greenmedinfo--2020-11-28--Morin hydrate sensitizes hepatoma cells and xenograft tumor towards cisplatin.

The cross-talk between apoptosis and autophagy influences anticancer drug sensitivity and cellular death in various cancer cell lines .
However , the fundamental mechanisms behind this phenomenon are still unidentified .
We demonstrated anti-cancerous role of cisplatin ( CP ) and morin hydrate ( Mh ) as an individual and/or in combination ( CP-Mh ) in hepatoma cells and tumor model .
Exposure of CP resulted in the production of intracellular reactive oxygen species ( ROS ) -mediated cellular vacuolization , expansion of mitochondria membrane and activation of endoplasmic reticulum ( ER ) -stress .
Consequently , Cyttranslocation led to @ @ @ @ @ @ @ simultaneously triggered caspase-mediated cellular apoptosis .
In addition , CP-induced PARP-1 activation led to ADP-ribosylation of HMGB1 , which consequently developed autophagy as evident by the LC3I/II ratio .
Chemically-induced inhibition of autophagy marked by increased cell death signified a protective role of autophagy against CP treatment .
CP-Mh abrogates the PARP-1 expression and significantly reduced HMGB1-cytoplasmic translocation with subsequent inhibition of the HMGB1-Beclin1 complex formation .
In the absence of PARP-1 , a reduced HMGB1 mediated autophagy was observed followed by induced caspase-dependent apoptosis .
To confirm the role of PARP-1-HMGB1 signaling @ @ @ @ @ @ @ inhibitor , 4-amino-1,8-naphthalimide ( ANI ) , HMGB1 inhibitor , ethyl pyruvate ( EP ) , autophagy inhibitors , 3-methyl adenine ( 3-MA ) and bafilomycin ( baf ) and small interfering RNAs ( siRNA ) to target Atg5 in combination of CP and Mh .
Exposure to these inhibitors enhanced the sensitivity of HepG2 cells to CP .
Collectively , our findings indicate that CP-Mh in combination served as a prominent regulator of autophagy and significant inducer of apoptosis that maintains a homeostatic balance towards HepG2 cells and the subcutaneous tumor model @

The cross-talk between apoptosis and autophagy influences anticancer drug sensitivity and cellular death in various cancer cell lines. However, the fundamental mechanisms behind this phenomenon are still unidentified. We demonstrated anti-cancerous role of cisplatin (CP) and morin hydrate (Mh) as an individual and/or in combination (CP-Mh) in hepatoma cells and tumor model. Exposure of CP resulted in the production of intracellular reactive oxygen species (ROS)-mediated cellular vacuolization, expansion of mitochondria membrane and activation of endoplasmic reticulum (ER)-stress. Consequently, Cyttranslocation led to the increase of Bax/Bcl-2 ratio, which simultaneously triggered caspase-mediated cellular apoptosis. In addition, CP-induced PARP-1 activation led to ADP-ribosylation of HMGB1, which consequently developed autophagy as evident by the LC3I/II ratio. Chemically-induced inhibition of autophagy marked by increased cell death signified a protective role of autophagy against CP treatment. CP-Mh abrogates the PARP-1 expression and significantly reduced HMGB1-cytoplasmic translocation with subsequent inhibition of the HMGB1-Beclin1 complex formation. In the absence of PARP-1, a reduced HMGB1 mediated autophagy was observed followed by induced caspase-dependent apoptosis. To confirm the role of PARP-1-HMGB1 signaling in autophagy, we used the PARP-1 inhibitor, 4-amino-1,8-naphthalimide (ANI), HMGB1 inhibitor, ethyl pyruvate (EP), autophagy inhibitors, 3-methyl adenine (3-MA) and bafilomycin (baf) and small interfering RNAs (siRNA) to target Atg5 in combination of CP and Mh. Exposure to these inhibitors enhanced the sensitivity of HepG2 cells to CP. Collectively, our findings indicate that CP-Mh in combination served as a prominent regulator of autophagy and significant inducer of apoptosis that maintains a homeostatic balance towards HepG2 cells and the subcutaneous tumor model.


greenmedinfo--2020-11-28--Inhibitory effect of morin against Candida albicans pathogenicity and virulence.

is considered an exclusive etiologic agent of candidiasis , a very common fungal infection in human .
The expression of virulence factors contributes highly to the pathogenicity of .
These factors include biofilm formation , yeast-to-hyphal transition , adhesins , aspartyl proteases , and phospholipases secretion .
Moreover , resistance development is a critical issue for the therapeutic failure of antifungal agents against systemic candidiasis .
To circumvent resistance development , the present study investigated the virulence targeted therapeutic activity of the phyto-bioactive compound morin against .
Morin is a natural compound commonly found in medicinal plants and widely used @ @ @ @ @ @ @ The present study explicated the significant inhibitory potential of morin against biofilm formation and other virulence factors ' production , such as yeast-hyphal formation , phospholipase , and exopolymeric substances , in .
Further , qPCR analysis confirmed the downregulation of biofilm and virlence-related genes inupon morin treatment , which is in correspondence with thebioassays .
Further , the docking analysis revealed that morin shows strong affinity with Hwp-1 protein , which regulates the expression of biofilm and hyphal formation inand , thereby , abolishes fungal pathogenicity .
Moreover , the anti-infective potential @ @ @ @ @ @ @ through anapproach using biomedical model organism zebrafish ( ) .
The outcomes of thestudy demonstrate that the morin treatment effectively rescues animals frominfections and extends their survival rate by inhibiting the internal colonization of .
Histopathology analysis revealed extensive candidiasis-related pathognomonic changes in the gills , intestine , and kidney of animals infected with , while no extensive abnormalities were observed in morin-treated animals .
The results evidenced that morin has the ability to protect against the pathognomonic effect and histopathological lesions caused byinfection in zebrafish .
Thus , the present study suggests @ @ @ @ @ @ @ as a potent therapeutic medication forinstigated candidiasis .

is considered an exclusive etiologic agent of candidiasis, a very common fungal infection in human. The expression of virulence factors contributes highly to the pathogenicity of. These factors include biofilm formation, yeast-to-hyphal transition, adhesins, aspartyl proteases, and phospholipases secretion. Moreover, resistance development is a critical issue for the therapeutic failure of antifungal agents against systemic candidiasis. To circumvent resistance development, the present study investigated the virulence targeted therapeutic activity of the phyto-bioactive compound morin against. Morin is a natural compound commonly found in medicinal plants and widely used in the pharmaceutical and cosmetic products/industries. The present study explicated the significant inhibitory potential of morin against biofilm formation and other virulence factors' production, such as yeast-hyphal formation, phospholipase, and exopolymeric substances, in. Further, qPCR analysis confirmed the downregulation of biofilm and virlence-related genes inupon morin treatment, which is in correspondence with thebioassays. Further, the docking analysis revealed that morin shows strong affinity with Hwp-1 protein, which regulates the expression of biofilm and hyphal formation inand, thereby, abolishes fungal pathogenicity. Moreover, the anti-infective potential of morin against-associated systemic candidiasis is confirmed through anapproach using biomedical model organism zebrafish (). The outcomes of thestudy demonstrate that the morin treatment effectively rescues animals frominfections and extends their survival rate by inhibiting the internal colonization of. Histopathology analysis revealed extensive candidiasis-related pathognomonic changes in the gills, intestine, and kidney of animals infected with, while no extensive abnormalities were observed in morin-treated animals. The results evidenced that morin has the ability to protect against the pathognomonic effect and histopathological lesions caused byinfection in zebrafish. Thus, the present study suggests that the utilization of morin could act as a potent therapeutic medication forinstigated candidiasis.


greenmedinfo--2020-11-28--Morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

Influenza virus is the major cause of seasonal and pandemic flu .
Currently , oseltamivir , a potent and selective inhibitor of neuraminidase of influenza A and B viruses , is the drug of choice for treating patients with influenza virus infection .
However , recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy .
Morin hydrate ( 3,5,7,2',4'-pentahydroxyflavone ) is a flavonoid isolated fromL .
It has antioxidant , anti-inflammatory , neuroprotective , and anticancer effects partly by the inhibition of the NF-кB signaling pathway .
However , its effects on influenza virus have not been studied .
@ @ @ @ @ @ @ hydrate against influenza A/Puerto Rico/8/1934 ( A/PR/8 ; H1N1 ) and oseltamivir-resistant A/PR/8 influenza viruses .
To determine its mode of action , we carried out time course experiments , and time of addition , hemolysis inhibition , and hemagglutination assays .
The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection .
We found that morin hydrate reduced hemagglutination by A/PR/8 .
It alleviated the symptoms of A/PR/8-infection , and reduced the levels of pro-inflammatory cytokines and chemokines , such as TNF-α and @ @ @ @ @ @ @ of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation .
Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus .

Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid isolated fromL. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-кB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8. It alleviated the symptoms of A/PR/8-infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.


greenmedinfo--2020-11-28--Antioxidant role of morusin and mulberrofuran B in ethanol extract of Morus alba roots.

The white mulberry , , is distributed worldwide and known for its antioxidant properties .
Ethanol extract of six varieties @ @ @ @ @ 13/6 , IZ 40 , IZ 56/4 , IZ 64 , Indonesia and Tigreada ) @ @ @ @ @ , two secondary metabolites were isolated and unambiguously identified by 2 D NMR experiments as @ @ @ @ @ These were quantified in the varieties by liquid chromatography , recording 5.27-16.74 % for the @ @ @ @ @ for the latter .
Mulberrofuran B presented higher activity than morusin by phosphomolybdenum ( 1531.33 @ @ @ @ @ and ferrocyanide ( 14.39 % ) methods , ABTS ( 95.74 ± 4.21 µM ) @ @ @ @ @ 10.65 µM ) radical sequestration capacity , while morusin showed significant statistical correlation with antioxidant @ @ @ @ @ results suggested that morusin influences antioxidant activity ofin synergism with other compounds and can be @ @ @ @ @ this species .

The white mulberry,, is distributed worldwide and known for its antioxidant properties. Ethanol extract of six varieties ofroots were studied (IZ 13/6, IZ 40, IZ 56/4, IZ 64, Indonesia and Tigreada). From variety IZ 40, two secondary metabolites were isolated and unambiguously identified by 2 D NMR experiments as morusin and mulberrofuran B. These were quantified in the varieties by liquid chromatography, recording 5.27-16.74% for the first, and 0.54-3.55% for the latter. Mulberrofuran B presented higher activity than morusin by phosphomolybdenum (1531.33 ± 20.28 mmol ascorbicacid/g) and ferrocyanide (14.39%) methods, ABTS (95.74 ± 4.21 µM) and DPPH (843.87 ± 10.65 µM) radical sequestration capacity, while morusin showed significant statistical correlation with antioxidant activity for somevarieties. These results suggested that morusin influences antioxidant activity ofin synergism with other compounds and can be a good chemical marker in this species.


greenmedinfo--2020-11-28--Fermented mulberry leaves suppress high fat diet-induced hepatic steatosis.

BACKGROUND : A novel extract of mulberry leaves fermented with Cordyceps militaris ( EMfC ) is reported to exert anti-obesity activity , although their molecular mechanism during hepatic steatosis has not verified .
METHODS : To investigate the role of inflammation and autophagy during the anti-hepatic steatosis effects of EMfC , we measured alterations in the key parameters for inflammatory response and autophagy pathway in liver tissues of the high fat diet ( HFD ) treated C57BL/6N mice after exposure to EMfC for 12 weeks .
RESULTS : Significant anti-hepatic steatosis effects , including decreased number of lipid droplets and @ @ @ @ @ @ @ in the liver of the HFD + EMfC treated group .
The levels of mast cell infiltration , expression of two inflammatory mediators ( iNOS and COX-2 ) , and the MAPK signaling pathway were remarkably decreased in the liver of HFD + EMfC treated group as compared to the HFD + Vehicle treated group .
Furthermore , a similarinhibitory effect was measured for the expression levels of pro-inflammatory cytokines , including IL-1β , IL-6 , TNF-α and NF-κB .
The expression level of members in the AKT/mTOR signaling pathway ( a central @ @ @ @ @ @ @ treatment with EMfC , and autophagy-related proteins ( Beclin and LC3-II ) were remarkably decreased in the HFD + EMfC treated group compared to the HFD + Vehicle treated group .
Moreover , the HFD + EMfC treated group showed decreased transcript levels of autophagy-regulated genes including Atg4b , Atg5 , Atg7 and Atg12 .
CONCLUSIONS : Taken together , findings of the present study provide novel evidences that the anti-hepatic steatosis of EMfC is tightly linked to the regulation of the inflammatory response and autophagy pathway in the liver tissue of HFD-induced @ @ @

BACKGROUND: A novel extract of mulberry leaves fermented with Cordyceps militaris (EMfC) is reported to exert anti-obesity activity, although their molecular mechanism during hepatic steatosis has not verified.
METHODS: To investigate the role of inflammation and autophagy during the anti-hepatic steatosis effects of EMfC, we measured alterations in the key parameters for inflammatory response and autophagy pathway in liver tissues of the high fat diet (HFD) treated C57BL/6N mice after exposure to EMfC for 12 weeks.
RESULTS: Significant anti-hepatic steatosis effects, including decreased number of lipid droplets and expression of Klf2 mRNA, were detected in the liver of the HFD + EMfC treated group. The levels of mast cell infiltration, expression of two inflammatory mediators (iNOS and COX-2), and the MAPK signaling pathway were remarkably decreased in the liver of HFD + EMfC treated group as compared to the HFD + Vehicle treated group. Furthermore, a similarinhibitory effect was measured for the expression levels of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α and NF-κB. The expression level of members in the AKT/mTOR signaling pathway (a central regulator in autophagy) was recovered after treatment with EMfC, and autophagy-related proteins (Beclin and LC3-II) were remarkably decreased in the HFD + EMfC treated group compared to the HFD + Vehicle treated group. Moreover, the HFD + EMfC treated group showed decreased transcript levels of autophagy-regulated genes including Atg4b, Atg5, Atg7 and Atg12.
CONCLUSIONS: Taken together, findings of the present study provide novel evidences that the anti-hepatic steatosis of EMfC is tightly linked to the regulation of the inflammatory response and autophagy pathway in the liver tissue of HFD-induced obesity mice.


greenmedinfo--2020-11-28--Morusin induces apoptosis and autophagy via JNK, ERK and PI3K/Akt signaling in human lung carcinoma

Morusin induces apoptosis and autophagy via JNK, ERK and PI3K/Akt signaling in human lung carcinoma cells.

Due to drug resistance and side effects , the development of novel therapeutics for the treatment of lung cancer is still in an urgent need .
Morusin , a naturally occurring prenylated flavonoid isolated from the root bark of Morus alba , has been reported to be a promising candidate for cancer treatment including lung cancer .
This study aimed to validate the anti-cancer effects of morusin in human non-small cell lung cancer ( NSCLC ) cell lines A549 and NCI-H292 .
The results indicated that morusin had growth inhibitory , pro-apoptotic and pro-autophagic effects on A549 and NCI-H292 cells @ @ @ @ @ @ @ by chromatin condensation and PARP cleavage .
Mitochondrial membrane potential ( MMP ) loss , cytochrome c release , Bax/Bcl-2 dysregulation , and caspase-3 cleavage were also observed , indicating a mitochondria-dependent apoptosis was induced by morusin .
A pro-autophagic effect was demonstrated by the increased level of LC3-Ⅱ and decreased level of SQSTM1/p62 .
Furthermore , morusin inhibited PI3K/Akt signaling and activated JNK , ERK pathways as indicated by the alteration in the ratio of phosphorylation level over total protein expression level .
A PI3K/Akt inhibitor ( LY294002 ) , a JNK @ @ @ @ @ @ @ inhibitor ( U0126 ) contributed to the determination that these pathways were involved in both apoptosis and autophagy induced by morusin .
Moreover , morusin treatment strikingly enhanced intracellular ROS level , an ROS scavenger NAC blocked cell death and changes of Akt , JNK and ERK induced by morusin .

Due to drug resistance and side effects, the development of novel therapeutics for the treatment of lung cancer is still in an urgent need. Morusin, a naturally occurring prenylated flavonoid isolated from the root bark of Morus alba, has been reported to be a promising candidate for cancer treatment including lung cancer. This study aimed to validate the anti-cancer effects of morusin in human non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H292. The results indicated that morusin had growth inhibitory, pro-apoptotic and pro-autophagic effects on A549 and NCI-H292 cells. The induction of apoptosis was characterized by chromatin condensation and PARP cleavage. Mitochondrial membrane potential (MMP) loss, cytochrome c release, Bax/Bcl-2 dysregulation, and caspase-3 cleavage were also observed, indicating a mitochondria-dependent apoptosis was induced by morusin. A pro-autophagic effect was demonstrated by the increased level of LC3-Ⅱ and decreased level of SQSTM1/p62. Furthermore, morusin inhibited PI3K/Akt signaling and activated JNK, ERK pathways as indicated by the alteration in the ratio of phosphorylation level over total protein expression level. A PI3K/Akt inhibitor (LY294002), a JNK inhibitor (SP600125) and a MEK/ERK inhibitor (U0126) contributed to the determination that these pathways were involved in both apoptosis and autophagy induced by morusin. Moreover, morusin treatment strikingly enhanced intracellular ROS level, an ROS scavenger NAC blocked cell death and changes of Akt, JNK and ERK induced by morusin.


greenmedinfo--2020-11-28--These results revealed that astragalin may improve airway thickening and alveolar destruction with b

Lung inflammation and oxidative stress are the major contributors to the development of obstructive pulmonary diseases .
Macrophages are involved in pulmonary inflammation and alveolar damage in emphysema .
Astragalin is an anti-inflammatory flavonoid present in persimmon leaves and green tea seeds .
This study elucidated that astragalin inhibited inflammatory cell infiltration induced by 20μM HOand blocked airway thickening and alveolar emphysema induced by 20μg of ovalbumin ( OVA ) in mice .
OVA induced mouse pulmonary MCP-1 , and HOenhanced the expression of MCP-1/ICAM-1/αv integrin in bronchial airway epithelial BEAS-2B cells .
Such induction was inhibited by supplying 10-20 @ @ @ @ @ @ @ 1-20 μM astragalin to oxidant-stimulated cells .
Oral administration of 20 mg/kg of astragalin reduced the induction of F4/80/CD68/CD11b in airways of mice challenged with OVA .
Additionally , emphysema tissue damage was observed in OVA-exposed alveoli .
Mast cell recruitment in the airway subepithelium was blocked by supplementing astragalin to OVA-challenged mice .
Orally treating 20 mg/kg of astragalin reduced α-SMA induction in inflammation-occurring airways and appeared to reverse airway thickening and constriction induced by an OVA episode .
These results revealed that astragalin may improve airway thickening and alveolar destruction with @ @ @ @ @ @ @ Therefore , astragalin may be a therapeutic agent antagonizing asthma and obstructive pulmonary diseases .

Lung inflammation and oxidative stress are the major contributors to the development of obstructive pulmonary diseases. Macrophages are involved in pulmonary inflammation and alveolar damage in emphysema. Astragalin is an anti-inflammatory flavonoid present in persimmon leaves and green tea seeds. This study elucidated that astragalin inhibited inflammatory cell infiltration induced by 20μM HOand blocked airway thickening and alveolar emphysema induced by 20μg of ovalbumin (OVA) in mice. OVA induced mouse pulmonary MCP-1, and HOenhanced the expression of MCP-1/ICAM-1/αv integrin in bronchial airway epithelial BEAS-2B cells. Such induction was inhibited by supplying 10-20 mg/kg of astragalin to OVA-challenged mice and 1-20 μM astragalin to oxidant-stimulated cells. Oral administration of 20 mg/kg of astragalin reduced the induction of F4/80/CD68/CD11b in airways of mice challenged with OVA. Additionally, emphysema tissue damage was observed in OVA-exposed alveoli. Mast cell recruitment in the airway subepithelium was blocked by supplementing astragalin to OVA-challenged mice. Orally treating 20 mg/kg of astragalin reduced α-SMA induction in inflammation-occurring airways and appeared to reverse airway thickening and constriction induced by an OVA episode. These results revealed that astragalin may improve airway thickening and alveolar destruction with blockade of allergic inflammation in airways. Therefore, astragalin may be a therapeutic agent antagonizing asthma and obstructive pulmonary diseases.


greenmedinfo--2020-11-28--John Hopkins Researcher: No Excess Deaths from COVID-19; Official Stats Are Misleading, Indicating M

John Hopkins Researcher: No Excess Deaths from COVID-19; Official Stats Are Misleading, Indicating Misclassification

Genevieve Briand , assistant program director of the Applied Economics at John Hopkins University , critically analyzed the effect of COVID-19 on U.S. deaths using data from the Centers for Disease Control , only to find that there appear to be no excess deaths from COVID-19 in 2020 , and that the data has been presented in a misleading fashion .
An article written by Yanni Gu , published on Nov. 22nd , 2020 in the John Hopkins Newsletter , a student publication , summarizes Genevieve Briand 's followings in detail as follows : '' According to new data , @ @ @ @ @ @ @ COVID-19 cases , new cases per day and deaths .
Genevieve Briand , assistant program director of the Applied Economics master ’ s degree program at Hopkins , critically analyzed the effect of COVID-19 on U.S. deaths using data from the Centers for Disease Control and Prevention ( CDC ) in her webinar titled “ COVID-19 Deaths : A Look at U.S. Data.
” From mid-March to mid-September , U.S. total deaths have reached 1.7 million , of which 200,000 , or 12 % of total deaths , are COVID-19-related .
Instead of @ @ @ @ @ @ @ focused on total deaths per age group and per cause of death in the U.S. and used this information to shed light on the effects of COVID-19 .
She explained that the significance of COVID-19 on U.S. deaths can be fully understood only through comparison to the number of total deaths in the United States .
After retrieving data on the CDC website , Briand compiled a graph representing percentages of total deaths per age category from early February to early September , which includes the period from before COVID-19 was detected in @ @ @ @ @ @ @ .
Surprisingly , the deaths of older people stayed the same before and after COVID-19 .
Since COVID-19 mainly affects the elderly , experts expected an increase in the percentage of deaths in older age groups .
However , this increase is not seen from the CDC data .
In fact , the percentages of deaths among all age groups remain relatively the same .
“ The reason we have a higher number of reported COVID-19 deaths among older individuals than younger individuals is simply because every day in the U.S. older individuals @ @ @ @ @ @ @ , ” Briand said .
Briand also noted that 50,000 to 70,000 deaths are seen both before and after COVID-19 , indicating that this number of deaths was normal long before COVID-19 emerged .
Therefore , according to Briand , not only has COVID-19 had no effect on the percentage of deaths of older people , but it has also not increased the total number of deaths .
[ emphasis added ] According to new data , the U.S. currently ranks first in total COVID-19 cases , new cases per day and deaths @ @ @ @ @ @ @ of the Applied Economics master ’ s degree program at Hopkins , critically analyzed the effect of COVID-19 on U.S. deaths using data from the Centers for Disease Control and Prevention ( CDC ) in her webinar titled “ COVID-19 Deaths : A Look at U.S. Data.
” From mid-March to mid-September , U.S. total deaths have reached 1.7 million , of which 200,000 , or 12 % of total deaths , are COVID-19-related .
Instead of looking directly at COVID-19 deaths , Briand focused on total deaths per age group and per @ @ @ @ @ @ @ used this information to shed light on the effects of COVID-19 .
She explained that the significance of COVID-19 on U.S. deaths can be fully understood only through comparison to the number of total deaths in the United States .
[ emphasis added ] After retrieving data on the CDC website , Briand compiled a graph representing percentages of total deaths per age category from early February to early September , which includes the period from before COVID-19 was detected in the U.S. to after infection rates soared .
Surprisingly , the deaths @ @ @ @ @ @ @ and after COVID-19 .
Since COVID-19 mainly affects the elderly , experts expected an increase in the percentage of deaths in older age groups .
However , this increase is not seen from the CDC data .
In fact , the percentages of deaths among all age groups remain relatively the same .
“ The reason we have a higher number of reported COVID-19 deaths among older individuals than younger individuals is simply because every day in the U.S. older individuals die in higher numbers than younger individuals , ” Briand said .
@ @ @ @ @ @ @ deaths are seen both before and after COVID-19 , indicating that this number of deaths was normal long before COVID-19 emerged .
Therefore , according to Briand , not only has COVID-19 had no effect on the percentage of deaths of older people , but it has also not increased the total number of deaths .
[ emphasis added ] Graph depicts the number of deaths per cause during that period in 2020 to 2018 .
This trend is completely contrary to the pattern observed in all previous years .
Interestingly , as @ @ @ @ @ @ @ total decrease in deaths by other causes almost exactly equals the increase in deaths by COVID-19 .
This suggests , according to Briand , that the COVID-19 death toll is misleading .
Briand believes that deaths due to heart diseases , respiratory diseases , influenza and pneumonia may instead be recategorized as being due to COVID-19 .
[ emphasis added ] Graph depicts the total decrease in deaths by various causes , including COVID-19 .
The CDC classified all deaths that are related to COVID-19 simply as COVID-19 deaths .
Even patients dying @ @ @ @ @ @ @ with COVID-19 count as COVID-19 deaths .
This is likely the main explanation as to why COVID-19 deaths drastically increased while deaths by all other diseases experienced a significant decrease .
“ All of this points to no evidence that COVID-19 created any excess deaths .
Total death numbers are not above normal death numbers .
We found no evidence to the contrary , ” Briand concluded .
[ emphasis added ] In an interview with The News-Letter , Briand addressed the question of whether COVID-19 deaths can be called misleading since the @ @ @ @ @ @ @ to deaths by other underlying diseases .
“ If [ the COVID-19 death toll ] was not misleading at all , what we should have observed is an increased number of heart attacks and increased COVID-19 numbers .
But a decreased number of heart attacks and all the other death causes doesn ’ t give us a choice but to point to some misclassification , ” Briand replied .
In other words , the effect of COVID-19 on deaths in the U.S. is considered problematic only when it increases the total number of @ @ @ @ @ @ @ a significant amount in addition to the expected deaths by other causes .
Since the crude number of total deaths by all causes before and after COVID-19 has stayed the same , one can hardly say , in Briand ’ s view , that COVID-19 deaths are concerning .
[ emphasis ] Briand also mentioned that more research and data are needed to truly decipher the effect of COVID-19 on deaths in the United States .
Throughout the talk , Briand constantly emphasized that although COVID-19 is a serious national and global problem @ @ @ @ @ @ @ never lose focus of the bigger picture — death in general .
The death of a loved one , from COVID-19 or from other causes , is always tragic , Briand explained .
Each life is equally important and we should be reminded that even during a global pandemic we should not forget about the tragic loss of lives from other causes .
According to Briand , the over-exaggeration of the COVID-19 death number may be due to the constant emphasis on COVID-19-related deaths and the habitual overlooking of deaths by other natural @ @ @ @ @ @ @ ] During an interview with The News-Letter after the event , Poorna Dharmasena , a master ’ s candidate in Applied Economics , expressed his opinion about Briand ’ s concluding remarks .
“ At the end of the day , it ’ s still a deadly virus .
And over-exaggeration or not , to a certain degree , is irrelevant , ” Dharmasena said .
When asked whether the public should be informed about this exaggeration in death numbers , Dharmasena stated that people have a right to know the truth .
@ @ @ @ @ @ @ treated as a deadly disease to safeguard the vulnerable population . ''
[ Below is a very important and perceptive comment made on the original article posted on the newsletter site that we are including and encourage everyone to read ] '' Consider the following figures- US Total deaths by year per CDC : At present the US is experiencing a 1.12 % increase in overall mortality rates for 2020- not good- pandemicky numbers to be sure .
However , last year , 2019 , there was also a 1.12 % increase .
@ @ @ @ @ @ @ ?
But wait it ’ s even `` scarier '' - 2018 saw a 1.22 % increase in mortality rates , 2017 saw a 1.24 % increase , 2016 1.27 % increase , 2015 1.27 % increase , 2014 1.29 % increase- all exceeding 2020 ’ s increase in mortality rate- so does this mean we have had pandemics for the last 7 years ?
Does this indicate non-stop pandemics every year for the last 7 years and we just weren ’ t paying attention and didn ’ t have an 'honest '' @ @ @ @ @ @ @ beds in a proper state of fear ?
And BTW 2013 all the way back to 2009 all showed .09 % increases in mortality rates- don ’ t know where the cutoff is but certainly even these years were “ pandemic like ” if you feel this year was truly a pandemic .
It isn ’ t until we go back to the year 2008 that we see a decrease in overall mortality rates in the US .
For 20 straight years there were decreases in mortality rates and then in 2009 this @ @ @ @ @ @ @ increase in mortality rates .
Why is that ?
Could this point to the 2008 economic recession as being the leading indicator rather than some supernatural viral entity ?
In reality this year at present seems to be no different in overall mortality rates compared to last year and less of an increase than 5 of the 6 the preceding years .
How is this possible during a “ pandemic of biblical proportions ?
” It 's always important to look at the rates ( populations are increasing and rates vary ) and @ @ @ @ @ @ @ .
Consider the following figures- US Total deaths by year per CDC : At present the US is experiencing a 1.12 % increase in overall mortality rates for 2020- not good- pandemicky numbers to be sure .
However , last year , 2019 , there was also a 1.12 % increase .
Did we miss a pandemic in 2019 ?
But wait it ’ s even `` scarier '' - 2018 saw a 1.22 % increase in mortality rates , 2017 saw a 1.24 % increase , 2016 1.27 % increase , 2015 @ @ @ @ @ @ @ increase- all exceeding 2020 ’ s increase in mortality rate- so does this mean we have had pandemics for the last 7 years ?
Does this indicate non-stop pandemics every year for the last 7 years and we just weren ’ t paying attention and didn ’ t have an 'honest '' media to keep us pinned to our beds in a proper state of fear ?
And BTW 2013 all the way back to 2009 all showed .09 % increases in mortality rates- don ’ t know where the cutoff is but @ @ @ @ @ @ @ like ” if you feel this year was truly a pandemic .
It isn ’ t until we go back to the year 2008 that we see a decrease in overall mortality rates in the US .
For 20 straight years there were decreases in mortality rates and then in 2009 this changed- since then we have had an increase in mortality rates .
Why is that ?
Could this point to the 2008 economic recession as being the leading indicator rather than some supernatural viral entity ?
In reality this year at @ @ @ @ @ @ @ overall mortality rates compared to last year and less of an increase than 5 of the 6 the preceding years .
How is this possible during a “ pandemic of biblical proportions ?
”

Genevieve Briand, assistant program director of the Applied Economics at John Hopkins University, critically analyzed the effect of COVID-19 on U.S. deaths using data from the Centers for Disease Control, only to find that there appear to be no excess deaths from COVID-19 in 2020, and that the data has been presented in a misleading fashion.
An article written by Yanni Gu, published on Nov. 22nd, 2020 in the Johns Hopkins Newsletter, a student publication, summarizes Genevieve Briand's followings in detail as follows:
"According to new data, the U.S. currently ranks first in total COVID-19 cases, new cases per day and deaths. Genevieve Briand, assistant program director of the Applied Economics master's degree program at Hopkins, critically analyzed the effect of COVID-19 on U.S. deaths using data from the Centers for Disease Control and Prevention (CDC) in her webinar titled "COVID-19 Deaths: A Look at U.S. Data."
From mid-March to mid-September, U.S. total deaths have reached 1.7 million, of which 200,000, or 12% of total deaths, are COVID-19-related. Instead of looking directly at COVID-19 deaths, Briand focused on total deaths per age group and per cause of death in the U.S. and used this information to shed light on the effects of COVID-19.
She explained that the significance of COVID-19 on U.S. deaths can be fully understood only through comparison to the number of total deaths in the United States.
After retrieving data on the CDC website, Briand compiled a graph representing percentages of total deaths per age category from early February to early September, which includes the period from before COVID-19 was detected in the U.S. to after infection rates soared.
Surprisingly, the deaths of older people stayed the same before and after COVID-19. Since COVID-19 mainly affects the elderly, experts expected an increase in the percentage of deaths in older age groups. However, this increase is not seen from the CDC data. In fact, the percentages of deaths among all age groups remain relatively the same.
"The reason we have a higher number of reported COVID-19 deaths among older individuals than younger individuals is simply because every day in the U.S. older individuals die in higher numbers than younger individuals," Briand said.
Briand also noted that 50,000 to 70,000 deaths are seen both before and after COVID-19, indicating that this number of deaths was normal long before COVID-19 emerged. Therefore, according to Briand, not only has COVID-19 had no effect on the percentage of deaths of older people, but it has also not increased the total number of deaths. [emphasis added]
According to new data, the U.S. currently ranks first in total COVID-19 cases, new cases per day and deaths. Genevieve Briand, assistant program director of the Applied Economics master's degree program at Hopkins, critically analyzed the effect of COVID-19 on U.S. deaths using data from the Centers for Disease Control and Prevention (CDC) in her webinar titled "COVID-19 Deaths: A Look at U.S. Data."
From mid-March to mid-September, U.S. total deaths have reached 1.7 million, of which 200,000, or 12% of total deaths, are COVID-19-related. Instead of looking directly at COVID-19 deaths, Briand focused on total deaths per age group and per cause of death in the U.S. and used this information to shed light on the effects of COVID-19.
She explained that the significance of COVID-19 on U.S. deaths can be fully understood only through comparison to the number of total deaths in the United States. [emphasis added]
After retrieving data on the CDC website, Briand compiled a graph representing percentages of total deaths per age category from early February to early September, which includes the period from before COVID-19 was detected in the U.S. to after infection rates soared.
Surprisingly, the deaths of older people stayed the same before and after COVID-19. Since COVID-19 mainly affects the elderly, experts expected an increase in the percentage of deaths in older age groups. However, this increase is not seen from the CDC data. In fact, the percentages of deaths among all age groups remain relatively the same.
"The reason we have a higher number of reported COVID-19 deaths among older individuals than younger individuals is simply because every day in the U.S. older individuals die in higher numbers than younger individuals," Briand said.
Briand also noted that 50,000 to 70,000 deaths are seen both before and after COVID-19, indicating that this number of deaths was normal long before COVID-19 emerged. Therefore, according to Briand, not only has COVID-19 had no effect on the percentage of deaths of older people, but it has also not increased the total number of deaths. [emphasis added]
COURTESY OF GENEVIEVE BRIAND
Graph depicts the number of deaths per cause during that period in 2020 to 2018.
This trend is completely contrary to the pattern observed in all previous years. Interestingly, as depicted in the table below, the total decrease in deaths by other causes almost exactly equals the increase in deaths by COVID-19. This suggests, according to Briand, that the COVID-19 death toll is misleading. Briand believes that deaths due to heart diseases, respiratory diseases, influenza and pneumonia may instead be recategorized as being due to COVID-19. [emphasis added]
COURTESY OF GENEVIEVE BRIAND Graph depicts the total decrease in deaths by various causes, including COVID-19.
The CDC classified all deaths that are related to COVID-19 simply as COVID-19 deaths. Even patients dying from other underlying diseases but are infected with COVID-19 count as COVID-19 deaths. This is likely the main explanation as to why COVID-19 deaths drastically increased while deaths by all other diseases experienced a significant decrease.
"All of this points to no evidence that COVID-19 created any excess deaths. Total death numbers are not above normal death numbers. We found no evidence to the contrary," Briand concluded. [emphasis added]
In an interview with The News-Letter, Briand addressed the question of whether COVID-19 deaths can be called misleading since the infection might have exacerbated and even led to deaths by other underlying diseases.
"If [the COVID-19 death toll] was not misleading at all, what we should have observed is an increased number of heart attacks and increased COVID-19 numbers. But a decreased number of heart attacks and all the other death causes doesn't give us a choice but to point to some misclassification," Briand replied.
In other words, the effect of COVID-19 on deaths in the U.S. is considered problematic only when it increases the total number of deaths or the true death burden by a significant amount in addition to the expected deaths by other causes. Since the crude number of total deaths by all causes before and after COVID-19 has stayed the same, one can hardly say, in Briand's view, that COVID-19 deaths are concerning. [emphasis]
Briand also mentioned that more research and data are needed to truly decipher the effect of COVID-19 on deaths in the United States.
Throughout the talk, Briand constantly emphasized that although COVID-19 is a serious national and global problem, she also stressed that society should never lose focus of the bigger picture -- death in general.


greenmedinfo--2020-11-28--Astragalin-induced cell death is caspase-dependent and enhances the susceptibility of lung cancer ce

Astragalin-induced cell death is caspase-dependent and enhances the susceptibility of lung cancer cells to tumor necrosis factor.

Flavonoids are naturally occurring polyphenolic compounds and are among the most promising anticancer agents .
Here , we demonstrate that @ @ @ @ @ ) , also known as kaempferol-3-O-β-D-glucoside , induces cell death .
This was prevented by @ @ @ @ @ z-LEHD-FMK .
AG-induced cell death was associated with an increase in the Bax : Bcl-2 @ @ @ @ @ inhibition of extracellular signal-regulated kinase ( ERK ) -1/2 and Akt signaling .
Meanwhile , @ @ @ @ @ Additional studies revealed that AG inhibited tumor necrosis factor-alpha ( TNFα ) -induced NF-κB activity @ @ @ @ @ apoptosis in A549 cells .
Furthermore , using a mouse xenograft model , we demonstrated @ @ @ @ @ induced cancer cell apoptosis in vivo .
Taken together , these results suggest that AG @ @ @ @ @ therapeutic drug that warrants further investigation into its potential clinical applications .

Flavonoids are naturally occurring polyphenolic compounds and are among the most promising anticancer agents. Here, we demonstrate that the flavonoid astragalin (AG), also known as kaempferol-3-O-β-D-glucoside, induces cell death. This was prevented by the caspase inhibitors z-DEVD-FMK and z-LEHD-FMK. AG-induced cell death was associated with an increase in the Bax:Bcl-2 ratio and amplified by the inhibition of extracellular signal-regulated kinase (ERK)-1/2 and Akt signaling. Meanwhile, AGsuppressed LPS-induced NF-κB activation. Additional studies revealed that AG inhibited tumor necrosis factor-alpha (TNFα)-induced NF-κB activity. AG also potentiated TNFα-induced apoptosis in A549 cells. Furthermore, using a mouse xenograft model, we demonstrated that AG suppressed tumor growthand induced cancer cell apoptosis in vivo. Taken together, these results suggest that AG may be a promising cancer therapeutic drug that warrants further investigation into its potential clinical applications.


greenmedinfo--2020-11-28--Astragalin reduces hexokinase 2 through increasing miR-125b to inhibit the proliferation of hepatoce

Astragalin reduces hexokinase 2 through increasing miR-125b to inhibit the proliferation of hepatocellular carcinoma cells.

Astragalin ( ASG ) can be found in a variety of food components .
ASG exhibits cytotoxic effects on several different types of malignant cells .
However , its effects on hepatocellular carcinoma ( HCC ) cells and the underlying molecular mechanisms have remained to be fully elucidated .
Here , we revealed that ASG remarkably suppressed the proliferation of HCC cells .
In HCC cells , ASG inhibited glucose glycolysis and promoted oxidative phosphorylation , resulting in a surge of reactive oxygen species ( ROS ) .
Mechanistically , ASG suppressed the expression of hexokinase 2 ( HK2 ) @ @ @ @ @ @ @ metabolic reprogramming , ROS accumulation , and subsequent growth arrest .
Our further investigations unveiled that ASG repressed HK2 expression via increasing miR-125b .
In vivo experiments showed that gavage of ASG decreased the proliferation of Huh-7 HCC xenografts in nude mice and inhibited the growth of transplanted H22 HCC cells in Kunming mice .
Declined HCC tumor growth in vivo was associated with boosted miR-125b and reduced expression of HK2 in tumor tissues .
Collectively , our results demonstrated that ASG is able to suppress the proliferation of HCC cells both in @ @ @ @ @ @ @ HK2 through upregulating miR-125b and subsequent metabolic reprogramming is implicated in the antiproliferative effects of ASG on HCC cells .

Astragalin (ASG) can be found in a variety of food components. ASG exhibits cytotoxic effects on several different types of malignant cells. However, its effects on hepatocellular carcinoma (HCC) cells and the underlying molecular mechanisms have remained to be fully elucidated. Here, we revealed that ASG remarkably suppressed the proliferation of HCC cells. In HCC cells, ASG inhibited glucose glycolysis and promoted oxidative phosphorylation, resulting in a surge of reactive oxygen species (ROS). Mechanistically, ASG suppressed the expression of hexokinase 2 (HK2). This event was indispensible for ASG-mediated metabolic reprogramming, ROS accumulation, and subsequent growth arrest. Our further investigations unveiled that ASG repressed HK2 expression via increasing miR-125b. In vivo experiments showed that gavage of ASG decreased the proliferation of Huh-7 HCC xenografts in nude mice and inhibited the growth of transplanted H22 HCC cells in Kunming mice. Declined HCC tumor growth in vivo was associated with boosted miR-125b and reduced expression of HK2 in tumor tissues. Collectively, our results demonstrated that ASG is able to suppress the proliferation of HCC cells both in vitro and in vivo. Inhibition of HK2 through upregulating miR-125b and subsequent metabolic reprogramming is implicated in the antiproliferative effects of ASG on HCC cells.


greenmedinfo--2020-11-28--Apoptotic effect of astragalin in melanoma skin cancers.

Though Astragalin ( kaempferol-3-glucoside ) contained in Paeonia lactiflora and other plants was known to have anti-oxidant , antiinflammatory , and anti-tumor activity , the anti-tumor mechanism of Astragalin has never been reported in melanomas until now .
Thus , in the present study , the underlying apoptotic mechanism of Astragalin isolated from Aceriphyllum rossii was elucidated in A375P and SK-MEL-2 melanoma cells .
Astragalin exerted cytotoxicity in A375P and SK-MEL-2 cells in a concentration-dependent manner .
Also , Astragalin significantly increased the number of TdT-mediated dUTP nick end labeling positive cells and sub-G1 population as a feature of apoptosis @ @ @ @ @ @ @ untreated control .
Consistently , western blotting revealed that Astragalin activated caspase 9/3 and Bax , cleaved poly ( ADP-ribose ) polymerase , and attenuated the expression of cyclin D1 , Mcl-1 , and Sry-related HMg-Box gene 10 ( SOX10 ) in A375P and SK-MEL-2 cells .
Of note , ectopic expression of SOX10 reduced the apoptotic ability of Astragalin to inhibit proliferation , cleave poly ( ADP-ribose ) polymerase , and caspase 3 in A375P and SK-MEL-2 melanoma cells .
Overall , our findings provide evidence that Astragalin induces apoptosis in A375P @ @ @ @ @ @ @ caspase9/3 and inhibition of SOX10 signaling .
Copyright© 2017 John Wiley & Sons , Ltd .

Though Astragalin (kaempferol-3-glucoside) contained in Paeonia lactiflora and other plants was known to have anti-oxidant, antiinflammatory, and anti-tumor activity, the anti-tumor mechanism of Astragalin has never been reported in melanomas until now. Thus, in the present study, the underlying apoptotic mechanism of Astragalin isolated from Aceriphyllum rossii was elucidated in A375P and SK-MEL-2 melanoma cells. Astragalin exerted cytotoxicity in A375P and SK-MEL-2 cells in a concentration-dependent manner. Also, Astragalin significantly increased the number of TdT-mediated dUTP nick end labeling positive cells and sub-G1 population as a feature of apoptosis in A375P and SK-MEL-2 cells compared with untreated control. Consistently, western blotting revealed that Astragalin activated caspase 9/3 and Bax, cleaved poly (ADP-ribose) polymerase, and attenuated the expression of cyclin D1, Mcl-1, and Sry-related HMg-Box gene 10 (SOX10) in A375P and SK-MEL-2 cells. Of note, ectopic expression of SOX10 reduced the apoptotic ability of Astragalin to inhibit proliferation, cleave poly (ADP-ribose) polymerase, and caspase 3 in A375P and SK-MEL-2 melanoma cells. Overall, our findings provide evidence that Astragalin induces apoptosis in A375P and SK-MEL-2 melanoma cells via activation of caspase9/3 and inhibition of SOX10 signaling. Copyright© 2017 John Wiley&Sons, Ltd.


greenmedinfo--2020-11-28--Astragalin attenuates UVB radiation-induced actinic keratosis formation.

BACKGROUND : Actinic Keratosis ( AK ) , is the most common precancerous skin lesion induced by the excessive Ultraviolet B ( UVB ) and is a significant threat to the public health .
UVB exposure causes oxidative DNA damage and is considered to be a significant contributor to AK and subsequent development of skin cancer .
Besides , activation of p38 MAPK also plays a significant role in the development of AK .
OBJECTIVE : This study aimed at the development of a nature compound which can inhibit UVB-induced AK .
METHOD : MTS Cell Proliferation Assay Kit was @ @ @ @ @ @ @ .
HE-staining , Immunohistochemical , Western blot and Enzyme Linked Immunosorbent Assay were applied to examine the clinicopathologic feature of AK and the change of p38 MAPK signal pathway treated with astraglin under the condition of UVB in vitro and in vivo .
Results：In our clinical findings revealed that p38 MAPK , phospho-MSK1 , and γ -H2AX were significantly highly expressed in human AK tissue than the normal healthy skin tissue .
Moreover , in vitro studies showed that UVB induced the phospho-MSK1 and γ-H2AX in a time- and dose-dependent manner in HaCaT @ @ @ @ @ @ @ assay demonstrated that astragalin could directly bind to p38 MAPK and suppress p38 MAPK activity .
Furthermore , astragalin exhibited no toxicity and suppressed the UVB-induced expression of phospho- MSK1 and γ -H2AX by suppressing p38 MAPK activity in a time-dependent and dose-dependent manner in HaCaT cells .
The in vivo studies with animal UV model demonstrated that astragalin inhibited UVB-induced expression of phospho-MSK1 and γ-H2AX in Babl/c mice .
CONCLUSION : These results suggested that p38 MAPK is a direct valid molecular target of astragalin for the attenuation of UVB-induced AK .
@ @ @ @ @ @ @ promising novel natural therapeutic agent for the prevention and management of UVB-induced AK with high target specificity and low toxicity .

BACKGROUND: Actinic Keratosis (AK), is the most common precancerous skin lesion induced by the excessive Ultraviolet B (UVB) and is a significant threat to the public health. UVB exposure causes oxidative DNA damage and is considered to be a significant contributor to AK and subsequent development of skin cancer. Besides, activation of p38 MAPK also plays a significant role in the development of AK.
OBJECTIVE: This study aimed at the development of a nature compound which can inhibit UVB-induced AK.
METHOD: MTS Cell Proliferation Assay Kit was used to detect the toxicity of astragalin. HE-staining, Immunohistochemical, Western blot and Enzyme Linked Immunosorbent Assay were applied to examine the clinicopathologic feature of AK and the change of p38 MAPK signal pathway treated with astraglin under the condition of UVB in vitro and in vivo. Results：In our clinical findings revealed that p38 MAPK, phospho-MSK1, and γ -H2AX were significantly highly expressed in human AK tissue than the normal healthy skin tissue. Moreover, in vitro studies showed that UVB induced the phospho-MSK1 and γ-H2AX in a time- and dose-dependent manner in HaCaT cells. Further, in vitro kinase assay demonstrated that astragalin could directly bind to p38 MAPK and suppress p38 MAPK activity. Furthermore, astragalin exhibited no toxicity and suppressed the UVB-induced expression of phospho- MSK1 and γ -H2AX by suppressing p38 MAPK activity in a time-dependent and dose-dependent manner in HaCaT cells. The in vivo studies with animal UV model demonstrated that astragalin inhibited UVB-induced expression of phospho-MSK1 and γ-H2AX in Babl/c mice.
CONCLUSION: These results suggested that p38 MAPK is a direct valid molecular target of astragalin for the attenuation of UVB-induced AK. Furthermore, astragalin could be a potential promising novel natural therapeutic agent for the prevention and management of UVB-induced AK with high target specificity and low toxicity.


greenmedinfo--2020-11-29--Ocimum tenuiflorum L. may pave the way to the development of new agents for the treatment of diabete

Ocimum tenuiflorum L. may pave the way to the development of new agents for the treatment of diabetes and its complications.

The current study aimed to determine the best dose of methanol extract ofL .
leaves extract , and it is a fraction to blood-glucose-lowering in diabetic rats , and evaluated theα-amylase , α-glucosidase inhibitors and insulin level of diabetic rats used to achieve greater control over hyperglycemia .
The result of the antihyperglycaemic of oral administration of a different dose of methanol extract in streptozotocin-induced rats showed that the highest dose of methanol extract significantly reduced the blood glucose level compared to another dose .
Also , the result of repeated administration of methanol fractions indicates that ethyl acetate-butanol fraction @ @ @ @ @ @ @ and ethanol-water fractions .
Moreover , the resultshowed that effect of methanol extract and its fraction on α-glucosidase and α-amylase enzymes activities and its insulin level by in vitro study , ethyl acetate-butanol fraction could control with low concentration compared to other fractions and acarbose that used as a positive control .
From theresult of insulin level , methanol extract and fraction did not show any significant .
These findings indicated that the active crude extract ( methanol ) and its active fractions ( ethyl acetate/butanol ) could exert significant glucose-lowering effect due @ @ @ @ @ @ @ .
In conclusion , isolation of the active components ofL .
may pave the way to the development of new agents for the treatment of diabetes and its complications .

The current study aimed to determine the best dose of methanol extract ofL. leaves extract, and it is a fraction to blood-glucose-lowering in diabetic rats, and evaluated theα-amylase, α-glucosidase inhibitors and insulin level of diabetic rats used to achieve greater control over hyperglycemia. The result of the antihyperglycaemic of oral administration of a different dose of methanol extract in streptozotocin-induced rats showed that the highest dose of methanol extract significantly reduced the blood glucose level compared to another dose. Also, the result of repeated administration of methanol fractions indicates that ethyl acetate-butanol fraction exhibited a stronger antihyperglycemic effect than chloroform and ethanol-water fractions. Moreover, the resultshowed that effect of methanol extract and its fraction on α-glucosidase and α-amylase enzymes activities and its insulin level by in vitro study, ethyl acetate-butanol fraction could control with low concentration compared to other fractions and acarbose that used as a positive control. From theresult of insulin level, methanol extract and fraction did not show any significant. These findings indicated that the active crude extract (methanol) and its active fractions (ethyl acetate/butanol) could exert significant glucose-lowering effect due to the presence of polyphenolics active constituents. In conclusion, isolation of the active components ofL. may pave the way to the development of new agents for the treatment of diabetes and its complications.


greenmedinfo--2020-11-29--Ocimum sanctum Linn. ethanolic extract inhibits angiogenesis in human lung adenocarcinoma (a549) cel

Ocimum sanctum Linn. ethanolic extract inhibits angiogenesis in human lung adenocarcinoma (a549) cells.

Background and Aim : ( OS ) is a herbal plant , which is easy to find and is widely used as an alternative medication .
The previous studies have shown that several species of OS extract have therapeutic properties , and in some cases , antitumor properties .
Furthermore , several data have shown the antiproliferative effects of OS extract in cases of breast cancer , human fibrosarcoma , and oral cancer .
Lung adenocarcinoma is a major cause of male cancer worldwide ; however , the effect of OS ( of Indonesian origin ) on the metastasis of @ @ @ @ @ @ @ unclear .
This study aimed to analyze the antiangiogenic effects of OS ethanolic extract in A549 lung adenocarcinoma cells .
Materials and Methods : An angiogenesis assay was performed by seeding A549 cells on extracellular matrix solution and observing tube formation using an inverted microscope .
Enzyme-linked immunosorbent assay forαvβ3 , matrix metalloproteinase ( MMP ) -2 , and MMP-9 was performed by analyzing the cell lysate after a given treatment .
Results : OS ethanolic extract significantly inhibited tube formation of A549 cells and suppressed the expression of integrinαvβ3 , MMP-2 , @ @ @ @ @ @ @ indicate that OS ethanolic extract disrupts angiogenesis of A549 cells , which may result from the disruption of cell migration and proliferation as a consequence of downregulation ofαvβ3 , MMP-2 , and MMP-9 .
Taken together , OS ethanolic extract may represent a good therapeutic candidate for the treatment of metastasis in lung adenocarcinoma .
Further studies are warranted to further establish the efficacy of OS in the treatment of lung adenocarcinoma .

Background and Aim: (OS) is a herbal plant, which is easy to find and is widely used as an alternative medication. The previous studies have shown that several species of OS extract have therapeutic properties, and in some cases, antitumor properties. Furthermore, several data have shown the antiproliferative effects of OS extract in cases of breast cancer, human fibrosarcoma, and oral cancer. Lung adenocarcinoma is a major cause of male cancer worldwide; however, the effect of OS (of Indonesian origin) on the metastasis of human alveolar pulmonary adenocarcinoma A549 cells remains unclear. This study aimed to analyze the antiangiogenic effects of OS ethanolic extract in A549 lung adenocarcinoma cells.
Materials and Methods: An angiogenesis assay was performed by seeding A549 cells on extracellular matrix solution and observing tube formation using an inverted microscope. Enzyme-linked immunosorbent assay forαvβ3, matrix metalloproteinase (MMP)-2, and MMP-9 was performed by analyzing the cell lysate after a given treatment.
Results: OS ethanolic extract significantly inhibited tube formation of A549 cells and suppressed the expression of integrinαvβ3, MMP-2, and MMP-9.
Conclusion: Our findings indicate that OS ethanolic extract disrupts angiogenesis of A549 cells, which may result from the disruption of cell migration and proliferation as a consequence of downregulation ofαvβ3, MMP-2, and MMP-9. Taken together, OS ethanolic extract may represent a good therapeutic candidate for the treatment of metastasis in lung adenocarcinoma. Further studies are warranted to further establish the efficacy of OS in the treatment of lung adenocarcinoma.


greenmedinfo--2020-11-29--The neuroprotective effect of ethanolic extract Ocimum sanctum Linn.

The aim of this study was to identify the effects of Ocimum sanctum Linn .
ethanolic extract ( OSE ) on the neurons of the CA1 , CA3 , and DG hippocampal areas with the use of in vivo and in vitro models of Alzheimer 's diseases ( AD ) .
Twenty-one two-month-old male rats were divided into three groups : untreated ( Group A , n = 3 ) , AD rats model pretreated with OSE followed by induction for Trimethyltin ( TMT ) on day 7 ( group B , n = 9 ) , and AD rats @ @ @ @ @ @ @ introduction for 7 days and post-TMT induction for 21 days ( group C , n = 9 ) .
AD rats were sacrificed on days 7 , 14 , and 21 , and brain samples were collected and analyzed for neuronal density and neuropeptide Y ( NPY ) immunoreactivity .
To corroborate the in vivo observations , HEK-293 cells were treated with TMT and used as an in vitro model of AD .
The results were then analyzed using FITC Annexin V and flow cytometry .
Nuclear fragmentation was observed in cells stained @ @ @ @ @ @ @ The results showed a significant increase in the number of neurons and NPY expression in the AD rats that were pre- and post-treated with OSE ( p

The aim of this study was to identify the effects of Ocimum sanctum Linn. ethanolic extract (OSE) on the neurons of the CA1, CA3, and DG hippocampal areas with the use of in vivo and in vitro models of Alzheimer's diseases (AD). Twenty-one two-month-old male rats were divided into three groups: untreated (Group A, n = 3), AD rats model pretreated with OSE followed by induction for Trimethyltin (TMT) on day 7 (group B, n = 9), and AD rats model treated with OSE both as pre-TMT introduction for 7 days and post-TMT induction for 21 days (group C, n = 9). AD rats were sacrificed on days 7, 14, and 21,and brain samples were collected and analyzed for neuronal density and neuropeptide Y (NPY) immunoreactivity. To corroborate the in vivo observations, HEK-293 cells were treated with TMT and used as an in vitro model of AD. The results were then analyzed using FITC Annexin V and flow cytometry. Nuclear fragmentation was observed in cells stained with Hoechst 33342 by confocal microscopy. The results showed a significant increase in the number of neurons and NPY expression in the AD rats that were pre- and post-treated with OSE (p < 0.05). Indeed, OSE was able to retain and promote neuronal density in the rat model of AD. Further studies of an in vitro model of neurodegeneration with Ocimum sanctum Linn. ethanolic extract inhibited apoptosis in TMT-induced HEK-293 cells. Moreover, OSE prevented nuclear fragmentation, which was confirmed by staining the nuclei of HEK-293 cells. Taken together, there findings suggest that OSE has the potential as a neuroprotective agent (retaining the autobiographical memory),and the neuroproliferation of neurons in the CA1, CA3, and DG hippocampal areas in the rats¡ model of neurodegeneration was mediated by activation of NPY expression.


greenmedinfo--2020-11-29--Radioprotective effects of plants from the Lamiaceae family.

BACKGROUND : Edible and medicinal plants are still an interesting source of promising biologically active substances to drug discovery and development .
At a time of increasing cancer incidence in the world , alleviating the bothersome side effects of radiotherapy in debilitated cancer patients is becoming an important challenge .
OBJECTIVE : The aim of the study was to overview the literature data concerning the radioprotective activity of extracts , essential oils , and some chemical compounds obtained from 12 species belonging to the Lamiaceae family , gathering of numerous spice and medicinal plants rich in valuable phytochemicals .
RESULTS @ @ @ @ @ @ @ publications showed radioprotective effectiveness of essential oils and complex extracts containing phenolic acids and flavonoids in various in vitro and in vivo models .
Relatively welldocumented preventive properties exhibited the following species : Mentha× piperita , Ocimum tenuiflorum , Origanum vulgare , and Rosmarinus officinalis .
However , few plants such as Lavandula angustifolia , Mentha arvensis , M. spicata , Plectranthus amboinicus , Salvia miltiorrhiza , S. officinalis , Scutellaria baicalensis , and Zataria multiflora should be more investigated inthe future .
Among the mechanisms of radioprotective effects of well-studied extracts and @ @ @ @ @ @ @ the protection against chromosomal damage , scavenging free radicals , decreasing of lipid peroxidation and elevating of glutathione , superoxide dismutase , catalase , andalkaline phosphatase enzyme levels as well as the reduction the cell death .
The plant substances protected the gastrointestinal tract , bone marrow and lung fibroblasts .
In conclusion , studied species of Lamiaceae family and their active chemical compounds are potent in alleviating the side effectsof radiotherapy and should be considered as a complementary therapy .

BACKGROUND: Edible and medicinal plants are still an interesting source of promising biologically active substances to drug discovery and development. At a time of increasing cancer incidence in the world, alleviating the bothersome side effects of radiotherapy in debilitated cancer patients is becoming an important challenge.
OBJECTIVE: The aim of the study was to overview the literature data concerning the radioprotective activity of extracts, essential oils, and some chemical compounds obtained from 12 species belonging to the Lamiaceae family, gathering of numerous spice and medicinal plants rich in valuable phytochemicals.
RESULTS AND CONCLUSION: The analysis of available publications showed radioprotective effectiveness of essential oils and complex extracts containing phenolic acids and flavonoids in various in vitro and in vivo models. Relatively welldocumented preventive properties exhibited the following species: Mentha× piperita, Ocimum tenuiflorum, Origanum vulgare, and Rosmarinus officinalis. However, few plants such as Lavandula angustifolia, Mentha arvensis, M. spicata, Plectranthus amboinicus, Salvia miltiorrhiza, S. officinalis, Scutellaria baicalensis, and Zataria multiflora should be more investigated inthe future. Among the mechanisms of radioprotective effects of well-studied extracts and phytochemicals, it can be mentioned mainly the protection against chromosomal damage, scavenging free radicals, decreasing of lipid peroxidation and elevating of glutathione, superoxide dismutase, catalase, andalkaline phosphatase enzyme levels as well as the reduction the cell death. The plant substances protected the gastrointestinal tract, bone marrow and lung fibroblasts. In conclusion, studied species of Lamiaceae family and their active chemical compounds are potent in alleviating the side effectsof radiotherapy and should be considered as a complementary therapy.


greenmedinfo--2020-11-29--Peppermint oil use significantly reduced the frequency of nausea, vomiting, retching and the severit

Peppermint oil use significantly reduced the frequency of nausea, vomiting, retching and the severity of nausea in cancer patients undergoing chemotherapy.

OBJECTIVES : The current study evaluated the effects of peppermint oil on the frequency of nausea , vomiting , retching , and the severity of nausea in cancer patients undergoing chemotherapy .
SETTING : Patients were recruited from the ambulatory chemotherapy unit of a public hospital located ( Batman , Turkey ) between September 2017 and September 2018 .
INTERVENTIONS : The participants in the intervention group applied one drop the aromatic mixture on the spot between their upper lip and their nose , three times a day for the five days following chemotherapy administration , in addition to the @ @ @ @ @ @ @ control group underwent only the routine antiemetic treatment .
Main outcome measures VAS-the severity of nausea and the Index of Nausea , Vomiting , and Retching .
RESULTS : The VAS nausea score was significantly lower after peppermint oil applying in the patients receiving Folfirinox ( treatment effect ( mean dif . )
: 4.00±2.28 ; P < 0.001 ) , Paclitaxel-Trastuzumab ( treatment effect ( mean dif . )
: 1.70±0.90 ; P=0.014 ) , Carboplatin-Paclitaxel ( treatment effect ( mean dif . )
: 3.71±1.41 ; P < 0.001 ) , @ @ @ @ @ @ @ dif . )
: 1.41±0.73 ; P=0.005 ) excluding cisplatin scedule ( treatment effect ( mean dif . )
: 0.56±2,18 ; P=0.642 ) .
We detected a statistical significant difference in the change in frequency of nausea , vomiting , retching in the other all schedules excluding cisplatin schedule ( P < 0.05 ) .
CONCLUSIONS : The peppermint oil was significantly reduced the frequency of nausea , vomiting , retching and the severity of nausea in cancer patients undergoing chemotherapy .
Therefore , usage of peppermint oil together with antiemetics after @ @ @ @ @ @ @ may be recommended to cope with CINV .

OBJECTIVES: The current study evaluated the effects of peppermint oil on the frequency of nausea, vomiting, retching, and the severity of nausea in cancer patients undergoing chemotherapy.
DESIGN: A quasi-randomized controlled study.
SETTING: Patients were recruited from the ambulatory chemotherapy unit of a public hospital located (Batman, Turkey) between September 2017 and September 2018.
INTERVENTIONS: The participants in the intervention group applied one drop the aromatic mixture on the spot between their upper lip and their nose, three times a day for the five days following chemotherapy administration, in addition to the routine antiemetic treatment. Participants in the control group underwent only the routine antiemetic treatment. Main outcome measures VAS-the severity of nausea and the Index of Nausea, Vomiting, and Retching.
RESULTS: The VAS nausea score was significantly lower after peppermint oil applying in the patients receiving Folfirinox (treatment effect (mean dif.): 4.00±2.28; P<0.001), Paclitaxel-Trastuzumab (treatment effect (mean dif.): 1.70±0.90; P=0.014), Carboplatin-Paclitaxel (treatment effect (mean dif.): 3.71±1.41; P<0.001), and Cyclophosphamide-Adriamycin (treatment effect (mean dif.): 1.41±0.73; P=0.005) excluding cisplatin scedule (treatment effect (mean dif.): 0.56±2,18; P=0.642). We detected a statistical significant difference in the change in frequency of nausea, vomiting, retching in the other all schedules excluding cisplatin schedule (P<0.05).
CONCLUSIONS: The peppermint oil was significantly reduced the frequency of nausea, vomiting, retching and the severity of nausea in cancer patients undergoing chemotherapy. Therefore, usage of peppermint oil together with antiemetics after chemotherapy with moderate and low emetic risk may be recommended to cope with CINV.


greenmedinfo--2020-11-29--Combination of white tea and peppermint demonstrated synergistic antibacterial and anti-inflammatory

Combination of white tea and peppermint demonstrated synergistic antibacterial and anti-inflammatory activities.

BACKGROUND : White tea , considered to be the oldest form of tea , is becoming a popular beverage for its organoleptic characteristics .
Peppermint tea , used as a herbal remedy for centuries , is now also very popular throughout the world as herbal tea .
What interested us was that in ancient China , peppermint was used in combination with tea as a detoxification or anti-inflammatory agent .
However , there are few reports on the combined use of white tea and peppermint .
Therefore , this study aims to investigate the antibacterial and anti-inflammatory activities of white @ @ @ @ @ @ @ : A synergistic inhibitory effect against four bacterial strains , especially against Staphylococcus argenteus , was observed in the combination of white tea and peppermint in vitro .
In addition , the combined formula demonstrated a stronger anti-inflammatory effect in vivo than either of the two used alone , which was associated with the decrease of the pro-inflammatory cytokines of interleukin-6 ( IL-6 ) , interleukin-1beta ( IL-1β ) , tumor necrosis factor-alpha ( TNF-α ) , cyclooxygenase-2 ( COX-2 ) and inducible nitric oxide synthase ( iNOS ) .
In a further @ @ @ @ @ @ @ white tea and peppermint inhibited the phosphorylation of p-IκB-α and mitogen-activated protein kinase ( MAPK ) at different degrees .
Whilethe enhanced anti-inflammatory effect of the combined formula was associated with the combination of NF-κB down-regulation and p-MAPK inhibition .
CONCLUSION : In our study , it was for the first time shown that when white tea was combined with peppermint , the antibacterial and anti-inflammatory effects were enhanced .
The results suggested an effective application of white tea in combination with peppermint as a potential antibacterial and anti-inflammatory functional food.© 2020 Society @ @ @ @

BACKGROUND: White tea, considered to be the oldest form of tea, is becoming a popular beverage for its organoleptic characteristics. Peppermint tea, used as a herbal remedy for centuries, is now also very popular throughout the world as herbal tea. What interested us was that in ancient China, peppermint was used in combination with tea as a detoxification or anti-inflammatory agent. However, there are few reports on the combined use of white tea and peppermint. Therefore, this study aims to investigate the antibacterial and anti-inflammatory activities of white tea in combination with peppermint.
RESULTS: A synergistic inhibitory effect against four bacterial strains, especially against Staphylococcus argenteus, was observed in the combination of white tea and peppermint in vitro. In addition, the combined formula demonstrated a stronger anti-inflammatory effect in vivo than either of the two used alone, which was associated with the decrease of the pro-inflammatory cytokines of interleukin-6 (IL-6), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). In a further mechanism study, it was found that white tea and peppermint inhibited the phosphorylation of p-IκB-α and mitogen-activated protein kinase (MAPK) at different degrees. Whilethe enhanced anti-inflammatory effect of the combined formula was associated with the combination of NF-κB down-regulation and p-MAPK inhibition.
CONCLUSION: In our study, it was for the first time shown that when white tea was combined with peppermint, the antibacterial and anti-inflammatory effects were enhanced. The results suggested an effective application of white tea in combination with peppermint as a potential antibacterial and anti-inflammatory functional food.© 2020 Society of Chemical Industry.


greenmedinfo--2020-11-29--Raspberry ketones attenuate cyclophosphamide-induced pulmonary toxicity.

Cyclophosphamide ( CP ) was found to have a potential toxic effect on lung tissues .
Raspberry ketones ( RKs ) are natural antioxidant chemicals isolated from red raspberries ( Rubus ideaus ) .
They are commonly used for weight loss and obesity .
The current study aimed to evaluate the possible protective effects of RKs against lung toxicity induced by CP .
Mice were allocated into six groups : ( 1 ) control group ; ( 2 ) CP group : received a single intraperitoneal dose of CP ( 150 mg/kg , i.p . )
; and ( 3-6 @ @ @ @ @ @ @ doses of RKs ( 25 , 50 , 100 , and 200 mg/kg ) for 14 consecutive days , respectively , before the administration of an intraperitoneal dose of CP ( 150 mg/kg , i.p. )
.
Mice were then sacrificed under anesthesia , then lungs were removed for histopathological and biochemical investigations .
A single dose of CP markedly altered the levels of some oxidative stress biomarkers and resulted in the fragmentation of DNA in lung homogenates .
Histological examination of CP-treated mice demonstrated diffuse alveolar damage that involved apparent hyalinization of @ @ @ @ @ @ @ , and proliferation of type II pneumocytes .
The immunohistochemical results of CP-treated mice revealed strongly positive Bax and weakly positive proliferating cell nuclear antigen ( PCNA ) staining reactivity of the nuclei of the liningepithelium of the bronchioles and alveoli .
CP activated the cyclooxygenase-2/nuclear factor-kappa B pathway .
However , pre-treatment with RKs significantly attenuated CP-evoked alterations in the previously mentioned parameters , highlighting their antioxidant , anti-inflammatory , and anti-apoptotic potential .
RKs may be suggested to be a potential candidate to ameliorate CP-induced pulmonary toxicity .

Cyclophosphamide (CP) was found to have a potential toxic effect on lung tissues. Raspberry ketones (RKs) are natural antioxidant chemicals isolated from red raspberries (Rubus ideaus). They are commonly used for weight loss and obesity. The current study aimed to evaluate the possible protective effects of RKs against lung toxicity induced by CP. Mice were allocated into six groups: (1) control group; (2) CP group: received a single intraperitoneal dose of CP (150 mg/kg, i.p.); and (3-6) mice were pre-treated orally with different doses of RKs (25, 50, 100, and 200 mg/kg) for 14 consecutive days, respectively, before the administration of an intraperitoneal dose of CP (150 mg/kg, i.p.). Mice were then sacrificed under anesthesia, then lungs were removed for histopathological and biochemical investigations. A single dose of CP markedly altered the levels of some oxidative stress biomarkers and resulted in the fragmentation of DNA in lung homogenates. Histological examination of CP-treated mice demonstrated diffuse alveolar damage that involved apparent hyalinization of membranes, thickening of inter alveolar septa, and proliferation of type II pneumocytes. The immunohistochemical results of CP-treated mice revealed strongly positive Bax and weakly positive proliferating cell nuclear antigen (PCNA) staining reactivity of the nuclei of the liningepithelium of the bronchioles and alveoli. CP activated the cyclooxygenase-2/nuclear factor-kappa B pathway. However, pre-treatment with RKs significantly attenuated CP-evoked alterations in the previously mentioned parameters, highlighting their antioxidant, anti-inflammatory, and anti-apoptotic potential. RKs may be suggested to be a potential candidate to ameliorate CP-induced pulmonary toxicity.


greenmedinfo--2020-11-30--Repurposing of N-acetylcysteine for the treatment of dengue virus-induced acute liver failure.

The prevalence of dengue infection-induced acute liver damage is increasing from time to time .
Since it has no specific @ @ @ @ @ , people in endemic areas suffer more from dengue disorders .
Thus , there is @ @ @ @ @ for the treatment of dengue-induced acute liver failure .
N-acetylcysteine , which is used for @ @ @ @ @ disorder and paracetamol overdose toxicity , could be used as a definitive therapy for dengue @ @ @ @ @ Therefore , this review discusses the therapeutic use of N-acetylcysteine for dengue-induced acute liver disease @ @ @ @ @ case series showed that patients received NAC recovered from their clinical status .
Additionally , @ @ @ @ @ N-acetylcysteine has anti-dengue virus activity .
Thus , N-acetylcysteine could be used as a definitive @ @ @ @ @ .
This might encourage researchers to further investigate the importance of N-acetylcysteine for dengue virus-induced @ @

The prevalence of dengue infection-induced acute liver damage is increasing from time to time. Since it has no specific antiviral treatment in the world, people in endemic areas suffer more from dengue disorders. Thus, there is a need for searching options for the treatment of dengue-induced acute liver failure. N-acetylcysteine, which is used for the treatment of nasal congestion disorder and paracetamol overdose toxicity, could be used as a definitive therapy for dengue virus-induced acute liver disease. Therefore, this review discusses the therapeutic use of N-acetylcysteine for dengue-induced acute liver disease. Various case reports and case series showed that patients received NAC recovered from their clinical status. Additionally, a preclinical study showed that N-acetylcysteine has anti-dengue virus activity. Thus, N-acetylcysteine could be used as a definitive therapy in dengue virus-induced hepatitis. This might encourage researchers to further investigate the importance of N-acetylcysteine for dengue virus-induced hepatitis.


greenmedinfo--2020-11-30--Legacy effect of antioxidant N-acetylcysteine in cellular senescence of diet-induced obesity mice.

BACKGROUND : Cellular senescence is a state of stable growth arrest triggered by mitogenic and metabolic stressors .
Ageing and a high-fat diet ( HFD ) are proven inducers of senescence in various organs , presenting a challenge for ageing populations worldwide .
Our previous study demonstrated that ROS scavenger N-acetylcysteine ( NAC ) can improve insulin resistance ( IR ) and chronic inflammation in diet-induced obesity mice , an effect better achieved through early intervention .
We herein investigate whether NAC can improve cellular senescence in a diet-induced obesity mouse model , and whether a legacy effect is presented @ @ @ @ @ @ @ : For a twelve-month treatment course , all C57B/L6 mice were fed a chow diet ( CD ) , high-fat high sucrose diet ( HFD ) , CD+NAC1-12 ( NAC intervention 1st-12th month ) , HFD+NAC1-12 , and HFD+NAC1-6 ( NAC intervention 1st-6th month ) .
Statical analysis was used to analyze the different of markers of cellular senescence and inflammation .
RESULTS : Throughout the study , the HFD group exhibited significantly increased body weight ( BW ) and body fat , markers of senescence , decreased motor activity ( MA ) @ @ @ @ @ @ @ the HFD group , the HFD+NAC1-12 group exhibited increased MA , decreased BW and body fat , improved glucose tolerance , and decreased senescence markers .
The HFD+NAC1-6 group showed similar effects to the HFD+NAC1-12 group , despite discontinuing NAC for6 months .
Our study showed that NAC significantly increased MA in the both HFD+NAC1-12 and HFD+NAC1-6 groups , and improved HFD-induced mitochondrial and intracellular ROS expression , DNA and protein oxidative damage , and adipose tissue inflammation .
CONCLUSION : Legacy effect was indeed presented in HFD-induced cellular senescence with NAC intervention @ @ @ @ @ @ @ motor activity and anti-oxidative stress effects .

BACKGROUND: Cellular senescence is a state of stable growth arrest triggered by mitogenic and metabolic stressors. Ageing and a high-fat diet (HFD) are proven inducers of senescence in various organs, presenting a challenge for ageing populations worldwide. Our previous study demonstrated that ROS scavenger N-acetylcysteine (NAC) can improve insulin resistance(IR) and chronic inflammation in diet-induced obesity mice, an effect better achieved through early intervention. We herein investigate whether NAC can improve cellular senescence in a diet-induced obesity mouse model, and whether a legacy effect is presented with early intervention.
MATERIALS AND METHODS: For a twelve-month treatment course, all C57B/L6 mice were fed a chow diet (CD), high-fat high sucrose diet (HFD), CD+NAC1-12 (NAC intervention 1st-12th month), HFD+NAC1-12, and HFD+NAC1-6 (NAC intervention 1st-6th month). Statical analysis was used to analyze the different of markers of cellular senescence and inflammation.
RESULTS: Throughout the study, the HFD group exhibited significantly increased body weight (BW) and body fat, markers of senescence, decreased motor activity (MA) and impaired glucose tolerance. Compared to the HFD group, the HFD+NAC1-12 group exhibited increased MA, decreased BW and body fat, improved glucose tolerance, and decreased senescence markers. The HFD+NAC1-6 group showed similar effects to the HFD+NAC1-12 group, despite discontinuing NAC for6 months. Our study showed that NAC significantly increased MA in the both HFD+NAC1-12 and HFD+NAC1-6 groups, and improved HFD-induced mitochondrial and intracellular ROS expression, DNA and protein oxidative damage, and adipose tissue inflammation.
CONCLUSION: Legacy effect was indeed presented in HFD-induced cellular senescence with NAC intervention, with possible mechanisms being persistently increased motor activity and anti-oxidative stress effects.


greenmedinfo--2020-11-30--Comparative protective effects of N-acetylcysteine, and melatonin against obesity-induced testicular

Comparative protective effects of N-acetylcysteine, and melatonin against obesity-induced testicular dysfunction.

N-acetylcysteine ( NAC ) and melatonin were reported to exert protective effects on testicular tissues .
Thus , this study aimed to determine which of these is more efficient against obesity-induced testicular dysfunction in albino rats .
Total 32 adult male rats ( 195± 10g ) were divided into 4 groups : control , obese rats fed a high-fat diet ( HFD ) , HFD+ NAC ( 150 mg/kg/d , ip ) and HFD+melatonin ( 10 mg/kg/d , ip ) group , for five weeks .
Testes and epididymis were weighted .
Lipid profile , pituitary-testicular hormones , tumor necrosis @ @ @ @ @ @ @ parameters , testicular oxidant/antioxidant system , testicular and the epididymal histopathology , immunohistochemical localization for androgen receptors ( AR ) and Bax reaction were analyzed .
Administration of NAC or melatonin significantly improved the lipid parameters , gonadal hormones , TNFα level , sperm count and abnormal morphology , oxidant/antioxidant system and the absolute testicular and epididymal mass with an enhancement of testicular architecture , AR expression and apoptosis as compared to that in the obese group .
Additionally , as compared to the NAC group , the melanin group had significantly reduced @ @ @ @ @ @ @ and TNFα and increased testosterone , sperm count , motility , superoxide-dismutase activity , mitigated histo-morphometrical changes , BAX expression , and increased testicular AR expression .
Therefore , melatonin was more efficient than NAC in affording fortification against HFD-induced testicular dysfunction .

N-acetylcysteine (NAC) and melatonin were reported to exert protective effects on testicular tissues. Thus, this study aimed to determine which of these is more efficient against obesity-induced testicular dysfunction in albino rats. Total 32 adult male rats (195± 10g) were divided into 4 groups: control, obese rats fed a high-fat diet (HFD), HFD+ NAC (150 mg/kg/d, ip) and HFD+melatonin (10 mg/kg/d, ip) group, for five weeks. Testes and epididymis were weighted. Lipid profile, pituitary-testicular hormones, tumor necrosis factor-α (TNFα), epididymal sperm parameters, testicular oxidant/antioxidant system, testicular and the epididymal histopathology, immunohistochemical localization for androgen receptors (AR) and Bax reaction were analyzed. Administration of NAC or melatonin significantly improved the lipid parameters, gonadal hormones, TNFα level, sperm count and abnormal morphology, oxidant/antioxidant system and the absolute testicular and epididymal mass with an enhancement of testicular architecture, AR expression and apoptosis as compared to that in the obese group. Additionally, as compared to the NAC group, the melanin group had significantly reduced BMI, total cholesterol, triglyceride, and TNFα and increased testosterone, sperm count, motility, superoxide-dismutase activity, mitigated histo-morphometrical changes, BAX expression, and increased testicular AR expression. Therefore, melatonin was more efficient than NAC in affording fortification against HFD-induced testicular dysfunction.


greenmedinfo--2020-11-30--[VIDEO] 'TRUTH' With RFK, Jr. and Catherine Austin Fitts: How Wall Street Cashes in on Lockdowns

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This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
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greenmedinfo--2020-11-30--Could N-acetylcysteine improve the safety of clozapine?

Clozapine is an atypical antipsychotic indicated in patients with treatment-resistant schizophrenia which remains underused due to safety issues .
Mechanisms behind these adverse effects are complex and not fully understood .
They may involve immune-related mechanisms , direct toxic effects and oxidative stress .
Clozapine-induced oxidative stress might indeed notably be involved in the onset of neutropenia , agranulocytosis , myocarditis , sialorrhea , and metabolic alterations .
Therefore , the association of N-acetylcysteine ( NAC ) , an easily accessible , low-cost and well tolerated antioxidant drug could be of interest in clozapine-treated patients to improve clozapine safety .
@ @ @ @ @ @ @ could help to improve schizophrenia symptoms .
We believe that the use of NAC in the context of clozapine prescribing merits further study , as it could improve clozapine safety which may lead to a wider use and ultimately improve the healthcare of thousands of patients .
NAC could also secondarily show positive knock-on effects for the patients by improving clinical symptoms of schizophrenia in synergy with clozapine , and by reducing substance abuse and thus by improving the patient 's overall condition .
However , given the rarity of clozapine-induced severe adverse @ @ @ @ @ @ @ data ( e.g.
, National adverse events monitoring ) could assess the benefits of NAC on clozapine safety .

Clozapine is an atypical antipsychotic indicated in patients with treatment-resistant schizophrenia which remains underused due to safety issues. Mechanisms behind these adverse effects are complex and not fully understood. They may involve immune-related mechanisms, direct toxic effects and oxidative stress. Clozapine-induced oxidative stress might indeed notably be involved in the onset of neutropenia, agranulocytosis, myocarditis, sialorrhea, and metabolic alterations. Therefore, the association of N-acetylcysteine (NAC), an easily accessible, low-cost and well tolerated antioxidant drug could be of interest in clozapine-treated patients to improve clozapine safety. Furthermore, according to recent studies NAC could help to improve schizophrenia symptoms. We believe that the use of NAC in the context of clozapine prescribing merits further study, as it could improve clozapine safety which may lead to a wider use and ultimately improve the healthcare of thousands of patients. NAC could also secondarily show positive knock-on effects for the patients by improving clinical symptoms of schizophrenia in synergy with clozapine, and by reducing substance abuse and thus by improving the patient's overall condition. However, given the rarity of clozapine-induced severe adverse effects, only a large volume of data (e.g., National adverse events monitoring) could assess the benefits of NAC on clozapine safety.


greenmedinfo--2020-11-30--The effect of acetylcysteine on renal function in experimental models of cyclophosphamide-and ifosfa

The effect of acetylcysteine on renal function in experimental models of cyclophosphamide-and ifosfamide-induced cystitis.

Introduction : Urotoxicity is a characteristic attribute of cy-clophosphamide and ifosfamide .
Acetylcysteine is perceived as a uroprotective and possible nephroprotective compound .
The purpose of the study was to assess the effect of acetylcysteine treatment on the morphology of the kidneys and the urinary bladder , and renal function in rats with cystitis induced by cyclophosphamide or ifosfamide .
Methods : Cystitis was induced in rats belonging to groups 2 and 3 , as well as 4 and 5 , by five administrations of cyclophosphamide ( 75 mg/kg ) or ifosfamide ( 80 mg/kg ) respectively .
Additionally , @ @ @ @ @ @ @ 200 mg/kg ) .
Group 1 was '' sham treated '' as a control .
Upon conclusion of the experiment , the animals were euthanized and their kidneys and urinary bladders were collected for histopathological analysis .
The assessment of renal function was based on classic nitrogen blood parameters ( urea , creatinine , and uric acid ) , as well as proteinuria and cystatin C ( CysC ) and kidney injury molecule-1 ( KIM-1 ) urinary concentrations , and their 24-hour elimination with urine .
Results : Reduction of blood urea nitrogen @ @ @ @ @ @ @ with a significant increase of CysC and KIM-1 urinary concentrations , and their 24-hour elimination with urine were observed in groups 2 and 4 .
The acetylcysteine treatment did not cause a significant change of blood parameters , but significantly decreased 24-hour elimination of CysC and KIM-1 with urine , and accounted for alleviation of the histopathological abnormalities of urinary bladders , with no significant effects on the structure of the kidneys .
Conclusions : Acetylcysteine used in the experimental model of cyclophosphamide- and ifosfamide-induced cystitis had a uroprotective effect and also reduced @ @ @ @ @ @ @ use as a nephroprotective compound in cyclophosphamide/ifosfamide therapy .

Introduction: Urotoxicity is a characteristic attribute of cy-clophosphamide and ifosfamide. Acetylcysteine is perceived as a uroprotective and possible nephroprotective compound. The purpose of the study was to assess the effect of acetylcysteine treatment on the morphology of the kidneys and the urinary bladder, and renal function in rats with cystitis induced by cyclophosphamide or ifosfamide.
Methods: Cystitis was induced in rats belonging to groups 2 and 3, as well as 4 and 5, by five administrations of cyclophosphamide (75 mg/kg) or ifosfamide (80 mg/kg) respectively. Additionally, groups 3 and 5 received acetylcysteine (200 mg/kg). Group 1 was"sham treated"as a control. Upon conclusion of the experiment, the animals were euthanized and their kidneys and urinary bladders were collected for histopathological analysis. The assessment of renal function was based on classic nitrogen blood parameters (urea, creatinine, and uric acid), as well as proteinuria and cystatin C (CysC) and kidney injury molecule-1 (KIM-1) urinary concentrations, and their 24-hour elimination with urine.
Results: Reduction of blood urea nitrogen and uric acid, and urinary pH with a significant increase of CysC and KIM-1 urinary concentrations, and their 24-hour elimination with urine were observed in groups 2 and 4. The acetylcysteine treatment did not cause a significant change of blood parameters, but significantly decreased 24-hour elimination of CysC and KIM-1 with urine, and accounted for alleviation of the histopathological abnormalities of urinary bladders, with no significant effects on the structure of the kidneys.
Conclusions: Acetylcysteine used in the experimental model of cyclophosphamide- and ifosfamide-induced cystitis had a uroprotective effect and also reduced renal dysfunction, which suggests its potential use as a nephroprotective compound in cyclophosphamide/ifosfamide therapy.


greenmedinfo--2020-11-30--COVID Vaccine Hesitancy Widespread, Even Among Medical Professionals