Showing papers by "Rama Shanker Verma published in 2020"

SARS-CoV, MERS-CoV, and 2019-nCoV viruses: an overview of origin, evolution, and genetic variations.

Abstract: Coronaviruses are single stranded RNA viruses usually present in bats (reservoir hosts), and are generally lethal, highly transmissible, and pathogenic viruses causing sever morbidity and mortality rates in human. Several animals including civets, camels, etc. have been identified as intermediate hosts enabling effective recombination of these viruses to emerge as new virulent and pathogenic strains. Among the seven known human coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 (2019-nCoV) have evolved as severe pathogenic forms infecting the human respiratory tract. About 8096 cases and 774 deaths were reported worldwide with the SARS-CoV infection during year 2002; 2229 cases and 791 deaths were reported for the MERS-CoV that emerged during 2012. Recently ~ 33,849,737 cases and 1,012,742 deaths (data as on 30 Sep 2020) were reported from the recent evolver SARS-CoV-2 infection. Studies on epidemiology and pathogenicity have shown that the viral spread was potentially caused by the contact route especially through the droplets, aerosols, and contaminated fomites. Genomic studies have confirmed the role of the viral spike protein in virulence and pathogenicity. They target the respiratory tract of the human causing severe progressive pneumonia affecting other organs like central nervous system in case of SARS-CoV, severe renal failure in MERS-CoV, and multi-organ failure in SARS-CoV-2. Herein, with respect to current awareness and role of coronaviruses in global public health, we review the various factors involving the origin, evolution, and transmission including the genetic variations observed, epidemiology, and pathogenicity of the three potential coronaviruses variants SARS-CoV, MERS-CoV, and 2019-nCoV.

Deacetylation of LAMP1 drives lipophagy-dependent generation of free fatty acids by Abrus agglutinin to promote senescence in prostate cancer.

Abstract: Therapy-induced senescence in cancer cells is an irreversible antiproliferative state, which inhibits tumor growth and is therefore a potent anti-neoplastic mechanism. In this study, low doses of Abrus agglutinin (AGG)-induced senescence through autophagy in prostate carcinoma cells (PC3) and inhibited proliferation. The inhibition of autophagy with 3-methyl adenine reversed AGG-induced senescence, thus confirming that AGG-triggered senescence required autophagy. AGG treatment also led to lipophagy-mediated accumulation of free fatty acids (FFAs), with a concomitant decrease in the number of lipid droplets. Lalistat, a lysosomal acid lipase inhibitor, abrogated AGG-induced lipophagy and senescence in PC3 cells, indicating that lipophagy is essential for AGG-induced senescence. The accumulation of FFAs increased reactive oxygen species generation, a known facilitator of senescence, which was also reduced in the presence of lalistat. Furthermore, AGG upregulated silent mating type information regulator 2 homolog 1 (SIRT1), while the presence of sirtinol reduced autophagy flux and the senescent phenotype in the AGG-treated cells. Mechanistically, AGG-induced cytoplasmic SIRT1 deacetylated a Lys residue on the cytoplasmic domain of lysosome-associated membrane protein 1 (LAMP1), an autolysosomal protein, resulting in lipophagy and senescence. Taken together, our findings demonstrate a novel SIRT1/LAMP1/lipophagy axis mediating AGG-induced senescence in prostate cancer cells.

Human Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells Labeled with Mn2+ and Gd3+ Co-Doped CuInS2-ZnS Nanocrystals for Multimodality Imaging in a Tumor Mice Model.

Abstract: Mesenchymal stem cell (MSCs) therapy has recently received profound interest as a targeting platform in cancer theranostics because of inherent tumor-homing abilities. However, the terminal tracking of MSCs engraftment by fluorescent in situ hybridization, immuno-histochemistry, and flow-cytometry techniques to translate into clinics is still challenging because of a dearth of inherent MSCs-specific markers and FDA approval for genetic modifications of MSCs. To address this challenge, a cost-effective noninvasive imaging technology based on multifunctional nanocrystals (NCs) with enhanced detection sensitivity, spatial-temporal resolution, and deep-tissue diagnosis is needed to be developed to track the transplanted stem cells. A hassle-free labeling of human umbilical cord Wharton's Jelly (WJ)-derived MSCs with Mn2+ and Gd3+ co-doped CuInS2-ZnS (CIS-ZMGS) NCs has been demonstrated in 2 h without requiring an electroporation process or transfection agents. It has been found that WJ-MSCs labeling did not affect their multilineage differentiation (adipocyte, osteocyte, chondrocyte), immuno-phenotypes (CD44+, CD105+, CD90+), protein (β-actin, vimentin, CD73, α-SMCA), and gene expressions. Interestingly, CIS-ZMGS-NCs-labeled WJ-MSCs exhibit near-infrared (NIR) fluorescence with a quantum yield of 84%, radiant intensity of ∼3.999 × 1011 (p/s/cm2/sr)/(μW/cm2), magnetic relaxivity (longitudinal r1 = 2.26 mM-1 s-1, transverse r2 = 16.47 mM-1 s-1), and X-ray attenuation (78 HU) potential for early noninvasive multimodality imaging of a subcutaneous melanoma in B16F10-tumor-bearing C57BL/6 mice in 6 h. The ex vivo imaging and inductively coupled plasma mass-spectroscopy analyses of excised organs along with confocal microscopy and immunofluorescence of tumor results also significantly confirmed the positive tropism of CIS-ZMGS-NCs-labeled WJ-MSCs in the tumor environment. Hence, we propose the magnetofluorescent CIS-ZMGS-NCs-labeled WJ-MSCs as a next-generation nanobioprobe of three commonly used imaging modalities for stem cell-assisted anticancer therapy and tracking tissue/organ regenerations.

Bacterial diversity and functional analysis of severe early childhood caries and recurrence in India.

Abstract: Dental caries is the most prevalent oral disease affecting nearly 70% of children in India and elsewhere. Micro-ecological niche based acidification due to dysbiosis in oral microbiome are crucial for caries onset and progression. Here we report the tooth bacteriome diversity compared in Indian children with caries free (CF), severe early childhood caries (SC) and recurrent caries (RC). High quality V3-V4 amplicon sequencing revealed that SC exhibited high bacterial diversity with unique combination and interrelationship. Gracillibacteria_GN02 and TM7 were unique in CF and SC respectively, while Bacteroidetes, Fusobacteria were significantly high in RC. Interestingly, we found Streptococcus oralis subsp. tigurinus clade 071 in all groups with significant abundance in SC and RC. Positive correlation between low and high abundant bacteria as well as with TCS, PTS and ABC transporters were seen from co-occurrence network analysis. This could lead to persistence of SC niche resulting in RC. Comparative in vitro assessment of biofilm formation showed that the standard culture of S. oralis and its phylogenetically similar clinical isolates showed profound biofilm formation and augmented the growth and enhanced biofilm formation in S. mutans in both dual and multispecies cultures.

Benefits of aged garlic extract in modulating toxicity biomarkers against p-dimethylaminoazobenzene and phenobarbital induced liver damage in Rattus norvegicus.

Abstract: Garlic (Allium sativum L), a popular spice, has been used for decades in treating several medical conditions Although Allicin, an active ingredient of garlic has been extensively studied on carci

Mineral wool composite with the use of saponite-containing mining industry waste

Abstract: the paper shows the possibility of producing a thermal insulating composite based on basalt fibers and sapo-nite-containing mining waste. A method for manufacturing thermal insulating composites from hydro-mass with different contents of the mixture components is proposed. Basalt fibers were used as a filler, and pre-mechanoactivated saponite-containing material (SCM) was used as a binder. It was found experimentally that depending on the composition of composites, the coefficient of thermal conductivity varies from 0.1109 to 0.1342 W/(m•K), and the compressive strength – from 0.45 to 0.93 MPa. In addition, it was found that thermal modification of composites at temperatures up to 1200°C significantly (up to 3 times) increases the compressive strength of composites, while not affecting the coefficient of thermal conductivity. The ex-periments to determine the conductivity of the composite “basalt fiber – SСM” depending on its moisture content showed that the obtained composite is characterized by intense and linear increase in the values of conductivity when the humidity of the sample to 12% and further increase in humidity practically does not change the values of the coefficient of thermal conductivity. Comparison of the studied thermal insulation composite with known structural thermal insulation materials in terms of its thermal insulation and strength characteristics showed that it is comparable to gas and foam blocks. It should also be noted that this material is environmentally safe and can withstand high temperatures without collapsing.

Establishing the promising role of novel combination of triple therapeutics delivery using polymeric nanoparticles for Triple negative breast cancer therapy.

Abstract: Introduction: Triple-negative breast cancer (TNBC) is a lethal tumor with an advanced degree of metastasis and poor survivability as compared to other subtypes of breast cancer. TNBC which consists of 15 % of all types of breast cancer is categorized by the absence of expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor-2 (HER2). This is the main reason for the failure of current hormonal receptor-based therapies against TNBCs, thus leading to poor patient outcomes. Therefore, there is a necessity to develop novel therapies targeting this devastating disease. Methods: In this study, we have targeted TNBC by simultaneous activation of apoptosis through DNA damage via cytotoxic agent such as paclitaxel (PAC), inhibition of PARP activity via PARP inhibitor, olaparib (OLA) and inhibiting the activity of FOXM1 proto-oncogenic transcription factor by using RNA interference technology (FOXM1-siRNA) in nanoformulations. Experiments conducted in this investigation include cellular uptake, cytotoxicity and apoptosis study using MDA-MB-231 cells. Results: The present study validates that co-delivery of two drugs (PAC and OLA) along with FOXM1-siRNA by cationic NPs, enhances the therapeutic outcome leading to greater cytotoxicity in TNBC cells. Conclusion: The current investigation focuses on designing a multifunctional drug delivery platform for concurrent delivery of either PAC or PARP inhibitor (olaparib) and FOXM1 siRNA in chitosan-coated poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) with the ability to emerge as a front runner therapeutic for TNBC therapy.

A Multiparametric Fluorescence Probe to Understand the Physicochemical Properties of Small Unilamellar Lipid Vesicles in Poly(ethylene glycol)-Water Medium

Abstract: FDAPT (2-formyl-5-(4′-N,N-dimethylaminophenyl)thiophene) efficiently senses the minimum alteration of lipid bilayer microenvironment with all six different fluorescence parameters namely emission w...

Nanomedicine in Cancer Stem Cell Therapy

Abstract: It is now well established that most of the tumors are heterogeneous in nature that comprise a population of cancer stem cells (CSCs) and differentiated cancer cells. Like normal stem cells, CSCs have also self-renewal, proliferation, and differentiation capacities that are responsible for the development of drug resistance and relapse. Therefore, targeting CSCs is essential for the elimination of tumor recurrence condition. Although several anti-CSC therapeutics have been used in clinics, they are found to have limited efficacy due to poor solubility, lesser stability, and short circulation time in the blood. Therefore, tools in nanomedicines are being used to tackle these limitations. Recently, nanodrug carriers have been used to target CSCs and somewhat eliminate drug resistance by targeting CSC metabolism, inhibiting drug transporters, disturbing CSC survival pathways, etc. Even with these progress, the challenges for targeting CSCs by nanomedicines still remain and open up plenty of space for further development and improvement in synthesizing drug carriers with higher efficacy. In this chapter, we summarize about CSCs and their biological characterization toward resistance, then discuss several anti-CSC therapeutic approaches based on nanomedicines in the current state of research and development, and finally overview their future directions.

System and method for encoding and decoding ethnic data into genetic codes

Abstract: A system and method for encoding and decoding ethnic data including but not limited to, ancient mantras, slogans, and verses into genetic codes. A VKRSV encoding module for encoding the ethnic data into a genetic code wherein the genetic code stores the ethnic data securely for a longer time periods. The encoded data can be stored as a DNA nucleotide sequence in order to hide data in an original format. Further, the encoded data as a DNA nucleotide sequence is cloned into a pET-28a + plasmid vector of 5.369 kbps size. The cloned plasmid DNA is transformed into a bacterial system (E.coli) and stored at –80°C.