Edible mushrooms: The potential game changer in alleviating vitamin D deficiency and improving human health

The present review attempts to critically examine and evaluate research findings on mushrooms as sources of vitamin D and other nutraceuticals. Recently, there is a growing concern about diseases associated with the deficiency of vitamin D in humans. As people tend to stay indoors, in present times, due to the COVID‐19 pandemic, vitamin D levels are further affected. Research indicates vitamin D as a promising defensive or therapeutic agent against COVID, making this review more crucial. Mushrooms, as a rich source of vitamin D along with various bioactive compounds, perform a significant role in resolving health issues. Robust analyses of various strategies for enhancing vitamin D content in mushrooms holds significance in this study;moreover, this will help stakeholders of the mushroom industry in enriching the overall mushroom quality and human health. Mushroom‐based medicinal formulations and functional foods serve to deliver vitamins and nutrients to humans, thus helping to combat malnutrition and other health problems, especially in developing countries. Evidence from pre‐clinical and clinical analyses suggests that vitamin D₂ bioavailability in mushrooms is comparable with vitamin D from other sources. The review also emphasises molecular findings from mushrooms related to genes responsible for morphology and metabolic production of pro‐vitamin‐D₂.

The SARS-CoV-2 UTR's Intrudes Host RBP's and Modulates Cellular Splicing.

SARS-CoV-2 is a novel coronavirus that causes a potentially fatal respiratory disease known as coronavirus disease (COVID-19) and is responsible for the ongoing pandemic with increasing mortality. Understanding the host-virus interaction involved in SARS-CoV-2 pathophysiology will enhance our understanding of the mechanistic basis of COVID-19 infection. The characterization of post-transcriptional gene regulatory networks, particularly pre-mRNA splicing, and the identification and characterization of host proteins interacting with the 5' and 3'UTRs of SARS-CoV-2 will improve our understanding of post-transcriptional gene regulation during SARS-CoV-2 pathogenesis. Here, we demonstrate that either SARS-CoV-2 infection or exogenous overexpression of the 5' and 3'UTRs of the viral genomic RNAs, results in reduced mRNA levels possibly due to modulation of host cell pre-mRNA splicing. Further, we have investigated the potential RNA-binding proteins interacting with the 5' and 3'UTRs, using in-silico approaches. Our results suggest that 5' and 3'UTRs indeed interact with many RNA-binding proteins. Our results provide a primer for further investigations into the UTR-mediated regulation of splicing and related molecular mechanisms in host cells.

Deciphering the Potential of Pre and Pro-Vitamin D of Mushrooms against Mpro and PLpro Proteases of COVID-19: An In Silico Approach.

Vitamin D's role in combating the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus causing COVID-19, has been established in unveiling viable inhibitors of COVID-19. The current study investigated the role of pre and pro-vitamin D bioactives from edible mushrooms against Mpro and PLpro proteases of SARS-CoV-2 by computational experiments. The bioactives of mushrooms, specifically ergosterol (provitamin D2), 7-dehydrocholesterol (provitamin-D3), 22,23-dihydroergocalciferol (provitamin-D4), cholecalciferol (vitamin-D3), and ergocalciferol (vitamin D2) were screened against Mpro and PLpro. Molecular docking analyses of the generated bioactive protease complexes unravelled the differential docking energies, which ranged from -7.5 kcal/mol to -4.5 kcal/mol. Ergosterol exhibited the lowest binding energy (-7.5 kcal/mol) against Mpro and PLpro (-5.9 kcal/mol). The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) and MD simulation analyses indicated that the generated complexes were stable, thus affirming the putative binding of the bioactives to viral proteases. Considering the pivotal role of vitamin D bioactives, their direct interactions against SARS-CoV-2 proteases highlight the promising role of bioactives present in mushrooms as potent nutraceuticals against COVID-19.

Long-term implications of COVID-19 on bone health: pathophysiology and therapeutics.

BACKGROUND: SARS-CoV-2 is a highly infectious respiratory virus associated with coronavirus disease (COVID-19). Discoveries in the field revealed that inflammatory conditions exert a negative impact on bone metabolism; however, only limited studies reported the consequences of SARS-CoV-2 infection on skeletal homeostasis. Inflammatory immune cells (T helper-Th17 cells and macrophages) and their signature cytokines such as interleukin (IL)-6, IL-17, and tumor necrosis factor-alpha (TNF-α) are the major contributors to the cytokine storm observed in COVID-19 disease. Our group along with others has proven that an enhanced population of both inflammatory innate (Dendritic cells-DCs, macrophages, etc.) and adaptive (Th1, Th17, etc.) immune cells, along with their signature cytokines (IL-17, TNF-α, IFN-γ, IL-6, etc.), are associated with various inflammatory bone loss conditions. Moreover, several pieces of evidence suggest that SARS-CoV-2 infects various organs of the body via angiotensin-converting enzyme 2 (ACE2) receptors including bone cells (osteoblasts-OBs and osteoclasts-OCs). This evidence thus clearly highlights both the direct and indirect impact of SARS-CoV-2 on the physiological bone remodeling process. Moreover, data from the previous SARS-CoV outbreak in 2002-2004 revealed the long-term negative impact (decreased bone mineral density-BMDs) of these infections on bone health. METHODOLOGY: We used the keywords "immunopathogenesis of SARS-CoV-2," "SARS-CoV-2 and bone cells," "factors influencing bone health and COVID-19," "GUT microbiota," and "COVID-19 and Bone health" to integrate the topics for making this review article by searching the following electronic databases: PubMed, Google Scholar, and Scopus. CONCLUSION: Current evidence and reports indicate the direct relation between SARS-CoV-2 infection and bone health and thus warrant future research in this field. It would be imperative to assess the post-COVID-19 fracture risk of SARS-CoV-2-infected individuals by simultaneously monitoring them for bone metabolism/biochemical markers. Importantly, several emerging research suggest that dysbiosis of the gut microbiota-GM (established role in inflammatory bone loss conditions) is further involved in the severity of COVID-19 disease. In the present review, we thus also highlight the importance of dietary interventions including probiotics (modulating dysbiotic GM) as an adjunct therapeutic alternative in the treatment and management of long-term consequences of COVID-19 on bone health.

Human gingival mesenchymal stem cells retain their growth and immunomodulatory characteristics independent of donor age.

Aging has been reported to deteriorate the quantity and quality of mesenchymal stem cells (MSCs), which affect their therapeutic use in regenerative medicine. A dearth of age-related stem cell research further restricts their clinical applications. The present study explores the possibility of using MSCs derived from human gingival tissues (GMSCs) for studying their ex vivo growth characteristics and differentiation potential with respect to donor age. GMSCs displayed decreased in vitro adipogenesis and in vitro and in vivo osteogenesis with age, but in vitro neurogenesis remained unaffected. An increased expression of p53 and SIRT1 with donor age was correlated to their ability of eliminating tumorigenic events through apoptosis or autophagy, respectively. Irrespective of donor age, GMSCs displayed effective immunoregulation and regenerative potential in a mouse model of LPS-induced acute lung injury. Thus, we suggest the potential of GMSCs for designing cell-based immunomodulatory therapeutic approaches and their further extrapolation for acute inflammatory conditions such as acute respiratory distress syndrome and COVID-19.

How Losing Sleep Following Vaccination May Weaken the Response to SARS-CoV Vaccines.

With the emergence of new SARS-CoV-2 variants, a close analysis of factors that affect the efficacy of the vaccine in different groups is a must. It is important to elucidate the role of clinical, behavioral and host factors on modulation of immunogenicity of the SARS-CoV-2 vaccine. Data from other vaccines have shown that duration and efficiency of sleep affect the immunogenicity of the vaccine. There is a need for identification of circadian influence and sleep on SARS-CoV-2 vaccine using validated immune correlates of protection. We propose that sleep acts as a natural adjuvant by promoting the immunological synapse formation between the antigen presenting cells and CD4+ T cells thereby leading to activation of cellular and humoral immunity in SARS-CoV-2 infection. Thus, apart from the titer of neutralizing antibodies, the cellular immunity including CD4+ T cells and memory T cells must be assessed to clearly demarcate the long-term effect of sleep duration and efficiency on vaccine immunogenicity.

Edible mushrooms: The potential game changer in alleviating vitamin D deficiency and improving human health

The present review attempts to critically examine and evaluate research findings on mushrooms as sources of vitamin D and other nutraceuticals. Recently, there is a growing concern about diseases associated with the deficiency of vitamin D in humans. As people tend to stay indoors, in present times, due to the COVID‐19 pandemic, vitamin D levels are further affected. Research indicates vitamin D as a promising defensive or therapeutic agent against COVID, making this review more crucial. Mushrooms, as a rich source of vitamin D along with various bioactive compounds, perform a significant role in resolving health issues. Robust analyses of various strategies for enhancing vitamin D content in mushrooms holds significance in this study;moreover, this will help stakeholders of the mushroom industry in enriching the overall mushroom quality and human health. Mushroom‐based medicinal formulations and functional foods serve to deliver vitamins and nutrients to humans, thus helping to combat malnutrition and other health problems, especially in developing countries. Evidence from pre‐clinical and clinical analyses suggests that vitamin D2 bioavailability in mushrooms is comparable with vitamin D from other sources. The review also emphasises molecular findings from mushrooms related to genes responsible for morphology and metabolic production of pro‐vitamin‐D2. [ABSTRACT FROM AUTHOR] Copyright of International Journal of Food Science & Technology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Phytotherapy for treatment of cytokine storm in COVID-19.

In 2020, a novel strain of coronavirus (COVID-19) has led to a significant morbidity and mortality worldwide. As of the date of this writing, a total of 116 M cases has been diagnosed worldwide leading to 2.5 M deaths. The number of mortalities is directly correlated with the rise of innate immune cells (especially macrophages) in the lungs that secrete inflammatory cytokines (IL-1ß and IL-6) leading to the development of "Cytokine Storm Syndrome" (CSS), multi-organ-failure and death. Given that currently the treatment of this condition is rare and release of effective vaccine might be months away, here, we review the plants and their pharmacologically active-compounds as potential phytopharmaceuticals for the virus induced inflammatory response. Experimental validation of the effectiveness of these natural compounds to prevent or reduce the cytokine storm might be beneficial as an adjunct treatment of SARS-CoV-2.

COVID-19: Immunology, Immunopathogenesis and Potential Therapies.

The Coronavirus Disease-2019 (COVID-19) imposed public health emergency and affected millions of people around the globe. As of January 2021, 100 million confirmed cases of COVID-19 along with more than 2 million deaths were reported worldwide. SARS-CoV-2 infection causes excessive production of pro-inflammatory cytokines thereby leading to the development of "Cytokine Storm Syndrome." This condition results in uncontrollable inflammation that further imposes multiple-organ-failure eventually leading to death. SARS-CoV-2 induces unrestrained innate immune response and impairs adaptive immune responses thereby causing tissue damage. Thus, understanding the foremost features and evolution of innate and adaptive immunity to SARS-CoV-2 is crucial in anticipating COVID-19 outcomes and in developing effective strategies to control the viral spread. In the present review, we exhaustively discuss the sequential key immunological events that occur during SARS-CoV-2 infection and are involved in the immunopathogenesis of COVID-19. In addition to this, we also highlight various therapeutic options already in use such as immunosuppressive drugs, plasma therapy and intravenous immunoglobulins along with various novel potent therapeutic options that should be considered in managing COVID-19 infection such as traditional medicines and probiotics.