greenmedinfo--2020-07-26--Effect of 3,3'-diindolylmethane on pulmonary injury following thoracic irradiation in CBA mice

The molecule 3,3'-diindolylmethane ( DIM ) is small , a major bioactive metabolite of indole-3 carbinol ( 13C ) , and a phytochemical compound from cruciferous vegetables released upon exposure to the gut acid environment .
DIM is a proposed anti-cancer agent and was previously demonstrated to prevent radiation damage in the bone marrow and the gastrointestinal tract .
Here we investigated the effect of DIM on radiation-induced injury to the lung in a murine model through untargeted metabolomics and gene expression studies of select genes .
CBA mice were exposed to thoracic irradiation ( 17.5 Gy ) .
Mice @ @ @ @ @ @ @ 250 mg kg , subcutaneous injection ) on days -1 pre-irradiation through +14 post-irradiation .
DIM induced a significant improvement in survival by day 150 post-irradiation .
Fibrosis-related gene expression and metabolomics were examined using lung tissue from days 15 , 45 , 60 , 90 , and 120 post-irradiation .
Our qRT-PCR experiments showed that DIM treatment reduced radiation-induced late expression of collagen Iα and the cell cycle checkpoint proteins p21/waf1 ( CDKN1A ) and p16ink ( CDKN2A ) .
Metabolomic studies of lung tissue demonstrated a significant dampening of radiation-induced changes @ @ @ @ @ @ @ pro-inflammatory responses and increased oxidative stress , such as fatty acids , were suppressed by DIM treatment compared to irradiated samples .
Together these data suggest that DIM reduces radiation-induced sequelae in the lung .

The molecule 3,3'-diindolylmethane (DIM) is small, a major bioactive metabolite of indole-3 carbinol (13C), and a phytochemical compound from cruciferous vegetables released upon exposure to the gut acid environment. DIM is a proposed anti-cancer agent and was previously demonstrated to prevent radiation damage in the bone marrow and the gastrointestinal tract. Here we investigated the effect of DIM on radiation-induced injury to the lung in a murine model through untargeted metabolomics and gene expression studies of select genes. CBA mice were exposed to thoracic irradiation (17.5 Gy). Mice were treated with vehicle or DIM (250 mg kg, subcutaneous injection) on days -1 pre-irradiation through +14 post-irradiation. DIM induced a significant improvement in survival by day 150 post-irradiation. Fibrosis-related gene expression and metabolomics were examined using lung tissue from days 15, 45, 60, 90, and 120 post-irradiation. Our qRT-PCR experiments showed that DIM treatment reduced radiation-induced late expression of collagen Iα and the cell cycle checkpoint proteins p21/waf1 (CDKN1A) and p16ink (CDKN2A). Metabolomic studies of lung tissue demonstrated a significant dampening of radiation-induced changes following DIM treatment. Metabolites associated with pro-inflammatory responses and increased oxidative stress, such as fatty acids, were suppressed by DIM treatment compared to irradiated samples. Together these data suggest that DIM reduces radiation-induced sequelae in the lung.


greenmedinfo--2020-07-26--3,3-Diindolylmethane (DIM): A nutritional intervention and its impact on breast density in healthy B

3,3-Diindolylmethane (DIM): A nutritional intervention and its impact on breast density in healthy BRCA carriers.

Women who carry the BRCA mutation are at high lifetime risk of breast cancer , but there is no consensus regarding an effective and safe chemoprevention strategy .
A large body of evidence suggests that 3,3-diindolylmethane ( DIM ) , a dimer of indole-3-carbinol ( I3C ) found in cruciferous vegetables , can potentially prevent carcinogenesis and tumor development .
The primary aim of this prospective single-arm study was to investigate the effect of DIM supplementation on breast density , a recognized predictive factor of breast-cancer risk .
Participants were 23 healthy female BRCA carriers ( median age 47 years @ @ @ @ @ @ @ treated with oral DIM 100 mgx1/d for one year .
The amount of fibroglandular tissue ( FGT ) and background parenchymal enhancement ( BPE ) on magnetic resonance imaging ( MRI ) performed before and after the intervention were scored by two independent expert radiologists using the Breast Imaging and Reporting Data System ( BI-RADS ) .
The results showed a decrease in the average score for FGT amount from 2.8±0.8 at onset to 2.65±0.842.8 after one year ( p=0.031 ) , with no significant change in BPE ( p=0.429 ) .
A @ @ @ @ @ @ @ women did not show a significant change in FGT amount ( p=0.33 ) or BPE ( p=0.814 ) in a parallel year .
Mean estradiol level decreasedfrom 159 to 102 pmol/L ( p=0.01 ) , and mean testosterone level , from 0.42 to 0.31 pmol/L ( p=0.007 ) .
Side effects were grade 1 .
In conclusion , one year 's supplementation with DIM 100 mgX1/d in BRCA carriers was associated with a significant decline in FGT amount on MRI .
Larger randomized studies are warranted to corroborate these findings .

Women who carry the BRCA mutation are at high lifetime risk of breast cancer, but there is no consensus regarding an effective and safe chemoprevention strategy. A large body of evidence suggests that 3,3-diindolylmethane (DIM), a dimer of indole-3-carbinol (I3C) found in cruciferous vegetables, can potentially prevent carcinogenesis and tumor development. The primary aim of this prospective single-arm study was to investigate the effect of DIM supplementation on breast density, a recognized predictive factor of breast-cancer risk. Participants were 23 healthy female BRCA carriers (median age 47 years; 78% postmenopausal) who were treated with oral DIM 100 mgx1/d for one year. The amount of fibroglandular tissue (FGT) and background parenchymal enhancement (BPE) on magnetic resonance imaging (MRI) performed before and after the intervention were scored by two independent expert radiologists using the Breast Imaging and Reporting Data System (BI-RADS). The results showed a decrease in the average score for FGT amount from 2.8±0.8 at onset to 2.65±0.842.8 after one year (p=0.031), with no significant change in BPE (p=0.429). A group of DIM-untreated age- and menopausal-status-matched clinic women did not show a significant change in FGT amount (p=0.33) or BPE (p=0.814) in a parallel year. Mean estradiol level decreasedfrom 159 to 102 pmol/L (p=0.01), and mean testosterone level, from 0.42 to 0.31 pmol/L (p=0.007). Side effects were grade 1. In conclusion, one year's supplementation with DIM 100 mgX1/d in BRCA carriers was associated with a significant decline in FGT amount on MRI. Larger randomized studies are warranted to corroborate these findings.


greenmedinfo--2020-07-26--3,3′-Diindolylmethane modulates aryl hydrocarbon receptor of esophageal squamous cell carcinoma to r

3,3′-Diindolylmethane modulates aryl hydrocarbon receptor of esophageal squamous cell carcinoma to reverse epithelial-mesenchymal transition.

BACKGROUND : Esophageal squamous cell carcinoma ( ESCC ) is one of the most aggressive tumors in the world .
Aryl hydrocarbon receptor ( AHR ) has been reported to promote tumor metastasis and epithelial-mesenchymal transition ( EMT ) is a vital process of conferring cancer cells capabilities of migration and invasion .
However , the mechanism by which modulation of AHR can inhibit tumor metastasis remains unknown .
Thus , we aim to investigate the underlying mechanism regarding reversing EMT process of ESCC through modulation of AHR .
METHODS : We used AHR selective modulator 3,3'-diindolylmethane ( DIM ) @ @ @ @ @ @ @ KYSE150 so as to examine alterations of migration and invasion by wound healing and Transwell assay .
Western blotting ( WB ) and qPCR were performed to detect relative genes and proteins changes regarding EMT process .
Cell transfection was utilized for confirming pathways involved in DIM-induced reversal of EMT and in vivo assay was conducted for verification of the underlying mechanism .
Co-IP assay was conducted for detecting protein-protein interactions .
RESULTS : AHR was overexpressed in ESCC and modulation of AHR by DIM could inhibit migration and invasion as well as @ @ @ @ @ @ @ Slug and upregulate epithelial cell marker Claudin-1 .
Meanwhile , synergically overexpression of AHR , RhoA and ROCK1 correlated with poor clinical outcomes .
DIM could inhibit COX2/PGEpathway by targeting AHR , and COX2 selective inhibitor Celecoxib could suppress EMT and metastasis .
Results of PGEtreatment were opposite to that of Celecoxib .
Meanwhile , blockade of RhoA/ROCK1 pathway also exerted prohibitive effects on EMT and metastasis .
WB results showed COX2/PGEpathway could be regulated by RhoA/ROCK1 pathway and DIM could inhibit RhoA/ROCK1 pathway through modulation of AHR .
In vivo assay verified @ @ @ @ @ @ @ showed DIM could modulate AHR to reverse EMT directly through inhibition of interaction between AHR and EGFR ( epidermal growth factor receptor ) so as to block RhoA/ROCK1-mediated COX2/PGEpathway which was connected by NF-κB .
CONCLUSIONS : In brief , modulation of AHR by DIM can reverse EMT process and inhibit metastasis of ESCC through repressing RhoA/ROCK1-mediated COX2/PGEpathway .

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive tumors in the world. Aryl hydrocarbon receptor (AHR) has been reported to promote tumor metastasis and epithelial-mesenchymal transition (EMT) is a vital process of conferring cancer cells capabilities of migration and invasion. However, the mechanism by which modulation of AHR can inhibit tumor metastasis remains unknown. Thus, we aim to investigate the underlying mechanism regarding reversing EMT process of ESCC through modulation of AHR.
METHODS: We used AHR selective modulator 3,3'-diindolylmethane (DIM) to treat ESCC cell lines TE1 and KYSE150 so as to examine alterations of migration and invasion by wound healing and Transwell assay. Western blotting (WB) and qPCR were performed to detect relative genes and proteins changes regarding EMT process. Cell transfection was utilized for confirming pathways involved in DIM-induced reversal of EMT and in vivo assay was conducted for verification of the underlying mechanism. Co-IP assay was conducted for detecting protein-protein interactions.
RESULTS: AHR was overexpressed in ESCC and modulation of AHR by DIM could inhibit migration and invasion as well as downregulate mesenchymal cell markersβ-Catenin, Vimentin and Slug and upregulate epithelial cell marker Claudin-1. Meanwhile, synergically overexpression of AHR, RhoA and ROCK1 correlated with poor clinical outcomes. DIM could inhibit COX2/PGEpathway by targeting AHR, and COX2 selective inhibitor Celecoxib could suppress EMT and metastasis. Results of PGEtreatment were opposite to that of Celecoxib. Meanwhile, blockade of RhoA/ROCK1 pathway also exerted prohibitive effects on EMT and metastasis. WB results showed COX2/PGEpathway could be regulated by RhoA/ROCK1 pathway and DIM could inhibit RhoA/ROCK1 pathway through modulation of AHR. In vivo assay verified the results in vitro. Co-IP results showed DIM could modulate AHR to reverse EMT directly through inhibition of interaction between AHR and EGFR (epidermal growth factor receptor) so as to block RhoA/ROCK1-mediated COX2/PGEpathway which was connected by NF-κB.
CONCLUSIONS: In brief, modulation of AHR by DIM can reverse EMT process and inhibit metastasis of ESCC through repressing RhoA/ROCK1-mediated COX2/PGEpathway.


greenmedinfo--2020-07-26--Chemopreventive agent 3,3′-diindolylmethane inhibits MDM2 in colorectal cancer cells.

3,3'-Diindolylmethane ( DIM ) is a naturally derived chemopreventive compound .
It comes from glucobrassicin , an indole glucosinolate enriched in cruciferous vegetables , and is formed in the acidic environment of the stomach after ingestion .
Mouse double minute 2 homolog ( MDM2 ) is an important , multi-functional oncogenic protein and it has been well recognized for its negative regulation of the tumor suppressor protein p53 .
We discovered a novel mechanism of action of DIM , that it directly inhibits MDM2 in multiple colorectal cancer ( CRC ) cell lines .
Treatment with DIM decreased MDM2 at @ @ @ @ @ @ @ levels , inhibited cancer cell proliferation , and induced cell cycle arrest and apoptosis .
DIM-induced decrease of MDM2 is p53-independent and is partly mediated by proteasome degradation of MDM2 , as blocking of the proteasome activity reversed MDM2 protein inhibition .
Overexpression of MDM2 blocked DIM 's effects in growth suppression and apoptosis induction .
When combined with imidazoline MDM2 inhibitors ( Nutlin-3a and Idasanutlin/RG-7388 ) , synergism was observed in cancer cell growth inhibition .
In summary , our data support a new mechanism of action for DIM in direct inhibition @ @ @ @ @ @ @ as a novel DIM target may help develop a new strategy in CRC prevention .

3,3'-Diindolylmethane (DIM) is a naturally derived chemopreventive compound. It comes from glucobrassicin, an indole glucosinolate enriched in cruciferous vegetables, and is formed in the acidic environment of the stomach after ingestion. Mouse double minute 2 homolog (MDM2) is an important, multi-functional oncogenic protein and it has been well recognized for its negative regulation of the tumor suppressor protein p53. We discovered a novel mechanism of action of DIM, that it directly inhibits MDM2 in multiple colorectal cancer (CRC) cell lines. Treatment with DIM decreased MDM2 at messenger RNA (mRNA) and protein levels, inhibited cancer cell proliferation, and induced cell cycle arrest and apoptosis. DIM-induced decrease of MDM2 is p53-independent and is partly mediated by proteasome degradation of MDM2, as blocking of the proteasome activity reversed MDM2 protein inhibition. Overexpression of MDM2 blocked DIM's effects in growth suppression and apoptosis induction. When combined with imidazoline MDM2 inhibitors (Nutlin-3a and Idasanutlin/RG-7388), synergism was observed in cancer cell growth inhibition. In summary, our data support a new mechanism of action for DIM in direct inhibition of MDM2. The identification of MDM2 as a novel DIM target may help develop a new strategy in CRC prevention.


greenmedinfo--2020-07-26--Fucoidan from Fucus vesiculosus attenuates doxorubicin-induced acute cardiotoxicity.

Doxorubicin ( DOX ) is well-known for its potent antitumor activity but limited by its multiple and serious adverse effects .
A major adverse effect is acute cardiotoxicity ; yet , its mechanism has not been elucidated .
Fucoidan is a multifunctional and nontoxic polysaccharide that is widely studied because of its favorable biological activities and safety .
Hence , we proposed that fucoidan may play a protective role in DOX-induced acute cardiotoxicity without causing additional side effects .
Sprague-Dawley rats were injected intraperitoneally with a single high dose of DOX to induce acute cardiac injury .
Fucoidan was administered @ @ @ @ @ @ @ a JAK2 inhibitor , was applied to verify the participation of the JAK2/STAT3 pathway .
In vitro , H9C2 cells were treated with the same drugs at different concentrations and intervention times .
in vivo and in vitro results demonstrated that DOX administration induced myocardial damage accompanied by acceleratory apoptosis and deficient autophagy in heart tissues or cells , which could be significantly improved by fucoidan supplement .
AG490 partly abolished the cardioprotective effects of fucoidan , suggesting the involvement of JAK2 signaling .
Additionally , western blotting revealed DOX-induced JAK2/STAT3 pathway activation @ @ @ @ @ @ @ weaken by AG490 .
Hence , fucoidan exerted a favorable effect on DOX-induced cardiotoxicity by enhancing autophagy and suppressing apoptosis in a JAK2/STAT3-dependent manner , which may provide a promising and novel therapeutic strategy against negative chemotherapy-induced effects .

Doxorubicin (DOX) is well-known for its potent antitumor activity but limited by its multiple and serious adverse effects. A major adverse effect is acute cardiotoxicity; yet, its mechanism has not been elucidated. Fucoidan is a multifunctional and nontoxic polysaccharide that is widely studied because of its favorable biological activities and safety. Hence, we proposed that fucoidan may play a protective role in DOX-induced acute cardiotoxicity without causing additional side effects. Sprague-Dawley rats were injected intraperitoneally with a single high dose of DOX to induce acute cardiac injury. Fucoidan was administered orally before DOX injection and AG490, a JAK2 inhibitor, was applied to verify the participation of the JAK2/STAT3 pathway. In vitro, H9C2 cells were treated with the same drugs at different concentrations and intervention times. in vivo and in vitro results demonstrated that DOX administration induced myocardial damage accompanied by acceleratory apoptosis and deficient autophagy in heart tissues or cells, which could be significantly improved by fucoidan supplement. AG490 partly abolished the cardioprotective effects of fucoidan, suggesting the involvement of JAK2 signaling. Additionally, western blotting revealed DOX-induced JAK2/STAT3 pathway activation, which was enhanced by fucoidan and weaken by AG490. Hence, fucoidan exerted a favorable effect on DOX-induced cardiotoxicity by enhancing autophagy and suppressing apoptosis in a JAK2/STAT3-dependent manner, which may provide a promising and novel therapeutic strategy against negative chemotherapy-induced effects.


greenmedinfo--2020-07-26--Anthocyanin-fucoidan nanocomplex for preventing carcinogen induced cancer.

Anthocyanins , commonly extracted from aronia , exhibit excellent in antioxidant activity and anti-cancer activity .
However , anthocyanins are @ @ @ @ @ water but also rapidly disappear from the body , thus requiring a large amount of @ @ @ @ @ limitations , we selected fucoidan , an anionic polymer , to produce an anthocyanin-fucoidan nanocomplex @ @ @ @ @ absorption and chemical stability by ionic bonding andπ-π stacking between anthocyanins .
In vitro , @ @ @ @ @ absorption and plasma chemical stability than free anthocyanins .
AFNC suppressed the epithelial mesenchymal transition @ @ @ @ @ IκBα/NF-κB signaling pathway and the release of pro-inflammatory cytokines .
In vivo , AFNC exhibited @ @ @ @ @ anthocyanin in rats .
AFNC effectively suppressed the generation of carcinogenesis in the 7,12-Dimethylbenz ( @ @ @ @ @ ) /12-O-tetradecanoylphorbol-13-acetate ( TPA ) well-known tumorigenesis model .
These results could beused to extend @ @ @ @ @ anti-cancer treatment and in health care foods , and various pharmaceutical industries .

Anthocyanins, commonly extracted from aronia, exhibit excellent in antioxidant activity and anti-cancer activity. However, anthocyanins are not only easily oxidized in water but also rapidly disappear from the body, thus requiring a large amount of administration. To solve these limitations, we selected fucoidan, an anionic polymer, to produce an anthocyanin-fucoidan nanocomplex (AFNC) with enhanced absorption and chemical stability by ionic bonding andπ-π stacking between anthocyanins. In vitro, AFNC showed increased cell permeability absorption and plasma chemical stability than free anthocyanins. AFNC suppressed the epithelial mesenchymal transition (EMT) signal including IκBα/NF-κB signaling pathway and the release of pro-inflammatory cytokines. In vivo, AFNC exhibited 3.24-fold higher bioavailability than free anthocyanin in rats. AFNC effectively suppressed the generation of carcinogenesis in the 7,12-Dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) well-known tumorigenesis model. These results could beused to extend the applications of anthocyanins in anti-cancer treatment and in health care foods, and various pharmaceutical industries.


greenmedinfo--2020-07-26--Anticancer effects of extracts from three different chokeberry species.

Colon cancer risk appears to be lowered by consumption of a diet rich in fruits and vegetables .
Chokeberries are rich in phytochemicals that may act as potent anticancer agents .
Phytochemicals that are particularly abundant in chokeberries include anthocyanins and phenolic acids .
In this study , we compared the growth inhibitory activity of three chokeberry extracts in HT-29 human colon cancer cells .
The three extracts tested were derived from ( red ) , ( purple ) , and ( black ) .
Cells were incubated with either red , purple , or black chokeberry extracts and cell @ @ @ @ @ @ @ tetrazolium bromide ( MTT ) assay .
The black chokeberry extract had the greatest effect in reducing cell proliferation .
The extracts were also characterized for total phenols ( Folin-Ciocalteu assay ) , total antioxidant activity ( oxygen radical absorbance capacity assay ) , and levels of bioactive phenolic acids ( high-performance liquid chromatography ) .
The growth inhibitory activities of the extracts correlated well with total phenolic content , antioxidant activity , and levels of caffeic and chlorogenic acids .
The black chokeberry extract had the greatest level of total phenols , @ @ @ @ @ @ @ .
This research suggests that the phenolic profile of foods such as chokeberries can help determine their cancer cell growth inhibitory activity .

Colon cancer risk appears to be lowered by consumption of a diet rich in fruits and vegetables. Chokeberries are rich in phytochemicals that may act as potent anticancer agents. Phytochemicals that are particularly abundant in chokeberries include anthocyanins and phenolic acids. In this study, we compared the growth inhibitory activity of three chokeberry extracts in HT-29 human colon cancer cells. The three extracts tested were derived from(red),(purple), and(black). Cells were incubated with either red, purple, or black chokeberry extracts and cell viability was quantified using the thiazolyl blue tetrazolium bromide (MTT) assay. The black chokeberry extract had the greatest effect in reducing cell proliferation. The extracts were also characterized for total phenols (Folin-Ciocalteu assay), total antioxidant activity (oxygen radical absorbance capacity assay), and levels of bioactive phenolic acids (high-performance liquid chromatography). The growth inhibitory activities of the extracts correlated well with total phenolic content, antioxidant activity, and levels of caffeic and chlorogenic acids. The black chokeberry extract had the greatest level of total phenols, antioxidant activity, and individual phenolic acids. This research suggests that the phenolic profile of foods such as chokeberries can help determine their cancer cell growth inhibitory activity.


greenmedinfo--2020-07-26--The polyphenol-rich extract from chokeberry modulates gut microbiota and improves lipid metabolism i

The polyphenol-rich extract from chokeberry modulates gut microbiota and improves lipid metabolism in diet-induced obesity.

The gut microbiota plays a critical role in obesity and lipid metabolism disorder .
Chokeberry ( L ) are rich in polyphenols with various physiological and pharmacological activities .
We determined serum physiological parameters and fecal microbial components by using related kits , liquid chromatography-mass spectrometry ( LC-MS ) and 16S rRNA gene sequencing every 10 days .
Real-time PCR analysis was used to measure gene expression of bile acids ( BAs ) and lipid metabolism in liver and adipose tissues .
We analyzed the effects of different Chokeberry polyphenol ( CBPs ) treatment time on obesity and lipid metabolism @ @ @ @ @ @ @ -fed rats .
The results indicated that CBPs treatment prevents obesity , liver steatosis and improves dyslipidemia in HFD-fed rats .
CBPs modulated the composition of the gut microbiota with the extended treatment time , reducing the/ratio ( F/B ratio ) and increasing the relative abundance of , ,and other bacterial species associated with anti-obesity properties .
We found that CBPs treatment gradually decreased the total BAs pool and particularly reduced the relative content of cholic acid ( CA ) , deoxycholic acid ( DCA ) and enhanced the relative content of chenodeoxycholic @ @ @ @ @ @ @ were positively correlated , and negatively correlated with , , .
In liver and white adipose tissues , the gene expression of lipogenesis , lipolysis and BAs metabolism were regulated after CBPs treatment in HFD-fed rats , which was most likely mediated through FXR and TGR-5 signaling pathway to improve lipid metabolism .
In addition , the mRNA expression of PPARγ , UCP1 and PGC-1α were upregulated markedly in interscapular brown adipose tissue ( iBAT ) after CBPs treatment .
We confirmed that CBPs could reduce the body weight of HFD-fed rats by @ @ @ @ @ @ @ .
Finally , the fecal microbiota transplantation ( FMT ) experiment results demonstrated that FMT from CBPs-treated rats failed to reduce the weight of HFD-fed rats .
However , FMT from CBPs-treated rats improved dyslipidemia and reshaped gut microbiota in HFD-fed rats .
In conclusion , CBPs treatment improved obesity and complications by regulating gut microbiota in HFD-fed rats .
The gut microbiota plays an important role in BAs metabolism after CBPs treatment , and BAs have therefore emerged as major effectors in microbe-host signaling events that influence host lipid metabolism , energy @ @ @ @

The gut microbiota plays a critical role in obesity and lipid metabolism disorder. Chokeberry (L) are rich in polyphenols with various physiological and pharmacological activities. We determined serum physiological parameters and fecal microbial components by using related kits, liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA gene sequencing every 10 days. Real-time PCR analysis was used to measure gene expression of bile acids (BAs) and lipid metabolism in liver and adipose tissues. We analyzed the effects of different Chokeberry polyphenol (CBPs) treatment time on obesity and lipid metabolism in high fat diet (HFD)-fed rats. The results indicated that CBPs treatment prevents obesity, liver steatosis and improves dyslipidemia in HFD-fed rats. CBPs modulated the composition of the gut microbiota with the extended treatment time, reducing the/ratio (F/B ratio) and increasing the relative abundance of,,and other bacterial species associated with anti-obesity properties. We found that CBPs treatment gradually decreased the total BAs pool and particularly reduced the relative content of cholic acid (CA), deoxycholic acid (DCA) and enhanced the relative content of chenodeoxycholic acid (CDCA). These changes were positively correlated,and negatively correlated with,,. In liver and white adipose tissues, the gene expression of lipogenesis, lipolysis and BAs metabolism were regulated after CBPs treatment in HFD-fed rats, which was most likely mediated through FXR and TGR-5 signaling pathway to improve lipid metabolism. In addition, the mRNA expression of PPARγ, UCP1 and PGC-1α were upregulated markedly in interscapular brown adipose tissue (iBAT) after CBPs treatment. We confirmed that CBPs could reduce the body weight of HFD-fed rats by accelerating energy homeostasis and thermogenesis in iBAT. Finally, the fecal microbiota transplantation (FMT) experiment results demonstrated that FMT from CBPs-treated rats failed to reduce the weight of HFD-fed rats. However, FMT from CBPs-treated rats improved dyslipidemia and reshaped gut microbiota in HFD-fed rats. In conclusion, CBPs treatment improved obesity and complications by regulating gut microbiota in HFD-fed rats. The gut microbiota plays an important role in BAs metabolism after CBPs treatment, and BAs have therefore emerged as major effectors in microbe-host signaling events that influence host lipid metabolism, energy metabolism and thermogenesis.


greenmedinfo--2020-07-26--Phenolic constituents and anticancer properties of white mulberry leaves.

Flavonoids are by far the most dominant class of phenolic compounds isolated from Morus alba leaves ( MAL ) .
@ @ @ @ @ benzofurans , phenolic acids , alkaloids , coumarins , chalcones and stilbenes .
Major flavonoids @ @ @ @ @ moragrols and morkotins .
Other major compounds include moracins ( benzofurans ) , caffeoylquinic acids @ @ @ @ @ morachalcones ( chalcones ) .
Research on the anticancer properties of MAL entailed in vitro @ @ @ @ @ extracts or isolated compounds .
Flavonoids , benzofurans , chalcones and alkaloids are classes of @ @ @ @ @ been found to be cytotoxic towards human cancer cell lines .
Further studies on the @ @ @ @ @ are suggested .
Sources of information were PubMed , PubMed Central , ScienceDirect , Google @ @ @ @ @ , PubChem and China National Knowledge Infrastructure .

Flavonoids are by far the most dominant class of phenolic compounds isolated from Morus alba leaves (MAL). Other classes of compounds are benzofurans, phenolic acids, alkaloids, coumarins, chalcones and stilbenes. Major flavonoids are kuwanons, moracinflavans, moragrols and morkotins. Other major compounds include moracins (benzofurans), caffeoylquinic acids (phenolic acids) and morachalcones (chalcones). Research on the anticancer properties of MAL entailed in vitro and in vivo cytotoxicity of extracts or isolated compounds. Flavonoids, benzofurans, chalcones and alkaloids are classes of compounds from MAL that have been found to be cytotoxic towards human cancer cell lines. Further studies on the phytochemistry and anticancer of MAL are suggested. Sources of information were PubMed, PubMed Central, ScienceDirect, Google, Google Scholar, J-Stage, PubChem and China National Knowledge Infrastructure.


greenmedinfo--2020-07-26--Mulberry fruit extract ameliorates adipogenesis.

Mulberry ( L. ) fruits have long been used in traditional medicine and as edible berries in many countries .
@ @ @ @ @ effect of high hydrostatic pressure mulberry fruit extract ( MFE ) during 3T3-L1 adipocyte differentiation @ @ @ @ @ triglyceride accumulation and glycerol-3-phosphate dehydrogenase activity .
The mRNA expression levels of genes related to @ @ @ @ @ adipocyte protein 2 , proliferator-activated receptor- , and CCAAT/enhancer binding protein- , were suppressed by @ @ @ @ @ microRNA ( miR ) -21 and miR-143 expression , which are involved in adipogenesis .
@ @ @ @ @ protein kinase ( AMPK ) activity was increased by MFE .
These results suggested that @ @ @ @ @ modulating miR-21/143 expression and AMPK activity in 3T3-L1 adipocytes , which may be useful as @ @ @ @

Mulberry (L.) fruits have long been used in traditional medicine and as edible berries in many countries. This study investigated the antiadipogenic effect of high hydrostatic pressure mulberry fruit extract (MFE) during 3T3-L1 adipocyte differentiation. MFE decreased lipid and triglyceride accumulation and glycerol-3-phosphate dehydrogenase activity. The mRNA expression levels of genes related to adipogenesis, such as the adipocyte protein 2, proliferator-activated receptor-, and CCAAT/enhancer binding protein-, were suppressed by MFE. They also reduced microRNA (miR)-21 and miR-143 expression, which are involved in adipogenesis. In contrast, adenosine monophosphate-activated protein kinase (AMPK) activity was increased by MFE. These results suggested that MFE may suppress adipogenesis through modulating miR-21/143 expression and AMPK activity in 3T3-L1 adipocytes, which may be useful as antiobesity food agents.


greenmedinfo--2020-07-26--The root bark of Morus alba L. regulates tumor-associated macrophages by blocking recruitment and M2

The root bark of Morus alba L. regulates tumor-associated macrophages by blocking recruitment and M2 polarization of macrophages.

Tumor-associated macrophages ( TAMs ) promote tumor growth and metastasis , and are closely related with poor prognosis of cancers .
Therefore , TAMs have been an attractive target in cancer therapy .
This study investigated whether the root bark of Morus alba L. ( MA ) regulates TAMs .
Methylene chloride extract of MA ( MEMA ) decreased the migration of RAW264.7 cells and THP-1 macrophages toward cancer cells via inhibition of focal adhesion kinase and Src activity .
In addition , MEMA inhibited the phorbol myristate acetate-stimulated secretion of plasminogen activator inhibitor-1 from cancer cells , leading to @ @ @ @ @ @ @ , MEMA-suppressed M2 macrophage polarization induced by interleukin ( IL ) -4/IL-13 or IL-6 .
MEMA downregulated the mRNA expression of M2 macrophage markers and decreased the phosphorylation of signal transducer and activator of transcription ( STAT ) 6 and STAT3 in RAW264.7 cells .
Suppression of M2 polarization of macrophages by MEMA resulted in the reduced migration of Lewis lung carcinoma cells when the conditioned media from RAW264.7 cells was used as a chemoattractant .
Taken together , our results demonstrate that MEMA regulates TAMs by blocking the recruitment of macrophages into @ @ @ @ @ @ @ of macrophages .

Tumor-associated macrophages (TAMs) promote tumor growth and metastasis, and are closely related with poor prognosis of cancers. Therefore, TAMs have been an attractive target in cancer therapy. This study investigated whether the root bark of Morus alba L. (MA) regulates TAMs. Methylene chloride extract of MA (MEMA) decreased the migration of RAW264.7 cells and THP-1 macrophages toward cancer cells via inhibition of focal adhesion kinase and Src activity. In addition, MEMA inhibited the phorbol myristate acetate-stimulated secretion of plasminogen activator inhibitor-1 from cancer cells, leading to the decreased chemotaxis of macrophages. Finally, MEMA-suppressed M2 macrophage polarization induced by interleukin (IL)-4/IL-13 or IL-6. MEMA downregulated the mRNA expression of M2 macrophage markers and decreased the phosphorylation of signal transducer and activator of transcription (STAT) 6 and STAT3 in RAW264.7 cells. Suppression of M2 polarization of macrophages by MEMA resulted in the reduced migration of Lewis lung carcinoma cells when the conditioned media from RAW264.7 cells was used as a chemoattractant. Taken together, our results demonstrate that MEMA regulates TAMs by blocking the recruitment of macrophages into tumor microenvironments and by inhibiting M2 polarization of macrophages.


greenmedinfo--2020-07-28--Murotal Al-Quran therapy on decreasing labor pain and anxiety in maternity mothers first phase.

BACKGROUND : Childbirth is a physiological event in every development of a woman to become a mother .
This event can cause trauma because of the pain she experienced .
The main factors in labor are passage , passager and power , psychological ( psychological factors ) and childbirth helpers .
A woman needs physical , emotional , psychosexual and psychosocial maturity before marriage and becomes pregnant .
Feelings of anxiety , fear of pain will make women uneasy facing pregnancy , childbirth and childbirth , non-pharmacological therapy that can be given in various ways , namely ; acupressure , @ @ @ @ @ @ @ , hydrotherapy , hypnotherapy , endorphin massage , relaxation and distraction techniques .
The effectiveness of giving murotal Al-Quran audio will increase the power of faith and provide peace of mind .
OBJECTIVES : The purpose of this study is to determine the effectiveness of Murotal Al Quran Therapy on Decreasing Labor Pain and Anxiety in Maternity in the First Phase in Maternity Clinic Ar-Rahmah Indralaya Ogan Ilir .
The population of this research was maternity inpartu when I was an active phase which amounted to 20 people .
METHODS : The type @ @ @ @ @ @ @ quasi-experiment .
The research design used was one group comparison pretest-posttest design to test the intensity of pain intensity using Shapiro-Wilk .
RESULT : From the results of the study obtained the normality test obtained p=0.039 and 0.069 which showed the data did not normally distribute , the difference between before and after being given Murotal Al-Quran 0.30 with p=0.008 showed that there was a difference in pain scale before and after therapy Murotal Al-Quran , for the anxiety of the difference between before and after being given therapeutic Murotal Al-Quran 0.021 with @ @ @ @ @ @ @ in pain scale before and after the Murotal Al-Quran is concluded .
CONCLUSION : It can be concluded that Murotal Al-Quran can reduce pain and anxiety in maternity when I was an active phase .
It is expected that midwives can improve services through the development of midwifery care , especially for women who experience severe pain .

BACKGROUND: Childbirth is a physiological event in every development of a woman to become a mother. This event can cause trauma because of the pain she experienced. The main factors in labor are passage, passager and power, psychological (psychological factors) and childbirth helpers. A woman needs physical, emotional, psychosexual and psychosocial maturity before marriage and becomes pregnant. Feelings of anxiety, fear of pain will make women uneasy facing pregnancy, childbirth and childbirth, non-pharmacological therapy that can be given in various ways, namely; acupressure, acupuncture, cold compresses, warm compresses, hydrotherapy, hypnotherapy, endorphin massage, relaxation and distraction techniques. The effectiveness of giving murotal Al-Quran audio will increase the power of faith and provide peace of mind.
OBJECTIVES: The purpose of this study is to determine the effectiveness of Murotal Al Quran Therapy on Decreasing Labor Pain and Anxiety in Maternity in the First Phase in Maternity Clinic Ar-Rahmah Indralaya Ogan Ilir. The population of this research was maternity inpartu when I was an active phase which amounted to 20 people.
METHODS: The type of research used in this study was quasi-experiment. The research design used was one group comparison pretest-posttest design to test the intensity of pain intensity using Shapiro-Wilk.
RESULT: From the results of the study obtained the normality test obtained p=0.039 and 0.069 which showed the data did not normally distribute, the difference between before and after being given Murotal Al-Quran 0.30 with p=0.008 showed that there was a difference in pain scale before and after therapy Murotal Al-Quran, for the anxiety of the difference between before and after being given therapeutic Murotal Al-Quran 0.021 with p=0.025 which shows that there are differences in pain scale before and after the Murotal Al-Quran is concluded.
CONCLUSION: It can be concluded that Murotal Al-Quran can reduce pain and anxiety in maternity when I was an active phase. It is expected that midwives can improve services through the development of midwifery care, especially for women who experience severe pain.


greenmedinfo--2020-07-28--A nanofiber sheet incorporating vitamin B12 promotes nerve regeneration.

: Outcomes of peripheral nerve repair after injury are often suboptimal .
Therefore , developing biological approaches to augment nerve regeneration is important .
In this in vivo study , we tested the hypothesis that augmentation with an electrospun nanofiber sheet incorporating methylcobalamin ( MeCbl ) would be effective for regeneration after peripheral nerve transection and repair .
Methods : Rats were divided into 3 groups that either underwent sciatic nerve repair with or without the MeCbl sheet , or a sham operation .
At 4 and/or 8 weeks after the operation , sensory and motor functional recovery , along @ @ @ @ @ @ @ the groups using the toe-spreading test , mechanical and thermal algesimetry tests , tibialis anterior muscle weight measurements , electrophysiological analyses , which included nerve conduction velocity ( NCV ) , compound muscle action potential ( CMAP ) , and terminal latency ( TL ) , and histological analyses involving the myelinated axon ratio , axon diameter , and total axon number .
Results : Compared with the repair group without the MeCbl sheet , the repair group with the MeCbl sheet showed significant recovery in terms of tibialis anterior muscle weight , @ @ @ @ @ @ @ to improve in the toe-spreading test , mechanical and thermal algesimetry tests , and TL .
Histological analyses also demonstrated that the myelinated axon ratios and axon diameters were significantly higher .
Among these findings , the repair group with the MeCbl sheet demonstrated the same recovery in NCV as the sham group .
Conclusion : This study demonstrated that electrospun nanofiber MeCbl sheets promoted nerve regeneration and functional recovery , indicating that this treatment strategy may be viable for human peripheral nerve injuries .

: Outcomes of peripheral nerve repair after injury are often suboptimal. Therefore, developing biological approaches to augment nerve regeneration is important. In this in vivo study, we tested the hypothesis that augmentation with an electrospun nanofiber sheet incorporating methylcobalamin (MeCbl) would be effective for regeneration after peripheral nerve transection and repair.
Methods: Rats were divided into 3 groups that either underwent sciatic nerve repair with or without the MeCbl sheet, or a sham operation. At 4 and/or 8 weeks after the operation, sensory and motor functional recovery, along with histological findings, were compared among the groups using the toe-spreading test, mechanical and thermal algesimetry tests, tibialis anterior muscle weight measurements, electrophysiological analyses, which included nerve conduction velocity (NCV), compound muscle action potential (CMAP), and terminal latency (TL), and histological analyses involving the myelinated axon ratio, axon diameter, and total axon number.
Results: Compared with the repair group without the MeCbl sheet, the repair group with the MeCbl sheet showed significant recovery in terms of tibialis anterior muscle weight, NCV and CMAP, and also tended to improve in the toe-spreading test, mechanical and thermal algesimetry tests, and TL. Histological analyses also demonstrated that the myelinated axon ratios and axon diameters were significantly higher. Among these findings, the repair group with the MeCbl sheet demonstrated the same recovery in NCV as the sham group.
Conclusion: This study demonstrated that electrospun nanofiber MeCbl sheets promoted nerve regeneration and functional recovery, indicating that this treatment strategy may be viable for human peripheral nerve injuries.


greenmedinfo--2020-07-28--Nutritional and medical food therapies for diabetic retinopathy.

Diabetic retinopathy ( DR ) is a form of microangiopathy .
Reducing oxidative stress in the mitochondria and cell membranes decreases ischemic injury and end-organ damage to the retina .
New approaches are needed , which reduce the risk and improve the outcomes of DR while complementing current therapeutic approaches .
Homocysteine ( Hcy ) elevation and oxidative stress are potential therapeutic targets in DR. Common genetic polymorphisms such as those of methylenetetrahydrofolate reductase ( MTHFR ) , increase Hcy and DR risk and severity .
Patients with DR have high incidences of deficiencies of crucial vitamins , minerals , @ @ @ @ @ @ @ to elevation of Hcy and oxidative stress .
Addressing the effects of the MTHFR polymorphism and addressing comorbid deficiencies and insufficiencies reduce the impact and severity of the disease .
This approach provides safe and simple strategies that support conventional care and improve outcomes .
Suboptimal vitamin co-factor availability also impairs the release of neurotrophic and neuroprotective growth factors .
Collectively , this accounts for variability in presentation and response of DR to conventional therapy .
Fortunately , there are straightforward recommendations for addressing these issues and supporting traditional treatment plans .
We @ @ @ @ @ @ @ that support conventional therapies to reduce disease risk and severity .
Optimal combinations of vitamins B1 , B2 , B6 , L-methylfolate , methylcobalamin ( B12 ) , C , D , natural vitamin E complex , lutein , zeaxanthin , alpha-lipoic acid , and n-acetylcysteine are identified for protecting the retina and choroid .
Certain medical foods have been successfully used as therapy for retinopathy .
Recommendations based on this review and our clinical experience are developed for clinicians to use to support conventional therapy for DR. DR from both type 1 @ @ @ @ @ @ @ 2 diabetes mellitus ( T2DM ) have similar retinal findings and responses to nutritional therapies .

Diabetic retinopathy (DR) is a form of microangiopathy. Reducing oxidative stress in the mitochondria and cell membranes decreases ischemic injury and end-organ damage to the retina. New approaches are needed, which reduce the risk and improve the outcomes of DR while complementing current therapeutic approaches. Homocysteine (Hcy) elevation and oxidative stress are potential therapeutic targets in DR. Common genetic polymorphisms such as those of methylenetetrahydrofolate reductase (MTHFR), increase Hcy and DR risk and severity. Patients with DR have high incidences of deficiencies of crucial vitamins, minerals, and related compounds, which also lead to elevation of Hcy and oxidative stress. Addressing the effects of the MTHFR polymorphism and addressing comorbid deficiencies and insufficiencies reduce the impact and severity of the disease. This approach provides safe and simple strategies that support conventional care and improve outcomes. Suboptimal vitamin co-factor availability also impairs the release of neurotrophic and neuroprotective growth factors. Collectively, this accounts for variability in presentation and response of DR to conventional therapy. Fortunately, there are straightforward recommendations for addressing these issues and supporting traditional treatment plans. We have reviewed the literature for nutritional interventions that support conventional therapies to reduce disease risk and severity. Optimal combinations of vitamins B1, B2, B6, L-methylfolate, methylcobalamin (B12), C, D, natural vitamin E complex, lutein, zeaxanthin, alpha-lipoic acid, and n-acetylcysteine are identified for protecting the retina and choroid. Certain medical foods have been successfully used as therapy for retinopathy. Recommendations based on this review and our clinical experience are developed for clinicians to use to support conventional therapy for DR. DR from both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) have similar retinal findings and responses to nutritional therapies.


greenmedinfo--2020-07-28--Lutein was found to be an extremely good cell protector against hydroxyl radicals at all oxygen conc

The interactions of dietary carotenoids , and particularly the xanthophylls in the macula , with singlet oxygen and three different @ @ @ @ @ , nitrogen dioxide and the superoxide radical anion ) are compared using pulsed laser andγ-techniques @ @ @ @ @ molecular mechanisms for the switch from anti-oxidant ( protection ) by carotenoids to pro-oxidant ( @ @ @ @ @ The participation of oxygen in radical mechanisms in the presence of different carotenoids is compared @ @ @ @ @ It isshown that the mechanistic role of oxygen differs very significantly for anti-/pro-oxidation by hydroxyl @ @ @ @ @ dioxide .
Lutein was found to be an extremely good cell protector against hydroxyl radicals @ @ @ @ @ including under physiological conditions .

The interactions of dietary carotenoids, and particularly the xanthophylls in the macula, with singlet oxygen and three different oxy-radicals, (hydroxyl radical, nitrogen dioxide and the superoxide radical anion) are compared using pulsed laser andγ-techniques. The results give possible molecular mechanisms for the switch from anti-oxidant (protection) by carotenoids to pro-oxidant (damage) by carotenoids. The participation of oxygen in radical mechanisms in the presence of different carotenoids is compared for the different radicals. It isshown that the mechanistic role of oxygen differs very significantly for anti-/pro-oxidation by hydroxyl radicals when compared to nitrogen dioxide. Lutein was found to be an extremely good cell protector against hydroxyl radicals at all oxygen concentrations, including under physiological conditions.


greenmedinfo--2020-07-28--Identification of fatty acid, lipid and polyphenol compounds from Prunus armeniaca kernel extracts.

Apart from its essential oil , L .
kernel extract has received only scarce attention .
The present study aimed to describe the lipid and polyphenolic composition of the dichloromethane , chloroform , ethyl acetate , and ethanol extracts on the basis of hot extraction , performing analysis by gas chromatography and high-performance liquid chromatography coupled with mass spectrometry .
A total of 6 diacylglycerols ( DAGs ) and 18 triacylglycerols ( TAGs ) were detected as being present in all extracts , with the predominance of OLL ( dilinoleyl-olein ) , OOL ( dioleoyl-linolein ) , and OOO ( @ @ @ @ @ @ @ 19.0-32.8 % , 20.3-23.6 % , and 12.1-20.1 % , respectively .
In further detail , the extraction with ethyl acetate ( medium polarity solvent ) gave the highest signal for all peaks , followed by chloroform and dichloromethane ( more apolar solvent ) , while the extraction with ethanol ( polar solvent ) was the least efficient .
Ethanol showed very poor signal for the most saturated TAGs , while dichloromethane showed the lowest percentages of DAGs .
Accordingly , the screening of the total fatty acid composition revealed the lowest percentage @ @ @ @ @ @ @ the dichloromethane extract , which instead contained the highest amount ( greater than 60 % ) of oleic acid ( C18:1n9 ) .
Polyphenolic compounds with pharmacological effects ( anti-tumor , anti-coagulant , and inflammatory ) , such as coumarin derivative and amygdalin , occurred at a higher amount in ethyl acetate and ethanol extracts .

Apart from its essential oil,L. kernel extract has received only scarce attention. The present study aimed to describe the lipid and polyphenolic composition of the dichloromethane, chloroform, ethyl acetate, and ethanol extracts on the basis of hot extraction, performing analysis by gas chromatography and high-performance liquid chromatography coupled with mass spectrometry. A total of 6 diacylglycerols (DAGs) and 18 triacylglycerols (TAGs) were detected as being present in all extracts, with the predominance of OLL (dilinoleyl-olein), OOL (dioleoyl-linolein), and OOO (triolein), with percentages ranging from 19.0-32.8%, 20.3-23.6%, and 12.1-20.1%, respectively. In further detail, the extraction with ethyl acetate (medium polarity solvent) gave the highest signal for all peaks, followed by chloroform and dichloromethane (more apolar solvent), while the extraction with ethanol (polar solvent) was the least efficient. Ethanol showed very poor signal for the most saturated TAGs, while dichloromethane showed the lowest percentages of DAGs. Accordingly, the screening of the total fatty acid composition revealed the lowest percentage of linoleic acid (C18:2n6) in the dichloromethane extract, which instead contained the highest amount (greater than 60%) of oleic acid (C18:1n9). Polyphenolic compounds with pharmacological effects (anti-tumor, anti-coagulant, and inflammatory), such as coumarin derivative and amygdalin, occurred at a higher amount in ethyl acetate and ethanol extracts.


greenmedinfo--2020-07-28--Protective effect of lutein on oxidative stress damage caused by acute PM2.5 exposure.

BACKGROUND : Particulate matter ( PM ) is the sum of organic and inorganic substances suspended in air .
Particles with a diameter equal to or smaller than 2.5μm ( PM2.5 ) can induce extensive oxidative stress damage in lung tissues .
Lutein can prevent oxidative stress and the production of pro-inflammatory cytokines .
However , its role in lung injury induced by PM2.5 is still unclear .
This study used lutein to intervene in lung injury induced by PM2.5 in rats to confirm the protective function of lutein in PM2.5- induced lung injury .
METHODS : A total of @ @ @ @ @ @ @ according to body weight ( bw ) .
Rats in the blank control group and the PM2.5 exposure group were treated with normal saline .
The low- , medium- , and high-dose lutein groups were treated with 12.5 , 25.0 , and 50.0 mg/kg·bw lutein continuously for 28 days .
In addition , on days 22-28 , 10 mg/kg PM2.5 was introduced by intratracheal instillation into the PM2.5 exposure group and all lutein dose groups continuously for 7 days to establish PM2.5 injury models .
Lung tissues were collected and subjected to hematoxylin-eosin @ @ @ @ @ @ @ changes .
Bronchoalveolar lavage fluid ( BALF ) was collected to detect the expression of cell damage indicators including lactate dehydrogenase ( LDH ) , acidic phosphatase ( ACP ) , alkaline phosphatase ( AKP ) , interleukin-6 ( IL-6 ) , interleukin-8 ( IL-8 ) , and tumor necrosis factor-alpha ( TNF-α ) .
In addition , the levels of serum oxidative stress indicators in rats , including methane dicarboxylic aldehyde ( MDA ) , superoxide dismutase ( SOD ) , glutathione ( GSH ) , nitric oxide synthase ( NOS ) @ @ @ @ @ @ @ as well as cytokines , including IL-6 , IL-8 , and TNF-α , were analyzed .
RESULTS : Lung tissues of rats after PM2.5 exposure exhibited different degrees of pathological changes .
In serum , oxidative damage indicators MDA , NOS , and 8-OHdG and inflammatory cytokines IL-6 , IL-8 , and TNF-α significantly increased whereas GSH levels significantly decreased ( P < 0.05 ) .
In BALF , cell damage indicators ACP and AKP and inflammatory cytokines IL-6 , IL-8 , and TNF-α all increased ( P < 0.05 ) .
After @ @ @ @ @ @ @ inflammatory cytokines in serum and BALF all significantly decreased ( P < 0.05 ) whereas serum GSH levels increased ( P < 0.05 ) .
CONCLUSIONS : PM2.5 caused significant oxidative damage and inflammatory injury in rat lungs .
Lutein alleviated these effects , playing a protective role in lung tissues .

BACKGROUND: Particulate matter (PM) is the sum of organic and inorganic substances suspended in air. Particles with a diameter equal to or smaller than 2.5μm (PM2.5) can induce extensive oxidative stress damage in lung tissues. Lutein can prevent oxidative stress and the production of pro-inflammatory cytokines. However, its role in lung injury induced by PM2.5 is still unclear. This study used lutein to intervene in lung injury induced by PM2.5 in rats to confirm the protective function of lutein in PM2.5- induced lung injury.
METHODS: A total of 80 rats were divided into five groups according to body weight (bw). Rats in the blank control group and the PM2.5 exposure group were treated with normal saline. The low-, medium-, and high-dose lutein groups were treated with 12.5, 25.0, and 50.0 mg/kg·bw lutein continuously for 28 days. In addition, on days 22-28, 10 mg/kg PM2.5 was introduced by intratracheal instillation into the PM2.5 exposure group and all lutein dose groups continuously for 7 days to establish PM2.5 injury models. Lung tissues were collected and subjected to hematoxylin-eosin (HE) staining to observe histomorphological changes. Bronchoalveolar lavage fluid (BALF) was collected to detect the expression of cell damage indicators including lactate dehydrogenase (LDH), acidic phosphatase (ACP), alkaline phosphatase (AKP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α). In addition, the levels of serum oxidative stress indicators in rats, including methane dicarboxylic aldehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), nitric oxide synthase (NOS), and 8-hydroxy-2'-deoxyguanosine (8-OHdG), as well as cytokines, including IL-6, IL-8, and TNF-α, were analyzed.
RESULTS: Lung tissues of rats after PM2.5 exposure exhibited different degrees of pathological changes. In serum, oxidative damage indicators MDA, NOS, and 8-OHdG and inflammatory cytokines IL-6, IL-8, and TNF-α significantly increased whereas GSH levels significantly decreased (P<0.05). In BALF, cell damage indicators ACP and AKP and inflammatory cytokines IL-6, IL-8, and TNF-α all increased (P<0.05). After lutein intervention, oxidative damage and cellular inflammatory cytokines in serum and BALF all significantly decreased (P<0.05) whereas serum GSH levels increased (P<0.05).
CONCLUSIONS: PM2.5 caused significant oxidative damage and inflammatory injury in rat lungs. Lutein alleviated these effects, playing a protective role in lung tissues.


greenmedinfo--2020-07-28--Aspirin & Your Heart: The Continuing Devaluation of Aspirin's Resume

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Before beginning any type of @ @ @ @ @ treatment regimen , it is advisable to seek the advice of a licensed healthcare professional @

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
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greenmedinfo--2020-07-28--Lutein inhibits breast cancer cell growth by suppressing antioxidant and cell survival signals and i

Lutein inhibits breast cancer cell growth by suppressing antioxidant and cell survival signals and induces apoptosis.

Reduced risk of breast cancer upon intake of lutein-rich food supplements creates an interest to investigate the molecular mechanism underlying the growth inhibitory potential of lutein in MCF-7 and MDA-MB-231 cells .
Lutein purified from Spinacia oleracea was identified by high-performance liquid chromatography and liquid chromatography-mass spectrometry .
The cell viability was measured by water-soluble tetrazolium-1 assay .
The intracellular reactive oxygen species level was examined by 2',7'-dichlorofluorescein assay .
The protein expression of the markers of antioxidant defense , cell survival , and apoptosis was analyzed by western blot analysis .
The induction of apoptosis by lutein was measured @ @ @ @ @ @ @ .
The purified lutein inhibited the viability of MCF-7 and MDA-MB-231 cells .
The growth inhibitory effect of lutein was associated with suppressed protein expression of superoxide dismutase-2 and heme oxygenase-1 , and its transcription factor nuclear factor erythroid 2-related factor-2 .
Lutein treatment subsequently blocked the expression of intracellular cell survival proteins , phosphorylated protein kinase B , phosphorylated extracellular-regulated kinase 1/2 , and nuclear factor-kB .
Suppression of antioxidant defense and cell survival markers by lutein was further linked to apoptosis induction with elevated caspase-3 activity and downregulated expression of Bcl-2 @ @ @ @ @ @ @ emphasize a significant role of lutein as an effective inhibitor of human breast cancer cell growth that activates cell death partly through the modulation of antioxidant defense response-linked cell survival signaling markers .

Reduced risk of breast cancer upon intake of lutein-rich food supplements creates an interest to investigate the molecular mechanism underlying the growth inhibitory potential of lutein in MCF-7 and MDA-MB-231 cells. Lutein purified from Spinacia oleracea was identified by high-performance liquid chromatography and liquid chromatography-mass spectrometry. The cell viability was measured by water-soluble tetrazolium-1 assay. The intracellular reactive oxygen species level was examined by 2',7'-dichlorofluorescein assay. The protein expression of the markers of antioxidant defense, cell survival, and apoptosis was analyzed by western blot analysis. The induction of apoptosis by lutein was measured by 4',6-diamidino-2-phenylindole staining and caspase-3 activity assay. The purified lutein inhibited the viability of MCF-7 and MDA-MB-231 cells. The growth inhibitory effect of lutein was associated with suppressed protein expression of superoxide dismutase-2 and heme oxygenase-1, and its transcription factor nuclear factor erythroid 2-related factor-2. Lutein treatment subsequently blocked the expression of intracellular cell survival proteins, phosphorylated protein kinase B, phosphorylated extracellular-regulated kinase 1/2, and nuclear factor-kB. Suppression of antioxidant defense and cell survival markers by lutein was further linked to apoptosis induction with elevated caspase-3 activity and downregulated expression of Bcl-2 and poly-ADP ribose polymerase. Our results emphasize a significant role of lutein as an effective inhibitor of human breast cancer cell growth that activates cell death partly through the modulation of antioxidant defense response-linked cell survival signaling markers.


greenmedinfo--2020-07-28--A comprehensive review of the relationship between nutrients and their role in age-related macular d

A comprehensive review of the relationship between nutrients and their role in age-related macular degeneration and retina disease prevention.

Age-related macular degeneration ( AMD ) is the leading cause of severe vision loss in developed countries and is highly common among aging individuals .
Considering the rate at which the global population is aging , the increasing prevalence of AMD and age-related eye disease is cause for concern .
AMD is associated with the degeneration of the macula , the most central region of the retina , leading to a loss of central vision .
A wide array of research has focused on the ability of lipid soluble nutrients to prevent and mitigate the harmful effects of AMD .
@ @ @ @ @ @ @ highly saturated within retinal tissues including the carotenoids lutein and zeaxanthin and the polyunsaturated fatty acid docosahexaenoic acid ( DHA ) .
Additionally , the unique presence of very long chain polyunsaturated fatty acids ( VLCPUFAs , C24-C36 ) in the retina may be essential to prevent retinal degeneration as demonstrated by abnormal retinal functioning in the absence of these novel fatty acids .
Existing literature has suggested that lutein , zeaxanthin and DHA consumption tend to enhance the health of the retina , protecting against the development of AMD .
However , @ @ @ @ @ @ @ is demonstrated and more research is required to understand the role of these nutrients in the retina and for the prevention of AMD .
Considering the global impact of AMD and age-related eye disease , utilizing nutrients to prevent the formation of these debilitating diseases is a highly affordable and promising strategy .

Age-related macular degeneration (AMD) is the leading cause of severe vision loss in developed countries and is highly common among aging individuals. Considering the rate at which the global population is aging, the increasing prevalence of AMD and age-related eye disease is cause for concern. AMD is associated with the degeneration of the macula, the most central region of the retina, leading to a loss of central vision. A wide array of research has focused on the ability of lipid soluble nutrients to prevent and mitigate the harmful effects of AMD. These nutrients in question tend to be highly saturated within retinal tissues including the carotenoids lutein and zeaxanthin and the polyunsaturated fatty acid docosahexaenoic acid (DHA). Additionally, the unique presence of very long chain polyunsaturated fatty acids (VLCPUFAs, C24-C36) in the retina may be essential to prevent retinal degeneration as demonstrated by abnormal retinal functioning in the absence of these novel fatty acids. Existing literature has suggested that lutein, zeaxanthin and DHA consumption tend to enhance the health of the retina, protecting against the development of AMD. However, little improvement to the previously deteriorated retina is demonstrated and more research is required to understand the role of these nutrients in the retina and for the prevention of AMD. Considering the global impact of AMD and age-related eye disease, utilizing nutrients to prevent the formation of these debilitating diseases is a highly affordable and promising strategy.


greenmedinfo--2020-07-29--This report highlights the potential benefits of high-dose intravenous vitamin C in critically ill C

This report highlights the potential benefits of high-dose intravenous vitamin C in critically ill COVID-19 patients in terms of rapid recovery.

BACKGROUND Coronavirus disease 2019 ( COVID-19 ) continues to spread , with confirmed cases now in more than 200 countries .
Thus far there are no proven therapeutic options to treat COVID-19 .
We report a case of COVID-19 with acute respiratory distress syndrome who was treated with high-dose vitamin C infusion and was the first case to have early recovery from the disease at our institute .
CASE REPORT A 74-year-old woman with no recent sick contacts or travel history presented with fever , cough , and shortness of breath .
Her vital signs were normal except for oxygen @ @ @ @ @ @ @ on lung auscultation .
Chest radiography revealed air space opacity in the right upper lobe , suspicious for pneumonia .
A nasopharyngeal swab for severe acute respiratory syndrome coronavirus-2 came back positive while the patient was in the airborne-isolation unit .
Laboratory data showed lymphopenia and elevated lactate dehydrogenase , ferritin , and interleukin-6 .
The patient was initially started on oral hydroxychloroquine and azithromycin .
On day 6 , she developed ARDS and septic shock , for which mechanical ventilation and pressor support were started , along with infusion of high-dose intravenous @ @ @ @ @ @ @ was able to be taken off mechanical ventilation within 5 days .
CONCLUSIONS This report highlights the potential benefits of high-dose intravenous vitamin C in critically ill COVID-19 patients in terms of rapid recovery and shortened length of mechanical ventilation and ICU stay .
Further studies will elaborate on the efficacy of intravenous vitamin C in critically ill COVID-19 .

BACKGROUND Coronavirus disease 2019 (COVID-19) continues to spread, with confirmed cases now in more than 200 countries. Thus far there are no proven therapeutic options to treat COVID-19. We report a case of COVID-19 with acute respiratory distress syndrome who was treated with high-dose vitamin C infusion and was the first case to have early recovery from the disease at our institute. CASE REPORT A 74-year-old woman with no recent sick contacts or travel history presented with fever, cough, and shortness of breath. Her vital signs were normal except for oxygen saturation of 87% and bilateral rhonchi on lung auscultation. Chest radiography revealed air space opacity in the right upper lobe, suspicious for pneumonia. A nasopharyngeal swab for severe acute respiratory syndrome coronavirus-2 came back positive while the patient was in the airborne-isolation unit. Laboratory data showed lymphopenia and elevated lactate dehydrogenase, ferritin, and interleukin-6. The patient was initially started on oral hydroxychloroquine and azithromycin. On day 6, she developed ARDS and septic shock, for which mechanical ventilation and pressor support were started, along with infusion of high-dose intravenous vitamin C. The patient improved clinically and was able to be taken off mechanical ventilation within 5 days. CONCLUSIONS This report highlights the potential benefits of high-dose intravenous vitamin C in critically ill COVID-19 patients in terms of rapid recovery and shortened length of mechanical ventilation and ICU stay. Further studies will elaborate on the efficacy of intravenous vitamin C in critically ill COVID-19.


greenmedinfo--2020-07-29--Serum vitamin D levels could be implicated in the COVID-19 prognosis.

BACKGROUND : As an immune modulator , vitamin D has been implicated in the Coronavirus disease-2019 ( COVID-19 ) outcome .
We aim to systematically explore the association of vitamin D serum levels with COVID-19 severity and prognosis .
METHODS : The standardized mean difference ( SMD ) or odds ratio and 95 % confidence interval ( CI ) were applied to estimate pooled results from seven studies .
The prognostic performance of vitamin D serum levels for predicting adverse outcomes with detection of the best cutoff threshold was determined by ROC curve analysis .
Decision tree analysis by combining @ @ @ @ @ @ @ applied to predict severity in COVID-19 patients .
RESULTS : Mean vitamin D serum level of 1,368 patients , was 22.9 nmol/L ( 21.9-23.8 ) .
Significant heterogeneity was found ( I= 99.9 % , P < 0.001 ) .
Patients with poor prognosis ( N=634 ) had significantly lower serum levels of vitamin D compared to those with good prognosis ( N=669 ) , representing an adjusted standardized mean difference of -5.12 ( 95 % Cl= -9.14 to -1.10 , P = 0.012 ) .
CONCLUSION : Serum vitamin D levels could @ @ @ @ @ @ @ Diagnosis of vitamin D deficiency could be a helpful adjunct in assessing patients ' potential of developing severe COVID-19 .
Appropriate preventative and/or therapeutic intervention may improve COVID-19 outcomes .
This article is protected by copyright .
All rights reserved .

BACKGROUND: As an immune modulator, vitamin D has been implicated in the Coronavirus disease-2019 (COVID-19) outcome. We aim to systematically explore the association of vitamin D serum levels with COVID-19 severity and prognosis.
METHODS: The standardized mean difference (SMD) or odds ratio and 95% confidence interval (CI) were applied to estimate pooled results from seven studies. The prognostic performance of vitamin D serum levels for predicting adverse outcomes with detection of the best cutoff threshold was determined by ROC curve analysis. Decision tree analysis by combining vitamin D levels and clinical features was applied to predict severity in COVID-19 patients.
RESULTS: Mean vitamin D serum level of 1,368 patients, was 22.9 nmol/L (21.9-23.8). Significant heterogeneity was found (I= 99.9%, P<0.001). Patients with poor prognosis (N=634) had significantly lower serum levels of vitamin D compared to those with good prognosis (N=669), representing an adjusted standardized mean difference of -5.12 (95% Cl= -9.14 to -1.10, P = 0.012).
CONCLUSION: Serum vitamin D levels could be implicated in the COVID-19 prognosis. Diagnosis of vitamin D deficiency could be a helpful adjunct in assessing patients' potential of developing severe COVID-19. Appropriate preventative and/or therapeutic intervention may improve COVID-19 outcomes. This article is protected by copyright. All rights reserved.


greenmedinfo--2020-07-29--Vitamin D high doses supplementation could represent a promising alternative to prevent or treat COV

Vitamin D high doses supplementation could represent a promising alternative to prevent or treat COVID-19 infection.

Although we lack enough evidence to justify supplementing with vitaminD in the prevention and treatment of COVID-19 infection , it is increasingly feasible that this hypothesis is valid .
Two general underlying mechanisms should be considered .
One would be the anti-infectious and immunomodulatory action that it exerts by improving intercellular barriers by stimulating innate immunity , as well as by modulating adaptive immunity .
Also , vitaminD reduces the production of inflammatory cytokines , such as IL-2 and interferon-gamma ( INF-γ ) .
More recently , multiple pleiotropic effects have been demonstrated on the actions of vitaminD at the @ @ @ @ @ @ @ in studies with influenza , coronavirus , and other respiratory infections .
An inverse relationship between serum vitaminD levelsand the prevalence of the respiratory infectious disease has been described .
Of interest , another mechanistic approach responds to considering the inhibition of the renin-angiotensin-aldosterone system ( RAAS ) , which is exacerbated in COVID-19 infection because the virus binds to the enzyme ACE2 , making more angiotensinII available to cause damage .
VitaminD inhibits mediators of RAAS - present in all cells of the body - and by inhibiting ACE activity and increasing @ @ @ @ @ @ @ We present studies with proposals for recommended doses of vitaminD , and although a single guideline is not specified , the possible benefits are promising .
Finally , the purpose of this review is to share this idea with health professionals to ignite the debate and call for critical reflection , so that it can contribute to the undertaking of more and better clinical designs to validate thebenefits of using high doses of vitaminD for the benefit of public health and especially in times of crisis for COVID-19 .

Although we lack enough evidence to justify supplementing with vitaminD in the prevention and treatment of COVID-19 infection, it is increasingly feasible that this hypothesis is valid. Two general underlying mechanisms should be considered. One would be the anti-infectious and immunomodulatory action that it exerts by improving intercellular barriers by stimulating innate immunity, as well as by modulating adaptive immunity. Also, vitaminD reduces the production of inflammatory cytokines, such as IL-2 and interferon-gamma (INF-γ). More recently, multiple pleiotropic effects have been demonstrated on the actions of vitaminD at the anti-inflammatory and immunomodulatory level with positive results in studies with influenza, coronavirus, and other respiratory infections. An inverse relationship between serum vitaminD levelsand the prevalence of the respiratory infectious disease has been described. Of interest, another mechanistic approach responds to considering the inhibition of the renin-angiotensin-aldosterone system (RAAS), which is exacerbated in COVID-19 infection because the virus binds to the enzyme ACE2, making more angiotensinII available to cause damage. VitaminD inhibits mediators of RAAS - present in all cells of the body - and by inhibiting ACE activity and increasing ACE2, it lowers angiotensinII levels. We present studies with proposals for recommended doses of vitaminD, and although a single guideline is not specified, the possible benefits are promising. Finally, the purpose of this review is to share this idea with health professionals to ignite the debate and call for critical reflection, so that it can contribute to the undertaking of more and better clinical designs to validate thebenefits of using high doses of vitaminD for the benefit of public health and especially in times of crisis for COVID-19.


greenmedinfo--2020-07-29--Serum homocysteine levels were higher and vitamin B12 levels were lower among individuals with syste

Serum homocysteine levels were higher and vitamin B12 levels were lower among individuals with systemic lupus erythematosus.

BACKGROUND : Patients with systemic lupus erythematosus ( SLE ) have elevated cardiovascular risk .
Hyperhomocysteinemia may be one of the contributing factors to this phenomenon .
This study therefore aimed to compare the serum homocysteine levels and the levels of folate and vitamin B12 , cofactors for homocysteine metabolism , between individuals with and without SLE .
METHODS : A literature search was performed in PubMed , Embase , and the Cochrane library ( from inception to March 31 , 2019 ) .
Studies comparing serum homocysteine , folate or vitamin Blevels between individuals with and without SLE were @ @ @ @ @ @ @ , 50 studies met the inclusion criteria .
RESULTS : A total of 50 studies involving 4396 patients with SLE were included .
Patients with SLE had a significantly higher serum level of homocysteine ( standardized mean difference [ SMD ] , 1.134 ; 95 % CI , 0.795-1.474 ) and lower level of vitamin B ( SMD , -0.359 ; 95 % CI , -0.638 to -0.080 ) than controls .
The folate level did n't differ markedly between SLE patients and the control group ( SMD , -0.276 ; 95 % @ @ @ @ @ @ @ showed consistent results in adult SLE patients .
A random effects meta-regression analysis revealed a significantly inverse correlation between the SMD of homocysteine levels and C3 levels ( coefficient , -0.0356 , 95 % CI , -0.054 to -0.0171 ; P CONCLUSIONS : Serum homocysteine levels were higher and vitamin Blevels were lower among individuals with SLE than those without SLE .
Physicians are encouraged to monitor these parameters and offer timely interventions for patients with SLE .

BACKGROUND: Patients with systemic lupus erythematosus (SLE) have elevated cardiovascular risk. Hyperhomocysteinemia may be one of the contributing factors to this phenomenon. This study therefore aimed to compare the serum homocysteine levels and the levels of folate and vitamin B12, cofactors for homocysteine metabolism, between individuals with and without SLE.
METHODS: A literature search was performed in PubMed, Embase, and the Cochrane library (from inception to March 31, 2019). Studies comparing serum homocysteine, folate or vitamin Blevels between individuals with and without SLE were selected. Of the 1040 screened studies, 50 studies met the inclusion criteria.
RESULTS: A total of 50 studies involving 4396 patients with SLE were included. Patients with SLE had a significantly higher serum level of homocysteine (standardized mean difference [SMD], 1.134; 95% CI, 0.795-1.474) and lower level of vitamin B(SMD, -0.359; 95% CI, -0.638 to -0.080) than controls. The folate level didn't differ markedly between SLE patients and the control group (SMD, -0.276; 95% CI, -0.674-0.123). Subgroup analysis showed consistent results in adult SLE patients. A random effects meta-regression analysis revealed a significantly inverse correlation between the SMD of homocysteine levels and C3 levels (coefficient, -0.0356, 95% CI, -0.054 to -0.0171; P<.001) and C4 levels (coefficient, -0.0876, 95% CI, -0.1407 to -0.0345; P = .0012).
CONCLUSIONS: Serum homocysteine levels were higher and vitamin Blevels were lower among individuals with SLE than those without SLE. Physicians are encouraged to monitor these parameters and offer timely interventions for patients with SLE.


greenmedinfo--2020-07-29--Pyridoxine induces glutathione synthesis via PKM2-mediated Nrf2 transactivation and confers neuropro

Pyridoxine induces glutathione synthesis via PKM2-mediated Nrf2 transactivation and confers neuroprotection

Oxidative stress is a major pathogenic mechanism in Parkinson 's disease ( PD ) .
As an important cellular antioxidant @ @ @ @ @ balances the production and incorporation of free radicals to protect neurons from oxidative damage .
@ @ @ @ @ the brains of PD patients .
Hence , clarifying the molecular mechanism of GSH deficiency @ @ @ @ @ of PD pathogenesis .
Here we report that the astrocytic dopamine D2 receptor ( DRD2 @ @ @ @ @ PKM2-mediated Nrf2 transactivation .
In addition we find that pyridoxine can dimerize PKM2 to promote @ @ @ @ @ show that pyridoxine supplementation increases the resistance of nigral dopaminergic neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ( MPTP @ @ @ @ @ mice as well as in astrocytic Drd2 conditional knockout mice .
We conclude that dimerizing @ @ @ @ @ target for PD treatment .

Oxidative stress is a major pathogenic mechanism in Parkinson's disease (PD). As an important cellular antioxidant, glutathione (GSH) balances the production and incorporation of free radicals to protect neurons from oxidative damage. GSH level is decreased in the brains of PD patients. Hence, clarifying the molecular mechanism of GSH deficiency may help deepen our knowledge of PD pathogenesis. Here we report that the astrocytic dopamine D2 receptor (DRD2) regulates GSH synthesis via PKM2-mediated Nrf2 transactivation. In addition we find that pyridoxine can dimerize PKM2 to promote GSH biosynthesis. Further experiments show that pyridoxine supplementation increases the resistance of nigral dopaminergic neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in wild-type mice as well as in astrocytic Drd2 conditional knockout mice. We conclude that dimerizing PKM2 may be a potential target for PD treatment.


greenmedinfo--2020-07-29--Pyridoxine enhances chemo-responsiveness of breast cancer stem cells via redox reconditioning.

A plethora of molecular strategies are employed by breast cancer stem cells ( bCSCs ) to evade chemotherapy-induced death signals , redox modulation being a crucial factor among those .
Here , we observed that bCSCs are resistant to DNA damage and generate low ROS upon doxorubicin ( Dox ) treatment .
Further exploration revealed inherently high NEIL2 , a base excision repair ( BER ) enzyme that plays a key regulatory role in repairing DNA damage , in bCSCs .
However , its role in modulating the redox status of bCSCs remains unexplored .
In addition , Dox not @ @ @ @ @ @ @ transcriptional and translational levels but also declines p300-induced acetylation thus activating NEIL2 and providing a protective effect against the stress inflicted by the genotoxic drug .
However , when the redox status of bCSCs is altered by inducing high ROS , apoptosis of the resistant population is accomplished .
Subsequently , when NEIL2 is suppressed in bCSCs , chemo-sensitization of the resistant population is enabled by redox reconditioning via impaired DNA repair .
This signifies a possibility of therapeutically disrupting the redox balance in bCSCs to enhance their chemo-responsiveness .
Our search for @ @ @ @ @ @ @ B6 , i.e.
, pyridoxine ( PN ) , hinders NEIL2-mediated transcription-coupled repair process by not only decreasing NEIL2 expression but also inhibiting its association with RNA Pol II , thus stimulating DNA damage and triggering ROS .
As a consequence of altered redox regulation , bCSCs become susceptible towards Dox , which then induces apoptosis via caspase cascade .
These findings signify that PN enhances chemo-responsiveness of bCSCs via redox reconditioning .

A plethora of molecular strategies are employed by breast cancer stem cells (bCSCs) to evade chemotherapy-induced death signals, redox modulation being a crucial factor among those. Here, we observed that bCSCs are resistant to DNA damage and generate low ROS upon doxorubicin (Dox) treatment. Further exploration revealed inherently high NEIL2, a base excision repair (BER) enzyme that plays a key regulatory role in repairing DNA damage, in bCSCs. However, its role in modulating the redox status of bCSCs remains unexplored. In addition, Dox not only upregulates NEIL2 in bCSCs at both transcriptional and translational levels but also declines p300-induced acetylation thus activating NEIL2 and providing a protective effect against the stress inflicted by the genotoxic drug. However, when the redox status of bCSCs is altered by inducing high ROS, apoptosis of the resistant population is accomplished. Subsequently, when NEIL2 is suppressed in bCSCs, chemo-sensitization of the resistant population is enabled by redox reconditioning via impaired DNA repair. This signifies a possibility of therapeutically disrupting the redox balance in bCSCs to enhance their chemo-responsiveness. Our search for an inhibitor of NEIL2 revealed that vitamin B6, i.e., pyridoxine (PN), hinders NEIL2-mediated transcription-coupled repair process by not only decreasing NEIL2 expression but also inhibiting its association with RNA Pol II, thus stimulating DNA damage and triggering ROS. As a consequence of altered redox regulation, bCSCs become susceptible towards Dox, which then induces apoptosis via caspase cascade. These findings signify that PN enhances chemo-responsiveness of bCSCs via redox reconditioning.


greenmedinfo--2020-07-29--Pyridoxine, folate and cobalamin for migraine: A systematic review.

There is a possible relationship between migraine and hypercoagulability inducing factors , such as hyperhomocysteinemia .
In this context , homocysteine ( Hcy ) -lowering vitamins ( B6-folate-B12 ) may prove beneficial in the management-prophylaxis of migraine .
We performed a systematic literature search in order to retrieve studies assessing the supplementation of B6 , folate and B12 ( alone or as adjunctive therapies ) to migraine patients , as well as patients suffering from other primary headache disorders .
MEDLINE , EMBASE , CENTRAL , Google Scholar , trial registries and OpenGrey were searched .
Twelve relevant articles were @ @ @ @ @ @ @ attacks with Hcy-lowering vitamins has not provided promising results ( one randomized controlled trial-RCT-and one prospective uncontrolled trial ) .
On the contrary , significant benefits were registered for the use of B6 alone , in combination with folate and in combination with folate and B12 in the prophylaxis of migraine with aura ( MA ) in adults compared to placebo ( five RCTs , only one did not obtain significant results ) .
Folate supplementation alone was not more efficacious than placebo ( one RCT ) .
Limited data for the prophylaxis @ @ @ @ @ @ @ in children ( two prospective uncontrolled trials ) and adults ( two prospective uncontrolled trials involving both MA and MO participants ) impede the extraction of safe conclusions .
An overall attractive safety profile was exhibited with gastrointestinal adverse events being the most common .
Overall , a potential beneficial effect regarding the administration of B6 , folate and/or B12 in the prophylaxis of MA in adults was indicated .
Additional high-quality RCTs that will investigate MO in adults as well as MO and MA in children are warranted .

There is a possible relationship between migraine and hypercoagulability inducing factors, such as hyperhomocysteinemia. In this context, homocysteine (Hcy)-lowering vitamins (B6-folate-B12) may prove beneficial in the management-prophylaxis of migraine. We performed a systematic literature search in order to retrieve studies assessing the supplementation of B6, folate and B12 (alone or as adjunctive therapies) to migraine patients, as well as patients suffering from other primary headache disorders. MEDLINE, EMBASE, CENTRAL, Google Scholar, trial registries and OpenGrey were searched. Twelve relevant articles were retrieved. The management of acute migraine attacks with Hcy-lowering vitamins has not provided promising results (one randomized controlled trial-RCT-and one prospective uncontrolled trial). On the contrary, significant benefits were registered for the use of B6 alone, in combination with folate and in combination with folate and B12 in the prophylaxis of migraine with aura (MA) in adults compared to placebo (five RCTs, only one did not obtain significant results). Folate supplementation alone was not more efficacious than placebo (one RCT). Limited data for the prophylaxis of migraine without aura (MO) in children (two prospective uncontrolled trials) and adults (two prospective uncontrolled trials involving both MA and MO participants) impede the extraction of safe conclusions. An overall attractive safety profile was exhibited with gastrointestinal adverse events being the most common. Overall, a potential beneficial effect regarding the administration of B6, folate and/or B12 in the prophylaxis of MA in adults was indicated. Additional high-quality RCTs that will investigate MO in adults as well as MO and MA in children are warranted.


greenmedinfo--2020-07-29--Oral exposure to titanium dioxide nanoparticles for 90 days could disrupt the metabolism of the inte

Oral exposure to titanium dioxide nanoparticles for 90 days could disrupt the metabolism of the intestine and gut microbiota.

OBJECTIVE : To explore the effects and related mechanisms of oral exposure titanium dioxide nanoparticles ( TiONPs ) for 90 days on the intestinal and the gut microbiota of rats , through fecal metabolomics .
METHODS : Twelve 4-week-old clean-grade Sprague Dawley ( SD ) rats were randomly de-vided into 2 groups by body weight , treated with TiONPs at dose of 0 or 50 mg/kg body weight everyday respectively for 90 days .
The solution of each infection was freshly prepared and shocked fully by ultrasonic .
Characterization of the particle size , crystal form , purity , and @ @ @ @ @ @ @ .
And the fresh feces of the rats were collected on the 90th day .
After lyophilized and hydrophilic phase extraction , ultra performance liquid chromatography-Q-exactive orbitrap-high-resolution mass spectrometry system ( UPLC-QEMS ) was utilized for non-targeted determination of fecal meta-bolites .
The metabolites were identified and labeled through Compound Discoverer 3.0 software , and used for subsequent metabolomics analysis .
Bioinformatics analysis was carried out including unsupervised principal component analysis and supervised orthogonal projection to latent structure discriminant analysis for the differential metabolites between the two groups .
The differential metabolites were @ @ @ @ @ @ @ Genomes ( KEGG ) pathway analysis .
RESULTS : Compared with the control group , the body weight of the rats was significantly reduced ( < 0.05 ) in the treatment group .
A total of 22 metabolites in fecal metabolomics showed significant changes .
Among them , xanthine , 1-methyladenine , 3-hydroxypyridine , methionine sulfoxide , pyridoxine , 1,5-isoquinolinediol , N-acetylornithine , N-acetyl-D-galactosamine , L-citrulline , L-methionine , leucine , DL-tryptophan , L-ornithine , 4-methyl-5-thiazoleethanol , and L-glutamic acid totaled 15 metabolites increased significantly .
N-acetylhistamine , D-pipecolinic acid , imidazolelactic acid @ @ @ @ @ @ @ and histamine totaled 7 metabolites decreased significantly .
N-acetylhistamine , L-valine and methionine sulfoxide were changed more than 16 times .
Analysis of KEGG pathway revealed that the two metabolic pathways arginine biosynthesis and aminoacyl-tRNA biosynthesis were significantly changed ( false discover rate < 0.05 , pathway impact > 0.1 ) .
CONCLUSION : Oral exposure to TiONPs for 90 days could disrupt the metabolism of the intestine and gut microbiota , causing significant changes in metabolites and metabolic pathways which were related to inflammatory response , oxidative stress , glucose homeostasis , @ @ @ @ @ @ @ rat feces .
It is suggested that the toxic effect of TiONPs on rats may be closely related to intestinal and gut microbiota metabolism .

OBJECTIVE: To explore the effects and related mechanisms of oral exposure titanium dioxide nanoparticles (TiONPs) for 90 days on the intestinal and the gut microbiota of rats, through fecal metabolomics.
METHODS: Twelve 4-week-old clean-grade Sprague Dawley (SD) rats were randomly de-vided into 2 groups by body weight, treated with TiONPs at dose of 0 or 50 mg/kg body weight everyday respectively for 90 days. The solution of each infection was freshly prepared and shocked fully by ultrasonic. Characterization of the particle size, crystal form, purity, and specific surface area of TiONPs was conducted. And the fresh feces of the rats were collected on the 90th day. After lyophilized and hydrophilic phase extraction, ultra performance liquid chromatography-Q-exactive orbitrap-high-resolution mass spectrometry system (UPLC-QEMS) was utilized for non-targeted determination of fecal meta-bolites. The metabolites were identified and labeled through Compound Discoverer 3.0 software, and used for subsequent metabolomics analysis. Bioinformatics analysis was carried out including unsupervised principal component analysis and supervised orthogonal projection to latent structure discriminant analysis for the differential metabolites between the two groups. The differential metabolites were followed-up for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.
RESULTS: Compared with the control group, the body weight of the rats was significantly reduced (<0.05) in the treatment group. A total of 22 metabolites in fecal metabolomics showed significant changes. Among them, xanthine, 1-methyladenine, 3-hydroxypyridine, methionine sulfoxide, pyridoxine, 1,5-isoquinolinediol, N-acetylornithine, N-acetyl-D-galactosamine, L-citrulline, L-methionine, leucine, DL-tryptophan, L-ornithine, 4-methyl-5-thiazoleethanol, and L-glutamic acid totaled 15 metabolites increased significantly. N-acetylhistamine, D-pipecolinic acid, imidazolelactic acid, L-valine, 2,3,4,6-tetramethylpyrazine, caprolactam, and histamine totaled 7 metabolites decreased significantly. N-acetylhistamine, L-valine and methionine sulfoxide were changed more than 16 times. Analysis of KEGG pathway revealed that the two metabolic pathways arginine biosynthesis and aminoacyl-tRNA biosynthesis were significantly changed (false discover rate<0.05, pathway impact>0.1).
CONCLUSION: Oral exposure to TiONPs for 90 days could disrupt the metabolism of the intestine and gut microbiota, causing significant changes in metabolites and metabolic pathways which were related to inflammatory response, oxidative stress, glucose homeostasis, blood system and amino acid homeostasis in rat feces. It is suggested that the toxic effect of TiONPs on rats may be closely related to intestinal and gut microbiota metabolism.


greenmedinfo--2020-07-29--These results suggest that there is a possible link between migraine, mainly migraine with aura, and

These results suggest that there is a possible link between migraine, mainly migraine with aura, and elevated serum homocysteine.

BACKGROUND : Migraine , especially migraine with aura ( MA ) , has been linked to increased risk for ischemic cerebrovascular disease .
The possible role of elevated serum homocysteine ( Hcy , a cause of thrombophilia ) in migraine has been demonstrated by several studies .
OBJECTIVE : The present study aims to review and meta-analyze data from studies investigating the difference of serum Hcy and Hcy lowering vitamins between migraine patients and healthy controls ( HC ) , as well as between patients with MA and migraine without aura ( MO ) .
METHODS : Literature search involved @ @ @ @ @ @ @ Scholar , and trial registries .
The Newcastle-Ottawa Scale was used to evaluate the quality of the retrieved studies .
Standardized mean differences ( SMDs ) and 95 % confidence intervals ( 95 % CIs ) were calculated .
Funnel-plots were utilized for the evaluation of publication bias .
RESULTS : Overall , 29 ( 28 case-control and 1 cross-sectional ) studies were retrieved .
Meta-analysis was indicative of higher Hcy concentration in migraine patients vs HC overall [ adults and children : 16 studies , I = 81 % , SMD = @ @ @ @ @ @ @ 0.20 , 0.61 ) ] .
Hcy was consistently elevated in adults with migraine [ adults : 12 studies , I = 76 % , SMD = 0.35 , 95 % CI = ( 0.15 , 0.54 ) ; children : 1 study , SMD = 0.37 , 95 % CI = ( -0.05 , 0.79 ) ] .
Subgroup analyses reproduced the results for both adults with MA [ 7 studies , I = 83 % , SMD = 0.37 , 95 % CI = ( 0.03 , 0.71 ) ] and @ @ @ @ @ @ @ 84 % , SMD = 0.46 , 95 % CI = ( 0.03 , 0.89 ) ] .
Figures for serum folate were lower in the overall comparison of migraine patients with HC [ adults and children : 11 studies , I = 87 % , SMD = -0.36 , 95 % CI = ( -0.68 , -0.05 ) ; adults : 8 studies , I = 6 % , SMD = -0.11 , 95 % CI = ( -0.22 , 0.01 ) ; children : 1 study , SMD = -0.71 , @ @ @ @ @ @ @ -0.29 ) ; MA adults : 4 studies , I = 44 % , SMD = -0.16 , 95 % CI = ( -0.35 , 0.04 ) ; MO adults : 4 studies , I = 47 % , SMD = -0.17 , 95 % CI = ( -0.44 , 0.10 ) ] .
Serum vitamin B12 levels were not different between migraine patients and HC [ adults and children : 11 studies , I = 88 % , SMD = -0.24 , 95 % CI = ( -0.57 , 0.09 ) ; @ @ @ @ @ @ @ 57 % , SMD = -0.10 , 95 % CI = ( -0.28 , 0.08 ) ; children : 1 study , SMD = 0.29 , 95 % CI = ( -0.13 , 0.71 ) ; MA adults : 4 studies , I = 63 % , SMD = -0.14 , 95 % CI = ( -0.48 , 0.20 ) ; MO adults : 4 studies , I = 59 % , SMD = -0.15 , 95 % CI = ( -0.45 , 0.15 ) ] .
Serum Hcy was lower in MO @ @ @ @ @ @ @ 10 studies , I = 39 % , SMD = 0.30 , 95 % CI = ( 0.14 , 0.46 ) , adults : 6 studies , I = 29 % , SMD = 0.21 , 95 % CI = ( 0.09 , 0.36 ) , children : 1 study , SMD = 0.51 , 95 % CI = ( 0.22 , 0.80 ) ] .
Serum folate and vitamin B12 did not differ between MA and MO .
CONCLUSIONS : Our results suggest that there is a possible link between migraine , @ @ @ @ @ @ @ .

BACKGROUND: Migraine, especially migraine with aura (MA), has been linked to increased risk for ischemic cerebrovascular disease. The possible role of elevated serum homocysteine (Hcy, a cause of thrombophilia) in migraine has been demonstrated by several studies.
OBJECTIVE: The present study aims to review and meta-analyze data from studies investigating the difference of serum Hcy and Hcy lowering vitamins between migraine patients and healthy controls (HC), as well as between patients with MA and migraine without aura (MO).
METHODS: Literature search involved MEDLINE, Embase, CENTRAL, Google Scholar, and trial registries. The Newcastle-Ottawa Scale was used to evaluate the quality of the retrieved studies. Standardized mean differences (SMDs) and 95% confidence intervals (95%CIs) were calculated. Funnel-plots were utilized for the evaluation of publication bias.
RESULTS: Overall, 29 (28 case-control and 1 cross-sectional) studies were retrieved. Meta-analysis was indicative of higher Hcy concentration in migraine patients vs HC overall [adults and children: 16 studies, I = 81%, SMD = 0.41, 95%CI = (0.20, 0.61)]. Hcy was consistently elevated in adults with migraine [adults: 12 studies, I = 76%, SMD = 0.35, 95%CI = (0.15, 0.54); children: 1 study, SMD = 0.37, 95%CI = (-0.05, 0.79)]. Subgroup analyses reproduced the results for both adults with MA [7 studies, I = 83%, SMD = 0.37, 95%CI = (0.03, 0.71)] and MO [5 studies, I = 84%, SMD = 0.46, 95%CI = (0.03, 0.89)]. Figures for serum folate were lower in the overall comparison of migraine patients with HC [adults and children: 11 studies, I = 87%, SMD = -0.36, 95%CI = (-0.68, -0.05); adults: 8 studies, I = 6%, SMD = -0.11, 95%CI = (-0.22, 0.01); children: 1 study, SMD = -0.71, 95%CI = (-1.14, -0.29); MA adults: 4 studies, I = 44%, SMD = -0.16, 95%CI = (-0.35, 0.04); MO adults: 4 studies, I = 47%, SMD = -0.17, 95%CI = (-0.44, 0.10)]. Serum vitamin B12 levels were not different between migraine patients and HC [adults and children: 11 studies, I = 88%, SMD = -0.24, 95%CI = (-0.57, 0.09); adults: 8 studies, I = 57%, SMD = -0.10, 95%CI = (-0.28, 0.08); children: 1 study, SMD = 0.29, 95%CI = (-0.13, 0.71); MA adults: 4 studies, I = 63%, SMD = -0.14, 95%CI = (-0.48, 0.20); MO adults: 4 studies, I = 59%, SMD = -0.15, 95%CI = (-0.45, 0.15)]. Serum Hcy was lower in MO than MA [adults and children: 10 studies, I = 39%, SMD = 0.30, 95%CI = (0.14, 0.46), adults: 6 studies, I = 29%, SMD = 0.21, 95%CI = (0.09, 0.36), children: 1 study, SMD = 0.51, 95%CI = (0.22, 0.80)]. Serum folate and vitamin B12 did not differ between MA and MO.
CONCLUSIONS: Our results suggest that there is a possible link between migraine, mainly MA, and elevated serum Hcy.