Resveratrol regulates inflammation and improves oxidative stress via Nrf2 signaling pathway: Therapeutic and biotechnological prospects.

Usually, in aerobic metabolism, natural materials including nucleic acids, proteins, and lipids can experience auxiliary injury by oxidative responses. This damage produced by reactive oxygen/nitrogen species has been identified as "oxidative stress." As a natural polyphenol got from red wine and peanuts, resveratrol is one of the most eminent anti-aging mixtures. Based on many studies', resveratrol hinders destructive effects of inflammatory causes and reactive oxygen radicals in several tissues. The nuclear erythroid 2-related factor 2 is a factor related to transcription with anti-inflammatory, antioxidant possessions which is complicated by enzyme biotransformation and biosynthesis of lipids and carbohydrates. This review provides current understanding and information about the character of resveratrol against oxidative stress and regulation of inflammation via Nrf2 signaling pathway.

FAANG Stocks, Gold, and Islamic Equity: Implications for Portfolio Management during COVID-19

During the COVID-19 pandemic, technology stocks, such as FAANG stocks (Facebook, Amazon, Apple, Netflix, and Google), attracted the attention of global investors due to the vast use of technology in daily business. However, technology stocks are generally considered risky stocks;hence, efficient risk management is required to construct an optimal portfolio. In this study, we investigate the volatility spillovers and dynamic conditional correlations among the daily returns of FAANG company stocks, gold, and sharia-compliant equity to construct the optimal portfolio weights and hedge ratios during the COVID-19 pandemic period by utilizing a multivariate GARCH framework. The dynamic conditional correlations reveal that both gold and sharia-compliant equities exhibit lower correlations with FAANG stocks during the COVID-19 pandemic, implying opportunities for portfolio diversification. The findings indicate that gold and shariah-compliant equity are good candidates to hedge FAANG stocks. These findings are highly relevant for international investors, asset managers, hedgers, and portfolio managers.

Immunosuppressive Drugs

Immunosuppressant is a class of medicines that inhibit or decrease the intensity of the immune response in the body. Most of these medications are used to allow the body less likely to resist a transplanted organ. In solid organ transplantation, immunosuppressive agents are needed for the activation of early-stage immunosuppression, the management of late-stage immunosuppression or for the maintenance of organ rejection. The emergence of novel agents and improvements in immunosuppression regimens after transplantation are significant factors leading to this progress. However, these drugs also increase the risk of infection, cancers and specific adverse side effects specific to each agent in patients particularly in pregnant women and fertility issues. Corona virus disease being hot topic of debate is has given positive outcome to immunosuppressive drugs however need more attention in future. Transplant centers across the world utilize multiple immunosuppression protocols;nevertheless, each patient can require an individually formulated immunosuppression regimen to manage the advantages and possible damage of treatment thus eliminating the likelihood of their primary disease recurrence.

Antimicrobial Potential of Curcumin: Therapeutic Potential and Challenges to Clinical Applications.

Curcumin is a bioactive compound that is extracted from Curcuma longa and that is known for its antimicrobial properties. Curcuminoids are the main constituents of curcumin that exhibit antioxidant properties. It has a broad spectrum of antibacterial actions against a wide range of bacteria, even those resistant to antibiotics. Curcumin has been shown to be effective against the microorganisms that are responsible for surgical infections and implant-related bone infections, primarily Staphylococcus aureus and Escherichia coli. The efficacy of curcumin against Helicobacter pylori and Mycobacterium tuberculosis, alone or in combination with other classic antibiotics, is one of its most promising antibacterial effects. Curcumin is known to have antifungal action against numerous fungi that are responsible for a variety of infections, including dermatophytosis. Candidemia and candidiasis caused by Candida species have also been reported to be treated using curcumin. Life-threatening diseases and infections caused by viruses can be counteracted by curcumin, recognizing its antiviral potential. In combination therapy with other phytochemicals, curcumin shows synergistic effects, and this approach appears to be suitable for the eradication of antibiotic-resistant microbes and promising for achieving co-loaded antimicrobial pro-regenerative coatings for orthopedic implant biomaterials. Poor water solubility, low bioavailability, and rapid degradation are the main disadvantages of curcumin. The use of nanotechnologies for the delivery of curcumin could increase the prospects for its clinical application, mainly in orthopedics and other surgical scenarios. Curcumin-loaded nanoparticles revealed antimicrobial properties against S. aureus in periprosthetic joint infections.

Alkaloids and Colon Cancer: Molecular Mechanisms and Therapeutic Implications for Cell Cycle Arrest.

Cancer is the second most fatal disease worldwide, with colon cancer being the third most prevalent and fatal form of cancer in several Western countries. The risk of acquisition of resistance to chemotherapy remains a significant hurdle in the management of various types of cancer, especially colon cancer. Therefore, it is essential to develop alternative treatment modalities. Naturally occurring alkaloids have been shown to regulate various mechanistic pathways linked to cell proliferation, cell cycle, and metastasis. This review aims to shed light on the potential of alkaloids as anti-colon-cancer chemotherapy agents that can modulate or arrest the cell cycle. Preclinical investigated alkaloids have shown anti-colon cancer activities and inhibition of cancer cell proliferation via cell cycle arrest at different stages, suggesting that alkaloids may have the potential to act as anticancer molecules.

The impact of carbon pricing, climate financing, and financial literacy on COVID-19 cases: go-for-green healthcare policies.

Climate finance and carbon pricing are regarded as sustainable policy mechanisms for mitigating negative environmental externalities via the development of green financing projects and the imposition of taxes on carbon pollution generation. Financial literacy indicates that it is beneficial to invest in cleaner technology to advance the environmental sustainability goal. The current wave of the COVID-19 epidemic has had a detrimental effect on the world economies' health and income. The pandemic crisis dwarfs previous global financial crises in terms of scope and severity, collapsing global financial markets. The study's primary contribution is constructing a climate funding index (CFI) based on four critical factors: inbound foreign direct investment, renewable energy usage, research and development spending, and carbon damages. In a cross-sectional panel of 43 nations, the research evaluates the effect of climate funding, financial literacy, and carbon pricing in lowering exposure to coronavirus cases. The study utilized Newton-Raphson and Marquardt steps to estimate the current parameter estimates while evaluating the COVID-19 prediction model with level regressors using the robust least squares regression model (S-estimator). Additionally, the innovation accounting matrix predicts estimations over a specific period. The findings indicate that climate finance significantly reduces coronavirus exposure by introducing green financing initiatives that benefit human health, which eventually strengthens the immune system's ability to fight infectious illnesses. Financial literacy and carbon pricing, on the other hand, are ineffectual in controlling coronavirus infections due to rising economic activity and densely inhabited areas that enable the transmission of coronavirus cases across countries. Similar findings were obtained using the alternative regression apparatus. The COVID-19 predicted variable was used as a "response variable," and climate financing was shown to have a favorable impact on containing coronavirus exposure. As shown by the innovation accounting matrix, carbon pricing would drastically decrease coronavirus cases' exposure over a time horizon. The study concludes that climate finance and carbon pricing were critical in improving air quality indicators, which improved countries' health and wealth, allowing them to reduce coronavirus infections via sustainable healthcare reforms.

Combination of natural antivirals and potent immune invigorators: A natural remedy to combat COVID-19.

The flare-up in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in December 2019 in Wuhan, China, and spread expeditiously worldwide has become a health challenge globally. The rapid transmission, absence of anti-SARS-CoV-2 drugs, and inexistence of vaccine are further exacerbating the situation. Several drugs, including chloroquine, remdesivir, and favipiravir, are presently undergoing clinical investigation to further scrutinize their effectiveness and validity in the management of COVID-19. Natural products (NPs) in general, and plants constituents specifically, are unique sources for various effective and novel drugs. Immunostimulants, including vitamins, iron, zinc, chrysin, caffeic acid, and gallic acid, act as potent weapons against COVID-19 by reinvigorating the defensive mechanisms of the immune system. Immunity boosters prevent COVID-19 by stimulating the proliferation of T-cells, B-cells, and neutrophils, neutralizing the free radicals, inhibiting the immunosuppressive agents, and promoting cytokine production. Presently, antiviral therapy includes several lead compounds, such as baicalin, glycyrrhizin, theaflavin, and herbacetin, all of which seem to act against SARS-CoV-2 via particular targets, such as blocking virus entry, attachment to host cell receptor, inhibiting viral replication, and assembly and release.

Screening of potent phytochemical inhibitors against SARS-CoV-2 protease and its two Asian mutants.

BACKGROUND: COVID-19, declared a pandemic in March 2020 by the World Health Organization is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The virus has already killed more than 2.3 million people worldwide. OBJECT: The principal intent of this work was to investigate lead compounds by screening natural product library (NPASS) for possible treatment of COVID-19. METHODS: Pharmacophore features were used to screen a large database to get a small dataset for structure-based virtual screening of natural product compounds. In the structure-based screening, molecular docking was performed to find a potent inhibitor molecule against the main protease (Mpro) of SARS-CoV-2 (PDB ID: 6Y7M). The predicted lead compound was further subjected to Molecular Dynamics (MD) simulation to check the stability of the leads compound with the evolution of time. RESULTS: In pharmacophore-based virtual screening, 2,361 compounds were retained out of 30,927. In the structure-based screening, the lead compounds were filtered based on their docking scores. Among the 2,360 compounds, 12 lead compounds were selected based on their docking score. Kazinol T with NPASS ID: NPC474104 showed the highest docking score of -14.355 and passed criteria of Lipinski's drug-like parameters. Monitoring ADMET properties, Kazinol T showed its safety for consumption. Docking of Kazinol T with two Asian mutants (R60C and I152V) showed variations in binding and energy parameters. Normal mode analysis for ligand-bound and unbound form of protease along with its mutants, revealed displacement and correlation parameters for C-alpha atoms. MD simulation results showed that all ligand-protein complexes remained intact and stable in a dynamic environment with negative Gibbs free energy. CONCLUSIONS: The natural product Kazinol T was a predicted lead compound against the main protease of SARS-CoV-2 and will be the possible treatment for COVID-19.

Targeting pivotal inflammatory pathways in COVID-19: A mechanistic review.

As an emerging global health crisis, coronavirus disease 2019 (COVID-19) has been labeled a worldwide pandemic. Growing evidence is revealing further pathophysiological mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Amongst these dysregulated pathways inflammation seems to play a more critical role toward COVID-19 complications. In the present study, precise inflammatory pathways triggered by SARS-CoV-2, along with potential therapeutic candidates have been discussed. Prevailing evidence has indicated a close correlation of inflammatory cascades with severity, pathological progression, and organ damages in COVID-19 patients. From the mechanistic point of view, interleukin-6, interleukin-1ß receptor, interferon-gamma, tumor necrosis factor-alpha receptor, toll-like receptor, receptor tyrosine kinases, growth factor receptor, Janus kinase/signal transducers and transcription pathway, mammalian target of rapamycin, cytokine storm and macrophage activation have shown to play critical roles in COVID-19 complications. So, there is an urgent need to provide novel mechanistic-based anti-inflammatory agents. This review highlights inflammatory signaling pathways of SARS-CoV-2. Several therapeutic targets and treatment strategies have also been provided in an attempt to tackle COVID-19 complications.

Vaccine Design from the Ensemble of Surface Glycoprotein Epitopes of SARS-CoV-2: An Immunoinformatics Approach.

The present study aimed to work out a peptide-based multi-epitope vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We predicted different B-cell and T-cell epitopes by using the Immune Epitopes Database (IEDB). Homology modeling of the construct was done using SWISS-MODEL and then docked with different toll-like-receptors (TLR4, TLR7, and TLR8) using PatchDock, HADDOCK, and FireDock, respectively. From the overlapped epitopes, we designed five vaccine constructs C1-C5. Based on antigenicity, allergenicity, solubility, different physiochemical properties, and molecular docking scores, we selected the vaccine construct 1 (C1) for further processing. Docking of C1 with TLR4, TLR7, and TLR8 showed striking interactions with global binding energy of -43.48, -65.88, and -60.24 Kcal/mol, respectively. The docked complex was further simulated, which revealed that both molecules remain stable with minimum RMSF. Activation of TLRs induces downstream pathways to produce pro-inflammatory cytokines against viruses and immune system simulation shows enhanced antibody production after the booster dose. In conclusion, C1 was the best vaccine candidate among all designed constructs to elicit an immune response SARS-CoV-2 and combat the coronavirus disease (COVID-19).