greenmedinfo--2020-05-25--Griffithsin and carrageenan combination to target herpes simplex virus 2 and human papillomavirus.

Extensive preclinical evaluation of griffithsin ( GRFT ) has identified this lectin to be a promising broad-spectrum microbicide .
We set out to explore the antiviral properties of a GRFT and carrageenan ( CG ) combination product against herpes simplex virus 2 ( HSV-2 ) and human papillomavirus ( HPV ) as well as determine the mechanism of action ( MOA ) of GRFT against both viruses .
We performed the experiments in different cell lines , using time-of-addition and temperature dependence experiments to differentiate inhibition of viral attachment from entry and viral receptor internalization .
Surface plasmon resonance ( @ @ @ @ @ @ @ binding to viral glycoproteins , and immunoprecipitation and immunohistochemistry were used to identify the specific glycoprotein involved .
We determined the antiviral activity of GRFT against HSV-2 to be a 50 % effective concentration ( EC50 ) of 230 nM and provide the first evidence that GRFT has moderate anti-HPV activity ( EC50 = 0.429 to 1.39μM ) .
GRFT blocks the entry of HSV-2 and HPV into target cells but not the adsorption of HSV-2 and HPV onto target cells .
The results of the SPR , immunoprecipitation , and immunohistochemistry analyses @ @ @ @ @ @ @ block viral entry by binding to HSV-2 glycoprotein D. Cell-based assays suggest anti-HPV activity through α6 integrin internalization .
The GRFT-CG combination product but not GRFT or CG alone reduced HSV-2 vaginal infection in mice when given an hour before challenge ( P = 0.0352 ) .
While GRFT significantly protected mice against vaginal HPV infection when dosed during and after HPV16 pseudovirus challenge ( P < 0.026 ) , greater CG-mediated protection was afforded by the GRFT-CG combination for up to 8 h ( P < 0.0022 ) .
These findings support @ @ @ @ @ @ @ a broad-spectrum microbicide .

Extensive preclinical evaluation of griffithsin (GRFT) has identified this lectin to be a promising broad-spectrum microbicide. We set out to explore the antiviral properties of a GRFT and carrageenan (CG) combination product against herpes simplex virus 2 (HSV-2) and human papillomavirus (HPV) as well as determine the mechanism of action (MOA) of GRFT against both viruses. We performed the experiments in different cell lines, using time-of-addition and temperature dependence experiments to differentiate inhibition of viral attachment from entry and viral receptor internalization. Surface plasmon resonance (SPR) was used to assess GRFT binding to viral glycoproteins, and immunoprecipitation and immunohistochemistry were used to identify the specific glycoprotein involved. We determined the antiviral activity of GRFT against HSV-2 to be a 50% effective concentration (EC50) of 230 nM and provide the first evidence that GRFT has moderate anti-HPV activity (EC50 = 0.429 to 1.39μM). GRFT blocks the entry of HSV-2 and HPV into target cells but not the adsorption of HSV-2 and HPV onto target cells. The results of the SPR, immunoprecipitation, and immunohistochemistry analyses of HSV-2 combined suggest that GRFT may block viral entry by binding to HSV-2 glycoprotein D. Cell-based assays suggest anti-HPV activity through α6 integrin internalization. The GRFT-CG combination product but not GRFT or CG alone reduced HSV-2 vaginal infection in mice when given an hour before challenge (P = 0.0352). While GRFT significantly protected mice against vaginal HPV infection when dosed during and after HPV16 pseudovirus challenge (P<0.026), greater CG-mediated protection was afforded by the GRFT-CG combination for up to 8 h (P<0.0022). These findings support the development of the GRFT-CG combination as a broad-spectrum microbicide.


greenmedinfo--2020-05-25--Griffithsin tandemers: flexible and potent lectin inhibitors of the human immunodeficiency virus

BACKGROUND : The lectin griffithsin ( GRFT ) is a potent antiviral agent capable of prevention and treatment of infections caused by a number of enveloped viruses and is currently under development as an anti-HIV microbicide .
In addition to its broad antiviral activity , GRFT is stable at high temperature and at a broad pH range , displays little toxicity and immunogenicity , and is amenable to large-scale manufacturing .
Native GRFT is a domain-swapped homodimer that binds to viral envelope glycoproteins and has displayed mid-picomolar activity in cell-based anti-HIV assays .
Previously , we have engineered and analyzed @ @ @ @ @ @ @ mGRFT ) with anti-HIV EC50 values ranging up to 323 nM .
Based on our previous analysis of mGRFT , we hypothesized that the orientation and spacing of the carbohydrate binding domains GRFT were key to its antiviral activity .
RESULTS : Here we present data on engineered tandem repeats of mGRFT ( mGRFT tandemers ) with antiviral activity at concentrations as low as one picomolar in whole-cell anti-HIV assays .
mGRFT tandemers were analyzed thermodynamically , both individually and in complex with HIV-1 gp120 .
We also demonstrate by dynamic light scattering @ @ @ @ @ @ @ not aggregate HIV virions .
This establishes that , although the intra-virion crosslinking of HIV envelope glycoproteins is likely integral to their activity , the antiviral activity of these lectins is not due to virus aggregation caused by inter-virion crosslinking .
CONCLUSIONS : The engineered tandemer constructs of mGRFT may provide novel and powerful agents for prevention of infection by HIV and other enveloped viruses .

BACKGROUND: The lectin griffithsin (GRFT) is a potent antiviral agent capable of prevention and treatment of infections caused by a number of enveloped viruses and is currently under development as an anti-HIV microbicide. In addition to its broad antiviral activity, GRFT is stable at high temperature and at a broad pH range, displays little toxicity and immunogenicity, and is amenable to large-scale manufacturing. Native GRFT is a domain-swapped homodimer that binds to viral envelope glycoproteins and has displayed mid-picomolar activity in cell-based anti-HIV assays. Previously, we have engineered and analyzed several monomeric forms of this lectin (mGRFT) with anti-HIV EC50 values ranging up to 323 nM. Based on our previous analysis of mGRFT, we hypothesized that the orientation and spacing of the carbohydrate binding domains GRFT were key to its antiviral activity.
RESULTS: Here we present data on engineered tandem repeats of mGRFT (mGRFT tandemers) with antiviral activity at concentrations as low as one picomolar in whole-cell anti-HIV assays. mGRFT tandemers were analyzed thermodynamically, both individually and in complex with HIV-1 gp120. We also demonstrate by dynamic light scattering and cryo-electron microscopy that mGRFT tandemers do not aggregate HIV virions. This establishes that, although the intra-virion crosslinking of HIV envelope glycoproteins is likely integral to their activity, the antiviral activity of these lectins is not due to virus aggregation caused by inter-virion crosslinking.
CONCLUSIONS: The engineered tandemer constructs of mGRFT may provide novel and powerful agents for prevention of infection by HIV and other enveloped viruses.


greenmedinfo--2020-05-25--Potent strategy to inhibit HIV-1 by binding both gp120 and gp41.

The development of an anti-HIV microbicide is critical in the fight against the spread of HIV .
It is shown here that the covalent linking of compounds that bind gp120 with compounds that bind gp41 can inhibit HIV entry even more potently than individual inhibitors or noncovalent combinations .
The most striking example involves griffithsin , a potent HIV inhibitor that binds to the surface of HIV gp120 .
While griffithsin inhibits HIV Env-mediated fusion in a CCR5-tropic cell-cell fusion assay with a 50 % inhibitory concentration ( IC ( 50 ) ) of 1.31± 0.87 nM and the gp41-binding @ @ @ @ @ @ @ ) of 18.2 ± 7.6 nM , the covalently linked combination of griffithsin with C37 ( Griff37 ) has an IC ( 50 ) of 0.15 ± 0.05 nM , exhibiting a potency 8.7-fold greater than that of griffithsin alone .
Similarly , in CXCR4-tropic cell-cell fusion assays , Griff37 is 5.2-fold more potent than griffithsin alone .
In viral assays , both griffithsin and Griff37 inhibit HIV replication at midpicomolar levels , but the linked compound Griff37 is severalfold more potent than griffithsin alone against both CCR5- and CXCR4-tropic virus strains .
@ @ @ @ @ @ @ covalently linked combination of peptide C37 with a variant of the gp120-binding peptide CD4M33 ( L. Martin et al.
, Nat .
Biotechnol .
21:71-76 , 2003 ) .
Also , nuclear magnetic resonance ( NMR ) spectra for several of these compounds are shown , including , to our knowledge , the first published NMR spectrum for griffithsin .

The development of an anti-HIV microbicide is critical in the fight against the spread of HIV. It is shown here that the covalent linking of compounds that bind gp120 with compounds that bind gp41 can inhibit HIV entry even more potently than individual inhibitors or noncovalent combinations. The most striking example involves griffithsin, a potent HIV inhibitor that binds to the surface of HIV gp120. While griffithsin inhibits HIV Env-mediated fusion in a CCR5-tropic cell-cell fusion assay with a 50% inhibitory concentration (IC(50)) of 1.31± 0.87 nM and the gp41-binding peptide C37 shows an IC(50) of 18.2 ± 7.6 nM, the covalently linked combination of griffithsin with C37 (Griff37) has an IC(50) of 0.15 ± 0.05 nM, exhibiting a potency 8.7-fold greater than that of griffithsin alone. Similarly, in CXCR4-tropic cell-cell fusion assays, Griff37 is 5.2-fold more potent than griffithsin alone. In viral assays, both griffithsin and Griff37 inhibit HIV replication at midpicomolar levels, but the linked compound Griff37 is severalfold more potent than griffithsin alone against both CCR5- and CXCR4-tropic virus strains. Another example of this strategy is the covalently linked combination of peptide C37 with a variant of the gp120-binding peptide CD4M33 (L. Martin et al., Nat. Biotechnol. 21:71-76, 2003). Also, nuclear magnetic resonance (NMR) spectra for several of these compounds are shown, including, to our knowledge, the first published NMR spectrum for griffithsin.


greenmedinfo--2020-05-25--Griffithsin inhibits nipah virus entry and fusion and can protect Syrian golden hamsters from lethal

Griffithsin inhibits nipah virus entry and fusion and can protect Syrian golden hamsters from lethal nipah virus challenge.

Nipah virus ( NiV ) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis and respiratory disease in humans @ @ @ @ @ approved therapeutic for human use against NiV infection .
Griffithsin ( GRFT ) is high-mannose @ @ @ @ @ shown in vivo broad-spectrum activity against viruses , including severe acute respiratory syndrome coronavirus , @ @ @ @ @ hepatitis C virus , and Japanese encephalitis virus .
In this study , we evaluated @ @ @ @ @ of GRFT and its synthetic trimeric tandemer ( 3mG ) against NiV and other viruses @ @ @ @ @ The 3mG had comparatively greater potency than GRFT against NiV due to its enhanced ability @ @ @ @ @ formation .
Our initial in vivo prophylactic evaluation of an oxidation-resistant GRFT ( Q-GRFT ) @ @ @ @ @ NiV challenge in Syrian golden hamsters .
Our results warrant further development of Q-GRFT and @ @ @ @ @ .

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis and respiratory disease in humans. There is currently no approved therapeutic for human use against NiV infection. Griffithsin (GRFT) is high-mannose oligosaccharide binding lectin that has shown in vivo broad-spectrum activity against viruses, including severe acute respiratory syndrome coronavirus, human immunodeficiency virus 1, hepatitis C virus, and Japanese encephalitis virus. In this study, we evaluated the in vitro antiviral activities of GRFT and its synthetic trimeric tandemer (3mG) against NiV and other viruses from 4 virus families. The 3mG had comparatively greater potency than GRFT against NiV due to its enhanced ability to block NiV glycoprotein-induced syncytia formation. Our initial in vivo prophylactic evaluation of an oxidation-resistant GRFT (Q-GRFT) showed significant protection against lethal NiV challenge in Syrian golden hamsters. Our results warrant further development of Q-GRFT and 3mG as potential NiV therapeutics.


greenmedinfo--2020-05-25--Griffithsin inhibits Japanese encephalitis virus infection in vitro and in vivo

Griffithsin ( GRFT ) is a broad-spectrum antiviral protein that is effective against several glycosylated viruses .
Here , we @ @ @ @ @ and in vivo antiviral activities of GRFT against Japanese encephalitis virus ( JEV ) infection @ @ @ @ @ that treatment of JEV with GRFT before inoculation of BHK-21 cells inhibited infection in a @ @ @ @ @ % inhibition at 100 μg/ml and a 50 % inhibitory concentration ( IC ( 50 @ @ @ @ @ ( 20 nM ) .
Binding assays suggested that binding of GRFT to JEV virions @ @ @ @ @ vivo experiment showed that GRFT ( 5 mg/kg ) administered intraperitoneally before virus infection could @ @ @ @ @ challenged intraperitoneally with a lethal dose of JEV .
Our study also suggested that GRFT @ @ @ @ @ entry phase by targeting the virus .
Collectively , our data demonstrate that GRFT is @ @ @ @ @ application in the development of therapeutics against JEV or other flavivirus infections .

Griffithsin (GRFT) is a broad-spectrum antiviral protein that is effective against several glycosylated viruses. Here, we have evaluated the in vitro and in vivo antiviral activities of GRFT against Japanese encephalitis virus (JEV) infection. In vitro experiments showed that treatment of JEV with GRFT before inoculation of BHK-21 cells inhibited infection in a dose-dependent manner, with 99 % inhibition at 100 μg/ml and a 50 % inhibitory concentration (IC(50)) of 265 ng/ml (20 nM). Binding assays suggested that binding of GRFT to JEV virions inhibited JEV infection. In vivo experiment showed that GRFT (5 mg/kg) administered intraperitoneally before virus infection could completely prevent mortality in mice challenged intraperitoneally with a lethal dose of JEV. Our study also suggested that GRFT prevents JEV infection at the entry phase by targeting the virus. Collectively, our data demonstrate that GRFT is an antiviral agent with potential application in the development of therapeutics against JEV or other flavivirus infections.


greenmedinfo--2020-05-25--Meet Bill Gates - Part 4 Finale

Meet Bill Gates - Part 4 Finale

There can be no doubt that Bill Gates has worn many hats on his remarkable journey from his early life @ @ @ @ @ a Seattle-area power couple to his current status as one of the richest and most @ @ @ @ @ .
But , as we have seen in our exploration of Gates ' rise as @ @ @ @ @ population control advocate , the question of who Bill Gates really is is no mere @ @ @ @ @ will attempt to answer that question as we examine the motives , the ideology , @ @ @ @ @ man who has been so instrumental in shaping the post-coronavirus world .
This is Part @ @ @ @ @ James Corbett on the questionable origin of Bill Gates in global public health today .
@ @ @ @ @ series here .
Please support the work of James Corbett and the Corbett Report .
@ @ @ @ @ or primary funders beyond the micro-donations made by you and me !
You can become @ @ @ @ @ as $ 1 a month .

Visit our Re-post guidelines This article is copyrighted by GreenMedInfo LLC, 2020
There can be no doubt that Bill Gates has worn many hats on his remarkable journey from his early life as the privileged son of a Seattle-area power couple to his current status as one of the richest and most influential people on the planet. But, as we have seen in our exploration of Gates' rise as unelected global health czar and population control advocate, the question of who Bill Gates really is is no mere philosophical pursuit. Today we will attempt to answer that question as we examine the motives, the ideology, and the connections of this man who has been so instrumental in shaping the post-coronavirus world.
TRANSCRIPT AND SOURCES: www.corbettreport.com/gates
This is Part 4 of a series by James Corbett on the questionable origin of Bill Gates in global public health today. Watch the rest of the series here.
Please support the work of James Corbett and the Corbett Report. They have no hidden agendas or primary funders beyond the micro-donations made by you and me! You can become a member for as little as $1 a month.


greenmedinfo--2020-05-25--Griffithsin has antiviral activity against hepatitis C virus.

Hepatitis C virus ( HCV ) -infected patients undergoing liver transplantation universally experience rapid reinfection of their new liver graft .
Current treatment protocols do not prevent graft reinfection and , in addition , an accelerated disease progression is observed .
In the present study , we have evaluated a novel strategy to prevent HCV infection using a lectin , griffithsin ( GRFT ) that specifically binds N-linked high-mannose oligosaccharides that are present on the viral envelope .
The antiviral effect of GRFT was evaluated in vitro using the HCV pseudoparticle ( HCVpp ) and HCV cell culture ( HCVcc @ @ @ @ @ @ @ preincubation of HCVpp and HCVcc with GRFT prevents infection of Huh-7 hepatoma cells .
Furthermore , GRFT interferes with direct cell-to-cell transmission of HCV .
GRFT acts at an early phase of the viral life cycle by interfering in a genotype-independent fashion with the interaction between the viral envelope proteins and the viral receptor CD81 .
The capacity of GRFT to prevent infection in vivo was evaluated using uPA ( +/+ ) -SCID mice ( uPA stands for urokinase-type plasminogen activator ) that harbor human primary hepatocytes in their liver ( chimeric mice @ @ @ @ @ @ @ we demonstrated that GRFT can mitigate HCV infection of chimeric mice .
Treated animals that did become infected demonstrated a considerable delay in the kinetics of the viral infection .
Our data demonstrate that GRFT can prevent HCV infection in vitro and mitigate HCV infection in vivo .
GRFT treatment of chronically infected HCV patients undergoing liver transplantation may be a suitable strategy to prevent infection of the liver allograft .

Hepatitis C virus (HCV)-infected patients undergoing liver transplantation universally experience rapid reinfection of their new liver graft. Current treatment protocols do not prevent graft reinfection and, in addition, an accelerated disease progression is observed. In the present study, we have evaluated a novel strategy to prevent HCV infection using a lectin, griffithsin (GRFT) that specifically binds N-linked high-mannose oligosaccharides that are present on the viral envelope. The antiviral effect of GRFT was evaluated in vitro using the HCV pseudoparticle (HCVpp) and HCV cell culture (HCVcc) systems. We show here that preincubation of HCVpp and HCVcc with GRFT prevents infection of Huh-7 hepatoma cells. Furthermore, GRFT interferes with direct cell-to-cell transmission of HCV. GRFT acts at an early phase of the viral life cycle by interfering in a genotype-independent fashion with the interaction between the viral envelope proteins and the viral receptor CD81. The capacity of GRFT to prevent infection in vivo was evaluated using uPA(+/+)-SCID mice (uPA stands for urokinase-type plasminogen activator) that harbor human primary hepatocytes in their liver (chimeric mice). In this proof-of-concept trial, we demonstrated that GRFT can mitigate HCV infection of chimeric mice. Treated animals that did become infected demonstrated a considerable delay in the kinetics of the viral infection. Our data demonstrate that GRFT can prevent HCV infection in vitro and mitigate HCV infection in vivo. GRFT treatment of chronically infected HCV patients undergoing liver transplantation may be a suitable strategy to prevent infection of the liver allograft.


greenmedinfo--2020-05-25--High-level expression of the HIV entry inhibitor griffithsin from the plastid genome and retention o

High-level expression of the HIV entry inhibitor griffithsin from the plastid genome and retention of biological activity in dried tobacco leaves.

The potent anti-HIV microbicide griffithsin was expressed to high levels in tobacco chloroplasts , enabling efficient purification from both fresh and dried biomass , thus providing storable material for inexpensive production and scale-up on demand .
The global HIV epidemic continues to grow , with 1.8 million new infections occurring per year .
In the absence of a cure and an AIDS vaccine , there is a pressing need to prevent new infections in order to curb the disease .
Topical microbicides that block viral entry into human cells can potentially prevent HIV infection .
The antiviral lectin griffithsin has @ @ @ @ @ @ @ of HIV entry into human cells .
Here we have explored the possibility to use transplastomic plants as an inexpensive production platform for griffithsin .
We show that griffithsin accumulates in stably transformed tobacco chloroplasts to up to 5 % of the total soluble protein of the plant .
Griffithsin can be easily purified from leaf material and shows similarly high virus neutralization activity as griffithsin protein recombinantly expressed in bacteria .
We also show that dried tobacco provides a storable source material for griffithsin purification , thus enabling quick scale-up of production @ @ @

The potent anti-HIV microbicide griffithsin was expressed to high levels in tobacco chloroplasts, enabling efficient purification from both fresh and dried biomass, thus providing storable material for inexpensive production and scale-up on demand. The global HIV epidemic continues to grow, with 1.8 million new infections occurring per year. In the absence of a cure and an AIDS vaccine, there is a pressing need to prevent new infections in order to curb the disease. Topical microbicides that block viral entry into human cells can potentially prevent HIV infection. The antiviral lectin griffithsin has been identified as a highly potent inhibitor of HIV entry into human cells. Here we have explored the possibility to use transplastomic plants as an inexpensive production platform for griffithsin. We show that griffithsin accumulates in stably transformed tobacco chloroplasts to up to 5% of the total soluble protein of the plant. Griffithsin can be easily purified from leaf material and shows similarly high virus neutralization activity as griffithsin protein recombinantly expressed in bacteria. We also show that dried tobacco provides a storable source material for griffithsin purification, thus enabling quick scale-up of production on demand.


greenmedinfo--2020-05-25--Pharmacokinetics of the antiviral lectin griffithsin administered by different routes indicates mult

Pharmacokinetics of the antiviral lectin griffithsin administered by different routes indicates multiple potential uses.

Griffithsin ( GRFT ) is a red alga-derived lectin with demonstrated broad spectrum antiviral activity against enveloped viruses , including severe acute respiratory syndrome-Coronavirus ( SARS-CoV ) , Japanese encephalitis virus ( JEV ) , hepatitis C virus ( HCV ) , and herpes simplex virus-2 ( HSV-2 ) .
However , its pharmacokinetic profile remains largely undefined .
Here , Sprague Dawley rats were administered a single dose of GRFT at 10 or 20 mg/kg by intravenous , oral , and subcutaneous routes , respectively , and serum GRFT levels were measured at select time points .
In addition @ @ @ @ @ @ @ oral dosing was assessed in rats after 10 daily treatments with GRFT ( 20 or 40 mg/kg ) .
We found that parenterally-administered GRFT in rats displayed a complex elimination profile , which varied according to administration routes .
However , GRFT was not orally bioavailable , even after chronic treatment .
Nonetheless , active GRFT capable of neutralizing HIV-Env pseudoviruses was detected in rat fecal extracts after chronic oral dosing .
These findings support further evaluation of GRFT for pre-exposure prophylaxis against emerging epidemics for which specific therapeutics are not available , @ @ @ @ @ @ @ susceptible enveloped viruses .
In addition , GRFT should be considered for antiviral therapy and the prevention of rectal transmission of HIV-1 and other susceptible viruses .

Griffithsin (GRFT) is a red alga-derived lectin with demonstrated broad spectrum antiviral activity against enveloped viruses, including severe acute respiratory syndrome-Coronavirus (SARS-CoV), Japanese encephalitis virus (JEV), hepatitis C virus (HCV), and herpes simplex virus-2 (HSV-2). However, its pharmacokinetic profile remains largely undefined. Here, Sprague Dawley rats were administered a single dose of GRFT at 10 or 20 mg/kg by intravenous, oral, and subcutaneous routes, respectively, and serum GRFT levels were measured at select time points. In addition, the potential for systemic accumulation after oral dosing was assessed in rats after 10 daily treatments with GRFT (20 or 40 mg/kg). We found that parenterally-administered GRFT in rats displayed a complex elimination profile, which varied according to administration routes. However, GRFT was not orally bioavailable, even after chronic treatment. Nonetheless, active GRFT capable of neutralizing HIV-Env pseudoviruses was detected in rat fecal extracts after chronic oral dosing. These findings support further evaluation of GRFT for pre-exposure prophylaxis against emerging epidemics for which specific therapeutics are not available, including systemic and enteric infections caused by susceptible enveloped viruses. In addition, GRFT should be considered for antiviral therapy and the prevention of rectal transmission of HIV-1 and other susceptible viruses.


greenmedinfo--2020-05-25--These findings demonstrate that griffithsin inhibits HSV-2 by a unique mechanism of blocking cell-to

These findings demonstrate that griffithsin inhibits HSV-2 by a unique mechanism of blocking cell-to-cell spread.

Griffithsin , which binds N-linked glycans on gp120 to prevent HIV entry , has the most potent HIV-1 inhibitory activity described for any antiviral lectin and is being developed for topical preexposure prophylaxis .
The current studies were designed to further assess its potential by exploring its activity against herpes simplex virus 2 ( HSV-2 ) , a cofactor for HIV acquisition , in vitro and in a murine model .
Safety was evaluated by examining its impact on epithelial barrier integrity in polarized cultures and testing whether repeated intravaginal dosing potentiates the susceptibility of mice to genital herpes .
@ @ @ @ @ @ @ if present during viral entry but completely blocked plaque formation if present postentry , reduced plaque size , and prevented cell-to-cell spread .
These in vitro findings translated to significant protection against genital herpes in mice treated with 0.1 % griffithsin gel .
Griffithsin , but not placebo gel , prevented viral spread ( visualized with a luciferase-expressing virus ) , significantly reduced disease scores , and resulted in greater survival ( P < 0.05 , log rank test ) .
Protection persisted when HSV-2 was introduced in seminal plasma .
Although griffithsin @ @ @ @ @ @ @ resistance in polarized cultures , this did not translate to any significant increase in the ability of HIV to migrate from the apical to the basolateral chamber nor to an increase in susceptibility to HSV-2 in mice treated with griffithsin gel for 7 days .
These findings demonstrate that griffithsin inhibits HSV-2 by a unique mechanism of blocking cell-to-cell spread and support its further development for HIV and HSV-2 prevention .

Griffithsin, which binds N-linked glycans on gp120 to prevent HIV entry, has the most potent HIV-1 inhibitory activity described for any antiviral lectin and is being developed for topical preexposure prophylaxis. The current studies were designed to further assess its potential by exploring its activity against herpes simplex virus 2 (HSV-2), a cofactor for HIV acquisition, in vitro and in a murine model. Safety was evaluated by examining its impact on epithelial barrier integrity in polarized cultures and testing whether repeated intravaginal dosing potentiates the susceptibility of mice to genital herpes. Griffithsin displayed modest inhibitory activity against HSV-2 if present during viral entry but completely blocked plaque formation if present postentry, reduced plaque size, and prevented cell-to-cell spread. These in vitro findings translated to significant protection against genital herpes in mice treated with 0.1% griffithsin gel. Griffithsin, but not placebo gel, prevented viral spread (visualized with a luciferase-expressing virus), significantly reduced disease scores, and resulted in greater survival (P<0.05, log rank test). Protection persisted when HSV-2 was introduced in seminal plasma. Although griffithsin triggered a small decline in transepithelial electrical resistance in polarized cultures, this did not translate to any significant increase in the ability of HIV to migrate from the apical to the basolateral chamber nor to an increase in susceptibility to HSV-2 in mice treated with griffithsin gel for 7 days. These findings demonstrate that griffithsin inhibits HSV-2 by a unique mechanism of blocking cell-to-cell spread and support its further development for HIV and HSV-2 prevention.


greenmedinfo--2020-05-25--Infectivity of some asymptomatic SARS-CoV-2 carriers might be weak.

Background : An ongoing outbreak of coronavirus disease 2019 ( COVID-19 ) has spread around the world .
It is debatable whether asymptomatic COVID-19 virus carriers are contagious .
We report here a case of the asymptomatic patient and present clinical characteristics of 455 contacts , which aims to study the infectivity of asymptomatic carriers .
Material and methods : 455 contacts who were exposed to the asymptomatic COVID-19 virus carrier became the subjects of our research .
They were divided into three groups : 35 patients , 196 family members and 224 hospital staffs .
We extracted their epidemiological @ @ @ @ @ @ @ results and therapeutic schedules .
Results : The median contact time for patients was four days and that for family members was five days .
Cardiovascular disease accounted for 25 % among original diseases of patients .
Apart from hospital staffs , both patients and family members were isolated medically .
During the quarantine , seven patients plus one family member appeared new respiratory symptoms , where fever was the most common one .
The blood counts in most contacts were within a normal range .
All CT images showed no sign of @ @ @ @ @ @ @ syndrome coronavirus 2 ( SARS-CoV-2 ) infections was detected in 455 contacts by nucleic acid test .
Conclusion : In summary , all the 455 contacts were excluded from SARS-CoV-2 infection and we conclude that the infectivity of some asymptomatic SARS-CoV-2 carriers might be weak .

Background: An ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread around the world. It is debatable whether asymptomatic COVID-19 virus carriers are contagious. We report here a case of the asymptomatic patient and present clinical characteristics of 455 contacts, which aims to study the infectivity of asymptomatic carriers.
Material and methods: 455 contacts who were exposed to the asymptomatic COVID-19 virus carrier became the subjects of our research. They were divided into three groups: 35 patients, 196 family members and 224 hospital staffs. We extracted their epidemiological information, clinical records, auxiliary examination results and therapeutic schedules.
Results: The median contact time for patients was four days and that for family members was five days. Cardiovascular disease accounted for 25% among original diseases of patients. Apart from hospital staffs, both patients and family members were isolated medically. During the quarantine, seven patients plus one family member appeared new respiratory symptoms, where fever was the most common one. The blood counts in most contacts were within a normal range. All CT images showed no sign of COVID-19 infection. No severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections was detected in 455 contacts by nucleic acid test.
Conclusion: In summary, all the 455 contacts were excluded from SARS-CoV-2 infection and we conclude that the infectivity of some asymptomatic SARS-CoV-2 carriers might be weak.


greenmedinfo--2020-05-25--Seaweed secondary metabolites with beneficial health effects.

Macroalgae are increasingly viewed as a source of secondary metabolites with great potential for the development of new drugs .
In this development , in vitro studies are only the first step in a long process , while in vivo studies and clinical trials are the most revealing stages of the true potential and limitations that a given metabolite may have as a new drug .
This literature review aims to give a critical overview of the secondary metabolites that reveal the most interesting results in these two steps .
Phlorotannins show great pharmaceutical potential in in vivo models and @ @ @ @ @ @ @ anti-dyslipidemia activity of dieckol must be highlighted because it was more effective than lovastatin in an in vivo model .
The IRLIIVLMPILMA tridecapeptide that exhibits an in vivo level of activity similar to the hypotensive clinical drug captopril should still be stressed , as well as griffithsin which showed such stunning results over a variety of animal models and which will probably move onto clinical trials soon .
Regarding clinical trials , studies with pure algal metabolites are scarce , limited to those carried out with kahalalide F and fucoxanthin .
The majority @ @ @ @ @ @ @ the effect of algae consumption , as extracts or fractions , on obesity and diabetes .

Macroalgae are increasingly viewed as a source of secondary metabolites with great potential for the development of new drugs. In this development, in vitro studies are only the first step in a long process, while in vivo studies and clinical trials are the most revealing stages of the true potential and limitations that a given metabolite may have as a new drug. This literature review aims to give a critical overview of the secondary metabolites that reveal the most interesting results in these two steps. Phlorotannins show great pharmaceutical potential in in vivo models and, among the several examples, the anti-dyslipidemia activity of dieckol must be highlighted because it was more effective than lovastatin in an in vivo model. The IRLIIVLMPILMA tridecapeptide that exhibits an in vivo level of activity similar to the hypotensive clinical drug captopril should still be stressed, as well as griffithsin which showed such stunning results over a variety of animal models and which will probably move onto clinical trials soon. Regarding clinical trials, studies with pure algal metabolites are scarce, limited to those carried out with kahalalide F and fucoxanthin. The majority of clinical trials currently aim to ascertain the effect of algae consumption, as extracts or fractions, on obesity and diabetes.


greenmedinfo--2020-05-25--Synergistic activity profile of griffithsin in combination with tenofovir, maraviroc and enfuvirtide

Synergistic activity profile of griffithsin in combination with tenofovir, maraviroc and enfuvirtide against HIV-1 clade C.

Griffithsin ( GRFT ) is possibly the most potent anti-HIV peptide found in natural sources .
Due to its potent @ @ @ @ @ unique safety profile it has great potential as topical microbicide component .
Here , we @ @ @ @ @ against HIV-1 clade B and clade C isolates in primary peripheral blood mononuclear cells ( @ @ @ @ @ ( + ) MT-4 cells .
In all combinations tested , GRFT showed synergistic activity @ @ @ @ @ and enfuvirtide based on the median effect principle with combination indices ( CI ) varying @ @ @ @ @ the calculated EC ( 95 ) level .
Furthermore , the different glycosylation patterns on @ @ @ @ @ B and clade C gp120 had no observable effect on the synergistic interactions .
Overall @ @ @ @ @ the evaluated two-drug combination increases their antiviral potency and supports further clinical investigations in pre-exposure @ @ @ @ @ the context of HIV-1 clade C infection .

Griffithsin (GRFT) is possibly the most potent anti-HIV peptide found in natural sources. Due to its potent and broad-spectrum antiviral activity and unique safety profile it has great potential as topical microbicide component. Here, we evaluated various combinations of GRFT against HIV-1 clade B and clade C isolates in primary peripheral blood mononuclear cells (PBMCs) and in CD4(+) MT-4 cells. In all combinations tested, GRFT showed synergistic activity profile with tenofovir, maraviroc and enfuvirtide based on the median effect principle with combination indices (CI) varying between 0.34 and 0.79 at the calculated EC(95) level. Furthermore, the different glycosylation patterns on the viral envelope of clade B and clade C gp120 had no observable effect on the synergistic interactions. Overall, we can conclude that the evaluated two-drug combination increases their antiviral potency and supports further clinical investigations in pre-exposure prophylaxis for GRFT combinations in the context of HIV-1 clade C infection.


greenmedinfo--2020-05-25--Sustained-release griffithsin nanoparticle-fiber composites against HIV-1 and HSV-2 infections.

Human immunodeficiency virus ( HIV-1 ) and herpes simplex virus 2 ( HSV-2 ) affect hundreds of millions of people worldwide .
The antiviral lectin , Griffithsin ( GRFT ) , has been shown to be both safe and efficacious against HSV-2 and HIV-1 infections in vivo .
The goal of this work was to develop a multilayered nanoparticle ( NP ) -electrospun fiber ( EF ) composite to provide sustained-release of GRFT , and to examine its safety and efficacy in a murine model of lethal HSV-2 infection .
Composites were fabricated from polycaprolactone ( PCL ) fibers surrounding @ @ @ @ @ @ @ incorporated methoxy poly ( ethylene glycol ) -b-poly ( lactide-co-glycolide ) ( mPEG-PLGA ) GRFT NPs .
GRFT loading and release were determined via ELISA , showing that NP-EF composites achieved high GRFT loading , and provided sustained-release of GRFT for up to 90 d. The in vitro efficacy of GRFT NP-EFs was assessed using HIV-1 pseudovirus assays , demonstrating complete in vitro protection against HIV-1 infection .
Additionally , sustained-release NP-EFs , administered 24 h prior to infection , prevented against a lethal dose of HSV-2 infection in a murine model .
@ @ @ @ @ @ @ from murine reproductive tracts and vaginal lavages collected 24 and 72 h post-administration were similar to untreated mice , suggesting that NP-EF compositesmay be a promising and safe sustained-delivery platform to prevent HSV-2 infection .
Future work will evaluate the ability to provide prolonged protection against multiple virus challenges , and different administration times with respect to infection .

Human immunodeficiency virus (HIV-1) and herpes simplex virus 2 (HSV-2) affect hundreds of millions of people worldwide. The antiviral lectin, Griffithsin (GRFT), has been shown to be both safe and efficacious against HSV-2 and HIV-1 infections in vivo. The goal of this work was to develop a multilayered nanoparticle (NP)-electrospun fiber (EF) composite to provide sustained-release of GRFT, and to examine its safety and efficacy in a murine model of lethal HSV-2 infection. Composites were fabricated from polycaprolactone (PCL) fibers surrounding polyethylene oxide (PEO) fibers that incorporated methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-PLGA) GRFT NPs. GRFT loading and release were determined via ELISA, showing that NP-EF composites achieved high GRFT loading, and provided sustained-release of GRFT for up to 90 d. The in vitro efficacy of GRFT NP-EFs was assessed using HIV-1 pseudovirus assays, demonstrating complete in vitro protection against HIV-1 infection. Additionally, sustained-release NP-EFs, administered 24 h prior to infection, prevented against a lethal dose of HSV-2 infection in a murine model. In parallel, histology and cytokine expression from murine reproductive tracts and vaginal lavages collected 24 and 72 h post-administration were similar to untreated mice, suggesting that NP-EF compositesmay be a promising and safe sustained-delivery platform to prevent HSV-2 infection. Future work will evaluate the ability to provide prolonged protection against multiple virus challenges, and different administration times with respect to infection.


greenmedinfo--2020-05-25--Griffithsin could be used as a microbicide for HIV prevention.

Griffithsin ( GRFT ) , a lectin fromspecies , inhibits human immunodeficiency virus-1 ( HIV-1 ) replication at sub-nanomolar concentrations , with limited cellular toxicity .
However , in vivo safety of GRFT is not fully understood , especially following parenteral administration .
We first assessed GRFT 's effects in vitro , on mouse peripheral blood mononuclear cell ( mPBMC ) viability , mitogenicity , and activation using flow-cytometry , as well as cytokine secretion through enzyme-linked immunosorbent assay ( ELISA ) .
Toxicological properties of GRFT were determined after a single subcutaneous administration of 50 mg/kg or 14 daily @ @ @ @ @ @ @ .
In the context of microbicide development , toxicity of GRFT at 2 mg/kg was determined after subcutaneous , intravaginal , and intraperitoneal administrations , respectively .
Interestingly , GRFT caused no significant cell death , mitogenicity , activation , or cytokine release in mPBMCs , validating the usefulness of a mouse model .
An excellent safety profile for GRFT was obtained in vivo : no overt changes were observed inanimal fitness , blood chemistry or CBC parameters .
Following GRFT treatment , reversible splenomegaly was observed with activation of certain spleen B @ @ @ @ @ @ @ tissues were not pathologically altered by GRFT ( either with a single high dose or chronic doses ) .
Finally , no detectable toxicity was found after mucosal or systemic treatment with 2 mg/kg GRFT , which should be further developed as a microbicide for HIV prevention .

Griffithsin (GRFT), a lectin fromspecies, inhibits human immunodeficiency virus-1 (HIV-1) replication at sub-nanomolar concentrations, with limited cellular toxicity. However, in vivo safety of GRFT is not fully understood, especially following parenteral administration. We first assessed GRFT's effects in vitro, on mouse peripheral blood mononuclear cell (mPBMC) viability, mitogenicity, and activation using flow-cytometry, as well as cytokine secretion through enzyme-linked immunosorbent assay (ELISA). Toxicological properties of GRFT were determined after a single subcutaneous administration of 50 mg/kg or 14 daily doses of 10 mg/kg in BALB/c mice. In the context of microbicide development, toxicity of GRFT at 2 mg/kg was determined after subcutaneous, intravaginal, and intraperitoneal administrations, respectively. Interestingly, GRFT caused no significant cell death, mitogenicity, activation, or cytokine release in mPBMCs, validating the usefulness of a mouse model. An excellent safety profile for GRFT was obtained in vivo: no overt changes were observed inanimal fitness, blood chemistry or CBC parameters. Following GRFT treatment, reversible splenomegaly was observed with activation of certain spleen B and T cells. However, spleen tissues were not pathologically altered by GRFT (either with a single high dose or chronic doses). Finally, no detectable toxicity was found after mucosal or systemic treatment with 2 mg/kg GRFT, which should be further developed as a microbicide for HIV prevention.


greenmedinfo--2020-05-26--Xanthohumol induces DNA damages in colorectal cancer cells and sensitizes SW480 cells to the SN38 ch

Xanthohumol induces DNA damages in colorectal cancer cells and sensitizes SW480 cells to the SN38 chemotherapeutic agent.

In spite of chemotherapy and systematic screening for people at risk , the mortality rate of colorectal cancer ( CRC @ @ @ @ @ with 600,000 deaths per year .
This low success rate in the treatment of CRC @ @ @ @ @ with high resistance and the risk of metastasis .
Therefore , in response to these @ @ @ @ @ have been under development for several years aimed at increasing the effect of anticancer compounds @ @ @ @ @ effects on normal cells , thus enabling the host to better withstand chemotherapy .
This @ @ @ @ @ Xn ) concentrations under the ICvalues were able to induce apoptosis and to enhance the @ @ @ @ @ .
We demonstrate for the first time that Xn exerts its anticancer activity in models @ @ @ @ @ of the ataxia telangiectasia mutated ( ATM ) pathway .
Subsequently , the ability of @ @ @ @ @ in CRC cells can sensitize them to anticancer agents such as SN38 ( 7-ethyl-10-hydroxycamptothecin ) @ @ @ @

In spite of chemotherapy and systematic screening for people at risk, the mortality rate of colorectal cancer (CRC) remains consistently high, with 600,000 deaths per year. This low success rate in the treatment of CRC results from many failures associated with high resistance and the risk of metastasis. Therefore, in response to these therapeutic failures, new strategies have been under development for several years aimed at increasing the effect of anticancer compounds and/or at reducing their secondary effects on normal cells, thus enabling the host to better withstand chemotherapy. This study highlights that xanthohumol (Xn) concentrations under the ICvalues were able to induce apoptosis and to enhance the DNA-damage response (DDR). We demonstrate for the first time that Xn exerts its anticancer activity in models of colon cancer through activation of the ataxia telangiectasia mutated (ATM) pathway. Subsequently, the ability of Xn to restore DNA damage in CRC cells can sensitize them to anticancer agents such as SN38 (7-ethyl-10-hydroxycamptothecin) used in chemotherapy.


greenmedinfo--2020-05-26--Our findings indicate that targeting survivin for degradation might a promising strategy for OSCC tr

BACKGROUND : Overexpression of survivin plays a crucial role in tumorigenesis and correlates with poor prognosis in human malignancies .
Thus , survivin has been proposed as an attractive target for new anti-tumor interventions .
METHODS : A natural product library was used for natural compound screening through MTS assay .
The expression of survivin in oral squamous cell carcinoma ( OSCC ) and the inhibitory effect of xanthohumol ( XN ) on OSCC were examined by anchorage-dependent and -independent growth assays , immunoblot , immunofluorescence , immunohistochemical staining , ubiquitination analysis , co-immunoprecipitation assay , CRISPR-Cas9-based gene knockout , @ @ @ @ @ @ @ is highly expressed in OSCC patient-derived tissues and cell lines .
Knockout of survivin reduced the tumorigenic properties of OSCC cells in vitro and in vivo .
With a natural compound screening , we identified that xanthohumol inhibited OSCC cells by reducing survivin protein level and activating mitochondrial apoptotic signaling .
Xanthohumol inhibited the Akt-Wee1-CDK1 signaling , which in turn decreased survivin phosphorylation on Thr34 , and facilitated E3 ligase Fbxl7-mediated survivin ubiquitination and degradation .
Xanthohumol alone or in combination with radiation overcame radioresistance in OSCC xenograft tumors .
CONCLUSION : Our @ @ @ @ @ @ @ might a promising strategy for OSCC treatment .

BACKGROUND: Overexpression of survivin plays a crucial role in tumorigenesis and correlates with poor prognosis in human malignancies. Thus, survivin has been proposed as an attractive target for new anti-tumor interventions.
METHODS: A natural product library was used for natural compound screening through MTS assay. The expression of survivin in oral squamous cell carcinoma (OSCC) and the inhibitory effect of xanthohumol (XN) on OSCC were examined by anchorage-dependent and -independent growth assays, immunoblot, immunofluorescence, immunohistochemical staining, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiment.
RESULTS: Survivin is highly expressed in OSCC patient-derived tissues and cell lines. Knockout of survivin reduced the tumorigenic properties of OSCC cells in vitro and in vivo. With a natural compound screening, we identified that xanthohumol inhibited OSCC cells by reducing survivin protein level and activating mitochondrial apoptotic signaling. Xanthohumol inhibited the Akt-Wee1-CDK1 signaling, which in turn decreased survivin phosphorylation on Thr34, and facilitated E3 ligase Fbxl7-mediated survivin ubiquitination and degradation. Xanthohumol alone or in combination with radiation overcame radioresistance in OSCC xenograft tumors.
CONCLUSION: Our findings indicate that targeting survivin for degradation might a promising strategy for OSCC treatment.


greenmedinfo--2020-05-26--Xanthohumol suppresses glioblastoma via modulation of Hexokinase 2 -mediated glycolysis

Deregulation of aerobic glycolysis is a common phenomenon in human cancers , including glioblastoma ( GBM ) .
In the @ @ @ @ @ that the natural compound xanthohumol has a profound anti-tumor effect on GBM via direct inhibition @ @ @ @ @ cell proliferation and colony formation of GBM cells , and significantly impaired glucose metabolism via @ @ @ @ @ ) expression .
We demonstrated that down-regulation of c-Myc was required for xanthohumol-induced decrease of @ @ @ @ @ c-Myc , and promoted FBW7-mediated ubiquitination of c-Myc .
Xanthohumol attenuated Akt activity and inhibited @ @ @ @ @ resulted in c-Myc degradation .
Overexpression of Myr-Akt1 significantly rescued xanthohumol-mediated c-Myc inhibition and glycolysis @ @ @ @ @ xanthohumol-mediated down-regulation of the PI3-K/Akt-GSK3beta-FBW7 signaling axis promoted the destabilization of c-Myc .
Finally , @ @ @ @ @ xanthohumol substantially inhibited tumor growth .
Collectively , xanthohumol appears to be a promising new @ @ @ @ @ potential for GBM .

Deregulation of aerobic glycolysis is a common phenomenon in human cancers, including glioblastoma (GBM). In the present study, we demonstrated that the natural compound xanthohumol has a profound anti-tumor effect on GBM via direct inhibition of glycolysis. Xanthohumol suppressed cell proliferation and colony formation of GBM cells, and significantly impaired glucose metabolism via inhibiting Hexokinase 2 (HK2) expression. We demonstrated that down-regulation of c-Myc was required for xanthohumol-induced decrease of HK2. Xanthohumol destabilization of c-Myc, and promoted FBW7-mediated ubiquitination of c-Myc. Xanthohumol attenuated Akt activity and inhibited the activation of GSK3β, resulted in c-Myc degradation. Overexpression of Myr-Akt1 significantly rescued xanthohumol-mediated c-Myc inhibition and glycolysis suppression. Finally, the xanthohumol-mediated down-regulation of the PI3-K/Akt-GSK3beta-FBW7 signaling axis promoted the destabilization of c-Myc. Finally, the animal results demonstrated that xanthohumol substantially inhibited tumor growth. Collectively, xanthohumol appears to be a promising new anti-tumor agent with the therapeutic potential for GBM.


greenmedinfo--2020-05-26--Xanthohumol regulates miR-4749-5p-inhibited RFC2 signalling in enhancing temozolomide cytotoxicity t

Xanthohumol regulates miR-4749-5p-inhibited RFC2 signalling in enhancing temozolomide cytotoxicity to glioblastoma.

AIMS : Xanthohumol ( XN ) , a natural prenylated flavonoid isolated from Humulus lupulus L. ( hops ) , possess the therapeutic effects in glioblastoma multiforme ( GBM ) , which is a grade IV aggressive glioma in adults .
However , low bioavailability and extractive yield limit the clinical applications of XN .
To comprehensively investigate XN-mediated gene networks in inducing cell death is helpful for drug development and cancer research .
Therefore , we aim to identify the detailed molecular mechanisms of XN 's effects on exhibiting cytotoxicity for GBM therapy .
METHODS AND KEY FINDINGS : @ @ @ @ @ @ @ enhanced temozolomide ( TMZ ) cytotoxicity , a first-line therapeutic drug of GBM .
XN-mediated transcriptome profiles and canonical pathways were identified .
DNA repair signaling , a well-established mechanism against TMZ cytotoxicity , was significantly correlated with XN-downregulated genes .
Replication factor C subunit 2 ( RFC2 ) , a DNA repair-related gene , was obviously downregulated in XN-treated cells .
Higher RFC2 levels which occupied poor patient survival were also observed in high grade GBM patients and tumors .
Inhibition of RFC2 reduced cell viability , induced cell apoptosis , and @ @ @ @ @ @ @ By intersecting array data , bioinformatic prediction , and in vitro experiments , microRNA ( miR ) -4749-5p , a XN-upregulated microRNA , was identified to target to RFC2 3'UTR and inhibited RFC2 expression .
A negative correlation existed between miR-4749-5p and RFC2 in GBM patients .
Overexpression of miR-4749-5p significantly promoted XN- and TMZ-mediated cytotoxicity , and reduced RFC2 levels .
SIGNIFICANCE : Consequently , we suggest that miR-4749-5p targeting RFC2 signaling participates in XN-enhanced TMZ cytotoxicity of GBM .
Our findings provide new potential therapeutic directions for future GBM therapy .

AIMS: Xanthohumol (XN), a natural prenylated flavonoid isolated from Humulus lupulus L. (hops), possess the therapeutic effects in glioblastoma multiforme (GBM), which is a grade IV aggressive glioma in adults. However, low bioavailability and extractive yield limit the clinical applications of XN. To comprehensively investigate XN-mediated gene networks in inducing cell death is helpful for drug development and cancer research. Therefore, we aim to identify the detailed molecular mechanisms of XN's effects on exhibiting cytotoxicity for GBM therapy.
METHODS AND KEY FINDINGS: XN significantly induced GBM cell death and enhanced temozolomide (TMZ) cytotoxicity, a first-line therapeutic drug of GBM. XN-mediated transcriptome profiles and canonical pathways were identified. DNA repair signaling, a well-established mechanism against TMZ cytotoxicity, was significantly correlated with XN-downregulated genes. Replication factor C subunit 2 (RFC2), a DNA repair-related gene, was obviously downregulated in XN-treated cells. Higher RFC2 levels which occupied poor patient survival were also observed in high grade GBM patients and tumors. Inhibition of RFC2 reduced cell viability, induced cell apoptosis, and enhanced both XN and TMZ cytotoxicity. By intersecting array data, bioinformatic prediction, and in vitro experiments, microRNA (miR)-4749-5p, a XN-upregulated microRNA, was identified to target to RFC2 3'UTR and inhibited RFC2 expression. A negative correlation existed between miR-4749-5p and RFC2 in GBM patients. Overexpression of miR-4749-5p significantly promoted XN- and TMZ-mediated cytotoxicity, and reduced RFC2 levels.
SIGNIFICANCE: Consequently, we suggest that miR-4749-5p targeting RFC2 signaling participates in XN-enhanced TMZ cytotoxicity of GBM. Our findings provide new potential therapeutic directions for future GBM therapy.


greenmedinfo--2020-05-26--Therapeutic effect of seaweed derived xanthophyl carotenoid on obesity management; overview of the l

Therapeutic effect of seaweed derived xanthophyl carotenoid on obesity management; overview of the last decade.

Present-day lifestyles associated with high calorie-fat intake and accumulation , as well as energy imbalance , have led to the @ @ @ @ @ comorbidities , which have emerged as some of the major health issues globally .
To @ @ @ @ @ studies have reported the anti-obesity effects of natural compounds in foods , with some advantages @ @ @ @ @ , such as xanthophyll derived from seaweeds , have attracted the attention of researchers due @ @ @ @ @ , which are associated mainly with their antioxidant properties .
Their involvement in oxidative stress @ @ @ @ @ major transcription factors and enzymes , and their antagonistic effects on various obesity parameters have @ @ @ @ @ vitro and in vivo studies .
The present review is a collation of published research @ @ @ @ @ the antioxidant properties of seaweed xanthophyll carotenoids , with a focus on fucoxanthin and astaxanthin @ @ @ @ @ in obesity prevention and treatment .

Present-day lifestyles associated with high calorie-fat intake and accumulation, as well as energy imbalance, have led to the development of obesity and its comorbidities, which have emerged as some of the major health issues globally. To combat the disease, many studies have reported the anti-obesity effects of natural compounds in foods, with some advantages over chemical treatments. Carotenoids, such as xanthophyll derived from seaweeds, have attracted the attention of researchers due to their notable biological activities, which are associated mainly with their antioxidant properties. Their involvement in oxidative stress modulation, the regulation of major transcription factors and enzymes, and their antagonistic effects on various obesity parameters have been examined in both in vitro and in vivo studies. The present review is a collation of published research over the last decade on the antioxidant properties of seaweed xanthophyll carotenoids, with a focus on fucoxanthin and astaxanthin and their mechanisms of action in obesity prevention and treatment.


greenmedinfo--2020-05-26--Fucoxanthin treatment inhibits nasopharyngeal carcinoma cell proliferation.

Nasopharyngeal carcinoma ( NPC ) arises from the epithelium of the nasopharyngeal mucosa .
Elderly people above the age of 65 years are more susceptible to NPC .
Nasopharyngectomy is the renowned treatment procedure to NPC ; however , it is too risky due to its complicated surgical procedure .
Other treatment methods also reported with serious side effects such brain injury ; hence , the alternative anticancer drug without any side effects was needed .
Fucoxanthin is a carotenoid derived from marine algae with the numerous pharmacological functions .
This study aims to examine the inhibitory potential in NPC @ @ @ @ @ @ @ The cytotoxicity of fucoxanthin on C666-1 cells was observed by theMTT assay .
The expression of autophagy-linked proteins was assessed with immunoblotting analysis .
The expression of autophagy protein LC3 was estimated using immunocytochemical analysis in C666-1 and GFP-LC3 transfected cells .
Furthermore , the fucoxanthin-treated C666-1 cells were analyzed with TUNEL assay .
The apoptotic level in the fucoxanthin-treated C666-1 cells was evaluated using acridine orange staining .
Fucoxanthin significantly increased the expression of autophagy-linked proteins which is clearly depicted in the immunoblotting analysis and immunocytochemical analysis of GFP-tagged LC3 protein .
@ @ @ @ @ @ @ C666-1 in the presence autophagy inhibitors demonstrated the induction of autophagy by fucoxanthin .
Acridine orange staining results of C666-1 confirmed fucoxanthin decreases the expression of autophagy-linked proteins during stressed condition thereby causes apoptosis .
Our overall results authentically conclude that fucoxanthin induces autophagy and apoptosis in NPC cell line , and it can be ideal agent to treat nasopharyngeal cancer in future with further investigations .

Nasopharyngeal carcinoma (NPC) arises from the epithelium of the nasopharyngeal mucosa. Elderly people above the age of 65 years are more susceptible to NPC. Nasopharyngectomy is the renowned treatment procedure to NPC; however, it is too risky due to its complicated surgical procedure. Other treatment methods also reported with serious side effects such brain injury; hence, the alternative anticancer drug without any side effects was needed. Fucoxanthin is a carotenoid derived from marine algae with the numerous pharmacological functions. This study aims to examine the inhibitory potential in NPC cell proliferation via apoptosis and autophagy. The cytotoxicity of fucoxanthin on C666-1 cells was observed by theMTT assay. The expression of autophagy-linked proteins was assessed with immunoblotting analysis. The expression of autophagy protein LC3 was estimated using immunocytochemical analysis in C666-1 and GFP-LC3 transfected cells. Furthermore, the fucoxanthin-treated C666-1 cells were analyzed with TUNEL assay. The apoptotic level in the fucoxanthin-treated C666-1 cells was evaluated using acridine orange staining. Fucoxanthin significantly increased the expression of autophagy-linked proteins which is clearly depicted in the immunoblotting analysis and immunocytochemical analysis of GFP-tagged LC3 protein. The results of TUNEL assay of fucoxanthin-treated C666-1 in the presence autophagy inhibitors demonstrated the induction of autophagy by fucoxanthin. Acridine orange staining results of C666-1 confirmed fucoxanthin decreases the expression of autophagy-linked proteins during stressed condition thereby causes apoptosis. Our overall results authentically conclude that fucoxanthin induces autophagy and apoptosis in NPC cell line, and it can be ideal agent to treat nasopharyngeal cancer in future with further investigations.


greenmedinfo--2020-05-26--The fucoidan has reduced LPS induced cytotoxicity in IC-21 macrophage at a dose depended on manner.

In the present study , the anti-nociception and anti-inflammatory activity of fucoidan isolated from T. Decurrens on formalin induced paw-edema in mice model were investigated .
The extracted fucoidan contain 54.86 % of total sugar , 23.51 % of sulfate and 3.4 % of protein .
The monosaccharide composition analysis revealed that fucoidan encompassed of fucose ( 59.3 % ) , galactose ( 12.6 % ) , mannose ( 9.6 % ) , rhamnose ( 6.4 % ) and xylose ( 11.4 % ) .
Further , the structural characterization was done by UV-visible spectroscopy , X-ray diffraction , FT-IR @ @ @ @ @ @ @ licking time thereby suggesting anti-nociceptive effect and decreased the size of paw swelling in the formalin induced inflammatory edema condition .
The isolated fucoidan could significantly decreased the MDA and also increase the SOD , CAT , GPx , GST and GSH activity in paw edema tissue of formalin injected mice .
Furthermore , fucoidan administration retained p65/NF-κB transcription factor in the cytosol thereby showing down regulation of the gene expression of pro-inflammatory mediators such as IL-1β , COX-2and MMP-9 in fucoidan treated mice .
The anti-inflammatory effect of fucoidan was attributed to @ @ @ @ @ @ @ enzymatic antioxidants , master regulator NF-κB and pro-inflammatory cytokines .
The fucoidan has reduced LPS induced cytotoxicity in IC-21 macrophage at a dose depended on manner .

In the present study, the anti-nociception and anti-inflammatory activity of fucoidan isolated from T. Decurrens on formalin induced paw-edema in mice model were investigated. The extracted fucoidan contain 54.86% of total sugar, 23.51% of sulfate and 3.4% of protein. The monosaccharide composition analysis revealed that fucoidan encompassed of fucose (59.3%), galactose (12.6%), mannose (9.6%), rhamnose (6.4%) and xylose (11.4%). Further, the structural characterization was done by UV-visible spectroscopy, X-ray diffraction, FT-IR andHNMR analysis. The fucoidan reduced the licking time thereby suggesting anti-nociceptive effect and decreased the size of paw swelling in the formalin induced inflammatory edema condition. The isolated fucoidan could significantly decreased the MDA and also increase the SOD, CAT, GPx, GST and GSH activity in paw edema tissue of formalin injected mice. Furthermore, fucoidan administration retained p65/NF-κB transcription factor in the cytosol thereby showing down regulation of the gene expression of pro-inflammatory mediators such as IL-1β, COX-2and MMP-9 in fucoidan treated mice. The anti-inflammatory effect of fucoidan was attributed to its capacity on modulating the levels of enzymatic antioxidants, master regulator NF-κB and pro-inflammatory cytokines. The fucoidan has reduced LPS induced cytotoxicity in IC-21 macrophage at a dose depended on manner.


greenmedinfo--2020-05-26--Immunomodulating properties of carrageenan From Tichocarpus Crinitus.

Several in vivo immunotropic effects ofκ/β-carrageenan isolated from the red algae Tichocarpus crinitus were studied , by orally administering it at 100 mg/kg/day to mice for 7 days .
Serum levels of IFN-γ , IL-12 , IL-1β , and IL-4 were measured .
Carrageenan 's ability to influence development of LPS-induced inflammation was also assessed .
Oral administration of κ/β-carrageenan increased serum levels of all the studied cytokines at least twice in comparison to the intact mice , while intraperitoneal LPS injection at 1 mg/kg increased concentration of only the pro-inflammatory cytokines : IFN-γ , IL-12 , and IL-1β .
@ @ @ @ @ @ @ at inducing IFN-γ production than LPS .
Previous 7-day-long oral carrageenan administration impaired development of LPS-induced inflammation : level of IL-1β dropped below that found in intact mice , while IFN-γ and IL-12 concentrations were at least 40 % lower than in mice with LPS-induced inflammation .
Murine peritoneal macrophages were also affected by the oral administration of the κ/β-carrageenan : their motility was increased , and morphology altered .
In sum , we have demonstrated that κ/β-carrageenan , when administered orally , is not only not immunologically inert , but at the @ @ @ @ @ @ @ effects .

Several in vivo immunotropic effects ofκ/β-carrageenan isolated from the red algae Tichocarpus crinitus were studied, by orally administering it at 100 mg/kg/day to mice for 7 days. Serum levels of IFN-γ, IL-12, IL-1β, and IL-4 were measured. Carrageenan's ability to influence development of LPS-induced inflammation was also assessed. Oral administration of κ/β-carrageenan increased serum levels of all the studied cytokines at least twice in comparison to the intact mice, while intraperitoneal LPS injection at 1 mg/kg increased concentration of only the pro-inflammatory cytokines: IFN-γ, IL-12, and IL-1β. Furthermore, κ/β-carrageenan demonstrated a higher efficacy at inducing IFN-γ production than LPS. Previous 7-day-long oral carrageenan administration impaired development of LPS-induced inflammation: level of IL-1β dropped below that found in intact mice, while IFN-γ and IL-12 concentrations were at least 40% lower than in mice with LPS-induced inflammation. Murine peritoneal macrophages were also affected by the oral administration of the κ/β-carrageenan: their motility was increased, and morphology altered. In sum, we have demonstrated that κ/β-carrageenan, when administered orally, is not only not immunologically inert, but at the dose of 100 mg/kg possesses pharmacologically exploitable effects.


greenmedinfo--2020-05-26--The comparative analysis of antiviral activity of native and modified fucoidans from brown algae Fuc

The comparative analysis of antiviral activity of native and modified fucoidans from brown algae Fucus evanescens.

The enzymatic depolymerization of fucoidans from brown algae allowed the production of their standardized derivatives with different biological activities .
This work aimed to compare the antiviral activities of native ( FeF ) and modified with enzyme ( FeHMP ) fucoidans from .
The cytotoxicity and antiviral activities of the FeF and FeHMP against herpes viruses ( HSV-1 , HSV-2 ) , enterovirus ( ECHO-1 ) , and human immunodeficiency virus ( HIV-1 ) in Vero and human MT-4 cell lines were examined by methylthiazolyltetrazolium bromide ( MTT ) and cytopathic effect ( CPE ) reduction assays , respectively .
@ @ @ @ @ @ @ evaluated in the outbred mice model of vaginitis caused by HSV-2 .
We have shown that both FeF and FeHMP significantly inhibited virus-induced CPE in vitro and were more effective against HSV .
FeF exhibited antiviral activity against HSV-2 with a selective index ( SI ) > 40 , and FeHMP with SI˃ 20 , when they were added before virus infection or at the early stages of the HSV-2 lifecycle .
Furthermore , in vivo studies showed that after intraperitoneal administration ( 10 mg/kg ) , both FeF and FeHMP protected mice @ @ @ @ @ @ @ the same degree ( 44-56 % ) .
Thus , FeF and FeHMP have comparable potency against several DNA and RNA viruses , allowing us to consider the studied fucoidans as promising broad-spectrum antivirals .

The enzymatic depolymerization of fucoidans from brown algae allowed the production of their standardized derivatives with different biological activities. This work aimed to compare the antiviral activities of native (FeF) and modified with enzyme (FeHMP) fucoidans from. The cytotoxicity and antiviral activities of the FeF and FeHMP against herpes viruses (HSV-1, HSV-2), enterovirus (ECHO-1), and human immunodeficiency virus (HIV-1) in Vero and human MT-4 cell lines were examined by methylthiazolyltetrazolium bromide (MTT) and cytopathic effect (CPE) reduction assays, respectively. The efficacy of fucoidans in vivo was evaluated in the outbred mice model of vaginitis caused by HSV-2. We have shown that both FeF and FeHMP significantly inhibited virus-induced CPE in vitro and were more effective against HSV. FeF exhibited antiviral activity against HSV-2 with a selective index (SI)>40, and FeHMP with SI˃ 20, when they were added before virus infection or at the early stages of the HSV-2 lifecycle. Furthermore, in vivo studies showed that after intraperitoneal administration (10 mg/kg), both FeF and FeHMP protected mice from lethal intravaginal HSV-2 infection to approximately the same degree (44-56%). Thus, FeF and FeHMP have comparable potency against several DNA and RNA viruses, allowing us to consider the studied fucoidans as promising broad-spectrum antivirals.


greenmedinfo--2020-05-26--Rhamnan sulphate is a potential candidate for the treatment of influenza virus infections.

Influenza viruses cause a significant public health burden each year despite the availability of anti-influenza drugs and vaccines .
Therefore , new anti-influenza virus agents are needed .
Rhamnan sulfate ( RS ) is a sulfated polysaccharide derived from the green alga .
Here , we aimed to demonstrate the antiviral activity of RS , especially against influenza A virus ( IFV ) infection , in vitro and in vivo .
RS showed inhibitory effects on viral proliferation of enveloped viruses in vitro .
Evaluation of the anti-IFV activity of RS in vitro showed that it inhibited both virus adsorption @ @ @ @ @ @ @ of RS in IFV-infected immunocompetent and immunocompromised mice suppressed viral proliferation in both mouse types .
The oral administration of RS also had stimulatory effects on neutralizing antibody production .
Fluorescent analysis showed that RS colocalized with M cells in Peyer 's patches , suggesting that RS bound to the M cells and may be incorporated into the Peyer 's patches , which are essential to intestinal immunity .
In summary , RS inhibits influenza virus infection and promotes antibody production , suggesting that RS is a potential candidate for the treatment of @ @ @ @

Influenza viruses cause a significant public health burden each year despite the availability of anti-influenza drugs and vaccines. Therefore, new anti-influenza virus agents are needed. Rhamnan sulfate (RS) is a sulfated polysaccharide derived from the green alga. Here, we aimed to demonstrate the antiviral activity of RS, especially against influenza A virus (IFV) infection, in vitro and in vivo. RS showed inhibitory effects on viral proliferation of enveloped viruses in vitro. Evaluation of the anti-IFV activity of RS in vitro showed that it inhibited both virus adsorption and entry steps. The oral administration of RS in IFV-infected immunocompetent and immunocompromised mice suppressed viral proliferation in both mouse types. The oral administration of RS also had stimulatory effects on neutralizing antibody production. Fluorescent analysis showed that RS colocalized with M cells in Peyer's patches, suggesting that RS bound to the M cells and may be incorporated into the Peyer's patches, which are essential to intestinal immunity. In summary, RS inhibits influenza virus infection and promotes antibody production, suggesting that RS is a potential candidate for the treatment of influenza virus infections.


greenmedinfo--2020-05-26--Microalgae extracts: potential anti-Trypanosoma cruzi agents?

INTRODUCTION : Chagas disease , caused by the protozoan parasiteTrypanosoma cruzi , has no effective treatment available .
On the @ @ @ @ @ aquatic organisms that constitute an interesting reservoir of biologically active metabolites .
Moreover , some @ @ @ @ @ algae present anti-protozoan activity .
Our aim was to study the antiparasitic effects of aqueous @ @ @ @ @ from different microalgae .
METHODS AND RESULTS : Our results show that the methanolic extracts @ @ @ @ @ suecica as well as the ethanolic extracts of C. reinhardtii and T. suecica present trypanocidal @ @ @ @ @ trypomastigotes and intracellular amastigotes .
In addition , the ethanolic extract of C. reinhardtii potentiates @ @ @ @ @ antichagasic drug nifurtimox .
In order to identify some potential compounds with trypanocidal activity , @ @ @ @ @ analyzing the presence of phenolic compounds , pigments and terpenoids .
CONCLUSION : The different @ @ @ @ @ ethanolic extract ofC .
reinhardtii , are promising potential candidates for the development of future @ @ @ @

INTRODUCTION: Chagas disease, caused by the protozoan parasiteTrypanosoma cruzi, has no effective treatment available. On the other hand, microalgae are aquatic organisms that constitute an interesting reservoir of biologically active metabolites. Moreover, some species of green and red algae present anti-protozoan activity. Our aim was to study the antiparasitic effects of aqueous, methanolic and ethanolic extracts from different microalgae.
METHODS AND RESULTS: Our results show that the methanolic extracts of S. obliquus and T. suecica as well as the ethanolic extracts of C. reinhardtii and T. suecica present trypanocidal activity on the infective extracellular trypomastigotes and intracellular amastigotes. In addition, the ethanolic extract of C. reinhardtii potentiates the activity of the conventional antichagasic drug nifurtimox. In order to identify some potential compounds with trypanocidal activity, we performed a phytochemical screening analyzing the presence of phenolic compounds, pigments and terpenoids.
CONCLUSION: The different microalgae extracts, particularly the ethanolic extract ofC. reinhardtii, are promising potential candidates for the development of future natural antichagasic drugs.


greenmedinfo--2020-05-26--Bioavailable phytoprostanes and phytofurans from Gracilaria Longissima have anti-inflammatory effect

Bioavailable phytoprostanes and phytofurans from Gracilaria Longissima have anti-inflammatory effects in endothelial cells.

BACKGROUND : An array of bioactive compounds with health-promoting effects has been described in several species of macroalgae .
Among them , phytoprostanes ( PhytoPs ) and phytofurans ( PhytoFs ) , both autoxidation products ofα-linolenic acid , have been seen to exert immunomodulatory and antiinflammatory activities in vitro .
The purpose of this study was to explore the bioaccesibility , bioavailability , and bioactivity of PhytoPs and PhytoFs obtained from the edible red algae Gracilaria longissima , and to gain insight into the anti-inflammatory activity of their bioavailable fraction in human endothelial cells .
METHODS : The PhytoPs and @ @ @ @ @ @ @ were determined by UHPLC-QqQ-MS/MS .
Algal samples were processed following a standardised digestion method including gastric , intestinal , and gastrointestinal digestion .
The bioavailability of the PhytoPs and PhytoFs in the characterized fractions was assessed in a Caco-2 cell monolayer model of the intestinal barrier .
The inflammation response of these prostaglandin-like compounds in human endothelial cells , after intestinal absorption , was investigated in vitro .
RESULTS : Simulated digestions significantly reduced the concentration of PhytoPs and PhytoFs up to 1.17 and 0.42μg per 100 g , respectively , on average @ @ @ @ @ @ @ monolayer was high ( up to 88.2 and 97.7 % , on average , respectively ) .
PhytoP and PhytoF-enriched extracts of raw algae impaired the expression of ICAM-1 and IL-6 inflammation markers .
The inflammation markers progressed in contrast to the relative concentrations of bioactive oxylipins , suggesting pro- or anti-inflammatory activity on their part .
In this aspect , the cross-reactivity of these compounds with diverse receptors , and their relative concentration could explain the diversity of the effects found in the current study .
CONCLUSIONS : The results indicate that @ @ @ @ @ @ @ probably mediated through their different actions and affinities in the endothelium .

BACKGROUND: An array of bioactive compounds with health-promoting effects has been described in several species of macroalgae. Among them, phytoprostanes (PhytoPs) and phytofurans (PhytoFs), both autoxidation products ofα-linolenic acid, have been seen to exert immunomodulatory and antiinflammatory activities in vitro. The purpose of this study was to explore the bioaccesibility, bioavailability, and bioactivity of PhytoPs and PhytoFs obtained from the edible red algae Gracilaria longissima, and to gain insight into the anti-inflammatory activity of their bioavailable fraction in human endothelial cells.
METHODS: The PhytoPs and PhytoFs profile and concentration of G. longissima were determined by UHPLC-QqQ-MS/MS. Algal samples were processed following a standardised digestion method including gastric, intestinal, and gastrointestinal digestion. The bioavailability of the PhytoPs and PhytoFs in the characterized fractions was assessed in a Caco-2 cell monolayer model of the intestinal barrier. The inflammation response of these prostaglandin-like compounds in human endothelial cells, after intestinal absorption, was investigated in vitro.
RESULTS: Simulated digestions significantly reduced the concentration of PhytoPs and PhytoFs up to 1.17 and 0.42μg per 100 g, respectively, on average, although permeability through the Caco-2 cell monolayer was high (up to 88.2 and 97.7%, on average, respectively). PhytoP and PhytoF-enriched extracts of raw algae impaired the expression of ICAM-1 and IL-6 inflammation markers. The inflammation markers progressed in contrast to the relative concentrations of bioactive oxylipins, suggesting pro- or anti-inflammatory activity on their part. In this aspect, the cross-reactivity of these compounds with diverse receptors, and their relative concentration could explain the diversity of the effects found in the current study.
CONCLUSIONS: The results indicate that PhytoPs and PhytoFs display complex pharmacological profiles probably mediated through their different actions and affinities in the endothelium.


greenmedinfo--2020-05-26--Sulfated polysaccharide from the red algae Gelidiella Acerosa: anticoagulant, antiplatelet and antit

Sulfated polysaccharide from the red algae Gelidiella Acerosa: anticoagulant, antiplatelet and antithrombotic effects.

A sulfated polysaccharide from the red algae Gelidiella acerosa ( GaSP ) was obtained through enzymatic extraction and subjected to @ @ @ @ @ elemental microanalysis , FT-IR and NMR spectroscopies .
The GaSP anticoagulant activity was investigated through @ @ @ @ @ platelet aggregation assessed by turbidimetry .
The antithrombotic and hemorrhagic activities were evaluated by venous @ @ @ @ @ , respectively .
FT-IR and NMR demonstrated that GaSP is a sulfated agaran .
HPSEC @ @ @ @ @ peak molar mass of 284.8 kDa and a degree of sulfation of 0.63 , respectively @ @ @ @ @ coagulation time in 2.1 times and inhibited the platelet aggregation by 45 % .
Furthermore @ @ @ @ @ antithrombotic effect of 40 % , 64 % and 80 % at 0.1 , 0.5 @ @ @ @ @ , without hemorrhage .
These results suggest that GaSP has promising antithrombotic .

A sulfated polysaccharide from the red algae Gelidiella acerosa (GaSP) was obtained through enzymatic extraction and subjected to chemical characterization by HPSEC, elemental microanalysis, FT-IR and NMR spectroscopies. The GaSP anticoagulant activity was investigated through APTT and PT tests and platelet aggregation assessed by turbidimetry. The antithrombotic and hemorrhagic activities were evaluated by venous thrombosis and hemorrhagic tendency models, respectively. FT-IR and NMR demonstrated that GaSP is a sulfated agaran. HPSEC and elemental microanalysis revealed a peak molar mass of 284.8 kDa and a degree of sulfation of 0.63, respectively. This molecule prolonged the coagulation time in 2.1 times and inhibited the platelet aggregation by 45%. Furthermore, it showed significant dose-dependent antithrombotic effect of 40%, 64% and 80% at 0.1, 0.5 and 1 mg/kg, respectively, without hemorrhage. These results suggest that GaSP has promising antithrombotic.


greenmedinfo--2020-05-26--Alleviation effects of Bifidobacterium breve on DSS-induced colitis.

PURPOSE : The study aimed to investigate the discrepancy and potential mechanisms of different CLA-producing B. breve on dextran sulphate sodium ( DSS ) -induced colitis .
METHODS : Colitis was induced in C57BL/6 J mice using DSS .
Disease activity index ( DAI ) , histopathological changes , epithelial barrier integrity and epithelial apoptosis were determined .
Gut microbiota were gauged to evaluate the systemic effects of CLA-producing B. breve .
RESULTS : Oral administration of different B. breve showed different effects , in which B. breve M1 and B. breve M2 alleviated the inflammation induced by DSS as @ @ @ @ @ @ @ mucin2 ( MUC2 ) and goblet cells , but neither B. breve M3 nor B. breve M4 had those protective effects .
Meanwhile , B. breve M1 and B. breve M2 treatments significantly up-regulated the tight junction ( TJ ) proteins and ameliorated the epithelial apoptosis lead by DSS challenge .
Moreover , inflammatory cytokines ( TNF-α , IL-6 ) were modulated by B. breve M1 and B. breve M2 , neither B. breve M3 nor B. breve M4 .
Furthermore , B. breve M1 and B. breve M2 reduced the abundance of @ @ @ @ @ @ @ , then rebalanced the damaged gut microbiota .
Colonic CLA concentrations in mice fed with B. breve M1 , B. breve M2 , B. breve M3 and B. breve M4 decreased successively , which showed significant positive correlation with the effectiveness of relieving colitis .
CONCLUSIONS : Bifidobacterium breve M1 and B. breve M2 alleviated DSS-induced colitis by producing CLA , inhibiting the inflammatory cytokines , maintaining of the intestinal epithelial barrier and regulating the gut microbiota .

PURPOSE: The study aimed to investigate the discrepancy and potential mechanisms of different CLA-producing B. breve on dextran sulphate sodium (DSS)-induced colitis.
METHODS: Colitis was induced in C57BL/6 J mice using DSS. Disease activity index (DAI), histopathological changes, epithelial barrier integrity and epithelial apoptosis were determined. Gut microbiota were gauged to evaluate the systemic effects of CLA-producing B. breve.
RESULTS: Oral administration of different B. breve showed different effects, in which B. breve M1 and B. breve M2 alleviated the inflammation induced by DSS as well as significantly increased the concentration of mucin2 (MUC2) and goblet cells, but neither B. breve M3 nor B. breve M4 had those protective effects. Meanwhile, B. breve M1 and B. breve M2 treatments significantly up-regulated the tight junction (TJ) proteins and ameliorated the epithelial apoptosis lead by DSS challenge. Moreover, inflammatory cytokines (TNF-α, IL-6) were modulated by B. breve M1 and B. breve M2, neither B. breve M3 nor B. breve M4. Furthermore, B. breve M1 and B. breve M2 reduced the abundance of Bacteroides and increased the abundance of Odoribacter, then rebalanced the damaged gut microbiota. Colonic CLA concentrations in mice fed with B. breve M1, B. breve M2, B. breve M3 and B. breve M4 decreased successively, which showed significant positive correlation with the effectiveness of relieving colitis.
CONCLUSIONS: Bifidobacterium breve M1 and B. breve M2 alleviated DSS-induced colitis by producing CLA, inhibiting the inflammatory cytokines, maintaining of the intestinal epithelial barrier and regulating the gut microbiota.


greenmedinfo--2020-05-26--Anti-cancer effects of bifidobacterium species in colon cancer cells and a mouse model of carcinogen

Anti-cancer effects of bifidobacterium species in colon cancer cells and a mouse model of carcinogenesis.

INTRODUCTION : Probiotics are suggested to prevent colorectal cancer ( CRC ) .
This study aimed to investigate the anticancer properties of some potential probiotics in vitro and in vivo .
MATERIALS AND METHODS : Anticancer effects of potential probiotic groups were investigated following of in LS174T cancer cells compared to IEC-18 normal cells .
1. a single strain of Bifidobacterium .
breve , 2. a single strain of Lactobacillus .
reuteri , 3. a cocktail of 5 strains of Lactobacilli ( LC ) , 4. a cocktail of 5 strains of Bifidobacteria ( BC ) , 5. a cocktail @ @ @ @ @ @ @ ( L+B ) .
Apoptosis rate , EGFR , HER-2 and PTGS-2 ( COX-2 protein ) expression levels were assessed as metrics of evaluating anticancer properties .
Effect of BC , as the most effective group in vitro , was further assessed in mice models .
RESULTS : BC induced ~21 % and only ~3 % apoptosis among LS174T and IEC-18 cells respectively .
BC decreased the expression of EGFR by 4.4 folds , HER-2 by 6.7 folds , and PTGS-2 by 20 folds among the LS174T cells .
In all these cases @ @ @ @ @ @ @ the expression of the genes in IEC-18 cells .
This cocktail has caused only 1.1 folds decrease , 1.8 folds increase and 1.7 folds decrease in EGFR , HER-2 and PTGS-2 expression , respectively .
Western blot analysis confirmed these results in the protein level .
BC significantly ameliorated the disease activity index , restored colon length , inhibited the increase in incidence and progress of tumors to higher stages and grades .
CONCLUSIONS : BC was the most efficient treatment in this study .
It had considerable '' protective '' anti-cancer properties @ @ @ @ @ @ @ and PTGS-2 ( COX-2 ) , while having significant anti-CRC effects on CRC mice models .
In general , this potential probiotic could be considered as a suitable nutritional supplement to treat and prevent CRC .

INTRODUCTION: Probiotics are suggested to prevent colorectal cancer (CRC). This study aimed to investigate the anticancer properties of some potential probiotics in vitro and in vivo.
MATERIALS AND METHODS: Anticancer effects of potential probiotic groups were investigated following of in LS174T cancer cells compared to IEC-18 normal cells. 1. a single strain of Bifidobacterium. breve, 2. a single strain of Lactobacillus. reuteri, 3. a cocktail of 5 strains of Lactobacilli (LC), 4. a cocktail of 5 strains of Bifidobacteria (BC), 5. a cocktail of 10 strains from Lactobacillus and Bifidobacterium (L+B). Apoptosis rate, EGFR, HER-2 and PTGS-2 (COX-2 protein) expression levels were assessed as metrics of evaluating anticancer properties. Effect of BC, as the most effective group in vitro, was further assessed in mice models.
RESULTS: BC induced ~21% and only ~3% apoptosis among LS174T and IEC-18 cells respectively. BC decreased the expression of EGFR by 4.4 folds, HER-2 by 6.7 folds, and PTGS-2 by 20 folds among the LS174T cells. In all these cases, BC did not interfere significantly with the expression of the genes in IEC-18 cells. This cocktail has caused only 1.1 folds decrease, 1.8 folds increase and 1.7 folds decrease in EGFR, HER-2 and PTGS-2 expression, respectively. Western blot analysis confirmed these results in the protein level. BC significantly ameliorated the disease activity index, restored colon length, inhibited the increase in incidence and progress of tumors to higher stages and grades.
CONCLUSIONS: BC was the most efficient treatment in this study. It had considerable"protective"anti-cancer properties and concomitantly down regulated EGFR, HER-2 and PTGS-2 (COX-2), while having significant anti-CRC effects on CRC mice models. In general, this potential probiotic could be considered as a suitable nutritional supplement to treat and prevent CRC.


greenmedinfo--2020-05-26--Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsi

Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models.

Griffithsin ( GRFT ) is a red-alga-derived lectin that binds the terminal mannose residues of N-linked glycans found on the surface of human immunodeficiency virus type 1 ( HIV-1 ) , HIV-2 , and other enveloped viruses , including hepatitis C virus ( HCV ) , severe acute respiratory syndrome coronavirus ( SARS-CoV ) , and Ebola virus .
GRFT displays no human T-cell mitogenic activity and does not induce production of proinflammatory cytokines in treated human cell lines .
However , despite the growing evidence showing the broad-spectrum nanomolar or better antiviral activity of GRFT , no study has @ @ @ @ @ @ @ as a potential systemic antiviral treatment .
The results presented in this work show that minimal toxicity was induced by a range of single and repeated daily subcutaneous doses of GRFT in two rodent species , although we noted treatment-associated increases in spleen and liver mass suggestive of an antidrug immune response .
The drug is systemically distributed , accumulating to high levels in the serum and plasma after subcutaneous delivery .
Further , we showed that serum from GRFT-treated animals retained antiviral activity against HIV-1-enveloped pseudoviruses in a cell-based neutralization assay .
@ @ @ @ @ @ @ that GRFT accumulates to relevant therapeutic concentrations which are tolerated with minimal toxicity .
These studies support further development of GRFT as a systemic antiviral therapeutic agent against enveloped viruses , although deimmunizing the molecule may be necessary if it is to be used in long-term treatment of chronic viral infections .

Griffithsin (GRFT) is a red-alga-derived lectin that binds the terminal mannose residues of N-linked glycans found on the surface of human immunodeficiency virus type 1 (HIV-1), HIV-2, and other enveloped viruses, including hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Ebola virus. GRFT displays no human T-cell mitogenic activity and does not induce production of proinflammatory cytokines in treated human cell lines. However, despite the growing evidence showing the broad-spectrum nanomolar or better antiviral activity of GRFT, no study has reported a comprehensive assessment of GRFT safety as a potential systemic antiviral treatment. The results presented in this work show that minimal toxicity was induced by a range of single and repeated daily subcutaneous doses of GRFT in two rodent species, although we noted treatment-associated increases in spleen and liver mass suggestive of an antidrug immune response. The drug is systemically distributed, accumulating to high levels in the serum and plasma after subcutaneous delivery. Further, we showed that serum from GRFT-treated animals retained antiviral activity against HIV-1-enveloped pseudoviruses in a cell-based neutralization assay. Overall, our data presented here show that GRFT accumulates to relevant therapeutic concentrations which are tolerated with minimal toxicity. These studies support further development of GRFT as a systemic antiviral therapeutic agent against enveloped viruses, although deimmunizing the molecule may be necessary if it is to be used in long-term treatment of chronic viral infections.


greenmedinfo--2020-05-26--How To Detox Your Body With Oil Pulling

How To Detox Your Body With Oil Pulling

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By providing the information contained herein we are not diagnosing , treating @ @ @ @ @ or preventing any type of disease or medical condition .
Before beginning any type of @ @ @ @ @ treatment regimen , it is advisable to seek the advice of a licensed healthcare professional @

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
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greenmedinfo--2020-05-26--Combinations of griffithsin with other carbohydrate-binding agents demonstrate superior activity aga

Combinations of griffithsin with other carbohydrate-binding agents demonstrate superior activity against HIV type 1, HIV type 2.

Carbohydrate-binding agents ( CBAs ) are potential HIV microbicidal agents with a high genetic barrier to resistance .
We wanted to evaluate whether two mannose-specific CBAs , recognizing multiple and often distinct glycan structures on the HIV envelope gp120 , can interact synergistically against HIV-1 , HIV-2 , and HIV-1 strains that were selected for resistance against particular CBAs [ i.e.
, 2G12 mAb and microvirin ( MVN ) ] .
Paired CBA/CBA combinations mainly showed synergistic activity against both wild-type HIV-1 and HIV-2 but also 2G12 mAb- and MVN-resistant HIV-1 strains as based on the median effect principle with @ @ @ @ @ @ @ 0.29 and 0.97 .
Upon combination , an increase in antiviral potency of griffithsin ( GRFT ) up to∼12-fold ( against HIV-1 ) , ∼8-fold ( against HIV-2 ) , and ∼6-fold ( against CBA-resistant HIV-1 ) was observed .
In contrast , HHA/GNA combinations showed additive activity against wild-type HIV-1 and HIV-2 strains , but remarkable synergy with HHA and GNA was observed against 2G12 mAb- and MVN-resistant HIV-1 strains ( CI , 0.64 and 0.49 , respectively ) .
Overall , combinations of GRFT and other CBAs showed synergistic activity against @ @ @ @ @ @ @ certain CBA-resistant HIV-1 strains .
The CBAs tested appear to have distinct binding patterns on the gp120 envelope and therefore do not necessarily compete with each other 's glycan binding sites on gp120 .
As a result , there might be no steric hindrance between two different CBAs in their competition for glycan binding ( except for the HHA/GNA combination ) .
These data are encouraging for the use of paired CBA combinations in topicalmicrobicide applications ( e.g.
, creams , gels , or intravaginal rings ) to prevent HIV transmission .

Carbohydrate-binding agents (CBAs) are potential HIV microbicidal agents with a high genetic barrier to resistance. We wanted to evaluate whether two mannose-specific CBAs, recognizing multiple and often distinct glycan structures on the HIV envelope gp120, can interact synergistically against HIV-1, HIV-2, and HIV-1 strains that were selected for resistance against particular CBAs [i.e., 2G12 mAb and microvirin (MVN)]. Paired CBA/CBA combinations mainly showed synergistic activity against both wild-type HIV-1 and HIV-2 but also 2G12 mAb- and MVN-resistant HIV-1 strains as based on the median effect principle with combination indices (CIs) ranging between 0.29 and 0.97. Upon combination, an increase in antiviral potency of griffithsin (GRFT) up to∼12-fold (against HIV-1), ∼8-fold (against HIV-2), and ∼6-fold (against CBA-resistant HIV-1) was observed. In contrast, HHA/GNA combinations showed additive activity against wild-type HIV-1 and HIV-2 strains, but remarkable synergy with HHA and GNA was observed against 2G12 mAb- and MVN-resistant HIV-1 strains (CI, 0.64 and 0.49, respectively). Overall, combinations of GRFT and other CBAs showed synergistic activity against HIV-1, HIV-2, and even against certain CBA-resistant HIV-1 strains. The CBAs tested appear to have distinct binding patterns on the gp120 envelope and therefore do not necessarily compete with each other's glycan binding sites on gp120. As a result, there might be no steric hindrance between two different CBAs in their competition for glycan binding (except for the HHA/GNA combination). These data are encouraging for the use of paired CBA combinations in topicalmicrobicide applications (e.g., creams, gels, or intravaginal rings) to prevent HIV transmission.


greenmedinfo--2020-05-26--Griffithsin, a potent HIV entry inhibitor, is an excellent candidate for anti-HIV microbicide.

BACKGROUND : The predominant mode of HIV-1 transmission is by heterosexual contact .
The cervical/vaginal mucosa is the main port of HIV entry in women .
A safe and effective topical microbicide against HIV is urgently needed to prevent sexual transmission .
Hence , we evaluated griffithsin ( GRFT ) , a 12.7 kDa carbohydrate-binding protein , both native and recombinant GRFT , potently inhibited both CXCR4-and CCR5-tropic HIV infection and transmission in vitro .
METHODS : The antiviral efficacy of native and recombinant GRFT against CXCR4-and CCR5-tropic HIV and SHIV strains and SIVmac251 was evaluated by in vitro assays @ @ @ @ @ @ @ of antiviral activity and stability of GRFT in cervical/vaginal lavage as a function of pH 4-8 .
RESULTS : Griffithsin blocked CXCR4-and CCR5-tropic viruses at less than 1 nm concentrations and exhibited a high potency .
GRFT was stable in cervical/vaginal lavage fluid and maintained a similar potency of anti-HIV activity .
GRFT is not only a highly potent HIV entry inhibitor , but also prevents cell fusion and cell-to-cell transmission of HIV .
CONCLUSIONS : The in vitro efficacy of GRFT revealed low cytotoxicity , high potency , rapid onset of antiviral @ @ @ @ @ @ @ .
GRFT is an excellent candidate for anti-HIV microbicide development .

BACKGROUND: The predominant mode of HIV-1 transmission is by heterosexual contact. The cervical/vaginal mucosa is the main port of HIV entry in women. A safe and effective topical microbicide against HIV is urgently needed to prevent sexual transmission. Hence, we evaluated griffithsin (GRFT), a 12.7 kDa carbohydrate-binding protein, both native and recombinant GRFT, potently inhibited both CXCR4-and CCR5-tropic HIV infection and transmission in vitro.
METHODS: The antiviral efficacy of native and recombinant GRFT against CXCR4-and CCR5-tropic HIV and SHIV strains and SIVmac251 was evaluated by in vitro assays. We also evaluated the time course of antiviral activity and stability of GRFT in cervical/vaginal lavage as a function of pH 4-8.
RESULTS: Griffithsin blocked CXCR4-and CCR5-tropic viruses at less than 1 nm concentrations and exhibited a high potency. GRFT was stable in cervical/vaginal lavage fluid and maintained a similar potency of anti-HIV activity. GRFT is not only a highly potent HIV entry inhibitor, but also prevents cell fusion and cell-to-cell transmission of HIV.
CONCLUSIONS: The in vitro efficacy of GRFT revealed low cytotoxicity, high potency, rapid onset of antiviral activity and long-term stability in cervical/vaginal lavage. GRFT is an excellent candidate for anti-HIV microbicide development.