greenmedinfo--2020-04-15--Immune-stimulating effect of Lactobacillus plantarum Ln1 isolated from the traditional Korean fermen

Immune-stimulating effect of Lactobacillus plantarum Ln1 isolated from the traditional Korean fermented Food, Kimchi.

This study aimed to determine the immune-stimulating effects of heat-killedLn1 ( HK-Ln1 ) through the production of nitric oxide ( @ @ @ @ @ achieved by inducing NF-κB and mitogen-activated protein kinase ( MAPK ) -signaling pathways in macrophages @ @ @ @ @ and cytokine production compared to control ( non-stimulated lipopolysaccharide ) ; in addition , the @ @ @ @ @ synthase ( iNOS ) was induced through HK-Ln1treatment .
The phosphorylation of IκB-α and p65 @ @ @ @ @ , which implicates IκB-α degradation and the translocation of p65 to nucleus .
In addition @ @ @ @ @ , ERK 1/2 , JNK , and p38 was induced following HK-Ln1 treatment .

This study aimed to determine the immune-stimulating effects of heat-killedLn1 (HK-Ln1) through the production of nitric oxide (NO) and pro-inflammatory cytokine achieved by inducing NF-κB and mitogen-activated protein kinase (MAPK)-signaling pathways in macrophages. HK-Ln1 showed higher NO and cytokine production compared to control (non-stimulated lipopolysaccharide); in addition, the expression of inducible nitric oxide synthase (iNOS) was induced through HK-Ln1treatment. The phosphorylation of IκB-α and p65 increased following treatment by HK-Ln1, which implicates IκB-α degradation and the translocation of p65 to nucleus. In addition, the phosphorylation of MAPKs, ERK 1/2, JNK, and p38 was induced following HK-Ln1 treatment.


greenmedinfo--2020-04-15--Antioxidant and anti-inflammatory effect of probiotic Lactobacillus plantarum KU15149 derived from K

Antioxidant and anti-inflammatory effect of probiotic Lactobacillus plantarum KU15149 derived from Korean homemade diced-radish kimchi.

KU15149 was demonstrated to have probiotic behavior and functions , including antioxidant and anti-inflammatory activity.KU15149 obtained from homemade diced-radish kimchi @ @ @ @ @ rate under artificial gastric acid ( pH 2.5 , 0.3 % pepsin ) and bile @ @ @ @ @ ) conditions .
However , KU15149 did not produceβ-glucuronidase , which is known to be @ @ @ @ @ to several antibiotics , such as gentamycin , kanamycin , streptomycin , tetracycline , and @ @ @ @ @ cells and had a high antioxidant activity in terms of 2,2-diphenyl-1-picrylhydrazyl ( DPPH ) free @ @ @ @ @ exhibited a pronounced inhibition of nitric oxide ( NO ) production , along with expression @ @ @ @ @ ) and cyclooxygenase -2 ( ) as well as pro-inflammatory cytokines , such as , @ @ @ @ @ 264.7 cells were stimulated with LPS .
Therefore , KU15149 was demonstrated to have pharmaceutical @ @ @ @ @ .

KU15149 was demonstrated to have probiotic behavior and functions, including antioxidant and anti-inflammatory activity.KU15149 obtained from homemade diced-radish kimchi and has a high survival rate under artificial gastric acid (pH 2.5, 0.3% pepsin) and bile salt (0.3% oxgall) conditions. However,KU15149 did not produceβ-glucuronidase, which is known to be a carcinogenic enzyme with resistance to several antibiotics, such as gentamycin, kanamycin, streptomycin, tetracycline, and ciprofloxacin.KU15149 strongly adhered to HT-29 cells and had a high antioxidant activity in terms of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging andβ-carotene bleaching assays.KU15149 also exhibited a pronounced inhibition of nitric oxide (NO) production, along with expression of nitric oxide synthase () and cyclooxygenase -2 () as well as pro-inflammatory cytokines, such as,, and, when RAW 264.7 cells were stimulated with LPS. Therefore,KU15149 was demonstrated to have pharmaceutical functionality as a potential probiotic.


greenmedinfo--2020-04-15--Was the COVID-19 Test Meant to Detect a Virus?

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greenmedinfo--2020-04-15--Lactic acid bacteria isolated from Korean kimchi activate the vitamin D receptor-autophagy signallin

Lactic acid bacteria isolated from Korean kimchi activate the vitamin D receptor-autophagy signalling pathways.

BACKGROUND : Probiotic lactic acid bacteria ( LAB ) have been used in the anti-inflammation and anti-infection process of various diseases , including inflammatory bowel disease ( IBD ) .
Vitamin D receptor ( VDR ) plays an essential role in pathogenesis of IBD and infectious diseases .
Previous studies have demonstrated that the human VDR gene is a key host factor to shape gut microbiome .
Furthermore , intestinal epithelial VDR conditional knockout ( VDRΔIEC ) leads to dysbiosis .
Low expressions of VDR is associated with impaired autophagy , accompanied by a reduction of ATG16L1 and LC3B .
@ @ @ @ @ @ @ investigate probiotic effects and mechanism in modulating the VDR-autophagy pathways .
METHODS : Five LAB strains were isolated from Korean kimchi .
Conditional medium ( CM ) from these strains was used to treat a human cell line HCT116 or intestinal organoids to measure the expression of VDR and autophagy .
Mouse embryonic fibroblast ( MEF ) cells with or without VDR were used to investigate the dependence on the VDR signaling .
To test the role of LAB in anti-inflammation , VDR+/+ organoids were treated with 121-CM before infection with Salmonella enterica @ @ @ @ @ @ @ role of LAB in regulating VDR-autophagy signaling was examined using LAB 121-CM orally administrated to VDRLoxp and VDRΔIEC mice .
RESULTS : The LAB-CM-treated groups showed higher mRNA expression of VDR and its target genes cathelicidin compared with the control group .
LAB treatment also enhanced expressions of Beclin-1 and ATG16L1 and changed the ratio of LC3B I and II , indicating the activation of autophagic responses .
Furthermore , 121-CM treatment before Salmonella enterica serovar Enteritidis infection dramatically increased VDR and ATG16L1 and inhibited the inflammation .
Administration of 121-CM to VDRLoxp @ @ @ @ @ @ @ hours resulted in an increase of VDR and LC3B II : I ratio .
Furthermore , we identified that probiotic proteins P40 and P75 in the LAB-CM contributed to the anti-inflammatory function by increasing VDR .
CONCLUSIONS : Probiotic LAB exert anti-inflammation activity and induces autophagy .
These effects depend on the VDR expression .
Our data highlight the beneficial effects of these 5 LAB strains isolated from food in anti-infection and anti-inflammation .

BACKGROUND: Probiotic lactic acid bacteria (LAB) have been used in the anti-inflammation and anti-infection process of various diseases, including inflammatory bowel disease (IBD). Vitamin D receptor (VDR) plays an essential role in pathogenesis of IBD and infectious diseases. Previous studies have demonstrated that the human VDR gene is a key host factor to shape gut microbiome. Furthermore, intestinal epithelial VDR conditional knockout (VDRΔIEC) leads to dysbiosis. Low expressions of VDR is associated with impaired autophagy, accompanied by a reduction of ATG16L1 and LC3B. The purpose of this study is to investigate probiotic effects and mechanism in modulating the VDR-autophagy pathways.
METHODS: Five LAB strains were isolated from Korean kimchi. Conditional medium (CM) from these strains was used to treat a human cell line HCT116 or intestinal organoids to measure the expression of VDR and autophagy. Mouse embryonic fibroblast (MEF) cells with or without VDR were used to investigate the dependence on the VDR signaling. To test the role of LAB in anti-inflammation, VDR+/+ organoids were treated with 121-CM before infection with Salmonella enterica serovar Enteritidis. In vivo, the role of LAB in regulating VDR-autophagy signaling was examined using LAB 121-CM orally administrated to VDRLoxp and VDRΔIEC mice.
RESULTS: The LAB-CM-treated groups showed higher mRNA expression of VDR and its target genes cathelicidin compared with the control group. LAB treatment also enhanced expressions of Beclin-1 and ATG16L1 and changed the ratio of LC3B I and II, indicating the activation of autophagic responses. Furthermore, 121-CM treatment before Salmonella enterica serovar Enteritidis infection dramatically increased VDR and ATG16L1 and inhibited the inflammation. Administration of 121-CM to VDRLoxp and VDRΔIEC mice for 12 and 24 hours resulted in an increase of VDR and LC3B II:I ratio. Furthermore, we identified that probiotic proteins P40 and P75 in the LAB-CM contributed to the anti-inflammatory function by increasing VDR.
CONCLUSIONS: Probiotic LAB exert anti-inflammation activity and induces autophagy. These effects depend on the VDR expression. Our data highlight the beneficial effects of these 5 LAB strains isolated from food in anti-infection and anti-inflammation.


greenmedinfo--2020-04-15--Microbiome modulation of the host adaptive immunity through bile acid modification.


greenmedinfo--2020-04-15--Acute phase proteins and vitamin D seasonal variation in end-stage renal disease patients.

End-stage renal disease ( ESRD ) patients are vulnerable to vitamin D deficiency due to impaired renal hydroxylation , low dietary intake and inadequate sun exposure .
Vitamin D plays a role in innate and adaptive immunity and its seasonal variation has been linked to mortality .
ESRD is associated with inadequate removal of pro-inflammatory cytokines regulating acute phase protein ( APP ) synthesis .
Our aim was to look for associations between lifestyle factors , diet , and vitamin D seasonal variation and their relationship with selected APPs and calcium-phosphate metabolism .
The study included 59 ESRD patients treated @ @ @ @ @ @ @ recall was conducted in the post-summer ( November 2018 , PS ) and post-winter ( February/March 2019 , PW ) period , and blood was collected for the measurements of serum total vitamin D , α-acid glycoprotein ( AGP ) , C-reactive protein ( CRP ) , albumin , prealbumin ( PRE ) , parathormone , calcium and phosphate .
A self-constructed questionnaire gathered information on vitamin D supplementation , sun exposure and physical activity .
Higher caloric intake was observed PW compared PS .
Less than 15 % of participants met the @ @ @ @ @ @ @ fiber , vitamin D and magnesium intake .
Vitamin D supplementation was associated with higher serum vitamin D regardless of season .
AGP , PRE , albumin , and vitamin D presented seasonal changes ( higher values PS ) .
In patients with serum vitamin D below 25 ng/mL , vitamin D seasonal change correlated with CRP and prealbumin change .
Phosphate and Ca× P correlated positively with AGP .
A low vitamin D serum level could impact the inflammatory process ; however , more studies are needed to confirm the relationship .

End-stage renal disease (ESRD) patients are vulnerable to vitamin D deficiency due to impaired renal hydroxylation, low dietary intake and inadequate sun exposure. Vitamin D plays a role in innate and adaptive immunity and its seasonal variation has been linked to mortality. ESRD is associated with inadequate removal of pro-inflammatory cytokines regulating acute phase protein (APP) synthesis. Our aim was to look for associations between lifestyle factors, diet, and vitamin D seasonal variation and their relationship with selected APPs and calcium-phosphate metabolism. The study included 59 ESRD patients treated with maintenance hemodialysis. A 24-hour dietary recall was conducted in the post-summer (November 2018, PS) and post-winter (February/March 2019, PW) period, and blood was collected for the measurements of serum total vitamin D,α-acid glycoprotein (AGP), C-reactive protein (CRP), albumin, prealbumin (PRE), parathormone, calcium and phosphate. A self-constructed questionnaire gathered information on vitamin D supplementation, sun exposure and physical activity. Higher caloric intake was observed PW compared PS. Less than 15% of participants met the dietary recommendations for energy, protein, fiber, vitamin D and magnesium intake. Vitamin D supplementation was associated with higher serum vitamin D regardless of season. AGP, PRE, albumin, and vitamin D presented seasonal changes (higher values PS). In patients with serum vitamin D below 25 ng/mL, vitamin D seasonal change correlated with CRP and prealbumin change. Phosphate and Ca× P correlated positively with AGP. A low vitamin D serum level could impact the inflammatory process; however, more studies are needed to confirm the relationship.


greenmedinfo--2020-04-15--Bill Gates and Intellectual Ventures Funds Microchip Implant Vaccine Technology


greenmedinfo--2020-04-15--Correlation of vitamin D with inflammatory factors, oxidative stress and T cell subsets in patients

Correlation of vitamin D with inflammatory factors , oxidative stress and T cell subsets in patients with autoimmune hepatitis were investigated .
Patients with liver diseases ( n=635 ) treated in The Sixth People 's Hospital of Qingdao City from March 2015 to January 2018 were selected , among which 80 cases diagnosed with autoimmune hepatitis were included into observation group , and 80 healthy cases were included into control group .
Patients with autoimmune hepatitis were further divided into normal 25-hydroxyvitamin D [ 25- ( OH ) D ] group ( n=40 ) and abnormal 25- ( OH ) @ @ @ @ @ @ @ the level of 25- ( OH ) D , and divided into normal liver function group ( n=40 ) and abnormal liver function group ( n=40 ) .
25- ( OH ) D , liver function , inflammatory factors , oxidative stress level and T cell subsets were compared .
In the observation group , levels of 25- ( OH ) D , superoxide dismutase ( SOD ) , total antioxidant capacity , and T cell subsets were lower than those in the control group ( P < 0.05 ) , while levels @ @ @ @ @ @ @ indirect BIL ( IBIL ) , direct BIL ( DBIL ) , aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) , inflammatory factors and malondialdehyde ( MDA ) were higher than those in the control group ( P < 0.05 ) .
In the normal 25- ( OH ) D group , levels of inflammatory factors and oxidative stress factor were lower than those in the abnormal 25- ( OH ) D group ( P < 0.05 ) , while the SOD level , total antioxidant capacity and T cell @ @ @ @ @ @ @ the abnormal 25- ( OH ) D group ( P < 0.05 ) .
Moreover , the 25- ( OH ) D level in patients with autoimmune hepatitis was negatively correlated with hs-CRP , tumor necrosis factor-α ( TNF-α ) , ALT and MDA , but positively correlated with CD3and CD4counts , SOD and total antioxidant capacity .
Patients with autoimmune hepatitis , especially those with decreased level of vitamin D , are more prone to enhanced inflammatory and stress responses , decreased levels of T cell subsets and decline in immunity .

Correlation of vitamin D with inflammatory factors, oxidative stress and T cell subsets in patients with autoimmune hepatitis were investigated. Patients with liver diseases (n=635) treated in The Sixth People's Hospital of Qingdao City from March 2015 to January 2018 were selected, among which 80 cases diagnosed with autoimmune hepatitis were included into observation group, and 80 healthy cases were included into control group. Patients with autoimmune hepatitis were further divided into normal 25-hydroxyvitamin D [25-(OH) D] group (n=40) and abnormal 25-(OH) D group (n=40) according to the level of 25-(OH) D, and divided into normal liver function group (n=40) and abnormal liver function group (n=40). 25-(OH) D, liver function, inflammatory factors, oxidative stress level and T cell subsets were compared. In the observation group, levels of 25-(OH) D, superoxide dismutase (SOD), total antioxidant capacity, and T cell subsets were lower than those in the control group (P<0.05), while levels of total bilirubin (TBIL), indirect BIL (IBIL), direct BIL (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), inflammatory factors and malondialdehyde (MDA) were higher than those in the control group (P<0.05). In the normal 25-(OH) D group, levels of inflammatory factors and oxidative stress factor were lower than those in the abnormal 25-(OH) D group (P<0.05), while the SOD level, total antioxidant capacity and T cell subset counts were higher than those in the abnormal 25-(OH) D group (P<0.05). Moreover, the 25-(OH) D level in patients with autoimmune hepatitis was negatively correlated with hs-CRP, tumor necrosis factor-α (TNF-α), ALT and MDA, but positively correlated with CD3and CD4counts, SOD and total antioxidant capacity. Patients with autoimmune hepatitis, especially those with decreased level of vitamin D, are more prone to enhanced inflammatory and stress responses, decreased levels of T cell subsets and decline in immunity.


greenmedinfo--2020-04-15--Preconception optimization of vitamin D status should be considered in women with recurrent implanta

Preconception optimization of vitamin D status should be considered in women with recurrent implantation failure.

PROBLEM : This study aims to evaluate the modulatory effects of vitamin D on peripheral blood and endometrial cellular immunity in women with recurrent implantation failure ( RIF ) .
METHOD OF STUDY : One hundred and fifty-four women with RIF were identified at a fertility center from January 2018 and March 2019 .
Blood and endometrium samples were collected during the mid-luteal phase before IVF treatment or pregnancy .
The serum vitamin D status , NK cell cytotoxicity , Th1 cytokine production and endometrial immune cells were detected before and after vitamin D supplementation .
RESULTS : The NK @ @ @ @ @ @ @ : T ) ratio of 50:1 or 25:1 was significantly higher in vitamin D insufficiency group ( VDI ) than those in vitamin D normal group ( VDN ) ( P < 0.05 each ) .
The percentage of IFN-γ- or TNF-α-producing Th cells was significantly increased in VDI or vitamin D deficiency group ( VDD ) when compared with VDN ( P < 0.05 each ) .
The percentage of CD68macrophages on all endometrial cells in VDI and VDD was significantly higher than in VDN ( P < 0.05 each ) , @ @ @ @ @ @ @ of other endometrial immune cells among the three groups were observed .
This dysregulation was significantly reduced with vitamin D supplementation .
CONCLUSION : Our findings highlighted that vitamin D may have an important role in the regulation of not only systemic but also local immune response for optimization of maternal tolerance for implantation in women with RIF .
Preconception optimization of vitamin D status should be considered in women with RIF .

PROBLEM: This study aims to evaluate the modulatory effects of vitamin D on peripheral blood and endometrial cellular immunity in women with recurrent implantation failure (RIF).
METHOD OF STUDY: One hundred and fifty-four women with RIF were identified at a fertility center from January 2018 and March 2019. Blood and endometrium samples were collected during the mid-luteal phase before IVF treatment or pregnancy. The serum vitamin D status, NK cell cytotoxicity, Th1 cytokine production and endometrial immune cells were detected before and after vitamin D supplementation.
RESULTS: The NK cell cytotoxicity at an effector-to-target (E:T) ratio of 50:1 or 25:1 was significantly higher in vitamin D insufficiency group (VDI) than those in vitamin D normal group (VDN) (P<0.05 each). The percentage of IFN-γ- or TNF-α-producing Th cells was significantly increased in VDI or vitamin D deficiency group (VDD) when compared with VDN (P<0.05 each). The percentage of CD68macrophages on all endometrial cells in VDI and VDD was significantly higher than in VDN (P<0.05 each), while no significant differences in the percentage of other endometrial immune cells among the three groups were observed. This dysregulation was significantly reduced with vitamin D supplementation.
CONCLUSION: Our findings highlighted that vitamin D may have an important role in the regulation of not only systemic but also local immune response for optimization of maternal tolerance for implantation in women with RIF. Preconception optimization of vitamin D status should be considered in women with RIF.


greenmedinfo--2020-04-15--Caught the Corona Virus Blues? Research Shows That Music Medicine is a Powerful Antidote


greenmedinfo--2020-04-15--Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of A

Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease

Increased levels of a 40-42 amino-acid peptide called the amyloid beta protein ( A beta ) and evidence of oxidative @ @ @ @ @ of Alzheimer 's disease ( AD ) .
Previous investigations have demonstrated that melatonin is @ @ @ @ @ and that patients with AD have more profound reductions of this hormone .
It has @ @ @ @ @ melatonin protects neuronal cells from A beta-mediated oxidative damage and inhibits the formation of amyloid @ @ @ @ @ , a direct relationship between melatonin and the biochemical pathology of AD had not been @ @ @ @ @ transgenic mouse model of Alzheimer 's amyloidosis and monitored over time the effects of administering @ @ @ @ @ A beta , abnormal protein nitration , and survival of the mice .
We report @ @ @ @ @ partially inhibited the expected time-dependent elevation of beta-amyloid , reduced abnormal nitration of proteins , @ @ @ @ @ treated transgenic mice .
These findings may bear relevance to the pathogenesis and therapy of @ @

Increased levels of a 40-42 amino-acid peptide called the amyloid beta protein (A beta) and evidence of oxidative damage are early neuropathological markers of Alzheimer's disease (AD). Previous investigations have demonstrated that melatonin is decreased during the aging process and that patients with AD have more profound reductions of this hormone. It has also been recently shown that melatonin protects neuronal cells from A beta-mediated oxidative damage and inhibits the formation of amyloid fibrils in vitro. However, a direct relationship between melatonin and the biochemical pathology of AD had not been demonstrated. We used a transgenic mouse model of Alzheimer's amyloidosis and monitored over time the effects of administering melatonin on brain levels of A beta, abnormal protein nitration, and survival of the mice. We report here that administration of melatonin partially inhibited the expected time-dependent elevation of beta-amyloid, reduced abnormal nitration of proteins, and increased survival in the treated transgenic mice. These findings may bear relevance to the pathogenesis and therapy of AD.


greenmedinfo--2020-04-15--The melatonin immunomodulatory actions in radiotherapy

Radiotherapy has a key role in cancer treatment in more than half of patients with cancer .
The management of severe side effects of this treatment modality is a limiting factor to appropriate treatment .
Immune system responses play a pivotal role in many of the early and late side effects of radiation .
Moreover , immune cells have a significant role in tumor response to radiotherapy , such as angiogenesis and tumor growth .
Melatonin as a potent antioxidant has shown appropriate immune regulatory properties that may ameliorate toxicity induced by radiation in various organs .
These effects are @ @ @ @ @ @ @ in different levels of tissue reaction to ionizing radiation .
The effects on the DNA repair system , antioxidant enzymes , immune cells , cytokines secretion , transcription factors , and protein kinases are most important .
Moreover , anti-cancer properties of melatonin may increase the therapeutic ratio of radiotherapy .
Clinical applications of this agent for the management of malignancies such as breast cancer have shown promising results .
It seems anti-proliferative , anti-angiogenesis , and stimulation or suppression of some immune cell responses are the main anti-tumor effects of melatonin that @ @ @ @ @ @ @ tumor to radiotherapy .
In this review , the effects of melatonin on the modulation of immune responses in both normal and tumor tissues will be discussed .

Radiotherapy has a key role in cancer treatment in more than half of patients with cancer. The management of severe side effects of this treatment modality is a limiting factor to appropriate treatment. Immune system responses play a pivotal role in many of the early and late side effects of radiation. Moreover, immune cells have a significant role in tumor response to radiotherapy, such as angiogenesis and tumor growth. Melatonin as a potent antioxidant has shown appropriate immune regulatory properties that may ameliorate toxicity induced by radiation in various organs. These effects are mediated through various modulatory effects of melatonin in different levels of tissue reaction to ionizing radiation. The effects on the DNA repair system, antioxidant enzymes, immune cells, cytokines secretion, transcription factors, and protein kinases are most important. Moreover, anti-cancer properties of melatonin may increase the therapeutic ratio of radiotherapy. Clinical applications of this agent for the management of malignancies such as breast cancer have shown promising results. It seems anti-proliferative, anti-angiogenesis, and stimulation or suppression of some immune cell responses are the main anti-tumor effects of melatonin that may help to improve response of the tumor to radiotherapy. In this review, the effects of melatonin on the modulation of immune responses in both normal and tumor tissues will be discussed.


greenmedinfo--2020-04-15--Role of the pineal gland in immunity. III. Melatonin antagonizes the immunosuppressive effect of acu

Role of the pineal gland in immunity. III. Melatonin antagonizes the immunosuppressive effect of acute stress via an opiatergic mechanism.

We have recently demonstrated that the pineal neurohormone melatonin exerts important immunoregulatory functions .
We now report that exogenous melatonin @ @ @ @ @ acute anxiety-restraint stress on thymus weight and antibody response to sheep red blood cells ( @ @ @ @ @ , administration of melatonin in the evening prevented paralysis and death of mice infected with @ @ @ @ @ ( EMCV ) after acute stress .
The anti-stress activity of melatonin was present in @ @ @ @ @ , and it was abolished by the contemporary administration of the specific opioid-antagonist naltrexone .
@ @ @ @ @ its remarkable anti-stress effect on antigen-activated cells via an opiatergic mechanism .
These findings have @ @ @ @ @ and clinical levels .
They provide a new approach to a possible physiological 'up-regulation ' @ @ @ @ @ virus- and/or stress-related immunosuppression .

We have recently demonstrated that the pineal neurohormone melatonin exerts important immunoregulatory functions. We now report that exogenous melatonin counteracts completely the effect of acute anxiety-restraint stress on thymus weight and antibody response to sheep red blood cells (SRBC). In addition, administration of melatonin in the evening prevented paralysis and death of mice infected with sublethal doses of encephalomyocarditis virus (EMCV) after acute stress. The anti-stress activity of melatonin was present in mice injected with T-dependent antigens, and it was abolished by the contemporary administration of the specific opioid-antagonist naltrexone. This suggests that melatonin exerts its remarkable anti-stress effect on antigen-activated cells via an opiatergic mechanism. These findings have important implications at both basic and clinical levels. They provide a new approach to a possible physiological 'up-regulation' of the immune response under virus- and/or stress-related immunosuppression.


greenmedinfo--2020-04-15--Melatonin as a master regulator of cell death and inflammation: molecular mechanisms and clinical im

Melatonin as a master regulator of cell death and inflammation: molecular mechanisms and clinical implications for newborn care

Melatonin , more commonly known as the sleep hormone , is mainly secreted by the pineal gland in dark conditions @ @ @ @ @ of the organism .
Its intrinsic properties , including high cell permeability , the ability @ @ @ @ @ blood-brain and placenta barriers , and its role as an endogenous reservoir of free radical @ @ @ @ @ activities ) , confer it beneficial uses as an adjuvant in the biomedical field .
@ @ @ @ @ by acting through specific cellular receptors on the plasma membrane , similar to other hormones @ @ @ @ @ that involve complex molecular cross talk with other players .
There is increasing evidence regarding @ @ @ @ @ melatonin , also via exogenous administration .
Here , we summarize molecular pathways in which @ @ @ @ @ regulator , with attention to cell death and inflammation mechanisms from basic , translational and @ @ @ @ @ the context of newborn care .

Melatonin, more commonly known as the sleep hormone, is mainly secreted by the pineal gland in dark conditions and regulates the circadian rhythm of the organism. Its intrinsic properties, including high cell permeability, the ability to easily cross both the blood-brain and placenta barriers, and its role as an endogenous reservoir of free radical scavengers (with indirect extra activities), confer it beneficial uses as an adjuvant in the biomedical field. Melatonin can exert its effects by acting through specific cellular receptors on the plasma membrane, similar to other hormones, or through receptor-independent mechanisms that involve complex molecular cross talk with other players. There is increasing evidence regarding the extraordinary beneficial effects of melatonin, also via exogenous administration. Here, we summarize molecular pathways in which melatonin is considered a master regulator, with attention to cell death and inflammation mechanisms from basic, translational and clinical points of view in the context of newborn care.


greenmedinfo--2020-04-15--Modulation by melatonin of the pathogenesis of inflammatory autoimmune diseases.

Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation @ @ @ @ @ , and antioxidant and anti-inflammatory effects .
It also possesses the ability to modulate immune @ @ @ @ @ T helper 1/2 balance and cytokine production .
Autoimmune diseases , which result from the @ @ @ @ @ autoantigens released from normal tissues , affect around 5 % of the population .
Activation @ @ @ @ @ to subsequent damage of target tissues by these activated cells .
Melatonin therapy has been @ @ @ @ @ of autoimmune disease , where it has a beneficial effect in a number of models @ @ @ @ @ has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis .
This @ @ @ @ @ role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis @ @ @ @ @ rheumatoid arthritis , type 1 diabetes mellitus , and inflammatory bowel disease .

Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation of circadian and seasonal rhythms, and antioxidant and anti-inflammatory effects. It also possesses the ability to modulate immune responses by regulation of the T helper 1/2 balance and cytokine production. Autoimmune diseases, which result from the activation of immune cells by autoantigens released from normal tissues, affect around 5% of the population. Activation of autoantigen-specific immune cells leads to subsequent damage of target tissues by these activated cells. Melatonin therapy has been investigated in several animal models of autoimmune disease, where it has a beneficial effect in a number of models excepting rheumatoid arthritis, and has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis. This review summarizes and highlights the role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease.


greenmedinfo--2020-04-15--Melatonin and the immune system in aging.

Aging is associated with a decline in immune function ( immunosenescence ) , a condition known to correlate with increased @ @ @ @ @ as infectious and degenerative diseases .
Innate , cellular and humoral immunity all exhibit increased @ @ @ @ @ melatonin decreases with age , and in recent years much interest has been focused on @ @ @ @ @ stimulates the production of progenitor cells for granulocytes and macrophages .
It also stimulates the @ @ @ @ @ and CD4+ cells and inhibits CD8+ cells .
The production and release of various cytokines @ @ @ @ @ T helper lymphocytes are enhanced by melatonin .
Melatonin has the potential therapeutic value to @ @ @ @ @ individuals .

Aging is associated with a decline in immune function (immunosenescence), a condition known to correlate with increased incidence of cancer as well as infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. Circulating melatonin decreases with age, and in recent years much interest has been focused on its immunomodulatory effect. Melatonin stimulates the production of progenitor cells for granulocytes and macrophages. It also stimulates the production of natural killer cells and CD4+ cells and inhibits CD8+ cells. The production and release of various cytokines from natural killer cells and T helper lymphocytes are enhanced by melatonin. Melatonin has the potential therapeutic value to enhance immune function in aged individuals.


greenmedinfo--2020-04-15--Nutritional modulation of immune function: analysis of evidence, mechanisms, and clinical relevance.

It is well-established that the nutritional deficiency or inadequacy can impair immune functions .
Growing evidence suggests that for certain nutrients increased intake above currently recommended levels may help optimize immune functions including improving defense function and thus resistance to infection , while maintaining tolerance .
This review will examine the data representing the research on prominent intervention agents n-3 polyunsaturated fatty acids ( PUFA ) , micronutrients ( zinc , vitamins D and E ) , and functional foods including probiotics and tea components for their immunological effects , working mechanisms , and clinical relevance .
Many of these @ @ @ @ @ @ @ in their functions to maintain or improve immune function including inhibition of pro-inflammatory mediators , promotion of anti-inflammatory functions , modulation of cell-mediated immunity , alteration of antigen-presenting cell functions , and communication between the innate and adaptive immune systems .
Both animal and human studies present promising findings suggesting a clinical benefit of vitamin D , n-3 PUFA , and green tea catechin EGCG in autoimmune and inflammatory disorders , and vitamin D , vitamin E , zinc , and probiotics in reduction of infection .
However , many studies report divergent @ @ @ @ @ @ @ .
Chief among them , and thus call for attention , includes more standardized trial designs , better characterized populations , greater consideration for the intervention doses used , and more meaningful outcome measurements chosen .

It is well-established that the nutritional deficiency or inadequacy can impair immune functions. Growing evidence suggests that for certain nutrients increased intake above currently recommended levels may help optimize immune functions including improving defense function and thus resistance to infection, while maintaining tolerance. This review will examine the data representing the research on prominent intervention agents n-3 polyunsaturated fatty acids (PUFA), micronutrients (zinc, vitamins D and E), and functional foods including probiotics and tea components for their immunological effects, working mechanisms, and clinical relevance. Many of these nutritive and non-nutritive food components are related in their functions to maintain or improve immune function including inhibition of pro-inflammatory mediators, promotion of anti-inflammatory functions, modulation of cell-mediated immunity, alteration of antigen-presenting cell functions, and communication between the innate and adaptive immune systems. Both animal and human studies present promising findings suggesting a clinical benefit of vitamin D, n-3 PUFA, and green tea catechin EGCG in autoimmune and inflammatory disorders, and vitamin D, vitamin E, zinc, and probiotics in reduction of infection. However, many studies report divergent and discrepant results/conclusions due to various factors. Chief among them, and thus call for attention, includes more standardized trial designs, better characterized populations, greater consideration for the intervention doses used, and more meaningful outcome measurements chosen.


greenmedinfo--2020-04-15--Decreasing pro-inflammatory cytokine and reversing the immunosenescence with extracts of Pu-erh tea.

Immunosenescence , the progressive decline of adaptive immunity and chronic inflammation with ageing has been demonstrated to be the main @ @ @ @ @ cancer and autoimmune conditions in the elderly .
Senescence-accelerated mouse ( SAM ) was used @ @ @ @ @ of Pu-erh tea in the elderly .
The senile-prone sub-strain , SAM-P8 mice were administered @ @ @ @ @ Pu-erh tea at 125 , 250 or 500mg/kg .
The results showed that Pu-erh tea @ @ @ @ @ naïve T lymphocytes , CD8 ( + ) CD28 ( + ) T lymphocytes and @ @ @ @ @ blood , but decreased the levels of IL-6 in aged mice .
These data suggested @ @ @ @ @ the immunosenescence by restoring the immune deficiency and decreasing pro-inflammatory cytokine .
Thus , long @ @ @ @ @ may be beneficial for the aged population in terms of increasing the body 's resistance @ @ @ @ @

Immunosenescence, the progressive decline of adaptive immunity and chronic inflammation with ageing has been demonstrated to be the main factor responsible for infections, cancer and autoimmune conditions in the elderly. Senescence-accelerated mouse (SAM) was used to study the protective effects of Pu-erh tea in the elderly. The senile-prone sub-strain, SAM-P8 mice were administered individually with ripened or crude Pu-erh tea at 125, 250 or 500mg/kg. The results showed that Pu-erh tea significantly increased the fractions of naïve T lymphocytes, CD8(+)CD28(+) T lymphocytes and NK cells in the peripheral blood, but decreased the levels of IL-6 in aged mice. These data suggested that the Pu-erh tea reversed the immunosenescence by restoring the immune deficiency and decreasing pro-inflammatory cytokine. Thus, long term drinking of Pu-erh tea may be beneficial for the aged population in terms of increasing the body's resistance to infection and cancer.


greenmedinfo--2020-04-14--Phytochemicals inhibit the immunosuppressive functions of myeloid-derived suppressor cells.

Traditional herbal medicine has provided natural remedies against cancers and many age-related inflammatory diseases for thousands of years .
Modern drug discovery techniques have revealed several active ingredients and their medicinal targets have been characterized .
Concurrently , there has been great progress in understanding the pathological mechanisms underpinning cancers and inflammatory diseases .
These studies have demonstrated that immature myeloid-derived suppressor cells ( MDSCs ) have a crucial role in the immune escape of cancer cells thus promoting tumor growth .
Inflammatory factors stimulate the recruitment , expansion , and activation of MDSCs in tumors and inflamed tissues .
@ @ @ @ @ @ @ important role in the resolution of acute inflammation but in chronic inflammatory disorders , the activation of MDSCs suppresses the innate and adaptive immune responses thus aggravating the disease processes in association with tumors , chronic infections , and many degenerative diseases .
Currently , MDSCs are important drug discovery targets in cancers and chronic inflammatory diseases .
Interestingly , there are promising reports that certain phytochemicals can function as potent inhibitors of the immunosuppressive MDSCs that could partially explain the therapeutic benefits of herbal medicine .
We will briefly describe the immune @ @ @ @ @ @ @ age-related inflammatory diseases and then review in detail the chemically characterized phytochemicals of different herbal categories , e.g .
flavonoids , terpenoids , retinoids , curcumins , andβ-glucans , which possess the MDSC-dependent antitumor and anti-inflammatory properties .

Traditional herbal medicine has provided natural remedies against cancers and many age-related inflammatory diseases for thousands of years. Modern drug discovery techniques have revealed several active ingredients and their medicinal targets have been characterized. Concurrently, there has been great progress in understanding the pathological mechanisms underpinning cancers and inflammatory diseases. These studies have demonstrated that immature myeloid-derived suppressor cells (MDSCs) have a crucial role in the immune escape of cancer cells thus promoting tumor growth. Inflammatory factors stimulate the recruitment, expansion, and activation of MDSCs in tumors and inflamed tissues. The immunosuppression generated by MDSCs has an important role in the resolution of acute inflammation but in chronic inflammatory disorders, the activation of MDSCs suppresses the innate and adaptive immune responses thus aggravating the disease processes in association with tumors, chronic infections, and many degenerative diseases. Currently, MDSCs are important drug discovery targets in cancers and chronic inflammatory diseases. Interestingly, there are promising reports that certain phytochemicals can function as potent inhibitors of the immunosuppressive MDSCs that could partially explain the therapeutic benefits of herbal medicine. We will briefly describe the immune suppressive functions of MDSCs in cancers and age-related inflammatory diseases and then review in detail the chemically characterized phytochemicals of different herbal categories, e.g. flavonoids, terpenoids, retinoids, curcumins, andβ-glucans, which possess the MDSC-dependent antitumor and anti-inflammatory properties.


greenmedinfo--2020-04-14--Grape polyphenols corrects ageing-related detriments in neutrophil functionality via modulation of s

Grape polyphenols corrects ageing-related detriments in neutrophil functionality via modulation of specific molecular targets.

Oxidative stress and inflammation are intricately interlinked as aetiological factors in the context of ageing and chronic disease-related accelerated ageing .
Previous research by our group has highlighted the anti-oxidant and anti-inflammatory potential of grape-derived polyphenols in the context of acute inflammation and oxidative stress .
The aim here was to add to this by assessing efficacy of the treatment ( acutely ) to address ageing-associated cumulative pro-oxidant and pro-inflammatory changes in an in vitro model .
Blood from young and aged humans was analysed for baseline oxidative stress and inflammatory status .
Isolated neutrophils were acutely exposed to the @ @ @ @ @ @ @ capacity of treated and control neutrophils in response to fMLP was subsequently determined in a Dunn chamber , using live cell imaging .
Neutrophils were also analysed for the expression of selected molecular markers associated with functional capacity and oxidative stress .
Results indicate that the aged population had significantly worse oxidative stress and inflammatory profiles ( higher plasma conjugated dienes and MPO ) than young controls .
Neutrophils isolated from both young and aged individuals had improved chemokinetic accuracy and capacity after in vitro polyphenol treatment .
Additionally , increased shedding of @ @ @ @ @ @ @ via which the polyphenol achieved improved neutrophil motility .
We conclude that grape seed-derived polyphenols facilitated improved neutrophil functionality by acting on the molecular targets elucidated here .

Oxidative stress and inflammation are intricately interlinked as aetiological factors in the context of ageing and chronic disease-related accelerated ageing. Previous research by our group has highlighted the anti-oxidant and anti-inflammatory potential of grape-derived polyphenols in the context of acute inflammation and oxidative stress. The aim here was to add to this by assessing efficacy of the treatment (acutely) to address ageing-associated cumulative pro-oxidant and pro-inflammatory changes in an in vitro model. Blood from young and aged humans was analysed for baseline oxidative stress and inflammatory status. Isolated neutrophils were acutely exposed to the polyphenol treatment in vitro. The chemokinetic capacity of treated and control neutrophils in response to fMLP was subsequently determined in a Dunn chamber, using live cell imaging. Neutrophils were also analysed for the expression of selected molecular markers associated with functional capacity and oxidative stress. Results indicate that the aged population had significantly worse oxidative stress and inflammatory profiles (higher plasma conjugated dienes and MPO) than young controls. Neutrophils isolated from both young and aged individuals had improved chemokinetic accuracy and capacity after in vitro polyphenol treatment. Additionally, increased shedding of CD16 and expression of CD66b suggested sites via which the polyphenol achieved improved neutrophil motility. We conclude that grape seed-derived polyphenols facilitated improved neutrophil functionality by acting on the molecular targets elucidated here.


greenmedinfo--2020-04-14--Melatonin supplementation may enhance immunity in aged individuals by upregulating immunosenescence

Melatonin supplementation may enhance immunity in aged individuals by upregulating immunosenescence indices.

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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ 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 .

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.


greenmedinfo--2020-04-14--Can You Trust the WHO With COVID-19 Pandemic Response?


greenmedinfo--2020-04-14--Melatonin: Buffering the immune system

Melatonin: Buffering the immune system

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

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.


greenmedinfo--2020-04-14--Melatonin protects CD4+ T cells from activation-induced cell death by blocking NFAT-mediated CD95 li

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

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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ and potentially other downstream targets of NFAT activation .

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.


greenmedinfo--2020-04-14--Conspiracy FACT: Why does the WHO and CDC require ZERO virus testing for "COVID DEATHS"?

This website is for information purposes only .
By providing the information contained herein we are not diagnosing , treating @ @ @ @ @ or preventing any type of disease or medical condition .
Before beginning any type of @ @ @ @ @ treatment regimen , it is advisable to seek the advice of a licensed healthcare professional @

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
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greenmedinfo--2020-04-14--Bill Gates and Intellectual Ventures Funds Microchip Implant Vaccine Technology

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 The microneedle technology is also being wed to injectable technology , funded by the Bill and Melinda Gates Foundation , which embeds under the skin a vaccination record visible by near infrared light that can be read by smartphone technology .
The Bill and Melinda Gates Foundation is funding the technologies with aims to enable them @ @ @ @ @ @ @ by people with `` minimal training . ''
Researchers from the University of Pittsburgh reported in their study published April 1 in EBiomedicine , a Lancet Journal , that their microneedle patch vaccine against the SARS CoV-2 virus that causes COVID-19 `` prompted robust antibody production in the mice within two weeks . ''
The patches resemble a spiky piece of Velcro , with hundreds of tiny microneedles made of sugar .
The needles prick just into the skin and quickly dissolve , releasing the vaccine into the tiny abrasions and inducing a @ @ @ @ @ @ @ amount of the vaccine material - far more potent than an intramuscular injection .
The researchers had been testing vaccine using the microneedle patch for other coronaviruses , including the one that causes Middle East Respiratory System ( MERS ) and reported that three different experimental MERS vaccines induced the production of antibodies against the virus .
These responses were stronger than the responses generated by regular injection of one of the vaccines along with a powerful immune stimulant ( an adjuvant ) .
Antibody levels continued to increase over time in mice @ @ @ @ @ @ @ , when the experiments ended .
The researchers have now turned their technology to the COVID-19 virus , SARS CoV-2 .
`` Testing in patients would typically require at least a year and probably longer , '' senior co-author of the study , dermatology professor Louis Falo said .
`` This particular situation is different from anything we 've ever seen , so we do n't know how long the clinical development process will take .
Recently announced revisions to the normal processes suggest we may be able to advance this faster .
@ @ @ @ @ @ @ and Melinda Gates Foundation and published in December , 2019 by researchers from the Massachusetts Institute of Technology , the Institute of Chemistry of the Chinese Academy of Sciences in Beijing and the Global Good , Intellectual Ventures Laboratory in Bellevue , WA , describes how `` near-infrared quantum dots '' can be implanted under the skin along with a vaccine to encode information for `` decentralized data storage and bio-sensing . ''
`` To maximize the utility of this technology for vaccination campaigns , we aimed to create a platform compatible with @ @ @ @ @ @ @ on an individual for at least five years after administration , '' said the MIT paper , titled Biocompatible near-infrared quantum dots delivered to the skin by microneedle patches record vaccination .
`` In addition , this system also needed to be highly biocompatible , deliver a sufficient amount of dye after an application time of 2 min or less , and be detectable using a minimally adapted smartphone . ''
Fridrik Laurusson , an author of the microchip study , is from The Global Good , Intellectual Ventures Labarotory .
Its website @ @ @ @ @ @ @ front page and describes itself as a `` collaboration between Bill Gates and Intellectual Ventures '' a company founded by Nathan Myhrvold and Edward Jung of Microsoft .
Wikipedia describes Intellectual Ventures in Gates ' home state as a private American company that `` centers on the development and licensing of intellectual property '' and `` one of the top-five owners of U.S. patents , as of 2011 .
`` Its business model has a focus on buying patents and aggregating them into a large patent portfolio and licensing these patents to third @ @ @ @ @ @ @ The company has been described as the country 's largest and most notorious patent trolling company , the ultimate patent troll , and the most hated company in tech .
The website of the Bill and Melinda Gates lists multiple grants awarded to develop the `` microneedle array patch '' - for use in `` house-to-house campaigns via administration by minimally-trained personnel . ''
The most recent grant for $ 370,035 was awarded in February , 2020 to the Centers for Disease Control and Prevention for an MMR vaccine patch that does not @ @ @ @ @ @ @ '' via people without medical experience or training .
Bill Gates has awarded much larger grants for microneedle array patch technology to companies and organizations including : * Vaxxas Pty Ltd in Brisbane , Queensland ( $ 4.99 million in November , 2019 ) to develop a `` microneedle array patch for measles and rubella vaccination that enables house-to-house campaigns via administration by minimally-trained personnel '' Vaxxas was created in 2011 after Mark Kendall 's research group at the University of Queensland commercialized the nanotechnology under the company , UniQuest .
The company @ @ @ @ @ @ @ for the nanotechnology .
It 's partnered with vaccine manufacturer Merck - a company whose drug Vioxx caused more than 27,000 deaths by heart attack before the company revealed the risks it had hidden from the public .
Merck has repeatedly been accused by judges for `` egregious '' ethical breaches and of `` improper testing and data falsification '' on its Gardasil HPV and MMR vaccines .
Merck made Micron Biomedical Inc ( $ 6,744,906 in November , 2019 ) `` to develop a microneedle array patch for measles and rubella vaccination @ @ @ @ @ @ @ minimally-trained personnel '' Georgia Institute of Technology ( $ 958,849 in December , 2019 ) `` to develop a microneedle array patch for measles and rubella vaccination that enables house-to-house campaigns via administration by minimally-trained personnel '' Vaxess Inc , ( $ 2,967,741 in November , 2016 ) in Boston , MA `` to support the preclinical development and manufacture of a thermostable microneedle patch with the aim of lowering barriers to vaccine access by simplifying dosing and administration , alleviating cold chain constraints , and lowering costs Cardiff University ( $ $ @ @ @ @ @ @ @ to develop a dissolvable microneedle array patch for the sustained dermal delivery of a progestin contraceptive , including the conduct of preclinical proof of concept studies '' Gates began funding the implantable biotechnology back in 2011 via a small ( $ 100,000 ) grant to the Santa Cruz based company TransDerm Inc whose Linkedin page links to a website for the pharmaceutical giant Allergan .
Last month Reuters news service reported - falsely - that a popular Facebook post about Bill Gates planning to use microchip implants to fight the coronavirus pandemic was @ @ @ @ @ @ @ news service linked to the censored Facebook post .
Gates , whose father was the director of Planned Parenthood Federation of America and mother worked for PPFA 's funding affiliate United Way , has been noted for his population control ideology .
His wife , Melinda Gates , launched a Family Planning Summit on World Population Day in 2012 with the aim of garnering tax dollars from governments to expand reproductive health services aimed at lowering the global birth rate .
Difficult questions about vaccines are on BOTH sides of this huge debate @ @ @ @ @ @ @ and get the knowledge to make your own informed decision .
Do n't miss The Truth About Vaccines happening April 22-30 .

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
The microneedle technology is also being wed to injectable technology, funded by the Bill and Melinda Gates Foundation, which embeds under the skin a vaccination record visible by near infrared light that can be read by smartphone technology.
The Bill and Melinda Gates Foundation is funding the technologies with aims to enable them in "house-to-house" vaccine campaigns undertaken by people with "minimal training."
Researchers from the University of Pittsburgh reported in their study published April 1 in EBiomedicine, a Lancet Journal, that their microneedle patch vaccine against the SARS CoV-2 virus that causes COVID-19 "prompted robust antibody production in the mice within two weeks."
The patches resemble a spiky piece of Velcro, with hundreds of tiny microneedles made of sugar. The needles prick just into the skin and quickly dissolve, releasing the vaccine into the tiny abrasions and inducing a potent immune cell response despite the minute amount of the vaccine material - far more potent than an intramuscular injection.
The researchers had been testing vaccine using the microneedle patch for other coronaviruses, including the one that causes Middle East Respiratory System (MERS) and reported that three different experimental MERS vaccines induced the production of antibodies against the virus. These responses were stronger than the responses generated by regular injection of one of the vaccines along with a powerful immune stimulant (an adjuvant). Antibody levels continued to increase over time in mice vaccinated by microneedle patch-up to 55 weeks, when the experiments ended. The researchers have now turned their technology to the COVID-19 virus, SARS CoV-2.
"Testing in patients would typically require at least a year and probably longer," senior co-author of the study, dermatology professor Louis Falo said. "This particular situation is different from anything we've ever seen, so we don't know how long the clinical development process will take. Recently announced revisions to the normal processes suggest we may be able to advance this faster."
Another study funded by the Bill and Melinda Gates Foundation and published in December, 2019 by researchers from the Massachusetts Institute of Technology, the Institute of Chemistry of the Chinese Academy of Sciences in Beijing and the Global Good, Intellectual Ventures Laboratory in Bellevue, WA, describes how "near-infrared quantum dots" can be implanted under the skin along with a vaccine to encode information for "decentralized data storage and bio-sensing."
"To maximize the utility of this technology for vaccination campaigns, we aimed to create a platform compatible with microneedle-delivered vaccines that could reliably encode data on an individual for at least five years after administration," said the MIT paper, titled Biocompatible near-infrared quantum dots delivered to the skin by microneedle patches record vaccination. "In addition, this system also needed to be highly biocompatible, deliver a sufficient amount of dye after an application time of 2 min or less, and be detectable using a minimally adapted smartphone."
Fridrik Laurusson, an author of the microchip study, is from The Global Good, Intellectual Ventures Labarotory. Its website features Microsoft founder Bill Gates on its front page and describes itself as a "collaboration between Bill Gates and Intellectual Ventures" a company founded by Nathan Myhrvold and Edward Jung of Microsoft. Wikipedia describes Intellectual Ventures in Gates' home state as a private American company that "centers on the development and licensing of intellectual property" and "one of the top-five owners of U.S. patents, as of 2011.
"Its business model has a focus on buying patents and aggregating them into a large patent portfolio and licensing these patents to third parties," according to Wikipedia. The company has been described as the country's largest and most notorious patent trolling company, the ultimate patent troll, and the most hated company in tech.
The website of the Bill and Melinda Gates lists multiple grants awarded to develop the "microneedle array patch" - for use in "house-to-house campaigns via administration by minimally-trained personnel."
The most recent grant for $370,035 was awarded in February, 2020 to the Centers for Disease Control and Prevention for an MMR vaccine patch that does not require refrigeration and "enables house-to-house campaigns" via people without medical experience or training.
Bill Gates has awarded much larger grants for microneedle array patch technology to companies and organizations including:
* Vaxxas Pty Ltd in Brisbane, Queensland ($4.99 million in November, 2019) to develop a "microneedle array patch for measles and rubella vaccination that enables house-to-house campaigns via administration by minimally-trained personnel"
Vaxxas was created in 2011 after Mark Kendall's research group at the University of Queensland commercialized the nanotechnology under the company, UniQuest. The company has raised more than $35 million for the nanotechnology. It's partnered with vaccine manufacturer Merck - a company whose drug Vioxx caused more than 27,000 deaths by heart attack before the company revealed the risks it had hidden from the public. Merck has repeatedly been accused by judges for "egregious" ethical breaches and of "improper testing and data falsification" on its Gardasil HPV and MMR vaccines. Merck made
Micron Biomedical Inc ($6,744,906 in November, 2019) "to develop a microneedle array patch for measles and rubella vaccination that enables house-to-house campaigns via administration by minimally-trained personnel"
Georgia Institute of Technology ($958,849 in December, 2019) "to develop a microneedle array patch for measles and rubella vaccination that enables house-to-house campaigns via administration by minimally-trained personnel"
Vaxess Inc, ($2,967,741 in November, 2016) in Boston, MA "to support the preclinical development and manufacture of a thermostable microneedle patch with the aim of lowering barriers to vaccine access by simplifying dosing and administration, alleviating cold chain constraints, and lowering costs
Cardiff University ($$3,570,376 in December, 2019) "to develop a dissolvable microneedle array patch for the sustained dermal delivery of a progestin contraceptive, including the conduct of preclinical proof of concept studies"
Gates began funding the implantable biotechnology back in 2011 via a small ($100,000) grant to the Santa Cruz based company TransDerm Inc whose Linkedin page links to a website for the pharmaceutical giant Allergan.
Last month Reuters news service reported - falsely - that a popular Facebook post about Bill Gates planning to use microchip implants to fight the coronavirus pandemic was a "false claim." The news service linked to the censored Facebook post.
Gates, whose father was the director of Planned Parenthood Federation of America and mother worked for PPFA's funding affiliate United Way, has been noted for his population control ideology. His wife, Melinda Gates, launched a Family Planning Summit on World Population Day in 2012 with the aim of garnering tax dollars from governments to expand reproductive health services aimed at lowering the global birth rate.
Difficult questions about vaccines are on BOTH sides of this huge debate. Find out the pros and cons and get the knowledge to make your own informed decision. Don't miss The Truth About Vaccines happening April 22-30.


greenmedinfo--2020-04-16--Antiviral effect of epigallocatechin gallate via impairing porcine circovirus type 2 attachment to h

Antiviral effect of epigallocatechin gallate via impairing porcine circovirus type 2 attachment to host cell receptor.

The green tea catechin epigallocatechin gallate ( EGCG ) exhibits antiviral activity against various viruses .
Whether EGCG also inhibits the infectivity of circovirus remains unclear .
In this study , we demonstrated the antiviral effect of EGCG on porcine circovirus type 2 ( PCV2 ) .
EGCG targets PCV2 virions directly and blocks the attachment of virions to host cells .
The microscale thermophoresis assay showed EGCG could interact with PCV2 capsid protein in vitro with considerable affinity ( Kd = 98.03± 4.76 μM ) , thereby interfering with the binding of the capsid to the cell surface receptor @ @ @ @ @ @ @ of capsid-EGCG interaction identified the key amino acids which formed the binding pocket accommodating EGCG .
Amino acids ARG51 , ASP70 , ARG73 and ASP78 of capsid were found to be critical for maintaining the binding , and the arginine residues were also essential for the electrostatic interaction with heparan sulfate .
The rescued mutant viruses also confirm the importance of the key amino acids of the capsid to the antiviral effect of EGCG .
Our findings suggest that catechins could act as anti-infective agents against circovirus invasion , as well as provide @ @ @ @ @ @ @ synthesis of structure-based anti-circovirus drugs .

The green tea catechin epigallocatechin gallate (EGCG) exhibits antiviral activity against various viruses. Whether EGCG also inhibits the infectivity of circovirus remains unclear. In this study, we demonstrated the antiviral effect of EGCG on porcine circovirus type 2 (PCV2). EGCG targets PCV2 virions directly and blocks the attachment of virions to host cells. The microscale thermophoresis assay showed EGCG could interact with PCV2 capsid protein in vitro with considerable affinity (Kd = 98.03± 4.76 μM), thereby interfering with the binding of the capsid to the cell surface receptor heparan sulfate. The molecular docking analysis of capsid-EGCG interaction identified the key amino acids which formed the binding pocket accommodating EGCG. Amino acids ARG51, ASP70, ARG73 and ASP78 of capsid were found to be critical for maintaining the binding, and the arginine residues were also essential for the electrostatic interaction with heparan sulfate. The rescued mutant viruses also confirm the importance of the key amino acids of the capsid to the antiviral effect of EGCG. Our findings suggest that catechins could act as anti-infective agents against circovirus invasion, as well as provide the basic information for the development and synthesis of structure-based anti-circovirus drugs.


greenmedinfo--2020-04-16--Ginkgo biloba regulated innate immunity of human leukocytes by stimulating resistance and modulating

Ginkgo biloba regulated innate immunity of human leukocytes by stimulating resistance and modulating NF-κB activation.

Ginkgo biloba special extract EGb 761 and donepezil are drugs used in Alzheimer therapy .
The influence of donepezil and EGb 761 on two mechanisms of innate immunity , natural antiviral resistance of human leukocytes ex vivo and NF-κB activation , was studied .
Correlation between the innate immunity of leukocytes and NF-κB activation was investigated .
The effect of the two drugs on resistance of human leukocytes to vesicular stomatitis virus ( VSV ) infection was also assessed .
Two groups of healthy blood donors ( n=30 ) were distinguished : one with resistant leukocytes ( n=15 ) and @ @ @ @ @ @ @ to VSV .
The degree of natural resistance of human peripheral blood leukocytes ( PBLs ) was determined by studying the kinetics of VSV replication .
NF-κB activation was assayed by immunocytochemical staining .
Efficiency of donepezil and EGb 761 was determined by a special regression model .
The toxicity of the preparations to PBLs and the cell lines L ( 929 ) and A ( 549 ) and their effect on the different viruses was established .
Results showed that donepezil used in concentrations of 10-50 μg/ml and EGb761 of 25-100 μg/ml @ @ @ @ @ @ @ the same concentrations both preparations decreased activation of transcriptional factor NF-κB .
Correlation between innate immunity of PBLs and NF-κB activation was observed .
Comparison of the effects of these two drugs showed that EGb 761is more effective in stimulating leukocyte resistance .
Donepezil and EGb 761 regulated innate immunity of human leukocytes by stimulating resistance and modulating NF-κB activation .
The natural drug was more efficient in stimulating innate antiviral immunity of human leukocytes .

Ginkgo biloba special extract EGb 761 and donepezil are drugs used in Alzheimer therapy. The influence of donepezil and EGb 761 on two mechanisms of innate immunity, natural antiviral resistance of human leukocytes ex vivo and NF-κB activation, was studied. Correlation between the innate immunity of leukocytes and NF-κB activation was investigated. The effect of the two drugs on resistance of human leukocytes to vesicular stomatitis virus (VSV) infection was also assessed. Two groups of healthy blood donors (n=30) were distinguished: one with resistant leukocytes (n=15) and one (n=15) with leukocytes sensitive to VSV. The degree of natural resistance of human peripheral blood leukocytes (PBLs) was determined by studying the kinetics of VSV replication. NF-κB activation was assayed by immunocytochemical staining. Efficiency of donepezil and EGb 761 was determined by a special regression model. The toxicity of the preparations to PBLs and the cell lines L(929) and A(549) and their effect on the different viruses was established. Results showed that donepezil used in concentrations of 10-50 μg/ml and EGb761 of 25-100 μg/ml stimulated resistance of human leukocytes. At the same concentrations both preparations decreased activation of transcriptional factor NF-κB. Correlation between innate immunity of PBLs and NF-κB activation was observed. Comparison of the effects of these two drugs showed that EGb 761is more effective in stimulating leukocyte resistance. Donepezil and EGb 761 regulated innate immunity of human leukocytes by stimulating resistance and modulating NF-κB activation. The natural drug was more efficient in stimulating innate antiviral immunity of human leukocytes.


greenmedinfo--2020-04-16--Green tea extract and its major component epigallocatechin gallate inhibits hepatitis B virus in vit

Green tea extract and its major component epigallocatechin gallate inhibits hepatitis B virus in vitro.

Hepatitis B virus ( HBV ) infection is endemic in Asia and causes major public health problems worldwide .
Present treatment strategies for HBV infections are not satisfactory and the clinical limitation of current antiviral drugs for HBV , such as lamivudine , is causing rapid emergence of drug-resistant viral strains during the prolonged therapeutic treatment .
In this research , the efficacy of a natural green tea extract ( GTE ) against HBV in a stably expressed HBV cell line HepG2-N10 is examined .
The expression of viral antigens , HBsAg and HBeAg , were determined by using enzyme @ @ @ @ @ @ @ Quantitative real-time-PCR ( Q-PCR ) was used for the determination of extracellular HBV DNA and intracellular replicative intermediates and nuclear covalent closed circular DNA ( cccDNA ) .
HBV mRNAs were also analyzed by reverse transcription PCR ( RT-PCR ) .
Results showed that the 50 % effective concentration ( EC50 ) of GTE on HBsAg , HBeAg , extracellular HBV DNA and intracellular HBV DNA were 5.02 , 5.681 , 19.81 , and 10.76 microg/ml , respectively .
While the concentration of GTE with the inhibition percentage of 50 % on proliferating @ @ @ @ @ @ @ .
Similar analysis of the principal component of GTE , epigallocatechin gallate ( EGCG ) , revealed it has relative weaker efficacy compared to GTE .

Hepatitis B virus (HBV) infection is endemic in Asia and causes major public health problems worldwide. Present treatment strategies for HBV infections are not satisfactory and the clinical limitation of current antiviral drugs for HBV, such as lamivudine, is causing rapid emergence of drug-resistant viral strains during the prolonged therapeutic treatment. In this research, the efficacy of a natural green tea extract (GTE) against HBV in a stably expressed HBV cell line HepG2-N10 is examined. The expression of viral antigens, HBsAg and HBeAg, were determined by using enzyme linked immuno-absorbent assay (ELISA). Quantitative real-time-PCR (Q-PCR) was used for the determination of extracellular HBV DNA and intracellular replicative intermediates and nuclear covalent closed circular DNA (cccDNA). HBV mRNAs were also analyzed by reverse transcription PCR (RT-PCR). Results showed that the 50% effective concentration (EC50) of GTE on HBsAg, HBeAg, extracellular HBV DNA and intracellular HBV DNA were 5.02, 5.681, 19.81, and 10.76 microg/ml, respectively. While the concentration of GTE with the inhibition percentage of 50% on proliferating cells (CC50) was 171.8 microg/ml. Similar analysis of the principal component of GTE, epigallocatechin gallate (EGCG), revealed it has relative weaker efficacy compared to GTE.


greenmedinfo--2020-04-16--Antiviral activity of a nanoemulsion of polyprenols from Ginkgo leaves against influenza A H3N2 and

Antiviral activity of a nanoemulsion of polyprenols from Ginkgo leaves against influenza A H3N2 and hepatitis B virus in Vitro.

UNLABELLED : In order to improve the bioavailability levels of polyprenols ( derived from ginkgo leaves ( GBP ) ) in the human body , a GBP nanoemulsion was prepared , and its antiviral activity was evaluated against influenza A H3N2 and hepatitis B virus in vitro .
METHODS : A GBP nanoemulsion was prepared by inversed-phase emulsification ( IPE ) .
Next , we investigated the antiviral activity of the GBP nanoemulsion on influenza A H3N2 and hepatitis B virus in vitro by the MTT ( 3- ( 4,5-dimethylthiazol-2-yl ) -2,5-diphenlytetrezolium bromide ) method .
ELISA and the fluorescent @ @ @ @ @ @ @ the content of HBsAg , HBeAg and DNA virus in human samples .
RESULTS : The GBP nanoemulsion exhibited uniformity at an average particle size 97 nm with a hydrophilic-lipophilic balance ( HLB ) of 9.5 .
GBP is non-toxic to normal cells , hepatitis B virus DNA , hepatitis B virus antigen and HepG2215 .
Furthermore , GBP could reach a 70 % virucidal activity and a 74.9 % protection rate ( *** p < 0.001 ) on MDCK cells infected with H3N2 virus at a high concentration of 100μg/mL .
GBP @ @ @ @ @ @ @ ( 52.11 % , ** p < 0.01 ) at 50μg/mL and Day 9 of incubation , and a 67.32 % inhibition effect on HBeAg at a high concentration of 100 μg/mL and Day 9 .
GBP had good inhibition on HBV DNA with CT 18.6 and lower copies ( ** p < 0.01 ) at a middle concentration of 12.5 to 25μg/mL .
CONCLUSIONS : The GBP nanoemulsion was very stable and non-toxic and had very strong antiviral activity against influenza A H3N2 and hepatitis B virus in vitro .
The inhibitory @ @ @ @ @ @ @ the drug , 3TC ; by lengthening the incubation time and increasing the drug concentration , GBP has promising potential as an antiviral drug .

UNLABELLED: In order to improve the bioavailability levels of polyprenols (derived from ginkgo leaves (GBP)) in the human body, a GBP nanoemulsion was prepared, and its antiviral activity was evaluated against influenza A H3N2 and hepatitis B virus in vitro.
METHODS: A GBP nanoemulsion was prepared by inversed-phase emulsification (IPE). Next, we investigated the antiviral activity of the GBP nanoemulsion on influenza A H3N2 and hepatitis B virus in vitro by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenlytetrezolium bromide) method. ELISA and the fluorescent quantitative PCR method were used to measure the content of HBsAg, HBeAg and DNA virus in human samples.
RESULTS: The GBP nanoemulsion exhibited uniformity at an average particle size 97 nm with a hydrophilic-lipophilic balance (HLB) of 9.5. GBP is non-toxic to normal cells, hepatitis B virus DNA, hepatitis B virus antigen and HepG2215. Furthermore, GBP could reach a 70% virucidal activity and a 74.9% protection rate (*** p<0.001) on MDCK cells infected with H3N2 virus at a high concentration of 100μg/mL. GBP had a good inhibition rate on HBsAg (52.11%, ** p<0.01) at 50μg/mL and Day 9 of incubation, and a 67.32% inhibition effect on HBeAg at a high concentration of 100 μg/mL and Day 9. GBP had good inhibition on HBV DNA with CT 18.6 and lower copies (** p<0.01) at a middle concentration of 12.5 to 25μg/mL.
CONCLUSIONS: The GBP nanoemulsion was very stable and non-toxic and had very strong antiviral activity against influenza A H3N2 and hepatitis B virus in vitro. The inhibitory effects and reactive mechanisms were similar to the drug, 3TC; by lengthening the incubation time and increasing the drug concentration, GBP has promising potential as an antiviral drug.


greenmedinfo--2020-04-16--Berberine hampers Influenza A replication through inhibition of MAPK/ERK pathway.

BACKGROUND : Berberine ( BBR ) is an isoquinoline alkaloid which exhibits a variety of biological and therapeutic properties , and has been reported by some to block replication of the influenza virus .
However , contradictory results have also been presented , and the mechanistic explanation is lacking .
METHODS : A panel of cell lines ( Madin-Darby canine kidney ( MDCK ) , adenocarcinoma human alveolar basal epithelial cells ( A549 ) , lung epithelial type I ( LET1 ) ) and primary human airway epithelial cells ( HAE ) susceptible to influenza virus infection were infected with @ @ @ @ @ @ @ presence or absence of BBR .
Cytotoxicity towards cell lines was measured using XTT assay .
The yield of the virus was analyzed using RT-qPCR .
To study the molecular mechanism of BBR , confocal microscopy and Western blot analyses of cellular fractions were applied .
RESULTS AND CONCLUSIONS : Our results show cell-type-dependent anti-influenza properties of BBR in vitro which suggests that the compound acts on the cell and not the virus .
Importantly , BBR hampers influenza replication in primary human airway epithelium 3D cultures that mimic the natural replication site @ @ @ @ @ @ @ the influenza A virus upregulates the mitogen-activated protein kinase/extracellular signal-related kinase ( MAPK/ERK ) pathway and hijacks this pathway for nucleolar export of the viral ribonucleoprotein .
Our results suggest that BBR interferes with this process and hampers influenza A replication .

BACKGROUND: Berberine (BBR) is an isoquinoline alkaloid which exhibits a variety of biological and therapeutic properties, and has been reported by some to block replication of the influenza virus. However, contradictory results have also been presented, and the mechanistic explanation is lacking.
METHODS: A panel of cell lines (Madin-Darby canine kidney (MDCK), adenocarcinoma human alveolar basal epithelial cells (A549), lung epithelial type I (LET1)) and primary human airway epithelial cells (HAE) susceptible to influenza virus infection were infected with a seasonal influenza A virus in the presence or absence of BBR. Cytotoxicity towards cell lines was measured using XTT assay. The yield of the virus was analyzed using RT-qPCR. To study the molecular mechanism of BBR, confocal microscopy and Western blot analyses of cellular fractions were applied.
RESULTS AND CONCLUSIONS: Our results show cell-type-dependent anti-influenza properties of BBR in vitro which suggests that the compound acts on the cell and not the virus. Importantly, BBR hampers influenza replication in primary human airway epithelium 3D cultures that mimic the natural replication site of the virus. Studies show that the influenza A virus upregulates the mitogen-activated protein kinase/extracellular signal-related kinase (MAPK/ERK) pathway and hijacks this pathway for nucleolar export of the viral ribonucleoprotein. Our results suggest that BBR interferes with this process and hampers influenza A replication.


greenmedinfo--2020-04-16--Berberine suppresses influenza virus-triggered NLRP3 inflammasome activation in macrophages.

Berberine ( BBR ) is an isoquinoline alkaloid extracted from several commonly used Chinese herbs .
Our previous studies demonstrated BBR-mediated alleviation of lung injury due to inflammation and decrease in the mortality of mice with influenza viral pneumonia .
The recent argument of autophagy against inflammatory responses has aroused wide concerns .
This study focuses on the reactive oxygen species-Nod-like receptor protein 3 ( ROS-NLRP3 ) pathway to investigate whether BBR inhibits NLRP3 inflammasome activation by inducing mitophagy .
Our results demonstrate that BBR and mitochondrion-targeted superoxide dismutase mimetic ( Mito-TEMPO ; a specific mitochondrial ROS scavenger ) significantly @ @ @ @ @ @ @ membrane potential ( MMP ) , and decreased mitochondrial ROS ( mtROS ) generation in J774A.1 macrophages infected with PR8 influenza virus .
These observations suggest that the inhibitory effects of BBR on NLRP3 inflammasome activation were associated with the amelioration of mtROS generation .
BBR treatment induced regular mitophagy , as evident from the increase in microtubule-associated protein 1 light chain 3 II , decrease in p62 , colocalization of LC3 and mitochondria , and formation of autophagosomes .
However , 3-methyladenine , an autophagy inhibitor , reversed the inhibitory effects of @ @ @ @ @ @ @ activation in influenza virus-infected macrophages , indicating the involvement of mitophagy in mediating the inhibitory effects of BBR on NLRP3 inflammasome activation .
Furthermore , the knockdown of Bcl-2/adenovirus E18-19-kDa interacting protein 3 ( BNIP3 ) expression attenuated the effects of BBR on mitophagy induction to some extent , suggesting that the BBR-induced mitophagy may be , at least in part , mediated in a BNIP3-dependent manner .
Similar results were obtained in vivo using a mouse model of influenza viral pneumonia that was administered with BBR .
Taken together , these findings @ @ @ @ @ @ @ decreasing ROS generation through mitophagy induction may be crucial for the BBR-mediated alleviation of influenza virus-induced inflammatory lesions .

Berberine (BBR) is an isoquinoline alkaloid extracted from several commonly used Chinese herbs. Our previous studies demonstrated BBR-mediated alleviation of lung injury due to inflammation and decrease in the mortality of mice with influenza viral pneumonia. The recent argument of autophagy against inflammatory responses has aroused wide concerns. This study focuses on the reactive oxygen species-Nod-like receptor protein 3 (ROS-NLRP3) pathway to investigate whether BBR inhibits NLRP3 inflammasome activation by inducing mitophagy. Our results demonstrate that BBR and mitochondrion-targeted superoxide dismutase mimetic (Mito-TEMPO; a specific mitochondrial ROS scavenger) significantly restricted NLRP3 inflammasome activation, increased mitochondrial membrane potential (MMP), and decreased mitochondrial ROS (mtROS) generation in J774A.1 macrophages infected with PR8 influenza virus. These observations suggest that the inhibitory effects of BBR on NLRP3 inflammasome activation were associated with the amelioration of mtROS generation. BBR treatment induced regular mitophagy, as evident from the increase in microtubule-associated protein 1 light chain 3 II, decrease in p62, colocalization of LC3 and mitochondria, and formation of autophagosomes. However, 3-methyladenine, an autophagy inhibitor, reversed the inhibitory effects of BBR on mitochondrial damage and NLRP3 inflammasome activation in influenza virus-infected macrophages, indicating the involvement of mitophagy in mediating the inhibitory effects of BBR on NLRP3 inflammasome activation. Furthermore, the knockdown of Bcl-2/adenovirus E18-19-kDa interacting protein 3 (BNIP3) expression attenuated the effects of BBR on mitophagy induction to some extent, suggesting that the BBR-induced mitophagy may be, at least in part, mediated in a BNIP3-dependent manner. Similar results were obtained in vivo using a mouse model of influenza viral pneumonia that was administered with BBR. Taken together, these findings suggest that restricting NLRP3 inflammasome activation by decreasing ROS generation through mitophagy induction may be crucial for the BBR-mediated alleviation of influenza virus-induced inflammatory lesions.


greenmedinfo--2020-04-16--Antivirals against chikungunya virus: Is the solution in nature?

The worldwide outbreaks of the chikungunya virus ( CHIKV ) in the last years demonstrated the need for studies to @ @ @ @ @ The virus was first isolated in Tanzania in 1952 and was responsible for outbreaks in @ @ @ @ @ subsequent years .
Between 2007 and 2014 , some cases were documented in Europe and @ @ @ @ @ associated with low rates of death ; however , it can progress to a chronic @ @ @ @ @ in infected patients .
This infection is also associated with Guillain-Barré syndrome .
There is @ @ @ @ @ .
Treatment of infected patients is palliative and based on analgesics and non-steroidal anti-inflammatory drugs @ @ @ @ @ natural molecules have been described as antiviruses against viruses such as dengue , yellow fever @ @ @ @ @ influenza .
This review aims to summarize the natural compounds that have demonstrated antiviral activity @ @ @ @ @ .

The worldwide outbreaks of the chikungunya virus (CHIKV) in the last years demonstrated the need for studies to screen antivirals against CHIKV. The virus was first isolated in Tanzania in 1952 and was responsible for outbreaks in Africa and Southwest Asia in subsequent years. Between 2007 and 2014, some cases were documented in Europe and America. The infection is associated with low rates of death; however, it can progress to a chronic disease characterized by severe arthralgias in infected patients. This infection is also associated with Guillain-Barré syndrome. There is no specific antivirus against CHIKV. Treatment of infected patients is palliative and based on analgesics and non-steroidal anti-inflammatory drugs to reduce arthralgias. Several natural molecules have been described as antiviruses against viruses such as dengue, yellow fever,hepatitis C, and influenza. This review aims to summarize the natural compounds that have demonstrated antiviral activity against chikungunya virus in vitro.


greenmedinfo--2020-04-16--Hampering herpesviruses HHV-1 and HHV-2 infection by extract of Ginkgo biloba

Despite the availability of several anti-herpesviral agents , it should be emphasized that the need for new inhibitors is highly encouraged due to the increasing resistant viral strains as well as complications linked with periods of recurring viral replication and reactivation of latent herpes infection .
Extract of ( EGb ) is a common phytotherapeutics around the world with health benefits .
Limited studies , however , have addressed the potential antiviral activities of EGb , including herpesviruses such as ( HHV-1 ) and ( HHV-2 ) .
We evaluated the antiviral activity of EGb and its phytochemical constituents : @ @ @ @ @ @ @ .
Pretreatment of the herpesviruses with EGb prior to infection of cells produced a remarkable anti-HHV-1 and anti-HHV-2 activity .
The extract affected the viruses before adsorption to cell surface at non-cytotoxic concentrations .
In this work , through a comprehensive anti-HHV-1 and anti-HHV-2 activity study , it was revealed that flavonoids , especially isorhamnetin , are responsible for the antiviral activity of EGb .
Such activity was absent in quercetin and kaempferol .
However , EGb showed the most potent antiviral potency compared to isorhamnetin .
EGb could augment current therapies for @ @ @ @ @ @ @ , the potential use of EGb in multidrug therapy with synthetic anti-herpes compounds might be considered .

Despite the availability of several anti-herpesviral agents, it should be emphasized that the need for new inhibitors is highly encouraged due to the increasing resistant viral strains as well as complications linked with periods of recurring viral replication and reactivation of latent herpes infection. Extract of(EGb) is a common phytotherapeutics around the world with health benefits. Limited studies, however, have addressed the potential antiviral activities of EGb, including herpesviruses such as(HHV-1) and(HHV-2). We evaluated the antiviral activity of EGb and its phytochemical constituents: flavonoids and terpenes against HHV-1 and HHV-2. Pretreatment of the herpesviruses with EGb prior to infection of cells produced a remarkable anti-HHV-1 and anti-HHV-2 activity. The extract affected the viruses before adsorption to cell surface at non-cytotoxic concentrations. In this work, through a comprehensive anti-HHV-1 and anti-HHV-2 activity study, it was revealed that flavonoids, especially isorhamnetin, are responsible for the antiviral activity of EGb. Such activity was absent in quercetin and kaempferol. However, EGb showed the most potent antiviral potency compared to isorhamnetin. EGb could augment current therapies for herpes labialis and genital herpes. Moreover, the potential use of EGb in multidrug therapy with synthetic anti-herpes compounds might be considered.


greenmedinfo--2020-04-16--Curcumin may be a promising candidate for development as an anti-noroviral agent to prevent outbreak

Curcumin may be a promising candidate for development as an anti-noroviral agent to prevent outbreaks of foodborne illness.

Phytochemicals provide environmentally friendly and relatively inexpensive natural products , which could potentially benefit public health by controlling human norovirus ( HuNoV ) infection .
In this study , 18 different phytochemicals were evaluated for antiviral effects against norovirus using murine norovirus ( MNV ) as a model for norovirus biology .
Among these phytochemicals , curcumin ( CCM ) was the most potent anti-noroviral phytochemical , followed by resveratrol ( RVT ) .
In a cell culture infection model , exposure to CCM or RVT for 3 days reduced infectivity of norovirus by 91 % and 80 % , @ @ @ @ @ @ @ of CCM , we further evaluated its antiviral efficacy at various doses ( 0.25 , 0.5 , 0.75 , 1 , and 2 mg/mL ) and durations ( short-term : 10 , 30 , 60 , and 120 min ; long-term : 1 , 3 , 7 , and 14 days ) .
The anti-noroviral effect of CCM was verified to occur in a dose-dependent manner .
Additionally , we evaluated the inhibitory effect of each phytochemical on the replication of HuNoV using a HuNoV replicon-bearing cell line ( HG23 ) .
Neither @ @ @ @ @ @ @ effect on HuNoV replication , which suggests that their antiviral mechanism may involve viral entry or other life cycle stages rather than the replication of viral RNA .
Our results demonstrated that CCM may be a promising candidate for development as an anti-noroviral agent to prevent outbreaks of foodborne illness .

Phytochemicals provide environmentally friendly and relatively inexpensive natural products, which could potentially benefit public health by controlling human norovirus (HuNoV) infection. In this study, 18 different phytochemicals were evaluated for antiviral effects against norovirus using murine norovirus (MNV) as a model for norovirus biology. Among these phytochemicals, curcumin (CCM) was the most potent anti-noroviral phytochemical, followed by resveratrol (RVT). In a cell culture infection model, exposure to CCM or RVT for 3 days reduced infectivity of norovirus by 91% and 80%, respectively. To confirm the antiviral capability of CCM, we further evaluated its antiviral efficacy at various doses (0.25, 0.5, 0.75, 1, and 2 mg/mL) and durations (short-term: 10, 30, 60, and 120 min; long-term: 1, 3, 7, and 14 days). The anti-noroviral effect of CCM was verified to occur in a dose-dependent manner. Additionally, we evaluated the inhibitory effect of each phytochemical on the replication of HuNoV using a HuNoV replicon-bearing cell line (HG23). Neither CCM nor RVT had a strong inhibitory effect on HuNoV replication, which suggests that their antiviral mechanism may involve viral entry or other life cycle stages rather than the replication of viral RNA. Our results demonstrated that CCM may be a promising candidate for development as an anti-noroviral agent to prevent outbreaks of foodborne illness.