COVID-19 Linked Social Stigma Among Arab Survivors: A Cross-Sectional Experiences from the Active Phase of the Pandemic.

Objective: This study aimed to explore the magnitude and variability of the disease-linked stigma among COVID-19 survivors and their experiences of social stigma, coping strategies, contextual challenges, and preferences for support. Methods: An Arabic version of the social stigma survey questionnaire was designed and validated to obtain socio-demographic characteristics and quantitative measures of stigma encountered by the survivors. 482 COVID-19 survivors completed the survey, and the data were analyzed using descriptive statistics and thematic analysis. Results: The results of this study revealed the prevalence of high levels of both perceived external stigma and enacted stigma among participants. Enacted and Internalized stigma were associated with survivors' educational background/ status. The participants suggested three levels of support: organizational, social, and personal. Establishing an online stigma reduction program and national psychological crisis interventions at the organizational level. It is crucial to assist coping mechanisms and societal reintegration techniques at the social level. Conclusion: These results provide valuable insights for holistic health policy formation and preparedness strategies for future pandemics, helping survivors promote health and reintegrate into society, where stigma reduction and psychological crisis interventions are underdeveloped.

Corrigendum: Fabrication and evaluation of herbal beads to slow cell ageing.

[This corrects the article DOI: 10.3389/fbioe.2022.1025405.].

The Pharmacological Implications of Flavopiridol: An Updated Overview.

Flavopiridol is a flavone synthesized from the natural product rohitukine, which is derived from an Indian medicinal plant, namely Dysoxylum binectariferum Hiern. A deeper understanding of the biological mechanisms by which such molecules act may allow scientists to develop effective therapeutic strategies against a variety of life-threatening diseases, such as cancer, viruses, fungal infections, parasites, and neurodegenerative diseases. Mechanistic insight of flavopiridol reveals its potential for kinase inhibitory activity of CDKs (cyclin-dependent kinases) and other kinases, leading to the inhibition of various processes, including cell cycle progression, apoptosis, tumor proliferation, angiogenesis, tumor metastasis, and the inflammation process. The synthetic derivatives of flavopiridol have overcome a few demerits of its parent compound. Moreover, these derivatives have much improved CDK-inhibitory activity and therapeutic abilities for treating severe human diseases. It appears that flavopiridol has potential as a candidate for the formulation of an integrated strategy to combat and alleviate human diseases. This review article aims to unravel the potential therapeutic effectiveness of flavopiridol and its possible mechanism of action.

Microbial approaches for pharmaceutical wastewater recycling and management for sustainable development: A multicomponent approach.

A microbial-driven approach for effluent treatment, recycling, and management of Pharmaceutical and Personal Care Products (PPCPs) has been undertaken to mitigate the menace of water contamination. Bioremediation processes are mainly considered the first preference in pharmaceutical wastewater recycling and management. PPCPs are reported as one of the primary sources of emerging contaminants in various water matrices, which raises concern and requires efficient management. Their widespread utilization, persistently high level, and resistance to breaking down make them one of the potentially dangerous compounds causing harm to the ecosystem. Continually increasing PPCPs level PPCPs contaminants in water bodies raised concern for human health as they can produce potential risks with harmful and untoward impacts on our health. PPCPs are composed of multiple diverse compounds used by humans and animals, which include biopharmaceuticals, vitamins and nutritional supplements, antibiotics, counter-prescription drugs, cosmetics products, and unused pharmaceutical products. Personal care products are found to be bioaccumulative, reduce water quality and potentially impact ecological health. However, continual exposure to PPCPs in aquatic organisms, impacts their endocrine function disruption, gene toxicity, and antibiotic resistance. Decreased water quality may result in an outbreak of various water-borne diseases, which could have acute or long-term health complications and may result in an outbreak of various water-borne diseases, which could have acute or long-term effects on public and community health. Polluted water consumption by humans and animals produces serious health hazards and increased susceptibility to water-borne diseases such as carcinogenic organic or inorganic contaminants and infectious pathogens present in water bodies. Many water resource recovery facilities working on various conventional and advanced methods involve the utilization of microbes for filtration and advanced oxidation processes. Therefore, there is an immense need for bioremediation techniques facilitated by mixed cultures of bacteria, algae, and other microbes that can be used as an alternative approach for removing pharmaceutical content from effluent. This review highlights the various sources of PPCPs and their impacts on soil and water bodies, resulting in bioaccumulation. Different techniques are utilized to detect PPCPs, and various control strategies imply controlling, recycling, and managing waste.

Therapeutic Potential of Dillenia indica L. in Attenuating Hyperglycemia-Induced Oxidative Stress and Apoptosis in Alloxan-Administered Diabetic Mice.

BACKGROUND: Hyperglycemia-induced oxidative stress accelerates the process of apoptosis in tissues. Dilleniaindica (DI) is a medicinal plant, and its fruit contains many therapeutic properties. The therapeutic activity of the Methanolic Fruit Extract (MFE) of DI in attenuating oxidative stress and apoptosis in the liver and kidney tissues of alloxan-induced diabetic mice was analyzed in the present study. METHODS: High-Performance Thin Layer Chromatography (HPTLC) profiling of MFE was conducted. GLUT4 protein expression analysis and lipid peroxidation assays were conducted to check for MFE effect by administering in diabetic mice. An ultrastructural study was conducted for both the tissues. In apoptotic studies, the TUNEL assay and apoptotic protein expression analysis was conducted. RESULTS: High-Performance Thin Layer Chromatography (HPTLC) profiling of MFE showed the presence of two crucial antioxidants, ascorbic acid, and naringenin. In GLUT-4 protein expression analysis, MFE suppresses hyperglycemia by upregulating GLUT4 protein expression. Lipid peroxidation assay showed a decrease in malondialdehyde (MDA) upon MFE administration in diabetic mice. An ultrastructural study was conducted, and MFE was found to restore cellular alterations in diabetic tissues. In apoptotic studies, the TUNEL assay shows that MFE treatment showed fewer apoptotic cells than the diabetic group. The study also observed decreased caspase 3 protein expression and increased Bcl-2 protein expression. CONCLUSIONS: Therefore, it is inferred from the study that MFE can exert a protective effect by suppressing hyperglycemia and modulating oxidative stress and apoptosis in alloxan-administered diabetic mice.

Modulation of Insulin Resistance by Silybum marianum Leaves, and its Synergistic Efficacy with Gymnema sylvestre, Momordica charantia, Trigonella-foenum graecum Against Protein Tyrosine Phosphatase 1B.

Prolonged insulin resistance is considered one of the reasons for Type 2 Diabetes Mellitus. Upregulation of Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signalling, has been well studied as a key regulator in prognosis to insulin resistance. It has been widely studied as a desirable molecular therapeutic target. The study aimed to evaluate the efficacy of leaf extract of the medicinal plants Silybum marianum on the inhibition of PTP1B activity. It also explored the synergistic effect with extracts of Gymnema sylvestre (leaves), Momordica charantia (seeds), and Trigonella foenum graecum (seeds). The S. marianum leaves showed dose-dependent inhibition of PTP1B ranging from 9.48-47.95% (25-1000 µg mL-1). Assay with individual plant extracts showed comparatively lesser inhibition of PTP1B as compared to metformin as a control (38% inhibition). However, a synergistic effect showed nearly 45% PTP1B inhibition (higher than metformin) after the assay was done with selected four plant extracts in combination. The effect of leaf extracts of S. marianum was studied for glucose uptake efficiency in yeast cell lines which was found to be increased by 23% as compared to the control (without extract). Metformin improves glucose upake by yeast cells by ~15-31%. GC-MS analysis revealed 23 phytochemicals, some of which possessed anti-diabetic properties. A dose-dependent increase in antioxidant activity of S. marianum leaves extracts was observed (40-53%). The findings of the study highlighted the presence of various phytochemicals in leaves extracts that are effective against PTP1B inhibition and may help in reinvigorating drug development.

Green synthesis of nanostructures from rice straw food waste to improve the antimicrobial efficiency: New insight.

Applications for nanotechnology, which is constantly gaining prominence, have been found in a variety of industrial applications. Due to the multiple benefits associated with it, including an eco-friendly, pollution-free, cost-effective, and non-toxic synthesis method, the green way to synthesize nanostructures utilizing waste biomasses has become one of the key focuses of the current researches globally. Additionally, lignocellulasic biomass (LCB), which is a waste of the food crops, can be used as one of the potential substrates for the synthesis of a variety of nanostructures. Among different types of LCB, rice straw is a potential food waste biomass and can be efficiently employed during the synthesis of different types of nanostructures for a range of technological applications. Here, diverse phenolic compounds found in rice straw as well as reducing sugars can be used as natural reducing and capping agents to prepare a range of nanostructures. Based on the aforementioned facts, the objective of this review is to investigate the viability of using rice straw to produce nanostructured materials using rice straw as a renewable biosource following an environmentally friendly method. Additionally, it is noted that various organic compounds present on the surface of nanostructures produced using rice straw extract/hydrolyzate through a green approach may be more successful in terms of antibacterial efficacy, which might be of considerable interest for a variety of biomedical applications. Based on the possibility of enhancing the antimicrobial activity of developed nanostructures, the review also provides overview on the feasibility, characteristics, and availability of using rice straw extract in the synthesis of nanostructures. Additionally, the constraints of the present and potential futures of the green synthesis methods using rice straw wastes have been explored.

Enhancement in functional stability of microbial endoglanases produced using paddy straw via treatment with manganese oxide based porous nanocomposite synthesized from mixed fruit waste.

Microbial cellulases are the enzymes used in numerous industrial biotechnological applications. Efficiency of celluloytic cocktails plays a key role in the conversion of biomass into biofuels, but limited production, high cost and low efficiency are the main obstacles to sustainable biorefining. The current work aims to establish a feasible approach for boosting the production of fungal endoglucanse (EG) and its functional stability utilizing nanocomposite materials based on manganese oxide. Herein, aqueous extract from mixed fruit waste was used to synthesize the nanocomposite sample, which was subsequently subjected to several characterization techniques for analysis. Following the solid-state fermentation of paddy straw, and by employing 75 mg nanocomposite, 192 IU/gds EG was produced under the optimal conditions, while 19 IU/gds FP and 98 IU/gds BGL production were recorded. The crude EG enzyme treated with nanocomposite also shows complete stability at pH 5.0 for 3.5 h while retaining thermal activity at 70 °C for 4 h.

Fabrication and evaluation of herbal beads to slow cell ageing.

Several therapies and cosmetics are available commercially to prevent or delay cell ageing, which manifests as premature cell death and skin dullness. Use of herbal products such as Aloe vera, curcumin, vitamin C-enriched natural antioxidant, and anti-inflammatory biomolecules are potential ways to prevent or delay ageing. Eggshell membrane (ESM) is also a rich source of collagen; glycosaminoglycans (GAGs) also play an essential role in healing and preventing ageing. It is important to use an extended therapeutic process to prolong the effectiveness of these products, despite the fact that they all have significant anti-ageing properties and the ability to regenerate healthy cells. Encapsulated herbal components are therefore designed to overcome the challenge of ensuring continued treatment over time to prolong the effects of a bioactive component after in situ administration. To study their synergistic effects on a cellular level, alginate, Aloe vera, and orange peel extract were encapsulated in bio-polymeric foaming beads and modified with eggshell membrane protein (ESMP) at various concentrations (1 gm, 2 gm, and 5 gm): (A-Av-OP, A-Av-OP-ESMP1, ESMP2, and ESMP3). Analysis of the structural and functional properties of foaming beads showed interconnected 3D porous structure, a surface-functionalized group for entrapment of ESMP, and a significant reduction in pore size (51-35 m) and porosity (80%-60%). By performing DPPH assays, HRBC stabilization assays, and antibacterial tests, the beads were assessed as a natural anti-ageing product with sustained release of molecules effective against inflammatory response, oxidative stress, and microbial contamination. MTT assays were conducted using in vitro cell cultures to demonstrate cytocompatibility (in mouse 3T3 fibroblast cells) and cytotoxicity (in human carcinoma HeLa cells). Our study demonstrates that bio-polymeric ESMP beads up to 2 g (A-Av-OP-ESMP2) are practical and feasible natural remedies for suspending defective cell pathways, preventing cell ageing, and promoting healthy cell growth, resulting in a viable and practical natural remedy or therapeutic system.

Quorum Quenching-Guided Inhibition of Mixed Bacterial Biofilms and Virulence Properties by Protein Derived From Leaves of Carissa carandas.

The inhibition/degradation potential of Carissa carandas proteinaceous leaf extract against mixed bacterial biofilm of Staphylococcus aureus MTCC 96, Escherichia coli MTCC 1304, Pseudomonas aeruginosa MTCC 741, and Klebsiella pneumoniae MTCC 109, responsible for nosocomial infections, was evaluated. Distinct inhibition/degradation of mixed bacterial biofilm by the proteinaceous leaf extract of C. carandas was observed under a microscope, and it was found to be 80%. For mono-species biofilm, the maximum degradation of 70% was observed against S. aureus biofilm. The efficiency of aqueous plant extracts to inhibit the mono-species biofilm was observed in terms of minimum inhibitory concentration (MIC), and the best was found against P. aeruginosa (12.5 µg/ml). The presence of flavonoids, phenols, and tannins in the phytochemical analysis of the plant extract suggests the main reason for the antibiofilm property of C. carandas. From the aqueous extract, protein fraction was precipitated using 70% ammonium sulfate and dialyzed. This fraction was purified by ion-exchange chromatography and found to be stable and active at 10°C (pH 7). The purified fraction showed less than 40% cytotoxicity, which suggests that it can be explored for therapeutic purposes after in-depth testing. In order to investigate the mechanistic action of the biofilm inhibition, the plant protein was tested against Chromobacterium violaceum CV026, and its inhibitory effect confirmed its quorum quenching nature. Based on these experimental analyses, it can be speculated that the isolated plant protein might influence the signaling molecule that leads to the inhibition effect of the mixed bacterial biofilm. Further experimental studies are warranted to validate our current findings.

Antioxidant, cytotoxic and apoptotic activities of the rhizome of Zingiber zerumbet Linn. in Ehrlich ascites carcinoma bearing Swiss albino mice.

Due to having a long history of traditional uses as a functional food, Zingiber zerumbet was selected here to explore the inherent antioxidant and antineoplastic activities of methanolic extract of its rhizome (MEZZR) against Ehrlich ascites carcinoma (EAC) cells. The rich polyphenol containing MEZZR showed a marked DPPH, ABTS, nitric oxide radicals and lipid peroxidation inhibition activity with an IC50 of 3.43 ± 1.25, 11.38 ± 1.39, 23.12 ± 3.39 and 16.47 ± 1.47 µg/ml, respectively, when compared to the standard catechin. In vivo, MEZZR significantly inhibited EAC cell growth, decreased body weight gain, increased life span and restored the altered hematological characteristics of EAC-bearing mice. Moreover, MEZZR induced nuclear condensation and fragmentation, which are notable features of apoptosis as observed by fluorescence microscopy after staining EAC cells of MEZZR-treated mice with Hoechst 33342. Additionally, in vitro, the cell growth inhibition caused by the MEZZR in MTT assay, was remarkably decreased in the presence of caspase-3, -8 and -9 inhibitors. This study thus suggests that MEZZR may possess promising antiproliferative efficacy against EAC cells by inducing cell apoptosis.

Functional microbiome strategies for the bioremediation of petroleum-hydrocarbon and heavy metal contaminated soils: A review.

Petroleum hydrocarbons and heavy metals are the two major soil contaminants that are released into the environment in the forms of industrial effluents. These contaminants exert serious impacts on human health and the sustainability of the environment. In this context, remediation of these pollutants via a biological approach can be effective, low-cost, and eco-friendly approach. The implementation of microorganisms and metagenomics are regarded as the advanced solution for remediating such pollutants. Further, microbiomes can overcome this issue via adopting specific structural, functional and metabolic pathways involved in the microbial community to degrade these pollutants. Genomic sequencing and library can effectively channelize the degradation of these pollutants via microbiomes. Nevertheless, more advanced technology and reliable strategies are required to develop. The present review provides insights into the role of microbiomes to effectively remediate/degrade petroleum hydrocarbons and heavy metals in contaminated soil. The possible degradation mechanisms of these pollutants have also been discussed in detail along with their existing limitations. Finally, prospects of the bioremediation strategies using microbiomes are discussed.

The Interplay of the Unfolded Protein Response in Neurodegenerative Diseases: A Therapeutic Role of Curcumin.

Abnormal accumulation of misfolded proteins in the endoplasmic reticulum and their aggregation causes inflammation and endoplasmic reticulum stress. This promotes accumulation of toxic proteins in the body tissues especially brain leading to manifestation of neurodegenerative diseases. The studies suggest that deregulation of proteostasis, particularly aberrant unfolded protein response (UPR) signaling, may be a common morbific process in the development of neurodegeneration. Curcumin, the mixture of low molecular weight polyphenolic compounds from turmeric, Curcuma longa has shown promising response to prevents many diseases including current global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and neurodegenerative disorders. The UPR which correlates positively with neurodegenerative disorders were found affected by curcumin. In this review, we examine the evidence from many model systems illustrating how curcumin interacts with UPR and slows down the development of various neurodegenerative disorders (ND), e.g., Alzheimer's and Parkinson's diseases. The recent global increase in ND patients indicates that researchers and practitioners will need to develop a new pharmacological drug or treatment to manage and cure these neurodegenerative diseases.

Phytochemicals from Indian Ethnomedicines: Promising Prospects for the Management of Oxidative Stress and Cancer.

Oxygen is indispensable for most organisms on the earth because of its role in respiration. However, it is also associated with several unwanted effects which may sometimes prove fatal in the long run. Such effects are more evident in cells exposed to strong oxidants containing reactive oxygen species (ROS). The adverse outcomes of oxidative metabolism are referred to as oxidative stress, which is a staple theme in contemporary medical research. Oxidative stress leads to plasma membrane disruption through lipid peroxidation and has several other deleterious effects. A large body of literature suggests the involvement of ROS in cancer, ageing, and several other health hazards of the modern world. Plant-based cures for these conditions are desperately sought after as supposedly safer alternatives to mainstream medicines. Phytochemicals, which constitute a diverse group of plant-based substances with varying roles in oxidative reactions of the body, are implicated in the treatment of cancer, aging, and all other ROS-induced anomalies. This review presents a summary of important phytochemicals extracted from medicinal plants which are a part of Indian ethnomedicine and Ayurveda and describes their possible therapeutic significance.

Egypt's COVID-19 Recent Happenings and Perspectives: A Mini-Review.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected countries across the world. While the zoonotic aspects of SARS-CoV-2 are still under investigation, bats and pangolins are currently cited as the animal origin of the virus. Several types of vaccines against COVID-19 have been developed and are being used in vaccination drives across the world. A number of countries are experiencing second and third waves of the pandemic, which have claimed nearly four million lives out of the 180 million people infected globally as of June 2021. The emerging SARS-CoV-2 variants and mutants are posing high public health concerns owing to their rapid transmissibility, higher severity, and in some cases, ability to infect vaccinated people (vaccine breakthrough). Here in this mini-review, we specifically looked at the efforts and actions of the Egyptian government to slow down and control the spread of COVID-19. We also review the COVID-19 statistics in Egypt and the possible reasons behind the low prevalence and high case fatality rate (CFR%), comparing Egypt COVID-19 statistics with China (the epicenter of COVID-19 pandemic) and the USA, Brazil, India, Italy, and France (the first countries in which the numbers of patients infected with COVID-19). Additionally, we have summarized the SARS-CoV-2 variants, vaccines used in Egypt, and the use of medicinal plants as preventive and curative options.

Identification of new BACE1 inhibitors for treating Alzheimer's disease.

Alzheimer's disease (AD) is a type of brain disorder, wherein a person experiences gradual memory loss, state of confusion, hallucination, agitation, and personality change. AD is marked by the presence of extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs) and synaptic losses. Increased cases of AD in recent times created a dire need to discover or identify chemical compounds that can cease the development of AD. This study focuses on finding potential drug molecule(s) active against ß-secretase, also known as ß-site amyloid precursor protein cleaving enzyme 1 (BACE1). Clustering analysis followed by phylogenetic studies on microarray datasets retrieved from GEO browser showed that BACE1 gene has genetic relatedness with the RCAN1 gene. A ligand library comprising 60 natural compounds retrieved from literature and 25 synthetic compounds collected from DrugBank were screened. Further, 350 analogues of potential parent compounds were added to the library for the docking purposes. Molecular docking studies identified 11-oxotigogenin as the best ligand molecule. The compound showed the binding affinity of - 11.1 Kcal/mole and forms three hydrogen bonds with Trp124, Ile174, and Arg176. The protein-ligand complex was subjected to 25 ns molecular dynamics simulation and the potential energy of the complex was found to be - 1.24579e+06 Kcal/mole. In this study, 11-oxotigogenin has shown promising results against BACE1, which is a leading cause of AD, hence warrants for in vitro and in vivo validation of the same. In addition, in silico identification of 11-oxotigogenin as a potential anti-AD compound paves the way for designing of chemical scaffolds to discover more potent BACE1 inhibitors.Graphical abstract.

In Silico Studies Reveal Antiviral Effects of Traditional Indian Spices on COVID-19.

BACKGROUND: The global health emergency due to SARS-CoV-2 causing the COVID-19 pandemic emphasized the scientific community to intensify their research work for its therapeutic solution. In this study, Indian traditional spices owing to various medicinal properties were tested in silico for their inhibitory activity against SARS-CoV-2 proteins. SARS-CoV-2 spike proteins (SP) and main proteases (Mpro) play a significant role in infection development were considered as potential drug targets. METHODS: A total of 75 phytochemicals present in traditional Indian spices retrieved from the published literature and Dr. Duke's Phytochemical and Ethnobotanical Database, were docked with Mpro (PDB IDs: 6YNQ), and the SP (PDB IDs: 6LXT and 6YOR). RESULTS: Through the screening process, 75 retrieved phytochemicals were docked with spike protein (PDB IDs: 6LXT and 6YOR) and main protease (PDB ID: 6YNQ) of SARS-CoV-2. Among them, myricetin, a flavonoid (rank score: 6LXT: -11.72383; 6YOR: -9.87943; 6YNQ: -11.68164) from Allium sativum L and Isovitexin, an example of flavone (rank score: 6LXT: -12.14922; 6YOR: -10.19443; 6YNQ: -12.60603) from Pimpinella anisumL were the most potent ligands against SP and Mpro of SARS-CoV-2. Whereas, Astragalin from Crocus sativus L.; Rutin from Illicium verum, Oxyguttiferone from Garcinia cambogia; Scopolin from Apium graveolens L, Luteolin from Salvia officinalis, Emodin, Aloe-emodin from Cinnamomum zeylanicium and Apigenin from Allium sativum L showed better inhibition against Mpro than SP of SARS-CoV-2. The amino acid residues like SER, LYS, ASP and TYR were found playing important role in protein-ligand interactions via hydrogen bonding and Vander Waals forces. CONCLUSION: Optimal use of traditional spices in our daily meals may help fight against COVID-19. This study also paves the path for herbal drug formulation against SARS-CoV-2 after wet lab validation.

An Integrative Network Approach to Identify Common Genes for the Therapeutics in Tuberculosis and Its Overlapping Non-Communicable Diseases.

Tuberculosis (TB) is the leading cause of death from a single infectious agent. The estimated total global TB deaths in 2019 were 1.4 million. The decline in TB incidence rate is very slow, while the burden of noncommunicable diseases (NCDs) is exponentially increasing in low- and middle-income countries, where the prevention and treatment of TB disease remains a great burden, and there is enough empirical evidence (scientific evidence) to justify a greater research emphasis on the syndemic interaction between TB and NCDs. The current study was proposed to build a disease-gene network based on overlapping TB with NCDs (overlapping means genes involved in TB and other/s NCDs), such as Parkinson's disease, cardiovascular disease, diabetes mellitus, rheumatoid arthritis, and lung cancer. We compared the TB-associated genes with genes of its overlapping NCDs to determine the gene-disease relationship. Next, we constructed the gene interaction network of disease-genes by integrating curated and experimentally validated interactions in humans and find the 13 highly clustered modules in the network, which contains a total of 86 hub genes that are commonly associated with TB and its overlapping NCDs, which are largely involved in the Inflammatory response, cellular response to cytokine stimulus, response to cytokine, cytokine-mediated signaling pathway, defense response, response to stress and immune system process. Moreover, the identified hub genes and their respective drugs were exploited to build a bipartite network that assists in deciphering the drug-target interaction, highlighting the influential roles of these drugs on apparently unrelated targets and pathways. Targeting these hub proteins by using drugs combination or drug repurposing approaches will improve the clinical conditions in comorbidity, enhance the potency of a few drugs, and give a synergistic effect with better outcomes. Thus, understanding the Mycobacterium tuberculosis (Mtb) infection and associated NCDs is a high priority to contain its short and long-term effects on human health. Our network-based analysis opens a new horizon for more personalized treatment, drug-repurposing opportunities, investigates new targets, multidrug treatment, and can uncover several side effects of unrelated drugs for TB and its overlapping NCDs.

Developmental lead (Pb)-induced deficits in redox and bioenergetic status of cerebellar synapses are ameliorated by ascorbate supplementation.

Neurotoxicity induced by exposure to heavy metal lead (Pb) is a concern of utmost importance particularly for countries with industrial-based economies. The developing brain is especially sensitive to exposure to even minute quantities of Pb which can alter neurodevelopmental trajectory with irreversible effects on motor, emotive-social and cognitive attributes even into later adulthood. Chemical synapses form the major pathway of inter-neuronal communications and are prime candidates for higher order brain (motor, memory and behavior) functions and determine the resistance/susceptibility for neurological disorders, including neuropsychopathologies. The synaptic pathways and mechanisms underlying Pb-mediated alterations in neuronal signaling and plasticity are not completely understood. Employing a biochemically isolated synaptosomal fraction which is enriched in synaptic terminals and synaptic mitochondria, this study aimed to analyze the alterations in bioenergetic and redox/antioxidant status of cerebellar synapses induced by developmental exposure to Pb (0.2 %). Moreover, we test the efficacy of vitamin C (ascorbate; 500 mg/kg body weight), a neuroprotective and neuromodulatory antioxidant, in mitigation of Pb-induced neuronal deficits. Our results implicate redox and bioenergetic disruptions as an underlying feature of the synaptic dysfunction observed in developmental Pb neurotoxicity, potentially contributing to consequent deficits in motor, behavioral and psychological attributes of the organisms. In addition, we establish ascorbate as a key ingredient for therapeutic approach against Pb induced neurotoxicity, particularly for early-life exposures.

Aspartate-ß-semialdeyhyde dehydrogenase as a potential therapeutic target of Mycobacterium tuberculosis H37Rv: Evidence from in silico elementary mode analysis of biological network model.

The emergence of multi-drug resistant strains and co-occurrence of tuberculosis with HIV creates a major burden to the human health globally. Failure of primary antibacterial therapy necessitates the identification of new mycobacterial drugs. In this study, a comprehensive analysis involving bottom-up systems biology approach was applied wherein we have identified potential therapeutic targets of Mycobacterium tuberculosis infections. Our study prioritized M. tuberculosis therapeutic targets (aspartate-ß-semialdeyhde dehydrogenase [ASD], dihydrodipicolinate reductase and diaminopimelate decarboxylase) based on flux and elementary mode analysis using direct mathematical modeling of the relevant metabolic pathways. Molecular docking and simulation studies of the priority target (ie, ASD) revealed the therapeutic potential of the selected natural products (Huperzine A, Rosmarinic acid, and Curcumin) based ASD inhibitors. The study highlights the crucial role of systems biology in conjunction with molecular interaction (docking) for probing novel leads against an increasingly resistant pathogen, M. tuberculousis.