Showing papers by "Dr. Hari Singh Gour University published in 2017"

PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome.

Abstract: Several cancers are highly refractory to conventional chemotherapy. The survival of tumors in several cases is assisted by checkpoint immunomodulation to maintain the imbalance between immune surveillance and cancer cell proliferation. Check point antibody inhibitors, such as anti-PD-1/PD-L1, are a novel class of inhibitors that function as a tumor suppressing factor via modulation of immune cell-tumor cell interaction. These checkpoint blockers are rapidly becoming a highly promising cancer therapeutic approach that yields remarkable antitumor responses with limited side effects. In recent times, more than four check point antibody inhibitors have been commercialized for targeting PD-1, PDL-1, and CTLA-4. Despite the huge success and efficacy of the anti-PD therapy response, it is limited to specific types of cancers, which attributes to the insufficient and heterogeneous expression of PD-1 in the tumor microenvironment. Herein, we review the current landscape of the PD-1/PD-L1 mechanistic role in tumor immune evasion and therapeutic outcome for cancer treatment. We also review the current progress in clinical trials, combination of drug therapy with immunotherapy, safety, and future of check point inhibitors for multiple types of cancer.

Salicylic acid to decrease plant stress

Abstract: Pollution and climate change degrade plant health. Plant stress can be decreased by application of salicylic acid, an hormone involved in plant signaling. Salicylic acid indeed initiates pathogenesis-related gene expression and synthesis of defensive compounds involved in local resistance and systemic acquired resistance. Salicylic acid may thus be used against pathogen virulence, heavy metal stresses, salt stress, and toxicities of other elements. Applied salicylic acid improves photosynthesis, growth, and various other physiological and biochemical characteristics in stressed plants. Salicylic acid antagonizes the oxidative damaging effect of metal toxicity directly by acting as an antioxidant to scavenge the reactive oxygen species and by activating the antioxidant systems of plants and indirectly by reducing uptake of metals from their medium of growth. We review here the use of exogenous salicylic acid in alleviating bacterial, fungal, and viral diseases, heavy metal toxicity, toxicity of essential micronutrients, and salt stress.

Improvement Strategies, Cost Effective Production, and Potential Applications of Fungal Glucose Oxidase (GOD): Current Updates.

Abstract: Fungal glucose oxidase (GOD) is widely employed in the different sectors of food industries for use in baking products, dry egg powder, beverages, and gluconic acid production. GOD also has several other novel applications in chemical, pharmaceutical, textile and other biotechnological industries. The electrochemical suitability of GOD catalyzed reactions has enabled its successful use in bioelectronic devices, particularly biofuel cells, and biosensors. Other crucial aspects of GOD such as improved feeding efficiency in response to GOD supplemental diet, roles in antimicrobial activities and enhancing pathogen defense response, thereby providing induced resistance in plants have also been reported. Moreover, the medical science, another emerging branch where GOD was recently reported to induce several apoptosis characteristics as well as cellular senescence by downregulating Klotho gene expression. These widespread applications of GOD have led to increased demand for more extensive research to improve its production, characterization, and enhanced stability to enable long term usages. Currently, GOD is mainly produced and purified from Aspergillus niger and Penicillium species, but the yield is relatively low and the purification process is troublesome. It is practical to build an excellent GOD-producing strain. Therefore, the present review describes innovative methods of enhancing fungal GOD production by using genetic and non-genetic approaches in-depth along with purification techniques. The review also highlights current research progress in the cost effective production of GOD, including key advances, potential applications and limitations. Therefore, there is an extensive need to commercialize these processes by developing and optimizing novel strategies for cost effective GOD production.

Exploring the Role of Social Media in e-Government: an Analysis of Emerging Literature

Abstract: Driven by rising citizen expectations and the need for government innovation, social media has become a key component of e-government in a very short period of time. A number of research papers have been published on the role of social media in e-government in last few years. This study performs a literature review of the articles on the use of social media for getting access to e-government websites from the perspective of citizens. The database search through Scopus resulted in 115 articles, which formed the basis of this literature review. The keywords analysis of these articles indicates that 'e-government' and 'social media' were the most explored keywords across these studies. The methodological analysis indicates that the majority of the studies were analytical/conceptual/descriptive/theoretical in nature. The theoretical analysis, however, indicates that there is a lack of such research that has used some well-established theories or models to understand this concept. The review of literature further indicates that research themes such as 'electronic participation', 'engagement', 'transparency', 'communication/ interaction', 'trust' and 'collaboration' were found as some of the most frequently used categories under this area of research.

Efficient biodegradation of acephate by Pseudomonas pseudoalcaligenes PS-5 in the presence and absence of heavy metal ions [Cu(II) and Fe(III)], and humic acid

Abstract: The present study was intended to investigate the biodegradation of acephate in aqueous media in the presence and in the absence of metal ions [Fe(III) and Cu(II)], and humic acid (HA). Biodegradations were performed using Pseudomonas pseudoalcaligenes PS-5 (PS-5) isolated from the heavy metal polluted site. Biodegradations were monitored by UV–Visible, FTIR, and electron spray ionization–mass spectrometry (ESI–MS) analyses. ESI–MS analysis revealed that PS-5 degraded acephate to two metabolites showing intense ions at mass-to-charge ratios (m/z) 62 and 97. The observed kinetic was the pseudo-first order, and half-life periods (t 1/2) were 2.79 d−1 (of PS-5 + acephate), 3.45 d−1 [of PS-5 + acephate + Fe(III)], 3.16 d−1 [of PS-5 + acephate + Cu(II)], and 5.54 d−1 (of PS-5 + acephate + HA). A significant decrease in degradation rate of acephate was noticed in the presence of HA, and the same was confirmed by UV–Visible and TGA analyses. Strong aggregation behavior of acephate with humic acid in aqueous media was the major cause behind the slow degradation rate of acephate . New results on acephate metabolism by strain PS-5 in the presence and in the absence of metal ions [Fe(III) and Cu(II)] and humic acid were obtained. Results confirmed that Pseudomonas pseudoalcaligenes strain PS-5 was capable of mineralization of the acephate without formation of toxic metabolite methamidophos. More significantly, the Pseudomonas pseudoalcaligenes strain PS-5 could be useful as potential biological agents in effective bioremediation campaign for multi-polluted environments.

Adsorption-Driven Catalytic and Photocatalytic Activity of Phase Tuned In2S3 Nanocrystals Synthesized via Ionic Liquids

Abstract: Phase tuned quantum confined In2S3 nanocrystals are accessible solvothermally using task-specific ionic liquids (ILs) as structure directing agents. Selective tuning of size, shape, morphology, and, most importantly, crystal phase of In2S3 is achieved by changing the alkyl side chain length, the H-bonding, and aromatic π-stacking ability of the 1-alkyl-3- methylimidazolium bromide ILs, [Cnmim]Br (n = 2, 4, 6, 8, and 10). It is observed that crystallite size is significantly less when ILs are used compared to the synthesis without ILs keeping the other reaction parameters the same. At 150 °C, when no IL is used, pure tetragonal form of β-In2S3 appears however in the presence of [Cnmim]Br [n = 2,4], at the same reaction condition, a pure cubic phase crystallizes. However, in case of methylimidazolium bromides with longer pendant alkyl chains such as hexyl (C6), octyl (C8) or decyl (C10), nanoparticles of the tetragonal polymorph form. Likewise, judicious choice of reaction temperature and precursors has a profound effect to obtain phase pure and morphology controlled nanocrystals. Furthermore, the adsorption driven catalytic and photocatalytic activity of as-prepared nanosized indium sulfide is confirmed by studying the degradation of crystal violet (CV) dye in the presence of dark and visible light. A maximum of 94.8% catalytic efficiency is obtained for the In2S3 nanocrystals using tetramethylammonium bromide (TMAB) ionic liquid.

Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects

Abstract: Protection of the skin from the ultraviolet radiation is the prime concern of society. An increase in the adverse effects by ultraviolet (UV) radiation on the skin promoted cosmetic formulators to work in the area of UV blockers and their effective means of delivery. Nanostructured lipid carriers (NLCs) is a modern and successful lipid carrier system in the cosmetic world associated with various advantages i.e., stability, effective drug loading capacity etc. NLCs also permits to load 70% of UV blockers which are sufficient to obtain recommended Sun Protection Factor (SPF) which makes them suitable delivery systems for topical application of the UV blockers.

Design, synthesis, and characterization of 2,2-bis(2,4-dinitrophenyl)-2-(phosphonatomethylamino)acetate as a herbicidal and biological active agent

Abstract: The present study was designed to synthesize the bioactive molecule 2,2-bis(2,4-dinitrophenyl)-2-(phosphonatomethylamino)acetate (1), having excellent applications in the field of plant protection as a herbicide. Structure of newly synthesized molecule 1 was confirmed by using the elemental analysis, mass spectrometric, NMR, UV-visible, and FTIR spectroscopic techniques. To obtain better structural insights of molecule 1, 3D molecular modeling was performed using the GAMESS programme. Microbial activities of 1 were checked against the pathogenic strains Aspergillus fumigatus (NCIM 902) and Salmonella typhimurium (NCIM 2501). Molecule 1 has shown excellent activities against fungal strain A. fumigates (35 μg/l) and bacterial strain S. typhimurium (25 μg/l). To check the medicinal significance of molecule 1, interactions with bovine serum albumin (BSA) protein were checked. The calculated value of binding constant of molecule 1–BSA complex was 1.4 × 106 M−1, which were similar to most effective drugs like salicylic acid. More significantly, as compared to herbicide glyphosate, molecule 1 has exhibited excellent herbicidal activities, in pre- and post-experiments on three weeds; barnyard grass (Echinochloa Crus), red spranglitop (Leptochloa filiformis), and yellow nuts (Cyperus Esculenfus). Further, effects of molecule 1 on plant growth-promoting rhizobacterial (PGPR) strains were checked. More interestingly, as compared to glyphosate, molecule 1 has shown least adverse effects on soil PGPR strains including the Rhizobium leguminosarum (NCIM 2749), Pseudomonas fluorescens (NCIM 5096), and Pseudomonas putida (NCIM 2847).

Bacterial invertases: Occurrence, production, biochemical characterization, and significance of transfructosylation

Abstract: Invertase or β-D-fructofuranoside fructohydrolase (EC 3.2.1.26) was one of the foremost enzyme biocatalysts and established the primary concepts of most enzyme-kinetic principles. Invertases are glycoside hydrolases and occur mostly in microorganisms. Among microbial strains, for many decades yeast species have been extensively researched for invertase production, characterization, and applications in industries. Besides, limited literature is available on invertases from bacterial strains. The enzymic and molecular biological reports from bacterial invertases are scarce. In this minireview, occurrence, production, biochemical properties, and significance of transfructosylation of bacterial invertases are reported.

Dendrimers in Targeting and Delivery of Drugs

Abstract: Dendrimers are novel synthetic polymeric systems having improved physical and chemical properties due to their unique three-dimensional architectures Dendrimers have a well-defined size, shape, molecular weight and monodispersity These nanostructured macromolecules have shown their potential abilities in entrapping and/or conjugating the high molecular weight hydrophilic/hydrophobic entities by host-guest interactions and covalent bonding (prodrug approach) respectively Due to these properties, currently, dendrimers are of great interest for delivering drug molecules via different routes as a nanocarrier Toxicity problems associated with cationic dendrimers are overcome by PEGylation, which neutralizes the charge on them Dendrimers possess suitable properties to establish themselves as potential carriers for the delivery of therapeutic agents irrespective of certain synthetic and regulatory constraints This chapter contains various structural aspects and properties of dendrimers along with their pharmaceutical application as a potential novel drug delivery carrier

Neuroprotective Efficacy of Mitochondrial Antioxidant MitoQ in Suppressing Peroxynitrite-Mediated Mitochondrial Dysfunction Inflicted by Lead Toxicity in the Rat Brain

Abstract: Lead (Pb) is one of the most pollutant metals that accumulate in the brain mitochondria disrupting mitochondrial structure and function. Though oxidative stress mediated by reactive oxygen species remains the most accepted mechanism of Pb neurotoxicity, some reports suggest the involvement of nitric oxide (•NO) and reactive nitrogen species in Pb-induced neurotoxicity. But the impact of Pb neurotoxicity on mitochondrial respiratory enzyme complexes remains unknown with no relevant report highlighting the involvement of peroxynitrite (ONOO-) in it. Herein, we investigated these effects in in vivo rat model by oral application of MitoQ, a known mitochondria-specific antioxidant with ONOO- scavenging activity. Interestingly, MitoQ efficiently alleviated ONOO--mediated mitochondrial complexes II, III and IV inhibition, increased mitochondrial ATP production and restored mitochondrial membrane potential. MitoQ lowered enhanced caspases 3 and 9 activities upon Pb exposure and also suppressed synaptosomal lipid peroxidation and protein oxidation accompanied by diminution of nitrite production and protein-bound 3-nitrotyrosine. To ascertain our in vivo findings on mitochondrial dysfunction, we carried out similar experiments in the presence of different antioxidants and free radical scavengers in the in vitro SHSY5Y cell line model. MitoQ provided better protection compared to mercaptoethylguanidine, N-nitro-L-arginine methyl ester and superoxide dismutase suggesting the predominant involvement of ONOO- compared to •NO and O2•-. However, dimethylsulphoxide and catalase failed to provide protection signifying the noninvolvement of •OH and H2O2 in the process. The better protection provided by MitoQ in SHSY5Y cells can be attributed to the fact that MitoQ targets mitochondria whereas mercaptoethylguanidine, N-nitro-L-arginine methyl ester and superoxide dismutase are known to target mainly cytoplasm and not mitochondria. Taken together the results from the present study clearly brings out the potential of MitoQ against ONOO--induced toxicity upon Pb exposure indicating its therapeutic potential in metal toxicity.

Theranostic Nanomedicine; A Next Generation Platform for Cancer Diagnosis and Therapy.

Abstract: In the recent years, theranostic nanomedicine based strategies have gained much attention in the field of oncology particularly, in the development of new generation cancer diagnostic and therapeutic tools. Today, various approaches have been developed for bioactive(s) targeting to predefined pathological sites, as well as for quantification of physiological processes and visualization. Significant attempts have been made to combine therapeutic and diagnostic properties in to a single effective nanomedicine formulation. This concept, coined as "theranostics" is smart nanosystem(s), able to diagnose, bioactive(s) delivery and monitoring of therapeutic response. By combining therapeutic functionalities with molecular imaging, theranostic based strategies may be beneficial in the selection of therapy, planning of treatment, monitoring of objective response and planning of follow-up therapy based on the specific molecular characteristics of a disease. In this manuscript, we reviewed the recent development of theranostic approaches, various nanosystems as theranostic agents and applications of theranostic in cancer therapeutics and diagnostics.

pH Dependent Optical Switching and Fluorescence Modulation of Molybdenum Sulfide Quantum Dots

Abstract: Investigations on fluorescent molecules with fluorescence switching behavior as function of pH, temperature, ion concentration, etc. is highly desirable in the field of sensor device fabrication. In this study, the authors report an easy and eco-friendly hydrothermal route for the synthesis of pH dependent fluorescent MoS2 quantum dots (MoS2-QDs). The average size of the synthesized QDs is found to be ≈7 nm which was confirmed with transmission electron microscopy and atomic force microscopy. These MoS2-QDs show the pH dependent fluorescence switching behavior. Under pH ≈ 1 the fluorescence intensity of the MoS2-QDs is quenched while it shows ≈200 times enhancement under pH ≈ 13. This florescence ON/OFF switching is mainly due to the surface adsorbed functional groups (NH2, SO42−, OH−, etc.) and is a combined effect viz. protonation–deprotonation process, acid etching, quantum confined Stark effect and particle agglomeration. A plausible mechanism for this pH dependent ON/OFF switching behavior is also discussed in this study. The band gap calculation under different pH environment is also in good agreement to the hypothesis.

Ascorbic acid tethered polymeric nanoparticles enable efficient brain delivery of galantamine: An in vitro-in vivo study.

Abstract: The aim of this work was to enhance the transportation of the galantamine to the brain via ascorbic acid grafted PLGA-b-PEG nanoparticles (NPs) using SVCT2 transporters of choroid plexus. PLGA-b-PEG copolymer was synthesized and characterized by 1H NMR, gel permeation chromatography, and differential scanning calorimetry. PLGA-b-PEG-NH2 and PLGA-b-mPEG NPs were prepared by nanoprecipitation method. PLGA-b-PEG NPs with desirable size, polydispersity, and drug loading were used for the conjugation with ascorbic acid (PLGA-b-PEG-Asc) to facilitate SVCT2 mediated transportation of the same into the brain. The surface functionalization of NPs with ascorbic acid significantly increased cellular uptake of NPs in SVCT2 expressing NIH/3T3 cells as compared to plain PLGA and PLGA-b-mPEG NPs. In vivo pharmacodynamic efficacy was evaluated using Morris Water Maze Test, Radial Arm Maze Test and AChE activity in scopolamine induced amnetic rats. In vivo pharmacodynamic studies demonstrated significantly higher therapeutic and sustained action by drug loaded PLGA-b-PEG-Asc NPs than free drugs and drug loaded plain PLGA as well as PLGA-b-mPEG NPs. Additionally, PLGA-b-PEG-Asc NPs resulted in significantly higher biodistribution of the drug to the brain than other formulations. Hence, the results suggested that targeting of bioactives to the brain by ascorbic acid grafted PLGA-b-PEG NPs is a promising approach.

Combination of cationic dexamethasone derivative and STAT3 inhibitor (WP1066) for aggressive melanoma: a strategy for repurposing a phase I clinical trial drug

Abstract: Glucocorticoid, such as dexamethasone (Dex) is often used along with chemotherapy to antagonize side effects of chemotherapy. However, sustained use of Dex frequently develops drug resistance in patients. As a strategy to re-induce drug sensitivity, we planned to modify Dex by chemically conjugating it with twin ten carbon aliphatic chain containing cationic lipid. The resultant molecule, DX10, inhibited STAT3 activation through lowering the production of IL-6. To enhance the STAT3 inhibitory effect of DX10, we used WP (a commercially available STAT3 inhibitor) along with DX10. Combination treatment of both significantly inhibited STAT3 activation when compared to either of the individual treatment. The effect of DX10, either in combination or alone, was mediated through glucocorticoid receptor (GR), thereby repurposing the role of GR in the context of p-STAT3 inhibition-mediated cancer treatment. Cellular viability study proved the synergistic effect of WP and DX10. Further, combination treatment led to induction of early stage of apoptosis and cell cycle arrest. In vivo melanoma tumor regression study confirmed the enhanced anti-tumor activity of co-treatment over individual treatment of DX10 or WP. Thus, together our result demonstrates that DX10 may be used in combination therapy with STAT3 inhibitor like WP for combating cancer with constitutively active STAT3.

Biotechnological potential of microbial inulinases: Recent perspective

Abstract: Among microbial enzymes, inulinases or fructo-furanosylhydrolases have received considerable attention in the past decade, and as a result, a variety of applications based on enzymatic hydrolysis of inulin have been documented. Inulinases are employed for generation of fructose and inulo-oligosaccharides (IOS) in a single-step reaction with specificity. The high fructose syrup can be biotransformed into value-added products such as ethanol, single cell protein, while IOS are indicated in nutraceutical industry as prebiotic. Myriad microorganisms produce inulinases, and a number of exo- and endo-inulinases have been characterized and expressed in heterologous hosts. Initially, predominated by Aspergilli, Penicillia, and some yeasts (Kluyveromyces spp.), the list of prominent inulinase producers has gradually expanded and now includes extremophilic prokaryotes and marine-derived microorganisms producing robust inulinases. The present paper summarizes important developments about microbial inulinases and their applications made in the last decade.

Effects of laser peening on fretting wear behaviour of alloy 718 fretted against two different counterbody materials

Abstract: This paper deals with the effects of laser peening on fretting wear behaviour of a nickel-based superalloy, alloy 718, fretted against two different counterbody materials (alumina and SAE 52100 ste...

Synthesis and DNA-binding study of imidazole linked thiazolidinone derivatives

Abstract: A novel series of imidazole-linked thiazolidinone hybrid molecules were designed and synthesized through a feasible synthetic protocol. The molecules were characterized with Fourier transform infrared (FT-IR), 1 H nuclear magnetic resonance (NMR), 13 C NMR and high-resolution mass spectrometry (HRMS) techniques. In vitro susceptibility tests against Gram-positive (S. aureus and B. subtilis) and Gram-negative bacteria (E. coli and P. aeruginosa) gave highly promising results. The most active molecule (3e) gave a minimal inhibitory concentration (MIC) value of 3.125 μg/mL which is on par with the reference drug streptomycin. Structure-activity relationships revealed activity enhancement by nitro and chloro groups when they occupied meta position of the arylidene ring in 2-((3-(imidazol-1-yl)propyl)amino)-5-benzylidenethiazolidin-4-ones. DNA-binding study of the most potent molecule 3e with salmon milt DNA (sm-DNA) under simulated physiological pH was probed with UV-visible absorption, fluorescence quenching, gel electrophoresis and molecular docking techniques. These studies established that compound 3e has a strong affinity towards DNA and binds at DNA minor groove with a binding constant (Kb ) 0.18 × 102 L mol-1 . Molecular docking simulations predicted strong affinity of 3e towards DNA with a binding affinity (ΔG) -8.5 kcal/mol. Van der Waals forces, hydrogen bonding and hydrophobic interactions were predicted as the main forces of interaction. The molecule 3e exhibited specific affinity towards adenine-thiamine base pairs. Copyright © 2016 John Wiley & Sons, Ltd.

Investigation of enhancement mode HfO2 insulated N-polarity GaN/InN/GaN/In0.9Al0.1N heterostructure MISHEMT for high-frequency applications

Abstract: In this paper, we examined normally-OFF N-polar InN-channel Metal insulated semiconductor high-electron mobility transistors (MISHEMTs) device with a relaxed In0.9Al0.1N buffer layer. In addition, the enhancement-mode operation of the N-polar structure was investigated. The effect of scaling in N-polar MISHEMT, such as the dielectric and the channel thickness, alter the electrical behavior of the device. We have achieved a maximum drain current of 1.17 A/mm, threshold voltage (VT) =0.728 V, transconductance (gm) of 2.9 S mm−1, high ION/IOFF current ratio of 3.23×103, lowest ON-state resistance (RON) of 0.41 Ω mm and an intrinsic delay time (τ) of 1.456 Fs along with high-frequency performance with ft/ fmax of 90 GHz/109 GHz and 180 GHz/260 GHz for TCH =0.5 nm at Vds =0.5 V and 1.0 V. The numerically simulated results of highly confined GaN/InN/GaN/In0.9Al0.1N heterostructure MISHEMT exhibits outstanding potential as one of the possibility to replace presently used N-polar MISHEMTs for delivering high power density and frequency at RF/power amplifier applications.

Screening, statistical optimized production, and application of β‐mannanase from some newly isolated fungi

Abstract: Eighty-eight fungi isolated from soil and decaying organic matter were screened for mannanolytic activity. Twenty-eight fungi produced extracellular mannanase on locust bean gum as evidenced by zone of hydrolysis produced on mannan agar gel. Six prominent producers, including four Fusarium species namely Fusarium fusarioides NFCCI 3282, Fusarium solani NFCCI 3283, Fusarium equiseti NFCCI 3284, Fusarium moniliforme NFCCI 3287 with Cladosporium cladosporioides NFCCI 3285 and Acrophialophora levis NFCCI 3286 produced the β-mannanase in the range of 84–140 nkat/ml. All these grew well on particulate substrates in solid state fermentation (SSF), producing relatively higher titers on mannan rich palm kernel cake (PKC) and copra meal (CM). Two high yielding strains, F. equiseti (1747 nkat/gds) and A. levis (897 nkat/gds) were selected for statistical optimization of mannanase on PKC. Interaction of two critical SSF parameters, pH and moisture on mannanase production by these two molds was studied by response surface method. Optimized production on PKC resulted in three to four fold enhancement in enzyme yield was observed in case of F. equiseti (5945 nkat/gds) and A. levis (4726 nkat/gds). HPLC analysis of mannan hydrolysate indicated that F. equiseti and A. levis mannanase performed efficient hydrolysis of konjac gum (up to 99%) with exclusive manno-oligosaccahride (DP of 4) production. Saccharification of lignocellulosic biomass was attempted using mannanase preparation from F. equiseti and A. levis. A semi-native SDS-PAGE revealed that A. levis and F. solani produced three isoforms, F. moniliforme produced two isoforms while F. fusarioides, F. equiseti and C. cladosporioides produced a single enzyme. This article is protected by copyright. All rights reserved