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Since the onset of the COVID-19 pandemic, a number of approaches have been adopted by the scientific communities for developing efficient vaccine candidate against SARS-CoV-2. Conventional approaches of developing a vaccine require a long time and a series of trials and errors which indeed limit the feasibility of such approaches for developing a dependable vaccine in an emergency situation like the COVID-19 pandemic. Hitherto, most of the available vaccines have been developed against a particular antigen of SARS-CoV, spike protein in most of the cases, and intriguingly, these vaccines are not effective against all the pathogenic coronaviruses. In this context, immunoinformatics-based reverse vaccinology approaches enable a robust design of efficacious peptide-based vaccines against all the infectious strains of coronaviruses within a short frame of time. In this chapter, we enumerate the methodological trajectory of developing a universal anti-SARS-CoV-2 vaccine, namely, "AbhiSCoVac," through advanced computational biology-based immunoinformatics approach and its in-silico validation using molecular dynamics simulations.
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COVID-19 , Vacunas Virales , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19 , SARS-CoV-2 , Pandemias/prevención & control , Simulación del Acoplamiento Molecular , Epítopos de Linfocito B , Epítopos de Linfocito T , Vacunas de Subunidad , Biología ComputacionalRESUMEN
The bioconversion of jackfruit seed into a valuable product like Single-Cell Protein (SCP) was carried out using Generally Recognized As Safe (GRAS), five filamentous fungi such as Penicillium expansum, Aspergillus niger, Aspergillus oryzae, Rhizopus microsporus, and Candida intermedia by submerged fermentation. Data obtained from the study showed that supplementation of jackfruit seed extracts with inorganic nitrogen sources and glucose as a carbon source enhanced fungal biomass and SCP production. Among the various fungal strains, A. niger gave the highest biomass and protein yield of 4.01 ± 0.07 g/l and 1.82 ± 0.03 g/l, respectively, on the 9th day of fermentation followed by P. expansum (3.65 ± 0.04 g/l and 1.68 ± 0.03 g/l, respectively). C. intermedia growth was not recorded in all the experimental media. The present study revealed that fungal biomass has shown low crude fat, crude fiber, and total genomic DNA content ranged from 1.10 ± 0.20 to 4.95 ± 0.40%. A. niger and P. expansum were the most efficient in the conversion of sugar (55.83 ± 0.3% and 54.71 ± 0.4%, respectively) to yield biomass in sugar supplementation media. P. expansum and A. niger were the most promising fungal strains to produce fungal biomass protein using inexpensive agro-waste materials.
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Artocarpus , Fermentación , Biomasa , Proteínas Fúngicas , Aspergillus niger , AzúcaresRESUMEN
An environmentally benign, cost-effective and scalable process for the preparation of both the enantiomers of 3-hydroxytetrahydrofuran has been developed. pH-Controlled ring opening of enantiomerically pure epichlorohydrins with cyanohydrin is the key step of the process. The entire protocol does not require any column purification.
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Compuestos Epoxi , Nitrilos , Concentración de Iones de Hidrógeno , EstereoisomerismoRESUMEN
The evolution of viral variants and their impact on viral transmission have been an area of considerable importance in this pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed the viral variants in different phases of the pandemic in West Bengal, a state in India that is important geographically, and compared the variants with other states like Delhi, Maharashtra, and Karnataka, located in other regions of the country. We have identified 57 pango-lineages in 3,198 SARS-CoV-2 genomes, alteration in their distribution, as well as contrasting profiles of amino acid mutational dynamics across different waves in different states. The evolving characteristics of Delta (B.1.617.2) sublineages and alterations in hydrophobicity profiles of the viral proteins caused by these mutations were also studied. Additionally, implications of predictive host miRNA binding/unbinding to emerging spike or nucleocapsid mutations were highlighted. Our results throw considerable light on interesting aspects of the viral genomic variation and provide valuable information for improved understanding of wave-defining mutations in unfolding the pandemic. IMPORTANCE Multiple waves of infection were observed in many states in India during the coronavirus disease 2019 (COVID19) pandemic. Fine-scale evolution of major SARS-CoV-2 lineages and sublineages during four wave-window categories: Pre-Wave 1, Wave 1, Pre-Wave 2, and Wave 2 in four major states of India: Delhi (North), Maharashtra (West), Karnataka (South), and West Bengal (East) was studied using large-scale virus genome sequencing data. Our comprehensive analysis reveals contrasting molecular profiles of the wave-defining mutations and their implications in host miRNA binding/unbinding of the lineages in the major states of India.
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COVID-19 , MicroARNs , COVID-19/epidemiología , Genoma Viral , Humanos , India/epidemiología , Mutación , Pandemias , Filogenia , SARS-CoV-2/genéticaRESUMEN
Rice plants are known to be more susceptible to arsenic (As) contamination during the cultivation process. Arsenic is genotoxic and can be a big threat to the rice eating people at large. Studies on an effective mitigation mechanism are the need of the hour. This work was an approach using iron (Fe3+) to form Fe-plaque in the plant root that could trap As. The present research was designed with several experimental set ups for rice cultivation in pot culture using different Fe doses with fertilizer in the soil, and finally, the optimum dose was selected considering the translocation ability, plant health, and molecular and stress biomarkers. The study revealed that on an increase in Fe dose, translocation factor (TF) and stress marker (malondialdehyde content) of the plant decreased gradually and encountered minimum (0.12 and 0.03 mg/kg, respectively) at the dose of 4.5gm/kg. In contrast, higher values of chlorophyll (2.5 mg/kg) and carbohydrate (2.2 mg/kg) and intact DNA content were recorded highlighting the rich health condition of the plant. Thus, the experiment supported well the fact that the dose of Fe as fortified fertilizer can be considered the most effective in reducing soil arsenic accumulation in the rice plants. This approach might save the rice eating people from harmful effects of As contamination in this region of India.
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Arsénico , Oryza , Contaminantes del Suelo , Arsénico/farmacología , Fertilizantes , Humanos , Raíces de Plantas/química , SueloRESUMEN
Background: Fine-needle aspiration cytology (FNAC) is the most practiced initial method for evaluation of breast lesions. The International Academy of Cytology Yokohama System for Reporting Breast (IAC YSRB) Fine-Needle Aspiration Biopsy Cytopathology has been developed to standardize the reporting system. However, literature available on the inter-observer reproducibility of 5 IAC YSRB categories is limited. Aim: We investigated the inter-observer reproducibility of the IAC YSRB system. Method and Materials: A total of 70 consecutive specimens obtained from FNAC of breast lesions were reviewed retrospectively by 3 experienced cytopathologists who allotted 1 to 5 IAC YSRB categories. Results: The percent overall agreement between observers was 70.48% and the free marginal kappa was 0.63, which signifies substantial agreement. After combining "Suspicious" and "Malignant" categories, overall agreement was 80.95% and free marginal kappa became 0.75. Conclusions: Inter-observer agreement of three (70.48%) cytopathologists was substantial. Agreement can be improved by combining certain categories, especially "Suspicious" and "Malignant". Technical quality limitation plays a significant role in a proportion of cases, mainly the "Atypical" and "Suspicious of malignancy" categories. Application of the IAC YSRB system in day-to-day practice will increase the inter-observer agreement.
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Five filamentous fungal strains that grew in different whey-based media under submerged fermentation were investigated for antioxidant properties and phytochemicals. Phytochemical analysis revealed the presence of alkaloids, tannin, flavonoids, glycosides, phenols, saponins, and terpenes in the crude intra- and extracellular ethyl acetate extracts of different strains. All fungal extracts exhibited effective antioxidant activities in terms of TPC, TFC, DPPH, FRAP, ABTS, reducing power, and metal chelating capacity. The activities of intracellular extracts were higher than the extracellular metabolites. Fermentation media with sugar and salt supplementation significantly influenced antioxidant production. Aspergillus niger in glucose-supplemented whey medium was found to exhibit the highest antioxidant properties. The antimicrobial activity of A. niger and Penicillium expansum extracts by microtiter plate assay showed a promising result against some pathogenic bacterial strains. Chromatographic analysis of the fungal extracts revealed the presence of chlorogenic acid, trans-cinnamic acid, ferulic acid quercetin, myricetin, kaempferol, and catechin which are known for their antioxidant properties. Accumulation of nutrients in fungal biomass under constraint environment produces secondary metabolites which has demonstrated efficacy towards alleviation of several degenerative diseases. The antioxidative enriched phytochemicals present in these five different fungal strains will provide a breakthrough in the utilisation of whey as inexpensive source of substrate for the growth of these fungi. Moreover, phytochemicals could be utilized as therapeutic agents in a cost-effective and environmentally friendly manner.
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Antiinfecciosos , Antioxidantes , Antioxidantes/farmacología , Hongos , Penicillium , Fitoquímicos/farmacología , Extractos VegetalesRESUMEN
We report herein an operationally simple, efficient and versatile procedure for the synthesis of bis-indolylmethanes via the reaction of indoles with aldehydes or ketones in the presence of silica-supported ferric chloride under grindstone conditions. The prepared supported catalyst was characterized by SEM and EDX spectroscopy. The present protocol has several advantages such as shorter reaction time, high yield, avoidance of using harmful organic solvents during the reaction and tolerance of a wide range of functional groups. Molecular docking studies targeted toward the binding site of SARS-CoV-2 main protease (3CLpro or Mpro) enzymes were investigated with the synthesized bis-indoles. Our study revealed that some of the synthesized compounds have potentiality to inhibit the SARS-CoV-2 Mpro enzyme by interacting with key amino acid residues of the active sites via hydrophobic as well as hydrogen bonding interactions.
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The present study investigated the operational conditions for different pretreatment approaches and subsequent enzymatic hydrolysis of cauliflower wastes (stalk and leaf) for better release of fermentable sugars. The structural analysis of raw and pretreated lignocellulosic biomasses was investigated using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transforms infrared (FTIR) analysis. Results demonstrated that the highest cellulose conversion rate and removal of most of the hemicellulose and lignin were obtained with organosolvent pretreatment. Using methanol in presence of sodium (Na) acetate was most effective in delignification of cauliflower wastes. In the present study, methanol (100% v/v) in presence of 0.1 M Na-acetate at 121 °C for 45 and 60 min for stalk and leaf, respectively, gave maximum reducing sugar yield. Response surface methodology was used to optimize different process parameters for enzymatic saccharification using microbial cellulase and xylanase. The optimum operation condition of enzymatic hydrolysis of organosolvent pretreated cauliflower wastes were substrate loading (2.5% w/v for both stalk and leaf), enzyme loading (15 and 10 U/g for stalk and leaf, respectively), pH (4.46 and 5.48 for stalk and leaf, respectively), at 60 °C and for 180 min.
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Brassica , Compuestos Orgánicos/química , Solventes/química , Administración de Residuos/métodos , Biotecnología/métodos , Metabolismo de los Hidratos de Carbono , Celulasa/metabolismo , Celulosa/metabolismo , Microscopía Electrónica de Rastreo , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common age-related neurodegenerative disorders, affecting several millions of aged people globally. Among these disorders, AD is more severe, affecting about 7% of individuals aged 65 and above. AD is primarily a dementia-related disorder from progressive cognitive deterioration and memory impairment, while PD is primarily a movement disorder illness having three major kinesia or movement disorder symptoms, bradykinesia (slowness of movements), hypokinesia (reduction of movement amplitude), and akinesia (absence of normal unconscious movements) along with muscle rigidity and tremor at rest. AD is characterized by deposition of extracellular beta-amyloid (Aß) proteins and intracellular neurofibrillary tangles (NFT), composed of hyperphosphorylated tau proteins in the neurons located particularly in hippocampus and cerebral cortex regions of brain, resulting the neuronal loss, while PD is characterized by deposition of intraneuronal aggregates of mostly composed of alpha-synuclein gene as Lewy bodies (LB) in the striatal region, known as substantia nigra pars compacta (SNpc) of brain, leading to the death of dopaminergic neurons. These are known as pathological hallmarks of these diseases. However, in some overlapping cases, known as Alzheimer with Parkinson disease or vice versa, alpha-synuclein deposition in AD and tau deposition in PD patients are found. Oxidative stress-induced glial cells activation, neuroinflammation and mitochondrial dysfunction lead to various molecular events in brain neurons causing neuronal cell death in these neurodegenerative disorders. Currently used drugs for treatment of AD and PD only reduce the symptoms of these diseases, but unable to stop the process of neurodegeneration. Therefore, innovation of new synthetic drugs or discovery of natural drugs for the treatment of AD and PD, is a challenging task of basic science and clinical medicine. Plant iridoids such as catalpol and its 10-O-trans-p-coumaroyl derivative, geniposide, harpagoside, and loganin, and seco-iridoids, oleuropein and its aglycone and oleocanthal have been found to exhibit significant neuroprotective effect and the property of slowing down the process of neurogedeneration in AD and PD. These plant metabolites have been shown to ameliorate AD by increasing the expression of insulin degrading enzyme (IDE), neprilysin (NEP), PPAR-γ, and α-secretase, and decreasing the expression of ß-secretase (BACE-1) to reduce the levels of Aß oligomers (AßO) deposition in brain neurons. These plant metabolites reduced the expression of GSK-3ß and its receptor gene, PTEN to reduce hyperphosphorylation of tau proteins and neurofibrillary tangles (NFTs) formation. These metabolites improved the expressions of neuroprotective proteins, Bcl-2 via activations of growth-related protein-1 receptor (GLP-1R), PKC, MEK, MAPK/PI3K, and AMPK, and suppressed the expressions of pro-apoptotic proteins, Bax and caspase-3. Furthermore, these plant metabolites improved the lysosomal autophagy process by increasing the expression levels of Beclin-1, LC3II and cathepsin B genes for clearance of Aß and NFT, and increased the expression of transporter proteins, P-glycoprotein (P-gp) and low density lipoprotein receptor-related protein-1 (LRP-1) for the clearance of Aß load from brain across the blood-brain barrier (BBB) as well as increased the expression of PPAR-γ and ApoE proteins for clearance of Aß in ApoE mediated pathway from brain. Moreover, these plant metabolites reduced the cognitive impairment by increasing the expression of synaptic proteins, BDNF, PSD-95, SNAP-25, SYP and GAP-43 for improvement of learning and memory functions in AD. While among these iridoids, catalpol, 10-O-trans-p-coumaroylcatalpol, geniposide and harpagoside, in PD improved the expressions of GDNF and Bcl-2 proteins and TH-positive neurons by increasing the levels of antioxidant enzymes, SOD and GSH-PX and down-regulating insulin/IGF signalling via activation of MEK protein. Moreover, catalpol and its p-coumaroyl derivative in mutant nematode C. elegans model, up-regulated the expression of DAF-16, a FOXO family transcription factor and SKN-1 genes for improvement of lifespan and resistance against oxidative- and other stresses of mutated worms. Furthermore, geniposide increased the expression of autophagy-related LAMP-2A-protein for clearance of LB from dopaminergic neurons in PD brain via improving lysosomal autophagy process. The present review summarizes the neuroprotective activities and molecular mechanisms of these iridoids and secoiridoids, in prevention and/or treatment of both AD and PD. This review will be helpful to find out the research gap on these plant metabolites in this field to use them as potential drugs against these disorders.
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Enfermedad de Alzheimer/tratamiento farmacológico , Iridoides/uso terapéutico , Magnoliopsida/química , Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Animales , Humanos , Iridoides/química , Iridoides/metabolismo , Magnoliopsida/metabolismo , Estructura Molecular , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/metabolismoRESUMEN
The flavonoids, baicalin (5,6-dihydroxy-2-phenyl-4H-1-benzopyran-4-one-7-O-d-ß-glucuronic acid) 1 and its aglycone, baicalein 2 are found in edible medicinal plants, Scutellaria baicalensis Georgi and Oroxylum indicum (L.) Kurz in abundant quantities. The antioxidant and anti-inflammatory effects of these flavonoids have been demonstrated in various disease models, including diabetes, cardiovascular diseases, inflammatory bowel diseases, gout and rheumatoid arthritis, asthma, neurodegenerative-, liver- and kidney diseases, encephalomyelitis, and carcinogenesis. These flavonoids have almost no toxicity to human normal epithelial, peripheral and myeloid cells. Their antioxidant and anti-inflammatory activities are largely due to their abilities to scavenge the reactive oxygen species (ROS) and improvement of antioxidant status by attenuating the activity of NF-κB and suppressing the expression of several inflammatory cytokines and chemokines including monocyte chemotactic protein-1 (MCP-1), nitric oxide synthase, cyclooxygenases, lipoxygenases, cellular adhesion molecules, tumor necrosis factor and interleukins. In this review, we summarize the antioxidant and anti-inflammatory effects of baicalin and baicalein with molecular mechanisms for their chemopreventive and chemotherapeutic applications in the treatment of inflammatory-related diseases.