PMID: 

J Biomed Res. 2016 Jul ;30(4):314-21. Epub 2016 May 20. PMID: 27533940

Abstract Title: 

Pharmacological advantages of melatonin in immunosenescence by improving activity of T lymphocytes.

Abstract: 

Melatonin plays a critical role in regulating photoperiodic signals and has recently been shown to decrease immunosenescence with age. In this study, we examined whether melatonin activates T lymphocytes as major adaptive immune cells in in vitro and in vivo models. Splenocytes, CD4(+), and naïve CD4 T lymphocytes were isolated from the spleen of BALB/c mice and the cell population patterns and mRNA profiles associated with T cell activation (CD28 and p21) and the melatonin receptor (MT1A and MT1B) were assessed. The T cell activation-related proteins Ki67 and Bcl2 were also evaluated to confirm the relationship between gene and protein levels. Our data clearly revealed that CD28, p21, MT1A, and MT1B mRNA were highly expressed in the presence of melatonin. Co-culture of CD4(+) T lymphocyte and peritoneal macrophage 7 days after melatonin administration to young and aged mice significantly increased APRIL mRNA, suggesting induction or maintenance of T lymphocyte responses. We also found that the intracellular amount of Ki67 and Bcl2 proteins were significantly upregulated in aged CD4(+) T lymphocytes, suggesting enhancing T cell proliferation and ling-term maintenance of memory T cells. Taken together, we conclude that melatonin supplementation may enhance immunity in aged individuals by upregulating immunosenescence indices in association with T lymphocytes and may be an attractive pharmacological candidate for aged and immunocompromised individuals.

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The WHO serves its corporate masters and essentially is destroying, not improving, the health of world

PMID: 

Int J Mol Sci. 2013 Apr 22 ;14(4):8638-83. Epub 2013 Apr 22. PMID: 23609496

Abstract Title: 

Melatonin: buffering the immune system.

Abstract: 

Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed.

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PMID: 

J Immunol. 2010 Apr 1 ;184(7):3487-94. Epub 2010 Feb 24. PMID: 20181888

Abstract Title: 

Melatonin protects CD4+ T cells from activation-induced cell death by blocking NFAT-mediated CD95 ligand upregulation.

Abstract: 

Over the past 20 y, the hormone melatonin was found to be produced in extrapineal sites, including cells of the immune system. Despite the increasing data regarding the biological effects of melatonin on the regulation of the immune system, the effect of this molecule on T cell survival remains largely unknown. Activation-induced cell death plays a critical role in the maintenance of the homeostasis of the immune system by eliminating self-reactive or chronically stimulated T cells. Because activated T cells not only synthesize melatonin but also respond to it, we investigated whether melatonin could modulate activation-induced cell death. We found that melatonin protects human and murine CD4(+) T cells from apoptosis by inhibiting CD95 ligand mRNA and protein upregulation in response to TCR/CD3 stimulation. This inhibition is a result of the interference with calmodulin/calcineurin activation of NFAT that prevents the translocation of NFAT to the nucleus. Accordingly, melatonin has no effect on T cells transfected with a constitutively active form of NFAT capable of migrating to the nucleus and transactivating target genes in the absence of calcineurin activity. Our results revealed a novel biochemical pathway that regulates the expression of CD95 ligand and potentially other downstream targets of NFAT activation.

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Since my last personal note to you on April 8th, I received hundreds of powerfully affirmative responses. I am not able to respond to them all, but know that I do make my best effort.

The Bill and Melinda Gates Foundation has donated more than $21 million towards developing a vaccine technology that uses a tattoo-like mechanism which injects invisible nanoparticles under the skin that is now being tested in a vaccine against the virus that causes COVID-19.

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PMID: 

Planta Med. 2018 Jul ;84(9-10):684-695. Epub 2018 Mar 19. PMID: 29554706

Abstract Title: 

Discovery of Bioactive Natural Products for the Treatment of Acute Respiratory Infections – An Integrated Approach.

Abstract: 

In this work, an integrated approach for the identification of new antiviral agents from natural sources for the treatment of acute respiratory infections is presented. The approach comprises (i) the selection of starting material based on traditional knowledge, (ii) phenotypic screening of extracts for antiviral activity, and (iii) the implementation ofpredictions to identify antiviral compounds and derive the molecular mechanism underlying their biological activity. A variety of starting materials from plants and fungi was selected for the production of 162 extracts. These extracts were tested in cytopathic effect inhibition assays against influenza virus A/Hong Kong/68 (HK/68), rhinovirus A2 (RV-A2), and coxsackie virus B3 (CV-B3). All extracts were also evaluated regarding their cytotoxicity. At an ICthreshold of 50 µg/mL, 20, 11, and 14% of all tested extracts showed antiviral activity against HK/68, CV-B3, and RV-A2, respectively. Among all active extracts (n = 47), 68% showed antiviral activity against one of the investigated viruses, whereas 31% inhibited at least two viruses. Herein, we present a comprehensive dataset of probed extracts along with their antiviral activities and cytotoxicity. Application examples presented in this work illustrate the phytochemical workflow for the identification of antiviral natural compounds. We also discuss the challenges, pitfalls, and advantages of the integrated approach.

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PMID: 

Int J Biol Macromol. 2018 Mar ;108:300-306. Epub 2017 Dec 6. PMID: 29222012

Abstract Title: 

Macrophage immunomodulatory activity of the polysaccharide isolated from Collybia radicata mushroom.

Abstract: 

Polysaccharides from Collybia radicata mushroom (CRP) possess many functions, such as antiviral, anti-aging and hypolipidemic activities. However, little is known about their immunomodulatory activity. To address this issue, we did a thorough research into their immune effects on murine macrophages. The results showed that the 14942Da polysaccharide not only obviously improved the proliferation and phagocytosis of macrophages, but also induced the secretion of nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin factors (IL-1β, IL-6 and IL-10). At a concentration of 850.0μgmL, the polysaccharide stimulated their proliferation and phagocytosis to 2.1 and 3.4 times, respectively, as compared to the negative group. Meanwhile, it raised the production of NO by inducing iNOS in a concentration-dependent manner. Furthermore, it enhanced the release of these cytokines to multiples from 2.3 to 3.6 times. As an inhibitor of TLR4 (Toll-like Receptor 4), TAK242 suppressed the secretion of NO, iNOS and cytokines above 51%, and ORP acted on the cells mainly via TLR4. Consequently, the polysaccharide has a potent immunomodulatory activity by stimulating macrophages and can be considered as a novel potential immunopotentiator in medical and food industries.

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PMID: 

Org Lett. 2019 05 3 ;21(9):3286-3289. Epub 2019 Apr 22. PMID: 31008606

Abstract Title: 

Antiviral Meroterpenoid Rhodatin and Sesquiterpenoids Rhodocoranes A-E from the Wrinkled Peach Mushroom, Rhodotus palmatus.

Abstract: 

Rhodatin (1), a meroterpenoid featuring a unique pentacyclic scaffold with both spiro and spiroketal centers, and five unusual acorane-type sesquiterpenoids, named rhodocoranes A-E (2-6, respectively), are the first natural products isolated from the basidiomycete Rhodotus palmatus. Their structures were elucidated by two-dimensional NMR experiments and HRESIMS, while the absolute configuration of the substance family was determined by Mosher's method utilizing 2. Rhodatin strongly inhibited hepatitis C virus, whereas 4 displayed cytotoxicity and selective antifungal activity.

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PMID: 

Nat Prod Res. 2019 Oct 17:1-5. Epub 2019 Oct 17. PMID: 31621410

Abstract Title: 

Antiproliferative and antiviral activity of methanolic extracts from Sardinian Maltese Mushroom (L.).

Abstract: 

is a non-photosynthetic plant that grows in Mediterranean countries and that is amply used in the traditional medicine. The aim of this study was to extend previous studies on the chemical and biological properties ofevaluating the potential antiviral and antiproliferative activity of the methanolic extract. The MTT assay was used for thecytotoxic studies against human cancer-derived cell lines, while both MTT and plaque reduction (PRT) methods were used to evaluate the potential inhibitory effect of the extract against a panel of mammal viruses. The results obtained showed no selective activity against any DNA and RNA virus but revealed an interesting antiproliferative activity against human leukaemia-derived cell lines.

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