greenmedinfo--2020-07-03--Bisphenol A triggers the malignancy of nasopharyngeal carcinoma cells.

It is critical to understand the risk factors responsible for the tumorigenesis and progression of nasopharyngeal carcinoma ( NPC ) @ @ @ @ @ ) can regulate the estrogenic signals to modulate cancer progression , while its roles in @ @ @ @ @ Our present study revealed that the BPA can increase proliferation and migration of NPC cells @ @ @ @ @ doxorubicin ( Dox ) .
The inhibitor of GSK-3β/β-catenin ( LiCl ) can restore BPA-induced @ @ @ @ @ , which is due to that BPA can decrease phosphorylation while increase expression and nucleus @ @ @ @ @ , BPA can increase the mRNA stability of β-catenin ( encoded by CTNNB1 ) via @ @ @ @ @ which can direct target the 3'UTR of β-catenin mRNA .
Further , BPA can decrease @ @ @ @ @ the expression of CK1α .
Collectively , our data showed that BPA can trigger the @ @ @ @ @ cells via activation of Wnt/β-catenin pathway .
It indicated that body accumulation and inhalation exposure @ @ @ @ @ risk factor for NPC development .

It is critical to understand the risk factors responsible for the tumorigenesis and progression of nasopharyngeal carcinoma (NPC). Bisphenol A (BPA) can regulate the estrogenic signals to modulate cancer progression, while its roles in NC were not investigated. Our present study revealed that the BPA can increase proliferation and migration of NPC cells while decrease the chemosensitivity to doxorubicin (Dox). The inhibitor of GSK-3β/β-catenin (LiCl) can restore BPA-induced cell proliferation of NPC cells, which is due to that BPA can decrease phosphorylation while increase expression and nucleus localization of β-catenin. Mechanistically, BPA can increase the mRNA stability of β-catenin (encoded by CTNNB1) via suppressingthe expression of miR-214-3p, which can direct target the 3'UTR of β-catenin mRNA. Further, BPA can decrease phosphorylation of β-catenin via repressing the expression of CK1α. Collectively, our data showed that BPA can trigger the proliferation and malignancy of NPC cells via activation of Wnt/β-catenin pathway. It indicated that body accumulation and inhalation exposure of BPA might be a risk factor for NPC development.


greenmedinfo--2020-07-03--Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen recepto

Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor α.

Plasticizers released from microplastic are increasingly viewed with concern .
While adverse health effects induced by bisphenol A and its analogues on marine animals are well documented in the literature , the endocrine potential of bisphenolic compounds on human health remains elusive .
We applied next generation sequencing ( NGS ) with the estrogen receptorα ( ERα ) positive human breast cancer cell line MCF-7 treated with 17-β-estradiol ( E2 ) , bisphenol A ( BPA ) , bisphenol B ( BPB ) , bisphenol Z ( BPZ ) and tetramethyl bisphenol A ( 4MeBPA ) .
We used molecular @ @ @ @ @ @ @ assay , and cell cycle experiments on MCF-7 andERα overexpressing HEK293 cells to verify the impact of the compounds on ERα .
14 genes were found upregulated ( ADORA1 , DDIT4 , CELSR2 , FOSL2 , JUN , HSPA13 , IER3 , IGF1R , PGR , RUNX2 , SLC7A11 , SLC7A2 , SLC7A5 , STC2 ) and 3 genes were downregulated ( BCAS3 , PHF19 , PRKCD ) in almost all samples .
These genesare associated with cell growth , invasion , migration , apoptosis and cancer development .
We further confirmed the @ @ @ @ @ @ @ BPA , BPB , BPZ , and 4MeBPA on ERα .
We provide evidence for the endocrine potential of bisphenolic compounds and give insights into their molecular effects in MCF-7 cells .

Plasticizers released from microplastic are increasingly viewed with concern. While adverse health effects induced by bisphenol A and its analogues on marine animals are well documented in the literature, the endocrine potential of bisphenolic compounds on human health remains elusive. We applied next generation sequencing (NGS) with the estrogen receptorα (ERα) positive human breast cancer cell line MCF-7 treated with 17-β-estradiol (E2), bisphenol A (BPA), bisphenol B (BPB), bisphenol Z (BPZ) and tetramethyl bisphenol A (4MeBPA). We used molecular docking, microscale thermophoresis, ERα activation assay, and cell cycle experiments on MCF-7 andERα overexpressing HEK293 cells to verify the impact of the compounds on ERα. 14 genes were found upregulated (ADORA1, DDIT4, CELSR2, FOSL2, JUN, HSPA13, IER3, IGF1R, PGR, RUNX2, SLC7A11, SLC7A2, SLC7A5, STC2) and 3 genes were downregulated (BCAS3, PHF19, PRKCD) in almost all samples. These genesare associated with cell growth, invasion, migration, apoptosis and cancer development. We further confirmed the binding, activation and proliferative effect of BPA, BPB, BPZ, and 4MeBPA on ERα. We provide evidence for the endocrine potential of bisphenolic compounds and give insights into their molecular effects in MCF-7 cells.


greenmedinfo--2020-07-03--Oncogenic potential of bisphenol A and common environmental contaminants in human mammary epithelial

Oncogenic potential of bisphenol A and common environmental contaminants in human mammary epithelial cells.

There is an ample epidemiological evidence to support the role of environmental contaminants such as bisphenol A ( BPA ) in breast cancer development but the molecular mechanisms of their action are still not fully understood .
Therefore , we sought to analyze the effects of three common contaminants ( BPA ; 4-tert-octylphenol , OP ; hexabromocyclododecane , HBCD ) on mammary epithelial cell ( HME1 ) and MCF7 breast cancer cell line .
We also supplied some data on methoxychlor , MXC ; 4-nonylphenol , NP ; and 2-amino-1-methyl-6-phenylimidazo [ 4-b ] pyridine , PhIP .
We focused on @ @ @ @ @ @ @ exposure to low nano-molar concentrations ( 0.0015-0.0048 nM ) presumed to be oncogenic and found that they induced DNA damage ( evidenced by upregulation of pH2A.X , pCHK1 , pCHK2 , p-P53 ) and disrupted the cell cycle .
Some agents induced epigenetic ( methylation ) changes of tumor suppressor genes TIMP3 , CHFR , ESR1 , IGSF4 , CDH13 , and GSTP1 .
Obviously , the accumulation of these molecular alterations is an essential base for cancer development .
Consistent with this , we observed that these agents increased cellular invasiveness through @ @ @ @ @ @ @ in soft agar were increased for MCF7 .
Toxic agents induced phosphorylation of protein kinase such as EGFR , CREB , STAT6 , c-Jun , STAT3 , HSP6 , HSP27 , AMPKα1 , FAK , p53 , GSK-3α/β , and P70S6 in HME1 .
Most of these proteins are involved in potential oncogenic pathways .
Overall , these data clarify the molecular alterations that can be induced by some common environmental contaminants in mammary epithelial cells which could be a foundation to understandenvironmental carcinogenesis .

There is an ample epidemiological evidence to support the role of environmental contaminants such as bisphenol A (BPA) in breast cancer development but the molecular mechanisms of their action are still not fully understood. Therefore, we sought to analyze the effects of three common contaminants (BPA; 4-tert-octylphenol, OP; hexabromocyclododecane, HBCD) on mammary epithelial cell (HME1) and MCF7 breast cancer cell line. We also supplied some data on methoxychlor, MXC; 4-nonylphenol, NP; and 2-amino-1-methyl-6-phenylimidazo [4-b] pyridine, PhIP. We focused on testing the prolonged (two months) exposure to low nano-molar concentrations (0.0015-0.0048 nM) presumed to be oncogenic and found that they induced DNA damage (evidenced by upregulation of pH2A.X, pCHK1, pCHK2, p-P53) and disrupted the cell cycle. Some agents induced epigenetic (methylation) changes of tumor suppressor genes TIMP3, CHFR, ESR1, IGSF4, CDH13, and GSTP1. Obviously, the accumulation of these molecular alterations is an essential base for cancer development. Consistent with this, we observed that these agents increased cellular invasiveness through collagen. Cellular abilities to form colonies in soft agar were increased for MCF7. Toxic agents induced phosphorylation of protein kinase such as EGFR, CREB, STAT6, c-Jun, STAT3, HSP6, HSP27, AMPKα1, FAK, p53, GSK-3α/β, and P70S6 in HME1. Most of these proteins are involved in potential oncogenic pathways. Overall, these data clarify the molecular alterations that can be induced by some common environmental contaminants in mammary epithelial cells which could be a foundation to understandenvironmental carcinogenesis.


greenmedinfo--2020-07-03--Bisphenol A exposure induces gut microbiota dysbiosis and consequent activation of gut-liver axis le

Bisphenol A exposure induces gut microbiota dysbiosis and consequent activation of gut-liver axis leading to hepatic steatosis.

Interactions between the intestine and the liver , the so-called 'gut-liver axis ' , play a crucial role in the onset of hepatic steatosis and non-alcoholic fatty liver disease .
However , not much is known about the impact of environmental pollutants on the gut-liver axis and consequent hepatic steatosis .
Bisphenol A ( BPA ) , a widely used plasticiser , is an important environmental contaminant that affects gut microbiota .
We hypothesised that BPA induces hepatic steatosis by promoting gut microbiota dysbiosis and activating the gut-liver axis .
In this study , male CD-1 mice were fed with @ @ @ @ @ @ @ weight/day ) for 24 weeks .
Dietary exposure to BPA increased lipid contents and fat accumulation in the liver .
Analysis of 16 S rRNA gene sequencing revealed that the diversity of gut microbiota reduced and the composition of gut microbiota was altered in the BPA-fed mice .
Further , theabundance of Proteobacteria , a marker of dysbacteria , increased , whereas the abundance of Akkermansia , a gut microbe associated with increased gut barrier function and reduced inflammation , markedly decreased .
Expression levels of intestinal tight junction proteins ( zona occludens-1 @ @ @ @ @ @ @ leading to increased intestinal permeability and elevated levels of endotoxins .
Furthermore , BPA up-regulated the expression of Toll-like receptor 4 ( TLR4 ) and phosphorylation of nuclear factor-kappa B ( NF-κB ) in the liver and increased the production of inflammatory cytokines , including interleukin-1β , interleukin-18 , tumour necrosis factor-α , and interleukin-6 .
Take together , our work indicated that dietary intake of BPA induced hepatic steatosis , and this was closely related to dysbiosis of gut microbiota , elevated endotoxin levels , and increased liver inflammation through the TLR4/NF-κB @ @

Interactions between the intestine and the liver, the so-called 'gut-liver axis', play a crucial role in the onset of hepatic steatosis and non-alcoholic fatty liver disease. However, not much is known about the impact of environmental pollutants on the gut-liver axis and consequent hepatic steatosis. Bisphenol A (BPA), a widely used plasticiser, is an important environmental contaminant that affects gut microbiota. We hypothesised that BPA induces hepatic steatosis by promoting gut microbiota dysbiosis and activating the gut-liver axis. In this study, male CD-1 mice were fed with diet containing BPA (50 μg/kg body weight/day) for 24 weeks. Dietary exposure to BPA increased lipid contents and fat accumulation in the liver. Analysis of 16 S rRNA gene sequencing revealed that the diversity of gut microbiota reduced and the composition of gut microbiota was altered in the BPA-fed mice. Further, theabundance of Proteobacteria, a marker of dysbacteria, increased, whereas the abundance of Akkermansia, a gut microbe associated with increased gut barrier function and reduced inflammation, markedly decreased. Expression levels of intestinal tight junction proteins (zona occludens-1 and occludin) also decreased drastically, leading to increased intestinal permeability and elevated levels of endotoxins. Furthermore, BPA up-regulated the expression of Toll-like receptor 4 (TLR4) and phosphorylation of nuclear factor-kappa B (NF-κB) in the liver and increased the production of inflammatory cytokines, including interleukin-1β, interleukin-18, tumour necrosis factor-α, and interleukin-6. Take together, our work indicated that dietary intake of BPA induced hepatic steatosis, and this was closely related to dysbiosis of gut microbiota, elevated endotoxin levels, and increased liver inflammation through the TLR4/NF-κB pathway.


greenmedinfo--2020-07-03--Visceral obesity and cell cycle pathways serve as links in the association between bisphenol A expos

Visceral obesity and cell cycle pathways serve as links in the association between bisphenol A exposure and breast cancer.

It has been identified that bisphenol A ( BPA ) exposure causes developmental toxicity in breast cells .
However , the exact molecular mechanisms underlying the association between exposure to BPA and breast cancer remain unclear .
The aim of the present study was to investigate the BPA-regulated signaling pathways associated with the aggressiveness and the development of breast cancer .
Microarray technology and functional gene set analyses were used to evaluate BPA and breast cancer-associated biomarkers and pathways in a discovery-driven manner .
Using individual dataset analyses , it was indicated that two BPA-associated gene sets , the visceral @ @ @ @ @ @ @ deposits and the metabolic syndrome , and the cell cycle pathway , involved in cyclins and cell cycle regulation , were significantly associated with a high grade of aggressiveness and the development of estrogen receptor ( ER ) -positive breast cancer ( between P < 0.05 and 0.0001 ) .
The pooled analysis indicated that the most significant pathway was G/S checkpoint regulation , and the cyclin and cell cycle regulation pathway for BPA-associated ER-positive cancer .
Cancer cell signaling pathways were associated with healthy breast cells developing into breast cancer .
The @ @ @ @ @ @ @ were indicated to link BPA exposure to breast cancer .
The results of the present study demonstrate a significant association between breast cancer and BPA-regulated gene pathways .

It has been identified that bisphenol A (BPA) exposure causes developmental toxicity in breast cells. However, the exact molecular mechanisms underlying the association between exposure to BPA and breast cancer remain unclear. The aim of the present study was to investigate the BPA-regulated signaling pathways associated with the aggressiveness and the development of breast cancer. Microarray technology and functional gene set analyses were used to evaluate BPA and breast cancer-associated biomarkers and pathways in a discovery-driven manner. Using individual dataset analyses, it was indicated that two BPA-associated gene sets, the visceral obesity pathway, involved in visceral fat deposits and the metabolic syndrome, and the cell cycle pathway, involved in cyclins and cell cycle regulation, were significantly associated with a high grade of aggressiveness and the development of estrogen receptor (ER)-positive breast cancer (between P<0.05 and 0.0001). The pooled analysis indicated that the most significant pathway was G/S checkpoint regulation, and the cyclin and cell cycle regulation pathway for BPA-associated ER-positive cancer. Cancer cell signaling pathways were associated with healthy breast cells developing into breast cancer. The visceral obesity and the cell cycle pathways were indicated to link BPA exposure to breast cancer. The results of the present study demonstrate a significant association between breast cancer and BPA-regulated gene pathways.


greenmedinfo--2020-07-03--Neuroprotective role of luteolin against lead acetate-induced cortical damage.

Luteolin ( LUT ) is a glycosylated flavonoid compound that has multiple beneficial pharmacological and biological impacts .
The current investigation was undertaken to evaluate the putative neuroprotective potency of LUT against neuronal damage induced by lead acetate ( PbAc ) .
Twenty-eight rats were placed into four equal groups .
Group 1 : served as the control group , group 2 : rats were supplemented orally with LUT ( 50 mg kg ) , group 3 : rats were intraperitoneally injected with PbAc ( 20 mg kg ) , and group 4 : rats were pretreated with LUT before @ @ @ @ @ @ @ All animals were treated for 7 days .
The exposure to PbAc increased the concentration of lead in the cortical tissue , neuronal lipid peroxidation , and nitric oxide ( NO ) production and decreased the antioxidant enzymes .
Additionally , PbAc enhanced a neuroinflammatory response in the cortical tissue through increasing the pro-inflammatory cytokines secretion and inducible NO synthase expression .
Moreover , cortical cell death was recorded following PbAc intoxication as evidenced by the enhancement of the proapoptotic and inhibiting the antiapoptotic markers .
Interestingly , LUT supplementation reversed the cortical @ @ @ @ @ @ @ together , these findings may suggest that LUT may be useful for attenuating neuronal damage induced by PbAc through inhibiting the oxidative damage , neuroinflammation , and the cortical cell death .

Luteolin (LUT) is a glycosylated flavonoid compound that has multiple beneficial pharmacological and biological impacts. The current investigation was undertaken to evaluate the putative neuroprotective potency of LUT against neuronal damage induced by lead acetate (PbAc). Twenty-eight rats were placed into four equal groups. Group 1: served as the control group, group 2: rats were supplemented orally with LUT (50 mg kg), group 3: rats were intraperitoneally injected with PbAc (20 mg kg), and group 4: rats were pretreated with LUT before PbAc injection with the same doses. All animals were treated for 7 days. The exposure to PbAc increased the concentration of lead in the cortical tissue, neuronal lipid peroxidation, and nitric oxide (NO) production and decreased the antioxidant enzymes. Additionally, PbAc enhanced a neuroinflammatory response in the cortical tissue through increasing the pro-inflammatory cytokines secretion and inducible NO synthase expression. Moreover, cortical cell death was recorded following PbAc intoxication as evidenced by the enhancement of the proapoptotic and inhibiting the antiapoptotic markers. Interestingly, LUT supplementation reversed the cortical adverse reactions induced by PbAc. Taken together, these findings may suggest that LUT may be useful for attenuating neuronal damage induced by PbAc through inhibiting the oxidative damage, neuroinflammation, and the cortical cell death.


greenmedinfo--2020-07-03--Protective effects of luteolin on nephrotoxicity induced by long-term hyperglycaemia.

Objective : This study aimed to investigate whether luteolin delays the progress of diabetic nephropathy ( DN ) induced by streptozotocin .
Methods : Fifty-three healthy , 8-week-old , male Sprague–Dawley rats were randomly divided into the control ( n = 6 ) , model ( n = 23 ) , and experimental groups ( n = 24 ) .
The rat model of diabetic nephropathy was established by intraperitoneal injection of streptozotocin .
Rats in the experimental group were administered luteolin suspension of 80 mg/kg daily for 8 weeks .
Blood glucose levels and body weight were recorded until @ @ @ @ @ @ @ , blood flow and the protective effect of luteolin on diabetic nephropathy were evaluated .
Results : The degree of renal apoptosis and fibrosis in the experimental group was milder , and glomerular structure was more complete compared with the model group .
Nphs2 staining suggested that luteolin delayed apoptosis and deletion and fusion of podocytes under high glucose levels , and protected the filtration function of the basement membrane by upregulating Nphs2 protein expression .
Time intensity curve results suggested that luteolin delayed deterioration of renal haemodynamics under hyperglycaemia .
Conclusions : @ @ @ @ @ @ @ of diabetic nephropathy .
This drug has potential wide applicability in future clinical application .

Objective: This study aimed to investigate whether luteolin delays the progress of diabetic nephropathy (DN) induced by streptozotocin. Methods: Fifty-three healthy, 8-week-old, male Sprague–Dawley rats were randomly divided into the control (n = 6), model (n = 23), and experimental groups (n = 24). The rat model of diabetic nephropathy was established by intraperitoneal injection of streptozotocin. Rats in the experimental group were administered luteolin suspension of 80 mg/kg daily for 8 weeks. Blood glucose levels and body weight were recorded until the fourth week. After intragastric administration, blood flow and the protective effect of luteolin on diabetic nephropathy were evaluated. Results: The degree of renal apoptosis and fibrosis in the experimental group was milder, and glomerular structure was more complete compared with the model group. Nphs2 staining suggested that luteolin delayed apoptosis and deletion and fusion of podocytes under high glucose levels, and protected the filtration function of the basement membrane by upregulating Nphs2 protein expression. Time intensity curve results suggested that luteolin delayed deterioration of renal haemodynamics under hyperglycaemia. Conclusions: This study shows that luteolin delays progression of diabetic nephropathy. This drug has potential wide applicability in future clinical application.


greenmedinfo--2020-07-03--This data indicate that luteolin plays a role in controlling lung cancer cells' migration and invasi

This data indicate that luteolin plays a role in controlling lung cancer cells' migration and invasion.

BACKGROUND/OBJECTIVES : Non-small cell lung cancer is mostly recognized among other types of lung cancer with a poor prognosis by cause of chemotherapeutic resistance and increased metastasis .
Luteolin has been found to decrease cell metastasis .
However , its underlying mechanisms remain unresolved .
The objective of this study was to examine the effect ( and its mechanism ) of luteolin on the migration and invasion of human non-small cell lung cancer A549 cells .
MATERIALS/METHODS : Cell viability was investigated by 3- ( 4,5-dimethylthiazol-2-yl ) -2,5-diphenyltetrazolium bromide assay .
Wound healing and transwell assays were evaluated to assess @ @ @ @ @ @ @ blot analysis and immunofluorescence were further performed to investigate the role of luteolin and its mechanisms of action .
RESULTS : Administration with up to 40µM luteolin showed no cytotoxic activity on lung cancer A549 cells or non-cancer MRC-5 cells .
Additionally , luteolin at 20-40 µM significantly suppressed A549 cells ' migration , invasion , and the formation of filopodia in a concentration-dependent manner at 24 h. This is similar with western blot analysis , which revealed diminished the phosphorylated focal adhesion kinase ( pFAK ) , phosphorylated non-receptor tyrosine kinase ( @ @ @ @ @ @ @ substrate 1 ( Rac1 ) , cell division control protein 42 ( Cdc42 ) , and Ras homolog gene family member A ( RhoA ) expression levels .
CONCLUSIONS : Overall , our data indicate that luteolin plays a role in controlling lung cancer cells ' migration and invasion via Src/FAK and its downstream Rac1 , Cdc42 , and RhoA pathways .
Luteolin might be considered a promising candidate for suppressing invasion and metastasis of lung cancer cells .

BACKGROUND/OBJECTIVES: Non-small cell lung cancer is mostly recognized among other types of lung cancer with a poor prognosis by cause of chemotherapeutic resistance and increased metastasis. Luteolin has been found to decrease cell metastasis. However, its underlying mechanisms remain unresolved. The objective of this study was to examine the effect (and its mechanism) of luteolin on the migration and invasion of human non-small cell lung cancer A549 cells.
MATERIALS/METHODS: Cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Wound healing and transwell assays were evaluated to assess migration and invasion, respectively. Western blot analysis and immunofluorescence were further performed to investigate the role of luteolin and its mechanisms of action.
RESULTS: Administration with up to 40µM luteolin showed no cytotoxic activity on lung cancer A549 cells or non-cancer MRC-5 cells. Additionally, luteolin at 20-40 µM significantly suppressed A549 cells' migration, invasion, and the formation of filopodia in a concentration-dependent manner at 24 h. This is similar with western blot analysis, which revealed diminished the phosphorylated focal adhesion kinase (pFAK), phosphorylated non-receptor tyrosine kinase (pSrc), Ras-related C3 botulinum toxin substrate 1 (Rac1), cell division control protein 42 (Cdc42), and Ras homolog gene family member A (RhoA) expression levels.
CONCLUSIONS: Overall, our data indicate that luteolin plays a role in controlling lung cancer cells' migration and invasion via Src/FAK and its downstream Rac1, Cdc42, and RhoA pathways. Luteolin might be considered a promising candidate for suppressing invasion and metastasis of lung cancer cells.


greenmedinfo--2020-07-03--Antitumor activity of luteolin in human colon cancer SW620 cells.

The aim of this study was to investigate the mechanism of the anticancer activity of luteolin in metastatic human colon cancer SW620 cells .
Luteolin dose-dependently reduced the viability and proliferation of SW620 cells and increased the expression of antioxidant enzymes .
The expression of antiapoptotic protein Bcl-2 decreased whereas the expression of proapoptotic proteins Bax and caspase-3 increased by luteolin treatment , resulting in increased poly ( ADP-ribose ) polymerase ( PARP ) cleavage and terminal deoxynucleotidyl transferase dUTP nick end labeling ( TUNEL ) positivity .
Luteolin also increased the expression of autophagic proteins Beclin-1 , autophagy-related protein @ @ @ @ @ @ @ 1A/1B-light chain 3 beta-I/II ( LC3B-I/II ) , while the usage of 3-methyladenine suggested a prosurvival role of autophagy .
Moreover , treatment with luteolin induced reversal of the epithelial-mesenchymal transition process through the suppression of the wingless-related integration site protein ( Wnt ) /β-catenin pathway .
The cytotoxic activity of luteolin coincided with the activation of extracellular signal-regulated kinase 1/2 ( ERK1/2 ) and forkhead box O3a ( FOXO3a ) .
Treatment with the mitogen-activated protein kinase kinase ( MEK ) inhibitor PD0325901 inhibited ERK-dependent FOXO3a phosphorylation , resulting in increased FOXO3a @ @ @ @ @ @ @ of autophagy .
The results of the current study suggest the antitumor activity of luteolin in SW620 cells through the ERK/FOXO3a-dependent mechanism , as well as its antimetastatic potential .

The aim of this study was to investigate the mechanism of the anticancer activity of luteolin in metastatic human colon cancer SW620 cells. Luteolin dose-dependently reduced the viability and proliferation of SW620 cells and increased the expression of antioxidant enzymes. The expression of antiapoptotic protein Bcl-2 decreased whereas the expression of proapoptotic proteins Bax and caspase-3 increased by luteolin treatment, resulting in increased poly (ADP-ribose) polymerase (PARP) cleavage and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity. Luteolin also increased the expression of autophagic proteins Beclin-1, autophagy-related protein 5 (Atg5) and microtubule-associated protein 1A/1B-light chain 3 beta-I/II (LC3B-I/II), while the usage of 3-methyladenine suggested a prosurvival role of autophagy. Moreover, treatment with luteolin induced reversal of the epithelial-mesenchymal transition process through the suppression of the wingless-related integration site protein (Wnt)/β-catenin pathway. The cytotoxic activity of luteolin coincided with the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and forkhead box O3a (FOXO3a). Treatment with the mitogen-activated protein kinase kinase (MEK) inhibitor PD0325901 inhibited ERK-dependent FOXO3a phosphorylation, resulting in increased FOXO3a expression and apoptosis, with the suppression of autophagy. The results of the current study suggest the antitumor activity of luteolin in SW620 cells through the ERK/FOXO3a-dependent mechanism, as well as its antimetastatic potential.


greenmedinfo--2020-07-03--Low dose of luteolin activates Nrf2 in the liver of mice.

A flavone luteolin has various health-promoting activities .
Several studies reported that high dose of luteolin activates the Nrf2/ARE pathway in the liver .
However , the effect of the low dose of luteolin that can be taken from a dietary meal on the Nrf2 activation remain unclear .
It is expected that the flavonoid metabolism possesses a circadian rhythm , since nutritional metabolism processes daily cycle .
In this study we investigated whether an administration affects the Nrf2 activation .
ICR mice were orally administered 0.01-10 mg/kg body weight of luteolin once a day for 7 days at two @ @ @ @ @ @ @ phase ( ZT12 ) or at that of inactive phase ( ZT0 ) .
Luteolin increased the nuclear translocation of Nrf2 , resulting in the increases in its target gene products HO-1 and NQO1 at ZT12 but not at ZT0 .
The expression level of Nrf2 was lower at ZT12 than at ZT0 in the liver .
We also found that the level of luteolin aglycon in the plasma is higher at ZT12 than at ZT0 .
These results suggest that the low dose of luteolin can activate Nrf2 pathway and the aglycon @ @ @ @ @ @ @ activate the Nrf2 pathway at ZT12 in the liver .

A flavone luteolin has various health-promoting activities. Several studies reported that high dose of luteolin activates the Nrf2/ARE pathway in the liver. However, the effect of the low dose of luteolin that can be taken from a dietary meal on the Nrf2 activation remain unclear. It is expected that the flavonoid metabolism possesses a circadian rhythm, since nutritional metabolism processes daily cycle. In this study we investigated whether an administration affects the Nrf2 activation. ICR mice were orally administered 0.01-10 mg/kg body weight of luteolin once a day for 7 days at two time-points: at the start of active phase (ZT12) or at that of inactive phase (ZT0). Luteolin increased the nuclear translocation of Nrf2, resulting in the increases in its target gene products HO-1 and NQO1 at ZT12 but not at ZT0. The expression level of Nrf2 was lower at ZT12 than at ZT0 in the liver. We also found that the level of luteolin aglycon in the plasma is higher at ZT12 than at ZT0. These results suggest that the low dose of luteolin can activate Nrf2 pathway and the aglycon form of luteolin may mainly contribute to activate the Nrf2 pathway at ZT12 in the liver.


greenmedinfo--2020-07-03--Luteolin attenuates sepsis‑induced myocardial injury.

Sepsis‑induced cardiomyopathy ( SIC ) is a complication of severe sepsis and septic shock characterized by an invertible myocardial depression .
This study sought to explore the potential effects and mechanism of luteolin , a flavonoid polyphenolic compound , in lipopolysaccharide ( LPS ) ‑induced myocardialinjury .
Experimental mice were randomly allocated into 3 groups ( 25 mice in each group ) : The control group ( NC ) , the LPS group ( LPS ) and the LPS + luteolin group ( LPS + Lut ) .
Before the SIC model was induced , luteolin was dissolved in DMSO @ @ @ @ @ @ @ LPS + Lut group mice .
NC group and LPS group mice received an equal volume of DMSO for 10 days .
On day 11 , the animal model of sepsis‑induced cardiac dysfunction was induced by intraperitoneal injection of LPS .
A total of 12 h after LPS injection , measurements and comparisons were made among the groups .
Luteolin administration improved cardiac function , attenuated the inflammatory response , alleviated mitochondrial injury , decreased oxidative stress , inhibited cardiac apoptosis and enhanced autophagy .
In addition , luteolin significantly decreased the phosphorylation @ @ @ @ @ @ @ in septic heart tissue .
The protective effect of luteolin was abolished by 3‑methyladenine ( an autophagy inhibitor ) and dorsomorphin ( compound C , an AMPK inhibitor ) , as evidenced by decreased autophagic activity , destabilized mitochondrial membrane potential and increased apoptosis in LPS‑treated cardiomyocytes , but was mimicked by 5‑aminoimidazole‑4‑carboxamide ribonucleotide ( an AMPK activator ) , suggesting that luteolin attenuates LPS‑induced myocardial injury by increasing autophagy through AMPK activation .
Luteolin may be a promising therapeutic agent for treating SIC .

Sepsis‑induced cardiomyopathy (SIC) is a complication of severe sepsis and septic shock characterized by an invertible myocardial depression. This study sought to explore the potential effects and mechanism of luteolin, a flavonoid polyphenolic compound, in lipopolysaccharide (LPS)‑induced myocardialinjury. Experimental mice were randomly allocated into 3 groups (25 mice in each group): The control group (NC), the LPS group (LPS) and the LPS + luteolin group (LPS + Lut). Before the SIC model was induced, luteolin was dissolved in DMSO and injected intraperitoneally for 10 days into LPS + Lut group mice. NC group and LPS group mice received an equal volume of DMSO for 10 days. On day 11, the animal model of sepsis‑induced cardiac dysfunction was induced by intraperitoneal injection of LPS. A total of 12 h after LPS injection, measurements and comparisons were made among the groups. Luteolin administration improved cardiac function, attenuated the inflammatory response, alleviated mitochondrial injury, decreased oxidative stress, inhibited cardiac apoptosis and enhanced autophagy. In addition, luteolin significantly decreased the phosphorylation of AMP‑activated protein kinase (AMPK) in septic heart tissue. The protective effect of luteolin was abolished by 3‑methyladenine (an autophagy inhibitor) and dorsomorphin (compound C, an AMPK inhibitor), as evidenced by decreased autophagic activity, destabilized mitochondrial membrane potential and increased apoptosis in LPS‑treated cardiomyocytes, but was mimicked by 5‑aminoimidazole‑4‑carboxamide ribonucleotide (an AMPK activator), suggesting that luteolin attenuates LPS‑induced myocardial injury by increasing autophagy through AMPK activation. Luteolin may be a promising therapeutic agent for treating SIC.


greenmedinfo--2020-07-03--Luteolin can reduce the inflammatory response of acute gouty arthritis.

OBJECTIVES : To investigate the anti-inflammatory effect of luteolin on the acute gouty arthritis ( AGA ) rats and the underlying mechanisms .
METHODS : A total of sixty rats were chosen and randomly divided into 5 groups : A control group , a monosodium urate ( MSU ) group , a colchicine group , 2 luteolin groups ( 50 mg/kg , 150 mg/kg ) .
The AGA model of rats was established by injecting monosodium urate ( MSU ) at the concentration of 25 mg/mL into the ankle joint cavity .
Changes of joint swelling index at different time @ @ @ @ @ @ @ IL-1β ) , interleukin-6 ( IL-6 ) and tumor necrosis factor-α ( TNF-α ) in serum and synovial were measured .
The mRNA expression of TLR2 , TLR4 , and MyD88 in synovial tissue was detected by real-time PCR , and the protein expression of TLR2 , TLR4 , MyD88 , and NF-κB in synovial tissues was determined by Western blotting .
The inflammatory cells of the ankle joint and its surrounding soft tissues were observed after HE staining , and the expression of NF-κB was determined by immunohistochemistry .
RESULTS : Compared @ @ @ @ @ @ @ swelling indexes of the luteolin group and the colchicine group were significantly decreased ( < 0.05 ) , and the levels of IL-1β , IL-6 and TNF-α were also significantly decreased ( < 0.01 ) .
The mRNA levels of TLR2 , TLR4 , and MyD88 and the protein levels of TLR2 , TLR4 , MyD88 , and NF-κB were significantly decreased ( < 0.01 ) .
CONCLUSIONS : Luteolin can reduce the inflammatory response of acute gouty arthritis via down-regulating the TLR/MyD88/NF-κB pathway , and it is expected to be an effective @ @ @ @ @ @ @ arthritis .

OBJECTIVES: To investigate the anti-inflammatory effect of luteolin on the acute gouty arthritis (AGA) rats and the underlying mechanisms.
METHODS: A total of sixty rats were chosen and randomly divided into 5 groups:A control group, a monosodium urate (MSU) group, a colchicine group, 2 luteolin groups (50 mg/kg, 150 mg/kg). The AGA model of rats was established by injecting monosodium urate (MSU) at the concentration of 25 mg/mL into the ankle joint cavity. Changes of joint swelling index at different time points and the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum and synovial were measured. The mRNA expression of TLR2, TLR4, and MyD88 in synovial tissue was detected by real-time PCR, and the protein expression of TLR2, TLR4, MyD88, and NF-κB in synovial tissues was determined by Western blotting. The inflammatory cells of the ankle joint and its surrounding soft tissues were observed after HE staining, and the expression of NF-κB was determined by immunohistochemistry.
RESULTS: Compared with the MSU group, the joint swelling indexes of the luteolin group and the colchicine group were significantly decreased (<0.05), and the levels of IL-1β, IL-6 and TNF-α were also significantly decreased (<0.01). The mRNA levels of TLR2, TLR4, and MyD88 and the protein levels of TLR2, TLR4, MyD88, and NF-κB were significantly decreased (<0.01).
CONCLUSIONS: Luteolin can reduce the inflammatory response of acute gouty arthritis via down-regulating the TLR/MyD88/NF-κB pathway, and it is expected to be an effective drug for the treatment of acute gouty arthritis.


greenmedinfo--2020-07-03--Results from this study may provide the possible molecular mechanisms underlying cardiovascular prot

BACKGROUND AND AIMS : Luteolin is a common flavonoid that is abundantly present in various edible plants , it is known to exhibit beneficial effects on cardiovascular system .
However , the mechanisms which underlie the protective effects of luteolin on endothelial cell damage caused by oxidative stress remains unclear .
The purpose of this study is to test the hypothesis which states that luteolin protects against HO-induced oxidative stress via modulating ROS-mediated P38 MAPK/NF-κB and calcium-evoked mitochondrial apoptotic signalling pathways .
METHODS AND RESULTS : Human umbilical vein endothelial cells ( HUVECs ) were pretreated with luteolin prior to @ @ @ @ @ @ @ 24 h. The expression of native and phosphorylated-P38 , IκB , NF-κB , native eNOS , phosphorylated-eNOS , iNOS and several apoptosis-related proteins were analyzed by Western blot .
In addition , intracellular calcium was determined by fura-2 AM and mitochondrial membrane potential was examined by using JC1 .
Using the data gathered , we found indications that HOinduced P38 MAPK/NF-κB activation .
HOdownregulated the expression of eNOS and upregulated iNOS , which in turn contribute to an elevated NO generation and protein nitrosylation .
However , pretreatment with luteolin markedly reversed all @ @ @ @ @ @ @ an intracellular calcium rise and subsequent mitochondrial membrane potential collapse , P53 phosphorylation , reduced BcL-2/Bax ratio in the mitochondrial membrane , release cytochrome c from mitochondria , leading to the subsequent activation of caspase 3 activation by HOwere all markedly suppressed in the presence of luteolin .
CONCLUSION : Results from this study may provide the possible molecular mechanisms underlying cardiovascular protective effects of luteolin .

BACKGROUND AND AIMS: Luteolin is a common flavonoid that is abundantly present in various edible plants, it is known to exhibit beneficial effects on cardiovascular system. However, the mechanisms which underlie the protective effects of luteolin on endothelial cell damage caused by oxidative stress remains unclear. The purpose of this study is to test the hypothesis which states that luteolin protects against HO-induced oxidative stress via modulating ROS-mediated P38 MAPK/NF-κB and calcium-evoked mitochondrial apoptotic signalling pathways.
METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVECs) were pretreated with luteolin prior to being stimulated by 600 μM HOfor another 24 h. The expression of native and phosphorylated-P38, IκB, NF-κB, native eNOS, phosphorylated-eNOS, iNOS and several apoptosis-related proteins were analyzed by Western blot. In addition, intracellular calcium was determined by fura-2 AM and mitochondrial membrane potential was examined by using JC1. Using the data gathered, we found indications that HOinduced P38 MAPK/NF-κB activation. HOdownregulated the expression of eNOS and upregulated iNOS, which in turn contribute to an elevated NO generation and protein nitrosylation. However, pretreatment with luteolin markedly reversed all of these alterations dose-dependently. Additionally, an intracellular calcium rise and subsequent mitochondrial membrane potential collapse, P53 phosphorylation, reduced BcL-2/Bax ratio in the mitochondrial membrane, release cytochrome c from mitochondria, leading to the subsequent activation of caspase 3 activation by HOwere all markedly suppressed in the presence of luteolin.
CONCLUSION: Results from this study may provide the possible molecular mechanisms underlying cardiovascular protective effects of luteolin.


greenmedinfo--2020-07-03--Luteolin inhibits melanoma growth in vitro and in vivo.

Luteolin inhibited growth of several cancer cells in vitro in previous studies , with limited in vivo studies , and no comprehensive understanding of molecular mechanisms at genomics level .
This study identified luteolin as an effective agent to inhibit melanoma cell growth in vitro and in vivo .
Molecular studies and genomic profiling were used to identify the mechanism of action of luteolin in melanoma cells .
As a ROS ( reactive oxygen species ) scavenger , luteolin unexpectedly induced ROS ; but co-treatment with antioxidants NAC or mito-TEMPO did not rescue cell growth inhibition , although the levels @ @ @ @ @ @ @ , we profiled luteolin-induced differentially expressed genes ( DEGs ) in 4 melanoma cell lines using RNA-Seq , and performed pathway analysis using a combination of bioinformatics software including PharmetRx which was especially effective in discovering pharmacological pathways for potential drugs .
Our results show that luteolin induces changes in three main aspects : the cell-cell interacting pathway ( extracellular matrix , ECM ) , the oncogenic pathway and the immune response signaling pathway .
Based on these results , we further validated that luteolin was especially effective in inhibiting cell proliferation when @ @ @ @ @ @ @ concomitantly with down-regulation of fibronectin accumulation .
In conclusion , through extensive DEG profiling in a total of 4 melanoma cell lines , we found that luteolin-mediated growth inhibition in melanoma cells was perhaps not through ROS induction , but likely through simultaneously acting on multiple pathways including the ECM ( extracellular matrix ) pathway , the oncogenic signaling and the immune response pathways .
Further investigations on the mechanisms of this promising compound are warranted and likely result in application to cancer patients as its safety pharmacology has been validated in autism @ @

Luteolin inhibited growth of several cancer cells in vitro in previous studies, with limited in vivo studies, and no comprehensive understanding of molecular mechanisms at genomics level. This study identified luteolin as an effective agent to inhibit melanoma cell growth in vitro and in vivo. Molecular studies and genomic profiling were used to identify the mechanism of action of luteolin in melanoma cells. As a ROS (reactive oxygen species) scavenger, luteolin unexpectedly induced ROS; but co-treatment with antioxidants NAC or mito-TEMPO did not rescue cell growth inhibition, although the levels of ROS levels were reduced. Next, we profiled luteolin-induced differentially expressed genes (DEGs) in 4 melanoma cell lines using RNA-Seq, and performed pathway analysis using a combination of bioinformatics software including PharmetRx which was especially effective in discovering pharmacological pathways for potential drugs. Our results show that luteolin induces changes in three main aspects: the cell-cell interacting pathway (extracellular matrix, ECM), the oncogenic pathway and the immune response signaling pathway. Based on these results, we further validated that luteolin was especially effective in inhibiting cell proliferation when cells were seeded at low density, concomitantly with down-regulation of fibronectin accumulation. In conclusion, through extensive DEG profiling in a total of 4 melanoma cell lines, we found that luteolin-mediated growth inhibition in melanoma cells was perhaps not through ROS induction, but likely through simultaneously acting on multiple pathways including the ECM (extracellular matrix) pathway, the oncogenic signaling and the immune response pathways. Further investigations on the mechanisms of this promising compound are warranted and likely result in application to cancer patients as its safety pharmacology has been validated in autism patients.


greenmedinfo--2020-07-03--Luteolin alleviates ochratoxin A induced oxidative stress.

Ochratoxin A ( OTA ) is a ubiquitous food contaminant and a critical food safety concern due to its nephron toxic effects , which impacts all parts of the world .
Luteolin ( LUT ) had gained increasing interest as a health-promoting food antioxidant component .
However , the preventative effect of LUT against OTA induced oxidative stress was not yet clear and the elucidation of which would provide critical information to develop dietary LUT as a control strategy for OTA .
In the current study , the cytoprotective effect of LUT against OTA induced oxidative stress and the mechanism @ @ @ @ @ @ @ NRK-52E rat kidney cells .
The results showed that LUT exerted its preventative effect via restoring cell viability and preventing LDH release .
It alleviated the OTA-induced oxidative stress and lipid peroxidation by reducing ROS accumulation , ameliorating the mitochondrial membrane potential reduction and reversing the activities of antioxidant enzymes to the control levels .
The regulating roles of Nrf2 and HIF-1α in this process were evaluated by cell immunofluorescence assay , reporter plasmids transfection assay and qRT-PCR analysis .
The results showed that LUT activated Nrf2 pathway and increased the antioxidant defense @ @ @ @ @ @ @ , LUT also modulated HIF-1α pathway toinitiate the angiogenesis and epithelial restitution process .

Ochratoxin A (OTA) is a ubiquitous food contaminant and a critical food safety concern due to its nephron toxic effects, which impacts all parts of the world. Luteolin (LUT) had gained increasing interest as a health-promoting food antioxidant component. However, the preventative effect of LUT against OTA induced oxidative stress was not yet clear and the elucidation of which would provide critical information to develop dietary LUT as a control strategy for OTA. In the current study, the cytoprotective effect of LUT against OTA induced oxidative stress and the mechanism(s) behind was examined in NRK-52E rat kidney cells. The results showed that LUT exerted its preventative effect via restoring cell viability and preventing LDH release. It alleviated the OTA-induced oxidative stress and lipid peroxidation by reducing ROS accumulation, ameliorating the mitochondrial membrane potential reduction and reversing the activities of antioxidant enzymes to the control levels. The regulating roles of Nrf2 and HIF-1α in this process were evaluated by cell immunofluorescence assay, reporter plasmids transfection assay and qRT-PCR analysis. The results showed that LUT activated Nrf2 pathway and increased the antioxidant defense capacities of OTA treated cells. Additionally, LUT also modulated HIF-1α pathway toinitiate the angiogenesis and epithelial restitution process.


greenmedinfo--2020-07-03--Luteolin attenuates doxorubicin-induced cardiotoxicity.

Background : Luteolin ( LUT ) is a flavonoid found in vegetables and fruits that has diverse functions .
Doxorubicin ( DOX ) is an anthracycline antibiotic that is frequently used for the treatment of various cancers .
Unfortunately , the clinical efficacy of DOX is limited by its dose-related cardiotoxicity .
In this study , we aimed to investigate the potential mechanism through which LUT attenuates cardiotoxicity in vivo .
Methods : We evaluated the body weight , heart weight , electrocardiogram , and pathological changes before and after administration of LUT .
Moreover , the effects of LUT @ @ @ @ @ @ @ group , 100 mg/kg in the high dose group ) on biochemical parameters ( brain natriuretic peptide , creatine kinase MB , cardiac troponin T , and dehydrogenation of lactate enzyme ) and oxidative stress parameters ( malondialdehyde and superoxide dismutase ) were studied in the sera of cardiotoxicity model rats .
We also identified the apoptotic mediators whose expression was induced by LUT by quantitative real-time reverse transcription-polymerase chain reaction ( RT-qPCR ) evaluation .
In addition , we used network analysis to predict DOX-induced cardiotoxicity and protection afforded by LUT .
@ @ @ @ @ @ @ expression of associated proteins .
Results : LUT significantly improved DOX-induced cardiotoxicity in a dose-dependent fashion .
LUT ameliorated DOX-induced weight loss and heart weight changes , as well as changes in biochemical parameters and oxidative stress parameters in heart injury model rats .
LUT 's protective effect was observed via regulation of the apoptotic markers Bcl-2 , Bax , and caspase-3 mRNA and protein expression levels .
Network analysis showed that the AKT/Bcl-2 signalling pathway was activated ; specifically , the PH domain leucine-rich repeats protein phosphatase 1 ( phlpp1 ) was @ @ @ @ @ @ @ LUT inhibited the activity of phlpp1 leading to positive regulation of the AKT/Bcl-2 pathway , which attenuated doxorubicin-induced cardiotoxicity .
Conclusions : These results demonstrate that LUT exerted protective effects against DOX-induced cardiotoxicity in vivo by alleviating oxidative stress , suppressing phlpp1 activity , and activating the AKT/Bcl-2 signalling pathway .

Background: Luteolin (LUT) is a flavonoid found in vegetables and fruits that has diverse functions. Doxorubicin (DOX) is an anthracycline antibiotic that is frequently used for the treatment of various cancers. Unfortunately, the clinical efficacy of DOX is limited by its dose-related cardiotoxicity. In this study, we aimed to investigate the potential mechanism through which LUT attenuates cardiotoxicity in vivo.
Methods: We evaluated the body weight, heart weight, electrocardiogram, and pathological changes before and after administration of LUT. Moreover, the effects of LUT (50 mg/kg in the low dose group, 100 mg/kg in the high dose group) on biochemical parameters (brain natriuretic peptide, creatine kinase MB, cardiac troponin T, and dehydrogenation of lactate enzyme) and oxidative stress parameters (malondialdehyde and superoxide dismutase) were studied in the sera of cardiotoxicity model rats. We also identified the apoptotic mediators whose expression was induced by LUT by quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) evaluation. In addition, we used network analysis to predict DOX-induced cardiotoxicity and protection afforded by LUT. Western blotting was used to detect the expression of associated proteins.
Results: LUT significantly improved DOX-induced cardiotoxicity in a dose-dependent fashion. LUT ameliorated DOX-induced weight loss and heart weight changes, as well as changes in biochemical parameters and oxidative stress parameters in heart injury model rats. LUT's protective effect was observed via regulation of the apoptotic markers Bcl-2, Bax, and caspase-3 mRNA and protein expression levels. Network analysis showed that the AKT/Bcl-2 signalling pathway was activated; specifically, the PH domain leucine-rich repeats protein phosphatase 1 (phlpp1) was involved in the AKT/Bcl-2 signal pathway. LUT inhibited the activity of phlpp1 leading to positive regulation of the AKT/Bcl-2 pathway, which attenuated doxorubicin-induced cardiotoxicity.
Conclusions: These results demonstrate that LUT exerted protective effects against DOX-induced cardiotoxicity in vivo by alleviating oxidative stress, suppressing phlpp1 activity, and activating the AKT/Bcl-2 signalling pathway.


greenmedinfo--2020-07-03--Effect of bisphenols on telomerase expression and activity in breast cancer cell lines.

Bisphenol A ( BPA ) , a monomer of polycarbonates and resins , was shown to induce the expression of telomerase enzyme which has been associated with breast cancer development and progression .
However , the effects of BPA analogues , bisphenol F ( BPF ) and bisphenol S ( BPS ) on telomere-linked pathway have not been evaluated .
Herein , MCF-7 ( estrogen receptor ( ER ) -positive ) and MDA-MB-231 ( ER-negative ) cells were treated with BPA , BPF and BPS ± estrogen receptor inhibitor ( ERI ) , for 24 and/or 48 h. RNA expression @ @ @ @ @ @ @ using reverse transcription quantitative polymerase chain reaction ( RT-qPCR ) and telomeric repeat amplification protocol ( TRAP ) ; respectively .
Relative telomere length ( RTL ) was also measured using quantitative PCR .
After 24 h , the three bisphenols resulted in a 2-3 folds increase in expression and activity of telomerase in MCF-7 but not in MDA-MB-231 cells , and this increase was prevented upon co-treatment with ERI .
The observed increase in the expression and activity of telomerase after 24 h of treatment with bisphenols was associated with differential and @ @ @ @ @ @ @ h. Our results show that telomerase potentially mediates the effects of the three bisphenols in ER-positive breast carcinoma .
Hence , further investigation iswarranted to elucidate the telomerase-linked pathways that could underlie bisphenol-related effects .

Bisphenol A (BPA), a monomer of polycarbonates and resins, was shown to induce the expression of telomerase enzyme which has been associated with breast cancer development and progression. However, the effects of BPA analogues, bisphenol F (BPF) and bisphenol S (BPS) on telomere-linked pathway have not been evaluated. Herein, MCF-7 (estrogen receptor (ER)-positive) and MDA-MB-231 (ER-negative) cells were treated with BPA, BPF and BPS ± estrogen receptor inhibitor (ERI), for 24 and/or 48 h. RNA expression and enzymatic activity of telomerase were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and telomeric repeat amplification protocol (TRAP); respectively. Relative telomere length (RTL) was also measured using quantitative PCR. After 24 h, the three bisphenols resulted in a 2-3 folds increase in expression and activity of telomerase in MCF-7 but not in MDA-MB-231 cells, and this increase was prevented upon co-treatment with ERI. The observed increase in the expression and activity of telomerase after 24 h of treatment with bisphenols was associated with differential and modest ER-dependent lengthening in RTL at 48 h. Our results show that telomerase potentially mediates the effects of the three bisphenols in ER-positive breast carcinoma. Hence, further investigation iswarranted to elucidate the telomerase-linked pathways that could underlie bisphenol-related effects.


greenmedinfo--2020-07-04--Morusin suppresses A549 cell migration and induces cell apoptosis.

The present study aimed to examine the inhibitory effects of morusin on the human lung cancer cell line A549 .
@ @ @ @ @ applied to A549 cells and the effects were assessed by wound‑healing and MTT assays , @ @ @ @ @ , a mitochondrial membrane potential assay and RT‑PCR .
The results indicated that the concentrations @ @ @ @ @ morusin significantly inhibited A549 cells and signs of apoptosis were observed .
In addition , @ @ @ @ @ that morusin inhibited cell migration .
Flow cytometry analysis demonstrated that the rates of apoptosis @ @ @ @ @ 70.80 % following treatment with 1 , 10 and 30 µg/ml of morusin , respectively @ @ @ @ @ membrane potentials also decreased with theincrease of morusin .
Furthermore , morusin increased the antioxidant @ @ @ @ @ .
RT‑PCR analysis revealed that the expression levels of COX‑2 and VEGF were downregulated following @ @ @ @ @ , morusin significantly inhibited the proliferation of the lung cancer cell line A549 , and @ @ @ @ @ and migration of the cells by downregulating the expression of tumor angiogenesis‑related genes .

The present study aimed to examine the inhibitory effects of morusin on the human lung cancer cell line A549. Various doses of morusin were applied to A549 cells and the effects were assessed by wound‑healing and MTT assays, flow cytometry analysis of apoptosis, a mitochondrial membrane potential assay and RT‑PCR. The results indicated that the concentrations of 10 and 30 µg/ml morusin significantly inhibited A549 cells and signs of apoptosis were observed. In addition, the wound‑healing assay results revealed that morusin inhibited cell migration. Flow cytometry analysis demonstrated that the rates of apoptosis were 16.46, 55.80 and 70.80% following treatment with 1, 10 and 30 µg/ml of morusin, respectively, and that the mitochondrial membrane potentials also decreased with theincrease of morusin. Furthermore, morusin increased the antioxidant activities of the A549 cells. RT‑PCR analysis revealed that the expression levels of COX‑2 and VEGF were downregulated following morusin treatment. In conclusion, morusin significantly inhibited the proliferation of the lung cancer cell line A549, and may have affected the invasion and migration of the cells by downregulating the expression of tumor angiogenesis‑related genes.


greenmedinfo--2020-07-03--These results demonstrate that morusin induced apoptosis in human NSCLC cells.

This study was designed to validate the anticancer effects of morusin in human non-small cell lung cancer ( NSCLC ) cells .
Morusin suppressed the cell growth and colony formation in a concentration-dependent manner in H1299 , H460 and H292 cells .
These anticancer activities were related with apoptosis induction proved by the accumulation of chromatin condensation , PARP cleavage , increase of sub-G1 phage and annexin V-positive cell population .
Interestingly , signal transducer and activator of transcription 3 ( STAT3 ) was dephosphorylated by morusin .
Morusin suppressed the transcriptional activity of STAT3 and down-regulated the expression of @ @ @ @ @ @ @ morusin inhibited the phosphorylation of epithelial growth factor receptor ( EGFR ) , an upstream regulator of STAT3 .
The docking study showed that morusin directly binds to the tyrosine kinase domain of EGFR .
Furthermore , the anticancer effects of morusin were consistently observed in erlotinib-resistant H1975 cells expressing L858R and T790 M mutant EGFR , suggesting that morusin can be used for the advanced NSCLC with acquired resistance to EGFR TKI .
Taken together , our results demonstrate that morusin induced apoptosis in human NSCLC cells regardless of EGFR mutation status @ @ @ @ @ @

This study was designed to validate the anticancer effects of morusin in human non-small cell lung cancer (NSCLC) cells. Morusin suppressed the cell growth and colony formation in a concentration-dependent manner in H1299, H460 and H292 cells. These anticancer activities were related with apoptosis induction proved by the accumulation of chromatin condensation, PARP cleavage, increase of sub-G1 phage and annexin V-positive cell population. Interestingly, signal transducer and activator of transcription 3 (STAT3) was dephosphorylated by morusin. Morusin suppressed the transcriptional activity of STAT3 and down-regulated the expression of STAT3 target genes. In addition, morusin inhibited the phosphorylation of epithelial growth factor receptor (EGFR), an upstream regulator of STAT3. The docking study showed that morusin directly binds to the tyrosine kinase domain of EGFR. Furthermore, the anticancer effects of morusin were consistently observed in erlotinib-resistant H1975 cells expressing L858R and T790 M mutant EGFR, suggesting that morusin can be used for the advanced NSCLC with acquired resistance to EGFR TKI. Taken together, our results demonstrate that morusin induced apoptosis in human NSCLC cells regardless of EGFR mutation status through inhibition of EGFR/STAT3 activation.


greenmedinfo--2020-07-03--Extract from the dried root of Morus australis exhibited antiinflammatory and hepatic protective act

Extract from the dried root of Morus australis exhibited antiinflammatory and hepatic protective activity.

BACKGROUND/AIMS : Inflammation is one of the main contributors to chronic diseases such as cancer .
It is of great value to identify the potential activity of various medicinal plants for regulating or blocking uncontrolled chronic inflammation .
We investigated whether the root extract of Morus australis possesses antiinflammatory and antioxidative stress potential and hepatic protective activity .
METHODS : The microwave-assisted extractionwere was used to prepare the ethanol extract from the dried root of Morus australis ( MRE ) , including polyphenolic and flavonoid contents .
Lipopolysaccharide ( LPS ) -stimulated RAW264.7 cells was examined the anti-inflammatory and anti-oxidative @ @ @ @ @ @ @ damage were performed to detect the hepatic protective potential in vivo .
Immunohistochemistry ( IHC ) and western blot assays were used to detect target proteins .
RESULTS : MRE contained approximately 23 % phenolic compounds and 3 % flavonoids .
The major flavonoid component of MRE was morusin .
MRE and morusin inhibited lipopolysaccharide-induced production of nitrite and prostaglandin E2 in RAW264.7 cells .
MRE and morusin also suppressed the formation of intracellular reactive oxygen species and the expression of iNOS and COX-2 .
In an in vivo study , a thiobarbituric @ @ @ @ @ @ @ inhibited CCl4-induced oxidative stress and expression of nitrotyrosine .
MRE also decreased CCl4-induced hepatic iNOS and COX-2 expression , as well as CCl4-induced hepatic inflammation and necrosis in mice .

BACKGROUND/AIMS: Inflammation is one of the main contributors to chronic diseases such as cancer. It is of great value to identify the potential activity of various medicinal plants for regulating or blocking uncontrolled chronic inflammation. We investigated whether the root extract of Morus australis possesses antiinflammatory and antioxidative stress potential and hepatic protective activity.
METHODS: The microwave-assisted extractionwere was used to prepare the ethanol extract from the dried root of Morus australis (MRE), including polyphenolic and flavonoid contents. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells was examined the anti-inflammatory and anti-oxidative potential of MRE. CCl4-induced mouse hepatic damage were performed to detect the hepatic protective potential in vivo. Immunohistochemistry (IHC) and western blot assays were used to detect target proteins.
RESULTS: MRE contained approximately 23% phenolic compounds and 3% flavonoids. The major flavonoid component of MRE was morusin. MRE and morusin inhibited lipopolysaccharide-induced production of nitrite and prostaglandin E2 in RAW264.7 cells. MRE and morusin also suppressed the formation of intracellular reactive oxygen species and the expression of iNOS and COX-2. In an in vivo study, a thiobarbituric acid reactive substances assay showed that MRE inhibited CCl4-induced oxidative stress and expression of nitrotyrosine. MRE also decreased CCl4-induced hepatic iNOS and COX-2 expression, as well as CCl4-induced hepatic inflammation and necrosis in mice.
CONCLUSION: MRE exhibited antiinflammatory and hepatic protective activity.


greenmedinfo--2020-07-03--Fractionation and antioxidant activities of the water-soluble polysaccharides from Lonicera japonica

Fractionation and antioxidant activities of the water-soluble polysaccharides from Lonicera japonica.

L. japonica has been used as food and healthy beverage due to the good nutrition .
Although the chemical compounds have been extensively studied , polysaccharide compositions remain unclear .
In this study , water-soluble polysaccharides of L. japonica were fractionated into one neutral fraction ( LJP-N ) and four acidic fractions ( LJP-A-1 ~ LJP-A-4 ) by a combination of ion-exchange and gel permeation chromatographies .
The structures and antioxidant activities of these factions were determined by HPLC , FT-IR and the radical scavenging activities , anti-hemolysis inhibitory ability , protective effect against DNA damage .
Results showed that @ @ @ @ @ @ @ arabinogalactan ; acidic fractions were all pectic polysaccharide , with the average molecular weights approximately ranging from 19.0 to 383.8 kDa .
LJP-A-2 ~ LJP-A-4 were similar to each other , mainly composed of GalA ( > 50 % ) with some Gal and Ara residues , while LJP-A-1 mainly composed of Gal and Ara ( > 70 % ) .
LJP-A-3 was defined as HG-type pectic polysacchride , with a trace of RG-I domain by NMR experiment .
The antioxidant activity of LJP fractions showed different activities , and LJP-A-3 and LJP-A-4 @ @ @ @ @ @ @ of evaluated methods comparable with others .
The results indicated that LJP-A-3 and LJP-A-4 could be used as a potential natural source of antioxidant .

L. japonica has been used as food and healthy beverage due to the good nutrition. Although the chemical compounds have been extensively studied, polysaccharide compositions remain unclear. In this study, water-soluble polysaccharides of L. japonica were fractionated into one neutral fraction (LJP-N) and four acidic fractions (LJP-A-1 ~ LJP-A-4) by a combination of ion-exchange and gel permeation chromatographies. The structures and antioxidant activities of these factions were determined by HPLC, FT-IR and the radical scavenging activities, anti-hemolysis inhibitory ability, protective effect against DNA damage. Results showed that LJP-N was a starch-like glucan with some arabinogalactan; acidic fractions were all pectic polysaccharide, with the average molecular weights approximately ranging from 19.0 to 383.8 kDa. LJP-A-2 ~ LJP-A-4 were similar to each other, mainly composed of GalA (>50%) with some Gal and Ara residues, while LJP-A-1 mainly composed of Gal and Ara (>70%). LJP-A-3 was defined as HG-type pectic polysacchride, with a trace of RG-I domain by NMR experiment. The antioxidant activity of LJP fractions showed different activities, and LJP-A-3 and LJP-A-4 exhibited noticeable antioxidant activities by six kinds of evaluated methods comparable with others. The results indicated that LJP-A-3 and LJP-A-4 could be used as a potential natural source of antioxidant.


greenmedinfo--2020-07-03--Morus nigra and syringic acid presented antidepressant-like and neuroprotective effects against glut

Morus nigra and syringic acid presented antidepressant-like and neuroprotective effects against glutamatergic excitotoxicity via PI3K/Akt/GSK-3β.

Depression is a common neuropsychiatric disorder whose pathophysiology has been associated with glutamatergic excitotoxicity .
Thus , the research for new antidepressant strategies with the ability to mitigate glutamate toxicity has received growing attention .
Given this background , the present study sought to investigate the antidepressant-like and neuroprotective effects of Morus nigra ( MN ) and its major phenolic , syringic acid ( SA ) , against glutamate-induced damage , as well as , the role of the PI3K/Akt/GSK-3β signaling pathway in these effects .
Treatment with MN ( 3 mg/kg ) and SA ( 1 mg/kg ) for @ @ @ @ @ @ @ 10 mg/kg ) , triggered an antidepressant-like effect .
Moreover , the treatments evoked neuroprotection against glutamatergic excitotoxicity in hippocampal slices , and MN treatment also afforded protection in cerebrocortical slices .
Notably , ex vivo neuroprotective effect of MN and SA was mediated , at least in part , by PI3K/Akt/GSK-3β signaling pathway .
Furthermore , the ability of MN and SA to counteract the glutamate-induced damage were evaluated in three different in vitro experiments .
The hippocampal slices pretreated with MN ( 0.05 and 0.1 μg/mL ) or SA ( 0.01-0.1 @ @ @ @ @ @ @ treatment with MN ( 0.01 and 0.05 μg/mL ) or SA ( 0.05 and 0.1 μg/mL ) exhibited protection against glutamate toxicity .
Interestingly , post-treatment with MN in alldoses ( 0.01-0.1 μg/mL ) and SA at dose of 0.1 μg/mL were capable of preventing glutamate-induced cell death .
In vitro neuroprotective effect of SA , but not MN , involves the activation of Akt , since the pretreatment with LY294002 completely abolished the protective effect .
Overall , MN and SA presented antidepressant-like and neuroprotective effects against glutamatergic excitotoxicity via PI3K/Akt/GSK-3β .

Depression is a common neuropsychiatric disorder whose pathophysiology has been associated with glutamatergic excitotoxicity. Thus, the research for new antidepressant strategies with the ability to mitigate glutamate toxicity has received growing attention. Given this background, the present study sought to investigate the antidepressant-like and neuroprotective effects of Morus nigra (MN) and its major phenolic, syringic acid (SA), against glutamate-induced damage, as well as, the role of the PI3K/Akt/GSK-3β signaling pathway in these effects. Treatment with MN (3 mg/kg) and SA (1 mg/kg) for 7 days, similar to fluoxetine (10 mg/kg), triggered an antidepressant-like effect. Moreover, the treatments evoked neuroprotection against glutamatergic excitotoxicity in hippocampal slices, and MN treatment also afforded protection in cerebrocortical slices. Notably, ex vivo neuroprotective effect of MN and SA was mediated, at least in part, by PI3K/Akt/GSK-3β signaling pathway. Furthermore, the ability of MN and SA to counteract the glutamate-induced damage were evaluated in three different in vitro experiments. The hippocampal slices pretreated with MN (0.05 and 0.1 μg/mL) or SA (0.01-0.1 μg/mL) as well as the concomitant treatment with MN (0.01 and 0.05 μg/mL) or SA (0.05 and 0.1 μg/mL) exhibited protection against glutamate toxicity. Interestingly, post-treatment with MN in alldoses (0.01-0.1 μg/mL) and SA at dose of 0.1 μg/mL were capable of preventing glutamate-induced cell death. In vitro neuroprotective effect of SA, but not MN, involves the activation of Akt, since the pretreatment with LY294002 completely abolished the protective effect. Overall, MN and SA presented antidepressant-like and neuroprotective effects against glutamatergic excitotoxicity via PI3K/Akt/GSK-3β.


greenmedinfo--2020-07-03--A literature review of the effects of mulberry on the central nervous system.

BACKGROUND : Mulberry , including several species belonging to genus Morus , has been widely used as a traditional medicine for a long time .
Extracts and active components of mulberry have many positive neurological and biological effects and can become potential candidates in the search for new drugs for neurological disorders .
OBJECTIVES : We aimed to systematically review the medical literature for evidence of mulberry effects on the central nervous system .
METHODS : We conducted a systematic search in nine databases .
We included all in vivo studies investigating the effect of mulberry on the central nervous @ @ @ @ @ @ @ We finally included 47 articles for quality synthesis .
Our findings showed that mulberry and its components possessed an antioxidant effect , showed a reduction in the cerebral infarct volume after stroke .
They also improved the cognitive function , learning process , and reduced memory impairment in many animal models .
M. alba and its extracts ameliorated Parkinson 's disease-like behaviors , limited the complications of diabetes mellitus on the central nervous system , possessed anti-convulsant , anti-depressive , and anxiolytic effects .
CONCLUSION : Mulberry species proved beneficial to many neurological @ @ @ @ @ @ @ ingredients of each species , especially M. alba , should be deeper studied for screening potentially candidates for future treatments .

BACKGROUND: Mulberry, including several species belonging to genus Morus, has been widely used as a traditional medicine for a long time. Extracts and active components of mulberry have many positive neurological and biological effects and can become potential candidates in the search for new drugs for neurological disorders.
OBJECTIVES: We aimed to systematically review the medical literature for evidence of mulberry effects on the central nervous system.
METHODS: We conducted a systematic search in nine databases. We included all in vivo studies investigating the effect of mulberry on the central nervous system with no restrictions.
RESULTS: We finally included 47 articles for quality synthesis. Our findings showed that mulberry and its components possessed an antioxidant effect, showed a reduction in the cerebral infarct volume after stroke. They also improved the cognitive function, learning process, and reduced memory impairment in many animal models. M. alba and its extracts ameliorated Parkinson's disease-like behaviors, limited the complications of diabetes mellitus on the central nervous system, possessed anti-convulsant, anti-depressive, and anxiolytic effects.
CONCLUSION: Mulberry species proved beneficial to many neurological functions in animal models. The active ingredients of each species, especially M. alba, should be deeper studied for screening potentially candidates for future treatments.


greenmedinfo--2020-07-03--Morus alba stem extract demonstrates the potential to be used as an alternative treatment for reduci

Morus alba stem extract demonstrates the potential to be used as an alternative treatment for reducing inflammation and preventing cartilage degradation.

This study aimed to investigate the effects ofstem extract ( MSE ) and oxyresveratrol on the suppression of pro-inflammatory mediators in LPS-stimulated RAW 264.7 macrophages and IL-1β-stimulated C28/I2 human chondrocyte cell line .
The chondroprotective effect was also investigated using the chondrocyte cell line .
First , MSE was prepared and analyzed for the amount of oxyresveratrol .
The anti-inflammatory effects of MSE at various concentrations were evaluated through the inhibition of nitric oxide ( NO ) , prostaglandin ( PG ) -Eand cyclooxygenase ( COX ) -2 production .
Oxyresveratrol at the equivalent amount found in the extract was @ @ @ @ @ @ @ chondroprotective effect was investigated through the suppression of MMP-13 production .
The results showed that oxyresveratrol content in MSE was 15 % .
In RAW 264.7 cells , MSE ( 5-50 μg/mL ) could inhibit the NO ( 24-30 % ) and PGE ( 11-82 % ) production .
Oxyresveratrol at 0.75 and 7.5 μg/mL could suppress NO and also inhibited PGEbut at only at high concentration .
In the chondrocyte cell line , MSE at 5-100 μg/mL significantly decreased the PGEand COX-2 production by 44-93 % and 17-65 % , respectively .
@ @ @ @ @ @ @ significantly inhibit PGEproduction by 50-92 % but it inhibited COX-2 only at high concentration .
In addition , MSE and oxyresveratrol was shown to significantly inhibit MMP-13 production by 14-57 % and 16-56 % , depending on their concentrations .
The MSE demonstrates the potential to be used as an alternative treatment for reducing inflammation and preventing cartilage degradation .
Its component , oxyresveratrol , may exert these effects to some extent .

This study aimed to investigate the effects ofstem extract (MSE) and oxyresveratrol on the suppression of pro-inflammatory mediators in LPS-stimulated RAW 264.7 macrophages and IL-1β-stimulated C28/I2 human chondrocyte cell line. The chondroprotective effect was also investigated using the chondrocyte cell line. First, MSE was prepared and analyzed for the amount of oxyresveratrol. The anti-inflammatory effects of MSE at various concentrations were evaluated through the inhibition of nitric oxide (NO), prostaglandin (PG)-Eand cyclooxygenase (COX)-2 production. Oxyresveratrol at the equivalent amount found in the extract was investigated in the same manner. The chondroprotective effect was investigated through the suppression of MMP-13 production. The results showed that oxyresveratrol content in MSE was 15%. In RAW 264.7 cells, MSE (5-50 μg/mL) could inhibit the NO (24-30%) and PGE(11-82%) production. Oxyresveratrol at 0.75 and 7.5 μg/mL could suppress NO and also inhibited PGEbut at only at high concentration. In the chondrocyte cell line, MSE at 5-100 μg/mL significantly decreased the PGEand COX-2 production by 44-93% and 17-65%, respectively. Again, oxyresveratrol at both concentrations could significantly inhibit PGEproduction by 50-92% but it inhibited COX-2 only at high concentration. In addition, MSE and oxyresveratrol was shown to significantly inhibit MMP-13 production by 14-57% and 16-56%, depending on their concentrations. The MSE demonstrates the potential to be used as an alternative treatment for reducing inflammation and preventing cartilage degradation. Its component, oxyresveratrol, may exert these effects to some extent.


greenmedinfo--2020-07-03--Morusin alleviates mycoplasma pneumonia via the inhibition of Wnt/β-catenin and NF-κB signaling

Morusin has been traditionally used for the treatment ofpneumonia ( MPP ) , but the underlying mechanism remains elusive .
@ @ @ @ @ explore the mechanism by which morusin achieves efficacy on mycoplasma pneumonia .
Mycoplasma pneumonia model @ @ @ @ @ and the effects of morusin were evaluated in the model .
Compared with the model @ @ @ @ @ by 24.6± 3.14 % and 47.6 ± 6.78 % in low morusin ( 20 mg/kg @ @ @ @ @ 50 mg/kg ) groups , respectively ( < 0.05 ) .
Moreover , morusin treatment @ @ @ @ @ pro-inflammatory cytokines such as interleukin ( IL ) -6 , IL-1β , and tumor necrosis @ @ @ @ @ of anti-inflammatory IL-10 in mice lung tissue .
Furthermore , morusin treatment inhibited the activation @ @ @ @ @ in mice lung tissue .
Taken together , our results suggest that morusin relieves mycoplasma @ @ @ @ @ the activation of Wnt/β-catenin and NF-κB pathways , and is a potential natural agent for @ @ @ @ @ .

Morusin has been traditionally used for the treatment ofpneumonia (MPP), but the underlying mechanism remains elusive. The present study aimed to explore the mechanism by which morusin achieves efficacy on mycoplasma pneumonia. Mycoplasma pneumonia model was established in BALB/c mouse and the effects of morusin were evaluated in the model. Compared with the model group, DNA amount ofdecreased by 24.6± 3.14% and 47.6 ± 6.78% in low morusin (20 mg/kg) and high morusin (50 mg/kg) groups, respectively (<0.05). Moreover, morusin treatment led to decreased levels of pro-inflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor α and increased level of anti-inflammatory IL-10 in mice lung tissue. Furthermore, morusin treatment inhibited the activation of Wnt/β-catenin and NF-κB pathways in mice lung tissue. Taken together, our results suggest that morusin relieves mycoplasma pneumonia via the inhibition of the activation of Wnt/β-catenin and NF-κB pathways, and is a potential natural agent for the treatment of mycoplasma pneumonia.


greenmedinfo--2020-07-04--Penetration of cloth masks by influenza particles was almost 97% and medical masks 44%.

OBJECTIVE : The aim of this study was to compare the efficacy of cloth masks to medical masks in hospital healthcare workers ( HCWs ) .
The null hypothesis is that there is no difference between medical masks and cloth masks .
INTERVENTION : Hospital wards were randomised to : medical masks , cloth masks or a control group ( usual practice , which included mask wearing ) .
Participants used the mask on every shift for 4 consecutive weeks .
RESULTS : The rates of all infection outcomes were highest in the cloth mask arm , with the rate @ @ @ @ @ @ @ cloth mask arm ( relative risk ( RR ) =13.00 , 95 % CI 1.69 to 100.07 ) compared with the medical mask arm .
Cloth masks also had significantly higher rates of ILI compared with the control arm .
An analysis by mask use showed ILI ( RR=6.64 , 95 % CI 1.45 to 28.65 ) and laboratory-confirmed virus ( RR=1.72 , 95 % CI 1.01 to 2.94 ) were significantly higher in the cloth masks group compared with the medical masks group .
Penetration of cloth masks by particles was almost @ @ @ @ @ @ @ .
CONCLUSIONS : This study is the first RCT of cloth masks , and the results caution against the use of cloth masks .
This is an important finding to inform occupational health and safety .
Moisture retention , reuse of cloth masks and poor filtration may result in increased risk of infection .
Further research is needed to inform the widespread use of cloth masks globally .
However , as a precautionary measure , cloth masks should not be recommended for HCWs , particularly in high-risk situations , and guidelines need to @ @ @

OBJECTIVE: The aim of this study was to compare the efficacy of cloth masks to medical masks in hospital healthcare workers (HCWs). The null hypothesis is that there is no difference between medical masks and cloth masks.
SETTING: 14 secondary-level/tertiary-level hospitals in Hanoi, Vietnam.
PARTICIPANTS: 1607 hospital HCWs aged≥18 years working full-time in selected high-risk wards.
INTERVENTION: Hospital wards were randomised to: medical masks, cloth masks or a control group (usual practice, which included mask wearing). Participants used the mask on every shift for 4 consecutive weeks.
MAIN OUTCOME MEASURE: Clinical respiratory illness (CRI), influenza-like illness (ILI) and laboratory-confirmed respiratory virus infection.
RESULTS: The rates of all infection outcomes were highest in the cloth mask arm, with the rate of ILI statistically significantly higher in the cloth mask arm (relative risk (RR)=13.00, 95% CI 1.69 to 100.07) compared with the medical mask arm. Cloth masks also had significantly higher rates of ILI compared with the control arm. An analysis by mask use showed ILI (RR=6.64, 95% CI 1.45 to 28.65) and laboratory-confirmed virus (RR=1.72, 95% CI 1.01 to 2.94) were significantly higher in the cloth masks group compared with the medical masks group. Penetration of cloth masks by particles was almost 97% and medical masks 44%.
CONCLUSIONS: This study is the first RCT of cloth masks, and the results caution against the use of cloth masks. This is an important finding to inform occupational health and safety. Moisture retention, reuse of cloth masks and poor filtration may result in increased risk of infection. Further research is needed to inform the widespread use of cloth masks globally. However, as a precautionary measure, cloth masks should not be recommended for HCWs, particularly in high-risk situations, and guidelines need to be updated.
TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry: ACTRN12610000887077.


greenmedinfo--2020-07-04--Bisphenol A analogues present a greater obesogenic capacity in 3T3-L1 cell line.

This study was aimed at comparing the toxicity effects on cell viability and the obesogenic activity of Bisphenol A ( @ @ @ @ @ , Bisphenol S ( BPS ) and Bisphenol F ( BPF ) , by in @ @ @ @ @ 3T3-L1 cell line .
To compare the toxic potential and select the concentrations of each @ @ @ @ @ in cell viability , MTT assay was performed .
The cell phenotype was determined in @ @ @ @ @ oil O staining .
To determine the expression levels of the different adipogenic proteins the @ @ @ @ @ .
The results from MTT assay showed a greater toxic effect of BPA - at @ @ @ @ @ its analogues .
However , BPS followed by BPF showed a greater neutral lipid storage @ @ @ @ @ was reflected in the increase of the protein expression of CCAAT/enhancer binding proteinα ( C/EBPα @ @ @ @ @ gamma γ ( PPARγ ) and acid-binding protein 4 ( FABP4 ) .
In summary @ @ @ @ @ BPS- present a greater endocrine potential activity than BPA .

This study was aimed at comparing the toxicity effects on cell viability and the obesogenic activity of Bisphenol A (BPA) and its analogues, Bisphenol S (BPS) and Bisphenol F (BPF), by in vitro assays with a preadipocytic 3T3-L1 cell line. To compare the toxic potential and select the concentrations of each chemical not showing a decrease in cell viability, MTT assay was performed. The cell phenotype was determined in differentiated 3T3-L1 adipocytes by red oil O staining. To determine the expression levels of the different adipogenic proteins the Western Blot test was performed. The results from MTT assay showed a greater toxic effect of BPA - at equal and even lower concentrations-than its analogues. However, BPS followed by BPF showed a greater neutral lipid storage capacity than BPA, which was reflected in the increase of the protein expression of CCAAT/enhancer binding proteinα (C/EBPα), peroxisome proliferator-activated receptor gamma γ (PPARγ) and acid-binding protein 4 (FABP4). In summary, these BPA analogues -especially BPS- present a greater endocrine potential activity than BPA.


greenmedinfo--2020-07-04--Effectiveness of cannabidiol in a prospective cohort of children with drug-resistant epileptic encep

Effectiveness of cannabidiol in a prospective cohort of children with drug-resistant epileptic encephalopathy.

OBJECTIVE : We report our preliminary findings regarding effectiveness , safety , and tolerability of cannabidiol ( CBD ) added to antiepileptic therapy in a cohort of children with drug-resistant epileptic encephalopathies ( EEs ) with a mean follow-up of 8.5 months ( range , 3-12 months ) .
METHODS : A prospective cohort study was designed with the aim of assessing the effectiveness , safety , and tolerability of the addition of CBD to standard antiseizure medications ( ASMs ) in children with drug-resistant EE enrolled at a single center ( Neurology Department , Hospital de Pediatría '' Juan @ @ @ @ @ @ @ Argentina ) .
RESULTS : Fifty patients were enrolled between October 2018 and October 2019 , 49 of whom had a follow-up of at least 3 months at the time this interim analysis was performed .
Mean age at enrollment was 10.5 years ( range 2-16 ) .
Median age at first seizure was 7 months .
Up to the last visit of each patient ( follow-up 3-12 months ) 39/49 children ( 80 % ) had responded to treatment with a decrease in seizure frequency .
Overall , 77.6 % of the @ @ @ @ @ @ @ least 25 % , 73.5 % had a≥ 50 % reduction , and 49 % had a ≥ 75 % reduction .
Mean monthly seizure frequency was reduced from 959 to 381 ( median decrease from 299 to 102 , range , 38-1900 ; median decrease 66 % , p < 0.001 ) .
All adverse effects were mild or moderate .
The most common adverse effect was drowsiness ( in 32 % ) , usually reversed by adjusting clobazam dose ( in 12 children ) .
CONCLUSION : In children with drug-resistant @ @ @ @ @ @ @ therapy to antiepileptic therapy seems safe , well tolerated , and effective .

OBJECTIVE: We report our preliminary findings regarding effectiveness, safety, and tolerability of cannabidiol (CBD) added to antiepileptic therapy in a cohort of children with drug-resistant epileptic encephalopathies (EEs) with a mean follow-up of 8.5 months (range, 3-12 months).
METHODS: A prospective cohort study was designed with the aim of assessing the effectiveness, safety, and tolerability of the addition of CBD to standard antiseizure medications (ASMs) in children with drug-resistant EE enrolled at a single center (Neurology Department, Hospital de Pediatría"Juan P. Garrahan", Buenos Aires, Argentina).
RESULTS: Fifty patients were enrolled between October 2018 and October 2019, 49 of whom had a follow-up of at least 3 months at the time this interim analysis was performed. Mean age at enrollment was 10.5 years (range 2-16). Median age at first seizure was 7 months. Up to the last visit of each patient (follow-up 3-12 months) 39/49 children (80 %) had responded to treatment with a decrease in seizure frequency. Overall, 77.6 % of the patients had a seizure reduction of at least 25 %, 73.5 % had a≥ 50 % reduction, and 49 % had a ≥ 75 % reduction. Mean monthly seizure frequency was reduced from 959 to 381 (median decrease from 299 to 102, range, 38-1900; median decrease 66 %, p<0.001). All adverse effects were mild or moderate. The most common adverse effect was drowsiness (in 32 %), usually reversed by adjusting clobazam dose (in 12 children).
CONCLUSION: In children with drug-resistant EEs, CBD oil as an adjuvant therapy to antiepileptic therapy seems safe, well tolerated, and effective.


greenmedinfo--2020-07-04--The potential of cannabidiol in the COVID‐19 pandemic: a hypothesis letter

Identifying candidate drugs effective in the new coronavirus disease 2019 ( Covid-19 ) is crucial , pending a vaccine against @ @ @ @ @ hypothesis that Cannabidiol ( CBD ) , a non-psychotropic phytocannabinoid , has the potential to @ @ @ @ @ of the disease for several reasons : 1 ) High-CBD Cannabis Sativa extracts are able @ @ @ @ @ the two key receptors for SARS-CoV2 in several models of human epithelia 2 ) CBD @ @ @ @ @ immunomodulatory and anti-inflammatory effects and it can mitigate the uncontrolled cytokine production featuring Acute Lung @ @ @ @ @ PPARγ agonist , it can display a direct antiviral activity 4 ) PPARγ agonists are @ @ @ @ @ can inhibit the development of pulmonary fibrosis , thus ameliorating lung function in recovered patients @ @ @ @ @ , corroborated by several preclinical evidence , will inspire further targeted studies to test CBD @ @ @ @ @ the COVID-19 pandemic .

Identifying candidate drugs effective in the new coronavirus disease 2019 (Covid-19) is crucial, pending a vaccine against SARS-CoV2. We suggest the hypothesis that Cannabidiol (CBD), a non-psychotropic phytocannabinoid, has the potential to limit the severity and progression of the disease for several reasons: 1) High-CBD Cannabis Sativa extracts are able to downregulate the expression of the two key receptors for SARS-CoV2 in several models of human epithelia 2) CBD exerts a wide range of immunomodulatory and anti-inflammatory effects and it can mitigate the uncontrolled cytokine production featuring Acute Lung Injury 3) Being a PPARγ agonist, it can display a direct antiviral activity 4) PPARγ agonists are regulators of fibroblast/myofibroblast activation and can inhibit the development of pulmonary fibrosis, thus ameliorating lung function in recovered patients. We hope our hypothesis, corroborated by several preclinical evidence, will inspire further targeted studies to test CBD as a support drug against the COVID-19 pandemic.


greenmedinfo--2020-07-04--Current application of cannabidiol in the management and treatment of neurological disorders.

Cannabidiol ( CBD ) , which is nonintoxicating pharmacologically relevant constituents of Cannabis , demonstrates several beneficial effects .
It @ @ @ @ @ antioxidative , anti-inflammatory , and neuroprotective effects .
As the medicinal use of CBD is @ @ @ @ @ various disorders , the recent flare-up of largely unproven and unregulated cannabis-based preparations on medical @ @ @ @ @ impact in the field of neurology .
Currently , as lot of clinical trials are @ @ @ @ @ potential to become a supplemental therapy in various neurological conditions .
It has shown promise @ @ @ @ @ disorders such as anxiety , chronic pain , trigeminal neuralgia , epilepsy , and essential @ @ @ @ @ disorders .
While recent FDA-approved prescription drugs have demonstrated safety , efficacy , and consistency @ @ @ @ @ spasticity in multiple sclerosis ( MS ) and in Dravet and Lennox-Gastaut Syndromes ( LGS @ @ @ @ @ still remain .
In the current review , the authors have shed light on the @ @ @ @ @ management and treatment of various neurological disorders .

Cannabidiol (CBD), which is nonintoxicating pharmacologically relevant constituents of Cannabis, demonstrates several beneficial effects. It has been found to have antioxidative, anti-inflammatory, and neuroprotective effects. As the medicinal use of CBD is gaining popularity for treatment of various disorders, the recent flare-up of largely unproven and unregulated cannabis-based preparations on medical therapeutics may have its greatest impact in the field of neurology. Currently, as lot of clinical trials are underway, CBD demonstrates remarkable potential to become a supplemental therapy in various neurological conditions. It has shown promise in the treatment of neurological disorders such as anxiety, chronic pain, trigeminal neuralgia, epilepsy, and essential tremors as well as psychiatric disorders. While recent FDA-approved prescription drugs have demonstrated safety, efficacy, and consistency enough for regulatory approval in spasticity in multiple sclerosis (MS) and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges still remain. In the current review, the authors have shed light on the application of CBD in the management and treatment of various neurological disorders.


greenmedinfo--2020-07-04--Cannabidiol anticonvulsant effect is mediated by the PI3Kγ pathway.

The phosphatidylinositol 3-kinase ( PI3K ) /protein kinase B ( PKB/Akt ) /mechanistic target of rapamycin ( mTOR ) signaling pathway has been associated with several pathologies in the central nervous system ( CNS ) , including epilepsy .
There is evidence supporting the hypothesis that the PI3Kγ signaling pathway may mediate the powerful anticonvulsant properties associated with the cannabinoidergic system .
This work aims to investigate if the anticonvulsant and neuroprotective effects of cannabidiol ( CBD ) are mediated by PI3Kγ .
In vitro and in vivo experiments were performed on C57Bl/6wild-type ( WT ) and PI3Kγmice .
Behavioral @ @ @ @ @ @ @ microinjection .
Twenty-four hours after the first behavioral seizure , animals were perfused and their brains removed and processed , for histological analysis of neurodegeneration , microgliosis and astrocytosis .
Primary cultures of hippocampal neurons were used for glutamate-induced cell death assay .
CDB increased latency and reduced the severity of pilocarpine-induced behavioral seizures , as well as prevented postictal changes , such as neurodegeneration , microgliosis and astrocytosis , in WT animals , but not in PI3Kγ .
CBD in vivo effects were abolished by pharmacological inhibition of cannabinoid receptor or mTOR @ @ @ @ @ @ @ deficiency also changed CBD protection observed in glutamate-induced cell death assay .
Thus , we suggest that the modulation of PI3K/mTOR signaling pathway is involved in the anticonvulsant and neuroprotective effects of CBD .
These findings are important not only for the elucidationof the mechanisms of action of CBD , which are currently poorly understood , but also to allow the prediction of therapeutic and side effects , ensuring efficacy and safety in the treatment of patients with epilepsy .

The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt)/mechanistic target of rapamycin (mTOR) signaling pathway has been associated with several pathologies in the central nervous system (CNS), including epilepsy. There is evidence supporting the hypothesis that the PI3Kγ signaling pathway may mediate the powerful anticonvulsant properties associated with the cannabinoidergic system. This work aims to investigate if the anticonvulsant and neuroprotective effects of cannabidiol (CBD) are mediated by PI3Kγ. In vitro and in vivo experiments were performed on C57Bl/6wild-type (WT) and PI3Kγmice. Behavioral seizures were induced by bilateral intra-hippocampal pilocarpine microinjection. Twenty-four hours after the first behavioral seizure, animals were perfused and their brains removed and processed, for histological analysis of neurodegeneration, microgliosis and astrocytosis. Primary cultures of hippocampal neurons were used for glutamate-induced cell death assay. CDB increased latency and reduced the severity of pilocarpine-induced behavioral seizures, as well as prevented postictal changes, such as neurodegeneration, microgliosis and astrocytosis, in WT animals, but not in PI3Kγ. CBD in vivo effects were abolished by pharmacological inhibition of cannabinoid receptor or mTOR. In vitro, PI3Kγ inhibition or deficiency also changed CBD protection observed in glutamate-induced cell death assay. Thus, we suggest that the modulation of PI3K/mTOR signaling pathway is involved in the anticonvulsant and neuroprotective effects of CBD. These findings are important not only for the elucidationof the mechanisms of action of CBD, which are currently poorly understood, but also to allow the prediction of therapeutic and side effects, ensuring efficacy and safety in the treatment of patients with epilepsy.