Publications by authors named "Amit K Yadav"

25 Publications

  • Page 1 of 1

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

Appl Microbiol Biotechnol 2021 Sep 27. 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
September 2021

Gut microbiota-derived metabolites in CRC progression and causation.

J Cancer Res Clin Oncol 2021 Jul 17. 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
July 2021

Fabrication of label-free and ultrasensitive electrochemical immunosensor based on molybdenum disulfide nanoparticles modified disposable ITO: An analytical platform for antibiotic detection in food samples.

Food Chem 2021 Nov 29;363:130245. Epub 2021 May 29.

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

Here, we aimed to fabricate a label-free immunosensing platform for the first time based on molybdenum disulfide nanoparticles (nMoSNPs) deposited on ITO) coated glass substrate for the electrochemical detection of ampicillin (AMP). The stable and high surface area of nMoSNPs were made by a low-temperature one-step hydrothermal route, bestowing the carrying capacity of anti-AMP (antibody against AMP) through an amide linkage. The spectroscopic, morphological, and structural characterization of the proposed electrodes were performed using various analytical and electrochemical techniques. The differential pulse voltammetry technique was utilized to evaluate anti-AMP and AMP interaction on the electrode surface. The developed immunosensor exhibits high sensitivity, a broad detection range having a significant detection limit towards detection of AMP having excellent selectivity, acceptable stability, and reproducibility. Furthermore, the applicability of the proposed immunosensor was tested in spiked milk, water, and orange juice, and the results confirmed the consistency of the immunosensor.
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http://dx.doi.org/10.1016/j.foodchem.2021.130245DOI Listing
November 2021

Brown carbon aerosols in the Indo-Gangetic Plain outflow: insights from excitation emission matrix (EEM) fluorescence spectroscopy.

Environ Sci Process Impacts 2021 May;23(5):745-755

Department of Earth Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur, 741246, Nadia, India and School of Engineering, Indian Institute of Technology (IIT) Mandi, Room No. F8, Building A8, Kamand, Himachal Pradesh 175075, India.

We report the first characterization of the aerosol brown carbon (BrC) composition in the Indian context using excitation emission matrix (EEM) fluorescence spectroscopy coupled with parallel factor (PARAFAC) analysis. We find that biomass burning (BB)-dominated wintertime aerosols in the Indo-Gangetic Plain (IGP) outflow are characterized by two humic-like (HULIS) (C1_aq and C2_aq) and one protein-like/fossil fuel-derived (C3_aq) component for aqueous-extractable BrC (BrCaq), and by one humic-like (C1_me) and one protein-like (C2_me) component for methanol-extractable BrC (BrCme). Strong correlations of the BB tracer nss-K+ with C1_aq and C2_aq (r = 0.75-0.84, p < 0.01) and C1_me (r = 0.77, p < 0.01) point towards the BB-dominated IGP outflow as the major source. This is also supported by the analysis of fluorescence indices, which suggest extensive humification of BB emissions during atmospheric transport. The HULIS components correlate significantly with BrC absorption (r = 0.85-0.94, p < 0.01), and contribute substantially to the BrC relative radiative forcing of 13-24% vis-à-vis elemental carbon (EC). There is strong evidence that the abundant BB-derived NOX leads to NO3- formation in the IGP plume and drives the formation of water-soluble nitroaromatics (NACs) that constrain BrCaq light absorption (r = 0.56, p < 0.01) to a considerable degree. Overall, the study uncovers complex atmospheric processing of the IGP outflow in winter, which has important implications for regional climate.
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http://dx.doi.org/10.1039/d1em00050kDOI Listing
May 2021

Carbon cloth-based immunosensor for detection of 25-hydroxy vitamin D.

Mikrochim Acta 2021 04 1;188(4):145. Epub 2021 Apr 1.

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

Vitamin D (VD) deficiency is a global health concern due to its serious health impacts, and at present, the monitoring of VD status is expensive. Here, a novel immunosensor for sensitive and label-free detection of 25-hydroxy vitamin D (25VD) is reported. Nanostructured cerium(IV) oxide (nCeO) was anchored onto carbon cloth (CC) via electrophoretic deposition to fabricate a nanoplatform (nCeO/CC). Subsequently, bioactive molecules (anti-25VD and BSA) were introduced to fabricate the nanobioplatform BSA/anti-25VD/nCeO/CC as an immunosensor. The analytical performance of the developed immunosensor was studied towards 25VD detection. The immunosensor provides a broad linear range of 1-200 ng mL, high sensitivity of 2.08 μA ng mL cm, a detection limit of 4.63 ng mL, and a response time of 15 min, which is better than that of previous reports. The biosensor exhibited high selectivity, good reproducibility, and excellent stability for about 45 days. The potential application of the proposed immunosensor was observed for real serum samples towards 25VD detection that demonstrated a high correlation with the conventional enzyme-linked immunosorbent assay. Graphical abstract.
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http://dx.doi.org/10.1007/s00604-021-04751-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012417PMC
April 2021

Divergent Gold Catalysis: Unlocking Molecular Diversity through Catalyst Control.

Chem Rev 2021 Jul 8;121(14):8478-8558. Epub 2021 Feb 8.

Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhauri, Bhopal 462 066, India.

The catalyst-directed divergent synthesis, commonly termed as "divergent catalysis", has emerged as a promising technique as it allows chartering of structurally distinct products from common substrates simply by modulating the catalyst system. In this regard, gold complexes emerged as powerful catalysts as they offer unique reactivity profiles as compared to various other transition metal catalysts, primarily due to their salient electronic and geometrical features. Owing to the tunable soft π-acidic nature, gold catalysts not only evolved as superior contenders for catalyzing the reactions of alkynes, alkenes, and allenes but also, more intriguingly, have been found to provide divergent reaction pathways over other π-acid catalysts such as Ag, Pt, Pd, Rh, Cu, In, Sc, Hg, Zn, etc. The recent past has witnessed a renaissance in such examples wherein, by choosing gold catalysts over other transition metal catalysts or by fine-tuning the ligands, counteranions or oxidation states of the gold catalyst itself, a complete reactivity switch was observed. However, reviews documenting such examples are sporadic; as a result, most of the reports of this kind remained scattered in the literature, thereby hampering further development of this burgeoning field. By conceptualizing the idea of "Divergent Gold Catalysis (DGC)", this review aims to consolidate all such reports and provide a unified approach necessary to pave the way for further advancement of this exciting area. Based on the factors governing the divergence in product formation, an explicit classification of DGC has been provided. To gain a fundamental understanding of the divergence in observed reactivities and selectivities, the review is accompanied by mechanistic insights at appropriate places.
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http://dx.doi.org/10.1021/acs.chemrev.0c00903DOI Listing
July 2021

Gut microbiota derived trimethylamine N-oxide (TMAO) detection through molecularly imprinted polymer based sensor.

Sci Rep 2021 01 14;11(1):1338. Epub 2021 Jan 14.

National Institute of Immunology, New Delhi, India.

Trimethylamine N-oxide (TMAO), a microbiota-derived metabolite has been implicated in human health and disease. Its early detection in body fluids has been presumed to be significant in understanding the pathogenesis and treatment of many diseases. Hence, the development of reliable and rapid technologies for TMAO detection may augment our understanding of pathogenesis and diagnosis of diseases that TMAO has implicated. The present work is the first report on the development of a molecularly imprinted polymer (MIP) based electrochemical sensor for sensitive and selective detection of TMAO in body fluids. The MIP developed was based on the polypyrrole (PPy), which was synthesized via chemical oxidation polymerization method, with and without the presence of TMAO. The MIP, NIP and the non-sonicated polymer (PPy-TMAO) were separately deposited electrophoretically onto the hydrolyzed indium tin oxide (ITO) coated glasses. The chemical, morphological, and electrochemical behavior of MIP, non-imprinted polymer (NIP), and PPy-TMAO were characterized using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and electrochemical techniques. The detection response was recorded using differential pulse voltammetry (DPV), which revealed a decrease in the peak current with the increase in concentration of TMAO. The MIP sensor showed a dynamic detection range of 1-15 ppm with a sensitivity of 2.47 µA mL ppm cm. The developed sensor is easy to construct and operate and is also highly selective to detect TMAO in body fluids such as urine. The present research provides a basis for innovative strategies to develop sensors based on MIP to detect other metabolites derived from gut microbiota that are implicated in human health and diseases.
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http://dx.doi.org/10.1038/s41598-020-80122-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809026PMC
January 2021

Insights of arsenic (III/V) adsorption and electrosorption mechanism onto multi synergistic (redox-photoelectrochemical-ROS) aluminum substituted copper ferrite impregnated rGO.

Chemosphere 2021 Mar 7;267:129246. Epub 2020 Dec 7.

Advanced Nanoengineering Materials Laboratory, Indian Institute of Technology Kanpur, Kanpur, 208016, India; Department of Mechanical Engineering, Indian Institute of Technology Kanpur, Kanpur, 208016, India; Materials Science Programme, Indian Institute of Technology Kanpur, Kanpur, 208016, India. Electronic address:

The understanding of mechanistic insights in environmental remediation and mitigation systems is attracting larger attention, in recent days. Here in, aluminium substituted copper ferrite impregnated rGO hybrid (CAF-rGO) is verified to understand the adsorption/electrosorption mechanism of arsenic in aqueous systems. Near-surface study (XPS: As 3d, Cu 2p, Fe 2p, Al 2p, O 1s, C 1s) proposes redox, and ligand exchange reactions between contaminant, and CAF-rGO. Adsorption capacities are observed around 128.8 mg g [As(III)], 153.5 mg g [As(V)] with Freundlich model isotherms. Kinetics study follows the PSO model with influence of solar light (> 420 nm). Cyclic voltammetry (CV) analysis in different molarity conditions observed with signals around +0.1 and -0.6 V confirm the redox abilities, and N/O purged environments understood that electrosorption occurred through both reduction and sorption. Electrosorption study with pH variation shows the effect of protonation on the redox activity of individual arsenic species. Consistent signal around -0.6 ± 0.05 V in all the CV plots (i.e., Molarity, Environment, pH) recommends the usage of CAF-rGO for arsenic mitigation. Possible influence of photo-current (∼40 μA/cm at ∼ 0 V) towards As(III/V) decontamination is understood though photoelectrochemical analysis. Impedance plot shows low-resistance and better diffusion of arsenic oxy-anions during light irradiation. Synergistic nature of CAF-rGO generates reactive oxygen species (i.e., OH/O/O) in mitigating highly toxic As(III) species is also detailed in the present work.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129246DOI Listing
March 2021

Potential amelioration of waterborne iron toxicity in channel catfish (Ictalurus punctatus) through dietary supplementation of vitamin C.

Ecotoxicol Environ Saf 2020 Dec 23;205:111337. Epub 2020 Sep 23.

Aquaculture Research Institute, Department of Animal, Veterinary and Food Sciences, University of Idaho, Moscow, ID, 83844, USA; Hagerman Fish Culture Experiment Station, University of Idaho, 3059F National Fish Hatchery Road, Hagerman, ID, 83332, USA. Electronic address:

Iron overload in water is a problem in many areas of the world, which could exert toxic effects on fish. To achieve maximum growth and overall fitness, iron induced toxicity must be alleviated. Therefore, this research was undertaken to investigate the potential mitigation of iron toxicity by dietary vitamin C supplementation in channel catfish (Ictalurus punctatus). Two doses of vitamin C (143 and 573 mg/kg diet) were tested against high environmental iron (HEI, 9.5 mg/L representing 25% of 96 h LC). Fish were randomly divided into six groups with four replicated tanks. The groups were Control (vitamin C deficient feed), LVc (143 mg vitamin C supplemented per kg diet), HVc (573 mg vitamin C supplemented per kg diet), Con + Fe (control exposed to HEI), LVc + Fe (LVc exposed to HEI) and HVc + Fe (HVc exposed to HEI). Following an 8 week trial, there was a significant reduction in weight gain (WG%) in Con + Fe compared to the control, indicating a toxic effect of HEI on fish growth performance. Interestingly, WG% in both LVc + Fe and HVc + Fe groups were significantly higher than Cont + Fe, signifying that HEI inhibited growth, but this was alleviated by vitamin C. Both hemoglobin content and hematocrit were higher in LVc + Fe compared to the control and Con + Fe. In addition, exposure to HEI (Con + Fe) incited hepatic oxidative stress based on an over-accumulation of malondialdehyde (MDA) along with a significant inhibition in superoxide dismutase (SOD) and catalase (CAT) activities; whereas in LVc + Fe and HVc + Fe, the MDA content restored to basal level. A series of histopathological alterations were observed in the liver and gills, with the most severe lesions in Con + Fe, which was also complemented with a remarkable increase in hepatic iron accumulation. Vitamin C supplementations reduced the augmented concentrations of iron accumulation to that of the control. No effect, regardless of the treatments, was noted for fatty acid composition of muscle. Overall, our findings suggest that the vitamin C supplementation can be an effective therapeutic approach for boosting growth as well as alleviating iron toxicity in catfish.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111337DOI 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

Gold-Catalyzed 1,2-Diarylation of Alkenes.

Angew Chem Int Ed Engl 2020 Jul 11;59(29):11808-11813. Epub 2020 May 11.

Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhauri, Bhopal, 462 066, India.

Herein, we disclose the gold-catalyzed 1,2-diarylation of alkenes through the interplay of ligand-enabled Au /Au catalysis with the idiosyncratic π-activation mode of gold complexes. Unlike the classical migratory-insertion-based approach to 1,2-diarylation, the present approach not only circumvents the formation of direct Ar-Ar' coupling and Heck-type side products but more intriguingly demonstrates reactivity and selectivity complementary to those of previously known metal catalysis (Pd, Ni, or Cu). Detailed investigations to underpin the mechanistic scenario revealed oxidative addition of aryl iodides to an Au complex to be the rate-limiting step owing to the non-innocent nature of the aryl alkene.
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http://dx.doi.org/10.1002/anie.202002141DOI Listing
July 2020

A highly sensitive label-free amperometric biosensor for norfloxacin detection based on chitosan-yttria nanocomposite.

Int J Biol Macromol 2020 May 11;151:566-575. Epub 2020 Feb 11.

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

Here, non-invasive and label-free detection of trace-level of norfloxacin (NF) in human urine samples has been reported using the electrochemical technique. Nanostructured yttrium oxide (nYO) was synthesized at low-temperature using a one-step hydrothermal process. These nYO were characterized by various methods including XRD, FT-IR, Raman spectroscopy, and TEM. A biosensing platform based on nYO modified with chitosan (CH) was fabricated for the detection of NF. The nanocomposite film (CH-YO/ITO) was characterized by FE-SEM, contact angle measurements, and electrochemical techniques. Further, fluoroquinolones antibodies (anti-FQ) were used to modify the CH-YO/ITO electrode via covalent interaction. Non-specific sites were blocked by bovine serum albumin (BSA), those present on the anti-FQ/CH-YO/ITO electrode surface. The response study of BSA/anti-FQ/CH-YO/ITO bioelectrode towards NF detection revealed a wide range (1 pM-10 μM) with a lower detection limit of 3.87 pM using differential pulse voltammetry (DPV). The sensitivity obtained is as high as 10.14 μA μM cm with a fast response time of ~10 min. Moreover, the diagnostic performance of the fabricated sensor was evaluated to detect NF in urine spiked sample. The recovery of NF from the spiked sample was observed from 90.5 to 101.1%, with a maximum relative standard deviation of 7.04. The obtained results of the fabricated bioelectrode (BSA/anti-FQ/CH-YO/ITO) was validated with ELISA. The results were found better when compared with earlier described biosensors and commercially existing ELISA in terms of sensitivity and lower detection limit.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.02.089DOI Listing
May 2020

Phyto-inspired cyclic peptides derived from plant Pin-II type protease inhibitor reactive center loops for crop protection from insect pests.

Biochim Biophys Acta Gen Subj 2019 08 9;1863(8):1254-1262. Epub 2019 May 9.

Biochemical Sciences Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:

Background: Natural defence of plants against insect pests involves protease inhibitors (PIs) that interfere with insect digestive proteases. Pin-II type plant PIs are wound inducible upon insect damage and possess multiple inhibitory repeat domains that can inhibit trypsin and chymotrypsin-like proteases in the insect midgut. Yet, their agricultural ex-vivo application is limited due to large molecular size and environmental instability, which could be overcome by small peptides.

Methods: Bicyclic peptides were designed by grafting Pin-II PIs derived reactive center loop (RCL) on synthetic tris(bromomethyl)benzene scaffold. In vitro binding with trypsin-like proteases was evaluated by biochemical and biophysical assays, followed by molecular dynamics simulations. In vivo effects on two major lepidopteran insect pests, Helicoverpa armigera and Spodoptera litura were studied upon feeding with peptide treated leaves. Affinity based pull down assays were used to identify target proteins in insect gut.

Results: Bicyclic RCLs showed ten-fold enhanced protease inhibition compared to their linear counterparts. They exhibited feeding deterrence and growth reduction of lepidopteran insects. Bicyclic peptides predominantly interact with midgut serine proteases. Possible binding modes involve simultaneous interaction with the active site and specificity-determining residues of insect gut trypsin.

Conclusion: Bicyclic peptides are potent inhibitors of serine proteases in the insect midgut. They cause feeding aversion and larval growth retardation. Bi-domain cyclic peptides interact with two sites on trypsin, leading to enhanced efficacy over linear RCL peptides.

General Significance: Bicyclic peptides mimic natural PIs by inhibiting insect proteases leading to growth reduction, thus, could be used as pest control molecules in agriculture.
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http://dx.doi.org/10.1016/j.bbagen.2019.05.003DOI Listing
August 2019

Advances in Higher Order Multiplexing Techniques in Proteomics.

J Proteome Res 2019 06 22;18(6):2360-2369. Epub 2019 May 22.

Drug Discovery Research Centre, Translational Health Science and Technology Institute , NCR Biotech Science Cluster , Third Milestone, Faridabad - Gurgaon Expressway , Faridabad , Haryana 121001 , India.

Proteomics by mass spectrometry (MS) allows the large-scale identification and quantitation of the cellular proteins in a given biological context. Systems biology studies from proteomics data are largely limited by the accuracy and coverage of quantitative proteomics along with missing values. Toward this end, statistically robust biological observations are required, comprising multiple replicates, preferably with little technical variations. Multiplexed labeling techniques in proteomics allow quantitative comparisons of several biological samples or conditions. In this focused Review, we discuss an emerging technique called higher order multiplexing or enhanced multiplexing, a unique combination of traditional MS- and MS-based quantitative proteomics methods that allows for expanding the multiplexing capability of MS methods to save valuable instrument time, achieve statistical robustness, enhance coverage and quantitation accuracy, and reduce the run-to-run variability. We discuss the various innovative studies and experimental designs that exploit the power of this technique and its variants to provide an overview of a rapidly growing area and also to highlight the advantages and challenges that lie ahead in the widespread adoption of this technique.
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http://dx.doi.org/10.1021/acs.jproteome.9b00228DOI Listing
June 2019

Physiological insights into largemouth bass (Micropterus salmoides) survival during long-term exposure to high environmental ammonia.

Aquat Toxicol 2019 Feb 30;207:72-82. Epub 2018 Nov 30.

Department of Aquaculture and Fisheries, University of Arkansas at Pine Bluff, 1200 North University Drive, Pine Bluff, 71601, AR, USA. Electronic address:

Waterborne ammonia is an environmental pollutant that is toxic to all aquatic animals. However, ammonia induced toxicity as well as compensatory mechanisms to defend against high environmental ammonia (HEA) are not well documented at present for largemouth bass (Micropterus salmoides), a high value fish for culture and sport fisheries in the United States. To provide primary information on the sensitivity of this species to ammonia toxicity, a 96 h-LC test was conducted. Thereafter, responses at physiological, ion-regulatory and transcript levels were determined to get insights into the underlying adaptive strategies to ammonia toxicity. For this purpose, fish were progressively exposed to HEA (8.31 mg/L representing 25% of 96 h-LC) for 3, 7, 14, 21 and 28 days. Temporal effects of HEA on oxygen consumption rate (MO), ammonia and urea dynamics, plasma ions (Na, Cl and K), branchial Na/K-ATPase (NKA) and H-ATPase activity, muscle water content (MWC), energy store (glycogen, lipid and protein) as well as branchial mRNA expression of Rhesus (Rh) glycoproteins were assessed. Probit analysis showed that 96 h-LC of (total) ammonia (as NHHCO) at 25 °C and pH 7.8 was 33.24 mg/L. Results from sub-lethal end-points shows that ammonia excretion rate (J) was strongly inhibited after 7 days of HEA, but was unaffected at 3, 14 and 21 days. At 28 days fish were able to increase J efficiently and concurrently, plasma ammonia re-established to the basal level. Urea production was increased as evidenced by a considerable elevation of plasma urea, but urea excretion rate remained unaltered. Expression of Rhcg isoform (Rhcg2) mRNA was up-regulated in parallel with restored or increased J, suggesting its ammonia excreting role in largemouth bass. Exposure to HEA also displayed pronounced augmentations in NKA activity, exemplified by a rise in plasma [Na]. Furthermore, [K], [Cl] and MWC homeostasis were disrupted followed by recovery to the control levels. H-ATPase activity was elevated but NKA did not appear to function preferentially as a Na/NH-ATPase. From 14 days onwards MO was depressed, potentially an attempt towards minimizing catabolism. Glycogen content in liver and muscle were temporarily depleted, whereas a remarkable increment in protein was evident at the last exposure period. Overall, these data suggest that ammonia induced toxicity can disturb several biological processes in largemouth bass, however, it can adapt to the long-term sub-lethal ammonia concentrations by activating various components of ammonia excretory, ion-regulatory and metabolic pathways.
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http://dx.doi.org/10.1016/j.aquatox.2018.11.027DOI Listing
February 2019

Commentary: Deep Phosphoproteomic Measurements Pinpointing Drug Induced Protective Mechanisms in Neuronal Cells.

Authors:
Amit K Yadav

Front Physiol 2017 21;8:174. Epub 2017 Mar 21.

Drug Discovery Research Center, Translational Health Science and Technology Institute, NCR Biotech Science Cluster Haryana, India.

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http://dx.doi.org/10.3389/fphys.2017.00174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359244PMC
March 2017

Efficient Cellular Entry of (r-x-r)-Type Carbamate-Plasmid DNA Complexes and Its Implication for Noninvasive Topical DNA Delivery to Skin.

Mol Pharm 2016 06 26;13(6):1779-90. Epub 2016 May 26.

Department of Structural Biology, CSIR-Institute of Genomics and Integrative Biology , South Campus, Mathura Road, New Delhi, India 110020.

Arginine-rich cell penetrating peptides are powerful tools for in vitro as well as in vivo delivery of a wide plethora of biomolecules. However, presence of consecutive arginine residues leads to enhanced amenability for proteolytic degradation as well as steric hindrances for membrane interactions which compromise its bioavailability. In order to overcome these limitations we previously reported a safe and stable octaarginine based oligomer, i.e., (r-x-r)4-carbamate, where the backbone amide linkages were replaced by carbamate linkages and 6-aminohexanoic acid based spacer moieties were incorporated for better flexibility, hydrophobicity, optimal spacing of guanidinium groups, and protection against proteolytic cleavage; resulting in improved transfection efficiency over its amide counterpart. In the present work we have investigated the mechanism behind this enhanced transfection efficiency and, based on our observations, demonstrate how the synergistic effect of rationalized oligomer designing, complex characteristics, and cell type contributes to overall effective intracellular delivery. Our results indicate that the (r-x-r)4-carbamate-plasmid DNA complexes primarily utilize lipid raft dependent pathway of cellular entry more than other pathways, and this possibly facilitates their increased entry in the lipid raft rich milieu of skin cells. We also emphasize the utility of oligomer (r-x-r)4-carbamate as an efficient carrier for topical delivery of nucleic acids in skin tissue. This carrier can be utilized for safe, efficient, and noninvasive delivery of therapeutically relevant macromolecular hydrophilic cargo like nucleic acids to skin.
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http://dx.doi.org/10.1021/acs.molpharmaceut.5b00915DOI Listing
June 2016

Enteric Duplication Cysts in Children: A Clinicopathological Dilemma.

J Clin Diagn Res 2015 Aug 1;9(8):EC08-11. Epub 2015 Aug 1.

Senior Resident, Department of Paediatric Surgery, Vardhman Mahavir Medical College & Safdarjung Hospital , New Delhi, India .

Aim: Enteric duplication cysts are rare and uncommon congenital malformations formed during the embryonic period of the development of human digestive system and are mainly encountered during infancy or early childhood, but seldom in adults. The clinical presentation is extremely variable depending upon its size, location and type. We present six cases of enteric duplication cysts with diverse clinico-pathological features.

Materials And Methods: This study was carried out in the Department of Pathology and Department of Paediatric Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India for a period of 2 years (January 2013 - December 2014). We retrospectively analyzed six patients of enteric duplication cysts based on data obtained, which consisted of patient's age, sex, clinical presentation, radiological features, operative findings and histopathology report. The data collected was analyzed by descriptive statistics.

Results: Six children between age range of 3 days to 10 years had enteric duplication cysts. Two had ileal and one each were of pyloroduodenal, colonic and rectal duplication cyst. In one patient a presumptive diagnosis of enteric duplication cyst was made. Radiology played an important contributory role in diagnosis of these cysts in all the patients but histopathology proved to be gold standard for its confirmation. All these patients were managed by surgical excision. The postoperative and follow up period in all the cases was uneventful.

Conclusion: It is important to be aware and make a definitive diagnosis of this rare congenital anomaly as they can present in various clinical forms and can cause significant morbidity and even mortality if left untreated by causing life threatening complications.
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http://dx.doi.org/10.7860/JCDR/2015/12929.6381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576543PMC
August 2015

Second generation, arginine-rich (R-X'-R)(4)-type cell-penetrating α-ω-α-peptides with constrained, chiral ω-amino acids (X') for enhanced cargo delivery into cells.

Bioorg Med Chem Lett 2014 Sep 19;24(17):4198-202. Epub 2014 Jul 19.

Organic Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, Maharashtra, India. Electronic address:

The syntheses of novel N-aminoalkyl proline-derived spacers (X') in polycationic (R-X'-R)-motif cell-penetrating α-ω-α-peptides are described as improved molecular transporters and their structural features studied by CD. FACS analysis shows enhanced cellular uptake and confocal microscopy indicates predominantly cytoplasmic localization. The oligomers are efficient at transporting pDNA into cells. The chirality together with the hydrophobicity and flexibility derived from the spacer chain are found to have marked influence on the cell-penetrating and cargo delivery properties of the cell-penetrating peptides (CPPs). The peptides containing N-(3-aminopropyl)-D-proline spacers are found to be the best at cell penetration and cargo delivery in the present study.
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http://dx.doi.org/10.1016/j.bmcl.2014.07.040DOI Listing
September 2014

Mitigation of chlorine gas lung injury in rats by postexposure administration of sodium nitrite.

Am J Physiol Lung Cell Mol Physiol 2011 Mar 10;300(3):L362-9. Epub 2010 Dec 10.

Departments of Environmental Health Sciences, Schools of Public Health and Medicine, University of Alabama at Birmingham, USA.

Nitrite (NO(2)(-)) has been shown to limit injury to the heart, liver, and kidneys in various models of ischemia-reperfusion injury. Potential protective effects of systemic NO(2)(-) in limiting lung injury or enhancing repair have not been documented. We assessed the efficacy and mechanisms by which postexposure intraperitoneal injections of NO(2)(-) mitigate chlorine (Cl(2))-induced lung injury in rats. Rats were exposed to Cl(2) (400 ppm) for 30 min and returned to room air. NO(2)(-) (1 mg/kg) or saline was administered intraperitoneally at 10 min and 2, 4, and 6 h after exposure. Rats were killed at 6 or 24 h. Injury to airway and alveolar epithelia was assessed by quantitative morphology, protein concentrations, number of cells in bronchoalveolar lavage (BAL), and wet-to-dry lung weight ratio. Lipid peroxidation was assessed by measurement of lung F(2)-isoprostanes. Rats developed severe, but transient, hypoxemia. A significant increase of protein concentration, neutrophil numbers, airway epithelia in the BAL, and lung wet-to-dry weight ratio was evident at 6 h after Cl(2) exposure. Quantitative morphology revealed extensive lung injury in the upper airways. Airway epithelial cells stained positive for terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL), but not caspase-3. Administration of NO(2)(-) resulted in lower BAL protein levels, significant reduction in the intensity of the TUNEL-positive cells, and normal lung wet-to-dry weight ratios. F(2)-isoprostane levels increased at 6 and 24 h after Cl(2) exposure in NO(2)(-)- and saline-injected rats. This is the first demonstration that systemic NO(2)(-) administration mitigates airway and epithelial injury.
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http://dx.doi.org/10.1152/ajplung.00278.2010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3064287PMC
March 2011

Ascorbate and deferoxamine administration after chlorine exposure decrease mortality and lung injury in mice.

Am J Respir Cell Mol Biol 2011 Aug 3;45(2):386-92. Epub 2010 Dec 3.

Department of Anesthesiology, School of Medicine and Public Health, University of Alabama at Birmingham, 35294, USA.

Chlorine (Cl(2)) gas exposure poses an environmental and occupational hazard that frequently results in acute lung injury. There is no effective treatment. We assessed the efficacy of antioxidants, administered after exposure, in decreasing mortality and lung injury in C57BL/6 mice exposed to 600 ppm of Cl(2) for 45 minutes and returned to room air. Ascorbate and deferoxamine were administered intramuscularly every 12 hours and by nose-only inhalation every 24 hours for 3 days starting after 1 hour after exposure. Control mice were exposed to Cl(2) and treated with vehicle (saline or water). Mortality was reduced fourfold in the treatment group compared with the control group (22 versus 78%; P = 0.007). Surviving animals in the treatment group had significantly lower protein concentrations, cell counts, and epithelial cells in their bronchoalveolar lavage (BAL). Lung tissue ascorbate correlated inversely with BAL protein as well as with the number of neutrophils and epithelial cells. In addition, lipid peroxidation was reduced threefold in the BAL of mice treated with ascorbate and deferoxamine when compared with the control group. Administration of ascorbate and deferoxamine reduces mortality and decreases lung injury through reduction of alveolar-capillary permeability, inflammation, and epithelial sloughing and lipid peroxidation.
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http://dx.doi.org/10.1165/rcmb.2010-0432OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175564PMC
August 2011

Comparative analysis of protein structure of common Hb Q variants.

Authors:
Amit K Yadav

Indian J Pathol Microbiol 2010 Oct-Dec;53(4):696-8

Department of Pathology, Super Religare Laboratories Ltd., Fortis Escorts Hospital and Research Centre, Faridabad, India.

Context: Hemoglobin (Hb) Q variant is a group of hemoglobinopathies prevalent in south, south-east and western Asia. The primary structure of all of these molecules is well known. However, very little is known about the secondary and tertiary structures of these molecules. Therefore, a study of their secondary and tertiary structures is needed.

Aim: The study was aimed at investigating the secondary and tertiary structures of common Hb Q variants using bioinformatics tool.

Settings And Design: The secondary and tertiary structures of common Hb Q variants were evaluated using NNPREDICT server and CPHmodels 2.0 server, respectively.

Materials And Methods: Amino acid sequence of alpha globin chain was searched using ExPASY and was used for further mutation to Hb Q variants. The derived sequences were further analyzed using NNPREDICT server and CPHmodels 2.0 server to calculate their secondary and tertiary structures, respectively. These were then compared and any differences noted.

Results: It was observed that there is no difference between the predicted secondary structures of normal alpha globin and Hb Q-India. Hb Q-Iran carries an extra helix while Hb Q-Thailand carries two extra helices. The results of tertiary structure prediction also support these findings.

Conclusions: Differences in secondary and tertiary structure of various Hb Q variants have been observed in the present study. The study provides valuable data for better understanding of these uncommon hemoglobinopathies.
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http://dx.doi.org/10.4103/0377-4929.72039DOI Listing
February 2011

Postexposure administration of a {beta}2-agonist decreases chlorine-induced airway hyperreactivity in mice.

Am J Respir Cell Mol Biol 2011 Jul 20;45(1):88-94. Epub 2010 Sep 20.

901 19th Street South, 224 BMR2, Birmingham, AL 35294, USA.

Exposure to chlorine (Cl(2)) damages airway and alveolar epithelia, resulting in acute lung injury and reactive airway dysfunction syndrome. We evaluated the efficacy and mechanisms by which arformoterol, a long-term β(2)-agonist, administered after exposure, mitigated the extent of this injury. Exposure of C57BL/6 mice to 400 ppm Cl(2) for 30 minutes increased respiratory system resistance and airway responsiveness to aerosolized methacholine (assessed by FlexiVent) up to 6 days after exposure, and decreased Na(+)-dependent alveolar fluid clearance (AFC). Inducible Nitric Oxide Synthase (iNOS) knockout mice developed similar degrees of airway hyperreactivity as wild-type controls after Cl(2) exposure, indicating that reactive intermediates from iNOS do not contribute to Cl(2)-induced airway dysfunction in our model. Intranasal administration of arformoterol mitigated the Cl(2) effects on airway reactivity and AFC, presumably by increasing lung cyclic AMP level. Arformoterol did not modify the inflammatory responses, as evidenced by the number of inflammatory cells and concentrations of IL-6 and TNF-α in the bronchoalveolar lavage. NF-κB activity (assessed by p65 Western blots and electrophoretic mobility shift assay) remained at control levels up to 24 hours after Cl(2) exposure. Our results provide mechanistic insight into the effectiveness of long-term β(2)-agonists in reversing Cl(2)-induced reactive airway dysfunction syndrome and injury to distal lung epithelial cells.
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http://dx.doi.org/10.1165/rcmb.2010-0226OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145072PMC
July 2011

Mechanisms and modification of chlorine-induced lung injury in animals.

Proc Am Thorac Soc 2010 Jul;7(4):278-83

Department of Anesthesiology, University of Alabama at Birmingham, 901 19th Street South, Birmingham, AL 35294, USA.

Chlorine (Cl(2)) is a reactive oxidant gas used extensively in industrial processes. Exposure of both humans and animals to high concentrations of Cl(2) results in acute lung injury, which may resolve spontaneously or progress to acute respiratory failure. Injury to airway and alveolar epithelium may result from chemical reactions of Cl(2), from HOCl (the hydrolysis product of Cl(2)), and/or from the various reaction products, such as chloramines, that are formed from the reactions of these chlorinating species with biological molecules. Subsequent reactions may initiate self-propagating reactions and induce the production of inflammatory mediators compounding injury to pulmonary surfactant, ion channels, and components of lung epithelial and airway cells. Low-molecular-weight antioxidants, such as ascorbate, glutathione, and urate, present in the lung epithelial lining fluid and tissue, remove Cl(2) and HOCl and thus decrease injury to critical target biological targets. However, levels of lung antioxidants of animals exposed to Cl(2) in concentrations likely to be encountered in the vicinity of industrial accidents decrease rapidly and irreversibly. Our measurements show that prophylactic administration of a mixture containing ascorbate and desferal N-acetyl-cysteine, a precursor of reduced glutathione, prevents Cl(2)-induced injury to the alveolar epithelium of rats exposed to Cl(2). The clinical challenge is to deliver sufficient quantities of antioxidants noninvasively, after Cl(2) exposure, to decrease morbidity and mortality.
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http://dx.doi.org/10.1513/pats.201001-009SMDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136964PMC
July 2010
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