greenmedinfo--2020-05-17--hnRNPA2B1 associated with recruitment of RNA into exosomes plays a key role in HSV-1 release from in

hnRNPA2B1 associated with recruitment of RNA into exosomes plays a key role in HSV-1 release from infected cells.

hnRNPA2B1 , an abundant cellular protein has been reported to recruit RNAs bearing a specific sequence ( EXO motif ) into exosomes .
We characterized an exosome population averaging 100+/- 50 nm in diameter and containing a defined set of constitutive exosome markers .
This population packages miRNAs and can be directed to block targeted gene expression in a dose dependent fashion .
The objectives of these studies were to characterize its role in the recruitment of miRNA .
We report 4 key findings ( i ) hnRNPA2B1 is not a component of exosomes produced in HEp-2 or in HEK293T @ @ @ @ @ @ @ at most to the site of exosome assembly but it is not itself incorporated into exosomes .
( ii ) The accumulation of exosomes produced by cells in which the gene encoding hnRNPA2B1 has been knocked out ( ΔhnRNPA2B1 ) was reduced 3 fold .
( iii ) In uninfected HEp-2 cells hnRNPA2B1 is localized in the nucleus .
In cells infected with herpes simplex virus 1 ( HSV-1 ) hnRNPA2B1 was quantitatively exported to the cytoplasm , at least a fraction of hnRNPA2B1 co-localized with a Golgi marker .
Lastly ( iv @ @ @ @ @ @ @ 2 to 3-fold reduction in virus yield but a significant ( > 10 fold ) reduction in the HSV-1 released through the apical surface into the extracellular environment .
The absence of hnRNPA2B1 had no significant impact on the basolateral export of HSV-1 from infected to uninfected cells by direct cell to cell contact .
The results suggest that hnRNPA2B1 plays a key role in the transport of enveloped virus from its site of assembly to the extracellular environment.In this report we show hnRNPA2B1 is not a component of exosomes produced in HEp-2 @ @ @ @ @ @ @ infected cells hnRNPA2B1 was quantitatively translocated from nucleus into the cytoplasm .
In infectedΔhnRNPA2B1 cells Golgi dependent transport of virus from the apical surface to the extracellular medium was significantly reduced .
In essence , this report supports the hypothesis that hnRNPA2B1 plays a key role in the egress of exosomes and of HSV-1 from infected cells .

hnRNPA2B1, an abundant cellular protein has been reported to recruit RNAs bearing a specific sequence (EXO motif) into exosomes. We characterized an exosome population averaging 100+/- 50 nm in diameter and containing a defined set of constitutive exosome markers. This population packages miRNAs and can be directed to block targeted gene expression in a dose dependent fashion. The objectives of these studies were to characterize its role in the recruitment of miRNA. We report 4 key findings (i) hnRNPA2B1 is not a component of exosomes produced in HEp-2 or in HEK293T cells. Hence hnRNPA2B1 carries its cargo at most to the site of exosome assembly but it is not itself incorporated into exosomes. (ii) The accumulation of exosomes produced by cells in which the gene encoding hnRNPA2B1 has been knocked out (ΔhnRNPA2B1) was reduced 3 fold. (iii) In uninfected HEp-2 cells hnRNPA2B1 is localized in the nucleus. In cells infected with herpes simplex virus 1 (HSV-1) hnRNPA2B1 was quantitatively exported to the cytoplasm, at least a fraction of hnRNPA2B1 co-localized with a Golgi marker. Lastly (iv) in ΔhnRNPA2B1 cells there was a 2 to 3-fold reduction in virus yield but a significant (>10 fold) reduction in the HSV-1 released through the apical surface into the extracellular environment. The absence of hnRNPA2B1 had no significant impact on the basolateral export of HSV-1 from infected to uninfected cells by direct cell to cell contact. The results suggest that hnRNPA2B1 plays a key role in the transport of enveloped virus from its site of assembly to the extracellular environment.In this report we show hnRNPA2B1 is not a component of exosomes produced in HEp-2 or in HEK293T cells. In HSV-1 infected cells hnRNPA2B1 was quantitatively translocated from nucleus into the cytoplasm. In infectedΔhnRNPA2B1 cells Golgi dependent transport of virus from the apical surface to the extracellular medium was significantly reduced. In essence, this report supports the hypothesis that hnRNPA2B1 plays a key role in the egress of exosomes and of HSV-1 from infected cells.


greenmedinfo--2020-05-17--Bill Gates and the Population Control Grid

The unimaginable wealth that Gates has accrued is now being used to purchase something much more useful : control .
@ @ @ @ @ global health bodies that can coordinate a worldwide vaccination program , or the governments that @ @ @ @ @ campaign , but control over the global population itself .
This is Part III of @ @ @ @ @ on the questionable origin of Bill Gates in global public health today .
Watch the @ @ @ @ @ .
Please support the work of James Corbett and the Corbett Report .
They have @ @ @ @ @ funders beyond the micro-donations made by you and me !
You can become a member @ @ @ @ @ 1 a month .

Visit our Re-post guidelines This article is copyrighted by GreenMedInfo LLC, 2020
The unimaginable wealth that Gates has accrued is now being used to purchase something much more useful: control. Control not just of the global health bodies that can coordinate a worldwide vaccination program, or the governments that will mandate such an unprecedented campaign, but control over the global population itself.
This is Part III of a series by James Corbett on the questionable origin of Bill Gates in global public health today. Watch the rest of the series here.
Please support the work of James Corbett and the Corbett Report. They have no hidden agendas or primary funders beyond the micro-donations made by you and me! You can become a member for as little as $1 a month.


greenmedinfo--2020-05-17--Exosomes facilitate transmission of Enterovirus A71 from human intestinal epithelial cells.

Enterovirus A71 ( EV-A71 ) has been noted for its tendency to lead to neurological manifestations in young children and @ @ @ @ @ tract has been identified as the primary replication site of this virus , how EV-A71 @ @ @ @ @ is transmitted to other organs remains unclear .
By using differentiated C2BBe1 cells as a @ @ @ @ @ intestinal epithelial cells ( IECs ) were permissive to EV-A71 infection and viral particles were @ @ @ @ @ .
The coexistence of active caspase 3 and EV-A71 protein was observed in the infected @ @ @ @ @ but not in the infected and differentiated C2BBe1 cells .
Furthermore , EV-A71 infection caused @ @ @ @ @ to secrete exosomes containing viral components and have the ability to establish active infection .
@ @ @ @ @ decreased EV-A71 replication and release in vitro and increased the survival rates of infected animals @ @ @ @ @ EV-A71 is able to be actively replicated in enterocytes , and that the exosome pathway @ @ @ @ @ release of viral particles , which may be useful for developing antiviral strategies .

Enterovirus A71 (EV-A71) has been noted for its tendency to lead to neurological manifestations in young children and infants. Although the alimentary tract has been identified as the primary replication site of this virus, how EV-A71 replicates in the gut and is transmitted to other organs remains unclear. By using differentiated C2BBe1 cells as a model, we observed that intestinal epithelial cells (IECs) were permissive to EV-A71 infection and viral particles were released in a nonlytic manner. The coexistence of active caspase 3 and EV-A71 protein was observed in the infected undifferentiated C2BBe1 and RD cells but not in the infected and differentiated C2BBe1 cells. Furthermore, EV-A71 infection caused differentiated C2BBe1 and intestinal organoids to secrete exosomes containing viral components and have the ability to establish active infection. Inhibition of the exosome pathway decreased EV-A71 replication and release in vitro and increased the survival rates of infected animals. Our findings showed that EV-A71 is able to be actively replicated in enterocytes, and that the exosome pathway is involved in the nonlytic release of viral particles, which may be useful for developing antiviral strategies.


greenmedinfo--2020-05-17--Exosomes from EV71-infected oral epithelial cells can transfer miR-30a to promote EV71 infection.

OBJECTIVE : As an extracellular vesicle , exosomes can release from virus-infected cells containing various viral or host cellular elements and could stimulate recipient 's cellular response .
Enterovirus 71 ( EV71 ) , a single-strand positive-sense RNA virus , is known to cause hand , foot , and mouth disease ( HFMD ) in children and bring about severe clinical diseases .
METHODS : Separated the human oral epithelial cells ( OE cells ) from normal buccal mucosa through enzyme digestion .
Performed a comprehensive miRNA profiling in exosomes from EV71-infected OE cells through deep small RNA-seq .
Using @ @ @ @ @ @ @ Array profiles to explore the interactions of innate immune signaling networks with exosomal miR-30a .
Knocked out the MyD88 gene in macrophages using CRISPR/Cas9-mediated genome editing method .
RESULTS : Our study demonstrated that the miR-30a was preferentially enriched in exosomes that released from EV71-infected human oral epithelial cells through small RNA-seq .
We found that the transfer of exosomal miR-30a to macrophages could suppress typeⅠ interferon response through targeting myeloid differentiation factor 88 ( MyD88 ) and subsequently facilitate the viral replication .
CONCLUSIONS : Exosomes released from EV71-infected OE cells selectively @ @ @ @ @ @ @ be functionally transferred to the recipient macrophages resulted in targeting MyD88 and subsequently inhibited type I interferon production in receipt cells , thus promoting the EV71 replication .

OBJECTIVE: As an extracellular vesicle, exosomes can release from virus-infected cells containing various viral or host cellular elements and could stimulate recipient's cellular response. Enterovirus 71 (EV71), a single-strand positive-sense RNA virus, is known to cause hand, foot, and mouth disease (HFMD) in children and bring about severe clinical diseases.
METHODS: Separated the human oral epithelial cells (OE cells) from normal buccal mucosa through enzyme digestion. Performed a comprehensive miRNA profiling in exosomes from EV71-infected OE cells through deep small RNA-seq. Using the Human Antiviral Response RT Profiler PCR Array profiles to explore the interactions of innate immune signaling networks with exosomal miR-30a. Knocked out the MyD88 gene in macrophages using CRISPR/Cas9-mediated genome editing method.
RESULTS: Our study demonstrated that the miR-30a was preferentially enriched in exosomes that released from EV71-infected human oral epithelial cells through small RNA-seq. We found that the transfer of exosomal miR-30a to macrophages could suppress typeⅠ interferon response through targeting myeloid differentiation factor 88 (MyD88) and subsequently facilitate the viral replication.
CONCLUSIONS: Exosomes released from EV71-infected OE cells selectively packaged high level of miR-30a that can be functionally transferred to the recipient macrophages resulted in targeting MyD88 and subsequently inhibited type I interferon production in receipt cells, thus promoting the EV71 replication.


greenmedinfo--2020-05-17--Dancing with Trojan horses: an interplay between the extracellular vesicles and viruses.

Extracellular vesicles ( EVs ) are membrane-encapsulated particles released by eukaryotic and prokaryotic cells into the extracellular environment .
Depending on their origin , size , and composition , EVs are grouped in several classes , with one of them being exosomes , which are small EVs ( SEVs ) generated within the endosomal compartment of eukaryotic cells via the unique multivesicular body pathway .
Being able to deliver their content ( proteins , lipids , small molecules , and nucleic acids ) to other cells , exosomes/SEVs are considered as bioactive vesicles with multiple biological functions .
Importantly , @ @ @ @ @ @ @ cell and tissue of origin including a set of specific proteins .
However , the pathological conditions may lead to the appearance of diseases-specific exosomes/SEVs containing pathology-specific cargoes utilized in the malicious cell-cell communication and spread of malady .
Viruses demonstrate complex 'dancing ' around the exosome biogenesis system , being able to hijack the host systems responsible for the exosome biogenesis .
They use the exosome biogenesis system to promote packaging of their capsids , regulate virion production , and virus secretion .
They also utilize a Trojan horse stratagem to place @ @ @ @ @ @ @ spread beyond their normal range of cell hosts using the normal EV uptake process .
Another illustration of the virus-based utilization of Trojan horse strategy is given by the ability of human viruses to use exosomes/SEVs as carriers of their exogenous miRNA or viral proteins to the non-infected cells .
Taken together , these strategies of dancing with Trojan horses can help viruses to fight with the host defense and to spread the infection.Communicated by Ramaswamy H. Sarma .

Extracellular vesicles (EVs) are membrane-encapsulated particles released by eukaryotic and prokaryotic cells into the extracellular environment. Depending on their origin, size, and composition, EVs are grouped in several classes, with one of them being exosomes, which are small EVs (SEVs) generated within the endosomal compartment of eukaryotic cells via the unique multivesicular body pathway. Being able to deliver their content (proteins, lipids, small molecules, and nucleic acids) to other cells, exosomes/SEVs are considered as bioactive vesicles with multiple biological functions. Importantly, the composition of exosomes/SEVs depends on the cell and tissue of origin including a set of specific proteins. However, the pathological conditions may lead to the appearance of diseases-specific exosomes/SEVs containing pathology-specific cargoes utilized in the malicious cell-cell communication and spread of malady. Viruses demonstrate complex 'dancing' around the exosome biogenesis system, being able to hijack the host systems responsible for the exosome biogenesis. They use the exosome biogenesis system to promote packaging of their capsids, regulate virion production, and virus secretion. They also utilize a Trojan horse stratagem to place virions inside the SEVs and thereby to spread beyond their normal range of cell hosts using the normal EV uptake process. Another illustration of the virus-based utilization of Trojan horse strategy is given by the ability of human viruses to use exosomes/SEVs as carriers of their exogenous miRNA or viral proteins to the non-infected cells. Taken together, these strategies of dancing with Trojan horses can help viruses to fight with the host defense and to spread the infection.Communicated by Ramaswamy H. Sarma.


greenmedinfo--2020-05-17--Exosomes as immune regulators in head and neck cancer.

Exosomes , virus-sized nanovesicles , are utilized as messenger systems of our body to communicate with other body cells and @ @ @ @ @ all cells produce exosomes and are able to interact with immune cells in the blood @ @ @ @ @ .
Different markers on the surface of exosomes are necessary for immune cell adhesion and @ @ @ @ @ types of exosome-immune cell interaction , such as surface receptor contact and phagocytosis , are @ @ @ @ @ different cargos , exosomes affect different immune cell types in head and neck cancers : @ @ @ @ @ , natural killer cells , macrophages , and dendritic cells have been described in this @ @ @ @ @ , a combined analysis of different parameters including protein amount , nucleic acid/protein expression , @ @ @ @ @ exosomes could empower exosomes asuseful tools for evaluation of tumor promotion and progression in the @ @

Exosomes, virus-sized nanovesicles, are utilized as messenger systems of our body to communicate with other body cells and regulate immune functions. Almost all cells produce exosomes and are able to interact with immune cells in the blood stream and peripheral body areas. Different markers on the surface of exosomes are necessary for immune cell adhesion and interaction. Furthermore, many types of exosome-immune cell interaction, such as surface receptor contact and phagocytosis, are known. As carriers of different cargos, exosomes affect different immune cell types in head and neck cancers: So far, T cells, natural killer cells, macrophages, and dendritic cells have been described in this context. For diagnostic purposes, a combined analysis of different parameters including protein amount, nucleic acid/protein expression, and the immunosuppressive impact of exosomes could empower exosomes asuseful tools for evaluation of tumor promotion and progression in the future.


greenmedinfo--2020-05-20--Should You Wear a Mask to Prevent COVID-19?

States are increasingly mandating the use of face masks in public places , but evidence suggests face coverings do little to reduce risk of illness and , in some cases , may even increase your likelihood of contamination .
As recently as February 29 , 2020 , U.S .
Surgeon General Jerome Adams tweeted , “ Seriously people — STOP BUYING MASKS !
They are NOT effective in preventing general public from catching coronavirus … ” [ i ] Yet , in a dramatic about-face , weeks later the U.S. Centers for Disease Control and Prevention ( CDC ) said @ @ @ @ @ @ @ public settings where social distancing measures are difficult to maintain , especially in areas with significant community-based transmission , and stated , “ CDC also advises the use of simple cloth face coverings to slow the spread of the virus and help people who may have the virus and do not know it from transmitting it to others.
” [ ii ] At the state level , an increasing number of states have put in place recommendations and requirements for workers and customers to wear face masks in public .
In Illinois , @ @ @ @ @ @ @ wear a mask basically anytime they leave their home , including while shopping at grocery stores , getting food from drive thrus or curbside pickups , visiting a health care provider or traveling on public transportation .
[ iii ] In a statement released by the Illinois State Police , it ’ s stated , “ Illinois State Police will work with local law enforcement to enforce this order but adhering to the order will save lives and it is the responsibility of every Illinoisan to do their part.
” [ iv ] @ @ @ @ @ @ @ , Texas , it ’ s been said that failing to wear masks in public could result in a $ 1,000 fine , [ v ] an order that ’ s being challenged in court for being unconstitutional .
[ vi ] But as widespread advice to wear masks proliferates the U.S. — and a police state to enforce their wearing grows — the question remains : does wearing a mask really prevent the spread of COVID-19 ?
The idea of wearing a face mask , according to the CDC , is not @ @ @ @ @ @ @ but rather to benefit the population overall .
If you ’ re infected with COVID-19 and don ’ t have symptoms , the theory is that wearing a mask could prevent you from inadvertently infecting someone else when you ’ re out and about .
[ vii ] Studies , however , don ’ t bear this out .
In a May 2020 systematic review published in Emerging Infectious Diseases — a journal published by the CDC — researchers identified 10 trials that reported estimates of the effectiveness of face masks in reducing @ @ @ @ @ @ @ “ In pooled analysis , ” they stated , “ we found no significant reduction in influenza transmission with the use of face masks.
” [ viii ] This included a study of face mask use among pilgrims from Australia during the Hajj pilgrimage — no major difference in the risk of influenza infection was found between the mask wearers and non-mask wearers .
Two studies in university settings were also included , looking into the effectiveness of face masks among student hall residents for five months .
“ The overall reduction in @ @ @ @ @ @ @ influenza cases in the face mask group was not significant in either studies , ” the researchers found .
[ ix ] A study of four patients with COVID-19 led to similar results — that wearing masks does little to block SARS-Cov-2 , the virus that causes COVID-19 .
[ x ] Researchers asked the patients to cough five times into a petri dish while wearing no mask , a surgical mask and then a cotton mask .
They swabbed the inner and outer mask surfaces afterward , finding that while most swabs @ @ @ @ @ @ @ for SARS-CoV-2 , all swabs from the outer mask surfaces were positive .
This raises two important points .
First , as the study noted , “ Neither surgical nor cotton masks effectively filtered SARS-CoV-2 during coughs by infected patients.
” Second , the fact that the outer surface was more contaminated highlights the problems that can occur if a person touches the outside of their mask — thereby contaminating their hands .
It ’ s possible that air leakage around the edge of the mask allowed the outer mask to become contaminated @ @ @ @ @ @ @ SARS-CoV-2 were able to penetrate the masks .
Either way , “ [ t ] hese observations support the importance of hand hygiene after touching the outer surface of masks , ” according to the researchers , but the likelihood of the general public , including children , washing their hands every time they touch their mask is small .
A 2010 study added that while some evidence suggests wearing masks or respirators when you ’ re ill may protect others , there is less evidence on mask wearing to prevent becoming infected @ @ @ @ @ @ @ In conclusion there remains a substantial gap in the scientific literature on the effectiveness of face masks to reduce transmission of influenza virus infection .
While there is some experimental evidence that masks should be able to reduce infectiousness under controlled conditions , there is less evidence on whether this translates to effectiveness in natural settings .
There is little evidence to support the effectiveness of face masks to reduce the risk of infection.
” [ xi ] If COVID-19 Is Aerosolized , Surgical and Cotton Masks Ineffective The idea of cloth face @ @ @ @ @ @ @ idea that COVID-19 is primarily spread via large respiratory droplets .
Research now suggests , however , that SARS-CoV-2 may remain suspended in aerosols for up to 16 hours .
[ xii ] It ’ s also been found that COVID-19 particles may be as small as 1 to 4 microns in size , [ xiii ] while surgical masks only protect against particles larger than 100 microns .
[ xiv ] , [ xv ] Again , surgical masks are intended to protect the wearer against large droplets or splashes of bodily @ @ @ @ @ @ @ wearer ’ s respiratory emissions .
Even the CDC states that surgical masks do “ not provide the wearer with a reliable level of protection from inhaling smaller airborne particles and is not considered respiratory protection.
” [ xvi ] On the contrary , an N95 respirator is a type of mask with a tight-fitting face seal designed for health care workers who may be exposed to hazardous small particle aerosols .
In the case of respiratory virus and influenza , rates of infection were double among those wearing surgical masks compared to @ @ @ @ @ @ @ ] This suggests N95 respirators offer some protection , but not only are they in short supply , they ’ re only typically worn by health care providers performing certain high-risk procedures .
The Emerging Infectious Diseases review pointed out that in lower-income settings reusable cloth masks are more likely to be used than disposable medical masks due to cost and availability .
Indeed , reusable cloth masks are what ’ s being promoted across much of the U.S. , even though research is scarce into the use of such masks , and @ @ @ @ @ @ @ could backfire .
“ Proper use of face masks is essential because improper use might increase the risk for transmission , ” according to the study .
[ xviii ] Speaking with Forbes , Dr. Eli Perencevich , a professor of medicine and epidemiology at the University of Iowa ’ s College of Medicine , agreed : “ The average healthy person does not need to have a mask , and they shouldn ’ t be wearing masks … There ’ s no evidence that wearing masks on healthy people will protect them @ @ @ @ @ @ @ they can increase the risk of infection because they ’ re touching their face more often.
” [ xix ] “ Wearing a mask is tricky , ” he added , “ because it can create a false sense of security .
If you don ’ t wash your hands before you take off the mask and after you take off your mask , you could increase your risk.
” [ xx ] There are some risks inherent to wearing a mask , as well , such as hypoxia .
One study found @ @ @ @ @ @ @ arterial pulsations ( SpO2 ) and a slight increase in pulse rates among surgeons wearing a surgical mask , and the decrease was more prominent in surgeons over the age of 35 .
[ xxi ] The risks may be higher for N95 respirators , which may impede gaseous exchange and increase workload on the metabolic system , particularly in pregnant health care workers .
“ The benefits of using N95 mask to prevent serious emerging infectious diseases should be weighed against potential respiratory consequences associated with extended N95 respirator usage , ” @ @ @ @ @ @ @ , [ xxiii ] dizziness , shortness of breath and even reduced working efficiency and ability to make correct decisions are also common following prolonged usage of N95 respirators .
[ xxiv ] Even WHO Warns of Mask Risks The World Health Organization ( WHO ) , while recommending that people with symptoms wear a medical mask , states , “ the wide use of masks by healthy people in the community setting is not supported by current evidence and carries uncertainties and critical risks.
” They also warn that the following potential @ @ @ @ @ @ @ [ xxv ] · Self-contamination that can occur by touching and reusing contaminated masks · Potential breathing difficulties , depending on type of mask used · False sense of security , leading to potentially less adherence to other preventive measures , such as physical distancing and hand hygiene · Diversion of mask supplies and consequent shortage of masks for health care workers · Diversion of resources from effective public health measures , such as hand hygiene The potential benefits of mask wearing become even more dubious when it comes to the cloth masks @ @ @ @ @ @ @ .
In a 2015 study led by Raina MacIntyre at the University of New South Wales in Sydney , 1,607 health care workers in Vietnam were given either disposable medical masks or reusable cloth masks that could be washed at home at the end of the day .
[ xxvi ] Penetration of cloth masks by particles was almost 97 % , compared to 44 % for medical masks , and those who wore cloth masks were much more likely to be infected with a virus .
The results were so poor that @ @ @ @ @ @ @ cloth masks in a health care setting , stating that moisture retention , reuse of cloth masks and poor filtration could increase infection risk , and researchers stated , “ Further research is needed to inform the widespread use of cloth masks globally.
” [ xxvii ] “ There 's just not a lot of evidence for cloth masks in the community , ” MacIntyre told New Scientist .
[ xxviii ] In Finland , meanwhile , COVID-19 restrictions are being eased without the recommendation for widespread mask wearing .
Since research findings @ @ @ @ @ @ @ , the government intends to conduct a detailed study before recommending that the general population wear them .
[ xxix ] While the evidence for wearing masks remains scarce , opposition to mask wearing is mounting among Americans , with reasons ranging from not believing it ’ s necessary to feeling it ’ s unjust for the government to force people to wear a face covering .
[ xxx ] Such moral and ethical controversies are likely to continue , especially since masks may fail to protect people from illness as intended .
@ @ @ @ @ @ @ of Cloth Face Coverings to Help Slow the Spread of COVID-19 [ iii ] Illinois Department of Public Health , Guidance on the Use of Masks by the General Public [ xxv ] World Health Organization April 6 , 2020 , Advice on the use of masks in the context of COVID-19

Visit our Re-post guidelines This article is copyrighted by GreenMedInfo LLC, 2020
States are increasingly mandating the use of face masks in public places, but evidence suggests face coverings do little to reduce risk of illness and, in some cases, may even increase your likelihood of contamination.
As recently as February 29, 2020, U.S. Surgeon General Jerome Adams tweeted, “Seriously people — STOP BUYING MASKS! They are NOT effective in preventing general public from catching coronavirus … ”[i]
Yet, in a dramatic about-face, weeks later the U.S. Centers for Disease Control and Prevention (CDC) said they recommend wearing cloth face coverings in public settings where social distancing measures are difficult to maintain, especially in areas with significant community-based transmission, and stated, “CDC also advises the use of simple cloth face coverings to slow the spread of the virus and help people who may have the virus and do not know it from transmitting it to others.”[ii]
At the state level, an increasing number of states have put in place recommendations and requirements for workers and customers to wear face masks in public. In Illinois, for instance, everyone is advised to wear a mask basically anytime they leave their home, including while shopping at grocery stores, getting food from drive thrus or curbside pickups, visiting a health care provider or traveling on public transportation.[iii]
In a statement released by the Illinois State Police, it’s stated, “Illinois State Police will work with local law enforcement to enforce this order but adhering to the order will save lives and it is the responsibility of every Illinoisan to do their part.”[iv] In other locales, like Harris County, Texas, it’s been said that failing to wear masks in public could result in a $1,000 fine,[v] an order that’s being challenged in court for being unconstitutional.[vi]
But as widespread advice to wear masks proliferates the U.S. — and a police state to enforce their wearing grows — the question remains: does wearing a mask really prevent the spread of COVID-19?
Face Masks Led to ‘No Significant Reduction’ in Virus Transmission
The idea of wearing a face mask, according to the CDC, is not so much to protect the wearer, but rather to benefit the population overall. If you’re infected with COVID-19 and don’t have symptoms, the theory is that wearing a mask could prevent you from inadvertently infecting someone else when you’re out and about.[vii]
Studies, however, don’t bear this out. In a May 2020 systematic review published in Emerging Infectious Diseases — a journal published by the CDC — researchers identified 10 trials that reported estimates of the effectiveness of face masks in reducing cases of influenza in the community. “In pooled analysis,” they stated, “we found no significant reduction in influenza transmission with the use of face masks.”[viii]
This included a study of face mask use among pilgrims from Australia during the Hajj pilgrimage — no major difference in the risk of influenza infection was found between the mask wearers and non-mask wearers. Two studies in university settings were also included, looking into the effectiveness of face masks among student hall residents for five months.
“The overall reduction in ILI [influenza-like illness] or laboratory-confirmed influenza cases in the face mask group was not significant in either studies,” the researchers found.[ix]
Surgical Masks, Cotton Masks Ineffective at Filtering SARS-Cov-2
A study of four patients with COVID-19 led to similar results — that wearing masks does little to block SARS-Cov-2, the virus that causes COVID-19.[x] Researchers asked the patients to cough five times into a petri dish while wearing no mask, a surgical mask and then a cotton mask. They swabbed the inner and outer mask surfaces afterward, finding that while most swabs from the inner mask surfaces were negative for SARS-CoV-2, all swabs from the outer mask surfaces were positive.
This raises two important points. First, as the study noted, “Neither surgical nor cotton masks effectively filtered SARS-CoV-2 during coughs by infected patients.” Second, the fact that the outer surface was more contaminated highlights the problems that can occur if a person touches the outside of their mask — thereby contaminating their hands. It’s possible that air leakage around the edge of the mask allowed the outer mask to become contaminated, or that the small aerosols of SARS-CoV-2 were able to penetrate the masks.
Either way, “[t]hese observations support the importance of hand hygiene after touching the outer surface of masks,” according to the researchers, but the likelihood of the general public, including children, washing their hands every time they touch their mask is small. A 2010 study added that while some evidence suggests wearing masks or respirators when you’re ill may protect others, there is less evidence on mask wearing to prevent becoming infected, especially in real-world settings:
“In conclusion there remains a substantial gap in the scientific literature on the effectiveness of face masks to reduce transmission of influenza virus infection.
While there is some experimental evidence that masks should be able to reduce infectiousness under controlled conditions, there is less evidence on whether this translates to effectiveness in natural settings. There is little evidence to support the effectiveness of face masks to reduce the risk of infection.”[xi]
If COVID-19 Is Aerosolized, Surgical and Cotton Masks Ineffective
The idea of cloth face coverings preventing transmission was based on the idea that COVID-19 is primarily spread via large respiratory droplets. Research now suggests, however, that SARS-CoV-2 may remain suspended in aerosols for up to 16 hours.[xii]
It’s also been found that COVID-19 particles may be as small as 1 to 4 microns in size,[xiii] while surgical masks only protect against particles larger than 100 microns.[xiv],[xv] Again, surgical masks are intended to protect the wearer against large droplets or splashes of bodily fluids, while protecting others from the wearer’s respiratory emissions.
Even the CDC states that surgical masks do “not provide the wearer with a reliable level of protection from inhaling smaller airborne particles and is not considered respiratory protection.”[xvi] On the contrary, an N95 respirator is a type of mask with a tight-fitting face seal designed for health care workers who may be exposed to hazardous small particle aerosols.
In the case of respiratory virus and influenza, rates of infection were double among those wearing surgical masks compared to those wearing N95 respirators.[xvii] This suggests N95 respirators offer some protection, but not only are they in short supply, they’re only typically worn by health care providers performing certain high-risk procedures.
Wearing a Mask May Increase Virus Transmission, Cause Adverse Effects
The Emerging Infectious Diseases review pointed out that in lower-income settings reusable cloth masks are more likely to be used than disposable medical masks due to cost and availability. Indeed, reusable cloth masks are what’s being promoted across much of the U.S., even though research is scarce into the use of such masks, and wearing them the “wrong” way could backfire.
“Proper use of face masks is essential because improper use might increase the risk for transmission,” according to the study.[xviii] Speaking with Forbes, Dr. Eli Perencevich, a professor of medicine and epidemiology at the University of Iowa’s College of Medicine, agreed:
“The average healthy person does not need to have a mask, and they shouldn’t be wearing masks … There’s no evidence that wearing masks on healthy people will protect them. They wear them incorrectly, and they can increase the risk of infection because they’re touching their face more often.”[xix]
“Wearing a mask is tricky,” he added, “because it can create a false sense of security. If you don’t wash your hands before you take off the mask and after you take off your mask, you could increase your risk.”[xx] There are some risks inherent to wearing a mask, as well, such as hypoxia.
One study found a decrease in the oxygen saturation of arterial pulsations (SpO2) and a slight increase in pulse rates among surgeons wearing a surgical mask, and the decrease was more prominent in surgeons over the age of 35.[xxi] The risks may be higher for N95 respirators, which may impede gaseous exchange and increase workload on the metabolic system, particularly in pregnant health care workers.
“The benefits of using N95 mask to prevent serious emerging infectious diseases should be weighed against potential respiratory consequences associated with extended N95 respirator usage,” researchers concluded.[xxii] Headaches,[xxiii] dizziness, shortness of breath and even reduced working efficiency and ability to make correct decisions are also common following prolonged usage of N95 respirators.[xxiv]
Even WHO Warns of Mask Risks
The World Health Organization (WHO), while recommending that people with symptoms wear a medical mask, states, “the wide use of masks by healthy people in the community setting is not supported by current evidence and carries uncertainties and critical risks.” They also warn that the following potential risks should be taken into account:[xxv]
· Self-contamination that can occur by touching and reusing contaminated masks
· Potential breathing difficulties, depending on type of mask used
· False sense of security, leading to potentially less adherence to other preventive measures, such as physical distancing and hand hygiene
· Diversion of mask supplies and consequent shortage of masks for health care workers
· Diversion of resources from effective public health measures, such as hand hygiene
The potential benefits of mask wearing become even more dubious when it comes to the cloth masks now being widely used across the U.S. In a 2015 study led by Raina MacIntyre at the University of New South Wales in Sydney, 1,607 health care workers in Vietnam were given either disposable medical masks or reusable cloth masks that could be washed at home at the end of the day.[xxvi]
Penetration of cloth masks by particles was almost 97%, compared to 44% for medical masks, and those who wore cloth masks were much more likely to be infected with a virus. The results were so poor that the study cautioned against the use of cloth masks in a health care setting, stating that moisture retention, reuse of cloth masks and poor filtration could increase infection risk, and researchers stated, “Further research is needed to inform the widespread use of cloth masks globally.”[xxvii]
“There's just not a lot of evidence for cloth masks in the community,” MacIntyre told New Scientist.[xxviii] In Finland, meanwhile, COVID-19 restrictions are being eased without the recommendation for widespread mask wearing. Since research findings into the benefits of face masks vary, the government intends to conduct a detailed study before recommending that the general population wear them.[xxix]
While the evidence for wearing masks remains scarce, opposition to mask wearing is mounting among Americans, with reasons ranging from not believing it’s necessary to feeling it’s unjust for the government to force people to wear a face covering.[xxx] Such moral and ethical controversies are likely to continue, especially since masks may fail to protect people from illness as intended.


greenmedinfo--2020-05-19--The leaves of M. oleifera have antimicrobial phytochemicals.

Moringa oleifera is a tree native to tropical and subtropical regions of South India and used in traditional medicine .
@ @ @ @ @ was characterize the phytochemicals present in M. oleifera leaf extracts and study their antimicrobial activities @ @ @ @ @ apparatus of leaves were obtained using hexane , benzene , isopropanol , methanol , and @ @ @ @ @ were concentrated and screened for qualitative phytochemical analysis , and the antibacterial , antifungal and @ @ @ @ @ were measured by in vitro methods .
Alkaloids , carbohydrates , tannins , phenolic compounds @ @ @ @ @ , amino acids , oils and fats were found in the different crude extracts analyzed @ @ @ @ @ showed antibacterial activity against all selected bacteria , hexane and benzene extracts showed antifungal activity @ @ @ @ @ and hexane , benzene and isopropanol extracts showed activity against Hepatitis B virus .
In @ @ @ @ @ M. oleifera have antimicrobial phytochemicals .

Moringa oleifera is a tree native to tropical and subtropical regions of South India and used in traditional medicine. The aim of this study was characterize the phytochemicals present in M. oleifera leaf extracts and study their antimicrobial activities. Solvent extractions with Soxhlet apparatus of leaves were obtained using hexane, benzene, isopropanol, methanol, and water. The crude extracts were concentrated and screened for qualitative phytochemical analysis, and the antibacterial, antifungal and antiviral activities of crude extracts were measured by in vitro methods. Alkaloids, carbohydrates, tannins, phenolic compounds, terpenoids, cardiac glycosides, amino acids, oils and fats were found in the different crude extracts analyzed. Water and methanol extracts showed antibacterial activity against all selected bacteria, hexane and benzene extracts showed antifungal activity against all fungi tested, and hexane, benzene and isopropanol extracts showed activity against Hepatitis B virus. In conclusion, the leaves of M. oleifera have antimicrobial phytochemicals.


greenmedinfo--2020-05-19--These results provided a scientific approach for using Moringa oleifera leaves as an alternative the

Malignant melanoma is a very aggressive and serious type of cutaneous cancer .
Previous studies indicated the anti-cancer activity of aqueous extract of Moringa oleifera Lam .
leaves ( MOE ) against a variety of cell lines .
However , there has not been much research about the effect of MOE on melanoma .
Therefore , this study was about to investigate the anti-proliferation mediated by apoptosis of MOE on human melanoma cell lines .
Furthermore , the related molecular mechanisms of the apoptosis were also examined .
An aqueous extract of Moringa oleifera leaves was prepared and the anti-proliferative @ @ @ @ @ @ @ was tested using WST-1 assay .
The apoptotic hallmarks including DNA condensation and phosphatidylserine ( PS ) externalization were assessed .
The expression of apoptosis-related genes and the depolarization of mitochondrial membrane potential were then examined to clarify the underlying molecular mechanisms .
MOE inhibited cell growth of A375 cells and A2058 cells in a dose-dependent manner but had little effect on human normal fibroblasts .
The cell growth inhibition was induced by apoptosis which was expressed via chromatin condensation and PS externalization .
MOE decreased mitochondrial membrane potential .
Additionally , MOE @ @ @ @ @ @ @ Caspase-9 , PARP and AIF translocation , leading to apoptotic cell death .
Our study indicated that MOE exerted significant anti-cancer effects on melanoma cells in vitro which involved mitochondria-mediated Caspase-dependent and Caspase-independent apoptosis pathways .
These results provided a scientific approach for using Moringa oleifera leaves as an alternative therapy to treat skin cancer .

Malignant melanoma is a very aggressive and serious type of cutaneous cancer. Previous studies indicated the anti-cancer activity of aqueous extract of Moringa oleifera Lam. leaves (MOE) against a variety of cell lines. However, there has not been much research about the effect of MOE on melanoma. Therefore, this study was about to investigate the anti-proliferation mediated by apoptosis of MOE on human melanoma cell lines. Furthermore, the related molecular mechanisms of the apoptosis were also examined. An aqueous extract of Moringa oleifera leaves was prepared and the anti-proliferative activity on melanoma cells and normal cells was tested using WST-1 assay. The apoptotic hallmarks including DNA condensation and phosphatidylserine (PS) externalization were assessed. The expression of apoptosis-related genes and the depolarization of mitochondrial membrane potential were then examined to clarify the underlying molecular mechanisms. MOE inhibited cell growth of A375 cells and A2058 cells in a dose-dependent manner but had little effect on human normal fibroblasts. The cell growth inhibition was induced by apoptosis which was expressed via chromatin condensation and PS externalization. MOE decreased mitochondrial membrane potential. Additionally, MOE increased Bax/Bcl-2 ratio, activated Caspase-3/7, Caspase-9, PARP and AIF translocation, leading to apoptotic cell death. Our study indicated that MOE exerted significant anti-cancer effects on melanoma cells in vitro which involved mitochondria-mediated Caspase-dependent and Caspase-independent apoptosis pathways. These results provided a scientific approach for using Moringa oleifera leaves as an alternative therapy to treat skin cancer.


greenmedinfo--2020-05-19--Moringa oleifera Lam. leaf extract might be a good alternative herbal choice in the treatment of met

Moringa oleifera Lam. leaf extract might be a good alternative herbal choice in the treatment of metabolic syndrome disease.

Lam .
has been used traditionally for the treatment of different cardio-metabolic disorders .
So , the aim was to @ @ @ @ @ metabolic syndrome rat model.Out of the total 36-rats , 6 rats were given normal matched @ @ @ @ @ the rest were provided high-fat diet and 20 % fructose ( HFD-20 % F ) @ @ @ @ @ for 30 days .
Body weight , blood glucose , BMI , blood pressure , @ @ @ @ @ resistance , MCP-1 , visceral fat and liver weight were evaluated.Sixty-days feeding with HFD-20 % @ @ @ @ @ features like hyperinsulinemia , insulin resistance , and increase in low-density lipoprotein ( LDL ) @ @ @ @ @ liver weight significantly (

Lam. has been used traditionally for the treatment of different cardio-metabolic disorders. So, the aim was to assess its leaf extracts in metabolic syndrome rat model.Out of the total 36-rats, 6 rats were given normal matched diet (NMD) while the rest were provided high-fat diet and 20% fructose (HFD-20%F).leaf extracts were administered orally for 30 days. Body weight, blood glucose, BMI, blood pressure, lipids, insulin, insulin resistance, MCP-1, visceral fat and liver weight were evaluated.Sixty-days feeding with HFD-20%F produced the metabolic syndrome features like hyperinsulinemia, insulin resistance, and increase in low-density lipoprotein (LDL), visceral fat, and liver weight significantly (<.05) than the rats receiving (NMD).treatment for 30 days significantly provided the mitigation against metabolic syndrome features.Lam. leaf extract might be a good alternative herbal choice in the treatment of metabolic syndrome disease.


greenmedinfo--2020-05-19--Administration of Moringa oleifera extract mitigated cyclophosphamide-induced testicular damage.

ETHNOPHARMACOLOGICAL RELEVANCE : Moringa oleifera Lam .
is known for its nutritional and ethno medicinal values due to the presence of wide array of phytochemicals with multiple biological activities .
We have previously reported that ethanolic extract of Moringa oleifera leaves ( MOE ) ameliorated cyclophosphamide ( CP ) -induced testicular toxicity and improved functional integrity of spermatozoa as well as spermatogenic cells .
AIM OF THE STUDY : The present study was planned to investigate whether the mitigation of CP-induced testicular toxicity by MOE is mediated via modulation of endocrine profile , genes associated with function of different cell @ @ @ @ @ @ @ in spermatogonial cells .
MATERIAL AND METHODS : Adult Swiss albino mice ( 8 week ) were injected with CP ( 100 mg/kg , one dose in a week for 3 weeks ) and MOE ( 100 mg/kg , 5 doses in a week for 4 weeks ) either alone or in combination intraperitoneally .
At 35 day post CP injection ( first dose ) , the functional characteristics such as count , motility , head morphology and DNA integrity were assessed in epididymal spermatozoa .
Key reproductive hormones like testosterone , follicle @ @ @ @ @ @ @ B concentration were analyzed in serum and testis .
In addition , m-RNA expression of genes pertaining to the function of Leydig , Sertoli and spermatogonial cells as well as antioxidant enzymes were evaluated in the testis .
To understand the DNA damage and repair process in germ cells , pre-pubertal ( 2 week ) mice were administered with single dose of CP ( 200 mg/kg ) and/or MOE ( 100 mg/kg ) and analyzed for expression of DNA damage ( γ-HAX , P53 and Caspase3 ) and repair genes ( Rad51 and @ @ @ @ @ @ @ various time points after treatment .
RESULTS : CP administration resulted in decrease in count , motility and increase in morphological defects and DNA damage in spermatozoa .
Testosterone level was marginally decreased while there was a significant increase in FSH ( p CONCLUSION : Administration of MOE mitigated CP-induced testicular damage by improving blood and , intra-testicular hormonal milieu as well as modulating the expression of genes pertaining to Sertoli and spermatogonial cells .

ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera Lam. is known for its nutritional and ethno medicinal values due to the presence of wide array of phytochemicals with multiple biological activities. We have previously reported that ethanolic extract of Moringa oleifera leaves (MOE) ameliorated cyclophosphamide (CP)-induced testicular toxicity and improved functional integrity of spermatozoa as well as spermatogenic cells.
AIM OF THE STUDY: The present study was planned to investigate whether the mitigation of CP-induced testicular toxicity by MOE is mediated via modulation of endocrine profile, genes associated with function of different cell types and enhancement of DNA repair response in spermatogonial cells.
MATERIAL AND METHODS: Adult Swiss albino mice (8 week) were injected with CP (100 mg/kg, one dose in a week for 3 weeks) and MOE (100 mg/kg, 5 doses in a week for 4 weeks) either alone or in combination intraperitoneally. At 35 day post CP injection (first dose), the functional characteristics such as count, motility, head morphology and DNA integrity were assessed in epididymal spermatozoa. Key reproductive hormones like testosterone, follicle stimulating hormone (FSH) and Inhibin B concentration were analyzed in serum and testis. In addition, m-RNA expression of genes pertaining to the function of Leydig, Sertoli and spermatogonial cells as well as antioxidant enzymes were evaluated in the testis. To understand the DNA damage and repair process in germ cells, pre-pubertal (2 week) mice were administered with single dose of CP (200 mg/kg) and/or MOE (100 mg/kg) and analyzed for expression of DNA damage (γ-HAX, P53 and Caspase3) and repair genes (Rad51 and Ku80) in isolated spermatogonial cells at various time points after treatment.
RESULTS: CP administration resulted in decrease in count, motility and increase in morphological defects and DNA damage in spermatozoa. Testosterone level was marginally decreased while there was a significant increase in FSH (p < 0.001) and decrease in inhibin B (p < 0.05) observed in CP treated mice. Administration of MOE prior to CP, improved sperm functional characteristics, decreased FSH and increased inhibin B levels. Expression of Abp was down-regulated while Transferrin, Fshr and Gata4 (Sertoli cell specific genes) were up-regulated in testis treated with CP. Administration of CP down-regulated the expression of Oct4 and Ddx4 (Spermatogonia specific genes). MOE administration was shown to ameliorate CP-induced damage by modulating the expression of genes specific to Sertoli and spermatogenic cells. Furthermore, MOE treatment reduced CP-induced DNA damage as evident from lower percentage of γ-H2AX positive spermatogonial cells.
CONCLUSION: Administration of MOE mitigated CP-induced testicular damage by improving blood and, intra-testicular hormonal milieu as well as modulating the expression of genes pertaining to Sertoli and spermatogonial cells.


greenmedinfo--2020-05-19--Molecular mechanisms of the anti-cancer effects of isothiocyanates from cruciferous vegetables in bl

Molecular mechanisms of the anti-cancer effects of isothiocyanates from cruciferous vegetables in bladder cancer.

Bladder cancer ( BC ) is a representative of urological cancer with a high recurrence and metastasis potential .
Currently @ @ @ @ @ checkpoint inhibitors are used as standard therapy in patients with advanced/metastatic BC .
However , @ @ @ @ @ adverse events , and prolongation of survival is unsatisfactory .
Therefore , a treatment strategy @ @ @ @ @ great interest .
In this review , we focused on the anti-cancer effects of isothiocyanates @ @ @ @ @ cruciferous vegetables , which are widely cultivated and consumed in many regions worldwide .
Specifically @ @ @ @ @ effects of four ITC compounds-allyl isothiocyanate , benzyl isothiocyanate , sulforaphane , and phenethyl isothiocyanate-in @ @ @ @ @ underlying their anti-cancer effects ; current trends and future direction of ITC-based treatment strategies ; @ @ @ @ @ ITCs .
We also discuss the advantages and limitations of each ITC in BC treatment @ @ @ @ @ ITCs in treatment strategies and for improving the prognosis of patients with BC .

Bladder cancer (BC) is a representative of urological cancer with a high recurrence and metastasis potential. Currently, cisplatin-based chemotherapy and immune checkpoint inhibitors are used as standard therapy in patients with advanced/metastatic BC. However, these therapies often show severe adverse events, and prolongation of survival is unsatisfactory. Therefore, a treatment strategy using natural compounds is of great interest. In this review, we focused on the anti-cancer effects of isothiocyanates (ITCs) derived from cruciferous vegetables, which are widely cultivated and consumed in many regions worldwide. Specifically, we discuss the anti-cancer effects of four ITC compounds-allyl isothiocyanate, benzyl isothiocyanate, sulforaphane, and phenethyl isothiocyanate-in BC; the molecular mechanisms underlying their anti-cancer effects; current trends and future direction of ITC-based treatment strategies; and the carcinogenic potential of ITCs. We also discuss the advantages and limitations of each ITC in BC treatment, furthering the consideration of ITCs in treatment strategies and for improving the prognosis of patients with BC.


greenmedinfo--2020-05-19--White sweet potato ameliorates hyperglycemia and regenerates pancreatic islets in diabetic mice.

Background : White sweet potato ( WSP ) has many potential beneficial effects on metabolic control and on diabetes-related insulin resistance .
The antihyperglycemic effects of Tainung No .
10 ( TNG10 ) , a variety of WSP in Taiwan , warrant investigation .
Objective : To investigate the antidiabetic activity of WSP ( Ipomoea batatas L. TNG10 ) and the mechanisms for interventions using whole leaves or tubers of WSP in diabetic mice .
Design : Mice were co-administered with streptozotocin and nicotinamide to induce diabetes and then treated with an experimental diet including either 10 % WSP tuber @ @ @ @ @ @ @ % WSP tuber ( 30 % -T ) or 0.5 % WSP leaf ( 0.5 % -L ) and 5 % WSP leaf ( 5 % -L ) .
After 8 weeks ' treatment , their plasma glycemic parameters , lipid profiles , and inflammatory marker were analyzed .
Their pancreases were removed for histopathologic image analysis ; proteins were also extracted from their muscles for phosphoinositide 3-kinase pathway analysis .
Results : The 30 % -T or 5 % -L mice had lower plasma glucose , insulin , glucose area under the @ @ @ @ @ @ @ assessment of insulin resistance ( HOMA-IR ) , alanine transaminase , triglyceride , and tumor necrosis factor alpha levels .
In all diabetic mice , their Langerhans 's area was reduced by 60 % ; however , after 30 % WSP-T or 5 % WSP-L diets , the mice demonstrated significant restoration of the Langerhans 's areas ( approximately 30 % ) .
Only in 5 % -L mice , slightly increased expression of insulin-signaling pathway-related proteins , phosphorylated insulin receptor and protein kinase B and membrane glucose transporter 4 was noted .
@ @ @ @ @ @ @ inducing pancreatic islet regeneration and insulin resistance amelioration .
Therefore , WSP has potential applications in dietary diabetes management .

Background: White sweet potato (WSP) has many potential beneficial effects on metabolic control and on diabetes-related insulin resistance. The antihyperglycemic effects of Tainung No. 10 (TNG10), a variety of WSP in Taiwan, warrant investigation. Objective: To investigate the antidiabetic activity of WSP (Ipomoea batatas L. TNG10) and the mechanisms for interventions using whole leaves or tubers of WSP in diabetic mice. Design: Mice were co-administered with streptozotocin and nicotinamide to induce diabetes and then treated with an experimental diet including either 10% WSP tuber (10%-T) and 30% WSP tuber (30%-T) or 0.5% WSP leaf (0.5%-L) and 5% WSP leaf (5%-L). After 8 weeks' treatment, their plasma glycemic parameters, lipid profiles, and inflammatory marker were analyzed. Their pancreases were removed for histopathologic image analysis; proteins were also extracted from their muscles for phosphoinositide 3-kinase pathway analysis. Results: The 30%-T or 5%-L mice had lower plasma glucose, insulin, glucose area under the curve (AUC), homeostatic model assessment of insulin resistance (HOMA-IR), alanine transaminase, triglyceride, and tumor necrosis factor alpha levels. In all diabetic mice, their Langerhans's area was reduced by 60%; however, after 30% WSP-T or 5% WSP-L diets, the mice demonstrated significant restoration of the Langerhans's areas (approximately 30%). Only in 5%-L mice, slightly increased expression of insulin-signaling pathway-related proteins, phosphorylated insulin receptor and protein kinase B and membrane glucose transporter 4 was noted. Conclusions: WSP has antihyperglycemic effects by inducing pancreatic islet regeneration and insulin resistance amelioration. Therefore, WSP has potential applications in dietary diabetes management.


greenmedinfo--2020-05-19--Mangiferin alleviates ovalbumin-induced allergic rhinitis.

Mangiferin ( MF ) , extracted from mango trees , is considered to have anti-inflammatory , anti-apoptotic , and antioxidant @ @ @ @ @ effects on allergic rhinitis ( AR ) , remain unclear .
We investigated the mechanisms @ @ @ @ @ MF in ovalbumin ( OVA ) -induced AR models .
AR was induced by OVA @ @ @ @ @ Prior to this , MF and dexamethasone were administered .
Mice were examined for nasal @ @ @ @ @ of allergen-specific cytokine response , and histopathological changes in the nasal mucosa and lung tissue @ @ @ @ @ and nasal mucosa inflammation in OVA-induced AR and reduced inflammatory cell infiltration and epithelial disruption @ @ @ @ @ inhibited the overproduction of Th2/Th17 cytokines and transcription factors .
MF downregulated the HO-1/Nrf2 pathways @ @ @ @ @ levels , and the NF-κB signaling pathways were inhibited .
MF exerts protective effects in @ @ @ @ @ activating HO-1/Nrf2 pathways .
MF could be used for the treatment of AR .

Mangiferin (MF), extracted from mango trees, is considered to have anti-inflammatory, anti-apoptotic, and antioxidant effects. However, its effects on allergic rhinitis (AR), remain unclear. We investigated the mechanisms underlying the protective action of MF in ovalbumin (OVA)-induced AR models. AR was induced by OVA challenge in BALB/c mice. Prior to this, MF and dexamethasone were administered. Mice were examined for nasal mucosal inflammation, the generation of allergen-specific cytokine response, and histopathological changes in the nasal mucosa and lung tissue. MF ameliorated nasal symptoms and nasal mucosa inflammation in OVA-induced AR and reduced inflammatory cell infiltration and epithelial disruption in these tissues. MF inhibited the overproduction of Th2/Th17 cytokines and transcription factors. MF downregulated the HO-1/Nrf2 pathways, reduced oxidative stress biomarker levels, and the NF-κB signaling pathways were inhibited. MF exerts protective effects in AR by inhibiting NF-κB and activating HO-1/Nrf2 pathways. MF could be used for the treatment of AR.


greenmedinfo--2020-05-19--Mangiferin induces the expression of a thermogenic signature via AMPK signalling during brown-adipoc

Mangiferin induces the expression of a thermogenic signature via AMPK signalling during brown-adipocyte differentiation.

Mangiferin ( MF ) from Mangifera indica has been serendipitously found to ameliorate obesity and is used as an antioxidant , anti-inflammatory , antimicrobial , and anticancer agent .
Nonetheless , the mechanism of MF-induced brown-adipose-tissue activation has not been studied .
Therefore , we investigated the effect of MF on thermogenic features during brown-adipocyte differentiation .
Treatment with MF improved the expression of a brown-fat signature and of mitochondrial-mass-related genes , thus resulting in UCP1 induction .
MF also raised the expression of other thermogenic regulators , including peroxisome proliferator-activated receptor gamma coactivator 1 alpha ( PGC1α ) , @ @ @ @ @ @ @ , and peroxisome proliferator-activated receptors alpha and gamma ( PPAR-α and -γ ) .
MF promoted mitochondrial biogenesis , judging by increased expression of cell death-inducing DNA fragmentation factor α-like effector A ( CIDEA ) , mitochondrial transcription factor A ( TFAM ) , iodothyronine deiodinase 2 ( DIO2 ) , cytochrome c oxidase subunit 7A ( COX7A ) , cyclooxygenase 2 ( COX2 ) , sirtuin 1 ( SIRT1 ) , and nuclear respiratory factor 1 ( NRF1 ) .
MF treatment increased the mitochondrial DNA amount and improved mitochondrial respiratory function @ @ @ @ @ @ @ differentiation .
A gene knockdown assay involving small interfering RNA and competitive inhibition with dorsomorphin revealed that MF may promote thermogenesis in brown preadipocytes via activation of AMPK signaling .
Collectively , our findings suggest that MF may be a novel pharmaceutical agent that can ameliorate obesity via activation of brown adipose tissue .

Mangiferin (MF) from Mangifera indica has been serendipitously found to ameliorate obesity and is used as an antioxidant, anti-inflammatory, antimicrobial, and anticancer agent. Nonetheless, the mechanism of MF-induced brown-adipose-tissue activation has not been studied. Therefore, we investigated the effect of MF on thermogenic features during brown-adipocyte differentiation. Treatment with MF improved the expression of a brown-fat signature and of mitochondrial-mass-related genes, thus resulting in UCP1 induction. MF also raised the expression of other thermogenic regulators, including peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), PR domain-containing protein 16 (PRDM16), and peroxisome proliferator-activated receptors alpha and gamma (PPAR-α and -γ). MF promoted mitochondrial biogenesis, judging by increased expression of cell death-inducing DNA fragmentation factor α-like effector A (CIDEA), mitochondrial transcription factor A (TFAM), iodothyronine deiodinase 2 (DIO2), cytochrome c oxidase subunit 7A (COX7A), cyclooxygenase 2 (COX2), sirtuin 1 (SIRT1), and nuclear respiratory factor 1 (NRF1). MF treatment increased the mitochondrial DNA amount and improved mitochondrial respiratory function by increasing theoxygen consumption rate during brown-adipocyte differentiation. A gene knockdown assay involving small interfering RNA and competitive inhibition with dorsomorphin revealed that MF may promote thermogenesis in brown preadipocytes via activation of AMPK signaling. Collectively, our findings suggest that MF may be a novel pharmaceutical agent that can ameliorate obesity via activation of brown adipose tissue.


greenmedinfo--2020-05-19--Mangiferin is not only a remarkable anti-inflammatory compound but also an antitumor agent.

Non-small cell lung cancer ( NSCLC ) is often complicated by pulmonary infection , which affects treatment and prognosis .
Bacterial lipopolysaccharide ( LPS ) is an effective stimulator of inflammatory cytokine production , and previous studies have reported that LPS promotes tumor invasion and metastasis .
Mangiferin is a plant-derived C-glucosylxanthone with many biological activities , such as antioxidation and anti-inflammation .
This research mainly explored the mechanism of its antitumor activities on LPS-induced A549 , NCI-H460 , and NCI-H520 NSCLC cells .
We determined that mangiferin exhibits growth inhibiting activity against LPS-induced NSCLC cells through the 3- ( @ @ @ @ @ @ @ bromide ( MTT ) assay .
In addition , mangiferin reversed the LPS-induced downregulation of E-cadherin ( epithelial marker ) ; conversely , it significantly inhibited the expression of raised vimentin ( mesenchymal markers ) .
Moreover , the ability of NSCLC cells to migrate , as evidenced by the wound healing and transwell migration assays , and the expression of CXCR4 increased by LPS were significantly repressed by mangiferin .
In addition , mangiferin markedly mediated protein levels of PER1 and NLRP3 in LPS-induced NSCLC cells and reduced the secretion of IL-1β @ @ @ @ @ @ @ not only a remarkable anti-inflammatory compound but also an antitumor agent ; thus , it has the potential for being developed into anti-inflammatory and antitumor drugs in the future .

Non-small cell lung cancer (NSCLC) is often complicated by pulmonary infection, which affects treatment and prognosis. Bacterial lipopolysaccharide (LPS) is an effective stimulator of inflammatory cytokine production, and previous studies have reported that LPS promotes tumor invasion and metastasis. Mangiferin is a plant-derived C-glucosylxanthone with many biological activities, such as antioxidation and anti-inflammation. This research mainly explored the mechanism of its antitumor activities on LPS-induced A549, NCI-H460, and NCI-H520 NSCLC cells. We determined that mangiferin exhibits growth inhibiting activity against LPS-induced NSCLC cells through the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. In addition, mangiferin reversed the LPS-induced downregulation of E-cadherin (epithelial marker); conversely, it significantly inhibited the expression of raised vimentin (mesenchymal markers). Moreover, the ability of NSCLC cells to migrate, as evidenced by the wound healing and transwell migration assays, and the expression of CXCR4 increased by LPS were significantly repressed by mangiferin. In addition, mangiferin markedly mediated protein levels of PER1 and NLRP3 in LPS-induced NSCLC cells and reduced the secretion of IL-1β. These results indicate that mangiferin is not only a remarkable anti-inflammatory compound but also an antitumor agent; thus, it has the potential for being developed into anti-inflammatory and antitumor drugs in the future.


greenmedinfo--2020-05-19--Hepatoprotective effect of meal replacement seeds juice based on sweet potato.

A sweet potato-based Meal Replacement Seeds Juice ( MRSJ ) was developed by mixing sweet potatoes and carrots with four @ @ @ @ @ the MRSJ rather than the whole vegetables or whole seeds improved digestive function , proving @ @ @ @ @ the elderly .
Its rich composition of minerals , vitamins , and unsaturated fatty acids @ @ @ @ @ nutrient source .
Notably , the ethyl acetate fraction of MRSJ contains abundant phenolics .
@ @ @ @ @ that these phenolics have high radical scavenging activity , reducing power , and antioxidant capacity @ @ @ @ @ The ethyl acetate fraction exerted protective effects against CCl- or HO-induced hepatotoxicity via DNA protection @ @ @ @ @ and cell protection , wherein ALT and AST activities in the cell culture solution decreased @ @ @ @ @ that MRSJ consumption may protect against liver diseases .
Moreover , MRSJ as an excellent @ @ @ @ @ as an age-neutral food .

A sweet potato-based Meal Replacement Seeds Juice (MRSJ) was developed by mixing sweet potatoes and carrots with four types of seeds. Consuming the MRSJ rather than the whole vegetables or whole seeds improved digestive function, proving that it is suitable for the elderly. Its rich composition of minerals, vitamins, and unsaturated fatty acids implicates it as an excellent nutrient source. Notably, the ethyl acetate fraction of MRSJ contains abundant phenolics. The antioxidant activity assays showed that these phenolics have high radical scavenging activity, reducing power, and antioxidant capacity similar to l-ascorbic acid. The ethyl acetate fraction exerted protective effects against CCl- or HO-induced hepatotoxicity via DNA protection, lipid accumulation inhibition, and cell protection, wherein ALT and AST activities in the cell culture solution decreased significantly. These findings suggest that MRSJ consumption may protect against liver diseases. Moreover, MRSJ as an excellent nutrient source may be developed as an age-neutral food.


greenmedinfo--2020-05-19--Snacking on whole almonds for 6 weeks improves endothelial function and lowers LDL cholesterol.

BACKGROUND : There is convincing evidence that daily whole almond consumption lowers blood LDL cholesterol concentrations , but effects on other cardiometabolic risk factors such as endothelial function and liver fat are still to be determined .
OBJECTIVES : We aimed to investigate whether isoenergetic substitution of whole almonds for control snacks with the macronutrient profile of average snack intakes , had any impact on markers of cardiometabolic health in adults aged 30-70 y at above-average risk of cardiovascular disease ( CVD ) .
METHODS : The study was a 6-wk randomized controlled , parallel-arm trial .
Following a 2-wk @ @ @ @ @ @ @ ) , participants consumed either whole roasted almonds ( n = 51 ) or control snacks ( n = 56 ) , providing 20 % of daily estimated energy requirements .
Endothelial function ( flow-mediated dilation ) , liver fat ( MRI/magnetic resonance spectroscopy ) , and secondary outcomes as markers of cardiometabolic disease risk were assessed at baseline and end point .
RESULTS : Almonds , compared with control , increased endothelium-dependent vasodilation ( mean difference 4.1 % -units of measurement ; 95 % CI : 2.2 , 5.9 ) , but @ @ @ @ @ @ @ between groups .
Plasma LDL cholesterol concentrations decreased in the almond group relative to control ( mean difference -0.25 mmol/L ; 95 % CI : -0.45 , -0.04 ) , but there were no group differences in triglycerides , HDL cholesterol , glucose , insulin , insulin resistance , leptin , adiponectin , resistin , liver function enzymes , fetuin-A , body composition , pancreatic fat , intramyocellular lipids , fecal SCFAs , blood pressure , or 24-h heart rate variability .
However , the long-phase heart rate variability parameter , very-low-frequency power @ @ @ @ @ @ @ almond treatment compared with control ( mean difference 337 ms2 ; 95 % CI : 12 , 661 ) , indicating greater parasympathetic regulation .
CONCLUSIONS : Whole almonds consumed as snacks markedly improve endothelial function , in addition to lowering LDL cholesterol , in adults with above-average risk of CVD.This trial was registered at clinicaltrials.gov as NCT02907684 .

BACKGROUND: There is convincing evidence that daily whole almond consumption lowers blood LDL cholesterol concentrations, but effects on other cardiometabolic risk factors such as endothelial function and liver fat are still to be determined.
OBJECTIVES: We aimed to investigate whether isoenergetic substitution of whole almonds for control snacks with the macronutrient profile of average snack intakes, had any impact on markers of cardiometabolic health in adults aged 30-70 y at above-average risk of cardiovascular disease (CVD).
METHODS: The study was a 6-wk randomized controlled, parallel-arm trial. Following a 2-wk run-in period consuming control snacks (mini-muffins), participants consumed either whole roasted almonds (n = 51) or control snacks (n = 56), providing 20% of daily estimated energy requirements. Endothelial function (flow-mediated dilation), liver fat (MRI/magnetic resonance spectroscopy), and secondary outcomes as markers of cardiometabolic disease risk were assessed at baseline and end point.
RESULTS: Almonds, compared with control, increased endothelium-dependent vasodilation (mean difference 4.1%-units of measurement; 95% CI: 2.2, 5.9), but there were no differences in liver fat between groups. Plasma LDL cholesterol concentrations decreased in the almond group relative to control (mean difference -0.25 mmol/L; 95% CI: -0.45, -0.04), but there were no group differences in triglycerides, HDL cholesterol, glucose, insulin, insulin resistance, leptin, adiponectin, resistin, liver function enzymes, fetuin-A, body composition, pancreatic fat, intramyocellular lipids, fecal SCFAs, blood pressure, or 24-h heart rate variability. However, the long-phase heart rate variability parameter, very-low-frequency power, was increased during nighttime following the almond treatment compared with control (mean difference 337 ms2; 95% CI: 12, 661), indicating greater parasympathetic regulation.
CONCLUSIONS: Whole almonds consumed as snacks markedly improve endothelial function, in addition to lowering LDL cholesterol, in adults with above-average risk of CVD.This trial was registered at clinicaltrials.gov as NCT02907684.


greenmedinfo--2020-05-19--Mandatory Vaccines? The Supreme Court Said Yes! But Wait, There's More…

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By providing the information contained herein we are not diagnosing , treating @ @ @ @ @ or preventing any type of disease or medical condition .
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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--2020-05-19--Whole almond consumption is associated with better diet quality and cardiovascular disease risk fact

Whole almond consumption is associated with better diet quality and cardiovascular disease risk factors.

PURPOSE : This work aimed to estimate whole almond consumption in a nationally representative UK survey population and examine associations with diet quality and cardiovascular disease ( CVD ) risk .
METHODS : Four-day food record data from the National Diet and Nutrition Survey ( NDNS ) 2008-2017 ( n = 6802 , age ≥ 19 year ) were analyzed to investigate associations between whole almond consumption and diet quality , measured by the modified Mediterranean Diet Score ( MDS ) and modified Healthy Diet Score ( HDS ) , and CVD risk markers , using survey-adjusted multivariable linear regression @ @ @ @ @ @ @ reported in 7.6 % of the population .
Median intake in whole almond consumers was 5.0 g/day ( IQR 9.3 ) .
Consumers had higher diet quality scores relative to non-consumers ; higher intakes of protein , total fat , monounsaturated , n-3 and n-6 polyunsaturated fats , fiber , folate , vitamin C , vitamin E , potassium , magnesium , phosphorus , and iron ; and lower intakes of trans-fatty acids , total carbohydrate , sugar , and sodium .
BMI and WC were lower in whole almond consumers compared to @ @ @ @ @ @ @ CI 24.9 , 26.2 ) vs 26.3 kg/m ( 25.9 , 26.7 ) , and 88.0 cm ( 86.2 , 89.8 ) vs 90.1 cm ( 89.1 , 91.2 ) , respectively .
However , there were no dose-related fully adjusted significant associations between increasing almond intake ( g per 1000 kcal energy intake ) and lower CVD risk markers .
CONCLUSIONS : Almond intake is low in the UK population , but consumption was associated with better dietary quality and lower CVD risk factors .
Habitual consumption of whole almonds should be @ @ @ @ @ @ @ .

PURPOSE: This work aimed to estimate whole almond consumption in a nationally representative UK survey population and examine associations with diet quality and cardiovascular disease (CVD) risk.
METHODS: Four-day food record data from the National Diet and Nutrition Survey (NDNS) 2008-2017 (n = 6802, age ≥ 19 year) were analyzed to investigate associations between whole almond consumption and diet quality, measured by the modified Mediterranean Diet Score (MDS) and modified Healthy Diet Score (HDS), and CVD risk markers, using survey-adjusted multivariable linear regression.
RESULTS: Whole almond consumption was reported in 7.6% of the population. Median intake in whole almond consumers was 5.0 g/day (IQR 9.3). Consumers had higher diet quality scores relative to non-consumers; higher intakes of protein, total fat, monounsaturated, n-3 and n-6 polyunsaturated fats, fiber, folate, vitamin C, vitamin E, potassium, magnesium, phosphorus, and iron; and lower intakes of trans-fatty acids, total carbohydrate, sugar, and sodium. BMI and WC were lower in whole almond consumers compared to non-consumers: 25.5 kg/m(95% CI 24.9, 26.2) vs 26.3 kg/m(25.9, 26.7), and 88.0 cm (86.2, 89.8) vs 90.1 cm (89.1, 91.2), respectively. However, there were no dose-related fully adjusted significant associations between increasing almond intake (g per 1000 kcal energy intake) and lower CVD risk markers.
CONCLUSIONS: Almond intake is low in the UK population, but consumption was associated with better dietary quality and lower CVD risk factors. Habitual consumption of whole almonds should be encouraged as part of a healthy diet.


greenmedinfo--2020-05-19--Exploring the Body’s Self Healing Super Power


greenmedinfo--2020-05-19--HIV-1-infected cell-derived exosomes promote the growth and progression of cervical cancer.

: Women infected with HIV are more likely to have aggressive cervical cancer , and patients with HIV infection are often more severely ill than those without HIV infection .
However , the underlying mechanism for the progression of cervical cancer is not yet fully understood and requires further research .
: Exosomes were isolated from cell culture supernatants using differential ultracentrifugation .
Confirmation of exosome isolation was based upon identification by electron microscopy and NanoSight particle tracking analysis of the purified fraction .
The function of exosomes derived from HIV-infected T-cells in cervical cancer was determined by CCK8 and @ @ @ @ @ @ @ derived from HIV-infected T-cells promotes the proliferation , migration and invasion of cervical cancer cells .
Furthermore , we found that HIV-infected T-cells secrete exosomal miR-155-5p that directly targets ARID2 degradation , leading to activation of the NF-κB signaling pathway .
MiR-155-5p promotes cervical cancer progression by secreting proinflammatory cytokines , including IL-6 and IL-8 .
: In conclusion , we demonstrate that intercellular crosstalk between HIV-infected T-cells and cervical cancer is mediated by exosomes from HIV-infected T-cells that contribute to the malignant progression of cervical cancer , providing potential targets for the @ @ @ @ @ @ @ .

: Women infected with HIV are more likely to have aggressive cervical cancer, and patients with HIV infection are often more severely ill than those without HIV infection. However, the underlying mechanism for the progression of cervical cancer is not yet fully understood and requires further research.: Exosomes were isolated from cell culture supernatants using differential ultracentrifugation. Confirmation of exosome isolation was based upon identification by electron microscopy and NanoSight particle tracking analysis of the purified fraction. The function of exosomes derived from HIV-infected T-cells in cervical cancer was determined by CCK8 and Transwell invasion assays.: Exosomal miR-155-5p derived from HIV-infected T-cells promotes the proliferation, migration and invasion of cervical cancer cells. Furthermore, we found that HIV-infected T-cells secrete exosomal miR-155-5p that directly targets ARID2 degradation, leading to activation of the NF-κB signaling pathway. MiR-155-5p promotes cervical cancer progression by secreting proinflammatory cytokines, including IL-6 and IL-8.: In conclusion, we demonstrate that intercellular crosstalk between HIV-infected T-cells and cervical cancer is mediated by exosomes from HIV-infected T-cells that contribute to the malignant progression of cervical cancer, providing potential targets for the prevention and treatment of HIV-associated cervical cancer.


greenmedinfo--2020-05-19--Isolation/analysis of extracellular microvesicles from HSV-1-infected cells.

Extracellular vesicles ( EVs ) are secreted membrane vesicles , derived from endosomes or from the plasma membrane , which @ @ @ @ @ cell types and biological fluids .
Although EVs are highly heterogeneous and their classification is @ @ @ @ @ can be distinguished : microvesicles ( MVs ) , which derive from the shedding of @ @ @ @ @ exosomes , which correspond to intraluminal vesicles released to the extracellular milieu upon fusion of @ @ @ @ @ with the plasma membrane .
Cells infected with viruses may secrete MVs containing viral proteins @ @ @ @ @ some instances , infectious virions .
A recent study carried out by our laboratory has @ @ @ @ @ cells infected with HSV-1 contained virions and were endocytosed by naïve cells leading to a @ @ @ @ @ that HSV-1 may use MVs for spreading , expanding its tropism and evading the host @ @ @ @ @ describe in detail the methods used to isolate and analyse the MVs released from HSV-1-infected @ @

Extracellular vesicles (EVs) are secreted membrane vesicles, derived from endosomes or from the plasma membrane, which have been isolated from most cell types and biological fluids. Although EVs are highly heterogeneous and their classification is complex, two major categories can be distinguished: microvesicles (MVs), which derive from the shedding of the plasma membrane, and exosomes, which correspond to intraluminal vesicles released to the extracellular milieu upon fusion of multivesicular bodies (MVBs) with the plasma membrane. Cells infected with viruses may secrete MVs containing viral proteins, RNAs and, in some instances, infectious virions. A recent study carried out by our laboratory has shown that MVs released by cells infected with HSV-1 contained virions and were endocytosed by naïve cells leading to a productive infection. This suggests that HSV-1 may use MVs for spreading, expanding its tropism and evading the host immune response. Here we describe in detail the methods used to isolate and analyse the MVs released from HSV-1-infected cells.


greenmedinfo--2020-05-19--The RNA exosome and human disease.

The RNA exosome and human disease.

The evolutionarily conserved RNA exosome is a multisubunit ribonuclease complex that processes and/or degrades numerous RNAs .
Recently , mutations in genes encoding both structural and catalytic subunits of the RNA exosome have been linked to human disease .
Mutations in the structural exosome gene EXOSC2 cause a distinct syndrome that includes retinitis pigmentosa , hearing loss , and mild intellectual disability .
In contrast , mutations in the structural exosome genes EXOSC3 and EXOSC8 cause pontocerebellar hypoplasia type 1b ( PCH1b ) and type 1c ( PCH1c ) , respectively , which are related autosomal recessive , neurodegenerative diseases @ @ @ @ @ @ @ structural exosome gene EXOSC9 cause a PCH-like disease with cerebellar atrophy and spinal motor neuronopathy .
Finally , mutations in the catalytic exosome gene DIS3 have been linked to multiple myeloma , a neoplasm of plasma B cells .
How mutations in these RNA exosome genes lead to distinct , tissue-specific diseases is not currently well understood .
In this chapter , we examine the role of the RNA exosome complex in human disease and discuss the mechanisms by which mutations in different exosome subunit genes could impair RNA exosome function and give @ @ @ @ @

The evolutionarily conserved RNA exosome is a multisubunit ribonuclease complex that processes and/or degrades numerous RNAs. Recently, mutations in genes encoding both structural and catalytic subunits of the RNA exosome have been linked to human disease. Mutations in the structural exosome gene EXOSC2 cause a distinct syndrome that includes retinitis pigmentosa, hearing loss, and mild intellectual disability. In contrast, mutations in the structural exosome genes EXOSC3 and EXOSC8 cause pontocerebellar hypoplasia type 1b (PCH1b) and type 1c (PCH1c), respectively, which are related autosomal recessive, neurodegenerative diseases. In addition, mutations in the structural exosome gene EXOSC9 cause a PCH-like disease with cerebellar atrophy and spinal motor neuronopathy. Finally, mutations in the catalytic exosome gene DIS3 have been linked to multiple myeloma, a neoplasm of plasma B cells. How mutations in these RNA exosome genes lead to distinct, tissue-specific diseases is not currently well understood. In this chapter, we examine the role of the RNA exosome complex in human disease and discuss the mechanisms by which mutations in different exosome subunit genes could impair RNA exosome function and give rise to diverse diseases.


greenmedinfo--2020-05-19--L-ascorbic acid can be useful in breast cancer treatment.

Anticancer effects of L-ascorbic acid ( Vitamin C , L-AA ) have been reported in various types of cancers .
L-AA intake reduces breast cancer recurrence and mortality ; however , the role of L-AA in the treatment of breast cancer remains poorly understood .
In this study , we investigated the effect and mechanism action of L-AA on breast cancer growth .
L-AA inhibited the growth of breast cancer cells by inducing apoptotic cell death at the evaluated treatment concentrations without affecting normal cells .
Moreover , L-AA induces autophagosome formation via regulation of mammalian target of rapamycin ( @ @ @ @ @ @ @ ( ) and increased autophagic flux .
Notably , we observed that L-AA increased p62/SQSTM1 ( sequestosome 1 ) protein levels .
Accumulation of p62 protein in cancer cells in response to stress has been reported , but its role in cancer regulation remains controversial .
Here , we demonstrated that L-AA-induced p62 accumulation is related to L-AA-induced breast cancer growth inhibition .
Furthermore , L-AA induced endoplasmic reticulum ( ER ) stress via the -- ( inositol-requiring endonuclease-c-Jun N-terminal kinase-C/EBP homologous protein ) signaling pathways , which increased the nuclear levels of @ @ @ @ @ @ @ L-AA-induced ER stress could be crucial for p62 accumulation-dependent cell death , and L-AA can be useful in breast cancer treatment .

Anticancer effects of L-ascorbic acid (Vitamin C, L-AA) have been reported in various types of cancers. L-AA intake reduces breast cancer recurrence and mortality; however, the role of L-AA in the treatment of breast cancer remains poorly understood. In this study, we investigated the effect and mechanism action of L-AA on breast cancer growth. L-AA inhibited the growth of breast cancer cells by inducing apoptotic cell death at the evaluated treatment concentrations without affecting normal cells. Moreover, L-AA induces autophagosome formation via regulation of mammalian target of rapamycin (), Beclin1, and autophagy-related genes () and increased autophagic flux. Notably, we observed that L-AA increased p62/SQSTM1 (sequestosome 1) protein levels. Accumulation of p62 protein in cancer cells in response to stress has been reported, but its role in cancer regulation remains controversial. Here, we demonstrated that L-AA-induced p62 accumulation is related to L-AA-induced breast cancer growth inhibition. Furthermore, L-AA induced endoplasmic reticulum (ER) stress via the--(inositol-requiring endonuclease-c-Jun N-terminal kinase-C/EBP homologous protein) signaling pathways, which increased the nuclear levels of p62/SQSTM1. These findings provide evidence that L-AA-induced ER stress could be crucial for p62 accumulation-dependent cell death, and L-AA can be useful in breast cancer treatment.


greenmedinfo--2020-05-19--Vitamin C versus cancer: Ascorbic acid radical and impairment of mitochondrial respiration?

Vitamin C as a cancer therapy has a controversial history .
Much of the controversy arises from the lack of predictive biomarkers for stratification of patients , as well as a clear understanding of the mechanism of action and its multiple targets underlying the anticancer effect .
Our review expands the analysis of cancer vulnerabilities for high-dose vitamin C , based on several facts , illustrating the cytotoxic potential of the ascorbyl free radical ( AFR ) via impairment of mitochondrial respiration and the mechanisms of its elimination in mammals by the membrane-bound NADH : cytochrome b5 oxidoreductase 3 ( @ @ @ @ @ @ @ conversion of AFR to ascorbate , as well as reduction of other redox-active compounds , using NADH as an electron donor .
We propose that vitamin C can function in '' protective mode '' or '' destructive mode '' affecting cellular homeostasis , depending on the intracellular '' steady-state '' concentration of AFR and differential expression/activity of Cyb5R3 in cancerous and normal cells .
Thus , a specific anticancer effect can be achieved at high doses of vitamin C therapy .
The review is intended for a wide audience of readers-from students to @ @ @ @ @

Vitamin C as a cancer therapy has a controversial history. Much of the controversy arises from the lack of predictive biomarkers for stratification of patients, as well as a clear understanding of the mechanism of action and its multiple targets underlying the anticancer effect. Our review expands the analysis of cancer vulnerabilities for high-dose vitamin C, based on several facts, illustrating the cytotoxic potential of the ascorbyl free radical (AFR) via impairment of mitochondrial respiration and the mechanisms of its elimination in mammals by the membrane-bound NADH:cytochrome b5 oxidoreductase 3 (Cyb5R3). This enzyme catalyzes rapid conversion of AFR to ascorbate, as well as reduction of other redox-active compounds, using NADH as an electron donor. We propose that vitamin C can function in"protective mode"or"destructive mode"affecting cellular homeostasis, depending on the intracellular"steady-state"concentration of AFR and differential expression/activity of Cyb5R3 in cancerous and normal cells. Thus, a specific anticancer effect can be achieved at high doses of vitamin C therapy. The review is intended for a wide audience of readers-from students to specialists in the field.


greenmedinfo--2020-05-19--Exogenous vitamin C triggered structural changes of redox-activated dual core-crosslinked biodegrada

Exogenous vitamin C triggered structural changes of redox-activated dual core-crosslinked biodegradable nanogels for boosting the antitumor efficiency.

Premature leakage of drugs during blood circulation and slow drug release at the tumor site are two major challenges that nanocarriers have to overcome to achieve successful cancer therapy .
Herein , a dual core-crosslinked , redox-sensitive polymeric nanogel ( sDL ) was constructed by the self-assembly of two star-shaped amphiphilic copolymers ( 4sP ( EG-b-LLA ) -N3 , 4sP ( EG-b-DLA ) -N3 ) in the presence of a redox-sensitive crosslinker ( d-ss-Bu ) , where hydrophilic polyethylene glycol ( PEG ) was used as the shell and the functional hydrophobic poly ( l-lactide ) ( PLLA ) and @ @ @ @ @ @ @ were used as the dual crosslinked core via stereocomplex formation and chemical interactions .
The dual core-crosslinked structure of the nanogels allowed for almost 2-fold enhanced doxorubicin ( DOX ) -loading capacity , favorable structural stability to restrict the premature leakage of therapeutic drug and smaller particle size to accelerate the internalization efficiency compared to non-crosslinked nanocarriers .
Furthermore , exogenous vitamin C ( Vc ) can trigger the breakage of redox-sensitive bonds to accelerate drug release from nanogels for improved in vitro antitumor efficacy .
Notably , in vivo near-infrared imaging showed @ @ @ @ @ @ @ aggregated at the tumor site .
Sequential administration of DOX-loaded sDL and Vc exhibited the highest tumor inhibition effect without associated systemic toxicity compared to the corresponding single injection of Vc or DOX-loaded sDL control groups for in vivo studies , indicating that exogenous administration of Vc can synergistically impact the release of DOX from sDL .
Therefore , the developed nanogels proved to be promising smart carriers for achieving precise tunable-stability in response to relevant environments and the combination of Vc to activate reduction-sensitive drug delivery is a promising approach to maximize @ @ @ @

Premature leakage of drugs during blood circulation and slow drug release at the tumor site are two major challenges that nanocarriers have to overcome to achieve successful cancer therapy. Herein, a dual core-crosslinked, redox-sensitive polymeric nanogel (sDL) was constructed by the self-assembly of two star-shaped amphiphilic copolymers (4sP(EG-b-LLA)-N3, 4sP(EG-b-DLA)-N3) in the presence of a redox-sensitive crosslinker (d-ss-Bu), where hydrophilic polyethylene glycol (PEG) was used as the shell and the functional hydrophobic poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA) were used as the dual crosslinked core via stereocomplex formation and chemical interactions. The dual core-crosslinked structure of the nanogels allowed for almost 2-fold enhanced doxorubicin (DOX)-loading capacity, favorable structural stability to restrict the premature leakage of therapeutic drug and smaller particle size to accelerate the internalization efficiency compared to non-crosslinked nanocarriers. Furthermore, exogenous vitamin C (Vc) can trigger the breakage of redox-sensitive bonds to accelerate drug release from nanogels for improved in vitro antitumor efficacy. Notably, in vivo near-infrared imaging showed that the highly stable DOX-loaded sDL efficiently aggregated at the tumor site. Sequential administration of DOX-loaded sDL and Vc exhibited the highest tumor inhibition effect without associated systemic toxicity compared to the corresponding single injection of Vc or DOX-loaded sDL control groups for in vivo studies, indicating that exogenous administration of Vc can synergistically impact the release of DOX from sDL. Therefore, the developed nanogels proved to be promising smart carriers for achieving precise tunable-stability in response to relevant environments and the combination of Vc to activate reduction-sensitive drug delivery is a promising approach to maximize the therapeutic efficacy.


greenmedinfo--2020-05-19--Therapeutic target and molecular mechanism of vitamin C-treated pneumonia: a systematic study of net

Therapeutic target and molecular mechanism of vitamin C-treated pneumonia: a systematic study of network pharmacology.

Vitamin C ( VC ) , a well-reported antioxidant , is found with beneficial actions of preventing and treating pneumonia .
However , the detailed pharmacological target and mechanism of VC-treated pneumonia remain unclear .
Thus , the present bioinformatics approach using systematic network pharmacology aimed to reveal primary predictive targets , cellular processes , and molecular pathways of VC-treated pneumonia .
As shown in bioinformatics assays , the data included 90 primary presumptive targets of VC-treated pneumonia , and 5 other core targets of VC-treated pneumonia were identified as mitogen activated protein kinase 1 ( MAPK1 ) , c-c @ @ @ @ @ @ @ , mitogen activated protein kinase 3 ( MAPK3 ) , angiotensin II type 2 ( AT-2 ) receptor ( AGTR2 ) , and signal transducer and activator of transcription 3 ( STAT3 ) .
In addition , all biological processes ( including top 20 ) and signaling pathways ( including top 20 ) of VC-treated pneumonia were identified and illustrated through bioinformatics analyses .
In conclusion , VC-achieved anti-pneumonia effects are mechanically implicated with the suppression of inflammation and enhancement of immunoregulation associated with functional processes and signaling pathways .
More interestingly , @ @ @ @ @ @ @ biomarkers for the diagnosis and treatment of pneumonia .

Vitamin C (VC), a well-reported antioxidant, is found with beneficial actions of preventing and treating pneumonia. However, the detailed pharmacological target and mechanism of VC-treated pneumonia remain unclear. Thus, the present bioinformatics approach using systematic network pharmacology aimed to reveal primary predictive targets, cellular processes, and molecular pathways of VC-treated pneumonia. As shown in bioinformatics assays, the data included 90 primary presumptive targets of VC-treated pneumonia, and 5 other core targets of VC-treated pneumonia were identified as mitogen activated protein kinase 1 (MAPK1), c-c chemokine receptor type 5 (CCR5), mitogen activated protein kinase 3 (MAPK3), angiotensin II type 2 (AT-2) receptor (AGTR2), and signal transducer and activator of transcription 3 (STAT3). In addition, all biological processes (including top 20) and signaling pathways (including top 20) of VC-treated pneumonia were identified and illustrated through bioinformatics analyses. In conclusion, VC-achieved anti-pneumonia effects are mechanically implicated with the suppression of inflammation and enhancement of immunoregulation associated with functional processes and signaling pathways. More interestingly, the identified VC targets may act as biomarkers for the diagnosis and treatment of pneumonia.