greenmedinfo--2020-03-26--Quercetin reverses docetaxel resistance in prostate cancer via androgen receptor and PI3K/Akt signal

Quercetin reverses docetaxel resistance in prostate cancer via androgen receptor and PI3K/Akt signaling pathways.

Docetaxel is the first-line chemotherapy agent for metastatic prostate cancer .
However , the emergence of resistance diminishes its efficacy and limits the survival benefit .
Quercetin is a dietary flavonoid which has been shown to have multiple anti-cancer effects .
Also , quercetin has been reported to reverse chemo-resistance in many other cancers .
This study was to determine whether quercetin could reverse docetaxel resistance in prostate cancer cells and xenograft models , thereby exploring the underlying mechanism .
Depending on the docetaxel-resistant cells ( LNCaP/R , PC-3/R ) which were established from docetaxel-sensitive cells ( LNCaP , PC-3 @ @ @ @ @ @ @ could reverse docetaxel resistance in prostate cancer on proliferation , colony formation , migration , invasion and apoptosis .
Although single docetaxel application had little effect on docetaxel-resistant cells , combining docetaxel with quercetin was significantly effective .
Combination therapy could maximally inhibited PI3K/Akt pathway and promoted apoptosis .
As shown bystudy , xenograft tumors treated by docetaxel with quercetin had poorest growth .
Then , to investigate the underlying mechanisms , the differences among parental cells , docetaxel-resistant subclones and quercetin treated resistant subclones were evaluated .
It was found that docetaxel-resistant @ @ @ @ @ @ @ and PI3K/Akt pathway , more remarkable mesenchymal and stem-like cell phenotypes , and more P-gp expression than that of parental cells .
Interestingly , quercetin could reverse these transformations .
Our data revealed that quercetin had docetaxel-resistance reversal effect bothandand provided in-depth support for clinical use of quercetin in docetaxel-resistant prostate cancer .

Docetaxel is the first-line chemotherapy agent for metastatic prostate cancer. However, the emergence of resistance diminishes its efficacy and limits the survival benefit. Quercetin is a dietary flavonoid which has been shown to have multiple anti-cancer effects. Also, quercetin has been reported to reverse chemo-resistance in many other cancers. This study was to determine whether quercetin could reverse docetaxel resistance in prostate cancer cells and xenograft models, thereby exploring the underlying mechanism. Depending on the docetaxel-resistant cells (LNCaP/R, PC-3/R) which were established from docetaxel-sensitive cells (LNCaP, PC-3), it was demonstrated that quercetin could reverse docetaxel resistance in prostate cancer on proliferation, colony formation, migration, invasion and apoptosis. Although single docetaxel application had little effect on docetaxel-resistant cells, combining docetaxel with quercetin was significantly effective. Combination therapy could maximally inhibited PI3K/Akt pathway and promoted apoptosis. As shown bystudy, xenograft tumors treated by docetaxel with quercetin had poorest growth. Then, to investigate the underlying mechanisms, the differences among parental cells, docetaxel-resistant subclones and quercetin treated resistant subclones were evaluated. It was found that docetaxel-resistant subclones had stronger activation of androgen receptor and PI3K/Akt pathway, more remarkable mesenchymal and stem-like cell phenotypes, and more P-gp expression than that of parental cells. Interestingly, quercetin could reverse these transformations. Our data revealed that quercetin had docetaxel-resistance reversal effect bothandand provided in-depth support for clinical use of quercetin in docetaxel-resistant prostate cancer.


greenmedinfo--2020-03-26--Quercetin and cancer: new insights into its therapeutic effects on ovarian cancer cells.

Ovarian cancer is known as a serious malignancy that affects women 's reproductive tract and can considerably threat their health .
A wide range of molecular mechanisms and genetic modifications have been involved in ovarian cancer pathogenesis making it difficult to develop effective therapeutic platforms .
Hence , discovery and developing new therapeutic approaches are required .
Medicinal plants , as a new source of drugs , could potentially be used alone or in combination with other medicines in the treatment of various cancers such as ovarian cancer .
Among various natural compounds , quercetin has shown great anti-cancer and @ @ @ @ @ @ @ vivo experiments have revealed that quercetin possesses a cytotoxic impact on ovarian cancer cells .
Despite obtaining good results both in vitro and in vivo , few clinical studies have assessed the anti-cancer effects of quercetin particularly in the ovarian cancer .
Therefore , it seems that further clinical studies may introduce quercetin as therapeutic agent alone or in combination with other chemotherapy drugs to the clinical setting .
Here , we not only summarize the anti-cancer effects of quercetin but also highlight the therapeutic effects of quercetin in the ovarian cancer .

Ovarian cancer is known as a serious malignancy that affects women's reproductive tract and can considerably threat their health. A wide range of molecular mechanisms and genetic modifications have been involved in ovarian cancer pathogenesis making it difficult to develop effective therapeutic platforms. Hence, discovery and developing new therapeutic approaches are required. Medicinal plants, as a new source of drugs, could potentially be used alone or in combination with other medicines in the treatment of various cancers such as ovarian cancer. Among various natural compounds, quercetin has shown great anti-cancer and anti-inflammatory properties. In vitro and in vivo experiments have revealed that quercetin possesses a cytotoxic impact on ovarian cancer cells. Despite obtaining good results both in vitro and in vivo, few clinical studies have assessed the anti-cancer effects of quercetin particularly in the ovarian cancer. Therefore, it seems that further clinical studies may introduce quercetin as therapeutic agent alone or in combination with other chemotherapy drugs to the clinical setting. Here, we not only summarize the anti-cancer effects of quercetin but also highlight the therapeutic effects of quercetin in the ovarian cancer.


greenmedinfo--2020-03-26--Anti-fibrosis activity of quercetin attenuates rabbit tracheal stenosis via the TGF-β/AKT/mTOR signa

Anti-fibrosis activity of quercetin attenuates rabbit tracheal stenosis via the TGF-β/AKT/mTOR signaling pathway.

AIMS : This study aimed to explore the possible mechanism of trauma-induced laryngotracheal stenosis and potential protective and therapeutic efficacy of quercetin on trauma-induced laryngotracheal stenosis .
MAIN METHODS : The expression and activity of fibrotic factors [ interleukin ( IL ) -6 , IL-8 , autophagy related 5 ( ATG5 ) , collagen ( COL ) -1 , tumor growth factor ( TGF ) -β COL-3 , microtubule-associated proteins 1A/1B light chain 3A ( LC3 ) , and vascular endothelial growth factor ( VEGF ) ] and fibrotic signaling mediators [ mammalian target of rapamycin ( mTOR ) and @ @ @ @ @ @ @ detected by real-time quantitative PCR ( qRT-PCR ) , ELISA , Western blot , and immunohistochemical staining , respectively , in the lipopolysaccharide ( LPS ) -induced WI-38 ( a human embryonic lung fibroblast cell line ) cellular fibrotic model and a trauma-induced rabbit tracheal stenosis model , with and without quercetin treatment .
KEY FINDINGS : Pre-treatment with quercetin significantly reversed the LPS-induced upregulation of pro-fibrotic factors ( IL-6 , IL-8 , COL-1 , COL-3 , LC3 ) and fibrotic signaling mediators ( mTOR and AKT ) , and it induced the @ @ @ @ @ @ @ .
Furthermore , the anti-fibrotic activity of quercetin was confirmed in the trauma-induced rabbit tracheal stenosis model .
Thus , the nasogastric administration of quercetin attenuated the tracheal stenosis of the rabbit tracheal stenosis model , in addition to effectively reversing an increase in pro-fibrotic factors ( VEGF , IL-6 , TGF-β , COL-1 , and COL-3 ) and fibrotic signaling mediators ( mTOR and AKT ) , as well as downregulating ATG5 of the rabbit tracheal stenosis model .
SIGNIFICANCE : Quercetin exhibits anti-fibrotic activity by inhibiting pro-fibrotic factors and AKT/mTOR signaling @ @ @ @ @ @ @ activity .
This study provided experimental evidence supporting the application of quercetin in tracheal stenosis , clinically .

AIMS: This study aimed to explore the possible mechanism of trauma-induced laryngotracheal stenosis and potential protective and therapeutic efficacy of quercetin on trauma-induced laryngotracheal stenosis.
MAIN METHODS: The expression and activity of fibrotic factors [interleukin (IL)-6, IL-8, autophagy related 5 (ATG5), collagen (COL)-1, tumor growth factor (TGF)-β COL-3, microtubule-associated proteins 1A/1B light chain 3A (LC3), and vascular endothelial growth factor (VEGF)] and fibrotic signaling mediators [mammalian target of rapamycin (mTOR) and phosphorylated AKT (pAKT)] were detected by real-time quantitative PCR (qRT-PCR), ELISA, Western blot, and immunohistochemical staining, respectively, in the lipopolysaccharide (LPS)-induced WI-38 (a human embryonic lung fibroblast cell line) cellular fibrotic model and a trauma-induced rabbit tracheal stenosis model, with and without quercetin treatment.
KEY FINDINGS: Pre-treatment with quercetin significantly reversed the LPS-induced upregulation of pro-fibrotic factors (IL-6, IL-8, COL-1, COL-3, LC3) and fibrotic signaling mediators (mTOR and AKT), and it induced the downregulation of ATG5 in the WI-38 cells. Furthermore, the anti-fibrotic activity of quercetin was confirmed in the trauma-induced rabbit tracheal stenosis model. Thus, the nasogastric administration of quercetin attenuated the tracheal stenosis of the rabbit tracheal stenosis model, in addition to effectively reversing an increase in pro-fibrotic factors (VEGF, IL-6, TGF-β, COL-1, and COL-3) and fibrotic signaling mediators (mTOR and AKT), as well as downregulating ATG5 of the rabbit tracheal stenosis model.
SIGNIFICANCE: Quercetin exhibits anti-fibrotic activity by inhibiting pro-fibrotic factors and AKT/mTOR signaling pathway, in addition to activating autophagy activity. This study provided experimental evidence supporting the application of quercetin in tracheal stenosis, clinically.


greenmedinfo--2020-03-26--Quercetin could be an important therapeutic agent for treatment of autism spectrum disorders.

Autism is a neuropathology characterized by behavioral disorders .
Considering that oxidative stress is involved in the pathophysiology of this disease , we evaluated the effects of quercetin , a flavonoid with antioxidant and neuroprotective properties , in an experimental model of autism induced by valproic acid ( VPA ) .
Twelve pregnant female rats were divided into four groups ( control , quercetin , VPA , VPA+quercetin ) .
Quercetin ( 50 mg/kg ) was administered orally to the animals from gestational days 6.5 to 18.5 , and VPA ( 800 mg/kg ) was administered orally in a single @ @ @ @ @ @ @ tests such as open field , social interaction , and tail flick nociceptive assays were performed on pups between 30 and 40 days old , after which the animals were euthanized .
Cerebral cortex , hippocampus , striatum , and cerebellum were collected for evaluation of oxidative stress parameters .
The pups exposed to VPA during the gestational period showed reduced weight gain , increased latency in the open field and tail flick tests , reduced time of social interaction , accompanied by changes in oxidative stress parameters mainly in the hippocampus and @ @ @ @ @ @ @ the behavioral changes and damage caused by oxidative stress , possibly due to its antioxidant action .
Our findings demonstrated that quercetin has neuroprotective effects in an animal model of autism , suggesting that this natural molecule could be an important therapeutic agent for treatment of autism spectrum disorders .

Autism is a neuropathology characterized by behavioral disorders. Considering that oxidative stress is involved in the pathophysiology of this disease, we evaluated the effects of quercetin, a flavonoid with antioxidant and neuroprotective properties, in an experimental model of autism induced by valproic acid (VPA). Twelve pregnant female rats were divided into four groups (control, quercetin, VPA, VPA+quercetin). Quercetin (50 mg/kg) was administered orally to the animals from gestational days 6.5 to 18.5, and VPA (800 mg/kg) was administered orally in a single dosage on gestational day 12.5. Behavioral tests such as open field, social interaction, and tail flick nociceptive assays were performed on pups between 30 and 40 days old, after which the animals were euthanized. Cerebral cortex, hippocampus, striatum, and cerebellum were collected for evaluation of oxidative stress parameters. The pups exposed to VPA during the gestational period showed reduced weight gain, increased latency in the open field and tail flick tests, reduced time of social interaction, accompanied by changes in oxidative stress parameters mainly in the hippocampus and striatum. Prenatal treatment with quercetin prevented the behavioral changes and damage caused by oxidative stress, possibly due to its antioxidant action. Our findings demonstrated that quercetin has neuroprotective effects in an animal model of autism, suggesting that this natural molecule could be an important therapeutic agent for treatment of autism spectrum disorders.


greenmedinfo--2020-03-26--Quercetin-loaded nanoparticles enhance cytotoxicity and antioxidant activity on C6 glioma cells.

Quercetin ( Qu ) is a natural flavonoid present in many commonly consumed food items .
The dietary phytochemical quercetin prevents tumor proliferation and is a potent therapeutic cancer agent .
The purpose of this study was to synthesize and characterize quercetin-loaded poly ( lactic-co-glycolic acid ) nanoparticles ( QuNP , QuNP , and QuNP ) with different size and encapsulation properties and to evaluate theiractivity on C6 glioma cells .
Nanoparticles were synthesized by single emulsion solvent evaporation method .
Then , particle size , zeta potential , polydispersity index and encapsulation efficiency of nanoparticles were determined .
Particle @ @ @ @ @ @ @ QuNPs were determined as 215.2 ± 6.2 , 282.3 ± 7.9 , and 584.5 ± 15.2 nm respectively .
Treating C6 glioma cells with all nanoparticle formulations effectively inhibited the cell proliferation .
QuNPs were showed the lowest ICvalue in 48 h with 29.9 μg/ml and achieved higher cellular uptake among other nanoparticles and Qu .
Additionally , 48-h treatment with QuNPs significantly decreased MDA level ( 14.90 nmol/µg protein ) on C6 glioma cells which is related to reduced oxidative stress in cells .
Findings of this study revealed that quercetin 's @ @ @ @ @ @ @ by small-sized QuNPs in C6 glioma cells .

Quercetin (Qu) is a natural flavonoid present in many commonly consumed food items. The dietary phytochemical quercetin prevents tumor proliferation and is a potent therapeutic cancer agent. The purpose of this study was to synthesize and characterize quercetin-loaded poly(lactic-co-glycolic acid) nanoparticles (QuNP, QuNP, and QuNP) with different size and encapsulation properties and to evaluate theiractivity on C6 glioma cells. Nanoparticles were synthesized by single emulsion solvent evaporation method. Then, particle size, zeta potential, polydispersity index and encapsulation efficiency of nanoparticles were determined. Particle size of QuNP, QuNP, and QuNPs were determined as 215.2 ± 6.2, 282.3 ± 7.9, and 584.5 ± 15.2 nm respectively. Treating C6 glioma cells with all nanoparticle formulations effectively inhibited the cell proliferation. QuNPs were showed the lowest ICvalue in 48 h with 29.9 μg/ml and achieved higher cellular uptake among other nanoparticles and Qu. Additionally, 48-h treatment with QuNPs significantly decreased MDA level (14.90 nmol/µg protein) on C6 glioma cells which is related to reduced oxidative stress in cells. Findings of this study revealed that quercetin's cellular uptake and anti-oxidant activity is improved by small-sized QuNPs in C6 glioma cells.


greenmedinfo--2020-03-26--Quercetin lipid nanoparticles functionalized with transferrin for Alzheimer's disease.

Quercetin was encapsulated in lipid nanoparticles ( SLN and NLC ) to take advantage of its neuroprotective properties in Alzheimer @ @ @ @ @ were functionalized with transferrin to facilitate the passage across the blood-brain barrier through the transferrin @ @ @ @ @ cells .
NMR and FTIR confirmed the functionalization of the nanoparticles with transferrin .
TEM @ @ @ @ @ spherical morphology .
Nanoparticles exhibited size around 200 nm and zeta potential values higher than @ @ @ @ @ efficiency was around 80-90 % .
LDH cytotoxicity assays in hCMEC/D3 cell line demonstrated that @ @ @ @ @ ( 30μM ) nanoparticles did not reveal cytotoxicity after 4 hours of incubation .
Permeability @ @ @ @ @ showed NLC permeate more the blood-brain barrier , while amyloid-beta studies demonstrated NLC-transferrin have the @ @ @ @ @ .
Nanoparticles seemto be suitable for brain applications , mainly for Alzheimer 's disease due @ @ @ @ @ .

Quercetin was encapsulated in lipid nanoparticles (SLN and NLC) to take advantage of its neuroprotective properties in Alzheimer's disease. The nanoparticles were functionalized with transferrin to facilitate the passage across the blood-brain barrier through the transferrin receptors overexpressed in brain endothelial cells. NMR and FTIR confirmed the functionalization of the nanoparticles with transferrin. TEM results showed all nanoparticles presented spherical morphology. Nanoparticles exhibited size around 200 nm and zeta potential values higher than -30 mV. Quercetin entrapment efficiency was around 80-90%. LDH cytotoxicity assays in hCMEC/D3 cell line demonstrated that even for the highest concentration (30μM) nanoparticles did not reveal cytotoxicity after 4 hours of incubation. Permeability studies across hCMEC/D3 cell monolayers showed NLC permeate more the blood-brain barrier, while amyloid-beta studies demonstrated NLC-transferrin have the capacity to inhibit fibril formation. Nanoparticles seemto be suitable for brain applications, mainly for Alzheimer's disease due to inhibition of amyloid-beta aggregation.


greenmedinfo--2020-03-26--Propolis affects Pseudomonas aeruginosa growth, biofilm formation, eDNA release and phenazine produc

Propolis affects Pseudomonas aeruginosa growth, biofilm formation, eDNA release and phenazine production.

( ) is an opportunistic pathogen responsible for a wide range of clinical conditions , from mild infections to life-threatening nosocomial biofilm-associated diseases , which are particularly severe in susceptible individuals .
The aim of thisstudy was to assess the effects of an Albanian propolis on several virulence-related factors of , such as growth ability , biofilm formation , extracellular DNA ( eDNA ) release and phenazine production .
To this end , propolis was processed using three different solvents and the extracted polyphenolic compounds were identified by means of high performance liquid chromatography coupled to electrospray ionization mass spectrometry @ @ @ @ @ @ @ by a bioluminescence-based assay , among the three propolis extracts , the ethanol ( EtOH ) extract was the most effective in inhibiting both microbial growth and biofilm formation , followed by propylene glycol ( PG ) and polyethylene glycol 400 ( PEG 400 ) propolis extracts .
Furthermore , exposure to propolis EtOH extract caused a decrease in eDNA release and phenazine production .
Finally , caffeic acid phenethyl ester ( CAPE ) and quercetin decreased upon propolis EtOH extract exposure to bacteria .
Overall , our data add new insights on @ @ @ @ @ @ @ , such as propolis against .
The potential implications of these findings will be discussed .

() is an opportunistic pathogen responsible for a wide range of clinical conditions, from mild infections to life-threatening nosocomial biofilm-associated diseases, which are particularly severe in susceptible individuals. The aim of thisstudy was to assess the effects of an Albanian propolis on several virulence-related factors of, such as growth ability, biofilm formation, extracellular DNA (eDNA) release and phenazine production. To this end, propolis was processed using three different solvents and the extracted polyphenolic compounds were identified by means of high performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC-ESI-MS) analysis. As assessed by a bioluminescence-based assay, among the three propolis extracts, the ethanol (EtOH) extract was the most effective in inhibiting both microbial growth and biofilm formation, followed by propylene glycol (PG) and polyethylene glycol 400 (PEG 400) propolis extracts. Furthermore,exposure to propolis EtOH extract caused a decrease in eDNA release and phenazine production. Finally, caffeic acid phenethyl ester (CAPE) and quercetin decreased upon propolis EtOH extract exposure to bacteria. Overall, our data add new insights on the anti-microbial properties of a natural compound, such as propolis against. The potential implications of these findings will be discussed.


greenmedinfo--2020-03-26--Caffeic acid phenethyl ester has a preventive effect on early brain injury after subarachnoid hemorr

Caffeic acid phenethyl ester has a preventive effect on early brain injury after subarachnoid hemorrhage.

AIM : CAPE , a phenolic compound , besides being one of the biologically active components of propolis , is a compound with antioxidant , antiinflammatory , antiviral , reperfusion damage prevention , immune stimulant and carcinostatic , anticancer properties .
The aim of this study was to investigate the possible effects of CAPE on cerebral vasospasm and early brain injury , which were experimentally administered intraperitoneally in rats with subarachnoid hemorrhage .
MATERIAL AND METHODS : 32 Wistar Albino rats weighing 200-300 grams were used in our study .
The rats divided into three groups namely as Control group @ @ @ @ @ @ @ hemorrhage group ( n = 11 ) and subarachnoid hemorrhage + CAPE group ( n = 11 ) were evaluated according to the Ischemia index in hippocampal CA3 regions and the morphometric analysis of basilar artery diameter after being sacrified at the end of 72th hour .
RESULTS : A significant difference was found between group-1 and group-2 for the CA-3 region , it was concluded that early brain damage occurred after subarachnoid hemorrhage .
When the neuronal damage in CA-3 region was evaluated between group-2 and group-3 , a statistically significant difference @ @ @ @ @ @ @ was a statistically significant difference between group-1 and group-3 in terms of ischemia detection .
CONCLUSION : It was shown that CAPE has a preventive effect on early brain injury after SAH and has a positive effect on reducing cerebral vasospasm .
Our study is the first study in the literature showing that CAPE inhibits ischemic brain injury following SAH .

AIM: CAPE, a phenolic compound, besides being one of the biologically active components of propolis, is a compound with antioxidant, antiinflammatory, antiviral, reperfusion damage prevention, immune stimulant and carcinostatic, anticancer properties. The aim of this study was to investigate the possible effects of CAPE on cerebral vasospasm and early brain injury, which were experimentally administered intraperitoneally in rats with subarachnoid hemorrhage.
MATERIAL AND METHODS: 32 Wistar Albino rats weighing 200-300 grams were used in our study. The rats divided into three groups namely as Control group (n = 10), subarachnoid hemorrhage group (n = 11) and subarachnoid hemorrhage + CAPE group (n = 11) were evaluated according to the Ischemia index in hippocampal CA3 regions and the morphometric analysis of basilar artery diameter after being sacrified at the end of 72th hour.
RESULTS: A significant difference was found between group-1 and group-2 for the CA-3 region, it was concluded that early brain damage occurred after subarachnoid hemorrhage. When the neuronal damage in CA-3 region was evaluated between group-2 and group-3, a statistically significant difference was found between the groups. There was a statistically significant difference between group-1 and group-3 in terms of ischemia detection.
CONCLUSION: It was shown that CAPE has a preventive effect on early brain injury after SAH and has a positive effect on reducing cerebral vasospasm. Our study is the first study in the literature showing that CAPE inhibits ischemic brain injury following SAH.


greenmedinfo--2020-03-26--Effects of propolis and phenolic acids on triple-negative breast cancer cell lines.

Triple-negative breast cancer is an aggressive disease frequently associated with resistance to chemotherapy .
Evidence supports that small molecules showing DNA methyltransferase inhibitory activity ( DNMTi ) are important to sensitize cancer cells to cytotoxic agents , in part , by reverting the acquired epigenetic changes associated with the resistance to therapy .
The present study aimed to evaluate if chemical compounds derived from propolis could act as epigenetic drugs ( epi-drugs ) .
We selected three phenolic acids ( caffeic , dihydrocinnamic , and-coumaric ) commonly detected in propolis and the ( - ) -epigallocatechin-3-gallate ( EGCG ) from @ @ @ @ @ @ @ DNA demethylating agent , for further analysis .
The treatment with-coumaric acid and EGCG significantly reduced the cell viability of four triple-negative breast cancer cell lines ( BT-20 , BT-549 , MDA-MB-231 , and MDA-MB-436 ) .
Computational predictions by molecular docking indicated that both chemicals could interact with the MTAse domain of the human DNMT1 and directly compete with its intrinsic inhibitor-Adenosyl-l-homocysteine ( SAH ) .
Although the ethanolic extract of propolis ( EEP ) did not change the global DNA methylation content , by using MS-PCR ( Methylation-Specific Polymerase Chain Reaction @ @ @ @ @ @ @ were able to partly demethylate the promoter region ofin BT-549 cells .
Also , in vitro treatment with EEP altered the RASSF1 protein expression levels .
Our data indicated that some chemical compound present in the EEP has DNMTi activity and can revert the epigenetic silencing of the tumor suppressorThese findings suggest that propolis are a promising source for epi-drugs discovery .

Triple-negative breast cancer is an aggressive disease frequently associated with resistance to chemotherapy. Evidence supports that small molecules showing DNA methyltransferase inhibitory activity (DNMTi) are important to sensitize cancer cells to cytotoxic agents, in part, by reverting the acquired epigenetic changes associated with the resistance to therapy. The present study aimed to evaluate if chemical compounds derived from propolis could act as epigenetic drugs (epi-drugs). We selected three phenolic acids (caffeic, dihydrocinnamic, and-coumaric) commonly detected in propolis and the (-)-epigallocatechin-3-gallate (EGCG) from green tea, which is a well-known DNA demethylating agent, for further analysis. The treatment with-coumaric acid and EGCG significantly reduced the cell viability of four triple-negative breast cancer cell lines (BT-20, BT-549, MDA-MB-231, and MDA-MB-436). Computational predictions by molecular docking indicated that both chemicals could interact with the MTAse domain of the human DNMT1 and directly compete with its intrinsic inhibitor-Adenosyl-l-homocysteine (SAH). Although the ethanolic extract of propolis (EEP) did not change the global DNA methylation content, by using MS-PCR (Methylation-Specific Polymerase Chain Reaction) we demonstrated that EEP and EGCG were able to partly demethylate the promoter region ofin BT-549 cells. Also, in vitro treatment with EEP altered the RASSF1 protein expression levels. Our data indicated that some chemical compound present in the EEP has DNMTi activity and can revert the epigenetic silencing of the tumor suppressorThese findings suggest that propolis are a promising source for epi-drugs discovery.


greenmedinfo--2020-03-26--Propolis could be a chemopreventive agent against MNU-induced mammary carcinogenesis.

Currently , one of the central problems in cancer management is the relapse of disease following conventional treatments , yet few therapeutic agents targeting resistance and tolerance exist .
Propolis is known as a healing agent since ancient times .
Therefore , over time , its curative properties have kept the interest of scientists , thus leading permanently to investigations of its other possible undiscovered effects .
In this context , current experiments were performed to establish the chemopreventive potential of propolis extract ( PE ) ( 1.05 mg/kg BW/day ) in N-methyl-N-nitrosourea- ( MNU- ) induced rat mammary tumors @ @ @ @ @ @ @ physical attributes compared with control rats MNU-inoculated .
The number of developed tumors ( mean 49 % versus 100 % ) , incidence ( mean 49 % versus 100 % ) , multiplicity ( 1.8 versus 3.7 ( < 0.001 ) ) , tumor volume ( mean 10 cmversus 16 cm ( < 0.001 ) ) , and weight of the tumor mass ( mean 7.42 g versus 9.00 g ( < 0.05 ) ) were noted .
The numbers of grade I tumors recorded for MNU-inoculated rats were 24 ( Group 1 @ @ @ @ @ @ @ for MNU-induced/PE-treated rats .
In the serum of rats MNU-inoculated/PE-treated were found higher levels of antioxidative enzymes ( SOD , CAT , and GPx ) than in MNU-induced .
Taken together , these data indicate that propolis could be a chemopreventive agent against MNU-induced mammary carcinogenesis .

Currently, one of the central problems in cancer management is the relapse of disease following conventional treatments, yet few therapeutic agents targeting resistance and tolerance exist. Propolis is known as a healing agent since ancient times. Therefore, over time, its curative properties have kept the interest of scientists, thus leading permanently to investigations of its other possible undiscovered effects. In this context, current experiments were performed to establish the chemopreventive potential of propolis extract (PE) (1.05 mg/kg BW/day) in N-methyl-N-nitrosourea- (MNU-) induced rat mammary tumors. MNU-inoculated/PE-treated rats had tumors of different physical attributes compared with control rats MNU-inoculated. The number of developed tumors (mean 49% versus 100%), incidence (mean 49% versus 100%), multiplicity (1.8 versus 3.7 (<0.001)), tumor volume (mean 10 cmversus 16 cm(<0.001)), and weight of the tumor mass (mean 7.42 g versus 9.00 g (<0.05)) were noted. The numbers of grade I tumors recorded for MNU-inoculated rats were 24 (Group 1) and 7 (Group 2) for MNU-induced/PE-treated rats. In the serum of rats MNU-inoculated/PE-treated were found higher levels of antioxidative enzymes (SOD, CAT, and GPx) than in MNU-induced. Taken together, these data indicate that propolis could be a chemopreventive agent against MNU-induced mammary carcinogenesis.


greenmedinfo--2020-03-26--Propolis and honey trigona decrease leptin levels of central obesity patients.

OBJECTIVE : This study aimed to examine whether honey and propolis Trigona can reduce the level of leptin in central @ @ @ @ @ It was a quasi-experimental study , population and sample were central obesity and normal weight @ @ @ @ @ was 30 participants taken using purposive sampling .
RESULTS : Intervention as long as 14 @ @ @ @ @ of leptin as many as 97.076pg/ml in control group and decreasing respectively 171.803pg/ml and 245.293pg/ml @ @ @ @ @ group , both significant statistically .
The dose of honey given was 105mg/days divided into @ @ @ @ @ pack contains 35mg .
The dose of propolis was 60mg/days and divided into 3 capsules @ @ @ @ @ 20mg .
Intervention as long as 14 days and leptin levels examined using human ELISA @ @ @ @ @ is before intervention , 7 days after the intervention and 14 days after intervention .
@ @ @ @ @ Trigona has the ability to decrease leptin level of central obesity participants .
These honey @ @ @ @ @ be a dietary supplement for central obesity patients .

OBJECTIVE: This study aimed to examine whether honey and propolis Trigona can reduce the level of leptin in central obesity human.
METHODS: It was a quasi-experimental study, population and sample were central obesity and normal weight as control. Sample size was 30 participants taken using purposive sampling.
RESULTS: Intervention as long as 14 days make an increased level of leptin as many as 97.076pg/ml in control group and decreasing respectively 171.803pg/ml and 245.293pg/ml in honey and propolis intervention group, both significant statistically. The dose of honey given was 105mg/days divided into 3 packs, and each pack contains 35mg. The dose of propolis was 60mg/days and divided into 3 capsules, each of it contains 20mg. Intervention as long as 14 days and leptin levels examined using human ELISA Kit three times, that is before intervention, 7 days after the intervention and 14 days after intervention.
CONCLUSION: Honey and propolis Trigona has the ability to decrease leptin level of central obesity participants. These honey bee products are potential to be a dietary supplement for central obesity patients.


greenmedinfo--2020-03-26--hese findings suggest that the potent anti-inflammatory activity of T. officinale, possibly through

hese findings suggest that the potent anti-inflammatory activity of T. officinale, possibly through the regulation of Nrf2/HO-1 and NF-κB signaling pathway.

As a long-established medicinal and edible homologous plant , Wigg .
is widely distributed in Asia , Europe , and @ @ @ @ @ reported to exert a variety of biological and pharmacological activities , including anticancer , hepatoprotective @ @ @ @ @ In this study , we evaluated the anti-inflammatory effects of ethanol extracts of ( A-TOW @ @ @ @ @ of proinflammatory mediators in LPS-stimulated BV2 and mouse hippocampus .
Furthermore , A-TOW also inhibited @ @ @ @ @ factorB p65 caused by stimulation with LPS .
In addition , A-TOW regulates heme oxygenase @ @ @ @ @ through the nuclear translocation of nuclear factor E2-related factor 2 ( Nrf2 ) in BV2 @ @ @ @ @ A-TOW on the over-expression of proinflammatory mediators were partially reversed by transfection of the cells @ @ @ @ @ findings suggest that the potent anti-inflammatory activity of , possibly through the regulation of Nrf2/HO-1 @ @ @ @ @

As a long-established medicinal and edible homologous plant,Wigg. is widely distributed in Asia, Europe, and other parts of the world.is reported to exert a variety of biological and pharmacological activities, including anticancer, hepatoprotective, and anti-obesity effects. In this study, we evaluated the anti-inflammatory effects of ethanol extracts of(A-TOW) by examining the suppression of proinflammatory mediators in LPS-stimulated BV2 and mouse hippocampus. Furthermore, A-TOW also inhibited the nuclear translocation of nuclear factorB p65 caused by stimulation with LPS. In addition, A-TOW regulates heme oxygenase (HO)-1 expression through the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in BV2 cells. The effects of A-TOW on the over-expression of proinflammatory mediators were partially reversed by transfection of the cells with HO-1 siRNA. These findings suggest that the potent anti-inflammatory activity of, possibly through the regulation of Nrf2/HO-1 and NF-B signaling pathway.


greenmedinfo--2020-03-26--Janus kinase 2 inhibition by Licochalcone B suppresses esophageal squamous cell carcinoma growth.

Esophageal cancer ( EC ) is one of the leading causes to cancer death in the worldwide and major population of EC is esophageal squamous cell carcinoma ( ESCC ) .
Still , ESCC-targeted therapy has not been covered yet .
In the present study we have identified that Licochalcone B ( Lico B ) inhibited the ESCC growth by directly blocking the Janus kinase ( JAK ) 2 activity and its downstream signaling pathway .
Lico B suppressed KYSE450 and KYSE510 ESCC cell growth , arrested cell cycle at G2/M phase and induced apoptosis .
Direct target of Lico @ @ @ @ @ @ @ verified with in vitro and ex vivo binding .
Computational docking model predicted for Lico B interaction to ATP-binding pocket of JAK2 .
Furthermore , treatment of JAK2 clinical medicine AZD1480 to ESCC cells showed similar tendency with Lico B .
Thus , JAK2 downstream signaling proteins phosphorylation of STAT3 at Y705 and S727 as well as STAT3 target protein Mcl-1 expression was decreased with treatment of Lico B .
Our results suggest that Lico B inhibits ESCC cell growth , arrests cell cycle and induces apoptosis , revealing the underlying mechanism involved @ @ @ @ @ @ @ treatment .
It might provide potential role of Lico B in the treatment of ESCC .

Esophageal cancer (EC) is one of the leading causes to cancer death in the worldwide and major population of EC is esophageal squamous cell carcinoma (ESCC). Still, ESCC-targeted therapy has not been covered yet. In the present study we have identified that Licochalcone B (Lico B) inhibited the ESCC growth by directly blocking the Janus kinase (JAK) 2 activity and its downstream signaling pathway. Lico B suppressed KYSE450 and KYSE510 ESCC cell growth, arrested cell cycle at G2/M phase and induced apoptosis. Direct target of Lico B was identified by kinase assay and verified with in vitro and ex vivo binding. Computational docking model predicted for Lico B interaction to ATP-binding pocket of JAK2. Furthermore, treatment of JAK2 clinical medicine AZD1480 to ESCC cells showed similar tendency with Lico B. Thus, JAK2 downstream signaling proteins phosphorylation of STAT3 at Y705 and S727 as well as STAT3 target protein Mcl-1 expression was decreased with treatment of Lico B. Our results suggest that Lico B inhibits ESCC cell growth, arrests cell cycle and induces apoptosis, revealing the underlying mechanism involved in JAK2/STAT3 signaling pathways after Lico B treatment. It might provide potential role of Lico B in the treatment of ESCC.


greenmedinfo--2020-03-26--Licochalcone D induces ROS-dependent apoptosis in gefitinib-sensitive or resistant lung cancer cells

Licochalcone D induces ROS-dependent apoptosis in gefitinib-sensitive or resistant lung cancer cells.

Licochalcone D ( LCD ) , a flavonoid isolated from a Chinese medicinal plant , has a variety of pharmacological activities .
However , the anti-cancer effects of LCD on non-small cell lung cancer ( NSCLC ) have not been investigated yet .
The amplification of ( hepatocyte growth factor receptor ) compensates for the inhibition of epidermal growth factor receptor ( EGFR ) activity due to tyrosine kinase inhibitor ( TKI ) , leading to TKI resistance .
Therefore , EGFR and MET can be attractive targets for lung cancer .
We investigated the anti-proliferative and apoptotic effects of @ @ @ @ @ @ @ gefitinib-sensitive ) and HCC827GR ( gefitinib-resistant ) through 3- ( 4,5-dimethylthiazol-2-yl ) -2,5-diphenyltetrazolium bromide ( MTT ) assay , pull-down/kinase assay , cell cycle analysis , Annexin-V/7-ADD staining , reactive oxygen species ( ROS ) assay , mitochondrial membrane potential ( MMP ) assay , multi-caspase assay , and Western blot analysis .
The results showed that LCD inhibited phosphorylation and the kinase activity of EGFR and MET .
In addition , the predicted pose of LCD was competitively located at the ATP binding site .
LCD suppressed lung cancer cells growth by @ @ @ @ @ @ @ transition and inducing apoptosis .
LCD also induced caspases activation and poly ( ADP-ribose ) polymerase ( PARP ) cleavage , thus displaying features of apoptotic signals .
These results provide evidence that LCD has anti-tumor effects by inhibiting EGFR and MET activities and inducing ROS-dependent apoptosis in NSCLC , suggesting that LCD has the potential to treat lung cancer .

Licochalcone D (LCD), a flavonoid isolated from a Chinese medicinal plant, has a variety of pharmacological activities. However, the anti-cancer effects of LCD on non-small cell lung cancer (NSCLC) have not been investigated yet. The amplification of(hepatocyte growth factor receptor) compensates for the inhibition of epidermal growth factor receptor (EGFR) activity due to tyrosine kinase inhibitor (TKI), leading to TKI resistance. Therefore, EGFR and MET can be attractive targets for lung cancer. We investigated the anti-proliferative and apoptotic effects of LCD in lung cancer cells HCC827 (gefitinib-sensitive) and HCC827GR (gefitinib-resistant) through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, pull-down/kinase assay, cell cycle analysis, Annexin-V/7-ADD staining, reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) assay, multi-caspase assay, and Western blot analysis. The results showed that LCD inhibited phosphorylation and the kinase activity of EGFR and MET. In addition, the predicted pose of LCD was competitively located at the ATP binding site. LCD suppressed lung cancer cells growth by blocking cell cycle progression at the G2/M transition and inducing apoptosis. LCD also induced caspases activation and poly (ADP-ribose) polymerase (PARP) cleavage, thus displaying features of apoptotic signals. These results provide evidence that LCD has anti-tumor effects by inhibiting EGFR and MET activities and inducing ROS-dependent apoptosis in NSCLC, suggesting that LCD has the potential to treat lung cancer.


greenmedinfo--2020-04-16--The role of gut microbiota in the regulation of the immune response.

The gastrointestinal tract hosts around 10 ( 14 ) bacterial microorganisms , in a constantly growing density from the stomach to the distal colon .
This microbiota is composed by more than 500 species of bacteria , which are quickly acquired after birth , fairly stable during the hosts life , and essential for human homeostasis .
These bacteria have important functions , such as stimulating the immune system , protecting the host from invading bacteria and viruses , and improving digestion , especially of complex carbohydrates .
Also , the gut microbiota interacts directly with the immune system .
@ @ @ @ @ @ @ epithelium and its microbiota with the immune system has yet to be fully understood .
Secretory immunoglobulin A , produced by the plasma cells in Peyers patches and in the lamina propria , maintains non-invasive commensal bacteria and neutralize invasive pathogens .
Dendritic cells migrate from the lamina propria of the secondary lymphoid organs to regulate gut immunity .
They also have a key role maintaining luminal IgA and inducing the growth of regulatory T cells .
Dendritic cells supervise the gut microenvironment too , keeping an immunological equilibrium and tolerance .
The @ @ @ @ @ @ @ the immune system lies mostly in the homeostasis-or positive equilibrium .
Thus , many diseases are a consequence of poor interactions or a loss of this equilibrium .

The gastrointestinal tract hosts around 10(14) bacterial microorganisms, in a constantly growing density from the stomach to the distal colon. This microbiota is composed by more than 500 species of bacteria, which are quickly acquired after birth, fairly stable during the hosts life, and essential for human homeostasis. These bacteria have important functions, such as stimulating the immune system, protecting the host from invading bacteria and viruses, and improving digestion, especially of complex carbohydrates. Also, the gut microbiota interacts directly with the immune system. However, the interaction of the intestinal epithelium and its microbiota with the immune system has yet to be fully understood. Secretory immunoglobulin A, produced by the plasma cells in Peyers patches and in the lamina propria, maintains non-invasive commensal bacteria and neutralize invasive pathogens. Dendritic cells migrate from the lamina propria of the secondary lymphoid organs to regulate gut immunity. They also have a key role maintaining luminal IgA and inducing the growth of regulatory T cells. Dendritic cells supervise the gut microenvironment too, keeping an immunological equilibrium and tolerance. The importance of the gut microbiota in regulating the immune system lies mostly in the homeostasis-or positive equilibrium. Thus, many diseases are a consequence of poor interactions or a loss of this equilibrium.


greenmedinfo--2020-04-16--Lactobacillus rhamnosus Lcr35 as an effective treatment for preventing Candida albicans infection.

The increased recurrence of Candida albicans infections is associated with greater resistance to antifungal drugs .
This involves the establishment of alternative therapeutic protocols , such as probiotic microorganisms whose antifungal potential has already been demonstrated using preclinical models ( cell cultures , laboratory animals ) .
Understanding the mechanisms of action of probiotic microorganisms has become a strategic need for the development of new therapeutics for humans .
In this study , we investigated the prophylactic anti-C. albicans properties of Lactobacillus rhamnosus Lcr35® using the in vitro Caco-2 cell model and the in vivo Caenorhabditis elegans model .
In @ @ @ @ @ @ @ strain Lcr35® significantly inhibited the growth ( ~2 log CFU.mL-1 ) and adhesion ( 150 to 6,300 times less ) of the pathogen .
Moreover , in addition to having a pro-longevity activity in the nematode ( +42.9 % , p = 3.56.10-6 ) , Lcr35® protects the animal from the fungal infection ( +267 % of survival , p < 2.10-16 ) even if the yeast is still detectable in its intestine .
At the mechanistic level , we noticed the repression of genes of the p38 MAPK signalling pathway and genes @ @ @ @ @ @ @ Lcr35® , suggesting that the pathogen no longer appears to be detected by the worm immune system .
However , the DAF-16/FOXO transcription factor , implicated in the longevity and antipathogenic response of C. elegans , is activated by Lcr35® .
These results suggest that the probiotic strain acts by stimulating its host via DAF-16 but also by suppressing the virulence of the pathogen .

The increased recurrence of Candida albicans infections is associated with greater resistance to antifungal drugs. This involves the establishment of alternative therapeutic protocols, such as probiotic microorganisms whose antifungal potential has already been demonstrated using preclinical models (cell cultures, laboratory animals). Understanding the mechanisms of action of probiotic microorganisms has become a strategic need for the development of new therapeutics for humans. In this study, we investigated the prophylactic anti-C. albicans properties of Lactobacillus rhamnosus Lcr35® using the in vitro Caco-2 cell model and the in vivo Caenorhabditis elegans model. In Caco-2 cells, we showed that the strain Lcr35® significantly inhibited the growth (~2 log CFU.mL-1) and adhesion (150 to 6,300 times less) of the pathogen. Moreover, in addition to having a pro-longevity activity in the nematode (+42.9%, p = 3.56.10-6), Lcr35® protects the animal from the fungal infection (+267% of survival, p<2.10-16) even if the yeast is still detectable in its intestine. At the mechanistic level, we noticed the repression of genes of the p38 MAPK signalling pathway and genes involved in the antifungal response induced by Lcr35®, suggesting that the pathogen no longer appears to be detected by the worm immune system. However, the DAF-16/FOXO transcription factor, implicated in the longevity and antipathogenic response of C. elegans, is activated by Lcr35®. These results suggest that the probiotic strain acts by stimulating its host via DAF-16 but also by suppressing the virulence of the pathogen.


greenmedinfo--2020-04-16--Immunomodulatory properties of Lactobacillus plantarum NC8 expressing an anti-CD11c single-chain Fv

Immunomodulatory properties of Lactobacillus plantarum NC8 expressing an anti-CD11c single-chain Fv fragment.

The lactic acid bacteria species ( ) has been used extensively for vaccine delivery .
Considering to the critical role of dendritic cells in stimulating host immune response , in this study , we constructed a novel CD11c-targetingstrain with surface-displayed variable fragments of anti-CD11c , single-chain antibody ( scFv-CD11c ) .
The newly designedstrain , named 409-aCD11c , could adhere and invade more efficiently to bone marrow-derived DCs ( BMDCs ) in vitro due to the specific interaction between scFv-CD11c and CD11c located on the surface of BMDCs .
After incubation with BMDCs , the 409-aCD11c strain harboring a eukaryotic @ @ @ @ @ @ @ expression of GFP compared with wild-type strains shown by flow cytometry analysis , indicating the enhanced translocation of pValac-GFP fromto BMDCs .
Similar results were also observed in an in vivo study , which showed that oral administration resulted in efficient expression of GFP in both Peyer 's patches ( PP ) and mesenteric lymph nodes ( MLNs ) within 7 days after the last administration .
In addition , the CD11c-targeting strain significantly promoted the differentiation and maturation of DCs , the differentiation of IL-4⁺ and IL-17A⁺ T helper ( Th ) @ @ @ @ @ @ @ production of B220⁺ IgA⁺ B cells in the PP .
In conclusion , this study developed a novel DC-targetingstrain which could increase the ability to deliver eukaryotic expression plasmid to host cells , indicating a promising approach for vaccine study .

The lactic acid bacteria species() has been used extensively for vaccine delivery. Considering to the critical role of dendritic cells in stimulating host immune response, in this study, we constructed a novel CD11c-targetingstrain with surface-displayed variable fragments of anti-CD11c, single-chain antibody (scFv-CD11c). The newly designedstrain, named 409-aCD11c, could adhere and invade more efficiently to bone marrow-derived DCs (BMDCs) in vitro due to the specific interaction between scFv-CD11c and CD11c located on the surface of BMDCs. After incubation with BMDCs, the 409-aCD11c strain harboring a eukaryotic vector pValac-GFP could lead to more efficient expression of GFP compared with wild-type strains shown by flow cytometry analysis, indicating the enhanced translocation of pValac-GFP fromto BMDCs. Similar results were also observed in an in vivo study, which showed that oral administration resulted in efficient expression of GFP in both Peyer's patches (PP) and mesenteric lymph nodes (MLNs) within 7 days after the last administration. In addition, the CD11c-targeting strain significantly promoted the differentiation and maturation of DCs, the differentiation of IL-4⁺ and IL-17A⁺ T helper (Th) cells in MLNs, as well as production of B220⁺ IgA⁺ B cells in the PP. In conclusion, this study developed a novel DC-targetingstrain which could increase the ability to deliver eukaryotic expression plasmid to host cells, indicating a promising approach for vaccine study.


greenmedinfo--2020-04-16--Probiotics importance and their immunomodulatory properties.

Mammalian intestine contains a large diversity of commensal microbiota , which is far more than the number of host cells .
Probiotics play an insecure and protective role against the colonization of intestinal pathogenic microbes and increase mucosal integrity by stimulating epithelial cells .
Probiotics have innate capabilities in many ways , including receptor antagonism , receptor expression , binding and expression of adapter proteins , expression of negative regulatory signal molecules , induction of microRNAs , endotoxin tolerance , and ultimately secretion of immunomodulatory proteins , lipids , and metabolites to modulate the immune system .
Probiotic bacteria can @ @ @ @ @ @ @ through direct or indirect effects on signaling pathways as immunosuppressant or activators .
Probiotics suppress inflammation by inhibiting various signaling pathways such as the nuclear factor-κB ( NF-κβ ) pathway , possibly related to alterations in mitogen-activated protein kinases and pattern recognition receptors pathways .
Probiotics can also inhibit the binding of lipopolysaccharides to the CD14 receptor , thereby reducing the overall activation of NF-κβ and producing proinflammatory cytokines .
Some effects of modulation by probiotics include cytokine production by epithelial cells , increased mucin secretion , increased activity of phagocytosis , and @ @ @ @ @ @ @ cells , stimulation of immunoglobulin A production and decreased T cell proliferation .
Intestinal microbiota has a major impact on the systemic immune system .
Specific microbiota controls the differentiation of cells in lamina propria , in which Th17 cells secrete interleukin 17 .
The presence of Th17 and Treg cells in the small intestine is associated with intestinal microbiota , with the preferential Treg differentiation and the absence of Th17 cells , possibly reflecting alterations in the lamina propria cytokines and the intestinal gut microbiota .

Mammalian intestine contains a large diversity of commensal microbiota, which is far more than the number of host cells. Probiotics play an insecure and protective role against the colonization of intestinal pathogenic microbes and increase mucosal integrity by stimulating epithelial cells. Probiotics have innate capabilities in many ways, including receptor antagonism, receptor expression, binding and expression of adapter proteins, expression of negative regulatory signal molecules, induction of microRNAs, endotoxin tolerance, and ultimately secretion of immunomodulatory proteins, lipids, and metabolites to modulate the immune system. Probiotic bacteria can affect homeostasis, inflammation, and immunopathology through direct or indirect effects on signaling pathways as immunosuppressant or activators. Probiotics suppress inflammation by inhibiting various signaling pathways such as the nuclear factor-κB (NF-κβ) pathway, possibly related to alterations in mitogen-activated protein kinases and pattern recognition receptors pathways. Probiotics can also inhibit the binding of lipopolysaccharides to the CD14 receptor, thereby reducing the overall activation of NF-κβ and producing proinflammatory cytokines. Some effects of modulation by probiotics include cytokine production by epithelial cells, increased mucin secretion, increased activity of phagocytosis, and activation of T and natural killer T cells, stimulation of immunoglobulin A production and decreased T cell proliferation. Intestinal microbiota has a major impact on the systemic immune system. Specific microbiota controls the differentiation of cells in lamina propria, in which Th17 cells secrete interleukin 17. The presence of Th17 and Treg cells in the small intestine is associated with intestinal microbiota, with the preferential Treg differentiation and the absence of Th17 cells, possibly reflecting alterations in the lamina propria cytokines and the intestinal gut microbiota.


greenmedinfo--2020-04-16--Bifidobacterial dialogue with its human host and consequent modulation of the immune system.

Since bifidobacteria are among the pioneering colonizers of the human infant gut , their interaction with their host is believed @ @ @ @ @ .
Several members of thegenus are purported to exert various health-promoting effects at local and @ @ @ @ @ limiting pathogen colonization/invasion , influencing gut homeostasis , and influencing the immune system through changes @ @ @ @ @ responses .
This has promoted extensive research efforts to shed light on the precise mechanisms @ @ @ @ @ to stimulate and interact with the host immune system .
These studies uncovered a variety @ @ @ @ @ that act as essential mediators for the establishment of a bifidobacteria-host immune system dialogue , @ @ @ @ @ mucosa-associated immune cells .
Additionally , the by-products generated from bifidobacterial carbohydrate metabolism act as @ @ @ @ @ trigger the host immune response , the latter by stimulating growth of other commensal microorganisms @ @ @ @ @ bacteria .
This review is aimed to provide a comprehensive overview on the wide variety @ @ @ @ @ to engage with the host immune system .

Since bifidobacteria are among the pioneering colonizers of the human infant gut, their interaction with their host is believed to start soon following birth. Several members of thegenus are purported to exert various health-promoting effects at local and systemic levels, e.g., limiting pathogen colonization/invasion, influencing gut homeostasis, and influencing the immune system through changes in innate and/or adaptive immune responses. This has promoted extensive research efforts to shed light on the precise mechanisms by which bifidobacteria are able to stimulate and interact with the host immune system. These studies uncovered a variety of secreted or surface-associated molecules that act as essential mediators for the establishment of a bifidobacteria-host immune system dialogue, and that allow interactions with mucosa-associated immune cells. Additionally, the by-products generated from bifidobacterial carbohydrate metabolism act as vectors that directly and indirectly trigger the host immune response, the latter by stimulating growth of other commensal microorganisms such as propionate- or butyrate-producing bacteria. This review is aimed to provide a comprehensive overview on the wide variety of strategies employed by bifidobacteria to engage with the host immune system.


greenmedinfo--2020-04-16--Probiotics modulate the gut microbiota composition and immune responses in patients with atopic derm

Probiotics modulate the gut microbiota composition and immune responses in patients with atopic dermatitis.

PURPOSE : Many studies have investigated the association between intestinal barrier impairment and the onset of atopic dermatitis ( AD ) .
The gut microbiota is essential to maintain physiological homeostasis and immune regulation of host .
Therefore , the objectives were to determine the effects of probiotics on the clinical symptoms , immune responses , and gut microbiota in AD patients .
METHODS : 109 patients were randomly divided into 4 groups , including placebo group , oligosaccharides group , Bifidobacterium bifidum CCFM16 group , and Lactobacillus plantarum CCFM8610 group .
At the end of the experiment , serological @ @ @ @ @ @ @ were assessed .
V3-V4 region of the 16S ribosomal RNA gene was sequenced to evaluate changes in the gut microbiota .
Linear discriminant analysis ( LDA ) effect size was used to uncover microbial biomarkers and PICRUSt ( Phylogenetic Investigation of Communities by Reconstruction of Unobserved States ) was used to predict gene family abundances based on 16S information .
RESULTS : The results demonstrated that CCFM8610 significantly decreased the SCORAD index , and increased the serum IL-10 levels .
Supplement with CCFM8610 and CCFM16 significantly influenced the alpha diversity , increased the @ @ @ @ @ @ @ F/B ratio .
CCFM8610 treatment downregulated the functional genes of gut microbiota involving Staphylococcus aureus infection and upregulated the steroid hormone biosynthesis .
CONCLUSION : The results indicated a positive correlation between decreased SCORAD index and CCFM8610 treatment , and that CCFM8610 regulated the immune responses in AD patients .
CCFM8610 treatment influences the gut microbiota composition and functional changes .
In conclusion , L. plantarum CCFM8610 exerts the strain-specific amelioration effects on patients with AD .

PURPOSE: Many studies have investigated the association between intestinal barrier impairment and the onset of atopic dermatitis (AD). The gut microbiota is essential to maintain physiological homeostasis and immune regulation of host. Therefore, the objectives were to determine the effects of probiotics on the clinical symptoms, immune responses, and gut microbiota in AD patients.
METHODS: 109 patients were randomly divided into 4 groups, including placebo group, oligosaccharides group, Bifidobacterium bifidum CCFM16 group, and Lactobacillus plantarum CCFM8610 group. At the end of the experiment, serological indicators, SCORAD, and DLQI indices were assessed. V3-V4 region of the 16S ribosomal RNA gene was sequenced to evaluate changes in the gut microbiota. Linear discriminant analysis (LDA) effect size was used to uncover microbial biomarkers and PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) was used to predict gene family abundances based on 16S information.
RESULTS: The results demonstrated that CCFM8610 significantly decreased the SCORAD index, and increased the serum IL-10 levels. Supplement with CCFM8610 and CCFM16 significantly influenced the alpha diversity, increased the proportion of Bacteroidetes, and reduced the F/B ratio. CCFM8610 treatment downregulated the functional genes of gut microbiota involving Staphylococcus aureus infection and upregulated the steroid hormone biosynthesis.
CONCLUSION: The results indicated a positive correlation between decreased SCORAD index and CCFM8610 treatment, and that CCFM8610 regulated the immune responses in AD patients. CCFM8610 treatment influences the gut microbiota composition and functional changes. In conclusion, L. plantarum CCFM8610 exerts the strain-specific amelioration effects on patients with AD.
TRIAL REGISTRATION: ChiCTR1800015330 (Clinicaltrials.gov Identifier).


greenmedinfo--2020-04-16--Oligosaccharides modulate rotavirus-associated dysbiosis and TLR gene expression.

Colonization of the gut in early life can be altered through multiple environmental factors .
The present study aimed to investigate the effects of 2'-fucosyllactose ( 2'-FL ) , a mixture of short-chain galactooligosaccharides/long-chain fructooligosaccharides ( scGOS/lcFOS ) 9:1 and their combination ( scGOS/lcFOS/2'-FL ) on dysbiosis induced during rotavirus ( RV ) diarrhea in neonatal rats , elucidating crosstalk between bacteria and the immune system .
The dietary interventions were administered daily by oral gavage at days 2-8 of life in neonatal Lewis rats .
On day 5 , RV SA11 was intragastrically delivered to induce infection and diarrhea @ @ @ @ @ @ @ expression of Toll-like receptors ( TLRs ) in the small intestine were studied .
All dietary interventions showed reduction in clinical variables of RV-induced diarrhea .
RV infection increased TLR2 expression , whereas 2'-FL boosted TLR5 and TLR7 expressions and scGOS/lcFOS increased that of TLR9 .
RV-infected rats displayed an intestinal dysbiosis that was effectively prevented by the dietary interventions , and consequently , their microbiota was more similar to microbiota of the noninfected groups .
The preventive effect of 2'-FL , scGOS/lcFOS , and their combination on dysbiosis associated to RV diarrhea @ @ @ @ @ @ @ in the crosstalk between gut microbiota and the innate immune system .

Colonization of the gut in early life can be altered through multiple environmental factors. The present study aimed to investigate the effects of 2'-fucosyllactose (2'-FL), a mixture of short-chain galactooligosaccharides/long-chain fructooligosaccharides (scGOS/lcFOS) 9:1 and their combination (scGOS/lcFOS/2'-FL) on dysbiosis induced during rotavirus (RV) diarrhea in neonatal rats, elucidating crosstalk between bacteria and the immune system. The dietary interventions were administered daily by oral gavage at days 2-8 of life in neonatal Lewis rats. On day 5, RV SA11 was intragastrically delivered to induce infection and diarrhea assessment, microbiota composition, and gene expression of Toll-like receptors (TLRs) in the small intestine were studied. All dietary interventions showed reduction in clinical variables of RV-induced diarrhea. RV infection increased TLR2 expression, whereas 2'-FL boosted TLR5 and TLR7 expressions and scGOS/lcFOS increased that of TLR9. RV-infected rats displayed an intestinal dysbiosis that was effectively prevented by the dietary interventions, and consequently, their microbiota was more similar to microbiota of the noninfected groups. The preventive effect of 2'-FL, scGOS/lcFOS, and their combination on dysbiosis associated to RV diarrhea in rats could be due to changes in the crosstalk between gut microbiota and the innate immune system.


greenmedinfo--2020-04-16--Dietary oligosaccharides attenuate stress-induced disruptions in immune reactivity and microbial B-v

Dietary oligosaccharides attenuate stress-induced disruptions in immune reactivity and microbial B-vitamin metabolism.

Exposure to stressful stimuli dysregulates inflammatory processes and alters the gut microbiota .
Prebiotics , including long-chain fermentable fibers and milk oligosaccharides , have the potential to limit inflammation through modulation of the gut microbiota .
To determine whether prebiotics attenuate stress-induced inflammation and microbiota perturbations , mice were fed either a control diet or a diet supplemented with galactooligosaccharides , polydextrose and sialyllactose ( GOS+PDX+SL ) or sialyllactose ( SL ) for 2 weeks prior to and during a 6-day exposure to a social disruption stressor .
Spleens were collected for immunoreactivity assays .
Colon contents were examined for @ @ @ @ @ @ @ gut microbiome and metabolome through 16S rRNA gene sequencing , shotgun metagenomic sequencing and UPLC-MS/MS.Stress increased circulating IL-6 and enhanced splenocyte immunoreactivity to anLPS challenge .
Diets containing GOS+PDX+SL or SL alone attenuated these responses .
Stress exposure resulted in large changes to the gut metabolome , including robust shifts in amino acids , peptides , nucleotides/nucleosides , tryptophan metabolites , and B vitamins .
Multiple B vitamins were inversely associated with IL-6 and were augmented in mice fed either GOS+PDX+SL or SL diets .
Stressed mice exhibited distinct microbial communities with lower @ @ @ @ @ @ @ .
Diet supplementation with GOS+PDX+SL , but not SL alone , orthogonally altered the microbiome and enhanced the growth ofspp .
Metagenome-assembled genomes ( MAGs ) from mice fed the GOS+PDX+SL diet unveiled genes in aMAG forB vitamin synthesis .
B vitamers directly attenuated the stressor-induced exacerbation of cytokine production in LPS-stimulated splenocytes.Overall , these data indicate that colonic metabolites , including B vitamins , are responsive to psychosocial stress .
Dietary prebiotics reestablish colonic B vitamins and limit stress-induced inflammation .

Exposure to stressful stimuli dysregulates inflammatory processes and alters the gut microbiota. Prebiotics, including long-chain fermentable fibers and milk oligosaccharides, have the potential to limit inflammation through modulation of the gut microbiota. To determine whether prebiotics attenuate stress-induced inflammation and microbiota perturbations, mice were fed either a control diet or a diet supplemented with galactooligosaccharides, polydextrose and sialyllactose (GOS+PDX+SL) or sialyllactose (SL) for 2 weeks prior to and during a 6-day exposure to a social disruption stressor. Spleens were collected for immunoreactivity assays. Colon contents were examined for stressor- and diet- induced changes in the gut microbiome and metabolome through 16S rRNA gene sequencing, shotgun metagenomic sequencing and UPLC-MS/MS.Stress increased circulating IL-6 and enhanced splenocyte immunoreactivity to anLPS challenge. Diets containing GOS+PDX+SL or SL alone attenuated these responses. Stress exposure resulted in large changes to the gut metabolome, including robust shifts in amino acids, peptides, nucleotides/nucleosides, tryptophan metabolites, and B vitamins. Multiple B vitamins were inversely associated with IL-6 and were augmented in mice fed either GOS+PDX+SL or SL diets. Stressed mice exhibited distinct microbial communities with lower abundances ofspp. and higher abundances ofspp. Diet supplementation with GOS+PDX+SL, but not SL alone, orthogonally altered the microbiome and enhanced the growth ofspp. Metagenome-assembled genomes (MAGs) from mice fed the GOS+PDX+SL diet unveiled genes in aMAG forB vitamin synthesis. B vitamers directly attenuated the stressor-induced exacerbation of cytokine production in LPS-stimulated splenocytes.Overall, these data indicate that colonic metabolites, including B vitamins, are responsive to psychosocial stress. Dietary prebiotics reestablish colonic B vitamins and limit stress-induced inflammation.


greenmedinfo--2020-04-16--Evaluation of immune responses to group B Streptococcus type III oligosaccharides containing a minim

Evaluation of immune responses to group B Streptococcus type III oligosaccharides containing a minimal protective epitope.

Recent structural studies demonstrated that the epitope recognized by a monoclonal antibody representative of the protective response against the type @ @ @ @ @ was comprised within 2 of the repeating units that constitute the full-length native structure .
@ @ @ @ @ we took advantage of this discovery to design a novel vaccine based on multivalent presentation @ @ @ @ @ on a carrier protein .
We show that highly glycosylated short oligosaccharide conjugates elicit functional @ @ @ @ @ of the full-length native polysaccharide .
The obtained results pave the way to the design @ @ @ @ @ on short synthetic oligosaccharides .

Recent structural studies demonstrated that the epitope recognized by a monoclonal antibody representative of the protective response against the type III group B Streptococcus polysaccharide was comprised within 2 of the repeating units that constitute the full-length native structure. In the current study, we took advantage of this discovery to design a novel vaccine based on multivalent presentation of the identified minimal epitope on a carrier protein. We show that highly glycosylated short oligosaccharide conjugates elicit functional immune responses comparable to those of the full-length native polysaccharide. The obtained results pave the way to the design of well-defined glycoconjugate vaccines based on short synthetic oligosaccharides.


greenmedinfo--2020-04-16--Impacts of functional oligosaccharide on intestinal immune modulation in immunosuppressive mice.

In order to research the role of soybean oligosaccharides ( SBOSs ) on improvements in the microenvironment of intestinal flora and immune function of cyclophosphamide ( CTX ) immunosuppressive mice .
Via giving intragastric administration of Soybean oligosaccharide ( SBOS ) at the low dose ( 50/ ( kg·BW ) /d ) , the middle dose ( 200 mg/ ( kg·BW ) /d ) and the high dose ( 500 mg/ ( kg·BW ) /d ) partly once a day , which is also 28 days in a row .
At the same time , ( SBOS ) mice in @ @ @ @ @ @ @ mice in the positive control group were given intraabdominal injection of CTX ( 200 mg/kg/d ) .The immunosuppressive mouse model ( CY ) was established after 72 h in the model group and the positive control group ( CG ) was given intragastric administration of levamisole hydrochloric acid ( LMS ) for 3 days , with the data of 80ug/kg/d after injection of CTX ( for actually 72 h ) .
On the 8th , 15th and 22nd day , the number of Bifidobacterium , Lactobacillus , Enterococcus and Clostridium perfringens m in @ @ @ @ @ @ @ of drug group were determined .
After the test resulted , the cellular immune function , humoral immune function , monocyte/macrophage function , NK cell activity and cytokine secretion ( tumor necrosis factor-α , interferon-gamma and IL-4 ) were measured in immunosuppressive mice each group .
The results showed that 200 mg/ ( kg BW ) soybean oligosaccharide could significantly promote the proliferation and inhibit the increase of Enterococcus in immunosuppressive mice .
The soybean oligosaccharide of 500 mg/ ( kg BW ) could dramatically promote the proliferation of both Bifidobacillus and Lactobacillus @ @ @ @ @ @ @ both Enterobacteriaceae and Enterococcus in immunosuppressive mice .
The regulatory function of SBOS on intestinal flora was positive.Soybean oligosaccharide ( 500 mg/ ( kg BW ) could significantly promote the proliferation of Bifidobacillus and Lactobacillus in immunosuppressive mice and inhibit the increase of Enterococcus and Enterococcus .
The proliferation of spleen lymphocytes induced by ConA , LPS in immunosuppressive mice wasdose-dependent .
But it was still lower than that of the normal group ( CG0 ) ( p > 0.05 ) .
The serum hemolysin level of immunosuppressive mice was significantly increased in @ @ @ @ @

In order to research the role of soybean oligosaccharides (SBOSs) on improvements in the microenvironment of intestinal flora and immune function of cyclophosphamide (CTX) immunosuppressive mice. Via giving intragastric administration of Soybean oligosaccharide (SBOS) at the low dose (50/(kg·BW)/d), the middle dose (200 mg/(kg·BW)/d) and the high dose (500 mg/(kg·BW)/d) partly once a day, which is also 28 days in a row. At the same time, (SBOS) mice in the drug group and (CG) mice in the positive control group were given intraabdominal injection of CTX (200 mg/kg/d).The immunosuppressive mouse model (CY) was established after 72 h in the model group and the positive control group (CG) was given intragastric administration of levamisole hydrochloric acid (LMS) for 3 days, with the data of 80ug/kg/d after injection of CTX (for actually 72 h). On the 8th, 15th and 22nd day, the number of Bifidobacterium, Lactobacillus, Enterococcus and Clostridium perfringens m in the feces of mice in each dose of drug group were determined. After the test resulted, the cellular immune function, humoral immune function, monocyte/macrophage function, NK cell activity and cytokine secretion (tumor necrosis factor-α, interferon-gamma and IL-4) were measured in immunosuppressive mice each group. The results showed that 200 mg/(kg BW) soybean oligosaccharide could significantly promote the proliferation and inhibit the increase of Enterococcus in immunosuppressive mice. The soybean oligosaccharide of 500 mg/(kg BW) could dramatically promote the proliferation of both Bifidobacillus and Lactobacillus, and also inhibit the increase of both Enterobacteriaceae and Enterococcus in immunosuppressive mice. The regulatory function of SBOS on intestinal flora was positive.Soybean oligosaccharide (500 mg/(kg BW) could significantly promote the proliferation of Bifidobacillus and Lactobacillus in immunosuppressive mice and inhibit the increase of Enterococcus and Enterococcus. The proliferation of spleen lymphocytes induced by ConA, LPS in immunosuppressive mice wasdose-dependent. But it was still lower than that of the normal group (CG0) (p > 0.05). The serum hemolysin level of immunosuppressive mice was significantly increased in each dose group (p < 0.05), and the level of antibody forming cells in spleen cells of each dose group was significantly increased (P < 0.05), and the level of antibody forming cells in spleen cells of each dose group was significantly higher than that of low dose group (p < 0.005), and the level of serum hemolysin in immunosuppressive mice was significantly increased in each dose group (p < 0.05). In the detection of immune effector cell activity in immunosuppressive mice, the phagocytic function of macrophages in high dose group and the natural killing activity of spleen NK cells in high dose drug group were significantly increased, which were not significantly different from thosein positive control group (P < 0.05), but the expression of TNF-α, INF-γ and IL-4 cytokines in serum was increased in a dose dependent manner (p < 0.05). In conclusion, soybean oligosaccharide can significantly increase the diversity of intestinal microecology, increase the number of intestinal beneficial bacteria, has a correlation with the proliferation of Bifidobacterium and Lactobacillus in the intestinal tract, and inhibit the proliferation of harmful bacteria. The results showed that SBOS had a direct effect on the proliferation of intestinal flora under immunosuppression. Based on the improvement of intestinal microenvironment in immunosuppressive mice by soybean oligosaccharide for 25 days, the results showed that compared with the positive control group, the nonspecific and specific immunity of immunosuppressive mice in the drug group had a regulatory effect, which improved the phagocytic function of monocytes/macrophages, developed the level of antibody forming cells, enhanced the standard of the killing activity ofNK cells, and promoted the expression of cytokines as well. Compared with the model group, the transformation and proliferation of spleen lymphocytes in the high and middle dose groups were remarkably increased, but all of the indexes did not reach the level of the normal blank group. By studying the improvement of intestinal microenvironment in immunosuppressive mice, to some extent, it is concluded that the proliferation of intestinal flora can improve the immunomodulatory function of the body, but it still lowers the normal immune degree, which reflects the immunomodulatory effect of the body on the stimulation of continuous external intake. The results demonstrate that the immunomodulatory ability of immunosuppressive body was insensitive to SBOS and provided a theoretical basis for the study of health care function of intestinal microenvironment improvement when SBOS acted on abnormal immune function. The results also improved the practical application value of SBOS.


greenmedinfo--2020-04-16--Immune-enhancement effects of oligosaccharides from Codonopsis pilosula on cyclophosphamide induced

Immune-enhancement effects of oligosaccharides from Codonopsis pilosula on cyclophosphamide induced immunosuppression.

As an important edible traditional Chinese medicine , Codonopsis pilosula has good immunomodulation effects .
This study focuses on C. @ @ @ @ @ , which are the sweetness components of C. pilosula .
CPO were obtained through systematic @ @ @ @ @ yield is 14.3 % ) , and the effect of CPO on the immunological activities @ @ @ @ @ cyclophosphamide ( CTX ) was evaluated .
The results showed that CPO could increase immune @ @ @ @ @ and immunoglobulin contents , stimulate the proliferation of splenic lymphocytes ( coordinating with ConA and @ @ @ @ @ earlap swelling of the DTH reaction , promote the production of NO and cytokines ( @ @ @ @ @ upregulate the expression of the corresponding mRNA .
In addition , CPO upregulated the protein @ @ @ @ @ phosphorylated ERK1/2 and phosphorylated JNK , which indicated that CPO might exert immunomodulatory effects through @ @ @ @ @ These findings indicated that CPO are important immunomodulatory components in C. pilosula and could be @ @ @ @ @ or functional food areas .

As an important edible traditional Chinese medicine, Codonopsis pilosula has good immunomodulation effects. This study focuses on C. pilosula oligosaccharides (CPO), which are the sweetness components of C. pilosula. CPO were obtained through systematic separation and purification (the yield is 14.3%), and the effect of CPO on the immunological activities of immunocompromised mice induced by cyclophosphamide (CTX) was evaluated. The results showed that CPO could increase immune organ indices, phagocytic index and immunoglobulin contents, stimulate the proliferation of splenic lymphocytes (coordinating with ConA and LPS), enhance the earlap swelling of the DTH reaction, promote the production of NO and cytokines (IL-2 and IFN-γ) and upregulate the expression of the corresponding mRNA. In addition, CPO upregulated the protein expression of phosphorylated p38, phosphorylated ERK1/2 and phosphorylated JNK, which indicated that CPO might exert immunomodulatory effects through the MAPK signaling pathway. These findings indicated that CPO are important immunomodulatory components in C. pilosula and could be developed as immunomodulators in medicine or functional food areas.


greenmedinfo--2020-04-16--Immune-stimulating and gut health-promoting properties of short-chain fructo-oligosaccharides.

Short-chain fructo-oligosaccharides are a group of linear fructose oligomers with a degree of polymerization ranging from one up to five @ @ @ @ @ observations in animal models demonstrate that prebiotics and probiotics may exert beneficial effects on gut @ @ @ @ @ tissue responses either directly or indirectly through the production of short-chain fatty acids and the @ @ @ @ @ such as bifidobacteria and lactobacilli .
Demonstration of the potential health benefits of short-chain fructooligosaccharides @ @ @ @ @ an active field of research in animal and human nutrition .

Short-chain fructo-oligosaccharides are a group of linear fructose oligomers with a degree of polymerization ranging from one up to five (oligosaccharides). Recent observations in animal models demonstrate that prebiotics and probiotics may exert beneficial effects on gut health by enhancing gut-associated lymphoid tissue responses either directly or indirectly through the production of short-chain fatty acids and the enhanced growth of lactic bacteria such as bifidobacteria and lactobacilli. Demonstration of the potential health benefits of short-chain fructooligosaccharides on colon cancer risk is an active field of research in animal and human nutrition.


greenmedinfo--2020-04-16--Immunity Certificates: A Load of Nonsense and a Covert Op

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--2020-04-17--Therapeutic potential of volatile terpenes and terpenoids from forests for inflammatory diseases.

Forest trees are a major source of biogenic volatile organic compounds ( BVOCs ) .
Terpenes and terpenoids are known @ @ @ @ @ forest aerosols .
These compounds have been shown to display a broad range of biological @ @ @ @ @ models , thus implying that forest aerosols containing these compounds may be related to beneficial @ @ @ @ @ In this review , we surveyed studies analyzing BVOCs and selected the most abundant 23 @ @ @ @ @ forested areas of the Northern Hemisphere , which were reported to display anti-inflammatory activities .
@ @ @ @ @ to the functions of these compounds into six groups and summarized their molecular mechanisms of @ @ @ @ @ the major 23 compounds , we examined the therapeutic potentials of 12 compounds known to @ @ @ @ @ , atopic dermatitis , arthritis , and neuroinflammation among various inflammatory diseases .
In conclusion @ @ @ @ @ the beneficial effects of forest aerosols and propose their potential use as chemopreventive and therapeutic @ @ @ @ @ diseases .

Forest trees are a major source of biogenic volatile organic compounds (BVOCs). Terpenes and terpenoids are known as the main BVOCs of forest aerosols. These compounds have been shown to display a broad range of biological activities in various human disease models, thus implying that forest aerosols containing these compounds may be related to beneficial effects of forest bathing. In this review, we surveyed studies analyzing BVOCs and selected the most abundant 23 terpenes and terpenoids emitted in forested areas of the Northern Hemisphere, which were reported to display anti-inflammatory activities. We categorized anti-inflammatory processes related to the functions of these compounds into six groups and summarized their molecular mechanisms of action. Finally, among the major 23 compounds, we examined the therapeutic potentials of 12 compounds known to be effective against respiratory inflammation, atopic dermatitis, arthritis, and neuroinflammation among various inflammatory diseases. In conclusion, the updated studies support the beneficial effects of forest aerosols and propose their potential use as chemopreventive and therapeutic agents for treating various inflammatory diseases.


greenmedinfo--2020-04-17--This is evidence of a causal relationship between vitamin D– vitamin D receptor signalling and melan

This is evidence of a causal relationship between vitamin D– vitamin D receptor signalling and melanoma survival.

1α,25-Dihydroxyvitamin D3 signals via the vitamin D receptor ( VDR ) .
Higher serum vitamin D is associated with thinner primary melanoma and better outcome , although a causal mechanism has not been established .
As patients with melanoma commonly avoid sun exposure , and consequent vitamin D deficiencymight worsen outcomes , we interrogated 703 primary melanoma transcriptomes to understand the role of vitamin D-VDR signaling and replicated the findings in The Cancer Genome Atlas metastases.expression was independently protective for melanoma-related death in both primary and metastatic disease .
High tumorexpression was associated with upregulation of pathways mediating antitumor immunity @ @ @ @ @ @ @ scores and histologically detected tumor-infiltrating lymphocytes .
High-expressing tumors had downregulation of proliferative pathways , notably Wnt/β-catenin signaling .
Deleterious lowlevels resulted from promoter methylation and gene deletion in metastases .
Vitamin D deficiency ( < 25 nmol/L∼ 10 ng/mL ) shortened survival in primary melanoma in a-dependent manner.functional validation studies showed that elevated vitamin D-VDR signaling inhibited Wnt/β-catenin signaling genes .
Murine melanoma cells overexpressingproduced fewer pulmonary metastases than controls in tail-vein metastasis assays .
In summary , vitamin D-VDR signaling contributes to controlling pro-proliferative/immunosuppressive Wnt/β-catenin signaling in melanoma and this is @ @ @ @ @ @ @ host immune responses .
This is evidence of a causal relationship between vitamin D-VDR signaling and melanoma survival , which should be explored as a therapeutic target in primary resistance to checkpoint blockade .
SIGNIFICANCE : VDR expression could potentially be used as a biomarker to stratify patients with melanoma that may respond better to immunotherapy .

1α,25-Dihydroxyvitamin D3 signals via the vitamin D receptor (VDR). Higher serum vitamin D is associated with thinner primary melanoma and better outcome, although a causal mechanism has not been established. As patients with melanoma commonly avoid sun exposure, and consequent vitamin D deficiencymight worsen outcomes, we interrogated 703 primary melanoma transcriptomes to understand the role of vitamin D-VDR signaling and replicated the findings in The Cancer Genome Atlas metastases.expression was independently protective for melanoma-related death in both primary and metastatic disease. High tumorexpression was associated with upregulation of pathways mediating antitumor immunity and corresponding with higher imputed immune cell scores and histologically detected tumor-infiltrating lymphocytes. High-expressing tumors had downregulation of proliferative pathways, notably Wnt/β-catenin signaling. Deleterious lowlevels resulted from promoter methylation and gene deletion in metastases. Vitamin D deficiency (<25 nmol/L∼ 10 ng/mL) shortened survival in primary melanoma in a-dependent manner.functional validation studies showed that elevated vitamin D-VDR signaling inhibited Wnt/β-catenin signaling genes. Murine melanoma cells overexpressingproduced fewer pulmonary metastases than controls in tail-vein metastasis assays. In summary, vitamin D-VDR signaling contributes to controlling pro-proliferative/immunosuppressive Wnt/β-catenin signaling in melanoma and this is associated with less metastatic disease and stronger host immune responses. This is evidence of a causal relationship between vitamin D-VDR signaling and melanoma survival, which should be explored as a therapeutic target in primary resistance to checkpoint blockade. SIGNIFICANCE: VDR expression could potentially be used as a biomarker to stratify patients with melanoma that may respond better to immunotherapy.


greenmedinfo--2020-04-17--Effects of vitamin D supplementation and seasonality on circulating cytokines in adolescents.

Vitamin D deficiency is prevalent in human populations and has been linked to immune dysfunction .
Here we explored the effects of cholecalciferol supplementation on circulating cytokines in severely vitamin D deficient [ blood 25 ( OH ) D < 30 nmol/L ] adolescents aged 12-15 from Mongolia .
The study included 28 children receiving 800 IU daily cholecalciferol for 6 months spanning winter and spring , and 30 children receiving placebo during the same period .
The levels of 25 ( OH ) D were assessed at baseline , 3 and 6 months .
Twenty-one cytokines were measured in @ @ @ @ @ @ @ .
Changes in 25 ( OH ) D and cytokines were assessed using paired parametric tests .
The median blood 25 ( OH ) D concentration at baseline was 13.7 nmol/L ( IQR = 10.0-21.7 ) .
Supplementation tripled blood 25 ( OH ) D levels ( < 0.001 ) and was associated with elevated interleukin ( IL ) -6 ( = 0.043 ) .
The placebo group had reduced macrophage inflammatory protein ( MIP ) -1α ( = 0.007 ) and IL-8 ( = 0.034 ) at 6 months .
Although limited @ @ @ @ @ @ @ findings suggest that cholecalciferol supplementation and seasonality may impact systemic immunity in adolescents , identifying chemokines as potentially important biomarkers of vitamin D status in this Northeast Asian population .
Larger clinical trials are warranted to validate these results.www.ClinicalTrial.org , Identifier : NCT01244204 .

Vitamin D deficiency is prevalent in human populations and has been linked to immune dysfunction. Here we explored the effects of cholecalciferol supplementation on circulating cytokines in severely vitamin D deficient [blood 25(OH)D<30 nmol/L] adolescents aged 12-15 from Mongolia. The study included 28 children receiving 800 IU daily cholecalciferol for 6 months spanning winter and spring, and 30 children receiving placebo during the same period. The levels of 25(OH)D were assessed at baseline, 3 and 6 months. Twenty-one cytokines were measured in serum at baseline and at 6 months. Changes in 25(OH)D and cytokines were assessed using paired parametric tests. The median blood 25(OH)D concentration at baseline was 13.7 nmol/L (IQR = 10.0-21.7). Supplementation tripled blood 25(OH)D levels (<0.001) and was associated with elevated interleukin (IL)-6 (= 0.043). The placebo group had reduced macrophage inflammatory protein (MIP)-1α (= 0.007) and IL-8 (= 0.034) at 6 months. Although limited by a small sample size, these findings suggest that cholecalciferol supplementation and seasonality may impact systemic immunity in adolescents, identifying chemokines as potentially important biomarkers of vitamin D status in this Northeast Asian population. Larger clinical trials are warranted to validate these results.www.ClinicalTrial.org, Identifier: NCT01244204.


greenmedinfo--2020-04-17--Determination of some indicators of immunity and lipoperoxidation in the oral fluid in persons with

Determination of some indicators of immunity and lipoperoxidation in the oral fluid in persons with a low vitamin D level.

Oral fluid is a unique biological environment , containing a wide range of substances , coming from local and systemic sources , which makes it possible to use it as an object for assessing pathological changes in the body both at the local and systemic levels .
In comparison with the traditional method of blood analysis , the advantage of evaluating the parameters of the oral fluid is the non-invasive of this method of obtaining material .
All patients underwent oral fluid sampling using special plastic containers with a swab , which facilitate the selection of material , eliminating the @ @ @ @ @ @ @ sample , which helps to obtain more accurate analysis results .
The amount of secretory IgA , lipopolysaccharide-binding protein ( LBP ) , TBA-active products , the level of total antioxidant activity in the oral fluid in individuals with a low level of 25 ( OH ) D before and after taking the native solution of vitamin D '' Aqua Trim '' were determined .
The concentrations of secretory immunoglobulin A , lipopolysaccharide , binding protein and the level of total antioxidant activity are reduced in the oral fluid of people with vitamin @ @ @ @ @ @ @ intermediate products of lyoperoxidation increases .
The course intake of the native solution of vitamin D ( International Nonproprietary Name - Colecalciferol ) normalizes the functioning of the immunity of the oral cavity and restores the balance of the '' lipid peroxidation-antioxidants '' system .

Oral fluid is a unique biological environment, containing a wide range of substances, coming from local and systemic sources, which makes it possible to use it as an object for assessing pathological changes in the body both at the local and systemic levels. In comparison with the traditional method of blood analysis, the advantage of evaluating the parameters of the oral fluid is the non-invasive of this method of obtaining material. All patients underwent oral fluid sampling using special plastic containers with a swab, which facilitate the selection of material, eliminating the penetration of mucin into a clean test sample, which helps to obtain more accurate analysis results. The amount of secretory IgA, lipopolysaccharide-binding protein (LBP), TBA-active products, the level of total antioxidant activity in the oral fluid in individuals with a low level of 25(OH)D before and after taking the native solution of vitamin D"Aqua Trim"were determined. The concentrations of secretory immunoglobulin A, lipopolysaccharide, binding protein and the level of total antioxidant activity are reduced in the oral fluid of people with vitamin D deficiency, but the number of intermediate products of lyoperoxidation increases. The course intake of the native solution of vitamin D (International Nonproprietary Name - Colecalciferol) normalizes the functioning of the immunity of the oral cavity and restores the balance of the"lipid peroxidation-antioxidants"system.


greenmedinfo--2020-04-17--Ecological evidence for lower risk of lymphoma with greater exposure to sunlight and higher altitude

Ecological evidence for lower risk of lymphoma with greater exposure to sunlight and higher altitude.

Sunlight exposure increases vitamin D-related immune modulation and motility of T lymphocytes .
Blue light exposure from the sun can stimulate immune function and help promote healthy circadian rhythm .
Hence , greater sunlight exposure may lower the risk of Hodgkin lymphoma and non-Hodgkin lymphoma ( NHL ) .
Altitude may also lower the risk of these cancers through an oxygen-related mechanism , and because cosmic radiation has less shield from the atmosphere at higher levels , it allows for radiation hormesis.An ecological study design was used , with county-level lymphoma , sunlight , altitude , urban residency , poverty @ @ @ @ @ @ @ physical inactivity data for 16 cancer registries ( 607 counties ) in the contiguous United States , 2012-2016 .
Relative rate estimates were derived from two-level mixed effects Poisson regression models.Higher rates of NHL are associated with being older , male , and white .
Higher rates of Hodgkin lymphoma are associated with ages 20 years and older , male , and white or black .
The risk of NHL or Hodgkin lymphoma is lower among those living in poverty .
Urban residency , smoking , obesity , and physical inactivity are not @ @ @ @ @ @ @ sunlight exposure and higher altitude are simultaneously associated with lower rates of Hodgkin lymphoma and NHL in adjusted models .
The inverse association between sunlight and NHL is more pronounced with higher altitude .
The inverse association between sunlight and Hodgkin lymphoma is only in altitudes below 500 m.Greater sunlight exposure and higher altitude are simultaneously associated with lower rates of Hodgkin lymphoma and NHL .
The inverse associations are dependent on altitude , with the relationship only in lower altitudes for Hodgkin lymphoma and more pronounced in higher altitude for NHL .

Sunlight exposure increases vitamin D-related immune modulation and motility of T lymphocytes. Blue light exposure from the sun can stimulate immune function and help promote healthy circadian rhythm. Hence, greater sunlight exposure may lower the risk of Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). Altitude may also lower the risk of these cancers through an oxygen-related mechanism, and because cosmic radiation has less shield from the atmosphere at higher levels, it allows for radiation hormesis.An ecological study design was used, with county-level lymphoma, sunlight, altitude, urban residency, poverty, smoking, obesity, and leisure-time physical inactivity data for 16 cancer registries (607 counties) in the contiguous United States, 2012-2016. Relative rate estimates were derived from two-level mixed effects Poisson regression models.Higher rates of NHL are associated with being older, male, and white. Higher rates of Hodgkin lymphoma are associated with ages 20 years and older, male, and white or black. The risk of NHL or Hodgkin lymphoma is lower among those living in poverty. Urban residency, smoking, obesity, and physical inactivity are not associated with these cancers. Both increased sunlight exposure and higher altitude are simultaneously associated with lower rates of Hodgkin lymphoma and NHL in adjusted models. The inverse association between sunlight and NHL is more pronounced with higher altitude. The inverse association between sunlight and Hodgkin lymphoma is only in altitudes below 500 m.Greater sunlight exposure and higher altitude are simultaneously associated with lower rates of Hodgkin lymphoma and NHL. The inverse associations are dependent on altitude, with the relationship only in lower altitudes for Hodgkin lymphoma and more pronounced in higher altitude for NHL.