greenmedinfo--2020-08-30--Targeting AKT with oridonin inhibits growth of esophageal squamous cell carcinoma.

Overexpression or activation of AKT is very well known to control cell growth , survival , and gene expression in solid tumors .
Oridonin , an inflammatory medical and diterpenoid compound isolated from , has exhibited various pharmacologic and physiologic properties , including antitumor , antibacterial , and anti-inflammatory effects .
In this study , we demonstrated that oridonin is an inhibitor of AKT and suppresses proliferation of esophageal squamous cell carcinoma ( ESCC ) andThe role of AKT in ESCC was studied using immuno-histochemical analysis of a tumor microarray , the effect of AKT knockdown on cell growth , @ @ @ @ @ @ @ an AKT inhibitor .
Oridonin blocked AKT kinase activity and interacted with the ATP-binding pocket of AKT .
It inhibited growth of KYSE70 , KYSE410 , and KYSE450 esophageal cancer cells in a time- and concentration-dependent manner .
Oridonin induced arrest of cells in the G-M cell-cycle phase , stimulated apoptosis , and increased expression of apoptotic biomarkers , including cleaved PARP , caspase-3 , caspase-7 , and Bimin ESCC cell lines .
Mechanistically , we found that oridonin diminished the phosphorylation and activation of AKT signaling .
Furthermore , a combination of @ @ @ @ @ @ @ chemotherapeutic agents ) enhanced the inhibition of ESCC cell growth .
The effects of oridonin were verified in patient-derived xenograft tumors expressing high levels of AKT .
In summary , our results indicate that oridonin acts as an AKT inhibitor to suppress the growth of ESCC by attenuating AKT signaling..

Overexpression or activation of AKT is very well known to control cell growth, survival, and gene expression in solid tumors. Oridonin, an inflammatory medical and diterpenoid compound isolated from, has exhibited various pharmacologic and physiologic properties, including antitumor, antibacterial, and anti-inflammatory effects. In this study, we demonstrated that oridonin is an inhibitor of AKT and suppresses proliferation of esophageal squamous cell carcinoma (ESCC)andThe role of AKT in ESCC was studied using immuno-histochemical analysis of a tumor microarray, the effect of AKT knockdown on cell growth, and treatment of cells with MK-2206, an AKT inhibitor. Oridonin blocked AKT kinase activity and interacted with the ATP-binding pocket of AKT. It inhibited growth of KYSE70, KYSE410, and KYSE450 esophageal cancer cells in a time- and concentration-dependent manner. Oridonin induced arrest of cells in the G-M cell-cycle phase, stimulated apoptosis, and increased expression of apoptotic biomarkers, including cleaved PARP, caspase-3, caspase-7, and Bimin ESCC cell lines. Mechanistically, we found that oridonin diminished the phosphorylation and activation of AKT signaling. Furthermore, a combination of oridonin and 5-fluorouracil or cisplatin (clinical chemotherapeutic agents) enhanced the inhibition of ESCC cell growth. The effects of oridonin were verified in patient-derived xenograft tumors expressing high levels of AKT. In summary, our results indicate that oridonin acts as an AKT inhibitor to suppress the growth of ESCC by attenuating AKT signaling..


greenmedinfo--2020-08-30--Oridonin inhibits aberrant AKT activation in breast cancer.

Aberrant activation of phosphatidylinosito-4,5-bisphosphate 3-kinase/protein kinase B ( PI3K/AKT ) signaling in cancer has led to pursuit of inhibitors for @ @ @ @ @ , inhibitors of PI3K and AKT have failed to yield efficacious results without adverse effects @ @ @ @ @ a library containing 441 authenticated traditional chinese medicine ( TCM ) plant extracts by examining @ @ @ @ @ of a human mammary epithelial cell line HMEC-PIK3CA , which expresses mutant PIK3CAand has constitutively @ @ @ @ @ found that Oridonin , an extract from , reduced cell viability to the greatest extent @ @ @ @ @ and potentially functions as an ATP-competitive AKT inhibitor .
Importantly , Oridonin selectively impaired tumor @ @ @ @ @ cells with hyperactivation of PI3K/AKT signaling .
Moreover , Oridonin prevented the initiation of mouse @ @ @ @ @ .
Our results suggest that Oridonin may serve as a potent and durable therapeutic agent @ @ @ @ @ cancers with hyperactivation of PI3K/AKT signaling .

Aberrant activation of phosphatidylinosito-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT) signaling in cancer has led to pursuit of inhibitors for targeting this pathway. However, inhibitors of PI3K and AKT have failed to yield efficacious results without adverse effects. Here, we screened a library containing 441 authenticated traditional chinese medicine (TCM) plant extracts by examining their effect on cell viability of a human mammary epithelial cell line HMEC-PIK3CA, which expresses mutant PIK3CAand has constitutively active AKT signaling. We found that Oridonin, an extract from, reduced cell viability to the greatest extent. Oridonin binds to AKT1 and potentially functions as an ATP-competitive AKT inhibitor. Importantly, Oridonin selectively impaired tumor growth of human breast cancer cells with hyperactivation of PI3K/AKT signaling. Moreover, Oridonin prevented the initiation of mouse mammary tumors driven by PIK3CA. Our results suggest that Oridonin may serve as a potent and durable therapeutic agent for the treatment of breast cancers with hyperactivation of PI3K/AKT signaling.


greenmedinfo--2020-08-30--Oridonin enhances the cytotoxicity of 5-FU in renal carcinoma cells by inducting necroptotic death.

BACKGROUND : 5-fluorouracil ( 5-FU ) is widely used for the treatment of renal carcinoma .
However , drug resistance remains the reason for failure of chemotherapy .
Oridonin , extracted from Chinese herb medicine , displays anti-tumor effect in several types of cancer .
Whether oridonin could enhance the effect of 5-FU in renal carcinoma has not been studied .
METHODS : 786-O cells were used in the current study .
Cell death was measured by MTT assay or live- and dead-cell staining assay .
Glutathione ( GSH ) level was examined by ELISA .
Necroptosis was identified by @ @ @ @ @ @ @ RIP-1 ) and RIP-3 , lactate dehydrogenase ( LDH ) and high mobility group box-1 protein ( HMGB1 ) release , and poly [ ADP-ribose ] polymerase-1 ( Parp-1 ) activity .
Using a xenograft assay in nude mice , we tested the anti-tumor effects of the oridonin combined with 5-FU .
RESULTS : 5-FU only induced apoptosis in 786-O cells .
Oridonin activated both apoptosis and necroptosis in 786-O cells .
Oridonin-induced necroptosis was reversed by addition of GSH or its precursorN-acetylcysteine ( NAC ) .
Oridonin-induced necroptosis was associated by activated @ @ @ @ @ @ @ 786-O cells , which were abolished by GSH or NAC treatment .
However , JNK , p38 , and ERK inhibitors showed no effect on oridonin induced-cell death .
GSH or NAC treatment partly abolished the synergistic effects of oridonin and 5-FU on cell death .
Oridonin enhanced the cytotoxicity of 5-FU both in vitro and in vivo .
CONCLUSION : Oridonin enhances the cytotoxicity of 5-FU in renal cancer cells partially through inducing necroptosis , providing evidence of using necroptosis inducers in combination with chemotherapeutic agents for cancer treatment .

BACKGROUND: 5-fluorouracil (5-FU) is widely used for the treatment of renal carcinoma. However, drug resistance remains the reason for failure of chemotherapy. Oridonin, extracted from Chinese herb medicine, displays anti-tumor effect in several types of cancer. Whether oridonin could enhance the effect of 5-FU in renal carcinoma has not been studied.
METHODS: 786-O cells were used in the current study. Cell death was measured by MTT assay or live- and dead-cell staining assay. Glutathione (GSH) level was examined by ELISA. Necroptosis was identified by protein levels of receptors interaction protein-1 (RIP-1) and RIP-3, lactate dehydrogenase (LDH) and high mobility group box-1 protein (HMGB1) release, and poly [ADP-ribose] polymerase-1 (Parp-1) activity. Using a xenograft assay in nude mice, we tested the anti-tumor effects of the oridonin combined with 5-FU.
RESULTS: 5-FU only induced apoptosis in 786-O cells. Oridonin activated both apoptosis and necroptosis in 786-O cells. Oridonin-induced necroptosis was reversed by addition of GSH or its precursorN-acetylcysteine (NAC). Oridonin-induced necroptosis was associated by activated JNK, p38, and ERK in 786-O cells, which were abolished by GSH or NAC treatment. However, JNK, p38, and ERK inhibitors showed no effect on oridonin induced-cell death. GSH or NAC treatment partly abolished the synergistic effects of oridonin and 5-FU on cell death. Oridonin enhanced the cytotoxicity of 5-FU both in vitro and in vivo.
CONCLUSION: Oridonin enhances the cytotoxicity of 5-FU in renal cancer cells partially through inducing necroptosis, providing evidence of using necroptosis inducers in combination with chemotherapeutic agents for cancer treatment.


greenmedinfo--2020-08-30--Colorado School District Superintendent Hires Lobbyists for Vaccine Tracking Bill

During the legislative session of 2020 , Poudre School District ( PSD ) sent two lobbyists to the state capitol to lobby in favor of a bill , SB20-163 .
PSD has paid $ 48,801.45 of taxpayer money to the lobbying firm Mendez , Barkis , and Associates over the past 12 months , the firm sent to lobby in support of SB20-163 for PSD .
Why would PSD send lobbyists to support a bill that would harm up to 5 % of its students and their families ?
It is not common practice for a school district to send @ @ @ @ @ @ @ in fact , only one other school district in Colorado sent lobbyists to support this bill - Adams County .
Thousands of parents showed up at the state capitol to testify against this bill for both the Senate and House hearings .
Parents let it be known loud and clear that their children would be targets if this bill passed .
The Senate hearing , which was heard in February 2020 before the COVID lockdowns , went into the early morning hours with hundreds of parents testifying against the bill .
Until the @ @ @ @ @ @ @ the Senate majority ( Democrat ) leader showed up and had words with his party members , two of the Democrat Senators looked as if they were going to be no votes .
However , after the majority leader left , the bill passed through the Senate with a party-line vote .
Democrats voted yes and Republicans voted no .
One Democrat Senator admitted the pressure was too much to give a no vote .
The House hearing came after the COVID lockdowns in June 2020 .
The hearing was scheduled on a @ @ @ @ @ @ @ hearing , especially for such a controversial bill .
The committee chair allowed only 1.5 hours of testimony for each side .
This allowed plenty of time for the proponents to get all testimony heard , but only gave enough time for a minute percentage of the thousands of opponents who came to testify against the bill .
In fact , thousands of citizens who came out in opposition to the bill were forced to stay outside of the Capitol during the hearing .
SB20-163 is a bill that requires several new procedures @ @ @ @ @ @ @ troubling to parents is that it requires parents who choose to exempt their children from even one vaccine required for school entry , for personal or religious reasons , or children who are exempt for medical reasons , register their exemptions into a State tracking database full of personally identifying information on the child .
This database is an Immunization Information System or IIS .
It houses dozens of personal data fields of private medical , location , and age information that parents would not want anyone to have access to unless the @ @ @ @ @ @ @ over 6,000 people in Colorado currently have access to this Colorado IIS , also known as CIIS .
These types of medical tracking data bases are wrought with controversy including the very real threat of data breach .
These tracking data bases also erode public trust in government , doctors and hospitals .
Sandra Smyser is the superintendent for PSD and is the person responsible for the approval of over $ 48,000 being paid to the lobbying firm over the year that included the lobbying for SB20-163 .
The opposition to this bill @ @ @ @ @ @ @ the local media .
Thus , Ms. Smyser can not claim that parents wanted this bill to pass nor can she claim that she was working for her students .
If she was not working for her students , who was she working for ?
Who was she helping and why would she be willing to pay lobbyists , at the tax payer 's expense , to lobby for a bill that would bypass existing privacy laws such as FERPA and force parents to enter their children 's private medical data and choices @ @ @ @ @ @ @ must realize that the reality of tracking registries is about to become much more real and concerning to thousands of more parents who do not want their children to be used as Guinea pigs for an experimental Covid vaccine that may use never before tested mRNA technology .
Especially now that multiple news outlets are reporting that a mandatory COVID vaccine is a great possibility and polls show that about half of the population is reluctant to comply , the reality is that exemption tracking will affect even more children in the future @ @ @ @ @ @ @ Sandra Smyser did in fact have a reason to hire lobbyists to support SB20-163 , and that reason seems to be nepotism .
Sandra Smyser appears to be choosing her son and his interests over the interests of the students she is charged with serving .
So , Who is Sandra Smyser 's son ?
Sandra Smyser 's Son Tracks and Targets People and Organizations Who Do Not Agree With His Agenda The son of Sandra Smyser is Joe Smyser .
Joe Smyser has a Ph.D. in Public Health ; has worked for @ @ @ @ @ @ @ Liaison where he orchestrated donations from corporate medical donors such as Pfizer , Johnson & Johnson , Merck , and others ; and has run social media campaigns for health-related issues .
His recent endeavors include heading up several organizations and programs relating to public health and `` misinformation '' fighting campaigns .
Interestingly , Mr. Smyser names Bill Gates as his number one influencer on his Linked-In page .
This will prove even more interesting as we discover more about Sandra Smyser later in this article .
Joe Smyser is the CEO @ @ @ @ @ @ @ Project or PGP .
PGP has vaccination as one of its public health tracking and targeting goals .
PGP promotes large-scale behavior change programs through tracking and targeting on social media with the goal of stigmatizing or de-stigmatizing certain groups of people as described in this article from Wired which outlines one of his programs called Stronger .
PGP and Stronger 's goals are to fight what Joe calls vaccine misinformation by targeting and stigmatizing any person or organization that goes against the CDC or official government stance on vaccination , including the @ @ @ @ @ @ @ ) -funded World Health Organization .
As the largest donor to the WHO , the BMGF is currently the number one influencer for world health policy .
The BMGF also supports the CDC through grants to the CDC Foundation , further increasing the power of Gates to influence health policy .
Both the CDC and the WHO have conflicts of interest with vaccine manufacturers .
This fact makes Gate 's influence especially troubling now that we see him actively promoting experimental vaccine technology , developed at `` warp speed , '' and funded @ @ @ @ @ @ @ every citizen of this planet as a response to the Covid-19 pandemic .
Mr. Smyser has given several lectures describing how his programs track and target .
On May 20 , 2020 , he gave a presentation to the National Press Foundation ( NPF ) , urging them to use his VCTR program to find out who the organizations and people are that promote what Joe calls `` vaccine misinformation . ''
He implores the NPF to write targeted pieces that stigmatize anyone who questions vaccines , instead of promoting fair journalism .
@ @ @ @ @ @ @ health can not understand the reasons that parents question vaccines or have `` vaccine hesitancy . ''
Mr. Smyser blames vaccine hesitancy on misinformation about vaccines that are promoted on social media and asks the press to target the purveyors of such information .
If Mr. Smyser has truly been studying vaccine hesitancy as he says he has , he must know the real reasons for it .
He could improve vaccine research and safety , two of the many reasons for vaccine hesitancy .
Yet , he instead powers on with his @ @ @ @ @ @ @ behavioral manipulation .
In another 2020 presentation at MisinfoCon , Mr. Smyser describes his program targeting and tracking results to colleagues .
He gives a similar presentation to this crowd as he gives to the NPF but adds a few telling statements such as a blanket statement against chiropractors because , `` they believe that solutions to your medical problems come from inside your body not outside , '' and another generalization regarding `` anti-vaxxers . ''
He states , `` anti-vaxxers are not nice people , they find where you live , @ @ @ @ @ @ @ you . ''
Ironic coming from a man teaching people how to track and target others online .
He admits that many people do not trust the biggest public health agency , the CDC , and that he needs to get real people involved in public health messaging .
He highlights a Kaiser flu campaign that focused on vaccine-hesitant Latino and Black communities that he says are vaccine-hesitant `` for really damn good reasons . ''
Yet , in this campaign , instead of addressing the reasons behind the hesitancy , he partnered @ @ @ @ @ @ @ the targeted communities to promote the flu vaccine .
The old trick of appealing to authority to manage behavior .
Because , for Mr. Smyser , this is not about truth , it is about behavior manipulation .
In December of 2019 , Joe Smyser came to Colorado to give a presentation to the E-Health Commission and the Office of eHealth Innovation .
The Office of eHealth Innovation is focused on health information exchange and interoperable databases for `` whole-person care , '' which sounds nice and sounds like big brother data tracking @ @ @ @ @ @ @ .
Smyser presented a slide show of his `` vaccine misinformation '' tracking and targeting VCTR program to the commission and spoke about vaccine messaging strategies similar to his NPF presentation .
( He also presented the commission with de-stigmatizing strategies for opioid addiction , but that is another rabbit hole for another day . )
In his presentation , he explains how IMAGE 2 WRAP LEFT PGP partners with several US media and technology companies , including Google , Facebook , Twitter , the Ad Council , HBO , and more .
@ @ @ @ @ @ @ censorship across the internet span if anyone dares question the government 's narrative .
PGP also partners with federal and state health agencies such as the FDA and medical giants like Kaiser .
Is Mr. Smyser partnering with the Colorado state health agency , The Colorado Department of Health and Environment , who pushed for SB20-163 ?
This vaccine exemption data tracking bill was introduced in February 2020 , only two months after Joe Smyser 's visit to Colorado .
Representative Cathy Kipp from Fort Collins Who Used to Serve on the PSD @ @ @ @ @ @ @ , SB20-163 moved through the Senate first , and then moved on to the House for a committee hearing .
The House hearing for SB20-163 was heard by the House Health and Insurance Committee on June 7 , 2020 .
This committee has heard many other vaccine bills that have gone through the Colorado legislature .
The SB20-63 hearing , however , had several substitutions for committee members on the Democrat side .
A notable substitution was a freshman Representative from Fort Collins House District 52 named Cathy Kipp .
Cathy Kipp happened @ @ @ @ @ @ @ for seven years , five of them while Sandra Smyser was the superintendent , before being appointed to her House Representative seat by the Democratic party .
Kipp is not without controversy even in her PSD position when she paid the Democratic party to help her campaign for a seat on the school board , which is supposed to be a non-partisan position .
It is noteworthy that Cathy Kipp was president of PSD Board when the lobbying firm that lobbied for SB20-163 was first hired in 2017 .
As her opponent asked @ @ @ @ @ @ @ director who owes their election to the Democratic Party going to challenge the Democratic Party , leaders , and elected officials that helped them get elected , to address these critical school issues ? ''
In the end , it appears it did n't matter .
Kipp never intended to challenge the Democratic party , she intended to join them .
With Kipp 's House seat secured , Sandra Smyser had an ally in the legislature who helped her get a bill passed that her son helped promote .
What other agendas are @ @ @ @ @ @ @ Sandra Smyser Has Ties to The Bill and Melinda Gates Foundation As mentioned previously , Joe Smyser claims to be influenced by Bill Gates .
Could it be because Joe 's mother has ties to the Bill and Melinda Gates Foundation ?
Did Joe get his start from introductions by his mother ?
Before her position with PSD , Ms. Smyser was the superintendent of the Eagle County School District .
She was superintendent of the year in 2012 in Eagle County and she was mentioned in the 2013 annual letter written by @ @ @ @ @ @ @ A 2014 PolitiChicks article exposed Gates influence over education in Colorado , and Ms. Smyser was involved closely in this conflict of interest during her tenure in Eagle County .
The short of it is that Gates 's money influenced the adoption of the controversial Common Core curriculum and the subsequent Colorado Integration Project into Colorado schools through its almost $ 10 million grant to the Colorado Legacy Foundation in 2011 .
Sandra Smyser was on the board of the Colorado Legacy Foundation at the time .
Her school district received $ 565,000 @ @ @ @ @ @ @ other school districts its size .
Interestingly , all of the Colorado school districts that received the most money from this grant had Colorado State School Board Members with ties to Gates ' money .
As explained in the article , these grants influenced legislation .
Quoting from the article , `` how do this implementation and organizational support mentioned in the grant above look ?
The Colorado Integration Project 13 school districts in Colorado , through a grant from the Bill and Melinda Gates Foundation , were to integrate , in 2013 @ @ @ @ @ @ @ 191 into their schools . ''
Sandra Smyser 's Eagle County School district was one of these 13 districts .
It is worth noting that the Colorado Legacy Foundation changed its name to Colorado Education Initiative ( CEI ) shortly after the January 2014 PolitiChicks article was written .
The Colorado Education Initiative is still heavily funded by Bill and Melinda Gates .
PSD is one of the districts that `` won '' a Colorado Education Initiative grant in 2014 to deliver Social-Emotional data to the Colorado Education Initiative after Ms. Smyser became @ @ @ @ @ @ @ surprisingly , social- emotional and mental health tracking of children is another of Joe Smyser 's online targeting and tracking interests .
Joe Smyser 's Mental Health Tracking Programs Target Colorado Children in Both His Mother 's and His Brother 's School Districts Joe works closely with Kaiser on other campaigns besides the ones mentioned previously in this article .
His social media crisis campaign tracker rcaid.org is funded by Kaiser .
He partners with Kaiser in mental health , tracking what people are saying about mental health online , and encouraging people @ @ @ @ @ @ @ .
Could people who share mental health issues online now and who are monitored by tracking programs or encouraged to share stories and data online be targets of discrimination or stigma later in life ?
Likely , and interestingly the youth who are most consistently online are often gamers .
So it is not hard to guess that Kaiser and Mr. Smyser are also targeting the gaming community with their mental health tracking ?
Now in the wake of the COVID response , as children across the world are being forced into online @ @ @ @ @ @ @ Smyser and Kaiser are creating have a whole new collection of people to watch and target .
Similar types of mental health programs promoted by Joe Smyser and Kaiser described above are being implemented in Colorado schools through grants from the Colorado Education Initiative partnering with Kaiser .
In fact , in 2017 , the Colorado Education Initiative , the same group that was involved in influencing the adaption of the common core curriculum when Sandra Smyser was the Eagle County superintendent , gave a grant to 5 school districts in Colorado through @ @ @ @ @ @ @ The Colorado Education Initiative describes the program : `` CEI 's work with Thriving Schools is part of a national effort by Kaiser Permanente to impact health in schools on a broad scale .
In conjunction with the grant recipients ' announcement , Kaiser Permanente also launched Find Your Words , a public health awareness campaign that talks about depression in an honest and inspiring way .
The `` Find Your Words '' campaign drives viewers to FindYourWords.org , a website that provides basic information about depression , offers resources , and invites @ @ @ @ @ @ @ about mental health and wellness through an interactive component . ''
One of the school districts given this grant was Boulder Valley School District , where Joe Smyser 's brother Timothy works as the IT security specialist for the district .
In addition , in 2014 PSD started to 2014 deliver social , emotional data to the Colorado Education Initiative following the grant PSD received .
Could it be that children in school districts like PSD will be targeted with Joe Smyser 's tracking campaigns or mental health data grabs now that the @ @ @ @ @ @ @ to full-time online learning ?
Sandra Smyser is interested in promoting mental health and social , emotional skills , as described on her PSD homepage .
Is that one of the reasons that PSD seems to have no intention of getting kids back to in-person learning even though the majority of PSD parents want their children back to school ?
Are PSD children being data mined for behavioral health indicators during their full days of online learning ?
Are PSD students serving as another study group for Joe Smyser 's projects through the @ @ @ @ @ @ @ sound far fetched , but after analyzing the Smyser family 's entanglements and events of the 2020 legislative session , anything seems possible when it comes to the Smysers .
Sandra Smyser certainly has access to all the data for all students in her district .
How can any parent trust that any of their children 's data , such as mental health data or other medical data , is safe with Sandra Smyser at the helm ?
Given her blatant conflicts of interest , how can parents trust her with their children @ @ @ @ @ @ @ those with children in PSD should be asking a lot of questions and demanding answers .
The most important being , `` how can a superintendent like Smyser be trusted , and who will be her replacement ? ''
CBS .
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Visit our Re-post guidelines This article is copyrighted by GreenMedInfo LLC, 2020
During the legislative session of 2020, Poudre School District (PSD) sent two lobbyists to the state capitol to lobby in favor of a bill, SB20-163. PSD has paid $48,801.45 of taxpayer money to the lobbying firm Mendez, Barkis, and Associates over the past 12 months, the firm sent to lobby in support of SB20-163 for PSD.
Why would PSD send lobbyists to support a bill that would harm up to 5% of its students and their families?
It is not common practice for a school district to send lobbyists to support such a bill, in fact, only one other school district in Colorado sent lobbyists to support this bill - Adams County.
Thousands of parents showed up at the state capitol to testify against this bill for both the Senate and House hearings. Parents let it be known loud and clear that their children would be targets if this bill passed. The Senate hearing, which was heard in February 2020 before the COVID lockdowns, went into the early morning hours with hundreds of parents testifying against the bill.
Until the last minute of the hearing, before the Senate majority (Democrat) leader showed up and had words with his party members, two of the Democrat Senators looked as if they were going to be no votes. However, after the majority leader left, the bill passed through the Senate with a party-line vote. Democrats voted yes and Republicans voted no. One Democrat Senator admitted the pressure was too much to give a no vote.
The House hearing came after the COVID lockdowns in June 2020. The hearing was scheduled on a Sunday, an unprecedented day for a hearing, especially for such a controversial bill.
The committee chair allowed only 1.5 hours of testimony for each side. This allowed plenty of time for the proponents to get all testimony heard, but only gave enough time for a minute percentage of the thousands of opponents who came to testify against the bill. In fact, thousands of citizens who came out in opposition to the bill were forced to stay outside of the Capitol during the hearing.
SB20-163 is a bill that requires several new procedures relating to vaccine exemptions. The most troubling to parents is that it requires parents who choose to exempt their children from even one vaccine required for school entry, for personal or religious reasons, or children who are exempt for medical reasons, register their exemptions into a State tracking database full of personally identifying information on the child.
This database is an Immunization Information System or IIS. It houses dozens of personal data fields of private medical, location, and age information that parents would not want anyone to have access to unless the parent gave formal consent. Yet, over 6,000 people in Colorado currently have access to this Colorado IIS, also known as CIIS.
These types of medical tracking data bases are wrought with controversy including the very real threat of data breach. These tracking data bases also erode public trust in government, doctors and hospitals.
Sandra Smyser, Poudre School District Superintendent
Sandra Smyser is the superintendent for PSD and is the person responsible for the approval of over $48,000 being paid to the lobbying firm over the year that included the lobbying for SB20-163. The opposition to this bill was well known and was covered in the local media.
Thus, Ms. Smyser cannot claim that parents wanted this bill to pass nor can she claim that she was working for her students. If she was not working for her students, who was she working for? Who was she helping and why would she be willing to pay lobbyists, at the tax payer's expense, to lobby for a bill that would bypass existing privacy laws such as FERPA and force parents to enter their children's private medical data and choices into a state tracking registry?
Smyser must realize that the reality of tracking registries is about to become much more real and concerning to thousands of more parents who do not want their children to be used as Guinea pigs for an experimental Covid vaccine that may use never before tested mRNA technology.
Especially now that multiple news outlets are reporting that a mandatory COVID vaccine is a great possibility and polls show that about half of the population is reluctant to comply, the reality is that exemption tracking will affect even more children in the future.
Looking deeper, it appears that Sandra Smyser did in fact have a reason to hire lobbyists to support SB20-163, and that reason seems to be nepotism. Sandra Smyser appears to be choosing her son and his interests over the interests of the students she is charged with serving.
So, Who is Sandra Smyser's son?
Sandra Smyser's Son Tracks and Targets People and Organizations Who Do Not Agree With His Agenda
The son of Sandra Smyser is Joe Smyser. Joe Smyser has a Ph.D. in Public Health; has worked for the CDC; has been a Corporate Liaison where he orchestrated donations from corporate medical donors such as Pfizer, Johnson & Johnson, Merck, and others; and has run social media campaigns for health-related issues. His recent endeavors include heading up several organizations and programs relating to public health and "misinformation" fighting campaigns. Interestingly, Mr. Smyser names Bill Gates as his number one influencer on his Linked-In page. This will prove even more interesting as we discover more about Sandra Smyser later in this article.
Joe Smyser is the CEO of an organization called the Public Good Project or PGP. PGP has vaccination as one of its public health tracking and targeting goals. PGP promotes large-scale behavior change programs through tracking and targeting on social media with the goal of stigmatizing or de-stigmatizing certain groups of people as described in this article from Wired which outlines one of his programs called Stronger.
PGP and Stronger's goals are to fight what Joe calls vaccine misinformation by targeting and stigmatizing any person or organization that goes against the CDC or official government stance on vaccination, including the Bill and Melinda Gates Foundation (BMGF)-funded World Health Organization. As the largest donor to the WHO, the BMGF is currently the number one influencer for world health policy.
The BMGF also supports the CDC through grants to the CDC Foundation, further increasing the power of Gates to influence health policy. Both the CDC and the WHO have conflicts of interest with vaccine manufacturers. This fact makes Gate's influence especially troubling now that we see him actively promoting experimental vaccine technology, developed at "warp speed," and funded by his foundation to be delivered to every citizen of this planet as a response to the Covid-19 pandemic.
Mr. Smyser has given several lectures describing how his programs track and target. On May 20, 2020, he gave a presentation to the National Press Foundation (NPF), urging them to use his VCTR program to find out who the organizations and people are that promote what Joe calls "vaccine misinformation."
He implores the NPF to write targeted pieces that stigmatize anyone who questions vaccines, instead of promoting fair journalism. He explains to the NPF that public health cannot understand the reasons that parents question vaccines or have "vaccine hesitancy." Mr. Smyser blames vaccine hesitancy on misinformation about vaccines that are promoted on social media and asks the press to target the purveyors of such information.
If Mr. Smyser has truly been studying vaccine hesitancy as he says he has, he must know the real reasons for it. He could improve vaccine research and safety, two of the many reasons for vaccine hesitancy. Yet, he instead powers on with his message of tracking, censorship, and behavioral manipulation.
In another 2020 presentation at MisinfoCon, Mr. Smyser describes his program targeting and tracking results to colleagues. He gives a similar presentation to this crowd as he gives to the NPF but adds a few telling statements such as a blanket statement against chiropractors because, "they believe that solutions to your medical problems come from inside your body not outside," and another generalization regarding "anti-vaxxers." He states, "anti-vaxxers are not nice people, they find where you live, your friends and family and they attack you." Ironic coming from a man teaching people how to track and target others online.
He admits that many people do not trust the biggest public health agency, the CDC, and that he needs to get real people involved in public health messaging. He highlights a Kaiser flu campaign that focused on vaccine-hesitant Latino and Black communities that he says are vaccine-hesitant "for really damn good reasons."
Yet, in this campaign, instead of addressing the reasons behind the hesitancy, he partnered with Kaiser and used influential people in the targeted communities to promote the flu vaccine. The old trick of appealing to authority to manage behavior. Because, for Mr. Smyser, this is not about truth, it is about behavior manipulation.
Joe Smyser Helped Track and Target Children in Colorado
In December of 2019, Joe Smyser came to Colorado to give a presentation to the E-Health Commission and the Office of eHealth Innovation. The Office of eHealth Innovation is focused on health information exchange and interoperable databases for "whole-person care," which sounds nice and sounds like big brother data tracking, the perfect venue for Joe Smyser.
Smyser presented a slide show of his "vaccine misinformation" tracking and targeting VCTR program to the commission and spoke about vaccine messaging strategies similar to his NPF presentation. (He also presented the commission with de-stigmatizing strategies for opioid addiction, but that is another rabbit hole for another day.)
In his presentation, he explains how PGP partners with several US media and technology companies, including Google, Facebook, Twitter, the Ad Council, HBO, and more. These partnerships are interesting given the recent censorship across the internet span if anyone dares question the government's narrative. PGP also partners with federal and state health agencies such as the FDA and medical giants like Kaiser.
Is Mr. Smyser partnering with the Colorado state health agency, The Colorado Department of Health and Environment, who pushed for SB20-163? This vaccine exemption data tracking bill was introduced in February 2020, only two months after Joe Smyser's visit to Colorado.
Representative Cathy Kipp from Fort Collins Who Used to Serve on the PSD Board Aids the Smyser Agenda
As mentioned, SB20-163 moved through the Senate first, and then moved on to the House for a committee hearing. The House hearing for SB20-163 was heard by the House Health and Insurance Committee on June 7, 2020. This committee has heard many other vaccine bills that have gone through the Colorado legislature.
The SB20-63 hearing, however, had several substitutions for committee members on the Democrat side. A notable substitution was a freshman Representative from Fort Collins House District 52 named Cathy Kipp.
Cathy Kipp happened to be on the PSD School Board for seven years, five of them while Sandra Smyser was the superintendent, before being appointed to her House Representative seat by the Democratic party. Kipp is not without controversy even in her PSD position when she paid the Democratic party to help her campaign for a seat on the school board, which is supposed to be a non-partisan position. It is noteworthy that Cathy Kipp was president of PSD Board when the lobbying firm that lobbied for SB20-163 was first hired in 2017.
As her opponent asked, "How is any school board director who owes their election to the Democratic Party going to challenge the Democratic Party, leaders, and elected officials that helped them get elected, to address these critical school issues?"
In the end, it appears it didn't matter. Kipp never intended to challenge the Democratic party, she intended to join them. With Kipp's House seat secured, Sandra Smyser had an ally in the legislature who helped her get a bill passed that her son helped promote. What other agendas are the Smyser family promoting in Colorado?
Sandra Smyser Has Ties to The Bill and Melinda Gates Foundation
As mentioned previously, Joe Smyser claims to be influenced by Bill Gates. Could it be because Joe's mother has ties to the Bill and Melinda Gates Foundation? Did Joe get his start from introductions by his mother?
Before her position with PSD, Ms. Smyser was the superintendent of the Eagle County School District. She was superintendent of the year in 2012 in Eagle County and she was mentioned in the 2013 annual letter written by the Bill and Melinda Gates Foundation.
A 2014 PolitiChicks article exposed Gates influence over education in Colorado, and Ms. Smyser was involved closely in this conflict of interest during her tenure in Eagle County. The short of it is that Gates's money influenced the adoption of the controversial Common Core curriculum and the subsequent Colorado Integration Project into Colorado schools through its almost $10 million grant to the Colorado Legacy Foundation in 2011.
Sandra Smyser was on the board of the Colorado Legacy Foundation at the time. Her school district received $565,000 of the grant, much more than other school districts its size.
Interestingly, all of the Colorado school districts that received the most money from this grant had Colorado State School Board Members with ties to Gates' money. As explained in the article, these grants influenced legislation.
Quoting from the article, "how do this implementation and organizational support mentioned in the grant above look? The Colorado Integration Project 13 school districts in Colorado, through a grant from the Bill and Melinda Gates Foundation, were to integrate, in 2013, key educational reforms under Senate Bill 191 into their schools." Sandra Smyser's Eagle County School district was one of these 13 districts.
It is worth noting that the Colorado Legacy Foundation changed its name to Colorado Education Initiative (CEI) shortly after the January 2014 PolitiChicks article was written. The Colorado Education Initiative is still heavily funded by Bill and Melinda Gates. PSD is one of the districts that "won" a Colorado Education Initiative grant in 2014 to deliver Social-Emotional data to the Colorado Education Initiative after Ms. Smyser became the superintendent of the district.
Not surprisingly, social- emotional and mental health tracking of children is another of Joe Smyser's online targeting and tracking interests.
Joe Smyser's Mental Health Tracking Programs Target Colorado Children in Both His Mother's and His Brother's School Districts
Joe works closely with Kaiser on other campaigns besides the ones mentioned previously in this article. His social media crisis campaign tracker rcaid.org is funded by Kaiser.
He partners with Kaiser in mental health, tracking what people are saying about mental health online, and encouraging people to share their mental health stories online. Could people who share mental health issues online now and who are monitored by tracking programs or encouraged to share stories and data online be targets of discrimination or stigma later in life? Likely, and interestingly the youth who are most consistently online are often gamers.
So it is not hard to guess that Kaiser and Mr. Smyser are also targeting the gaming community with their mental health tracking? Now in the wake of the COVID response, as children across the world are being forced into online learning, tracking programs like those Mr. Smyser and Kaiser are creating have a whole new collection of people to watch and target.
Similar types of mental health programs promoted by Joe Smyser and Kaiser described above are being implemented in Colorado schools through grants from the Colorado Education Initiative partnering with Kaiser. In fact, in 2017, the Colorado Education Initiative, the same group that was involved in influencing the adaption of the common core curriculum when Sandra Smyser was the Eagle County superintendent, gave a grant to 5 school districts in Colorado through the Thriving Schools behavioral health grants.
The Colorado Education Initiative describes the program: "CEI's work with Thriving Schools is part of a national effort by Kaiser Permanente to impact health in schools on a broad scale. In conjunction with the grant recipients' announcement, Kaiser Permanente also launched Find Your Words, a public health awareness campaign that talks about depression in an honest and inspiring way.
The "Find Your Words" campaign drives viewers to FindYourWords.org, a website that provides basic information about depression, offers resources, and invites the public to engage in a conversation about mental health and wellness through an interactive component." One of the school districts given this grant was Boulder Valley School District, where Joe Smyser's brother Timothy works as the IT security specialist for the district. In addition, in 2014 PSD started to 2014 deliver social, emotional data to the Colorado Education Initiative following the grant PSD received.
Could it be that children in school districts like PSD will be targeted with Joe Smyser's tracking campaigns or mental health data grabs now that the children in that district have been sentenced to full-time online learning? Sandra Smyser is interested in promoting mental health and social, emotional skills, as described on her PSD homepage. Is that one of the reasons that PSD seems to have no intention of getting kids back to in-person learning even though the majority of PSD parents want their children back to school? Are PSD children being data mined for behavioral health indicators during their full days of online learning?
Are PSD students serving as another study group for Joe Smyser's projects through the help of his mother? This may sound far fetched, but after analyzing the Smyser family's entanglements and events of the 2020 legislative session, anything seems possible when it comes to the Smysers.
Sandra Smyser certainly has access to all the data for all students in her district. How can any parent trust that any of their children's data, such as mental health data or other medical data, is safe with Sandra Smyser at the helm? Given her blatant conflicts of interest, how can parents trust her with their children?
Parents across Colorado, and especially those with children in PSD should be asking a lot of questions and demanding answers. The most important being, "how can a superintendent like Smyser be trusted, and who will be her replacement?"
References
CBS. 2020. "Only Half of Americans Would Get a COVID-19 Vaccine, Poll Shows." May 27, 2020. https://www.cbsnews.com/news/coronavirus-vaccine-half-americans-would-get/.
CHD. 2020. "CDC and WHO Corrupt Financial Entanglements with the Vaccine Industry." 2020. https://childrenshealthdefense.org/cdc-who/.
CHD. 2020. "RFK, Jr. Rallies Health Freedom Advocates in Colorado." Children's Health Defense. June 12, 2020. https://childrenshealthdefense.org/video/rfk-jr-rallies-health-freedom-advocates-in-colorado/.
CHD. 2020. "Components of MRNA Technology 'Could Lead to Significant Adverse Events in One or More of Our Clinical Trials,' Says Moderna." Children's Health Defense. August 6, 2020. https://childrenshealthdefense.org/news/components-of-mrna-technology-could-lead-to-significant-adverse-events-in-one-or-more-of-our-clinical-trials-says-moderna/.
CO Integration Project. n.d. "Colorado Integration Project." Accessed August 15, 2020. https://web.archive.org/web/20140114203318/https://colegacy.org/colorado-integration-project/.
Colorado Secretary of State. n.d. "Colorado Secretary of State - Online Lobbyist System."
Colorado Secretary of State - Online Lobbyist System. Accessed August 15, 2020. https://www.sos.state.co.us/lobby/Home.do.
Flynn, Colleen, Jenna Carroll, and Fierro Nicole. 2020. "Colorado Lawmakers Advance Controversial Vaccine Bill." FOX31 Denver (blog). June 7, 2020. https://kdvr.com/news/local/health-freedom-advocates-to-speak-at-capitol-on-controversial-vaccine-bill/.
France, Macey. 2014. "CO School Board Seemingly Bought & Sold--Did Gates Buy Your School Board, Too? » Politichicks.Com." Politichicks.Com (blog). January 20, 2014. https://politichicks.com/2014/01/co-school-board-seemingly-bought-sold-gates-buy-school-board/.
Gates, Bill. 2013. "Annual Letter 2013." January 2013. https://www.gatesfoundation.org/Who-We-Are/Resources-and-Media/Annual-Letters-List/Annual-Letter-2013.
Gates Foundation. 2020. "CDC Foundation - Bill & Melinda Gates Foundation." February 2020. https://www.gatesfoundation.org/How-We-Work/Quick-Links/Grants-Database/Grants/2020/02/INV-005725.
Horizon. 2020. "Five Things You Need to Know about: MRNA Vaccines." Horizon: The EU Research & Innovation Magazine. April 1, 2020. https://horizon-magazine.eu/article/five-things-you-need-know-about-mrna-vaccines.html.
Kaiser. 2019. "Social Media Campaign Encourages Mental Health Conversations." December 18, 2019. https://about.kaiserpermanente.org/community-health/news/social-media-campaign-encourages-mental-health-conversations.
Maher, Jessica. 2013. "Grant Will Help School District Lead in Statewide Educational Reform - Loveland Reporter-Herald." March 13, 2013. https://www.reporterherald.com/2013/03/13/grant-will-help-school-district-lead-in-statewide-educational-reform/.
Molteni, Megan. 2020. "An Army of Volunteers Is Taking On Vaccine Disinformation Online." Wired, June 15, 2020. https://www.wired.com/story/can-a-keyboard-crusade-stem-the-vaccine-infodemic/.
OeHI. n.d. "Office of EHealth and Innovation." Accessed August 15, 2020. https://oehi.colorado.gov/.
PSD. 2018. "Superintendent's Office." 2018. https://www.psdschools.org/your-district/your-superintendent.
RCAID. n.d. "COVID-19 (RCAID)." Accessed August 15, 2020. https://covid19.rcaid.org/data.
Smyser, Joe. 2020a. "LinkedIn." 2020. https://www.linkedin.com/in/joesmyser.
Smyser, Joe. 2020b. Joe Smyser, Public Good Projects, MisinfoCon2020. National Academy of Sciences. https://www.youtube.com/watch?v=cTbiu9GLivI&feature=youtu.be.
Smyser, Joe. 2020c. Joe Smyser: Project VCTR Tool. https://www.youtube.com/watch?v=C11gRZugxIk.
Staupe, Vincent. 2020. "Mental Health Efforts to Reach the Gaming Community." May 13, 2020. https://about.kaiserpermanente.org/our-story/news/announcements/mental-health-efforts-to-reach-the-gaming-community.
"The Public Good Projects." n.d. Accessed August 15, 2020. https://publicgoodprojects.org.
White, Rob. 2015. "Two PSD Candidates Paid Larimer Dems for Campaign Help." USA TODAY. October 30, 2015. https://www.usatoday.com/story/news/2015/10/30/poudre-school-district-board-candidates-campaign-expenditures/74905946/.
World Economic Forum. 2020. "How Is the World Health Organization Funded?" World Economic Forum. April 15, 2020. https://www.weforum.org/agenda/2020/04/who-funds-world-health-organization-un-coronavirus-pandemic-covid-trump/.


greenmedinfo--2020-08-30--Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity.

Oridonin ( Ori ) is the major active ingredient of the traditional Chinese medicinal herb Rabdosia rubescens and has anti-inflammatory @ @ @ @ @ of Ori remains unknown .
NLRP3 is a central component of NLRP3 inflammasome and has @ @ @ @ @ variety of chronic inflammation-driven human diseases .
Here , we show that Ori is a @ @ @ @ @ NLRP3 inflammasome .
Ori forms a covalent bond with the cysteine 279 of NLRP3 in @ @ @ @ @ interaction between NLRP3 and NEK7 , thereby inhibiting NLRP3 inflammasome assembly and activation .
Importantly @ @ @ @ @ or therapeutic effects on mouse models of peritonitis , gouty arthritis and type 2 diabetes @ @ @ @ @ activation .
Our results thus identify NLRP3 as the direct target of Ori for mediating @ @ @ @ @ Ori could serve as a lead for developing new therapeutics against NLRP3-driven diseases .

Oridonin (Ori) is the major active ingredient of the traditional Chinese medicinal herb Rabdosia rubescens and has anti-inflammatory activity, but the target of Ori remains unknown. NLRP3 is a central component of NLRP3 inflammasome and has been involved in a wide variety of chronic inflammation-driven human diseases. Here, we show that Ori is a specific and covalent inhibitor for NLRP3 inflammasome. Ori forms a covalent bond with the cysteine 279 of NLRP3 in NACHT domain to block the interaction between NLRP3 and NEK7, thereby inhibiting NLRP3 inflammasome assembly and activation. Importantly, Ori has both preventive or therapeutic effects on mouse models of peritonitis, gouty arthritis and type 2 diabetes, via inhibition of NLRP3 activation. Our results thus identify NLRP3 as the direct target of Ori for mediating Ori's anti-inflammatory activity. Ori could serve as a lead for developing new therapeutics against NLRP3-driven diseases.


greenmedinfo--2020-08-30--Oridonin inhibits VEGF-A-associated angiogenesis and epithelial-mesenchymal transition of breast can

Oridonin inhibits VEGF-A-associated angiogenesis and epithelial-mesenchymal transition of breast cancer.

Metastasis is the primary cause of mortality in patients with breast cancer and lacks effective therapeutic agents .
Oridonin , an active diterpenoid compound isolated from , was identified to be the most potent anti-tumor ingredient .
However , the molecular mechanisms responsible for its anti-metastatic effects remain unclear .
In the present study , oridonin significantly suppressed the migration , invasion and adhesion of MDA-MB-231 and 4T1 breast cancer cells , and inhibited tube formation of human umbilical vein endothelial cells in a dose-dependent manner .
The expression levels of epithelial-mesenchymal transition ( EMT ) -associated marker and the @ @ @ @ @ @ @ /vascular endothelium growth factor ( VEGF ) signaling pathway mRNA and proteins were determined by reverse transcription-quantitative polymerase chain reaction and western blotting , respectively .
The results demonstrated that oridonin effectively inhibited EMT as demonstrated by the significant increases in the expression levels of E-cadherin , and decreased expression of N-cadherin , Vimentin and Snail .
In addition , oridonin exerted its anti-angiogenesis activity through significantly decreasing HIF-1α , VEGF-A and VEGF receptor-2 protein expression .
Furthermore , oridonin was demonstrated to decrease the micro-vessel density as evidenced by the decreased expression @ @ @ @ @ @ @ marker for neovasculature .
In brief , oridonin inhibits tumor cell migration , invasion and adhesion , as well as tumor angiogenesis , which are mediated by suppressing EMT and the HIF-1α/VEGF signaling pathway .
The results of the present study suggest that oridonin may be a promising anti-metastatic agent in breast cancer treatment .

Metastasis is the primary cause of mortality in patients with breast cancer and lacks effective therapeutic agents. Oridonin, an active diterpenoid compound isolated from, was identified to be the most potent anti-tumor ingredient. However, the molecular mechanisms responsible for its anti-metastatic effects remain unclear. In the present study, oridonin significantly suppressed the migration, invasion and adhesion of MDA-MB-231 and 4T1 breast cancer cells, and inhibited tube formation of human umbilical vein endothelial cells in a dose-dependent manner. The expression levels of epithelial-mesenchymal transition (EMT)-associated marker and the hypoxia inducible factor 1α (HIF-1α)/vascular endothelium growth factor (VEGF) signaling pathway mRNA and proteins were determined by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that oridonin effectively inhibited EMT as demonstrated by the significant increases in the expression levels of E-cadherin, and decreased expression of N-cadherin, Vimentin and Snail. In addition, oridonin exerted its anti-angiogenesis activity through significantly decreasing HIF-1α, VEGF-A and VEGF receptor-2 protein expression. Furthermore, oridonin was demonstrated to decrease the micro-vessel density as evidenced by the decreased expression of cluster of differentiation 31, a marker for neovasculature. In brief, oridonin inhibits tumor cell migration, invasion and adhesion, as well as tumor angiogenesis, which are mediated by suppressing EMT and the HIF-1α/VEGF signaling pathway. The results of the present study suggest that oridonin may be a promising anti-metastatic agent in breast cancer treatment.


greenmedinfo--2020-08-30--Oridonin can improve Salmonella-induced immune responses and protect intestinal health.

Background : The effects of dietary supplementation of oridonin ( ORI ) on growth performance , cecal microbiota , epithelium development and antioxidant and immune parameters of broilers infected withwere studied .
A total of 300 1-d-old male chicks were selected and divided into 5 trial groups ( 6 replicates of 10 chickens ) : 1 ) nonchallenge control chicks ( ) , 2 ) chicks treated with Salmonella Challenged Control ( ) , 3 ) chicks treated withchallenge and 50 mg/kg ORI ( O ) , 4 ) chicks treated withchallenge and 80 mg/kg ORI ( O ) , @ @ @ @ @ @ @ 100 mg/kg ORI ( O ) .
Results : The results showed thathad no effect on the feed intake ( FI ) , body weight gain ( BWG ) or feed conversion ratio ( FCR ) of broilers compared with the values measured for the CON group ( > 0.05 ) .
However , compared with the characteristics of CON , showed effects on the counts ofandat 7 d and at 14 d ( Conclusions : The results suggest that ORI can improve-induced immune responses and protect intestinal health , not only through @ @ @ @ @ @ @ its multi-protective effects on gut health .

Background: The effects of dietary supplementation of oridonin (ORI) on growth performance, cecal microbiota, epithelium development and antioxidant and immune parameters of broilers infected withwere studied. A total of 300 1-d-old male chicks were selected and divided into 5 trial groups (6 replicates of 10 chickens): 1) nonchallenge control chicks (), 2) chicks treated with Salmonella Challenged Control (), 3) chicks treated withchallenge and 50 mg/kg ORI (O), 4) chicks treated withchallenge and 80 mg/kg ORI (O), and 5) chicks treated withchallenge and 100 mg/kg ORI (O).
Results: The results showed thathad no effect on the feed intake (FI), body weight gain (BWG) or feed conversion ratio (FCR) of broilers compared with the values measured for the CON group ( > 0.05). However, compared with the characteristics of CON,showed effects on the counts ofandat 7 d and at 14 d ( < 0.05), on jejunal development at 7 d ( < 0.05), and on jejunal immunoglobulin A (IgA) concentration at 7 d ( < 0.05). The addition of 100 mg/kg ORI had the greatest effect on the counts ofandin cecal content ( < 0.05), malonaldehyde (MDA) content in the jejunum ( < 0.05), villi height of the small intestine, and IgA concentrations in the jejunum ( < 0.05).
Conclusions: The results suggest that ORI can improve-induced immune responses and protect intestinal health, not only through its immune inhibitory properties but also through its multi-protective effects on gut health.


greenmedinfo--2020-08-30--Oridonin possesses a novel mechanism to enhance radiation therapeutic responses.

Although many attempts have been made to improve the efficacy of radiotherapy to treat cancer , radiation resistance is still an obstacle in lung cancer treatment .
Oridonin is a natural compound with promising antitumor efficacy that can trigger cancer cell death ; however , its direct cellular targets , efficacy as a radiosensitizer , and underlying mechanisms of activity remain unclear .
Herein , we report that oridonin exhibits additive cytotoxic and antitumor activity with radiation using the H460 non-small cell lung cancer cell lines .
We assessed the effect of oridonin by proliferation , clonogenic , reactive oxygen @ @ @ @ @ @ @ damage , and apoptosis assays .
In vitro , oridonin enhanced the radiation-induced inhibition of cell growth and clonogenic survival .
Oridonin also facilitated radiation-induced ROS production and DNA damage and enhanced apoptotic cell death .
In vivo , the combination of oridonin and radiation effectively inhibited H460 xenograft tumor growth , with higher caspase-3 activation and H2A histone family member X ( H2AX ) phosphorylation compared with that of radiation alone .
Our findings suggest that oridonin possesses a novel mechanism to enhance radiation therapeutic responses by increasing DNA damage and apoptosis @ @ @ @ @ @ @ a novel small molecule to improve radiotherapy in non-small cell lung cancer .

Although many attempts have been made to improve the efficacy of radiotherapy to treat cancer, radiation resistance is still an obstacle in lung cancer treatment. Oridonin is a natural compound with promising antitumor efficacy that can trigger cancer cell death; however, its direct cellular targets, efficacy as a radiosensitizer, and underlying mechanisms of activity remain unclear. Herein, we report that oridonin exhibits additive cytotoxic and antitumor activity with radiation using the H460 non-small cell lung cancer cell lines. We assessed the effect of oridonin by proliferation, clonogenic, reactive oxygen species (ROS) production, DNA damage, and apoptosis assays. In vitro, oridonin enhanced the radiation-induced inhibition of cell growth and clonogenic survival. Oridonin also facilitated radiation-induced ROS production and DNA damage and enhanced apoptotic cell death. In vivo, the combination of oridonin and radiation effectively inhibited H460 xenograft tumor growth, with higher caspase-3 activation and H2A histone family member X (H2AX) phosphorylation compared with that of radiation alone. Our findings suggest that oridonin possesses a novel mechanism to enhance radiation therapeutic responses by increasing DNA damage and apoptosis. In conclusion, oridonin may be a novel small molecule to improve radiotherapy in non-small cell lung cancer.


greenmedinfo--2020-08-30--VIDEO: NY Times/AVAAZ spreads misinformation about Greenmedinfo.com + CDC New Death Stats Reveal the

VIDEO: NY Times/AVAAZ spreads misinformation about Greenmedinfo.com + CDC New Death Stats Reveal the "HOAX"

Two major events are addressed in this livestream conducted by Sayer Ji on August 30th : 1 ) The NY @ @ @ @ @ Greenmedinfo.com 's whistleblowing information as a target for further censorship 2 ) The CDC surreptitiously @ @ @ @ @ on August 26th , revealing that less than 10k of the so-called 'COVID-19 deaths '' @ @ @ @ @ the virus ( even though no virus testing is required to certify someone dead from @ @ @ @ @ living in exciting times .
People are waking up .
And this is causing both @ @ @ @ @ in touch as they continue to censor and reduce our reach by joining us on @ @ @ @ @ https : //t.me/sayeregengmi and by making sure you are on our daily newsletter //www.greenmedinfo.health Please @ @ @ @ @ or becoming a member : https : //www.greenmedinfo.com/membership CDC : `` For 6 % of @ @ @ @ @ the only cause mentioned .
For deaths with conditions or causes in addition to COVID-19 @ @ @ @ @ were 2.6 additional conditions or causes per death . ''
https : //www.cdc.gov/nchs/nvss/vsrr/covid_weekly/ ?

Visit our Re-post guidelines This article is copyrighted by GreenMedInfo LLC, 2020
Two major events are addressed in this livestream conducted by Sayer Ji on August 30th: 1) The NY TIMES and AVAAZ have identified Greenmedinfo.com's whistleblowing information as a target for further censorship 2) The CDC surreptitiously updated their COVID-19 death statistics on August 26th, revealing that less than 10k of the so-called 'COVID-19 deaths" were actually caused solely by the virus (even though no virus testing is required to certify someone dead from COVID-19)
We are living in exciting times. People are waking up. And this is causing both opportunity and challenges. Stay in touch as they continue to censor and reduce our reach by joining us on our new Telegram channel: https://t.me/sayeregengmi and by making sure you are on our daily newsletter www.greenmedinfo.com/newsletter
Please support our work by donating or becoming a member: https://www.greenmedinfo.com/membership
References cited in the video:
WATCH Plandemic: InDOCTORnation.
Crucial Viewing: Understanding the COVID-19 "CASEDEMIC"
EVENT 201: Live Coronavirus Pandemic Exercise, NYC, October 2019.
www.QuestioningCovid.com
CDC: Covid Symptoms
Vaccine Experts: Covid Vaccine Adverse Effects Symptoms
CDC: "For 6% of the deaths, COVID-19 was the only cause mentioned. For deaths with conditions or causes in addition to COVID-19, on average, there were 2.6 additional conditions or causes per death." www.cdc.gov/nchs/nvss/vsrr/covid_weekly/?
www.greenmedinfo.com/blog/who-announces-suspected-cases-covid-19-should-be-written-covid-19-deaths-no-virus-2
www.fox35orlando.com/news/fox-35-investigates-florida-department-of-health-says-some-labs-have-not-reported-negative-covid-19-results
www.greenmedinfo.com/blog/us-gov-health-statistics-agency-directs-hospitals-confirm-suspected-covid-19-deat1
www.greenmedinfo.com/blog/gates-foundation-funded-fact-checker-politifact-censors-greenmedinfo-facebook-rep


greenmedinfo--2020-08-30--Synergistic antitumor activity of oridonin and valproic acid on HL-60 leukemia cells.

BACKGROUND : Oridonin is a diterpenoid isolated from Rabdosia rubescens with potent anticancer activities .
Valproic acid ( VPA ) is a recently emerged antineoplastic histone deacetylase inhibitor .
The aim of the present study is to investigate the synergistic role of oridonin and VPA to inhibit the growth and metastasis of human leukemia cells .
METHODS : The effect of oridonin and VPA on proliferation was evaluated by the MTT assay .
Cell migration and invasion were evaluated by transwell and scratch assays , respectively .
In addition , cell apoptosis was examined by flow cytometry .
The inhibitive @ @ @ @ @ @ @ were determined by using xenografted nude mice .
RESULTS : The results demonstrated that oridonin in combination with VPA synergistically inhibited the proliferation of HL-60 cells , and induced obvious caspase-dependent apoptosis through activation of the intrinsic apoptosis pathway , which is involved in the downregulation of Bcl-2/Bax ratio .
Furthermore , the combination treatment in vivo remarkably reduced the xenograft tumor size and triggered tumor cell apoptosis .
CONCLUSION : Our results suggested that the novel combination of oridonin plus VPA exerted synergistic antiproliferative and apoptosis-inducing effects on human myeloid leukemia cells @ @ @ @ @ @ @ promising antileukemia strategy .

BACKGROUND: Oridonin is a diterpenoid isolated from Rabdosia rubescens with potent anticancer activities. Valproic acid (VPA) is a recently emerged antineoplastic histone deacetylase inhibitor. The aim of the present study is to investigate the synergistic role of oridonin and VPA to inhibit the growth and metastasis of human leukemia cells.
METHODS: The effect of oridonin and VPA on proliferation was evaluated by the MTT assay. Cell migration and invasion were evaluated by transwell and scratch assays, respectively. In addition, cell apoptosis was examined by flow cytometry. The inhibitive effects of oridonin and VPA in vivo were determined by using xenografted nude mice.
RESULTS: The results demonstrated that oridonin in combination with VPA synergistically inhibited the proliferation of HL-60 cells, and induced obvious caspase-dependent apoptosis through activation of the intrinsic apoptosis pathway, which is involved in the downregulation of Bcl-2/Bax ratio. Furthermore, the combination treatment in vivo remarkably reduced the xenograft tumor size and triggered tumor cell apoptosis.
CONCLUSION: Our results suggested that the novel combination of oridonin plus VPA exerted synergistic antiproliferative and apoptosis-inducing effects on human myeloid leukemia cells, and may serve as a potentially promising antileukemia strategy.


greenmedinfo--2020-08-30--The anti-tumor diterpene oridonin is a direct inhibitor of nucleolin in cancer cells.

The bioactive plant diterpene oridonin displays important pharmacological activities and is widely used in traditional Chinese medicine ; however , @ @ @ @ @ is still incompletely described .
In vitro and in vivo data have demonstrated anti-tumor activity @ @ @ @ @ to interfere with several cell pathways ; however , presently only the molecular chaperone HSP70 @ @ @ @ @ direct potential target of this compound .
Here , using a combination of different proteomic @ @ @ @ @ Shift Assay ( CETSA ) experiments , and classical biochemical methods , we demonstrate that @ @ @ @ @ effectively modulating the activity of this multifunctional protein .
The ability of oridonin to target @ @ @ @ @ for the bioactivity profile of this plant diterpene .
Recently , Nucleolin has attracted attention @ @ @ @ @ as its diverse functions are implicated in pathological processes such as cancer , inflammation , @ @ @ @ @ , up to now , no small molecule as Nucleolin binders has been reported , @ @ @ @ @ first evidence of Nucleolin modulation by a small inhibitor .

The bioactive plant diterpene oridonin displays important pharmacological activities and is widely used in traditional Chinese medicine; however, its molecular mechanism of action is still incompletely described. In vitro and in vivo data have demonstrated anti-tumor activity of oridonin and its ability to interfere with several cell pathways; however, presently only the molecular chaperone HSP70 has been identified as a direct potential target of this compound. Here, using a combination of different proteomic approaches, innovative Cellular Thermal Shift Assay (CETSA) experiments, and classical biochemical methods, we demonstrate that oridonin interacts with Nucleolin, effectively modulating the activity of this multifunctional protein. The ability of oridonin to target Nucleolin and/or HSP70 could account for the bioactivity profile of this plant diterpene. Recently, Nucleolin has attracted attention as a druggable target, as its diverse functions are implicated in pathological processes such as cancer, inflammation, and viral infection. However, up to now, no small molecule as Nucleolin binders has been reported, thus our finding represents the first evidence of Nucleolin modulation by a small inhibitor.


greenmedinfo--2020-08-30--Oridonin inhibits myofibroblast differentiation and bleomycin-induced pulmonary fibrosis.

BACKGROUND Idiopathic pulmonary fibrosis ( IPF ) is a progressive disease with unknow .
etiology and a high mortality rate .
Oridonin is a diterpenoid isolated from the Rabdosia rubesecens with diverse biological functions .
However , whether oridonin possess potential protective activity on IPF is still unclear .
MATERIAL AND METHODS The aim of the present study was to explore the therapeutic effects of oridonin on IPF .
First , TGF-β1-induced MRC-5 cells were employed for the evaluation of inhibitory activity in vitro .
Then , a bleomycin ( BLM ) -induced mice pulmonary fibrosis model was used to @ @ @ @ @ @ @ .
Several pathological changes , including alveolar space collapse , emphysema , and infiltration ofinflammatory cells , were observed in the BLM‑treated mice .
RESULTS Oridonin could significantly inhibit the mRNA and protein expression levels of α-SMA and COL1A1 in TGF-β1-induced MRC-5 cells .
Oridonin could attenuate pathological changes , including alveolar space collapse , emphysema , and infiltration of inflammatory cells induced by BLM .
In addition , oridonin could significantly inhibit BLM-induced upregulation of α-SMA and COL1A1 and the phosphorylation of Smad2/3 in lung tissues of mice .
CONCLUSIONS Oridonin could @ @ @ @ @ @ @ in treatment for patients with IPF .
The mechanisms of anti-fibrosis effect of oridonin might be inhibition of the TGF-β/Smad pathway .

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknow. etiology and a high mortality rate. Oridonin is a diterpenoid isolated from the Rabdosia rubesecens with diverse biological functions. However, whether oridonin possess potential protective activity on IPF is still unclear. MATERIAL AND METHODS The aim of the present study was to explore the therapeutic effects of oridonin on IPF. First, TGF-β1-induced MRC-5 cells were employed for the evaluation of inhibitory activity in vitro. Then, a bleomycin (BLM)-induced mice pulmonary fibrosis model was used to verify the activity of oridonin in vivo. Several pathological changes, including alveolar space collapse, emphysema, and infiltration ofinflammatory cells, were observed in the BLM‑treated mice. RESULTS Oridonin could significantly inhibit the mRNA and protein expression levels of α-SMA and COL1A1 in TGF-β1-induced MRC-5 cells. Oridonin could attenuate pathological changes, including alveolar space collapse, emphysema, and infiltration of inflammatory cells induced by BLM. In addition, oridonin could significantly inhibit BLM-induced upregulation of α-SMA and COL1A1 and the phosphorylation of Smad2/3 in lung tissues of mice. CONCLUSIONS Oridonin could be used as a potential therapeutic agent in treatment for patients with IPF. The mechanisms of anti-fibrosis effect of oridonin might be inhibition of the TGF-β/Smad pathway.


greenmedinfo--2020-08-30--Oridonin-loaded and GPC1-targeted gold nanoparticles for multimodal imaging and therapy in pancreati

Oridonin-loaded and GPC1-targeted gold nanoparticles for multimodal imaging and therapy in pancreatic cancer.

Purpose : Early diagnosis and therapy are critical to improve the prognosis of patients with pancreatic cancer .
However , conventional imaging does not significantly increase the capability to detect early stage disease .
In this study , we developed a multifunctional theranostic nanoplatform for accurate diagnosis and effective treatment of pancreatic cancer .
Methods : We developed a theranostic nanoparticle ( NP ) based on gold nanocages ( AuNCs ) modified with hyaluronic acid ( HA ) and conjugated with anti-Glypican-1 ( anti-GPC1 ) antibody , oridonin ( ORI ) , gadolinium ( Gd ) , and Cy7 dye @ @ @ @ @ @ @ @ HAuNCs-Cy7 NPs ( ORI-GPC1-NPs ) including morphology , hydrodynamic size , stability , and surface chemicals .
We measured the drug loading and release efficiency in vitro .
Near-infrared fluorescence ( NIRF ) /magnetic resonance imaging ( MRI ) and therapeutic capabilities were tested in vitro and in vivo .
Results : ORI-GPC1-NPs demonstrated long-time stability and fluorescent/MRI properties .
Bio-transmission electron microscopy ( bio-TEM ) imaging showed that ORI-GPC1-NPs were endocytosed into PANC-1 and BXPC-3 ( overexpression GPC1 ) but not in 293 T cells ( GPC1- negative ) .
Compared @ @ @ @ @ @ @ inhibited the viability and enhanced the apoptosis of pancreatic cancer cells in vitro .
Moreover , blood tests suggested that ORI-GPC1-NPs showed negligible toxicity .
In vivo studies showed that ORI-GPC1-NPs enabled multimodal imaging and targeted therapy in pancreatic tumor xenografted mice .
Conclusion : ORI-GPC1-NP is a promising theranostic platform for the simultaneous diagnosis and effective treatment of pancreatic cancer .

Purpose: Early diagnosis and therapy are critical to improve the prognosis of patients with pancreatic cancer. However, conventional imaging does not significantly increase the capability to detect early stage disease. In this study, we developed a multifunctional theranostic nanoplatform for accurate diagnosis and effective treatment of pancreatic cancer.
Methods: We developed a theranostic nanoparticle (NP) based on gold nanocages (AuNCs) modified with hyaluronic acid (HA) and conjugated with anti-Glypican-1 (anti-GPC1) antibody, oridonin (ORI), gadolinium (Gd), and Cy7 dye. We assessed the characteristics of GPC1-Gd-ORI@HAuNCs-Cy7 NPs (ORI-GPC1-NPs) including morphology, hydrodynamic size, stability, and surface chemicals. We measured the drug loading and release efficiency in vitro. Near-infrared fluorescence (NIRF)/magnetic resonance imaging (MRI) and therapeutic capabilities were tested in vitro and in vivo.
Results: ORI-GPC1-NPs demonstrated long-time stability and fluorescent/MRI properties. Bio-transmission electron microscopy (bio-TEM) imaging showed that ORI-GPC1-NPs were endocytosed into PANC-1 and BXPC-3 (overexpression GPC1) but not in 293 T cells (GPC1- negative). Compared with ORI and ORI-NPs, ORI-GPC1-NPs significantly inhibited the viability and enhanced the apoptosis of pancreatic cancer cells in vitro. Moreover, blood tests suggested that ORI-GPC1-NPs showed negligible toxicity. In vivo studies showed that ORI-GPC1-NPs enabled multimodal imaging and targeted therapy in pancreatic tumor xenografted mice.
Conclusion: ORI-GPC1-NP is a promising theranostic platform for the simultaneous diagnosis and effective treatment of pancreatic cancer.


greenmedinfo--2020-08-30--Oridonin induces growth inhibition and apoptosis in human gastric carcinoma cells.

The tumor suppressive role of oridonin , an active compound extracted from Rabdosia rubescens , has been proven in several gastric cancer ( GC ) cell lines .
The present study aimed to evaluate the effect of oridonin on another GC cell line , SNU-216 , and explore the potential mechanisms .
The viable cell numbers , cell migration , survival fraction , and cell viability were , respectively , evaluated by trypan blue exclusion assay , wound healing assay , clonogenic assay , and CCK-8 assay .
Cell apoptosis was determined by flow cytometry assay and western blot .
@ @ @ @ @ @ @ transient transfection , and the efficiency was verified by western blot .
qRT-PCR was performed to measure the mRNA expression of p53 .
Western blot was used to evaluate the protein expression of apoptosis , DNA damage and p53 function related factors .
We found that oridonin significantly inhibited cell proliferation , migration , and survivability , and enhanced cell apoptosis in SNU-216 cells .
However , it had no influence on HEK293 cell viability .
Oridonin also remarkably enhanced the anti-tumor effect of cisplatin on SNU-216 cells , as it significantly increased @ @ @ @ @ @ @ Moreover , the mRNA and protein expression of p53 was significantly up-regulated in oridonin-treated cells , while Mdm2 expression was down-regulated .
Furthermore , oridonin enhanced p53 function and induced DNA damage .
Knockdown of p53 or employing the caspase inhibitor , Boc-D-FMK , reversed the effect of oridonin on cell viability and apoptosis-related protein expression .
The present study demonstrated that oridonin exhibited an anti-tumor effect on GC SNU-216 cells through regulating p53 expression and function .

The tumor suppressive role of oridonin, an active compound extracted from Rabdosia rubescens, has been proven in several gastric cancer (GC) cell lines. The present study aimed to evaluate the effect of oridonin on another GC cell line, SNU-216, and explore the potential mechanisms. The viable cell numbers, cell migration, survival fraction, and cell viability were, respectively, evaluated by trypan blue exclusion assay, wound healing assay, clonogenic assay, and CCK-8 assay. Cell apoptosis was determined by flow cytometry assay and western blot. The expression of p53 was inhibited by transient transfection, and the efficiency was verified by western blot. qRT-PCR was performed to measure the mRNA expression of p53. Western blot was used to evaluate the protein expression of apoptosis, DNA damage and p53 function related factors. We found that oridonin significantly inhibited cell proliferation, migration, and survivability, and enhanced cell apoptosis in SNU-216 cells. However, it had no influence on HEK293 cell viability. Oridonin also remarkably enhanced the anti-tumor effect of cisplatin on SNU-216 cells, as it significantly increased apoptotic cells and decreased cell viability. Moreover, the mRNA and protein expression of p53 was significantly up-regulated in oridonin-treated cells, while Mdm2 expression was down-regulated. Furthermore, oridonin enhanced p53 function and induced DNA damage. Knockdown of p53 or employing the caspase inhibitor, Boc-D-FMK, reversed the effect of oridonin on cell viability and apoptosis-related protein expression. The present study demonstrated that oridonin exhibited an anti-tumor effect on GC SNU-216 cells through regulating p53 expression and function.


greenmedinfo--2020-08-30--Oridonin enhances the radiosensitivity of lung cancer cells by upregulating Bax and downregulating B

Oridonin enhances the radiosensitivity of lung cancer cells by upregulating Bax and downregulating Bcl-2.

Oridonin is an active component of the traditional Chinese herb .
The present study aimed to evaluate the antitumor effects @ @ @ @ @ cell lung cancer ( NSCLC ) cells and explore whether oridonin could enhance their radiosensitivity @ @ @ @ @ inhibit the proliferation of SPC-A-1 and HCC827 lung cancer cells in a time- and dose-dependent @ @ @ @ @ using the MTT assay .
In addition , pretreatment with oridonin for 24 h prior @ @ @ @ @ enhance the radiosensitivity of SPC-A-1 cells .
Furthermore , the levels of apoptosis regulator BAX @ @ @ @ @ regulator Bcl-2 ( Bcl-2 ) were detected by western blotting analysis .
The results demonstrated @ @ @ @ @ was increased and the level of Bcl-2 was decreased in SPC-A-1 cells treated with oridonin @ @ @ @ @ group that received irradiation alone .
These results indicate that oridonin may have a novel @ @ @ @ @ for the treatment of human NSCLC .

Oridonin is an active component of the traditional Chinese herb. The present study aimed to evaluate the antitumor effects of oridonin on human non-small cell lung cancer (NSCLC) cells and explore whether oridonin could enhance their radiosensitivity. Oridonin was demonstrated to inhibit the proliferation of SPC-A-1 and HCC827 lung cancer cells in a time- and dose-dependent manner, which was detected using the MTT assay. In addition, pretreatment with oridonin for 24 h prior to irradiation was identified to enhance the radiosensitivity of SPC-A-1 cells. Furthermore, the levels of apoptosis regulator BAX (Bax) and apoptosis regulator Bcl-2 (Bcl-2) were detected by western blotting analysis. The results demonstrated that the level of Bax was increased and the level of Bcl-2 was decreased in SPC-A-1 cells treated with oridonin and irradiation compared with the group that received irradiation alone. These results indicate that oridonin may have a novel application as a radiosensitizing agent for the treatment of human NSCLC.


greenmedinfo--2020-08-30--Oridonin could be a promising agent for a hepatic anti-inflammatory.

Hepatic stellate cells ( HSCs ) play an important role in hepatic fibrogenesis and inflammatory modulation .
Endotoxin is dramatically increased in portal venous blood after serious injury and can contribute to liver damage .
However , the mechanism underlying endotoxin 's effects on HSCs remains largely unknown .
Oridonin is a bioactive diterpenoid isolated fromthat exhibits anti-inflammatory properties in different tissues .
In the present study , we determined the effects of oridonin on endotoxin-induced inflammatory response and signaling pathwaysThe production of proinflammatory cytokines in activated human HSCs line LX-2 was measured by ELISA and Western blots .
Immunofluorescence @ @ @ @ @ @ @ determine NF-B activity .
Oridonin treatment significantly inhibited LPS-induced proinflammatory cytokines IL-1 , IL-6 , and MCP-1 production as well as cell adhesion molecules ICAM-1 and VCAM-1 .
Additionally , oridonin blocked LPS-induced NF-B p65 nuclear translocation and DNA binding activity .
Oridonin prevented LPS-stimulated NF-B regulator IKK/and IBphosphorylation and IBdegradation .
Combined treatment of oridonin and an Hsp70 substrate binding inhibitor synergistically suppressed LPS-stimulated proinflammatory cytokines and NF-B pathway activation .
Therefore , oridonin inhibits LPS-stimulated proinflammatory mediators through IKK/IB/NF-B pathway .
Oridonin could be a promising agent for a hepatic anti-inflammatory @

Hepatic stellate cells (HSCs) play an important role in hepatic fibrogenesis and inflammatory modulation. Endotoxin is dramatically increased in portal venous blood after serious injury and can contribute to liver damage. However, the mechanism underlying endotoxin's effects on HSCs remains largely unknown. Oridonin is a bioactive diterpenoid isolated fromthat exhibits anti-inflammatory properties in different tissues. In the present study, we determined the effects of oridonin on endotoxin-induced inflammatory response and signaling pathwaysThe production of proinflammatory cytokines in activated human HSCs line LX-2 was measured by ELISA and Western blots. Immunofluorescence and nuclear fractionation assay were used to determine NF-B activity. Oridonin treatment significantly inhibited LPS-induced proinflammatory cytokines IL-1, IL-6, and MCP-1 production as well as cell adhesion molecules ICAM-1 and VCAM-1. Additionally, oridonin blocked LPS-induced NF-B p65 nuclear translocation and DNA binding activity. Oridonin prevented LPS-stimulated NF-B regulator IKK/and IBphosphorylation and IBdegradation. Combined treatment of oridonin and an Hsp70 substrate binding inhibitor synergistically suppressed LPS-stimulated proinflammatory cytokines and NF-B pathway activation. Therefore, oridonin inhibits LPS-stimulated proinflammatory mediators through IKK/IB/NF-B pathway. Oridonin could be a promising agent for a hepatic anti-inflammatory.


greenmedinfo--2020-08-30--Oridonin inhibits IL-1β-induced inflammation in human osteoarthritis chondrocytes by activating PPAR

Oridonin inhibits IL-1β-induced inflammation in human osteoarthritis chondrocytes by activating PPAR-γ.

Osteoarthritis ( OA ) , a progressive disease of the joints , affects millions of people worldwide .
In the @ @ @ @ @ the effects of oridonin , a diterpenoid isolated from Rabdosia rubescens , on IL-1β-induced inflammation @ @ @ @ @ The results showed that oridonin significantly suppressed IL-1β-induced MMP1 , MMP3 , and MMP13 production @ @ @ @ @ , as well as inducible nitric oxide synthase ( iNOS ) and cyclooxygenase-2 ( COX-2 @ @ @ @ @ by oridonin .
Western blot analysis demonstrated IL-1β-induced NF-κB activation was reduced by oridonin .
@ @ @ @ @ PPAR-γ was increased by oridonin in a concentration-dependent manner .
PPAR-γ antagonist could reverse the @ @ @ @ @ The results suggested that oridonin could be a candidate agent forthe treatment of OA .

Osteoarthritis (OA), a progressive disease of the joints, affects millions of people worldwide. In the present study, we investigated the effects of oridonin, a diterpenoid isolated from Rabdosia rubescens, on IL-1β-induced inflammation using human osteoarthritis chondrocytes. The results showed that oridonin significantly suppressed IL-1β-induced MMP1, MMP3, and MMP13 production. IL-1β-induced NO and PGEproduction, as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression were also attenuated by oridonin. Western blot analysis demonstrated IL-1β-induced NF-κB activation was reduced by oridonin. Furthermore, the expression of PPAR-γ was increased by oridonin in a concentration-dependent manner. PPAR-γ antagonist could reverse the anti-inflammatory activity of oridonin. The results suggested that oridonin could be a candidate agent forthe treatment of OA.


greenmedinfo--2020-08-30--Oridonin inhibits growth and induces apoptosis of human neurocytoma cells via the Wnt/β-catenin path

Oridonin inhibits growth and induces apoptosis of human neurocytoma cells via the Wnt/β-catenin pathway.

Central neurocytoma ( CN ) is a rare periventricular tumor of the central nervous system in young adults .
Typically , patients with CN exhibit a favorable prognosis , but in certain cases the clinical course is more aggressive .
Therefore , investigating effective therapeutic approaches is important .
Oridonin has attracted attention due to its antitumor activities .
However , the role of oridonin in tumorigenesis and progression remains unknown .
The present study examined the antitumor function of oridonin in CN cells , and investigated the underlying molecular mechanism .
An MTT assay suggested that treatment with oridonin @ @ @ @ @ @ @ of CN cells .
The annexin V-fluorescein isothiocyanate/propidium iodide assay and western blot analysis demonstrated that oridonin was able to induce apoptosis and alter the expression of apoptosis-associated proteins by downregulating anti-apoptotic protein , B-cell lymphoma-2 ( Bcl-2 ) , and upregulating pro-apoptosis proteins , Bcl-2-like protein 4 , cleaved caspase-3 and cleaved poly ( ADP-ribose ) polymerase 1 .
Subsequently , the Wnt/β-catenin signaling pathway was examined .
Western blot analysis indicated that oridonin markedly decreased the expression of β-catenin , cyclin D1 and v-myc avian myelocytomatosis viral oncogene homolog .
Furthermore @ @ @ @ @ @ @ RNA or overexpressed in CN cells , and the effect on cell proliferation was examined .
The results indicated that silencing of β-catenin enhanced the inhibitory effect of oridonin on cell growth , whereas the overexpression of β-catenin attenuated this effect .
These data indicated that oridonin inhibited proliferation and induced apoptosis to exert its antitumor activity in CN cells by repressing Wnt/β-catenin signaling .
Therefore , the present study suggested that oridonin might be an effective adjuvant agent , and that the Wnt/β-catenin signaling pathway may be a potent target for the @ @ @ @

Central neurocytoma (CN) is a rare periventricular tumor of the central nervous system in young adults. Typically, patients with CN exhibit a favorable prognosis, but in certain cases the clinical course is more aggressive. Therefore, investigating effective therapeutic approaches is important. Oridonin has attracted attention due to its antitumor activities. However, the role of oridonin in tumorigenesis and progression remains unknown. The present study examined the antitumor function of oridonin in CN cells, and investigated the underlying molecular mechanism. An MTT assay suggested that treatment with oridonin was able to significantly inhibit the proliferation of CN cells. The annexin V-fluorescein isothiocyanate/propidium iodide assay and western blot analysis demonstrated that oridonin was able to induce apoptosis and alter the expression of apoptosis-associated proteins by downregulating anti-apoptotic protein, B-cell lymphoma-2 (Bcl-2), and upregulating pro-apoptosis proteins, Bcl-2-like protein 4, cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase 1. Subsequently, the Wnt/β-catenin signaling pathway was examined. Western blot analysis indicated that oridonin markedly decreased the expression of β-catenin, cyclin D1 and v-myc avian myelocytomatosis viral oncogene homolog. Furthermore, β-catenin was silenced by small interference RNA or overexpressed in CN cells, and the effect on cell proliferation was examined. The results indicated that silencing of β-catenin enhanced the inhibitory effect of oridonin on cell growth, whereas the overexpression of β-catenin attenuated this effect. These data indicated that oridonin inhibited proliferation and induced apoptosis to exert its antitumor activity in CN cells by repressing Wnt/β-catenin signaling. Therefore, the present study suggested that oridonin might be an effective adjuvant agent, and that the Wnt/β-catenin signaling pathway may be a potent target for the therapy in CN.


greenmedinfo--2020-08-30--Oridonin might be an effective drug for the prevention and treatment of lipopolysaccharide-induced e

Oridonin might be an effective drug for the prevention and treatment of lipopolysaccharide-induced endometritis.

Endometritis is a health threat to both humans and animals and poses a huge economic burden .
Oridonin ( Ori @ @ @ @ @ isolated from the traditional Chinese herb Rabdosiarubescens ( R. rubescens ) and has multiple health-promoting @ @ @ @ @ anti-inflammatory , and antitumor effects .
There is little evidence showing that Ori can effectively @ @ @ @ @ relevant mechanisms need to be further clarified .
In this study , we investigated the @ @ @ @ @ endometritis in vivo .
Additionally , we examined the effects of Ori on LPS-stimulated mouse @ @ @ @ @ ) .
The results showed that Ori treatment significantly alleviated LPS-induced endometritis and reduced the @ @ @ @ @ and qPCR results indicated that Ori dose-dependently decreased the expression of TNF-α , IL-1β , @ @ @ @ @ and in mEECs .
In addition , Ori was found to inhibit LPS-induced TLR4/NF-κB signaling @ @ @ @ @ suggest that Ori effectively attenuates LPS-induced endometritis by inhibiting the TLR4/NF-κB signaling pathway and that @ @ @ @ @ drug for the prevention and treatment of LPS-induced endometritis .

Endometritis is a health threat to both humans and animals and poses a huge economic burden. Oridonin (Ori) is a natural diterpenoid isolated from the traditional Chinese herb Rabdosiarubescens (R. rubescens) and has multiple health-promoting effects, including antioxidant, anti-inflammatory, and antitumor effects. There is little evidence showing that Ori can effectively treat endometritis, and the relevant mechanisms need to be further clarified. In this study, we investigated the effects of Ori on LPS-induced endometritis in vivo. Additionally, we examined the effects of Ori on LPS-stimulated mouse endometrial epithelial cells (mEECs). The results showed that Ori treatment significantly alleviated LPS-induced endometritis and reduced the activity of myeloperoxidase. ELISA and qPCR results indicated that Ori dose-dependently decreased the expression of TNF-α, IL-1β, and IL-6 both in tissues and in mEECs. In addition, Ori was found to inhibit LPS-induced TLR4/NF-κB signaling pathway activation. These results suggest that Ori effectively attenuates LPS-induced endometritis by inhibiting the TLR4/NF-κB signaling pathway and that Ori might be an effective drug for the prevention and treatment of LPS-induced endometritis.