greenmedinfo--2020-05-16--From Cannabis sativa to cannabidiol: promising therapeutic candidate for the treatment of neurodegen

From Cannabis sativa to cannabidiol: promising therapeutic candidate for the treatment of neurodegenerative diseases.

, commonly known as marijuana , contains a pool of secondary plant metabolites with therapeutic effects .
BesidesΔ9-tetrahydrocannabinol that is the principal psychoactive constituent of , cannabidiol ( CBD ) is the most abundant nonpsychoactive phytocannabinoid and may represent a prototype for anti-inflammatory drug development for human pathologies where both the inflammation and oxidative stress ( OS ) play an important role to their etiology and progression .
To this regard , Alzheimer 's disease ( AD ) , Parkinson 's disease ( PD ) , the most common neurodegenerative disorders , are characterized by extensive oxidative damage to different @ @ @ @ @ @ @ by different pathways .
Most cases of neurodegenerative diseases have a complex etiology with a variety of factors contributing to the progression of the neurodegenerative processes ; therefore , promising treatment strategies should simultaneously target multiple substrates in order to stop and/or slow down the neurodegeneration .
In this context , CBD , which interacts with the eCB system , but has also cannabinoid receptor-independent mechanism , might be a good candidate as a prototype for anti-oxidant drug development for the major neurodegenerative disorders , such as PD and AD .
This review @ @ @ @ @ @ @ the positive effects of CBD , which may have a considerable impact on the progression of the major neurodegenerative disorders .

, commonly known as marijuana, contains a pool of secondary plant metabolites with therapeutic effects. BesidesΔ9-tetrahydrocannabinol that is the principal psychoactive constituent of, cannabidiol (CBD) is the most abundant nonpsychoactive phytocannabinoid and may represent a prototype for anti-inflammatory drug development for human pathologies where both the inflammation and oxidative stress (OS) play an important role to their etiology and progression. To this regard, Alzheimer's disease (AD), Parkinson's disease (PD), the most common neurodegenerative disorders, are characterized by extensive oxidative damage to different biological substrates that can cause cell death by different pathways. Most cases of neurodegenerative diseases have a complex etiology with a variety of factors contributing to the progression of the neurodegenerative processes; therefore, promising treatment strategies should simultaneously target multiple substrates in order to stop and/or slow down the neurodegeneration. In this context, CBD, which interacts with the eCB system, but has also cannabinoid receptor-independent mechanism, might be a good candidate as a prototype for anti-oxidant drug development for the major neurodegenerative disorders, such as PD and AD. This review summarizes the multiple molecular pathways that underlie the positive effects of CBD, which may have a considerable impact on the progression of the major neurodegenerative disorders.


greenmedinfo--2020-05-16--The anti-inflammatory and analgesic effects of formulated full-spectrum cannabis extract in the trea

The anti-inflammatory and analgesic effects of formulated full-spectrum cannabis extract in the treatment of neuropathic pain associated with multiple sclerosis.

PURPOSE : Cannabis has been used for thousands of years in many cultures for the treatment of several ailments including pain .
The benefits of cannabis are mediated largely by cannabinoids , the most prominent of which are tetrahydrocannabinol ( THC ) and cannabidiol ( CBD ) .
As such , THC and/or CBD have been investigated in clinical studies for the treatment of many conditions including neuropathic pain and acute or chronic inflammation .
While a plethora of studies have examined the biochemical effects of purified THC and/or CBD , only a few have focused on the effects of @ @ @ @ @ @ @ studies using purified THC or CBD may not accurately reflect the potential health benefits of full-spectrum cannabis extracts .
Indeed , the cannabis plant produces a wide range of cannabinoids , terpenes , flavonoids , and other bioactive molecules which are likely to contribute to the different biological effects .
The presence of all these bioactive molecules in cannabis extracts has garnered much attention of late especially with regard to their potential role in the treatment of neuropathic pain associated with multiple sclerosis .
METHODS : Literature review was performed to further understand @ @ @ @ @ @ @ extract in patients with multiple sclerosis .
RESULTS : Herein , the current knowledge about the potential beneficial effects of existing products of full-spectrum cannabis extract in clinical studies involving patients with multiple sclerosis is extensively reviewed .
In addition , the possible adverse effects associated with cannabis use is discussed along with how the method of extraction and the delivery mechanisms of different cannabis extracts contribute to the pharmacokinetic and biological effects of full-spectrum cannabis extracts.Herein , the current knowledge about the potential beneficial effects of existing products of full-spectrum cannabis extract @ @ @ @ @ @ @ sclerosis is extensively reviewed .
In addition , the possible adverse effects associated with cannabis use is discussed along with how the method of extraction and the delivery mechanisms of different cannabis extracts contribute to the pharmacokinetic and biological effects of full-spectrum cannabis extracts .

PURPOSE: Cannabis has been used for thousands of years in many cultures for the treatment of several ailments including pain. The benefits of cannabis are mediated largely by cannabinoids, the most prominent of which are tetrahydrocannabinol (THC) and cannabidiol (CBD). As such, THC and/or CBD have been investigated in clinical studies for the treatment of many conditions including neuropathic pain and acute or chronic inflammation. While a plethora of studies have examined the biochemical effects of purified THC and/or CBD, only a few have focused on the effects of full-spectrum cannabis plant extract. Accordingly, studies using purified THC or CBD may not accurately reflect the potential health benefits of full-spectrum cannabis extracts. Indeed, the cannabis plant produces a wide range of cannabinoids, terpenes, flavonoids, and other bioactive molecules which are likely to contribute to the different biological effects. The presence of all these bioactive molecules in cannabis extracts has garnered much attention of late especially with regard to their potential role in the treatment of neuropathic pain associated with multiple sclerosis.
METHODS: Literature review was performed to further understand the effect of clinically used full-spectrum cannabis extract in patients with multiple sclerosis.
RESULTS: Herein, the current knowledge about the potential beneficial effects of existing products of full-spectrum cannabis extract in clinical studies involving patients with multiple sclerosis is extensively reviewed. In addition, the possible adverse effects associated with cannabis use is discussed along with how the method of extraction and the delivery mechanisms of different cannabis extracts contribute to the pharmacokinetic and biological effects of full-spectrum cannabis extracts.Herein, the current knowledge about the potential beneficial effects of existing products of full-spectrum cannabis extract in clinical studies involving patients with multiple sclerosis is extensively reviewed. In addition, the possible adverse effects associated with cannabis use is discussed along with how the method of extraction and the delivery mechanisms of different cannabis extracts contribute to the pharmacokinetic and biological effects of full-spectrum cannabis extracts.


greenmedinfo--2020-05-16--Cannabinoids as anticancer therapeutic agents.

The recent announcement of marijuana legalization in Canada spiked many discussions about potential health benefits of .
Cannabinoids are active @ @ @ @ @ , and their numerous effects on the human body are primarily exerted through interactions with @ @ @ @ @ CB ) and 2 ( CB ) .
Cannabinoids are broadly classified as endo- , @ @ @ @ @ .
In this review , we will describe the activity of cannabinoids on the cellular @ @ @ @ @ activity of all groups of cannabinoids on various cancers and propose several potential mechanisms of @ @ @ @ @ cells .

The recent announcement of marijuana legalization in Canada spiked many discussions about potential health benefits of. Cannabinoids are active chemical compounds produced by cannabis, and their numerous effects on the human body are primarily exerted through interactions with cannabinoid receptor types 1 (CB) and 2 (CB). Cannabinoids are broadly classified as endo-, phyto-, and synthetic cannabinoids. In this review, we will describe the activity of cannabinoids on the cellular level, comprehensively summarize the activity of all groups of cannabinoids on various cancers and propose several potential mechanisms of action of cannabinoids on cancer cells.


greenmedinfo--2020-05-16--Synergistic cytotoxic activity of cannabinoids from cannabis sativa against cutaneous T-cell lymphom

Synergistic cytotoxic activity of cannabinoids from cannabis sativa against cutaneous T-cell lymphoma.

produces hundreds of phytocannabinoids and terpenes .
Mycosis fungoides ( MF ) is the most common type of cutaneous T-cell lymphoma ( CTCL ) , characterized by patches , plaques and tumors .
Sézary is a leukemic stage of CTCL presenting with erythroderma and the presence of neoplastic Sézary T-cells in peripheral blood .
This study aimed to identify active compounds from whole cannabis extracts and their synergistic mixtures , and to assess respective cytotoxic activity against CTCL cells .
Ethanol extracts ofwere analyzed by high-performance liquid chromatography ( HPLC ) and gas chromatography/mass spectrometry ( GC/MS ) .
Cytotoxic @ @ @ @ @ @ @ on My-La and HuT-78 cell lines as well as peripheral blood lymphocytes from Sézary patients ( SPBL ) .
Annexin V assay and fluorescence-activated cell sorting ( FACS ) were used to determine apoptosis and cell cycle .
RNA sequencing and quantitative PCR were used to determine gene expression .
Active cannabis compounds presenting high cytotoxic activity on My-La and HuT-78 cell lines were identified in crude extract fractions designated S4 and S5 , and their synergistic mixture was specified .
This mixture induced cell cycle arrest and cell apoptosis ; a relatively @ @ @ @ @ @ @ malignant CD4CD26SPBL cells .
Significant cytotoxic activity of the corresponding mixture of pure phytocannabinoids further verified genuine interaction between S4 and S5 .
The gene expression profile was distinct in My-La and HuT-78 cells treated with the S4 and S5 synergistic mixture .
We suggest that specifying formulations of synergistic active cannabis compounds and unraveling their modes of action may lead to new cannabis-based therapies .

produces hundreds of phytocannabinoids and terpenes. Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL), characterized by patches, plaques and tumors. Sézary is a leukemic stage of CTCL presenting with erythroderma and the presence of neoplastic Sézary T-cells in peripheral blood. This study aimed to identify active compounds from whole cannabis extracts and their synergistic mixtures, and to assess respective cytotoxic activity against CTCL cells. Ethanol extracts ofwere analyzed by high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). Cytotoxic activity was determined using the XTT assay on My-La and HuT-78 cell lines as well as peripheral blood lymphocytes from Sézary patients (SPBL). Annexin V assay and fluorescence-activated cell sorting (FACS) were used to determine apoptosis and cell cycle. RNA sequencing and quantitative PCR were used to determine gene expression. Active cannabis compounds presenting high cytotoxic activity on My-La and HuT-78 cell lines were identified in crude extract fractions designated S4 and S5, and their synergistic mixture was specified. This mixture induced cell cycle arrest and cell apoptosis; a relatively selective apoptosis was also recorded on the malignant CD4CD26SPBL cells. Significant cytotoxic activity of the corresponding mixture of pure phytocannabinoids further verified genuine interaction between S4 and S5. The gene expression profile was distinct in My-La and HuT-78 cells treated with the S4 and S5 synergistic mixture. We suggest that specifying formulations of synergistic active cannabis compounds and unraveling their modes of action may lead to new cannabis-based therapies.


greenmedinfo--2020-05-16--Cannabis may have a beneficial impact on HIV-associated blood-brain barrier injury.

BACKGROUND : HIV infection leads to blood-brain barrier ( BBB ) dysfunction that does not resolve despite viral suppression on antiretroviral therapy and is associated with adverse clinical outcomes .
In preclinical models , cannabis restores BBB integrity .
METHODS : We studied people with HIV ( PWH ) and HIV- individuals who had used cannabis recently .
We assessed two biomarkers of BBB permeability : the cerebrospinal fluid [ CSF ] -to-serum albumin ratio [ CSAR ] , and CSF levels of soluble urokinase plasminogen activator receptor [ suPAR ] , a receptor for uPA , a matrix-degrading proteolytic @ @ @ @ @ @ @ composite index of the BBB markers was created using principal components analysis .
Neural injury was assessed using neurofilament light ( NFL ) in CSF by immunoassay .
RESULTS : Participants were 45 PWH and 30 HIV- individuals of similar age and ethnicity .
Among PWH , higher CSF suPAR levels correlated with higher CSAR values ( r=0.47 ; p < 0.001 ) .
PWH had higher ( more abnormal ) BBB index values than HIV- individuals ( mean +/- SD 0.361 +/-1.20 versus -0.501 +/- 1.11 ; p=0.0214 ) .
HIV serostatus @ @ @ @ @ @ @ more frequent use of cannabis was associated with lower BBB index values in PWH but not in HIV- .
Worse BBB Index values was associated with higher NFL in CSF ( r=0.380 , p=0.0169 ) .
CONCLUSIONS : Cannabis may have a beneficial impact on HIV-associated BBB injury .
Since BBB disruption may permit increased entry of toxins such as microbial antigens and inflammatory mediators , with consequent CNS injury , these results support a potential therapeutic role of cannabis among PWH and may have important treatment implications for ART effectiveness and toxicity @

BACKGROUND: HIV infection leads to blood-brain barrier (BBB) dysfunction that does not resolve despite viral suppression on antiretroviral therapy and is associated with adverse clinical outcomes. In preclinical models, cannabis restores BBB integrity.
METHODS: We studied people with HIV (PWH) and HIV- individuals who had used cannabis recently. We assessed two biomarkers of BBB permeability: the cerebrospinal fluid [CSF]-to-serum albumin ratio [CSAR], and CSF levels of soluble urokinase plasminogen activator receptor [suPAR], a receptor for uPA, a matrix-degrading proteolytic enzyme that disrupts the BBB. A composite index of the BBB markers was created using principal components analysis. Neural injury was assessed using neurofilament light (NFL) in CSF by immunoassay.
RESULTS: Participants were 45 PWH and 30 HIV- individuals of similar age and ethnicity. Among PWH, higher CSF suPAR levels correlated with higher CSAR values (r=0.47; p<0.001). PWH had higher (more abnormal) BBB index values than HIV- individuals (mean +/- SD 0.361 +/-1.20 versus -0.501 +/- 1.11; p=0.0214). HIV serostatus interacted with cannabis use frequency such that more frequent use of cannabis was associated with lower BBB index values in PWH but not in HIV-. Worse BBB Index values was associated with higher NFL in CSF (r=0.380, p=0.0169).
CONCLUSIONS: Cannabis may have a beneficial impact on HIV-associated BBB injury. Since BBB disruption may permit increased entry of toxins such as microbial antigens and inflammatory mediators, with consequent CNS injury, these results support a potential therapeutic role of cannabis among PWH and may have important treatment implications for ART effectiveness and toxicity.


greenmedinfo--2020-05-16--Cannabis for symptom management in older adults.

The purpose of this article is to present evidence on the efficacy and safety of medical cannabis as a therapy @ @ @ @ @ care .
This article provides an overview of the evidence on the risks and benefits @ @ @ @ @ the indications of chronic pain , cancer-related pain , cancer cachexia , dementia , and @ @ @ @ @ , there is insufficient evidence to determine the effectiveness and safety of cannabinoids for most @ @ @ @ @ exception of chronic pain .
Future research is required before palliative care clinicians can make @ @ @ @ @ of medical cannabis as adjunct therapies .

The purpose of this article is to present evidence on the efficacy and safety of medical cannabis as a therapy for symptom management in palliative care. This article provides an overview of the evidence on the risks and benefits of using medical cannabis for the indications of chronic pain, cancer-related pain, cancer cachexia, dementia, and Alzheimer's disease. Currently, there is insufficient evidence to determine the effectiveness and safety of cannabinoids for most reviewed indications, with the exception of chronic pain. Future research is required before palliative care clinicians can make evidence-based decisions on the integration of medical cannabis as adjunct therapies.


greenmedinfo--2020-05-16--Cannabis and cannabinoids in cancer pain management.

PURPOSE OF REVIEW : An increasing number of patients are turning to cannabis and cannabinoids for management of their palliative and nonpalliative cancer pain and other cancer-related symptoms .
Canadians have a legal framework for access to medical cannabis , which provides a unique perspective in a setting lacking robust clinical evidence .
This review seeks to delineate the role of cannabis and cannabinoids in cancer pain management and offers insight into the Canadian practice .
RECENT FINDINGS : A cohort study using nabiximols on advanced cancer pain in patients already optimized on opioids , over 3 weeks , demonstrated @ @ @ @ @ @ @ observational study of cancer patients using cannabis over 6 months demonstrated a decreased number of patients with severe pain and decreased opioid use , whereas the number of patients reporting good quality of life increased .
SUMMARY : Good preclinical animal data and a large body of observational evidence point to the potential efficacy of cannabinoids for cancer pain management .
However , there are relatively weak data pointing to clinical efficacy from clinical trial data to date .
In Canada , the burgeoning cannabis industry has driven the population to embrace a @ @ @ @ @ @ @ a need for high-quality randomized controlled trials to properly assess the effectiveness and safety of medical cannabis , compared with placebo and standard treatments for cancer-related symptoms .

PURPOSE OF REVIEW: An increasing number of patients are turning to cannabis and cannabinoids for management of their palliative and nonpalliative cancer pain and other cancer-related symptoms. Canadians have a legal framework for access to medical cannabis, which provides a unique perspective in a setting lacking robust clinical evidence. This review seeks to delineate the role of cannabis and cannabinoids in cancer pain management and offers insight into the Canadian practice.
RECENT FINDINGS: A cohort study using nabiximols on advanced cancer pain in patients already optimized on opioids, over 3 weeks, demonstrated improved average pain score. A large observational study of cancer patients using cannabis over 6 months demonstrated a decreased number of patients with severe pain and decreased opioid use, whereas the number of patients reporting good quality of life increased.
SUMMARY: Good preclinical animal data and a large body of observational evidence point to the potential efficacy of cannabinoids for cancer pain management. However, there are relatively weak data pointing to clinical efficacy from clinical trial data to date. In Canada, the burgeoning cannabis industry has driven the population to embrace a medicine before clinical evidence. There remains a need for high-quality randomized controlled trials to properly assess the effectiveness and safety of medical cannabis, compared with placebo and standard treatments for cancer-related symptoms.


greenmedinfo--2020-05-18--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--2020-05-18--Exosomes mediate Zika virus transmission through SMPD3 neutral Sphingomyelinase in cortical neurons.

The harmful effects of ZIKA virus ( ZIKV ) infection are reflected by severe neurological manifestations such as microcephaly in neonates and other complications associated with Guillain-Barré syndrome in adults .
The transmission dynamics of ZIKV in or between neurons , or within the developing brains of the foetuses are not fully understood .
Using primary cultures of murine cortical neurons , we show that ZIKV uses exosomes as mediators of viral transmission between neurons .
Cryo-electron microscopy showed heterogeneous population of neuronal exosomes with a size range of 30-200 nm .
Increased production of exosomes from neuronal cells was @ @ @ @ @ @ @ contained both ZIKV viral RNA and protein ( s ) that were highly infectious to naïve cells .
RNaseAand neutralizing antibodies treatment studies suggest the presence of viral RNA/proteins inside exosomes .
Exosomes derived from time- and dose-dependent incubations showed increasing viral loads suggesting higher packaging and delivery of ZIKV RNA and proteins .
Furthermore , we noted that ZIKV induced both activity and gene expression of neutral Sphingomyelinase ( nSMase ) -2/SMPD3 , an important molecule that regulates production and release of exosomes .
Silencing of SMPD3 in neurons resulted in reduced @ @ @ @ @ @ @ Treatment with SMPD3 specific inhibitor GW4869 , significantly reduced ZIKV loads in both cortical neurons and in exosomes derived from these neuronal cells .
Taken together , our results suggest that ZIKV modulates SMPD3 activity in cortical neurons for its infection and transmission through exosomes perhaps leading to severe neuronal death that may result in neurological manifestations such as microcephaly in the developing embryonic brains .

The harmful effects of ZIKA virus (ZIKV) infection are reflected by severe neurological manifestations such as microcephaly in neonates and other complications associated with Guillain-Barré syndrome in adults. The transmission dynamics of ZIKV in or between neurons, or within the developing brains of the foetuses are not fully understood. Using primary cultures of murine cortical neurons, we show that ZIKV uses exosomes as mediators of viral transmission between neurons. Cryo-electron microscopy showed heterogeneous population of neuronal exosomes with a size range of 30-200 nm. Increased production of exosomes from neuronal cells was noted upon ZIKV infection. Neuronal exosomes contained both ZIKV viral RNA and protein(s) that were highly infectious to naïve cells. RNaseAand neutralizing antibodies treatment studies suggest the presence of viral RNA/proteins inside exosomes. Exosomes derived from time- and dose-dependent incubations showed increasing viral loads suggesting higher packaging and delivery of ZIKV RNA and proteins. Furthermore, we noted that ZIKV induced both activity and gene expression of neutral Sphingomyelinase (nSMase)-2/SMPD3, an important molecule that regulates production and release of exosomes. Silencing of SMPD3 in neurons resulted in reduced viral burden and transmission through exosomes. Treatment with SMPD3 specific inhibitor GW4869,significantly reduced ZIKV loads in both cortical neurons and in exosomes derived from these neuronal cells. Taken together, our results suggest that ZIKV modulates SMPD3 activity in cortical neurons for its infection and transmission through exosomes perhaps leading to severe neuronal death that may result in neurological manifestations such as microcephaly in the developing embryonic brains.


greenmedinfo--2020-05-18--Exosomes modulate the viral replication and host immune responses in hepatitis B virus infection.

Although current diagnosis and treatment of hepatitis B virus ( HBV ) infection can maintain viral suppression , new therapies @ @ @ @ @ sustain off-treatment virologic suppression and reduce side effects .
Exosomes act as intercellular communicators to @ @ @ @ @ , lipids , and nucleic acids between cellsand .
Pioneering work has demonstrated that exosomal @ @ @ @ @ infection .
An improved understanding of the functions of exosomes during HBV infection could lead @ @ @ @ @ for preventing and treating HBV .
In this review , we point out the role @ @ @ @ @ : ( 1 ) exosomes could directly participate in HBV replication ; ( 2 ) @ @ @ @ @ HBV infections ; ( 3 ) exosomal RNAs and proteins might be selected as novel @ @ @ @ @ HBV infections ; and ( 4 ) exosomes can also be designed as vaccines .

Although current diagnosis and treatment of hepatitis B virus (HBV) infection can maintain viral suppression, new therapies need to be invented to sustain off-treatment virologic suppression and reduce side effects. Exosomes act as intercellular communicators to facilitate direct transfer of proteins, lipids, and nucleic acids between cellsand. Pioneering work has demonstrated that exosomal cargos changed markedly during HBV infection. An improved understanding of the functions of exosomes during HBV infection could lead to a powerful new strategy for preventing and treating HBV. In this review, we point out the role of exosomes in HBV infection: (1) exosomes could directly participate in HBV replication; (2) exosomes modulate immune response during HBV infections; (3) exosomal RNAs and proteins might be selected as novel biomarkers for the diagnosis of HBV infections; and (4) exosomes can also be designed as vaccines.


greenmedinfo--2020-05-18--Excessive exosome release is the pathogenic pathway linking a lysosomal deficiency to generalized fi

Excessive exosome release is the pathogenic pathway linking a lysosomal deficiency to generalized fibrosis.

Lysosomal exocytosis is a ubiquitous process negatively regulated by neuraminidase 1 ( NEU1 ) , a sialidase mutated in the @ @ @ @ @ Inmice , excessive lysosomal exocytosis is at the basis of disease pathogenesis .
Yet , @ @ @ @ @ this deregulated pathway are still unfolding .
We now report that in muscle connective tissue @ @ @ @ @ myofibroblasts and are proliferative , migratory , and exocytose large amounts of exosomes .
These @ @ @ @ @ growth factor-β and wingless-related integration site ( WNT ) /β-catenin signaling molecules propagate fibrotic signals @ @ @ @ @ the tissue in a prolonged transitional status .
Myofibroblast-derived exosomes fed to normal fibroblasts convert @ @ @ @ @ the recipient cells'proliferative and migratory properties .
These findings reveal an unexpected exosome-mediated signaling pathway @ @ @ @ @ propagates a fibrotic disease and could be implicated in idiopathic forms of fibrosis in humans @

Lysosomal exocytosis is a ubiquitous process negatively regulated by neuraminidase 1 (NEU1), a sialidase mutated in the glycoprotein storage disease sialidosis. Inmice, excessive lysosomal exocytosis is at the basis of disease pathogenesis. Yet, the tissue-specific molecular consequences of this deregulated pathway are still unfolding. We now report that in muscle connective tissue,fibroblasts have features of myofibroblasts and are proliferative, migratory, and exocytose large amounts of exosomes. These nanocarriers loaded with activated transforming growth factor-β and wingless-related integration site (WNT)/β-catenin signaling molecules propagate fibrotic signals to other cells, maintaining the tissue in a prolonged transitional status. Myofibroblast-derived exosomes fed to normal fibroblasts convert them into myofibroblasts, changing the recipient cells'proliferative and migratory properties. These findings reveal an unexpected exosome-mediated signaling pathway downstream of NEU1 deficiency that propagates a fibrotic disease and could be implicated in idiopathic forms of fibrosis in humans.


greenmedinfo--2020-05-18--The Social, Psychic and Health Challenges of the Coronavirus Crisis Explored [Video]

Sayer Ji appears on the Robert Phoenix show and breaks down the social , psychic and health challenges of the @ @ @ @ @ the Coronavirus crisis .
Take action and join a community who cares about health freedom @ @ @ @ @ Sayer 's daily updates via his newsletter here : https : //www.greenmedinfo.com/newsletter Get his new @ @ @ @ @ best-selling book on cultivating radical resiliency through the lens of the New Biology : https @ @ @ @ @ Coronavirus and topics discussed in this interview via Sayer 's natural health website : https @ @ @ @ @ episode .
In the second hour , film maker and Qi Gong enthusiast , Sharron @ @ @ @ @ healing , the power of Qi and her latest work , documenting this powerful energy/lifestyle/practice @ @ @ @ @ v=PUdv3T-Wrsc

Visit our Re-post guidelines This article is copyrighted by GreenMedInfo LLC, 2020
Sayer Ji appears on the Robert Phoenix show and breaks down the social, psychic and health challenges of the current lockdown and state of the Coronavirus crisis.
Take action and join a community who cares about health freedom: https://www.standforhealthfreedom.com
Get Sayer's daily updates via his newsletter here: https://www.greenmedinfo.com/newsletter
Get his new book REGENERATE, an international best-selling book on cultivating radical resiliency through the lens of the New Biology: https://www.amazon.com/Regenerate-Biological-Reverse-Chronic-Disease/dp/1401956386
Learn more about Coronavirus and topics discussed in this interview via Sayer's natural health website: https://www.greenmedinfo.com/disease/coronavirus-disease
Watch the full episode. In the second hour, film maker and Qi Gong enthusiast, Sharron Rose joins us to discuss healing, the power of Qi and her latest work, documenting this powerful energy/lifestyle/practice: https://www.youtube.com/watch?v=PUdv3T-Wrsc


greenmedinfo--2020-05-18--Exosomes containing HIV protein Nef reorganize lipid rafts potentiating inflammatory response in bys

Exosomes containing HIV protein Nef reorganize lipid rafts potentiating inflammatory response in bystander cells.

HIV infection has a profound effect on '' bystander '' cells causing metabolic co-morbidities .
This may be mediated by exosomes secreted by HIV-infected cells and containing viral factors .
Here we show that exosomes containing HIV-1 protein Nef ( exNef ) are rapidly taken up by macrophages releasing Nef into the cell interior .
This caused down-regulation of ABCA1 , reduction of cholesterol efflux and sharp elevation of the abundance of lipid rafts through reduced activation of small GTPase Cdc42 and decreased actin polymerization .
Changes in rafts led to re-localization of TLR4 and TREM-1 to rafts , phosphorylation @ @ @ @ @ @ @ , and increased secretion of pro-inflammatory cytokines .
The effects of exNef on lipid rafts and on inflammation were reversed by overexpression of a constitutively active mutant of Cdc42 .
Similar effects were observed in macrophages treated with exosomes produced by HIV-infected cells or isolated from plasma of HIV-infected subjects , but not with exosomes from cells and subjects infected withΔNef-HIV or uninfected subjects .
Mice injected with exNef exhibited monocytosis , reduced ABCA1 in macrophages , increased raft abundance in monocytes and augmented inflammation .
Thus , Nef-containing exosomes potentiated pro-inflammatory response @ @ @ @ @ @ @ reorganizing lipid rafts .
These mechanisms may contribute to HIV-associated metabolic co-morbidities .

HIV infection has a profound effect on"bystander"cells causing metabolic co-morbidities. This may be mediated by exosomes secreted by HIV-infected cells and containing viral factors. Here we show that exosomes containing HIV-1 protein Nef (exNef) are rapidly taken up by macrophages releasing Nef into the cell interior. This caused down-regulation of ABCA1, reduction of cholesterol efflux and sharp elevation of the abundance of lipid rafts through reduced activation of small GTPase Cdc42 and decreased actin polymerization. Changes in rafts led to re-localization of TLR4 and TREM-1 to rafts, phosphorylation of ERK1/2, activation of NLRP3 inflammasome, and increased secretion of pro-inflammatory cytokines. The effects of exNef on lipid rafts and on inflammation were reversed by overexpression of a constitutively active mutant of Cdc42. Similar effects were observed in macrophages treated with exosomes produced by HIV-infected cells or isolated from plasma of HIV-infected subjects, but not with exosomes from cells and subjects infected withΔNef-HIV or uninfected subjects. Mice injected with exNef exhibited monocytosis, reduced ABCA1 in macrophages, increased raft abundance in monocytes and augmented inflammation. Thus, Nef-containing exosomes potentiated pro-inflammatory response by inducing changes in cholesterol metabolism and reorganizing lipid rafts. These mechanisms may contribute to HIV-associated metabolic co-morbidities.


greenmedinfo--2020-05-18--Exosome-delivered and Y RNA-derived small RNA suppresses influenza virus replication

BACKGROUND : Multiple interplays between viral and host factors are involved in influenza virus replication and pathogenesis .
Several small RNAs have recently emerged as important regulators of host response to viral infections .
The aim of this study was to characterize the functional role of hsa-miR-1975 , a Y5 RNA-derived small RNA , in defending influenza virus and delineate the mechanisms .
METHODS : We performed high throughput sequencing of small RNAs in influenza virus-infected cells to identify up- or down- regulated small RNA species .
The expression of the most abundant RNA species ( hsa-miR-1975 ) was validated @ @ @ @ @ @ @ RT-PCR ) .
Antiviral effects of hsa-miR-1975 were confirmed by Western Blot , RT-PCR and plaque assay .
In vitro perturbation of hsa-miR-1975 combined with exosomes isolation was used to elucidate the role and mechanism of hsa-miR-1975 in the context of antiviral immunity .
RESULTS : Small RNA sequencing revealed that hsa-miR-1975 was the most up-regulated small RNA in influenza virus-infected cells .
The amount of intracellular hsa-miR-1975 increased in the late stage of the influenza virus replication cycle .
The increased hsa-miR-1975 was at least partially derived from degradation of Y5RNA as @ @ @ @ @ @ @ , hsa-miR-1975 mimics inhibited influenza virus replication while hsa-miR-1975 sponges enhanced the virus replication .
Moreover , hsa-miR-1975 was secreted in exosomes and taken up by the neighboring cells to induce interferon expression .
CONCLUSIONS : Our findings unravel a critical role of Y-class small RNA in host 's defense against influenza virus infection and reveal its antiviral mechanism through exosome delivery .
This may provide a new candidate for targeting influenza virus .

BACKGROUND: Multiple interplays between viral and host factors are involved in influenza virus replication and pathogenesis. Several small RNAs have recently emerged as important regulators of host response to viral infections. The aim of this study was to characterize the functional role of hsa-miR-1975, a Y5 RNA-derived small RNA, in defending influenza virus and delineate the mechanisms.
METHODS: We performed high throughput sequencing of small RNAs in influenza virus-infected cells to identify up- or down- regulated small RNA species. The expression of the most abundant RNA species (hsa-miR-1975) was validated by stem-loop reverse transcription-polymerase chain reaction (RT-PCR). Antiviral effects of hsa-miR-1975 were confirmed by Western Blot, RT-PCR and plaque assay. In vitro perturbation of hsa-miR-1975 combined with exosomes isolation was used to elucidate the role and mechanism of hsa-miR-1975 in the context of antiviral immunity.
RESULTS: Small RNA sequencing revealed that hsa-miR-1975 was the most up-regulated small RNA in influenza virus-infected cells. The amount of intracellular hsa-miR-1975 increased in the late stage of the influenza virus replication cycle. The increased hsa-miR-1975 was at least partially derived from degradation of Y5RNA as a result of cellular apoptosis. Unexpectedly, hsa-miR-1975 mimics inhibited influenza virus replication while hsa-miR-1975 sponges enhanced the virus replication. Moreover, hsa-miR-1975 was secreted in exosomes and taken up by the neighboring cells to induce interferon expression.
CONCLUSIONS: Our findings unravel a critical role of Y-class small RNA in host's defense against influenza virus infection and reveal its antiviral mechanism through exosome delivery. This may provide a new candidate for targeting influenza virus.


greenmedinfo--2020-05-18--Pathogenic role of exosomes and microRNAs in HPV-mediated inflammation and cervical cancer.

Cervical cancer ( CC ) is the fourth most common cause of cancer death in women .
The most important risk factor for the development of CC is cervical infection with human papilloma virus ( HPV ) .
Inflammation is a protective strategy that is triggered by the host against pathogens such as viral infections that acts rapidly to activate the innate immune response .
Inflammation is beneficial if it is brief and well controlled ; however , if the inflammation is excessive or it becomes of chronic duration , it can produce detrimental effects .
HPV proteins are involved @ @ @ @ @ @ @ the development of chronic inflammation , which is a causal factor in the development of CC .
However , other factors may also have a potential role in stimulating chronic inflammation .
MicroRNAs ( miRNAs ) ( a class of noncoding RNAs ) are strong regulators of gene expression .
They have emerged as key players in several biological processes , including inflammatory pathways .
Abnormal expression of miRNAs may be linked to the induction of inflammation that occurs in CC .
Exosomes are a subset of extracellular vesicles shed by almost all @ @ @ @ @ @ @ as cargo transfer vehicles .
Exosomes contain proteins and genetic material ( including miRNAs ) derived from their parent cells and can potentially affect recipient cells .
Exosomes have recently been recognized to be involved in inflammatory processes and can also affect the immune response .
In this review , we discuss the role of HPV proteins , miRNAs and exosomes in the inflammation associated with CC .

Cervical cancer (CC) is the fourth most common cause of cancer death in women. The most important risk factor for the development of CC is cervical infection with human papilloma virus (HPV). Inflammation is a protective strategy that is triggered by the host against pathogens such as viral infections that acts rapidly to activate the innate immune response. Inflammation is beneficial if it is brief and well controlled; however, if the inflammation is excessive or it becomes of chronic duration, it can produce detrimental effects. HPV proteins are involved, both directly and indirectly, in the development of chronic inflammation, which is a causal factor in the development of CC. However, other factors may also have a potential role in stimulating chronic inflammation. MicroRNAs (miRNAs) (a class of noncoding RNAs) are strong regulators of gene expression. They have emerged as key players in several biological processes, including inflammatory pathways. Abnormal expression of miRNAs may be linked to the induction of inflammation that occurs in CC. Exosomes are a subset of extracellular vesicles shed by almost all types of cells, which can function as cargo transfer vehicles. Exosomes contain proteins and genetic material (including miRNAs) derived from their parent cells and can potentially affect recipient cells. Exosomes have recently been recognized to be involved in inflammatory processes and can also affect the immune response. In this review, we discuss the role of HPV proteins, miRNAs and exosomes in the inflammation associated with CC.


greenmedinfo--2020-05-18--Expression patterns of exosomal miRNAs are a promising tool to predict sustained viral response- hep

Expression patterns of exosomal miRNAs are a promising tool to predict sustained viral response- hepatocellular carcinoma.

Direct-acting antiviral ( DAA ) therapy for chronic hepatitis C virus ( HCV ) infection patients ( CH ) results in a sustained viral response ( SVR ) in over 95 % of patients .
However , hepatocellular carcinoma ( HCC ) occurs in 1-5 % of patients who achieved an SVR after treatment with interferon .
We attempted to develop a minimally invasive and highly reliable method of predicting the occurrence and recurrence of HCC in patients who achieved an SVR with DAA therapy .
The exosomal miRNA expression patterns of 69 CH patients who underwent HCC curative treatment @ @ @ @ @ @ @ microarray analysis .
We identified a miRNA expression pattern characteristic of SVR-HCC by using machine learning .
Twenty-five of 69 patients had HCC recurrence .
The expression of four exosomal miRNAs predicted HCC recurrence with 85.3 % accuracy .
Fifteen of 70 patients had HCC occurrence .
The expression of four exosomal miRNAs predicted the onset of HCC with 85.5 % accuracy .
The expression patterns of miR-4718 , 642a-5p , 6826-3p , and 762 in exosomes were positively correlated with those in the liver , and downregulation of these miRNAs induced cell @ @ @ @ @ @ @ Aberrant expression of four miRNAs , which was used for prediction , was associated with HCC onset after HCV eradication .
Expression patterns of exosomal miRNAs are a promising tool to predict SVR-HCC .

Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection patients (CH) results in a sustained viral response (SVR) in over 95% of patients. However, hepatocellular carcinoma (HCC) occurs in 1-5% of patients who achieved an SVR after treatment with interferon. We attempted to develop a minimally invasive and highly reliable method of predicting the occurrence and recurrence of HCC in patients who achieved an SVR with DAA therapy. The exosomal miRNA expression patterns of 69 CH patients who underwent HCC curative treatment and 70 CH patients were assessed using microarray analysis. We identified a miRNA expression pattern characteristic of SVR-HCC by using machine learning. Twenty-five of 69 patients had HCC recurrence. The expression of four exosomal miRNAs predicted HCC recurrence with 85.3% accuracy. Fifteen of 70 patients had HCC occurrence. The expression of four exosomal miRNAs predicted the onset of HCC with 85.5% accuracy. The expression patterns of miR-4718, 642a-5p, 6826-3p, and 762 in exosomes were positively correlated with those in the liver, and downregulation of these miRNAs induced cell proliferation and prevented apoptosis in vitro. Aberrant expression of four miRNAs, which was used for prediction, was associated with HCC onset after HCV eradication. Expression patterns of exosomal miRNAs are a promising tool to predict SVR-HCC.


greenmedinfo--2020-05-18--Dengue haemorrhagic fever: a job done via exosomes?

Dengue fever is one of those unique diseases where host immune responses largely determine the pathogenesis and its severity .
Earlier studies have established the fact that dengue virus ( DENV ) infection causes haemorrhagic fever and shock syndrome , but it is not directly responsible for exhibiting these clinical symptoms .
It is noteworthy that clinically , vascular leakage syndrome does not develop for several days after infection despite a robust innate immune response that elicits the production of proinflammatory and proangiogenic cytokines .
The onset of hyperpermeability in severe cases of dengue disease takes place around the time @ @ @ @ @ @ @ .
Extracellular vesicles are known to carry biological information ( mRNA , miRNA , transcription factors ) from their cells of origin and have emerged as a significant vehicle for horizontal transfer of stress signals .
In dengue virus infection , the relevance of exosomes can be instrumental since the majority of the immune responses in severe dengue involve heavy secretion and circulation of pro-inflammatory cytokines and chemokines .
Here , we present an updated review which will address the unique and puzzling features of hyperpermeability associated with DENV infection with a special @ @ @ @ @ @ @ vesicles .

Dengue fever is one of those unique diseases where host immune responses largely determine the pathogenesis and its severity. Earlier studies have established the fact that dengue virus (DENV) infection causes haemorrhagic fever and shock syndrome, but it is not directly responsible for exhibiting these clinical symptoms. It is noteworthy that clinically, vascular leakage syndrome does not develop for several days after infection despite a robust innate immune response that elicits the production of proinflammatory and proangiogenic cytokines. The onset of hyperpermeability in severe cases of dengue disease takes place around the time of defervescence and after clearance of viraemia. Extracellular vesicles are known to carry biological information (mRNA, miRNA, transcription factors) from their cells of origin and have emerged as a significant vehicle for horizontal transfer of stress signals. In dengue virus infection, the relevance of exosomes can be instrumental since the majority of the immune responses in severe dengue involve heavy secretion and circulation of pro-inflammatory cytokines and chemokines. Here, we present an updated review which will address the unique and puzzling features of hyperpermeability associated with DENV infection with a special focus on the role of secreted extracellular vesicles.


greenmedinfo--2020-05-18--CD81+ exosomes play a pivotal role in the establishment of hepatitis C persistent infection and cont

CD81+ exosomes play a pivotal role in the establishment of hepatitis C persistent infection and contribute toward the progression of hepatocellular carcinoma.

CD81 serves as an immune modulator , playing its role in tumor growth and metastasis of hepatitis C virus ( HCV ) -mediated hepatocellular carcinoma ( HCC ) .
CD81 serves as a coreceptor of viral entry and is found to be enriched in exosomes .
HCV E2 protein when associated with CD81 may be responsible for B cell lymphoproliferative disorders , as extrahepatic manifestation .
Studies predict that HCV association with exosomes , leads to the establishment of persistent infection , through immune evasion .
Herein , we confirm the association of HCV particles with CD81exosomes .
Breifly , @ @ @ @ @ @ @ chronic HCV patients who have developed HCC .
Sideways , exosomes were also enriched from peripheral blood of healthy individuals , who exhibited normal liver function test profile and had no known infection .
Isolation of subpopulation of CD81exosomes was performed through immunocapture , followed by detection using FACS .
Scanning electron microscopy confirmed the physical association of a fraction of exosome with HCV .
CD81exosomes from chronic HCV patients with HCC were more granulated and larger when compared with those enriched from a healthy individual and HCV RNA was also detected in @ @ @ @ @ @ @ patients only , through real-time quantitative polymerase chain reaction .
We concluded that CD81exosomes carry HCV particles and the association plays a pivotal role in establishing persistent infection , through immune evasion , thus leading to HCC progression .
Exosomal CD81 and its interacting proteins might , therefore , serve as a potential prognostic marker and therapeutic target in HCV progression mediated by active HCV infection .

CD81 serves as an immune modulator, playing its role in tumor growth and metastasis of hepatitis C virus (HCV)-mediated hepatocellular carcinoma (HCC). CD81 serves as a coreceptor of viral entry and is found to be enriched in exosomes. HCV E2 protein when associated with CD81 may be responsible for B cell lymphoproliferative disorders, as extrahepatic manifestation. Studies predict that HCV association with exosomes, leads to the establishment of persistent infection, through immune evasion. Herein, we confirm the association of HCV particles with CD81exosomes. Breifly, exosomes were enriched from peripheral blood of chronic HCV patients who have developed HCC. Sideways, exosomes were also enriched from peripheral blood of healthy individuals, who exhibited normal liver function test profile and had no known infection. Isolation of subpopulation of CD81exosomes was performed through immunocapture, followed by detection using FACS. Scanning electron microscopy confirmed the physical association of a fraction of exosome with HCV. CD81exosomes from chronic HCV patients with HCC were more granulated and larger when compared with those enriched from a healthy individual and HCV RNA was also detected in enriched fractions of CD81exosomes from HCV-positive HCC patients only, through real-time quantitative polymerase chain reaction. We concluded that CD81exosomes carry HCV particles and the association plays a pivotal role in establishing persistent infection, through immune evasion, thus leading to HCC progression. Exosomal CD81 and its interacting proteins might, therefore, serve as a potential prognostic marker and therapeutic target in HCV progression mediated by active HCV infection.


greenmedinfo--2020-05-17--Blueberry polyphenols play a preventive effect on alcoholic fatty liver disease.

BACKGROUND : This study aims to explore blueberry polyphenols and its roles in nonalcoholic fatty liver disease ( NAFLD ) by relieving hepatic steatosis , and to understand alcoholic fatty liver disease ( AFLD ) .
Cell autophagy has been proved to promote lipid metabolism and is involved in the pathogenesis of AFLD ; however , whether blueberry polyphenol affects autophagy is unknown .
Therefore , our study analyzes the functions of blueberry polyphenol on AFLD and if its mechanisms are engaged with hepatocytes autophagy .
METHODS : We built the AFLD mice model via alcohol abduction , and the @ @ @ @ @ @ @ steatosis through ORO and HE stains .
For blood lipid levels measurements , serum CHOL and TG concentrations were tests .
For mechanism analysis , the lipogenic genes of SREBP1 , FAS , and ACCα , and the lipodieretic genes of ATGL and Sirt1 were evaluated by qRT-PCR , as well as the autophagy proteins of p62 ; WB measured LC3-I and LC3-II .
RESULTS : We found that chronic alcohol intake successfully induced AFLD occurrence with increased TG lipid droplets content in liver and serum CHOL and TG levels that accompanied by @ @ @ @ @ @ @ , as well as enhancive p62 protein and decreased LC3-II/LC3-I proportion .
However , after blueberry polyphenol intake , there were opposite outcomes happened .
Moreover , blueberry polyphenol alone did not affect the lipid metabolism but promoted the hepatocytes autophagy at 200 mg/kg concentration .
CONCLUSIONS : In summary , we are unparalleled that illustrated blueberry polyphenols can prevent AFLD development by promoting autophagy to accelerate lipid metabolism than to lighten hepatic steatosis .

BACKGROUND: This study aims to explore blueberry polyphenols and its roles in nonalcoholic fatty liver disease (NAFLD) by relieving hepatic steatosis, and to understand alcoholic fatty liver disease (AFLD). Cell autophagy has been proved to promote lipid metabolism and is involved in the pathogenesis of AFLD; however, whether blueberry polyphenol affects autophagy is unknown. Therefore, our study analyzes the functions of blueberry polyphenol on AFLD and if its mechanisms are engaged with hepatocytes autophagy.
METHODS: We built the AFLD mice model via alcohol abduction, and the TG lipid droplets content detected the hepatic steatosis through ORO and HE stains. For blood lipid levels measurements, serum CHOL and TG concentrations were tests. For mechanism analysis, the lipogenic genes of SREBP1, FAS, and ACCα, and the lipodieretic genes of ATGL and Sirt1 were evaluated by qRT-PCR, as well as the autophagy proteins of p62; WB measured LC3-I and LC3-II.
RESULTS: We found that chronic alcohol intake successfully induced AFLD occurrence with increased TG lipid droplets content in liver and serum CHOL and TG levels that accompanied by increased lipogenic and reduced lipodieretic mRNA levels, as well as enhancive p62 protein and decreased LC3-II/LC3-I proportion. However, after blueberry polyphenol intake, there were opposite outcomes happened. Moreover, blueberry polyphenol alone did not affect the lipid metabolism but promoted the hepatocytes autophagy at 200 mg/kg concentration.
CONCLUSIONS: In summary, we are unparalleled that illustrated blueberry polyphenols can prevent AFLD development by promoting autophagy to accelerate lipid metabolism than to lighten hepatic steatosis.


greenmedinfo--2020-05-17--Blueberry-derived exosome-like nanoparticles counter the response to TNF-α-induced change on gene ex

Blueberry-derived exosome-like nanoparticles counter the response to TNF-α-induced change on gene expression in EA.hy926 cells.

Exosome-like nanoparticles ( ELNs ) are attracting interest as important vehicles of intercellular communication , both in prokaryotes and eukaryotes .
Recently , dietary nanoparticles similar to mammalian exosomes have attracted attention for these features .
In particular they appear to be relevant in the modulation of several cellular processes as well as candidate carriers of bioactive molecules ( proteins , lipids , and nucleic acids , including miRNAs ) with therapeutic value .
Herein , we investigated the cellular uptake of blueberry-derived ELNs ( B-ELNs ) by a human stabilized endothelial cell line ( EA.hy926 ) and the ability @ @ @ @ @ @ @ inflammatory genes as the response of tumor necrosis factor-α ( TNF-α ) .
Our results indicate that 1 ) EA.hy926 cells internalize B-ELNs in a dose-dependent manner ; 2 ) pretreatment with B-ELNs counters TNF-α-induced reactive oxygen species ( ROS ) generation and loss of cell viability and modulates the differential expression of 29 genes ( fold change > 1.5 ) induced by TNF-α compared to control ; 3 ) pathway analysis reveals their involvement in a total of 340 canonical pathways , 121 KEGG pathways , and 121 GO Biological processes ; @ @ @ @ @ @ @ expressed ( DE ) genes and miRNAs contained in B-ELNs unveils a set of candidate target genes , such as prostaglandin I2 synthase ( PTGIS ) , mitogen-activated protein kinase 14 ( MAPK14 ) , and phosphodiesterase 7A ( PDE7A ) , for ELNs-contained cargo .
In conclusion , our study indicates that B-ELNs can be considered candidate therapeutic carriers of bioactive compounds potentially able to protect vascular system against various stressors .

Exosome-like nanoparticles (ELNs) are attracting interest as important vehicles of intercellular communication, both in prokaryotes and eukaryotes. Recently, dietary nanoparticles similar to mammalian exosomes have attracted attention for these features. In particular they appear to be relevant in the modulation of several cellular processes as well as candidate carriers of bioactive molecules (proteins, lipids, and nucleic acids, including miRNAs) with therapeutic value. Herein, we investigated the cellular uptake of blueberry-derived ELNs (B-ELNs) by a human stabilized endothelial cell line (EA.hy926) and the ability of B-ELNs to modulate the expression of inflammatory genes as the response of tumor necrosis factor-α (TNF-α). Our results indicate that 1) EA.hy926 cells internalize B-ELNs in a dose-dependent manner; 2) pretreatment with B-ELNs counters TNF-α-induced reactive oxygen species (ROS) generation and loss of cell viability and modulates the differential expression of 29 genes (fold change>1.5) induced by TNF-α compared to control; 3) pathway analysis reveals their involvement in a total of 340 canonical pathways, 121 KEGG pathways, and 121 GO Biological processes; and 4) the intersection between differentially expressed (DE) genes and miRNAs contained in B-ELNs unveils a set of candidate target genes,such as prostaglandin I2 synthase (PTGIS), mitogen-activated protein kinase 14 (MAPK14), and phosphodiesterase 7A (PDE7A), for ELNs-contained cargo. In conclusion, our study indicates that B-ELNs can be considered candidate therapeutic carriers of bioactive compounds potentially able to protect vascular system against various stressors.


greenmedinfo--2020-05-17--Chemoprotective effect of carotenoids from Lycium barbarum L. on SH-SY5Y neuroblastoma cells treated

Chemoprotective effect of carotenoids from Lycium barbarum L. on SH-SY5Y neuroblastoma cells treated with beauvericin.

Goji berry has recently been introduced in Mediterranean diet and its consumption is increasing .
This study aims to determine cytoprotection of lutein ( LUT ) , zeaxanthin ( ZEAX ) and goji berry extract ( GBE ) rich in carotenoids against Beauvericin ( BEA ) -induced cytotoxicity on SH-SY5Y neuroblastoma cells .
Both carotenoids and GBE showed cytoprotective effects .
Cytoprotection was evaluated by simultaneous combination of the two xanthophylls LUT and ZEAX with BEA , as well as using pre-treatment assays .
The highest protective effect occurred in 16 % , 24 % and 12 % respectively for @ @ @ @ @ @ @ incubating simultaneously with BEA , while by pre-treatment assay LUT showed a cytoprotection effect over 30 % and ZEAX alone or LUT + ZEAX promoted only a slight cytoprotection ( < 10 % ) .
Pre-treatment assays with GBE , showed a cytoprotection , between 3 and 20 % , for BEA concentrations ranging from 0.1 to 6.25 μM , whereas no protective effect was observed when the cells were simultaneously incubated with GBE and BEA .
Finally , by means of CI-isobologram method , the interaction between LUT , ZEAX and BEA @ @ @ @ @ @ @ an synergism effect for almost all combinations tested .
The data presented shows a option of using goji berries to potentially mitigate the toxicity of beauvericin eventually present in foods .

Goji berry has recently been introduced in Mediterranean diet and its consumption is increasing. This study aims to determine cytoprotection of lutein (LUT), zeaxanthin (ZEAX) and goji berry extract (GBE) rich in carotenoids against Beauvericin (BEA)-induced cytotoxicity on SH-SY5Y neuroblastoma cells. Both carotenoids and GBE showed cytoprotective effects. Cytoprotection was evaluated by simultaneous combination of the two xanthophylls LUT and ZEAX with BEA, as well as using pre-treatment assays. The highest protective effect occurred in 16%, 24% and 12% respectively for LUT, ZEAX and LUT + ZEAX incubating simultaneously with BEA, while by pre-treatment assay LUT showed a cytoprotection effect over 30% and ZEAX alone or LUT + ZEAX promoted only a slight cytoprotection (<10%). Pre-treatment assays with GBE, showed a cytoprotection, between 3 and 20%, for BEA concentrations ranging from 0.1 to 6.25 μM, whereas no protective effect was observed when the cells were simultaneously incubated with GBE and BEA. Finally, by means of CI-isobologram method, the interaction between LUT, ZEAX and BEA were evaluated, and the results showed an synergism effect for almost all combinations tested. The data presented shows a option of using goji berries to potentially mitigate the toxicity of beauvericin eventually present in foods.


greenmedinfo--2020-05-17--Lycium barbarum polysaccharide may improve allergic asthma by altering gut microbiota and inhibiting

Lycium barbarum polysaccharide may improve allergic asthma by altering gut microbiota and inhibiting inflammation in mice.

This study was designed to explore the impact ofpolysaccharide ( LBP ) on inflammation and gut microbiota in mice with @ @ @ @ @ divided into four groups : control group , OVA ( ovalbumin ) group , Con+LBP @ @ @ @ @ After 28 days of LBP intervention , mice were euthanized and associated indications were investigated @ @ @ @ @ LBP reduced lung injury .
The results of our current study provide evidence that supplementation @ @ @ @ @ decreases , , , , andin plasma and bronchoalveolar lavage fluid ( BALF ) .
@ @ @ @ @ microbiota indicated that compared with the OVA group , andwere increased , but , , @ @ @ @ @ OVA+LBP group .
We also found that gut microbiota were related to inflammation-related factors .
@ @ @ @ @ LBP may improve allergic asthma by altering gut microbiota and inhibiting inflammation in mice .

This study was designed to explore the impact ofpolysaccharide (LBP) on inflammation and gut microbiota in mice with allergic asthma. Mice were divided into four groups: control group, OVA (ovalbumin) group, Con+LBP group, OVA+LBP group. After 28 days of LBP intervention, mice were euthanized and associated indications were investigated. Histopathological examination demonstrated that LBP reduced lung injury. The results of our current study provide evidence that supplementation with LBP in asthmatic mice decreases,,,, andin plasma and bronchoalveolar lavage fluid (BALF). Sequencing and analysis of gut microbiota indicated that compared with the OVA group,andwere increased, but,,, andwere decreased in the OVA+LBP group. We also found that gut microbiota were related to inflammation-related factors. Therefore, we speculate that LBP may improve allergic asthma by altering gut microbiota and inhibiting inflammation in mice.


greenmedinfo--2020-05-17--MicroRNAs and exosomes: key players in HIV pathogenesis.

OBJECTIVES : HIV infection is well known to cause impairment of the human immune system , and until recently was a leading cause of death .
It has been shown that T lymphocytes are the main targets of HIV .
The virus inactivates T lymphocytes by interfering with a wide range of cellular and molecular targets , leading to suppression of the immune system .
The objective of this review is to investigate to what extent microRNAs ( miRNAs ) are involved in HIV pathogenesis .
METHODS : The scientific literature ( Pubmed and Google scholar ) for the period @ @ @ @ @ @ @ evidence has revealed that miRNAs are involved in viral replication and immune response , whether by direct targeting of viral transcripts or through indirect modulation of virus-related host pathways .
In addition , exosomes have been found to act as nanoscale carriers involved in HIV pathogenesis .
These nanovehicles target their cargos ( i.e .
DNA , RNA , viral proteins and miRNAs ) leading to alteration of the behaviour of recipient cells .
CONCLUSIONS : miRNAs and exosomes are important players in HIV pathogenesis .
Additionally , there are potential diagnostic applications @ @ @ @ @ @ @ .

OBJECTIVES: HIV infection is well known to cause impairment of the human immune system, and until recently was a leading cause of death. It has been shown that T lymphocytes are the main targets of HIV. The virus inactivates T lymphocytes by interfering with a wide range of cellular and molecular targets, leading to suppression of the immune system. The objective of this review is to investigate to what extent microRNAs (miRNAs) are involved in HIV pathogenesis.
METHODS: The scientific literature (Pubmed and Google scholar) for the period 1988-2019 was searched.
RESULTS: Mounting evidence has revealed that miRNAs are involved in viral replication and immune response, whether by direct targeting of viral transcripts or through indirect modulation of virus-related host pathways. In addition, exosomes have been found to act as nanoscale carriers involved in HIV pathogenesis. These nanovehicles target their cargos (i.e. DNA, RNA, viral proteins and miRNAs) leading to alteration of the behaviour of recipient cells.
CONCLUSIONS: miRNAs and exosomes are important players in HIV pathogenesis. Additionally, there are potential diagnostic applications of miRNAs as biomarkers in HIV infection.


greenmedinfo--2020-05-17--Exosomes cloak the virion to transmit Enterovirus 71 non-lytically.

Enterovirus 71 ( EV71 ) is a non-enveloped virus and it can be released from host cells through a traditional cytolytic manner .
Now , we showed EV71 could be spread non-lytically between cells during early viral infection .
In order to explain this phenomenon , we separated supernatant fluids of rhabdomyosarcoma ( RD ) cells cultures infected with EV71 by isopycnic gradient centrifugation .
Two populations of virus particles were morphology indistinguishable by transmission electron microscope ( TEM ) .
It showed that some EV71 particles were wrapped inside extracellular vesicles which were verified to be exosomes by immunoassay @ @ @ @ @ @ @ exosomes containing viral RNA were shed in plasma of EV71-infected encephalitis in children .
Our findings indicate that the '' non-enveloped '' EV71 virions could be wrapped within exosomes which promote their spread in the absence of cell lysis .
: EV71 : enterovirus 71 ; EXO : exosome ; RD : rhabdomyosarcoma ; TEM : transmission electron microscope ; HFMD : hand , foot , and mouth disease ; HIV : immunodeficiency virus ; HCV : hepatitis C virus ; HTLV : Human T-cell lymphotropic virus ; HAV : hepatitis A virus @ @ @ @ @ @ @ EVs : extracellular vesicles ; VP1 : viral capsid protein 1 ; NTA : nanoparticle tracking analysis ; CNS : central nervous system .

Enterovirus 71 (EV71) is a non-enveloped virus and it can be released from host cells through a traditional cytolytic manner. Now, we showed EV71 could be spread non-lytically between cells during early viral infection. In order to explain this phenomenon, we separated supernatant fluids of rhabdomyosarcoma (RD) cells cultures infected with EV71 by isopycnic gradient centrifugation. Two populations of virus particles were morphology indistinguishable by transmission electron microscope (TEM). It showed that some EV71 particles were wrapped inside extracellular vesicles which were verified to be exosomes by immunoassay and morphologic analysis. In addition, exosomes containing viral RNA were shed in plasma of EV71-infected encephalitis in children. Our findings indicate that the"non-enveloped" EV71 virions could be wrapped within exosomes which promote their spread in the absence of cell lysis.: EV71: enterovirus 71; EXO: exosome; RD: rhabdomyosarcoma; TEM: transmission electron microscope; HFMD: hand, foot, and mouth disease; HIV: immunodeficiency virus; HCV: hepatitis C virus; HTLV: Human T-cell lymphotropic virus; HAV: hepatitis A virus; MOI: multiplicity of infection; EVs: extracellular vesicles; VP1: viral capsid protein 1; NTA: nanoparticle tracking analysis; CNS: central nervous system.


greenmedinfo--2020-05-17--Where does the cargo go?: Solutions to provide experimental support for the "extracellular vesicle c

Where does the cargo go?: Solutions to provide experimental support for the "extracellular vesicle cargo transfer hypothesis".

It is widely believed that extracellular vesicles ( EVs ) mediate intercellular communications by functioning as messengers .
EVs contain various biomolecules , including nucleic acids and proteins , as cargo in the internal space .
Thus , it has been postulated that this cargo can be transferred from donor cells to recipient cells , leading to phenotypic changes in the recipient cells .
However , there is a lack of experimental evidence for the aforementioned hypothesis , that EVs function as messengers .
This is presumably because of a lack of rigorous methodologies for EV research .
Although cells @ @ @ @ @ @ @ the extracellular space via endocytosis , these NPs are processed through the endo/lysosomal system and do not escape to the cytoplasm unless they disrupt or fuse with the endo/lysosomal membrane .
Whether EVs actually are capable of escaping endo/lysosomes is still debatable .
In contrast , viruses have evolved to efficiently deliver their cargo ( viral proteins and genetic material ) into the cytoplasm of host ( recipient ) cells by circumventing endo/lysosomal degradation .
Thus , it may be helpful to compare EVs to viruses in terms of cargo delivery .
The @ @ @ @ @ @ @ for the '' EV cargo transfer hypothesis '' are summarized and potential solutions for EV research are proposed .

It is widely believed that extracellular vesicles (EVs) mediate intercellular communications by functioning as messengers. EVs contain various biomolecules, including nucleic acids and proteins, as cargo in the internal space. Thus, it has been postulated that this cargo can be transferred from donor cells to recipient cells, leading to phenotypic changes in the recipient cells. However, there is a lack of experimental evidence for the aforementioned hypothesis, that EVs function as messengers. This is presumably because of a lack of rigorous methodologies for EV research. Although cells usually incorporate nanoparticles (NPs) from the extracellular space via endocytosis, these NPs are processed through the endo/lysosomal system and do not escape to the cytoplasm unless they disrupt or fuse with the endo/lysosomal membrane. Whether EVs actually are capable of escaping endo/lysosomes is still debatable. In contrast, viruses have evolved to efficiently deliver their cargo (viral proteins and genetic material) into the cytoplasm of host (recipient) cells by circumventing endo/lysosomal degradation. Thus, it may be helpful to compare EVs to viruses in terms of cargo delivery. The present technological issues that hinder obtaining support for the"EV cargo transfer hypothesis"are summarized and potential solutions for EV research are proposed.


greenmedinfo--2020-05-17--Extracellular vesicles in Epstein-barr virus pathogenesis.

Purpose of review : Epstein-Barr virus ( EBV ) is a known determinant for numerous malignancies and may contribute to @ @ @ @ @ mechanisms behind EBV pathologies is not completely understood .
Recently , extracellular vesicles ( EVs @ @ @ @ @ have been found to produce profound effects on cellular microenvironments .
Therefore , in this @ @ @ @ @ evaluate the roles of EVs in EBV pathogenesis and assess their potential therapeutic and diagnostic @ @ @ @ @ EBV-altered EVs are capable of activating signaling cascades and phenotypic changes in recipient cells through @ @ @ @ @ and RNAs .
Moreover , several EV-associated microRNAs have encouraging prognostic or diagnostic potential in @ @ @ @ @ Current evidence suggests that EBV-modified EVs affect viral pathogenesis and cancer progression .
However , @ @ @ @ @ investigate the direct role of both viral and host products on recipient cells and the @ @ @ @ @ RNA EV packaging and content modification .

Purpose of review: Epstein-Barr virus (EBV) is a known determinant for numerous malignancies and may contribute to autoimmune diseases. The underlining mechanisms behind EBV pathologies is not completely understood. Recently, extracellular vesicles (EVs) released from infected cells have been found to produce profound effects on cellular microenvironments. Therefore, in this review we sought to critically evaluate the roles of EVs in EBV pathogenesis and assess their potential therapeutic and diagnostic utility.
Recent findings: EBV-altered EVs are capable of activating signaling cascades and phenotypic changes in recipient cells through the transfer of viral proteins and RNAs. Moreover, several EV-associated microRNAs have encouraging prognostic or diagnostic potential in EBV-associated cancers.
Summary: Current evidence suggests that EBV-modified EVs affect viral pathogenesis and cancer progression. However, further research is needed to investigate the direct role of both viral and host products on recipient cells and the mechanisms driving viral protein and RNA EV packaging and content modification.


greenmedinfo--2020-05-17--Exosomes may cause immunosuppression and immune tolerance.

Avian leukosis virus ( ALV ) is oncogenic retrovirus that not only causes immunosuppression but also enhances the host 's susceptibility to secondary infection .
Exosomes play vital role in the signal transduction cascades that occur in response to viral infection .
We want to explore the function of exosomes in the spread of ALV and the body 's subsequent immunological response .
RNA-sequencing and the isobaric tags for relative and absolute quantitation ( iTRAQ ) method were used to detect differentially expressed genes ( DEGs ) and differentially expressed proteins ( DEPs ) in exosomes secreted by macrophage cells @ @ @ @ @ @ @ J ( ALV-J ) .
RNA-sequencing identified 513 DEGs in infected cells , with specific differential regulation in mRNA involved in tight junction signaling , TNF signaling , salmonella infection response , and immune response , among other important cellular processes .
Differential regulation was observed in 843 lncRNAs , with particular enrichment in those lncRNA targets involved in Rap1 signaling , HTLV-I infection , tight junction signaling , and other signaling pathways .
A total of 50 DEPs were identified in the infected cells by iTRAQ .
The proteins enriched are involved @ @ @ @ @ @ @ the formation of both MHC protein and myosin complexes , and transport .
Combined analysis of the transcriptome and proteome revealed that there were 337 correlations between RNA and protein enrichment , five of which were significant .
Pathways that were enriched on both the RNA and protein levels were involved in pathways in cancer , PI3K-Akt signaling pathway , Endocytosis , Epstein-Barr virus infection .
These data show that exosomes are transmitters of intercellular signaling in response to viral infection .
Exosomes can carry both viral nucleic acids and proteins , making @ @ @ @ @ @ @ in the viral infection of other cells and the transmission of immune signals between cells .
Our sequencing results confirme previous studies on exosomes and further find exosomes may cause immunosuppression and immune tolerance .

Avian leukosis virus (ALV) is oncogenic retrovirus that not only causes immunosuppression but also enhances the host's susceptibility to secondary infection. Exosomes play vital role in the signal transduction cascades that occur in response to viral infection. We want to explore the function of exosomes in the spread of ALV and the body's subsequent immunological response. RNA-sequencing and the isobaric tags for relative and absolute quantitation (iTRAQ) method were used to detect differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in exosomes secreted by macrophage cells in response to injection with ALV subgroup J (ALV-J). RNA-sequencing identified 513 DEGs in infected cells, with specific differential regulation in mRNA involved in tight junction signaling, TNF signaling, salmonella infection response, and immune response, among other important cellular processes. Differential regulation was observed in 843 lncRNAs, with particular enrichment in those lncRNA targets involved in Rap1 signaling, HTLV-I infection, tight junction signaling, and other signaling pathways. A total of 50 DEPs were identified in the infected cells by iTRAQ. The proteins enriched are involved in immune response, antigen processing, the formation of both MHC protein and myosin complexes, and transport. Combined analysis of the transcriptome and proteome revealed that there were 337 correlations between RNA and protein enrichment, five of which were significant. Pathways that were enriched on both the RNA and protein levels were involved in pathways in cancer, PI3K-Akt signaling pathway, Endocytosis, Epstein-Barr virus infection. These data show that exosomes are transmitters of intercellular signaling in response to viral infection. Exosomes can carry both viral nucleic acids and proteins, making it possible for exosomes to be involved in the viral infection of other cells and the transmission of immune signals between cells. Our sequencing results confirme previous studies on exosomes and further find exosomes may cause immunosuppression and immune tolerance.