ABSTRACT
Cancer has agonized the human race for millions of years. The present decade witnesses biological therapeutics to combat cancer effectively. Cancer Immunotherapy involves the use of therapeutics for manipulation of the immune system by immune agents like cytokines, vaccines, and transfection agents. Recently, this therapeutic approach has got vast attention due to the current pandemic COVID-19 and has been very effective. Concerning cancer, immunotherapy is based on the activation of the host's antitumor response by enhancing effector cell number and the production of soluble mediators, thereby reducing the host's suppressor mechanisms by induction of a tumour killing environment and by modulating immune checkpoints. In the present era, immunotherapies have gained traction and momentum as a pedestal of cancer treatment, improving the prognosis of many patients with a wide variety of haematological and solid malignancies. Food supplements, natural immunomodulatory drugs, and phytochemicals, with recent developments, have shown positive trends in cancer treatment by improving the immune system. The current review presents the systematic studies on major immunotherapeutics and their development for the effective treatment of cancers as well as in COVID-19. The focus of the review is to highlight comparative analytics of existing and novel immunotherapies in cancers, concerning immunomodulatory drugs and natural immunosuppressants, including immunotherapy in COVID-19 patients.
ABSTRACT
Face masks have been used as the most effective and economically viable preventive tool, which also creates a sense of social solidarity in collectively combatting the airborne health hazards. In spite of enormous research literature, massive production, and a competitive market, the use of modern age face masks-respirators (FMR) is restricted for specific purposes or during public health emergencies. It is attributed to lack of awareness, prominent myths, architect and manufacturing limitations, health concerns, and probable solid waste management. However, enormous efforts have been dedicated to address these issues through using modern age materials and textiles such as nanomaterials during mask fabrication. Conventional FMRs possess bottlenecks of breathing issues, skin problems, single use, fungal infections, communication barrier for differently abled, inefficiency to filter minute contaminants, sourcing secondary contamination and issue of solid-waste management upon usage. Contrary, FMR engineered with functional nanomaterials owing to the high specific surface area, unique physicochemical properties, and enriched surface chemistries address these challenges due to smart features like self-cleaning ability, biocompatibility, transparency, multiple usages, anti-contaminant, good breathability, excellent filtration capacity, and pathogen detecting and scavenging capabilities. This review highlights the state-of-the-art smart FMR engineered with different dimensional nanomaterials and nanocomposites to combat airborne health hazards, especially due to infectious outbreaks and air contamination. Besides, the myths and facts about smart FMR, associated challenges, potential sustainable solutions, and prospects for “point-of-action” intelligent operation of smart FMRs with the integration of internet-of-nano-things, 5G wireless communications, and artificial intelligence are discussed.
ABSTRACT
Alzheimer's disease (AD) is a severe neurodegenerative disorder of the brain that manifests as dementia, disorientation, difficulty in speech, and progressive cognitive and behavioral impairment. The emerging therapeutic approach to AD management is the inhibition of ß-site APP cleaving enzyme-1 (BACE1), known to be one of the two aspartyl proteases that cleave ß-amyloid precursor protein (APP). Studies confirmed the association of high BACE1 activity with the proficiency in the formation of ß-amyloid-containing neurotic plaques, the characteristics of AD. Only a few FDA-approved BACE1 inhibitors are available in the market, but their adverse off-target effects limit their usage. In this paper, we have used both ligand-based and target-based approaches for drug design. The QSAR study entails creating a multivariate GA-MLR (Genetic Algorithm-Multilinear Regression) model using 552 molecules with acceptable statistical performance (R 2 = 0.82, Q 2 loo = 0.81). According to the QSAR study, the activity has a strong link with various atoms such as aromatic carbons and ring Sulfur, acceptor atoms, sp2-hybridized oxygen, etc. Following that, a database of 26,467 food compounds was primarily used for QSAR-based virtual screening accompanied by the application of the Lipinski rule of five; the elimination of duplicates, salts, and metal derivatives resulted in a truncated dataset of 8,453 molecules. The molecular descriptor was calculated and a well-validated 6-parametric version of the QSAR model was used to predict the bioactivity of the 8,453 food compounds. Following this, the food compounds whose predicted activity (pKi) was observed above 7.0 M were further docked into the BACE1 receptor which gave rise to the Identification of 4-(3,4-Dihydroxyphenyl)-2-hydroxy-1H-phenalen-1-one (PubChem I.D: 4468; Food I.D: FDB017657) as a hit molecule (Binding Affinity = -8.9 kcal/mol, pKi = 7.97 nM, Ki = 10.715 M). Furthermore, molecular dynamics simulation for 150 ns and molecular mechanics generalized born and surface area (MMGBSA) study aided in identifying structural motifs involved in interactions with the BACE1 enzyme. Molecular docking and QSAR yielded complementary and congruent results. The validated analyses can be used to improve a drug/lead candidate's inhibitory efficacy against the BACE1. Thus, our approach is expected to widen the field of study of repurposing nutraceuticals into neuroprotective as well as anti-cancer and anti-viral therapeutic interventions.