greenmedinfo--2020-05-09--Physical activity has a positive impact on the prevention and treatment of Parkinson's disease.

Aim : This study was aimed at investigating the effects and molecular mechanisms of physical activity intervention on Parkinson 's disease ( PD ) and providing theoretical guidance for the prevention and treatment of PD .
Methods : Four electronic databases up to December 2019 were searched ( PubMed , Springer , Elsevier , and Wiley database ) , 176 articles were selected .
Literature data were analyzed by the logic analysis method .
Results : ( 1 ) Risk factors of PD include dairy products , pesticides , traumatic brain injury , and obesity .
Protective factors include alcohol @ @ @ @ @ @ @ , and physical activity .
( 2 ) Physical activity can reduce the risk and improve symptoms of PD and the beneficial forms of physical activity , including running , dancing , traditional Chinese martial arts , yoga , and weight training .
( 3 ) Different forms of physical activity alleviate the symptoms of PD through different mechanisms , including reducing the accumulation of-syn protein , inflammation , and oxidative stress , while enhancing BDNF activity , nerve regeneration , and mitochondrial function .
Conclusion : Physical activity has a positive impact @ @ @ @ @ @ @ .
Illustrating the molecular mechanism of physical activity-induced protective effect on PD is an urgent need for improving the efficacy of PD therapy regimens in the future .

Aim: This study was aimed at investigating the effects and molecular mechanisms of physical activity intervention on Parkinson's disease (PD) and providing theoretical guidance for the prevention and treatment of PD.
Methods: Four electronic databases up to December 2019 were searched (PubMed, Springer, Elsevier, and Wiley database), 176 articles were selected. Literature data were analyzed by the logic analysis method.
Results: (1) Risk factors of PD include dairy products, pesticides, traumatic brain injury, and obesity. Protective factors include alcohol, tobacco, coffee, black tea, and physical activity. (2) Physical activity can reduce the risk and improve symptoms of PD and the beneficial forms of physical activity, including running, dancing, traditional Chinese martial arts, yoga, and weight training. (3) Different forms of physical activity alleviate the symptoms of PD through different mechanisms, including reducing the accumulation of-syn protein, inflammation, and oxidative stress, while enhancing BDNF activity, nerve regeneration, and mitochondrial function.
Conclusion: Physical activity has a positive impact on the prevention and treatment of PD. Illustrating the molecular mechanism of physical activity-induced protective effect on PD is an urgent need for improving the efficacy of PD therapy regimens in the future.


greenmedinfo--2020-05-09--Mindfulness with paced breathing reduces blood pressure.

Elevated blood pressure ( BP ) is a major avoidable cause of premature morbidity and mortality in the United States ( US ) and worldwide , due primarily to increased risks of stroke as well as myocardial infarction .
While there are therapeutic lifestyle changes and adjunctive pharmacologic medications of proven benefit , recent interest has increasingly focused on Complementary and Alternative Medicine , in particular , Mind-Body Interventions .
With respect to BP , it is tempting to speculate that mindfulness with paced breathing will have beneficial effects in the short run that may translate into lowered risks of @ @ @ @ @ @ @ breathing is deep diaphragmatic breathing with typical rates equal to or less than 5-7 breaths per minute compared with the usual rate of 12-14 .
One plausible mechanism of benefit is that paced breathing stimulates the parasympathetic nervous system which alters neuronal function in specific areas of the brain and reduces stress chemicals .
The hypothesis that mindfulness with paced slow breathing reduces BP could be directly tested in randomized trials designed a priori to do so .
Subsequently , a finding that mindfulness with paced breathing reduces BP would also lead to @ @ @ @ @ @ @ of carotid atherosclerosis and , if so , a larger scale trial to test whether there is a direct impact of mindfulness with paced breathing on reducing the risks of stroke and MI .
If rigorous testing of this medical hypothesis led to positive results this would have large and important clinical and policy implications in the US and worldwide .

Elevated blood pressure (BP) is a major avoidable cause of premature morbidity and mortality in the United States (US) and worldwide, due primarily to increased risks of stroke as well as myocardial infarction. While there are therapeutic lifestyle changes and adjunctive pharmacologic medications of proven benefit, recent interest has increasingly focused on Complementary and Alternative Medicine, in particular, Mind-Body Interventions. With respect to BP, it is tempting to speculate that mindfulness with paced breathing will have beneficial effects in the short run that may translate into lowered risks of stroke in the long run. Paced breathing is deep diaphragmatic breathing with typical rates equal to or less than 5-7 breaths per minute compared with the usual rate of 12-14. One plausible mechanism of benefit is that paced breathing stimulates the parasympathetic nervous system which alters neuronal function in specific areas of the brain and reduces stress chemicals. The hypothesis that mindfulness with paced slow breathing reduces BP could be directly tested in randomized trials designed a priori to do so. Subsequently, a finding that mindfulness with paced breathing reduces BP would also lead to direct tests in randomized trials of reductions of carotid atherosclerosis and, if so, a larger scale trial to test whether there is a direct impact of mindfulness with paced breathing on reducing the risks of stroke and MI. If rigorous testing of this medical hypothesis led to positive results this would have large and important clinical and policy implications in the US and worldwide.


greenmedinfo--2020-05-09--Mindfulness based interventions can provide effective alternative therapies to assist in blood press

Mindfulness based interventions can provide effective alternative therapies to assist in blood pressure reduction for patients with non-communicable diseases.

Purpose : Mindfulness based interventions ( MBIs ) are an emerging area of empirical study , not only in positive psychology , but also in clinical health care .
This research aims to synthesize the evidence about whether MBIs reduce blood pressure ( BP ) in patients with non-communicable diseases ( NCDs ) .
Methods : Relevant studies were identified via PubMed , the Cochrane Library , Embase and the CINAHL database between 2009 and 2019 .
The papers selected focused on mindfulness and the effect of these on the BP of patients with NCDs .
The change in SBP @ @ @ @ @ @ @ type of intervention ( Breathing awareness meditation ( BAM ) , Mindfulness Meditation ( MM ) , and Mindfulness-based Stress Reduction ( MBSR ) .
Results : Fourteen articles met eligibility criteria and were included in the final review .
Among the studies using the type and duration of intervention , systolic BP was reduced after the mindfulness-based stress reduction for 8 weeks ( -6.90 mmHg [ 95 % CI : -10.82 , -2.97 ] , Conclusion : MBIs can provide effective alternative therapies to assist in blood pressure reduction for patients with @ @

Purpose: Mindfulness based interventions (MBIs) are an emerging area of empirical study, not only in positive psychology, but also in clinical health care. This research aims to synthesize the evidence about whether MBIs reduce blood pressure (BP) in patients with non-communicable diseases (NCDs).
Methods: Relevant studies were identified via PubMed, the Cochrane Library, Embase and the CINAHL database between 2009 and 2019. The papers selected focused on mindfulness and the effect of these on the BP of patients with NCDs. The change in SBP and DBP were meta-analyzed, stratified by type of intervention (Breathing awareness meditation (BAM), Mindfulness Meditation (MM), and Mindfulness-based Stress Reduction (MBSR).
Results: Fourteen articles met eligibility criteria and were included in the final review. Among the studies using the type and duration of intervention, systolic BP was reduced after the mindfulness-based stress reduction for 8 weeks (-6.90 mmHg [95% CI: -10.82, -2.97],<.050), followed by the breathing awareness meditation for 12 weeks (-4.10 mmHg [95% CI: -7.54, -0.66],<.050) and the mindfulness-based intervention for 8 weeks (-2.69 mmHg [95% CI: -3.90, -1.49],<.050) whereas diastolic BP was reduced after the mindfulness-based stress reduction for 8 weeks (-2.45 mmHg [95% CI: -3.74, -1.17],<.050) and the mindfulness-based intervention for 8 weeks (-2.24 mmHg [95% CI: -3.22, -1.26],<.050).
Conclusion: MBIs can provide effective alternative therapies to assist in blood pressure reduction for patients with NCDs.


greenmedinfo--2020-05-09--The Potential Benefits of Flavonoids in Treating Neurodegenerative Diseases

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greenmedinfo--2020-05-09--Bony Protrusions in Young Adults: Are Cellphones to Blame?


greenmedinfo--2020-05-09--Pterostilbene improves cardiac function in a rat model of right heart failure.

This study explored the effect of pterostilbene ( PTS ) complexed with hydroxypropyl-β-cyclodextrin ( HPβCD ) on right heart function , glutathione and glutaredoxin systems and the expression of intracellular calcium handling redox-sensitive proteins in the experimental model of pulmonary arterial hypertension ( PAH ) induced by monocrotaline ( MCT ) .
After 7 days of PAH induction , ratsreceived daily doses of the PTS : HPβCD complex ( corresponding to 25 , 50 or 100 mg kg-1 of PTS ) or vehicle ( control group , CTR0 ) ( an aqueous solution containing HPβCD , CTR0 and MCT0 ) @ @ @ @ @ @ @ The results showed that the PTS : HPβCD complex increased the content of reduced glutathione and the activity of glutathione-S-transferase and glutaredoxin in the right ventricle ( RV ) of MCT-treated rats in a dose-dependent manner .
Additionally , at higher doses , it also prevented the reduction of stroke volume and cardiac output , prevented MPI increase , reduced lipoperoxidation , reduced total phospholamban , and increased the expression of SERCA in the RV of MCT-treated rats .
These results demonstrate that the PTS : HPβCD complex has a dose-dependent antioxidant mechanism @ @ @ @ @ @ @ experimental right heart failure .
Our results open a field of possibilities to PTS administration as new therapeutic approach to conventional therapy for right ventricular dysfunction .
Novelty bullets : - Pterostilbene complexed with hydroxypropyl-β-cyclodextrin could be a new therapeutic approach ; - Pterostilbene complexed with hydroxypropyl-β-cyclodextrin re-establishes redox homeostasis , through glutathione metabolism modulation , leading to an improved myocardial performance index in pulmonary arterial hypertension-provoked right heart failure .

This study explored the effect of pterostilbene (PTS) complexed with hydroxypropyl-β-cyclodextrin (HPβCD) on right heart function, glutathione and glutaredoxin systems and the expression of intracellular calcium handling redox-sensitive proteins in the experimental model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). After 7 days of PAH induction, ratsreceived daily doses of the PTS:HPβCD complex (corresponding to 25, 50 or 100 mg kg-1 of PTS) or vehicle (control group, CTR0) (an aqueous solution containing HPβCD, CTR0 and MCT0) via oral administration during two weeks. The results showed that the PTS:HPβCD complex increased the content of reduced glutathione and the activity of glutathione-S-transferase and glutaredoxin in the right ventricle (RV) of MCT-treated rats in a dose-dependent manner. Additionally, at higher doses, it also prevented the reduction of stroke volume and cardiac output, prevented MPI increase, reduced lipoperoxidation, reduced total phospholamban, and increased the expression of SERCA in the RV of MCT-treated rats. These results demonstrate that the PTS:HPβCD complex has a dose-dependent antioxidant mechanism that results in improved cardiac function in experimental right heart failure. Our results open a field of possibilities to PTS administration as new therapeutic approach to conventional therapy for right ventricular dysfunction. Novelty bullets: - Pterostilbene complexed with hydroxypropyl-β-cyclodextrin could be a new therapeutic approach; - Pterostilbene complexed with hydroxypropyl-β-cyclodextrin re-establishes redox homeostasis, through glutathione metabolism modulation, leading to an improved myocardial performance index in pulmonary arterial hypertension-provoked right heart failure.


greenmedinfo--2020-05-09--Pterostilbene induces Nrf2/HO-1 and potentially regulates NF-κB and JNK-Akt/mTOR signaling in ischem

Pterostilbene induces Nrf2/HO-1 and potentially regulates NF-κB and JNK-Akt/mTOR signaling in ischemic brain injury.

Hypoxic-ischemic ( HI ) brain injury has a high occurrence rate of 1-4 per 1000 live births and is the leading cause of neurological disabilities .
Despite the improvement in neonatal care , the effectiveness of current therapeutic strategies is limited , and thus , additional therapies with better results are of much needed .
Pterostilbene is a stilbenoid possessing numerous preventive and therapeutic properties .
The current study aimed to assess whether pterostilbene exerted protective effects in neonatal rats against experimentally induced ischemic brain injury .
Pterostilbene was administered via oral gavage from postnatal day 3 to day 8 @ @ @ @ @ @ @ exposed to hypoxic-ischemic insult via ligation of the common carotid artery and hypoxic environment exposure .
Pterostilbene treatment reduced neuronal loss and infarct volume .
Pterostilbene administration regulated the NF-κB pathway , and the levels of inflammatory mediators ( Nitric oxide , TNF-α , IL-1β , and IL-6 ) were reduced .
HI-induced oxidative stress was significantly reduced by pterostilbene , as presented by decreased production of malondialdehyde and reactive oxygen species .
Levels of glutathione were enhanced by pterostilbene .
Pterostilbene regulated Nrf2/HO-1 and JNK expression and activated the PI3K/Akt-mTOR signals .
@ @ @ @ @ @ @ candidate compound for the treatment of neonatal HI .

Hypoxic-ischemic (HI) brain injury has a high occurrence rate of 1-4 per 1000 live births and is the leading cause of neurological disabilities. Despite the improvement in neonatal care, the effectiveness of current therapeutic strategies is limited, and thus, additional therapies with better results are of much needed. Pterostilbene is a stilbenoid possessing numerous preventive and therapeutic properties. The current study aimed to assess whether pterostilbene exerted protective effects in neonatal rats against experimentally induced ischemic brain injury. Pterostilbene was administered via oral gavage from postnatal day 3 to day 8. Rat pups that were seven-day-old were exposed to hypoxic-ischemic insult via ligation of the common carotid artery and hypoxic environment exposure. Pterostilbene treatment reduced neuronal loss and infarct volume. Pterostilbene administration regulated the NF-κB pathway, and the levels of inflammatory mediators (Nitric oxide, TNF-α, IL-1β, and IL-6) were reduced. HI-induced oxidative stress was significantly reduced by pterostilbene, as presented by decreased production of malondialdehyde and reactive oxygen species. Levels of glutathione were enhanced by pterostilbene. Pterostilbene regulated Nrf2/HO-1 and JNK expression and activated the PI3K/Akt-mTOR signals. These findings suggest that pterostilbene is a candidate compound for the treatment of neonatal HI.


greenmedinfo--2020-05-09--The preventive effects of pterostilbene on the exercise intolerance and circadian misalignment of mi

The preventive effects of pterostilbene on the exercise intolerance and circadian misalignment of mice subjected to sleep restriction.

SCOPE : The study investigates the effects of pterostilbene ( PTE ) on exercise endurance and circadian rhythm in sleep-restricted ( SR ) mice .
METHODS AND RESULTS : The SR model is established by keeping mice awake during the first 8 h of light period for 5 d and PTE ( 100 mg kgd ) is given once a day .
PTE improves endurance in SR mice by significantly prolonging the exhaustive swimming time and ameliorating exercise fatigue biochemical parameters , including creatine kinase and lactate dehydrogenase .
It is observed that PTE effectively regained mitochondrial function by improving @ @ @ @ @ @ @ genes expression , and inhibited the decrease of mitochondrial biogenesis-related genes expression .
Furthermore , PTE restores rhythms of AMP-activated protein kinase ( AMPK ) phosphorylation activity , silent information regulator 1 ( SIRT1 ) deacetylation activity , and SIRT1-mediated peroxisome proliferator-activated receptor coactivator 1α ( PGC-1α ) deacetylation in SR mice .
Finally , the results demonstrate that the AMPK/SIRT1/PGC-1α pathway may be correlated with the relationships between mitochondrial function and circadian rhythms , markedly regulating the expression of skeletal muscle clock genes , circadian locomotor output cycles kaput , and brain @ @ @ @ @ @ @ PTE ameliorates SR-induced exercise intolerance associated with circadian misalignment and mitochondrial dysfunction through AMPK/SIRT1/PGC-1α pathway .

SCOPE: The study investigates the effects of pterostilbene (PTE) on exercise endurance and circadian rhythm in sleep-restricted (SR) mice.
METHODS AND RESULTS: The SR model is established by keeping mice awake during the first 8 h of light period for 5 d and PTE (100 mg kgd) is given once a day. PTE improves endurance in SR mice by significantly prolonging the exhaustive swimming time and ameliorating exercise fatigue biochemical parameters, including creatine kinase and lactate dehydrogenase. It is observed that PTE effectively regained mitochondrial function by improving mitochondrial swelling and maintaining oxidative phosphorylation system-related genes expression, and inhibited the decrease of mitochondrial biogenesis-related genes expression. Furthermore, PTE restores rhythms of AMP-activated protein kinase (AMPK) phosphorylation activity, silent information regulator 1 (SIRT1) deacetylation activity, and SIRT1-mediated peroxisome proliferator-activated receptor coactivator 1α (PGC-1α) deacetylation in SR mice. Finally, the results demonstrate that the AMPK/SIRT1/PGC-1α pathway may be correlated with the relationships between mitochondrial function and circadian rhythms, markedly regulating the expression of skeletal muscle clock genes, circadian locomotor output cycles kaput, and brain and muscle arnt-like 1.
CONCLUSIONS: PTE ameliorates SR-induced exercise intolerance associated with circadian misalignment and mitochondrial dysfunction through AMPK/SIRT1/PGC-1α pathway.


greenmedinfo--2020-05-09--Pterostilbene enhances cytotoxicity and chemosensitivity in human pancreatic cancer cells.

Gemcitabine ( GEM ) drug resistance causes high mortality rates and poor outcomes in pancreatic ductal adenocarcinoma ( PDAC ) patients .
Receptor for advanced glycation end products ( RAGE ) involvement in the GEM resistance process has been demonstrated .
Therefore , finding a safe and effective way to inhibit receptors for RAGE-initiated GEM resistance is urgent .
Pterostilbene ( PTE ) , a natural methoxylated analogue derived from resveratrol and found in grapes and blueberries , has diverse bioactivities , such as antioxidative , anti-inflammatory , and anticancer qualities .
The overall research objective was to determine the @ @ @ @ @ @ @ and chemosensitivity in PDAC cells .
Our results have demonstrated that PTE induced S-phase cell cycle arrest , apoptosis , and autophagic cell death and inhibited multidrug resistance protein 1 ( MDR1 ) expression by downregulating RAGE/PI3K/Akt signaling in both MIA PaCa-2 and MIA PaCa-2cells ( GEM-resistant cells ) .
Remarkably , convincing evidence was established by RAGE small interfering RNA transfection .
Taken together , our study demonstrated that PTE promoted chemosensitivity by inhibiting cell proliferation and MDR1 expression via the RAGE/PI3K/Akt axis in PDAC cells .
The observations in these experiments @ @ @ @ @ @ @ role in MDR1 modulation for PDAC treatment .

Gemcitabine (GEM) drug resistance causes high mortality rates and poor outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. Receptor for advanced glycation end products (RAGE) involvement in the GEM resistance process has been demonstrated. Therefore, finding a safe and effective way to inhibit receptors for RAGE-initiated GEM resistance is urgent. Pterostilbene (PTE), a natural methoxylated analogue derived from resveratrol and found in grapes and blueberries, has diverse bioactivities, such as antioxidative, anti-inflammatory, and anticancer qualities. The overall research objective was to determine the potential of PTE to enhance tumor cytotoxicity and chemosensitivity in PDAC cells. Our results have demonstrated that PTE induced S-phase cell cycle arrest, apoptosis, and autophagic cell death and inhibited multidrug resistance protein 1 (MDR1) expression by downregulating RAGE/PI3K/Akt signaling in both MIA PaCa-2 and MIA PaCa-2cells (GEM-resistant cells). Remarkably, convincing evidence was established by RAGE small interfering RNA transfection. Taken together, our study demonstrated that PTE promoted chemosensitivity by inhibiting cell proliferation and MDR1 expression via the RAGE/PI3K/Akt axis in PDAC cells. The observations in these experiments indicate that PTE may play a crucial role in MDR1 modulation for PDAC treatment.


greenmedinfo--2020-05-09--Pterostilbene prevents LPS-induced early pulmonary fibrosis by suppressing oxidative stress, inflamm

Pterostilbene prevents LPS-induced early pulmonary fibrosis by suppressing oxidative stress, inflammation and apoptosis in vivo.

Early pulmonary fibrosis after acute lung injury leads to poor prognosis and high mortality .
Pterostilbene ( Pts ) , a bioactive component in blueberries , possesses anti-inflammatory , antioxidative and antifibrotic properties .
However , the effects of Pts on lipopolysaccharide ( LPS ) -induced pulmonary fibrosis are still unknown .
In our study , the Pts group showed lower lung injury and fibrosis scores , and lower levels of hydroxyproline and protein ( collagen I and transforming growth factor-β ) than the scores and levels in mice treated with LPS .
MMP-1 was the degrading enzyme of collagen @ @ @ @ @ @ @ MMP-1 , disturbing the degradation of collagen .
Additionally , Pts remarkably reversed the LPS-induced inhibition of interleukin-10 and the release of tumor necrosis factor-α , interleukin-6 and interleukin-1β .
In terms of cellular pathways , Pts treatment ameliorated LPS-activated nuclear factor kappa B ( NF-κB ) and NOD-like receptor NLRP3 signaling .
Besides , LPS-induced low levels of A20 could be activated by Pts .
In addition , Pts treatment reversed the high levels of Caspase-3 , poly ADP-ribose polymerase ( PARP ) and Bcl2-associated X protein ( Bax ) expression and @ @ @ @ @ @ @ ( Bcl2 ) that had been induced by LPS .
Moreover , oxidative stress is also involved in the pathogenesis of fibrosis .
Our findings indicate that LPS injection triggered the production of myeloperoxidase ( MPO ) and malondialdehyde ( MDA ) and the depletion of superoxide dismutase ( SOD ) and glutathione ( GSH ) , and that these effects were notably reversed by treatment with Pts .
In addition , Pts induced the dissociation of Kelch-like epichlorohydrin-associatedprotein-1 ( Keap-1 ) and NF-E2 related factor-2 ( Nrf2 ) and the activation of @ @ @ @ @ @ @ ( P ) H : quinine oxidoreductase , glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modifier ) .
In conclusion , oxidative stress , apoptosis and inflammation are involved in early pulmonary fibrosis and Pts exerts a protective effect by activating Keap-1/Nrf2 , inhibiting caspase-dependent A20/NF-κB and NLRP3 signaling pathways .

Early pulmonary fibrosis after acute lung injury leads to poor prognosis and high mortality. Pterostilbene (Pts), a bioactive component in blueberries, possesses anti-inflammatory, antioxidative and antifibrotic properties. However, the effects of Pts on lipopolysaccharide (LPS)-induced pulmonary fibrosis are still unknown. In our study, the Pts group showed lower lung injury and fibrosis scores, and lower levels of hydroxyproline and protein (collagen I and transforming growth factor-β) than the scores and levels in mice treated with LPS. MMP-1 was the degrading enzyme of collagen I and LPS caused the inhibition of MMP-1, disturbing the degradation of collagen. Additionally, Pts remarkably reversed the LPS-induced inhibition of interleukin-10 and the release of tumor necrosis factor-α, interleukin-6 and interleukin-1β. In terms of cellular pathways, Pts treatment ameliorated LPS-activated nuclear factor kappa B (NF-κB) and NOD-like receptor NLRP3 signaling. Besides, LPS-induced low levels of A20 could be activated by Pts. In addition, Pts treatment reversed the high levels of Caspase-3, poly ADP-ribose polymerase (PARP) and Bcl2-associated X protein (Bax) expression and the low levels of B cell lymphoma/lewkmia-2 (Bcl2) that had been induced by LPS. Moreover, oxidative stress is also involved in the pathogenesis of fibrosis. Our findings indicate that LPS injection triggered the production of myeloperoxidase (MPO) and malondialdehyde (MDA) and the depletion of superoxide dismutase (SOD) and glutathione (GSH), and that these effects were notably reversed by treatment with Pts. In addition, Pts induced the dissociation of Kelch-like epichlorohydrin-associatedprotein-1 (Keap-1) and NF-E2 related factor-2 (Nrf2) and the activation of downstream genes (heme oxygenase-1, NAD(P)H:quinine oxidoreductase, glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modifier). In conclusion, oxidative stress, apoptosis and inflammation are involved in early pulmonary fibrosis and Pts exerts a protective effect by activating Keap-1/Nrf2, inhibiting caspase-dependent A20/NF-κB and NLRP3 signaling pathways.


greenmedinfo--2020-05-09--Realizing the potential of blueberry as natural inhibitor of metastasis and powerful apoptosis induc

Realizing the potential of blueberry as natural inhibitor of metastasis and powerful apoptosis inducer.

Blueberries belong to the genus Vaccinium of the family Ericaceae .
Rapidly accumulating experimentally verified data is uncovering tremendous pharmacological @ @ @ @ @ of Blueberries against different diseases .
Our rapidly evolving knowledge about multifaceted nature of cancer @ @ @ @ @ search for different strategies to target multiple effectors of oncogenic networks to effectively inhibit cancer @ @ @ @ @ , Whole blueberry powder and various bioactive constituents ( Pterostilbene , malvidin-3-galactoside ) of Blueberries @ @ @ @ @ inhibit metastasis in animal models .
These results are encouraging and future studies must converge @ @ @ @ @ pathways effectively modulated by Blueberries in different cancers .
It seems exciting to note that @ @ @ @ @ inhibitory effects of Blueberry , however , to reap full benefits it is necessary to @ @ @ @ @ critically re-interpret the mechanisms used by active components of Blueberry to inhibit or prevent metastasis @ @ @ @ @ scientific evidence revealed visible knowledge gaps and better understanding of the targets of Blueberry will @ @ @ @ @ meaningful translation of laboratory findings to clinically effective therapeutics .

Blueberries belong to the genus Vaccinium of the family Ericaceae. Rapidly accumulating experimentally verified data is uncovering tremendous pharmacological properties of biologically active constituents of Blueberries against different diseases. Our rapidly evolving knowledge about multifaceted nature of cancer has opened new horizons to search for different strategies to target multiple effectors of oncogenic networks to effectively inhibit cancer onset and progression. Excitingly, Whole blueberry powder and various bioactive constituents (Pterostilbene, malvidin-3-galactoside) of Blueberries have been shown to efficiently inhibit metastasis in animal models. These results are encouraging and future studies must converge on identification of cell signaling pathways effectively modulated by Blueberries in different cancers. It seems exciting to note that researchers are focusing on metastasis inhibitory effects of Blueberry, however, to reap full benefits it is necessary to take a step back and critically re-interpret the mechanisms used by active components of Blueberry to inhibit or prevent metastasis. Overview of the existing scientific evidence revealed visible knowledge gaps and better understanding of the targets of Blueberry will be helpful in efficient and meaningful translation of laboratory findings to clinically effective therapeutics.


greenmedinfo--2020-05-09--This suggested that polyphenol-rich by-products might provide a similar health effect in high-fat di

This suggested that polyphenol-rich by-products might provide a similar health effect in high-fat diet individuals.

The barrier-improving functions of fermented blueberry pomace ( FBP ) and its potential mechanism were investigated in this study .
Polyphenols and the approximate composition of FBP were evaluated according to the National Standard of the People 's Republic of China and the UPLC-MS system .
Male C57BL/6 mice were fed a control diet ( CD ) or a high-fat diet ( HFD ) with or without FBP supplementation .
Oxidative stress , inflammation , histological morphology and the expression of functional proteins in the small intestine of mice were evaluated using the enzyme linked immunosorbent assay ( ELISA ) @ @ @ @ @ @ @ ) and western blotting .
The content of protein , fat , soluble dietary fiber , insoluble dietary fiber and carbohydrates ( non-dietary fiber ) was 114.5± 1.5 g kg , 5.0± 0.2 g kg , 48.0± 0.1 g kg , 360.3± 2.2 g kgand 423 g kg ( by difference ) , respectively .
Thirty-six polyphenols were identified in FBP .
FBP improved the growth of mice and attenuated hepatic and intestinal oxidative stress .
Intestinal inflammation was significantly reduced through the decrease of tumor necrosis factor-alpha ( TNF-α ) and myeloperoxidase @ @ @ @ @ @ @ increase of interleukin-10 ( IL-10 ) .
FBP supplementation significantly improved the intestinal morphology and barrier function , potentially by mediating the NF-κB-MLCK signaling pathway .
The supplementation of FBP in HFD mice enhanced the intestinal barrier function .
This suggested that polyphenol-rich by-products might provide a similar health effect in HFD individuals .

The barrier-improving functions of fermented blueberry pomace (FBP) and its potential mechanism were investigated in this study. Polyphenols and the approximate composition of FBP were evaluated according to the National Standard of the People's Republic of China and the UPLC-MS system. Male C57BL/6 mice were fed a control diet (CD) or a high-fat diet (HFD) with or without FBP supplementation. Oxidative stress, inflammation, histological morphology and the expression of functional proteins in the small intestine of mice were evaluated using the enzyme linked immunosorbent assay (ELISA), quantitative polymerase chain reaction (qPCR) and western blotting. The content of protein, fat, soluble dietary fiber, insoluble dietary fiber and carbohydrates (non-dietary fiber) was 114.5± 1.5 g kg, 5.0± 0.2 g kg, 48.0± 0.1 g kg, 360.3± 2.2 g kgand 423 g kg(by difference), respectively. Thirty-six polyphenols were identified in FBP. FBP improved the growth of mice and attenuated hepatic and intestinal oxidative stress. Intestinal inflammation was significantly reduced through the decrease of tumor necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) as well as an increase of interleukin-10 (IL-10). FBP supplementation significantly improved the intestinal morphology and barrier function, potentially by mediating the NF-κB-MLCK signaling pathway. The supplementation of FBP in HFD mice enhanced the intestinal barrier function. This suggested that polyphenol-rich by-products might provide a similar health effect in HFD individuals.


greenmedinfo--2020-05-09--Blueberry proanthocyanidins and anthocyanins improve metabolic health through a gut microbiota-depen

Blueberry proanthocyanidins and anthocyanins improve metabolic health through a gut microbiota-dependent mechanism in diet-induced obese mice.

Blueberry consumption can prevent obesity-linked metabolic diseases and it has been proposed that its polyphenol content may contribute to these effects .
Polyphenols have been shown to favourably impact metabolic health , but the role of specific polyphenol classes , and whether the gut microbiota is linked to these effects remains unclear .
We aimed to evaluate the impact of whole blueberry and blueberry polyphenols against the development of obesity and insulin resistance , and to determine the potential role of gut microbes in these effects by using fecal microbiota transplantation ( FMT ) .
Seventy C57BL/6 male mice were @ @ @ @ @ @ @ for 12 weeks : balanced diet ( Chow ) , high-fat high-sucrose ( HFHS ) diet , or HFHS supplemented with whole blueberry powder ( BB ) , anthocyanidin ( ANT ) or proanthocyanidin ( PAC ) -rich extracts .
After 8 weeks , mice were housed in metabolic cages and an oral glucose tolerance test ( oGTT ) was performed .
Sixty germ-free mice fed HFHS diet received FMT from one of the above groups bi-weekly for 8 weeks , followed by an oGTT .
PAC-treated mice were leaner than HFHS controls @ @ @ @ @ @ @ and were more physically active .
This observation was reproduced in germ-free mice receiving FMT from PAC-treated mice .
PAC and ANT-treated mice showed improved insulin responses during oGTT , and this finding was also reproduced in germ-free mice following FMT .
These results show that blueberry PAC and ANT polyphenols can reduce diet-induced body weight and improve insulin sensitivity , and that at least part of these beneficial effects are explained by modulation of the gut microbiota .

Blueberry consumption can prevent obesity-linked metabolic diseases and it has been proposed that its polyphenol content may contribute to these effects. Polyphenols have been shown to favourably impact metabolic health, but the role of specific polyphenol classes, and whether the gut microbiota is linked to these effects remains unclear. We aimed to evaluate the impact of whole blueberry and blueberry polyphenols against the development of obesity and insulin resistance, and to determine the potential role of gut microbes in these effects by using fecal microbiota transplantation (FMT). Seventy C57BL/6 male mice were assigned to one of the following diets for 12 weeks: balanced diet (Chow), high-fat high-sucrose (HFHS) diet, or HFHS supplemented with whole blueberry powder (BB), anthocyanidin (ANT) or proanthocyanidin (PAC)-rich extracts. After 8 weeks, mice were housed in metabolic cages and an oral glucose tolerance test (oGTT) was performed. Sixty germ-free mice fed HFHS diet received FMT from one of the above groups bi-weekly for 8 weeks, followed by an oGTT. PAC-treated mice were leaner than HFHS controls although they had the same energy intake and were more physically active. This observation was reproduced in germ-free mice receiving FMT from PAC-treated mice. PAC and ANT-treated mice showed improved insulin responses during oGTT, and this finding was also reproduced in germ-free mice following FMT. These results show that blueberry PAC and ANT polyphenols can reduce diet-induced body weight and improve insulin sensitivity, and that at least part of these beneficial effects are explained by modulation of the gut microbiota.


greenmedinfo--2020-05-09--Phytotherapy using blueberry leaf polyphenols to alleviate non-alcoholic fatty liver disease.

BACKGROUND : Since non-alcoholic fatty liver disease ( NAFLD ) pathogenesis is multi-factorial , pharmacotherapy with a specific target commonly exhibits limited efficacy .
Phytotherapy , whose therapeutic efficacy is based on the combined action of several active compounds , offers new treatment opportunity for NAFLD .
As a representative , many natural polyphenols could be utilized in phytotherapy for NAFLD .
PURPOSE : In present work , we aimed to investigate the therapeutic effects and underlying mechanism of polyphenols in blueberry leaves ( PBL ) on NAFLD from a mitochondria-centric perspective since mitochondrial dysfunction could play a dominant role @ @ @ @ @ @ @ quantification of PBL were performed using liquid chromatography coupled with tandem mass spectrometry .
The beneficial effects , especially improving mitochondrial function , and potential mechanism of PBL on NAFLD were studied by in vitro and in vivo study .
RESULTS : Polyphenols were abundant in blueberry leaves making it advantaged in NAFLD phytotherapy .
PBL effectively alleviated hepatic steatosis , oxidative stress and inflammation as indicated by both in vitro and in vivo study .
Furthermore , PBL mediated improvement of mitochondrial dysfunction and antioxidant capability through activation of AMPK/PGC-1α/SIRT3 signaling axis @ @ @ @ @ @ @ takes precedence over hepatic steatosis and induces NAFLD development , we conclude that PBL improve mitochondrial dysfunction and oxidative defense , subsequently alleviate hepatic steatosis , oxidative stress and inflammation , and eventually alleviate NAFLD .

BACKGROUND: Since non-alcoholic fatty liver disease (NAFLD) pathogenesis is multi-factorial, pharmacotherapy with a specific target commonly exhibits limited efficacy. Phytotherapy, whose therapeutic efficacy is based on the combined action of several active compounds, offers new treatment opportunity for NAFLD. As a representative, many natural polyphenols could be utilized in phytotherapy for NAFLD.
PURPOSE: In present work, we aimed to investigate the therapeutic effects and underlying mechanism of polyphenols in blueberry leaves (PBL) on NAFLD from a mitochondria-centric perspective since mitochondrial dysfunction could play a dominant role in NAFLD.
METHODS: Identification and quantification of PBL were performed using liquid chromatography coupled with tandem mass spectrometry. The beneficial effects, especially improving mitochondrial function, and potential mechanism of PBL on NAFLD were studied by in vitro and in vivo study.
RESULTS: Polyphenols were abundant in blueberry leaves making it advantaged in NAFLD phytotherapy. PBL effectively alleviated hepatic steatosis, oxidative stress and inflammation as indicated by both in vitro and in vivo study. Furthermore, PBL mediated improvement of mitochondrial dysfunction and antioxidant capability through activation of AMPK/PGC-1α/SIRT3 signaling axis.
CONCLUSION: Considering that mitochondrial dysfunction takes precedence over hepatic steatosis and induces NAFLD development, we conclude that PBL improve mitochondrial dysfunction and oxidative defense, subsequently alleviate hepatic steatosis, oxidative stress and inflammation, and eventually alleviate NAFLD.


greenmedinfo--2020-05-09--Chinese wild blueberries have potential as a natural preservative to prevent and control foodborne p

Chinese wild blueberries have potential as a natural preservative to prevent and control foodborne pathogens.

The objective of this study was to evaluate the antibacterial effect of Chinese wild blueberry extract and its fractions against Listeria monocytogenes , Staphylococcus aureus , Salmonella Enteritidis , and Vibrio parahaemolyticus .
Chinese wild blueberry ( Vaccinium uliginosum ) crude extract ( BBE ) was obtained using methanol extraction , and sugars plus organic acids ( F1 ) , phenolics fraction ( F2 ) , and anthocyanins plus proanthocyanidins ( F3 ) fractions were separated using C-18 Sep-Pak columns .
The minimal inhibitory concentration and minimal bactericidal concentration of each fractional component were determined using a two-fold-serial dilution method @ @ @ @ @ @ @ and protein release ( Bradford protein assay ) were determined by spectrophotometry , to evaluate the permeability of the cell membrane .
F3 was found to exhibit the greatest antimicrobial activity against the four tested strains , followed by F2 , F1 , and BBE .
V. parahaemolyticus was the most sensitive to the all fractions , followed by S. Enteritidis , L. monocytogenes , and S. aureus .
Survival curve analysis showed that the number of bacteria decreased from six log colony-forming units ( CFU ) to less than 10 CFU after @ @ @ @ @ @ @ hr , which demonstrated the bactericidal effect of blueberry fractions .
Furthermore , when the pathogens were treated with fractions for 2 hr , the ODand ODvalues increased significantly ( P

The objective of this study was to evaluate the antibacterial effect of Chinese wild blueberry extract and its fractions against Listeria monocytogenes, Staphylococcus aureus, Salmonella Enteritidis, and Vibrio parahaemolyticus. Chinese wild blueberry (Vaccinium uliginosum) crude extract (BBE) was obtained using methanol extraction, and sugars plus organic acids (F1), phenolics fraction (F2), and anthocyanins plus proanthocyanidins (F3) fractions were separated using C-18 Sep-Pak columns. The minimal inhibitory concentration and minimal bactericidal concentration of each fractional component were determined using a two-fold-serial dilution method. Nucleic acid leakage (OD) and protein release (Bradford protein assay) were determined by spectrophotometry, to evaluate the permeability of the cell membrane. F3 was found to exhibit the greatest antimicrobial activity against the four tested strains, followed by F2, F1, and BBE. V. parahaemolyticus was the most sensitive to the all fractions, followed by S. Enteritidis, L. monocytogenes, and S. aureus. Survival curve analysis showed that the number of bacteria decreased from six log colony-forming units (CFU) to less than 10 CFU after bacteria were treated with fractions for 12 hr, which demonstrated the bactericidal effect of blueberry fractions. Furthermore, when the pathogens were treated with fractions for 2 hr, the ODand ODvalues increased significantly (P< 0.01), which indicated the significant release of nucleic acid and protein. The results from this study indicated that blueberry fractions, especially F3, inhibited the growth of foodborne pathogens by damaging their cell membrane, and may be developed as a natural preservative to prevent and control foodborne pathogens. PRACTICAL APPLICATION: A blueberry crude extract and its sugars plus organic acids, phenolics, and anthocyanins plus proanthocyanidins fractions, inhibited the growth of foodborne pathogens by destroying their cell membrane. Therefore, Chinese wild blueberries have potentialas a natural preservative to prevent and control foodborne pathogens.


greenmedinfo--2020-05-09--Consumption of 22 g freeze-dried blueberries for 8 wk may beneficially affect cardiometabolic health

Background : Blueberries are dietary sources of polyphenols , specifically anthocyanins .
Anthocyanins have been identified as having a strong association with type 2 diabetes risk reduction ; however , to date few human clinical trials have evaluated the potential beneficial health effects of blueberries in populations with type 2 diabetes .
Objectives : We investigated the effects of blueberry consumption for 8 wk on cardiometabolic parameters in men with type 2 diabetes .
Methods : In a double-blind , parallel-arm , randomized controlled trial , 52 men who are US veterans [ mean baseline characteristics : age , 67 @ @ @ @ @ @ @ ; weight , 102 kg ( range : 80-130 kg ) ; BMI ( in kg/m ) , 34 ( range : 26-45 ) ] were randomly assigned to 1 of 2 intervention groups .
The interventions were either 22 g freeze-dried blueberries or 22 g placebo .
The study participants were asked to consume 11 g freeze-dried blueberries or placebo with each of their morning and evening meals along with their typical diet .
Results : Mean ± SE hemoglobin A1c ( 7.1 % ± 0.1 % compared with 7.5 % ± @ @ @ @ @ @ @ fructosamine ( 275.5 ± 4.1 compared with 292.4 ± 7.9 µmol/L ; = 0.04 ) , triglycerides ( 179.6 ± 10.1 compared with 199.6 ± 19.9 mg/dL ; = 0.03 ) , aspartate transaminase ( 23.2 ± 1.4 compared with 30.5 ± 2.7 units/L ; = 0.02 ) , and alanine transaminase ( 35.6 ± 1.5 compared with 48.3 ± 2.9 units/L ; = 0.0003 ) were significantly lower for those consuming blueberries for 8 wk than for those consuming the placebo .
Fasting plasma glucose concentrations ; serum insulin , total cholesterol @ @ @ @ @ @ @ protein concentrations ; blood pressure ; and body weight werenot significantly different after 8 wk consumption of blueberries compared with the placebo .
Conclusions : Consumption of 22 g freeze-dried blueberries for 8 wk may beneficially affect cardiometabolic health parameters in men with type 2 diabetes.This trial was registered at clinicaltrials.gov as NCT02972996 .

Background: Blueberries are dietary sources of polyphenols, specifically anthocyanins. Anthocyanins have been identified as having a strong association with type 2 diabetes risk reduction; however, to date few human clinical trials have evaluated the potential beneficial health effects of blueberries in populations with type 2 diabetes.
Objectives: We investigated the effects of blueberry consumption for 8 wk on cardiometabolic parameters in men with type 2 diabetes.
Methods: In a double-blind, parallel-arm, randomized controlled trial, 52 men who are US veterans [mean baseline characteristics: age, 67 y (range: 51-75 y); weight, 102 kg (range: 80-130 kg); BMI (in kg/m), 34 (range: 26-45)] were randomly assigned to 1 of 2 intervention groups. The interventions were either 22 g freeze-dried blueberries or 22 g placebo. The study participants were asked to consume 11 g freeze-dried blueberries or placebo with each of their morning and evening meals along with their typical diet.
Results: Mean ± SE hemoglobin A1c (7.1% ± 0.1% compared with 7.5% ± 0.2%; = 0.03), fructosamine (275.5 ± 4.1 compared with 292.4 ± 7.9 µmol/L; = 0.04), triglycerides (179.6 ± 10.1 compared with 199.6 ± 19.9 mg/dL; = 0.03), aspartate transaminase (23.2 ± 1.4 compared with 30.5 ± 2.7 units/L;= 0.02), and alanine transaminase (35.6 ± 1.5 compared with 48.3 ± 2.9 units/L; = 0.0003) were significantly lower for those consuming blueberries for 8 wk than for those consuming the placebo. Fasting plasma glucose concentrations; serum insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, and C-reactive protein concentrations; blood pressure; and body weight werenot significantly different after 8 wk consumption of blueberries compared with the placebo.
Conclusions: Consumption of 22 g freeze-dried blueberries for 8 wk may beneficially affect cardiometabolic health parameters in men with type 2 diabetes.This trial was registered at clinicaltrials.gov as NCT02972996.


greenmedinfo--2020-05-09--The intake of blueberries prevented the development of bladder dysfunction secondary to bladder outl

The intake of blueberries prevented the development of bladder dysfunction secondary to bladder outlet obstruction.

Various berries demonstrate antioxidant activity , and this effect is expected to prevent chronic diseases .
We examined whether a diet containing blueberry powder could prevent the development of bladder dysfunction secondary to bladder outlet obstruction ( BOO ) .
Eighteen 8-week-old male Sprague-Dawley rats were randomly divided into three groups : Sham ( sham operated + normal diet ) , N-BOO ( BOO operated + normal diet ) and B-BOO ( BOO operated + blueberry diet ) .
Four weeks after BOO surgery , the N-BOO group developed bladder dysfunction with detrusor overactivity .
The B-BOO group showed significantly @ @ @ @ @ @ @ The urinary levels of 8-hydroxy-2'-deoxyguanosine ( 8-OHdG ) and malondialdehyde ( MDA ) were measured as oxidative stress markers .
In the N-BOO group , 8-OHdG increased 1.6-fold and MDA increased 1.3-fold at 4 weeks after surgery , whereas the increase in 8-OHdG was significantly reduced by 1.1-fold , despite a similar increase in MDA , in the B-BOO group .
Bladder remodeling was confirmed due to bladder hypertrophy , fibrosis and increased connexin43 expression in the N-BOO group , but these histological changes were reduced in the B-BOO group .
The intake @ @ @ @ @ @ @ dysfunction secondary to BOO .
This effect seems to be related to antioxidation and the inhibition of bladder remodeling .

Various berries demonstrate antioxidant activity, and this effect is expected to prevent chronic diseases. We examined whether a diet containing blueberry powder could prevent the development of bladder dysfunction secondary to bladder outlet obstruction (BOO). Eighteen 8-week-old male Sprague-Dawley rats were randomly divided into three groups: Sham (sham operated + normal diet), N-BOO (BOO operated + normal diet) and B-BOO (BOO operated + blueberry diet). Four weeks after BOO surgery, the N-BOO group developed bladder dysfunction with detrusor overactivity. The B-BOO group showed significantly improved micturition volume and micturition interval. The urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) were measured as oxidative stress markers. In the N-BOO group, 8-OHdG increased 1.6-fold and MDA increased 1.3-fold at 4 weeks after surgery, whereas the increase in 8-OHdG was significantly reduced by 1.1-fold, despite a similar increase in MDA, in the B-BOO group. Bladder remodeling was confirmed due to bladder hypertrophy, fibrosis and increased connexin43 expression in the N-BOO group, but these histological changes were reduced in the B-BOO group. The intake of blueberries prevented the development of bladder dysfunction secondary to BOO. This effect seems to be related to antioxidation and the inhibition of bladder remodeling.


greenmedinfo--2020-05-09--Lycium barbarum polysaccharide protects against ethanol-induced spermiotoxicity and testicular degen

Lycium barbarum polysaccharide protects against ethanol-induced spermiotoxicity and testicular degeneration in Immp2l+/- mice.

Studies have indicated that high levels of ethanol exposure impaired spermatogenesis in mice .
However , the effects of chronic and low-dose alcohol consumption on susceptible populations remain unclear .
The previous studies have confirmed that Immp2l mutant mice ( Immp2lor Immp2l ) suffered from increased levels of oxidative stress ( OS ) and male infertility , heterozygous lmmp2l mice ( Immp2l ) showed no altered ROS levels under physiological condition .
Lycium barbarum polysaccharide ( LBP ) significantly scavenge oxygen free radicals and enhance antioxidant enzyme activity .
The objectives of present study were to research the effects of @ @ @ @ @ @ @ , explore the protective function of LBP and possible mechanism .
The results indicated that chronic ethanol exposure leads to spermatogenic impairment and triggered a toxic effect on germ cell , 10 mg/kg LBP administration improved the quality of spermatozoon , decreased the ratio of apoptotic germ cells and the expression of Col1a1 and Col1a2 , while increased the level of TNP2 and RPL31 .
In conclusion , the study may provide basic knowledge about LBP 's important role against ethanol-induced spermiotoxicity and testicular degeneration in Immp2lmice , and the mechanism may be @ @ @ @ @ @ @ spermatogenic epithelium by decreasing the expression of Collagen level leading to alterations in protein biosynthesis during the process of spermatogenesis .

Studies have indicated that high levels of ethanol exposure impaired spermatogenesis in mice. However, the effects of chronic and low-dose alcohol consumption on susceptible populations remain unclear. The previous studies have confirmed that Immp2l mutant mice (Immp2lor Immp2l) suffered from increased levels of oxidative stress(OS) and male infertility, heterozygous lmmp2l mice (Immp2l) showed no altered ROS levels under physiological condition. Lycium barbarum polysaccharide (LBP) significantly scavenge oxygen free radicals and enhance antioxidant enzyme activity. The objectives of present study were to research the effects of chronic and low-dose alcohol-induced damage on Immp2l, explore the protective function of LBP and possible mechanism. The results indicated that chronic ethanol exposure leads to spermatogenic impairment and triggered a toxic effect on germ cell, 10 mg/kg LBP administration improved the quality of spermatozoon, decreased the ratio of apoptotic germ cells and the expression of Col1a1 and Col1a2, while increased the level of TNP2 and RPL31. In conclusion, the study may provide basic knowledge about LBP's important role against ethanol-induced spermiotoxicity and testicular degeneration in Immp2lmice, and the mechanism may be that LBP influenced the state of the spermatogenic epithelium by decreasing the expression of Collagen level leading to alterations in protein biosynthesis during the process of spermatogenesis.


greenmedinfo--2020-05-09--Effects of extraction methods on immunology activity and chemical profiles of Lycium barbarum polysa

Effects of extraction methods on immunology activity and chemical profiles of Lycium barbarum polysaccharides.

It has been proven that polysaccharides have bioactivities and are beneficial to cure many diseases .
Lycium barbarum fruit is widely used as a functional food all over the world , which main active component is L. barbarum polysaccharides ( LBPs ) .
In this study , classical hot water extraction ( HWE ) , microwave assisted extraction ( MAE ) , ultrasonic assisted extraction ( UAE ) and pressurized liquid extraction ( PLE ) were used to extracted LBP .
The chemical properties of LBPs were evaluated in terms of total polysaccharide contents , uronic acid contents and protein @ @ @ @ @ @ @ coupled with multi angle laser light scattering and refractive index detector was applied to measure the characters such as molecular weight , radius of gyration and polydispersity index .
Then the immunomodulatory activity of LBPs was evaluated through RAW 264.7 cells .
The results showed that HWE was the best method to get the highest total sugar and acidic polysaccharides , MAE was preferable to extract polysaccharide-protein complex , but PLE , UAE and HWE could get better immunomodulatory activity polysaccharides than MAE .
Besides , the peak 3 in chromatogram of MAE @ @ @ @ @ @ @ of LBPs produced by other 3 extraction methods , which suggested that peak 1 and peak 2 might be biologically active polysaccharides fractions in LBPs .
Therefore , effect of different extraction methods on structure and composition of LBPs attributed to their variance of immunological activities .

It has been proven that polysaccharides have bioactivities and are beneficial to cure many diseases. Lycium barbarum fruit is widely used as a functional food all over the world, which main active component is L. barbarum polysaccharides (LBPs). In this study, classical hot water extraction (HWE), microwave assisted extraction (MAE), ultrasonic assisted extraction (UAE) and pressurized liquid extraction (PLE) were used to extracted LBP. The chemical properties of LBPs were evaluated in terms of total polysaccharide contents, uronic acid contents and protein contents. High performance size exclusion chromatography coupled with multi angle laser light scattering and refractive index detector was applied to measure the characters such as molecular weight, radius of gyration and polydispersity index. Then the immunomodulatory activity of LBPs was evaluated through RAW 264.7 cells. The results showed that HWE was the best method to get the highest total sugar and acidic polysaccharides, MAE was preferable to extract polysaccharide-protein complex, but PLE, UAE and HWE could get better immunomodulatory activity polysaccharides than MAE. Besides, the peak 3 in chromatogram of MAE extracted LBPs was obviously higher than those of LBPs produced by other 3 extraction methods, which suggested that peak 1 and peak 2 might be biologically active polysaccharides fractions in LBPs. Therefore, effect of different extraction methods on structure and composition of LBPs attributed to their variance of immunological activities.


greenmedinfo--2020-05-09--These results demonstrate the immunomodulatory effects of L. barbarium polysaccharides and its effec

These results demonstrate the immunomodulatory effects of L. barbarium polysaccharides and its effective uptake by macrophages and intestine.

L. is a widely used functional food and medicinal herb in Asian countries.polysaccharides ( LBP ) are considered as one of the major medicinal components offruit and exhibits a wide range of biological activities .
Here , we investigated the immunomodulatory effects of LBP and its uptake behaviors at the cellular level .
LBP was prepared by water extraction and ethanol precipitation , and divided into two fractions based on the molecular weight distribution by ultrafiltration ( LBP > 10 kDa and LBP < 10 kDa ) .
The physicochemical properties of LBP and LBP fractions were well characterized .
@ @ @ @ @ @ @ enhanced the viability of macrophages RAW264.7 cells and induced cell polarization , but had weak effects to other tested tumor cell lines and normal cell line .
This fraction could regulate the production of NO , TNF-α , IL-6 and ROS in RAW264.7 cells , suggesting both pro-inflammatory and anti-inflammatory effects .
The dye-labeled LBP could be internalized into all tested cell lines and accumulated in lysosomes .
The internalization of LBP in RAW264.7 cells is mainly through the clathrin-mediated endocytosis pathway .
The Caco-2 intestinal transport experiment demonstrated that the dye labeled @ @ @ @ @ @ @ cell monolayer ( mimic intestinal epithelium ) through clathrin-mediated endocytosis .
These results demonstrate the immunomodulatory effects of LBP and its effective uptake bymacrophages and intestine .

L. is a widely used functional food and medicinal herb in Asian countries.polysaccharides (LBP) are considered as one of the major medicinal components offruit and exhibits a wide range of biological activities. Here, we investigated the immunomodulatory effects of LBP and its uptake behaviors at the cellular level. LBP was prepared by water extraction and ethanol precipitation, and divided into two fractions based on the molecular weight distribution by ultrafiltration (LBP>10 kDa and LBP<10 kDa). The physicochemical properties of LBP and LBP fractions were well characterized. The LBP>10 kDa fraction greatly enhanced the viability of macrophages RAW264.7 cells and induced cell polarization, but had weak effects to other tested tumor cell lines and normal cell line. This fraction could regulate the production of NO, TNF-α, IL-6 and ROS in RAW264.7 cells, suggesting both pro-inflammatory and anti-inflammatory effects. The dye-labeled LBP could be internalized into all tested cell lines and accumulated in lysosomes. The internalization of LBP in RAW264.7 cells is mainly through the clathrin-mediated endocytosis pathway. The Caco-2 intestinal transport experiment demonstrated that the dye labeled LBP could be transported through the Caco-2 cell monolayer (mimic intestinal epithelium) through clathrin-mediated endocytosis. These results demonstrate the immunomodulatory effects of LBP and its effective uptake bymacrophages and intestine.


greenmedinfo--2020-05-09--Immunostimulating activity of Lycium chinense Miller root extract through enhancing cytokine and che

Immunostimulating activity of Lycium chinense Miller root extract through enhancing cytokine and chemokine production and phagocytic capacity of macrophages.

Whereas the fruits and a small portion of root bark of Lycium trees are commonly marketed in Korea as traditional medicine or functional foods , majority of their whole roots have been largely discarded .
To develop the whole root of these plants as more value-added materials , this study aimed to evaluate the potential immunostimulating activity of a water extract ( GTR-101 ) from L. chinense Miller roots using macrophages .
The GTR-101 ( 0-500 μg/ml ) significantly , dose-dependently increased the secretion of pro-inflammatory cytokines ( TNF-α and IL-6 ) , chemokines ( RANTES and MIP-1α ) , @ @ @ @ @ @ @ inducible nitric oxide synthase , and activated the Akt , NF-κB , and MAPKs ( ERK and p38 ) signaling proteins .
GTR-101also significantly enhanced the phagocytic activity of RAW 264.7 cells and bone marrow-derived macrophages .
These results suggest that GTR-101 stimulates the early innate immunity via inducing the pro-inflammatory cytokine and chemokine secretion and enhancing the phagocytic activity of macrophages.PRACTICAL APPLICATIONS : The GTR-101 prepared from L. chinense Miller roots may be useful for enhancing body 's defense systems especially in the elderly and cancer patients with an impaired or reduced @ @ @ @ @ @ @ used as a natural immunostimulating ingredient in health foods or complementary medicine .

Whereas the fruits and a small portion of root bark of Lycium trees are commonly marketed in Korea as traditional medicine or functional foods, majority of their whole roots have been largely discarded. To develop the whole root of these plants as more value-added materials, this study aimed to evaluate the potential immunostimulating activity of a water extract (GTR-101) from L. chinense Miller roots using macrophages. The GTR-101 (0-500 μg/ml) significantly, dose-dependently increased the secretion of pro-inflammatory cytokines (TNF-α and IL-6), chemokines (RANTES and MIP-1α), nitric oxide, and the expression of inducible nitric oxide synthase, and activated the Akt, NF-κB, and MAPKs (ERK and p38) signaling proteins. GTR-101also significantly enhanced the phagocytic activity of RAW 264.7 cells and bone marrow-derived macrophages. These results suggest that GTR-101 stimulates the early innate immunity via inducing the pro-inflammatory cytokine and chemokine secretion and enhancing the phagocytic activity of macrophages.PRACTICAL APPLICATIONS: The GTR-101 prepared from L. chinense Miller roots may be useful for enhancing body's defense systems especially in the elderly and cancer patients with an impaired or reduced immune response and may thus be effectively used as a natural immunostimulating ingredient in health foods or complementary medicine.


greenmedinfo--2020-05-09--Lycium barbarum polysaccharides ameliorate intestinal barrier dysfunction and inflammation through t

Lycium barbarum polysaccharides ameliorate intestinal barrier dysfunction and inflammation through the MLCK-MLC signaling pathway in Caco-2 cells.

Impairment of the intestinal barrier often occurs in inflammatory bowel diseases , and pro-inflammatory factors play a vital role in @ @ @ @ @ .
In our study , the potential protective effects of Lycium barbarum polysaccharides ( LBP @ @ @ @ @ evoked by pro-inflammatory factors and its anti-inflammatory effects were investigated .
Caco-2 cells were stimulated @ @ @ @ @ factor ( TNF ) -α in the presence or absence of LBP .
Our findings @ @ @ @ @ increase of paracellular permeability and the decrease of transepithelial electrical resistance ( TER ) in @ @ @ @ @ , LBP also prevented the secretion of pro-inflammatory markers ( IL-8 , IL-6 , ICAM-1 @ @ @ @ @ Caco-2 cells .
Moreover , LBP inhibited the overexpression of tight junction ( TJ ) @ @ @ @ @ , and occludin ) and the increase of MLCK , pMLC , p-IκBα and NFκBp65 @ @ @ @ @ was suppressed by LBP pre-incubation .
This finding indicated that LBP improve TNF-α-evoked intestinal barrier @ @ @ @ @ signaling pathway mediated by NFκB .

Impairment of the intestinal barrier often occurs in inflammatory bowel diseases, and pro-inflammatory factors play a vital role in the pathogenesis of intestinal diseases. In our study, the potential protective effects of Lycium barbarum polysaccharides (LBP) against intestinal barrier dysfunction evoked by pro-inflammatory factors and its anti-inflammatory effects were investigated. Caco-2 cells were stimulated with or without tumor necrosis factor (TNF)-α in the presence or absence of LBP. Our findings showed that LBP assuaged the increase of paracellular permeability and the decrease of transepithelial electrical resistance (TER) in Caco-2 cells. In addition, LBP also prevented the secretion of pro-inflammatory markers (IL-8, IL-6, ICAM-1 and MCP-1) in TNF-α-challenged Caco-2 cells. Moreover, LBP inhibited the overexpression of tight junction (TJ) proteins (claudin-1, ZO-3, and occludin) and the increase of MLCK, pMLC, p-IκBα and NFκBp65 protein expression evoked by TNF-α was suppressed by LBP pre-incubation. This finding indicated that LBP improve TNF-α-evoked intestinal barrier dysfunction via suppressing the MLCK-MLC signaling pathway mediated by NFκB.


greenmedinfo--2020-05-09--Lycium barbarum polysaccharides improve testicular spermatogenic function in streptozotocin-induced

Lycium barbarum polysaccharides improve testicular spermatogenic function in streptozotocin-induced diabetic rats.

The objective of this study was to investigate the protective effects ofpolysaccharides ( LBP ) on testicular spermatogenic function in streptozotocin ( STZ ) -induced diabetic rats .
Compared to the control group , blood glucose levels were significantly increased and the insulin resistance was markedly aggravated in STZ-induced diabetic rats .
Further , the weight of testis and epididymis and the sperm number and motility were decreased in diabetic rats .
Pathological changes were also observed in the spermatogenic tubules , along with a decreased number of spermatogenic cells , downregulated proliferating cell nuclear antigen ( PCNA ) expression @ @ @ @ @ @ @ testes .
Compared to the saline-treated diabetic rat group , metformin and LBP treatment significantly decreased the level of blood glucose and improved insulin resistance and testicular function .
After treatment with metformin and LBP , the pathological changes in the spermatogenic tubules improved significantly , with an increase in the number of spermatogenic cells , upregulation of PCNA , and suppression of apoptosis in the testes .
The expressions of sirtuin 1 ( SIRT1 ) and hypoxia-inducible factor 1-alpha ( HIF-1α ) in diabetic testes were also upregulated by metformin or LBP @ @ @ @ @ @ @ protective effects by increasing cell proliferation , inhibiting cell apoptosis , and regulating SIRT1/HIF-1α expression in the testes of diabetic rats .

The objective of this study was to investigate the protective effects ofpolysaccharides (LBP) on testicular spermatogenic function in streptozotocin (STZ)-induced diabetic rats. Compared to the control group, blood glucose levels were significantly increased and the insulin resistance was markedly aggravated in STZ-induced diabetic rats. Further, the weight of testis and epididymis and the sperm number and motility were decreased in diabetic rats. Pathological changes were also observed in the spermatogenic tubules, along with a decreased number of spermatogenic cells, downregulated proliferating cell nuclear antigen (PCNA) expression, and increased cell apoptosis in the testes. Compared to the saline-treated diabetic rat group, metformin and LBP treatment significantly decreased the level of blood glucose and improved insulin resistance and testicular function. After treatment with metformin and LBP, the pathological changes in the spermatogenic tubules improved significantly, with an increase in the number of spermatogenic cells, upregulation of PCNA, and suppression of apoptosis in the testes. The expressions of sirtuin 1 (SIRT1) and hypoxia-inducible factor 1-alpha (HIF-1α) in diabetic testes were also upregulated by metformin or LBP treatment. In summary, LBP exerted protective effects by increasing cell proliferation, inhibiting cell apoptosis, and regulating SIRT1/HIF-1α expression in the testes of diabetic rats.


greenmedinfo--2020-05-09--Green tea catechins alleviate autoimmune symptoms and visual impairment in a murine model for human

Green tea catechins alleviate autoimmune symptoms and visual impairment in a murine model for human chronic intraocular inflammation.

Autoimmune uveitis is a sight-threatening disease mainly caused by dysregulation of immunity .
We investigated the therapeutic effects of green @ @ @ @ @ and its major component , epigallocatechin-3-gallate ( EGCG ) , on a murine model of @ @ @ @ @ ) .
Oral administration of GTE , EGCG , dexamethasone , or water , which @ @ @ @ @ induction , was fed every two days to each group .
On day 21 post @ @ @ @ @ examined by confocal scanning laser ophthalmoscopy , optical coherence tomography ( OCT ) , fundus @ @ @ @ @ and electroretinography ( ERG ) prior to sacrificing the animals for histological assessments and gene @ @ @ @ @ ( RCT ) and major retinal vessel diameter were measured on OCT sections and FFA @ @ @ @ @ to water-treated EAU animals , GTE attenuated uveitis clinical manifestations , RCT increase ( 1.100 @ @ @ @ @ ± 0.012 times , P

Autoimmune uveitis is a sight-threatening disease mainly caused by dysregulation of immunity. We investigated the therapeutic effects of green tea extract (GTE) and its major component, epigallocatechin-3-gallate (EGCG), on a murine model of experimental autoimmune uveoretinitis (EAU). Oral administration of GTE, EGCG, dexamethasone, or water, which started 5 days before the induction, was fed every two days to each group. On day 21 post induction, the eyes were examined by confocal scanning laser ophthalmoscopy, optical coherence tomography (OCT), fundus fluorescein angiography (FFA) and electroretinography (ERG) prior to sacrificing the animals for histological assessments and gene expression studies. Retinal-choroidal thicknesses (RCT) and major retinal vessel diameter were measured on OCT sections and FFA images, respectively. Comparing to water-treated EAU animals, GTE attenuated uveitis clinical manifestations, RCT increase (1.100 ± 0.013 times vs 1.005 ± 0.012 times, P < 0.001), retinal vessel dilation (308.9 ± 6.189 units vs 240.8 units, P < 0.001), ERG amplitudes attenuation, histopathological ocular damages, and splenomegaly in EAU mice. The therapeutic effects of GTE were dose dependent and were comparable to dexamethasone. EGCG, a major active constituent of GTE, partially alleviated uveitic phenotypes including recovering visualfunction. Th-17 associated pro-inflammatory gene [interleukin 1 beta (IL-1β), IL-6, IL-17A, and tumor necrosis factor alpha (TNF-α)] expressions were down regulated by GTE and EGCG treatments, which showed no detectable morphological defects in liver and kidney in non-induced and EAU mice. Our findings suggest that GTE consumption can serve as a potent therapeutic agent as well as a food supplement for developing alternative treatments against autoimmune uveitis.


greenmedinfo--2020-05-09--Epigallocatechin-3-gallate suppresses neutrophil migration speed in a transgenic zebrafish model acc

Epigallocatechin-3-gallate suppresses neutrophil migration speed in a transgenic zebrafish model accompanied by reduced inflammatory mediators

Background : Polyphenol catechins from green tea , particularly ( - ) -epigallocatechin-3-gallate ( EGCG ) , exhibits numerous beneficial health effects , although the mechanisms remain unclear .
Methods : In this study , the mechanism of EGCG-mediated healing in an experimentally injured zebrafish model was examined at the cellular and molecular level using confocal microscopy and gene expression analysis .
Results : The mechanisms of action of EGCG were shown to involve : ( 1 ) reducing neutrophil response ( accumulation , travel speed , and distance ) and ( 2 ) downregulating the expression of IL-1β , @ @ @ @ @ @ @ As determined by dynamic time-lapse tracking studies , the local accumulation of neutrophils with high migration speeds after wounding ( n=33 cells , v=0.020 μm/s , d=37.8 μm ) , underwent significant reduction following treatment with EGCG doses of 300 μM ( n=22 cells , v=0.013 μm/s , d=39.5 μm ) and 600 μM ( n=18 cells , v=0.008 μm/s , d=9.53 μm ) .
Reverse transcription polymerase chain reaction studies revealed that several signature genes in the IL-1β , TNFα , and related signaling pathways were downregulated after EGCG treatment .
Conclusion @ @ @ @ @ @ @ simplicity of the zebrafish model facilitate tracking of fluorescent neutrophils in real time , in order to monitor inflammation , and assess the impact of therapeutic agents .

Background: Polyphenol catechins from green tea, particularly (-)-epigallocatechin-3-gallate (EGCG), exhibits numerous beneficial health effects, although the mechanisms remain unclear.
Methods: In this study, the mechanism of EGCG-mediated healing in an experimentally injured zebrafish model was examined at the cellular and molecular level using confocal microscopy and gene expression analysis.
Results: The mechanisms of action of EGCG were shown to involve: (1) reducing neutrophil response (accumulation, travel speed, and distance) and (2) downregulating the expression of IL-1β, TNFα, and related signaling pathways. As determined by dynamic time-lapse tracking studies, the local accumulation of neutrophils with high migration speeds after wounding (n=33 cells, v=0.020 μm/s, d=37.8 μm), underwent significant reduction following treatment with EGCG doses of 300 μM (n=22 cells, v=0.013 μm/s, d=39.5 μm) and 600 μM (n=18 cells, v=0.008 μm/s, d=9.53 μm). Reverse transcription polymerase chain reaction studies revealed that several signature genes in the IL-1β, TNFα, and related signaling pathways were downregulated after EGCG treatment.
Conclusion: The convenience, transparency, and simplicity of the zebrafish model facilitate tracking of fluorescent neutrophils in real time, in order to monitor inflammation, and assess the impact of therapeutic agents.


greenmedinfo--2020-05-09--These results provide new insight into the mechanism of EGCG-associated key pathways/genes in MDSCs

These results provide new insight into the mechanism of EGCG-associated key pathways/genes in MDSCs in the murine breast tumor model.

Several studies in the past decades have reported anti-tumor activity of the bioactive compounds extracted from tea leaves , with a focus on the compound epigallocatechin-3-gallate ( EGCG ) .
However , further investigations are required to unravel the underlying mechanisms behind the anti-tumor activity of EGCG .
In this study , we demonstrate that EGCG significantly inhibits the growth of 4T1 breast cancer cellsand .
EGCG ameliorated immunosuppression by significantly decreasing the accumulation of myeloid-derived suppressor cells ( MDSCs ) and increasing the proportions of CD4and CD8T cells in spleen and tumor sites in 4T1 breast tumor-bearing mice .
@ @ @ @ @ @ @ ( 0.5-5μg/mL ) effectively reduced the cell viability and increased the apoptosis rate of MDSCs .
EGCG down-regulated the canonical pathways in MDSCs , mainly through the Arg-1/iNOS/Nox2/NF-κB/STAT3 signaling pathway .
Moreover , transcriptomic analysis suggested that EGCG also affected the non-canonical pathways in MDSCs , such as ECM-receptor interaction and focal adhesion .
qRT-PCR further validated that EGCG restored nine key genes in MDSCs , including , , , , , , , and .
Our results provide new insight into the mechanism of EGCG-associated key pathways/genes in MDSCs in the murine @ @ @ @

Several studies in the past decades have reported anti-tumor activity of the bioactive compounds extracted from tea leaves, with a focus on the compound epigallocatechin-3-gallate (EGCG). However, further investigations are required to unravel the underlying mechanisms behind the anti-tumor activity of EGCG. In this study, we demonstrate that EGCG significantly inhibits the growth of 4T1 breast cancer cellsand. EGCG ameliorated immunosuppression by significantly decreasing the accumulation of myeloid-derived suppressor cells (MDSCs) and increasing the proportions of CD4and CD8T cells in spleen and tumor sites in 4T1 breast tumor-bearing mice. Surprisingly, a low dose of EGCG (0.5-5μg/mL) effectively reduced the cell viability and increased the apoptosis rate of MDSCs. EGCG down-regulated the canonical pathways in MDSCs, mainly through the Arg-1/iNOS/Nox2/NF-κB/STAT3 signaling pathway. Moreover, transcriptomic analysis suggested that EGCG also affected the non-canonical pathways in MDSCs, such as ECM-receptor interaction and focal adhesion. qRT-PCR further validated that EGCG restored nine key genes in MDSCs, including,,,,,,,and. Our results provide new insight into the mechanism of EGCG-associated key pathways/genes in MDSCs in the murine breast tumor model.


greenmedinfo--2020-05-09--Novel therapy of bicarbonate, glutathione and ascorbic acid improves cystic fibrosis mucus transport

Novel therapy of bicarbonate, glutathione and ascorbic acid improves cystic fibrosis mucus transport.

Defective airway mucus clearance is a defining characteristic of CF lung disease , and improvements to current mucolytic strategies are needed .
Novel approaches targeting a range of contributing mechanisms are in various stages of preclinical and clinical development .
ARINA-1 is a new , nebulized product comprised of ascorbic acid , glutathione , and bicarbonate .
Using micro-optical coherence tomography , we tested the effect of ARINA-1 on central features of mucociliary clearance in F508del/F508del primary human bronchial epithelial cells to assess its potential as a mucoactive therapy in CF .
We found that ARINA-1 significantly augmented mucociliary transport @ @ @ @ @ @ @ and with CFTR modulator therapy , whereas airway hydration and ciliary beating were largely unchanged compared to PBS vehicle control .
Analysis of mucus reflectivity and particle tracking microrheology indicated that ARINA-1 restores mucus clearance by principally reducing mucus layer viscosity .
The combination of bicarbonate and glutathione elicited increases to MCT rate comparable to those seen with ARINA-1 , indicating the importance of this interaction to the impact of ARINA-1 on mucus transport ; this effect was not recapitulated with bicarbonate alone or bicarbonate combined with ascorbic acid .
Assessment of CFTR @ @ @ @ @ @ @ chloride secretion in response to ARINA-1 in CFBE41o- cells expressing wild-type CFTR , driven by CFTR activity stimulation by ascorbate .
This response was absent in CFBE41o- F508del cells treated with VX-809 and primary HBE cells , implicating CFTR-independent mechanisms for the effect of ARINA-1 on CF mucus .
Together , these studies indicate that ARINA-1 is a novel potential therapy for the treatment of impaired mucus clearance in CF .

Defective airway mucus clearance is a defining characteristic of CF lung disease, and improvements to current mucolytic strategies are needed. Novel approaches targeting a range of contributing mechanisms are in various stages of preclinical and clinical development. ARINA-1 is a new, nebulized product comprised of ascorbic acid, glutathione, and bicarbonate. Using micro-optical coherence tomography, we tested the effect of ARINA-1 on central features of mucociliary clearance in F508del/F508del primary human bronchial epithelial cells to assess its potential as a mucoactive therapy in CF. We found that ARINA-1 significantly augmented mucociliary transport (MCT) rates, both alone and with CFTR modulator therapy, whereas airway hydration and ciliary beating were largely unchanged compared to PBS vehicle control. Analysis of mucus reflectivity and particle tracking microrheology indicated that ARINA-1 restores mucus clearance by principally reducing mucus layer viscosity. The combination of bicarbonate and glutathione elicited increases to MCT rate comparable to those seen with ARINA-1, indicating the importance of this interaction to the impact of ARINA-1 on mucus transport; this effect was not recapitulated with bicarbonate alone or bicarbonate combined with ascorbic acid. Assessment of CFTR chloride transport revealed an increase in CFTR-mediated chloride secretion in response to ARINA-1 in CFBE41o- cells expressing wild-type CFTR, driven by CFTR activity stimulation by ascorbate. This response was absent in CFBE41o- F508del cells treated with VX-809 and primary HBE cells, implicating CFTR-independent mechanisms for the effect of ARINA-1 on CF mucus. Together, these studies indicate that ARINA-1 is a novel potential therapy for the treatment of impaired mucus clearance in CF.


greenmedinfo--2020-05-09--Vitamin C decreases VEGF expression levels via hypoxia‑inducible factor‑1α dependent and independent

Vitamin C decreases VEGF expression levels via hypoxia‑inducible factor‑1α dependent and independent pathways in lens epithelial cells.

Posterior capsular opacification ( PCO ) is the main complication following cataract surgery .
The proliferation of the residual lens epithelial cells ( LECs ) serves an important role in PCO formation .
The authors ' previous study revealed that vitamin C inhibited the proliferation of human LECs by increasing the rapid degradation of hypoxia‑inducible factor‑1 ( HIF‑1α ) , and hence inhibited the expression of vascular endothelial growth factor ( VEGF ) .
The present study aimed to further investigate the mechanisms underlying the effects of vitamin C on the expression levels of VEGF .
The present study demonstrated @ @ @ @ @ @ @ inhibited the cell proliferation and the expression levels of VEGF in LECs through the use of colony formation , western blotting and ELISA assays .
Moreover , it was revealed that vitamin C could further inhibit the cell proliferation and the expression levels of VEGF in LECs following the cotreatment with the HIF‑1 inhibitor .
The proline hydroxylation of HIF‑1α by prolyl hydroxylases ( PHDs ) was previously discovered to be responsible for the rapid degradation of HIF‑1α .
Thus , the present study subsequently used three PHD inhibitors to investigate their effects @ @ @ @ @ @ @ it was found that the PHD2 specific inhibitor increased the expression levels of VEGF to the greatest extent .
Moreover , the genetic knockdown of PHD2 by lentiviral transfection also significantly increased the expression levels of VEGF , whereas the PHD2 specific inhibitor did not alter the expression levels of VEGF in the PHD2 knockdown LECs .
AKT kinase activity is an important mediator known to upregulate VEGF expression .
Using an immunoprecipitation assay to isolate endogenous AKT , it was demonstrated that AKT was prolyl hydroxylated by PHD2 , whichinhibited its activity @ @ @ @ @ @ @ C enhanced the proline‑hydroxylation and inhibited the activity of AKT .
Furthermore , an AKT inhibitor increased the effects of vitamin C on the expression levels of VEGF .
However , the AKT inhibitor did not affect the expression levels ofglucose transporter 1 , which is a HIF‑1α target gene .
In conclusion , the findings of the present study suggested that vitamin C may inhibit the expression levels of VEGF via HIF‑1α‑dependent and AKT‑dependent pathways in LECs .

Posterior capsular opacification (PCO) is the main complication following cataract surgery. The proliferation of the residual lens epithelial cells (LECs) serves an important role in PCO formation. The authors' previous study revealed that vitamin C inhibited the proliferation of human LECs by increasing the rapid degradation of hypoxia‑inducible factor‑1 (HIF‑1α), and hence inhibited the expression of vascular endothelial growth factor (VEGF). The present study aimed to further investigate the mechanisms underlying the effects of vitamin C on the expression levels of VEGF. The present study demonstrated that the HIF‑1 inhibitor BAY 87‑2243 significantly inhibited the cell proliferation and the expression levels of VEGF in LECs through the use of colony formation, western blotting and ELISA assays. Moreover, it was revealed that vitamin C could further inhibit the cell proliferation and the expression levels of VEGF in LECs following the cotreatment with the HIF‑1 inhibitor. The proline hydroxylation of HIF‑1α by prolyl hydroxylases (PHDs) was previously discovered to be responsible for the rapid degradation of HIF‑1α. Thus, the present study subsequently used three PHD inhibitors to investigate their effects on the expression levels of VEGF; it was found that the PHD2 specific inhibitor increased the expression levels of VEGF to the greatest extent. Moreover, the genetic knockdown of PHD2 by lentiviral transfection also significantly increased the expression levels of VEGF, whereas the PHD2 specific inhibitor did not alter the expression levels of VEGF in the PHD2 knockdown LECs. AKT kinase activity is an important mediator known to upregulate VEGF expression. Using an immunoprecipitation assay to isolate endogenous AKT, it was demonstrated that AKT was prolyl hydroxylated by PHD2, whichinhibited its activity. It was also revealed that vitamin C enhanced the proline‑hydroxylation and inhibited the activity of AKT. Furthermore, an AKT inhibitor increased the effects of vitamin C on the expression levels of VEGF. However, the AKT inhibitor did not affect the expression levels ofglucose transporter 1, which is a HIF‑1α target gene. In conclusion, the findings of the present study suggested that vitamin C may inhibit the expression levels of VEGF via HIF‑1α‑dependent and AKT‑dependent pathways in LECs.


greenmedinfo--2020-05-09--Mindfulness-based Interventions showed low but significant effects on health status related to bioma

Mindfulness-based Interventions showed low but significant effects on health status related to biomarkers of low-grade inflammation.

Mindfulness-Based Interventions ( MBIs ) present positive effects on mental health in diverse populations .
However , the detailed associations between MBIs and biomarkers in patients with psychiatric disorders remain poorly understood .
The aim of this study was to examine the effects of MBIs on biomarkers in psychiatric illness used to summarise the effects of low-grade inflammation .
A systematic review of PubMed , EMBASE , PsycINFO , and the Cochrane Library was conducted .
Effect sizes ( ESs ) were determined by Hedges ' g and the number needed to treat ( NNT ) .
Heterogeneity was evaluated @ @ @ @ @ @ @ 998 participants were included .
MBIs showed significant improvements in the event-related potential amplitudes in attention-deficit hyperactivity disorder , the methylation of serotonin transporter genes in post-traumatic stress disorder , the salivary levels of interleukin 6 ( IL-6 ) and tumour necrosis factor alpha ( TNF-α ) in depression , and the blood levels of adrenocorticotropic hormone ( ACTH ) , IL-6 , and TNF-α in generalised anxiety disorder .
MBIs showed low but significant effects on health status related to biomarkers of low-grade inflammation ( = -0.21 ; 95 % confidence interval @ @ @ @ @ @ @ NNT = 8.47 ) , with no heterogeneity ( = 0 ; 95 % CI 0 to 79 ) .
More trials are needed to establish the impact of MBIs on biomarkers in psychiatric illness .

Mindfulness-Based Interventions (MBIs) present positive effects on mental health in diverse populations. However, the detailed associations between MBIs and biomarkers in patients with psychiatric disorders remain poorly understood. The aim of this study was to examine the effects of MBIs on biomarkers in psychiatric illness used to summarise the effects of low-grade inflammation. A systematic review of PubMed, EMBASE, PsycINFO, and the Cochrane Library was conducted. Effect sizes (ESs) were determined by Hedges' g and the number needed to treat (NNT). Heterogeneity was evaluated. A total of 10 trials with 998 participants were included. MBIs showed significant improvements in the event-related potential amplitudes in attention-deficit hyperactivity disorder, the methylation of serotonin transporter genes in post-traumatic stress disorder, the salivary levels of interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) in depression, and the blood levels of adrenocorticotropic hormone (ACTH), IL-6, and TNF-α in generalised anxiety disorder. MBIs showed low but significant effects on health status related to biomarkers of low-grade inflammation (= -0.21; 95% confidence interval (CI) -0.41 to -0.01; NNT = 8.47), with no heterogeneity (= 0; 95% CI 0 to 79). More trials are needed to establish the impact of MBIs on biomarkers in psychiatric illness.


greenmedinfo--2020-05-09--Mindfulness-based stress reduction improves irritable bowel syndrome (IBS) symptoms via specific asp

Mindfulness-based stress reduction improves irritable bowel syndrome (IBS) symptoms via specific aspects of mindfulness.

BACKGROUND : Irritable bowel syndrome ( IBS ) is a common and often debilitating chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habits .
Pharmacological treatments are often ineffective , leading to the development of a variety of behavioral interventions .
Mindfulness-based stress reduction ( MBSR ) is one such program that has shown efficacy in reducing gastrointestinal ( GI ) symptoms and improving quality of life ( QOL ) .
This single-arm intervention study examines the association of clinical outcomes with changes in specific aspects of mindfulness .
METHODS : Adults with IBS ( 53 women , @ @ @ @ @ @ @ MBSR class .
Primary outcomes of GI symptom severity , quality of life , and GI-specific anxiety , as well as specific aspects of mindfulness using the Five Factor Mindfulness Questionnaire ( FFMQ ) , were assessed at baseline , post-treatment , and 6-month follow-up .
KEY RESULTS : Gastrointestinal symptom responder rate was 71 % , and there was a significant pre-post treatment change for three of the five FFMQ scales .
Regression analysis indicated that change in the Act with Awareness ( P = .02 ) facet of mindfulness was the @ @ @ @ @ @ @ improvement .
CONCLUSIONS & INFERENCES : Mindfulness-based stress reduction training was associated with robust improvements in GI symptoms and associated problems in participants with IBS .
Although significant increases in 3 of the 5 measured facets of mindfulness were found , regression analyses suggest that increases in the ability to retain present moment focus and act with awareness may be particularly important for improving outcomes in individuals with IBS .
These results may inform the refinement of mindfulness-based protocols specifically for treatment of IBS .

BACKGROUND: Irritable bowel syndrome (IBS) is a common and often debilitating chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habits. Pharmacological treatments are often ineffective, leading to the development of a variety of behavioral interventions. Mindfulness-based stress reduction (MBSR) is one such program that has shown efficacy in reducing gastrointestinal (GI) symptoms and improving quality of life (QOL). This single-arm intervention study examines the association of clinical outcomes with changes in specific aspects of mindfulness.
METHODS: Adults with IBS (53 women, 15 men) participated in an 8-week MBSR class. Primary outcomes of GI symptom severity, quality of life, and GI-specific anxiety, as well as specific aspects of mindfulness using the Five Factor Mindfulness Questionnaire (FFMQ), were assessed at baseline, post-treatment, and 6-month follow-up.
KEY RESULTS: Gastrointestinal symptom responder rate was 71%, and there was a significant pre-post treatment change for three of the five FFMQ scales. Regression analysis indicated that change in the Act with Awareness (P = .02) facet of mindfulness was the strongest predictor of GI symptom and QOL improvement.
CONCLUSIONS & INFERENCES: Mindfulness-based stress reduction training was associated with robust improvements in GI symptoms and associated problems in participants with IBS. Although significant increases in 3 of the 5 measured facets of mindfulness were found, regression analyses suggest that increases in the ability to retain present moment focus and act with awareness may be particularly important for improving outcomes in individuals with IBS. These results may inform the refinement of mindfulness-based protocols specifically for treatment of IBS.


greenmedinfo--2020-05-09--Depression, mindfulness, and psilocybin: possible complementary effects of mindfulness meditation an

Depression, mindfulness, and psilocybin: possible complementary effects of mindfulness meditation and psilocybin in the treatment of depression.

Depression is a major public health problem that affects approximately 4.4 % of the global population .
Since conventional pharmacotherapies and psychotherapies are only partially effective , as demonstrated by the number of patients failing to achieve remission , alternative treatments are needed .
Mindfulness meditation ( MM ) and psilocybin represent two promising novel treatments that might even have complementary therapeutic effects when combined .
Since the current literature is limited to theoretical and empirical underpinnings of either treatment alone , the present review aimed to identify possible complementary effects that may be relevant to the treatment of depression @ @ @ @ @ @ @ effects of MM and psilocybin , and their underlying working mechanisms , were compared on a non-exhaustive selection of six prominent psychological and biological processes that are well known to show impairments in patients suffering from major depression disorder , that is mood , executive functioning , social skills , neuroplasticity , core neural networks , and neuroendocrine and neuroimmunological levels .
Based on predefined search strings used in two online databases ( PubMed and Google Scholar ) 1129 articles were identified .
After screening title and abstract for relevance related to the @ @ @ @ @ @ @ 11 were added after reference list search , resulting in 93 articles included in the review .
Findings show that MM and psilocybin exert similar effects on mood , social skills , and neuroplasticity ; different effects were found on executive functioning , neural core networks , and neuroendocrine and neuroimmune system markers .
Potential mechanisms of MM 's effects are enhanced affective self-regulation through mental strategies , optimization of stress reactivity , and structural and functional adjustments of prefrontal and limbic areas ; psilocybin 's effects might be establishedattenuation of cognitive associations @ @ @ @ @ @ @ , and global neural network disintegration .
It is suggested that , when used in combination , MM and psilocybin could exert complementary effects by potentiating or prolonging mutual positive effects , for example , MM potentially facilitating psilocybin-induced peak experiences .
Future placebo-controlled double-blind randomized trials focusing on psilocybin-assisted mindfulness-based therapy will provide knowledge about whether the proposed combination of therapies maximizes their efficacy in the treatment of depression or depressive symptomatology .

Depression is a major public health problem that affects approximately 4.4% of the global population. Since conventional pharmacotherapies and psychotherapies are only partially effective, as demonstrated by the number of patients failing to achieve remission, alternative treatments are needed. Mindfulness meditation (MM) and psilocybin represent two promising novel treatments that might even have complementary therapeutic effects when combined. Since the current literature is limited to theoretical and empirical underpinnings of either treatment alone, the present review aimed to identify possible complementary effects that may be relevant to the treatment of depression. To that end, the individual effects of MM and psilocybin, and their underlying working mechanisms, were compared on a non-exhaustive selection of six prominent psychological and biological processes that are well known to show impairments in patients suffering from major depression disorder, that is mood, executive functioning, social skills, neuroplasticity, core neural networks, and neuroendocrine and neuroimmunological levels. Based on predefined search strings used in two online databases (PubMed and Google Scholar) 1129 articles were identified. After screening title and abstract for relevance related to the question, 82 articles were retained and 11 were added after reference list search, resulting in 93 articles included in the review. Findings show that MM and psilocybin exert similar effects on mood, social skills, and neuroplasticity; different effects were found on executive functioning, neural core networks, and neuroendocrine and neuroimmune system markers. Potential mechanisms of MM's effects are enhanced affective self-regulation through mental strategies, optimization of stress reactivity, and structural and functional adjustments of prefrontal and limbic areas; psilocybin's effects might be establishedattenuation of cognitive associations through deep personal insights, cognitive disinhibition, and global neural network disintegration. It is suggested that, when used in combination, MM and psilocybin could exert complementary effects by potentiating or prolonging mutual positive effects, for example, MM potentially facilitating psilocybin-induced peak experiences. Future placebo-controlled double-blind randomized trials focusing on psilocybin-assisted mindfulness-based therapy will provide knowledge about whether the proposed combination of therapies maximizes their efficacy in the treatment of depression or depressive symptomatology.