly elevated in controls versus Ct-infected subjects in SA group/RM group. Furthermore, IFN-γ, TNF-α, IL-6, IL-17A cytokines were significantly elevated in Ct-positive RM group versus Chlamydia-infected SA group. However, IL-2, IL-4 and IL-10 cytokines showed no significant difference between Ct-positive SA group versus infected RM group. Positive correlation was found between few cytokines (TNF-α and IFN-γ/IL-17A; IL-17A and IFN-γ/IL-6) in Ct-positive aborters. Our study clearly established the role of Th1/Th2/Th17 cytokines in the pathogenesis of spontaneous abortion in Ct-infected subjects and found that Chlamydia-positive recurrent aborters had a predominant Th1/Th17 bias.
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http://dx.doi.org/10.1016/j.micpath.2017.06.031DOI Listing
September 2017

Biomolecules for Removal of Heavy Metal.

Recent Pat Biotechnol 2017 ;11(3):197-203

School of Bioscience, Institute of Management Studies, UC Campus, Ghaziabad, UP- 201015. India.

Background: Patents reveal that heavy metals are natural constituents of the earth's crust, but some heavy metals like cadmium, lead, mercury, arsenic etc. are injurious to living organisms at higher concentration. Nowadays, anthropogenic activities have altered geochemical cycles and biochemical balance of heavy metals. Biomolecules are used nowadays for removal of heavy metals compared to other synthetic biosorbents due to their environmental friendly nature and cost effectiveness.

Objective: The goal of this work is to identify the role of biomolecules like polysaccharides, polypeptides, natural compounds containing aromatic acid etc. for heavy metal removal by bio sorption.

Discussion: It has been observed that efficiency of biomolecules can be increased by functionalization e.g. cellulose functionalization with EDTA, chitosan with sulphur groups, alginate with carboxyl/ hydroxyl group etc. It was found that the porous structure of aerogel beads improves both sorption and kinetic properties of the material. Out of polypeptides metallothionein has been widely used for removal of heavy metal up to 88% from seawater after a single centrifugation.

Conclusion: These cost effective functionalized biomolecules are significantly used for remediation of heavy metals by immobilizing these biomolecules onto materials.
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http://dx.doi.org/10.2174/1872208311666170223155019DOI Listing
May 2018
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