What in hell IS covid 911 July 2021 edition

CrackSmokeRepublican

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BTW...smoking Meth-Crack rocks damaged Hunter's Vipers....but anyway... here are articles on "The Toll-like receptors/protease inhibitors" and "Coronaviruses". Great material on this thread @anti-barabas-ite . If you get sick with any "influenza" causing a rise temperature....just take Licorice Root extract (Glycyrrhizin) as soon as symptoms are determined. Combine it with Oolong tea for better effects on Covid-19.

Licorice Root extract is like 5-8 dollars (cheap) and works for flu based lung infections :


Overall, I think Fauci's "Gain of Function" research idiocy is connected with the "Mpro-3CLpro" proteases:
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Structure and inhibition of the SARS-CoV-2 main protease reveal strategy for developing dual inhibitors against Mpro and cathepsin L


Science Advances 09 Dec 2020:
Vol. 6, no. 50, eabe0751
DOI: 10.1126/sciadv.abe0751


Abstract
The main protease (Mpro) of SARS-CoV-2 is a key antiviral drug target. While most Mpro inhibitors have a γ-lactam glutamine surrogate at the P1 position, we recently found that several Mpro inhibitors have hydrophobic moieties at the P1 site, including calpain inhibitors II and XII, which are also active against human cathepsin L, a host protease that is important for viral entry. In this study, we solved x-ray crystal structures of Mpro in complex with calpain inhibitors II and XII and three analogs of GC-376. The structure of Mpro with calpain inhibitor II confirmed that the S1 pocket can accommodate a hydrophobic methionine side chain, challenging the idea that a hydrophilic residue is necessary at this position. The structure of calpain inhibitor XII revealed an unexpected, inverted binding pose. Together, the biochemical, computational, structural, and cellular data presented herein provide new directions for the development of dual inhibitors as SARS-CoV-2 antivirals.

https://advances.sciencemag .org/content/6/50/eabe0751.full

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Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors

Science 24 Apr 2020:

Targeting a key enzyme in SARS-CoV-2
Scientists across the world are working to understand severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). Zhang et al. determined the x-ray crystal structure of a key protein in the virus' life cycle: the main protease. This enzyme cuts the polyproteins translated from viral RNA to yield functional viral proteins. The authors also developed a lead compound into a potent inhibitor and obtained a structure with the inhibitor bound, work that may provide a basis for development of anticoronaviral drugs.
Science, this issue p. 409

Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) is a global health emergency. An attractive drug target among coronaviruses is the main protease (Mpro, also called 3CLpro) because of its essential role in processing the polyproteins that are translated from the viral RNA. We report the x-ray structures of the unliganded SARS-CoV-2 Mpro and its complex with an α-ketoamide inhibitor. This was derived from a previously designed inhibitor but with the P3-P2 amide bond incorporated into a pyridone ring to enhance the half-life of the compound in plasma. On the basis of the unliganded structure, we developed the lead compound into a potent inhibitor of the SARS-CoV-2 Mpro. The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route.

https://science.sciencemag .org/content/368/6489/409.full

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https://en.wikipedia .org/wiki/3C-like_protease

Protease 3CLpro

Alternative names provided by the EC include 3CLpro, 3C-like protease, coronavirus 3C-like protease, Mpro, SARS 3C-like protease, SARS coronavirus 3CL protease, SARS coronavirus main peptidase, SARS coronavirus main protease, SARS-CoV 3CLpro enzyme, SARS-CoV main protease, SARS-CoV Mpro and severe acute respiratory syndrome coronavirus main protease.

The protease 3CLpro is a potential drug target for coronavirus infections due to its essential role in processing the polyproteins that are translated from the viral RNA. The X-ray structures of the unliganded SARS-CoV-2 protease 3CLpro and its complex with an α-ketoamide inhibitor provides a basis for design of α-ketoamide inhibitors[6] for a treatment of SARS-CoV-2 infection.[7][8][9][10][11] Potential protease inhibitors being developed against 3CLpro and homologous 3Cpro include CLpro-1, GC376, rupintrivir, PF-07304814, PF-07321332, chemical 11a, and chemical 11b.[12][13][14][15] The intravenous administered prodrug PF-07304814 entered clinical trials in September 2020,[16] and the orally-active follow-up drug PF-07321332 started recruiting patients in February 2021. The long-term molecular dynamics simulations (1.50 µs) study reported, oolonghomobisflavan-A (a tea bioactive) as a more potent inhibitor of the Mpro of SARS-CoV-2 than previously suggested repurposed anti-HIV drugs. [17] A robust computational strategy stated that the in-house synthesized acridinedione analogs DSPD-2 and DSPD-6 showed more favorable MM-PBSA interaction energies and were seated more deeply inside the binding pocket of Mpro than the antiviral drug (saquinavir). These acridinedione analogs have acceptable ADMET values and low toxicity profile. The binding potential of molecules to the binding site of SARS-CoV-2 Mpro could be increased by targeting the molecules to interact more efficiently with residues of the S1 subsite of the binding pocket.[18]

The 3C-like protease is able to catalytically cleave a peptide bond between a glutamine at position P1 and a small amino acid (serine, alanine, or glycine) at position P1'. The SARS coronavirus 3CLpro can for instance self-cleave the following peptides:[1][2][3]
TSAVLQ-SGFRK-NH2 and SGVTFQ-GKFKK are the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase
The protease is important in the processing of the coronavirus replicase polyprotein (P0C6U8). It is the main protease in coronaviruses and corresponds to nonstructural protein 5 (nsp5).[4] It cleaves the coronavirus polyprotein at 11 conserved sites. The 3CL protease has a cysteine-histidine catalytic dyad at its active site.[2] The sulfur of the cysteine acts as a nucleophile and the imidazole ring of the histidine as a general base.[5]

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Glycyrrhizin effectively neutralizes SARS-CoV-2 in vitro by inhibiting the viral main protease

L. van de Sand, M. Bormann, M. Alt, L. Schipper, C.S. Heilingloh, D. Todt, U. Dittmer, C. Elsner, O. Witzke, View ORCID ProfileA. Krawczyk

doi: https://doi.org/10.1101/2020.12.18.423104
Now published in Viruses doi: 10.3390/v13040609

Abstract
The newly emerged coronavirus, which was designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 disease. High effective and well-tolerated medication for hospitalized and non-hospitalized patients is urgently needed. Traditional herbal medicine substances were discussed as promising candidates for the complementary treatment of viral diseases and recently suggested for the treatment of COVID-19. In the present study, we investigated aqueous licorice root extract for its neutralizing activity against SARS-CoV-2 in vitro, identified the active compound glycyrrhizin and uncovered the respective mechanism of viral neutralization. We demonstrated that glycyrrhizin, the primary active ingredient of the licorice root, potently neutralizes SARS-CoV-2 by inhibiting the viral main protease. Our experiments highlight glycyrrhizin as a potential antiviral compound that should be further investigated for the treatment of COVID-19.

Competing Interest Statement
The authors have declared no competing interest.

Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv
 

CrackSmokeRepublican

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More on G

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Plant Products as Inhibitors of Coronavirus 3CL Protease
Anirban Mandal, 1 Ajeet Kumar Jha, 2 and Banasri Hazra 3 ,*
Author information Article notes Copyright and License information Disclaimer

Abstract
Background: The ongoing COVID-19 pandemic has created an alarming situation due to extensive loss of human lives and economy, posing enormous threat to global health security. Till date, no antiviral drug or vaccine against SARS-CoV-2 has reached the market, although a number of clinical trials are under way. The viral 3-chymotrypsin-like cysteine protease (3CLpro), playing pivotal roles in coronavirus replication and polyprotein processing, is essential for its life cycle. In fact, 3CLpro is already a proven drug discovery target for SARS- and MERS-CoVs. This underlines the importance of 3CL protease in the design of potent drugs against COVID-19.

Methods: We have collected one hundred twenty-seven relevant literatures to prepare the review article. PubMed, Google Scholar and other scientific search engines were used to collect the literature based on keywords, like “SARS-CoVs-3CL protease,” “medicinal plant and anti-SARS-CoVs-3CL protease” published during 2003–2020. However, earlier publications related to this topic are also cited for necessary illustration and discussion. Repetitive articles and non-English studies were excluded.

Results: From the literature search, we have enlisted medicinal plants reported to inhibit coronavirus 3CL protease. Some of the plants like Isatis tinctoria L. (syn. Isatis indigotica Fort.), Torreya nucifera (L.) Siebold and Zucc., Psoralea corylifolia L., and Rheum palmatum L. have exhibited strong anti-3CLpro activity. We have also discussed about the phytochemicals with encouraging antiviral activity, such as, bavachinin, psoralidin, betulinic acid, curcumin and hinokinin, isolated from traditional medicinal plants.

Conclusion: Currently, searching for a plant-derived novel drug with better therapeutic index is highly desirable due to lack of specific treatment for SARS-CoV-2. It is expected that in-depth evaluation of medicinally important plants would reveal new molecules with significant potential to inhibit coronavirus 3CL protease for development into approved antiviral drug against COVID-19 in future.

Introduction
Recently, a novel coronavirus was discovered in patients suffering from respiratory ailment accompanied by fever, dry cough and tiredness. Other symptoms, like sore throat, nasal congestion, headache, conjunctivitis, diarrhea, loss of taste or smell, were usually mild, and appeared gradually. This was coronavirus disease 2019 (COVID-19), unknown to the world before its outbreak in December 2019 in Wuhan, China (Burki, 2020). The highly infectious virus started to spread rapidly among the population in many countries all over the world, and created a pandemic situation within a couple of months (Bedford et al., 2020). Reports have indicated that even asymptomatic people can transmit the virus, mainly through respiratory droplets that can cause human-to-human transmission. The extremely contagious novel coronavirus 2019 (nCoV-19) was responsible for about 1.76 million deaths and 79.67 million confirmed cases globally till date (WHO, 2020).

The major phenotype of COVID-19 is severe acute respiratory distress syndrome (ARDS), similar to that caused by SARS-CoV and MERS-CoV (Hirano and Murakami, 2020). At present, there is no specific treatment for COVID-19, while vaccines will take some more time to come to the market. Hence, clinical management of COVID-19 is currently limited to preventive and supportive treatments, and mostly designed to alleviate further complications and organ damage (Rodríguez-Morales et al., 2020). Clinical studies have shown promising results in patients using the protease inhibitor drug lopinavir in combination with ritonavir, commonly used to treat HIV (Lu, 2020). Also, hydroxychloroquine, an antimalarial drug, and remdesivir, a nucleoside analogue of SARS-CoVs, were used to treat COVID-19 patients (Lee and Hsueh, 2020; Wu et al., 2020).

SARS-CoV-2 encodes two proteases, a papain like protease (PLPro), and a 3- chymotrypsin-like cysteine protease (3CLPro) also known as viral main protease (Mpro), for proteolytic processing during viral maturation. The PLPro of coronavirus cleaves at no less than two sites on the pp1a polyprotein, whereas 3CLPro has at least eleven inter-domain sites on the pp1a and pp1ab polyproteins (Krichel et al., 2020). The functional importance of this proteolytic enzyme in the viral life cycle makes 3CLpro a promising target for drug development against SARS-CoV-2 and other coronaviruses. Zhang et al. have successfully crystallized the 3CL protease from SARS-CoV-2 (Zhang et al., 2020a). This protease contains several highly conserved substrate-binding sites within the active site of the enzyme. Therefore, this is an opportunity for designing a wide variety of inhibitors against coronavirus 3CLpro. It is also exciting that the structures of 3CLpro in SARS-CoV-2 and SARS-CoV differ by only twelve amino acids with comparable ligand binding efficiency (Macchiagodena et al., 2020). This demonstrated the possibility that inhibitors of SARS-CoV-3CLpro will be active against SARS-CoV-2-3CLpro, too. In fact, protease inhibitors have drastically reduced the mortality against HCV/HIV, and maximized the therapeutic benefit (Kurt Yilmaz et al., 2016). Altogether, it is speculated that 3CL protease represents a potential target for the inhibition of CoV replication and this will definitely escalate the ongoing search for a new drug against SARS-CoV-2.

https://www.ncbi.nlm.nih .gov/pmc/articles/PMC7985176/

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Targeting the Dimerization of the Main Protease of Coronaviruses:
A Potential Broad-Spectrum Therapeutic Strategy

Bhupesh Goyal*and Deepti Goyal

https://pubs.acs .org/doi/pdf/10.1021/acscombsci.0c00058?ref=vi-chemistry_coronavirus_research&

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Pharmacologic perspective: glycyrrhizin may be an efficacious therapeutic agent for COVID-19
DOI:10.1016/j.ijantimicag.2020.105995

Coronavirus disease 2019 (COVID-19) caused by a previously unknown pathogen named severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has now become a pandemic threat to the whole world. However, there are no vaccines or specific treatment against the new virus. Therefore, there is an urgent need for advancing novel therapeutic interventions for COVID-19. Glycyrrhizin, a triterpene saponine, is valuable for its various biological functions and pharmacology effects. In this brief article, we will discuss the therapeutic potential of glycyrrhizin for COVID-19 from the perspective of its pharmacological action including binding angiotensin converting enzyme II (ACE2), down-regulating proinflammatory cytokines, inhibiting the accumulation of intracellular ROS, inhibiting thrombin, inhibiting the hyperproduction of airway exudates, and inducing endogenous interferon.

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Annu Rep Med Chem. 2007 Feb 1;41:183-196.
doi: 10.1016/S0065-7743(06)41011-3.
Progress in Anti-SARS Coronavirus Chemistry, Biology and Chemotherapy
Arun K Ghosh Kai Xi, Michael E Johnson, Susan C Baker, Andrew D Mesecar

Abstract

Proteolytic processing of the coronavirus replicase polyproteins is essential for ongoing viral ribonucleic acid (RNA) synthesis. Therefore, the severe acute respiratory syndrome (SARS)-coronaviruses (SARS-CoV) proteases are attractive targets for the development of antiviral drugs to reduce viral replication and pathogenicity. The structure and activity of the coronavirus 3C-like protease (3CLpro) has already been elucidated, and the design of inhibitors to 3CLpro as therapeutics has been proposed. The chapter discusses SARS-CoV 3CLpro inhibitors that include covalent inhibitors, noncovalent inhibitors, and inhibitors from screening. SARS-CoV papain-like protease (PLpro) is considered an equally viable target to 3CLpro for drug design because both are essential for viral replication. However, PLpro has likely not been pursued because of the paucity of structural information. Several compounds have been identified that have shown inhibitory activity against SARS-CoV. However, no information regarding their mechanism of action or the corresponding target is known. Glycyrrhizin showed inhibitory activity for SARS-CoV replication with EC50 = 300 mg/L after virus absorption in Vero cells. Some glycyrrhizin acid derivatives were found to inhibit SARS-CoV replication in vitro with EC50 values ranging from 5 to 50 μM. Unfortunately, these compounds show high cytotoxity.

(Just take only while infected...--CSR)
https://pubmed.ncbi.nlm.nih .gov/19649165/
 
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CrackSmokeRepublican

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A bit on CBNs causing heart inflammation. Not 100% sure if this was used as a delivery agent. Some research papers indicate that Carbon Based Nano-Tubes can be used for drug delivery and can stop influenzas. They act like spike proteins (this is an area that is not researched if it was used in the mRNA Covid-19 vaccines):


Fig. 2
The mechanisms by which carbon-based nanoparticles induce cytotoxicity of macrophages. Exposure of macrophages to carbon nanomaterials triggers a cascade of cellular and molecular events, such as ROS generation and lysosome damage, which serve as the mechanisms underlying carbon nanomaterial-induced cell death, including necrosis, apoptosis and pyroptosis. Carbon nanomaterials cause the mitochondrial dependent apoptotic cascades through ROS-activated MAPKs pathway. ROS could activate several transcription factors, such as NF-κB that regulates the inflammatory response. Carbon nanomaterials induce lysosomal membrane permeabilization (LMP), resulting in the translocation of cathepsins to the cytoplasm. ROS and LMP were reciprocal causation generating an amplification loop. LMP could potentially cause autophagy dysfunction. And inflammasome-dependent pyroptosis was initiated characterized by cleavage of caspase 1 and downstream IL-1β release

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Part Fibre Toxicol

. 2019 Apr 11;16(1):18.
doi: 10.1186/s12989-019-0299-z.
Cellular Toxicity and Immunological Effects of Carbon-based Nanomaterials

Abstract

Background:
Carbon nanomaterials are a growing family of materials featuring unique physicochemical properties, and their widespread application is accompanied by increasing human exposure.

Main body:
Considerable efforts have been made to characterize the potential toxicity of carbon nanomaterials in vitro and in vivo. Many studies have reported various toxicology profiles of carbon nanomaterials. The different results of the cytotoxicity of the carbon-based materials might be related to the differences in the physicochemical properties or structures of carbon nanomaterials, types of target cells and methods of particle dispersion, etc. The reported cytotoxicity effects mainly included reactive oxygen species generation, DNA damage, lysosomal damage, mitochondrial dysfunction and eventual cell death via apoptosis or necrosis. Despite the cellular toxicity, the immunological effects of the carbon-based nanomaterials, such as the pulmonary macrophage activation and inflammation induced by carbon nanomaterials, have been thoroughly studied. The roles of carbon nanomaterials in activating different immune cells or inducing immunosuppression have also been addressed.

Conclusion:
Here, we provide a review of the latest research findings on the toxicological profiles of carbon-based nanomaterials, highlighting both the cellular toxicities and immunological effects of carbon nanomaterials. This review provides information on the overall status, trends, and research needs for toxicological studies of carbon nanomaterials.

https://pubmed.ncbi.nlm.nih .gov/30975174/
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This paper mentions "Smart Phone Surveillance":

Focused role of nanoparticles against COVID-19: Diagnosis and treatment.
Dheyab MA1,
Khaniabadi PM2,
Aziz AA1
Jameel MS1,
Mehrdel B3,
Oglat AA4,
Khaleel HA5
Author information
Photodiagnosis and Photodynamic Therapy, 06 Apr 2021, 34:102287
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1627629149500.png
https://pubmed.ncbi.nlm.nih .gov/30975174/
1627629191200.png
 
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anti-barabas-ite

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if you get sick with a Flu toxicity event, there are things that you can and most likely should do.

first do not eat sugar! ha just kidding. but being a diabetic isn't going to help!

do everything to strengthen your mitochondrial health!
read GU for practical self help.

and be prepared in case you are skripal'ed by the ZOG terrorists in our midst.

be ready to inform your Dr. ahead of time with protocols other than a death Vent. IF you ever went to hospital.


STORY AT-A-GLANCE
  • Early in the pandemic, five critical care physicians formed the Front Line COVID-19 Critical Care Working Group (FLCCC), which developed the highly effective COVID-19 treatment protocol known as MATH+
  • MATH+ involves a combination of ivermectin, vitamin C, methylprednisolone, thiamine, vitamin D and other readily available substances to treat COVID-19
  • Other FLCCC protocols have been developed for COVID-19 prevention and early at-home treatment, as well as for long-haul symptoms
  • From March 20, 2021, to May 21, 2021, there were 1,293 hospitalized COVID-19 patients at United Memorial Medical Center. Eighty-six of them died, resulting in a 6.7% death rate; that’s about half the 12.5% death rate for hospitalized COVID-19 patients reported by the National Center for Health Statistics over the same period
  • One of the MATH+ creators, Dr. Joseph Varon, who leads the COVID-19 unit at United Memorial Medical Center (UMMC) in Houston, has been trying to get the word out about the success of MATH+, but has been censored by the media
  • The newest MATH+ protocol features ivermectin as a core drug and replaced hydroxychloroquine (HCQ) with quercetin

Have you heard of the MATH+ protocol to treat COVID-19? One of its creators, Dr. Joseph Varon, who leads the COVID-19 unit at United Memorial Medical Center (UMMC) in Houston, has been trying to get the word out about it since the start of the pandemic. "We have options for patients now. We just need to make those options available," he said, speaking with broadcast journalist Ivory Hecker.1

Hecker has a story in her own right, as she was fired from FOX 26 Houston in June 2021 after she interrupted a live news segment to tell viewers the station had prohibited her from sharing certain information, adding that she's "not the only reporter being subjected to this."2

Censorship is an ongoing problem that's reached unprecedented levels during the pandemic, and is the reason why you probably haven't heard of the MATH+ protocol, despite its immense success in saving lives over the last year. Varon has been at the frontlines throughout, marking his 366th consecutive day treating COVID-19 patients on March 20, 2021.3

From March 20, 2021, to May 21, 2021, there were 1,293 hospitalized COVID-19 patients at United Memorial Medical Center. Eighty-six of them died, resulting in a 6.7% death rate. That's about half the 12.5% death rate for hospitalized COVID-19 patients reported by the National Center for Health Statistics over the same period.4

MATH+ Protocol Saves Lives, but Media Is Ignoring It
Early on in the pandemic, five critical care physicians formed the Front Line COVID-19 Critical Care Working Group (FLCCC), which developed the highly effective COVID-19 treatment protocol known as MATH+. Varon was among them, as was Dr. Paul Marik, a critical care doctor at Sentara Norfolk General Hospital in East Virginia. The protocol for hospitalized patients was initially based on the following:

  • Intravenous Methylprednisolone
  • High-dose intravenous Ascorbic acid (vitamin C)
  • Plus optional treatments Thiamine, zinc and vitamin D
  • Full dose low molecular weight Heparin

In the beginning, only supportive care was offered to COVID-19 patients. Even today, people with COVID-19 are told to stay home and isolate until they're lacking oxygen, a recommendation that Marik believes is costing lives, since early treatment with MATH+ is so effective:5

"While we may not have the best answers, we do have some answers and to tell people to stay at home and isolate so they go blue is an absurdity that's actually causing lots of damage because we are now waiting for the virus to, in some people, cause the cytokine storm. And when they arrive with that state it is very difficult to reverse it and stop it and bring them back."
The MATH+ protocol led to high survival rates. Out of more than 100 hospitalized COVID-19 patients treated with the MATH+ protocol as of mid-April 2020, only two died. Both were in their 80s and had advanced chronic medical conditions.6 But according to Varon, despite their unusual successes, reporters weren't interested in why the patients at his hospital were more likely to survive.7

The physicians behind MATH+ are clear that their protocols are fluid and change in response to the data. As such, there have been two major changes since MATH+ was first released, one involving ivermectin and another involving hydroxychloroquine (HCQ).


Ivermectin Added to MATH+
Ivermectin was added as a core medication in FLCCC's protocols for the prevention and treatment of COVID-19 in October 2020.8 Ivermectin — a broad-spectrum antiparasitic that also has anti-inflammatory activity — has been found to reduce COVID-19 mortality by 81%.9 The drug is also safe, inexpensive and widely available, with decades of clinical usage suggesting it has a "high margin of safety."10

By December 2020, FLCCC, noting the extreme success of the drug, called for widespread adoption of ivermectin, both as a prophylactic and for the treatment of all phases of COVID-19.11,12 In one prevention trial, 58 volunteers took 12 milligrams of ivermectin once per month for four months.

Only four (6.96%) came down with mild COVID-19 symptoms during the May through August 2020 trial period.13 In comparison, 44 of 60 health care workers (73.3%) who had declined the medication were diagnosed with COVID-19. In June 2021, Varon and colleagues published a review in the American Journal of Therapeutics, which included meta-analyses based on 18 randomized controlled treatment trials of ivermectin in COVID-19.14 The results were impressive, showing:15

  • Large, statistically significant reductions in mortality, time to clinical recovery and time to viral clearance when used for treatment
  • Significantly reduced risks of contractive COVID-19 with regular ivermectin use
The data are so strong that, at the India Institute of Medical Sciences, all health care workers now take two 0.3 mg/kg doses of ivermectin 72 hours apart, then repeat the dose monthly to prevent COVID-19.16 And in regions that have implemented ivermectin distribution campaigns, associated reductions in case fatality rates results.17 According to the review:18

"Finally, the many examples of ivermectin distribution campaigns leading to rapid population-wide decreases in morbidity and mortality indicate that an oral agent effective in all phases of COVID-19 has been identified."
Marik believes that a mass distribution program of ivermectin, together with melatonin, vitamin D and aspirin, could end the pandemic. By assuming everyone is infected and treating with this safe combination of inexpensive compounds, Marik says, "We'll eliminate SARS-CoV-2. It will be gone."19 This isn't likely to happen, though, due to "economic and political factors that benefit from the ongoing pandemic."20

HCQ Replaced With Quercetin
HCQ, a zinc ionophore, was part of the MATH+ protocol for the first six months of the pandemic. (They have recently swapped quercetin for HCQ.) At this time, the death rate for COVID-19 patients at Varon's UMMC was 4.4%, compared to a death rate of about 20% at other hospitals.21

Hecker first spoke with Varon about HCQ in August 2020, and he spoke favorably about using the controversial drug, noting that out of more than 300 COVID-19 patients treated at UMMC, they had a 95% success rate.22

Misinformation and outright lies were spun about HCQ, including fabricated research, in an apparent effort to suppress and prevent its widespread use. Other physicians, including Dr. Vladimir Zelenko, a practicing physician in a Jewish community in Monroe, New York, have had great success using HCQ for COVID-19.23

However, in June 2020, the National Institutes of Health halted a clinical trial of HCQ after stating that, while the drug wasn't harmful, it also wasn't beneficial to hospitalized patients.24

Backlash ensued following the NIH announcement, and FLCCC phased out the use of HCQ in its protocols. Their latest I-MASK+ protocol, updated June 30, 2021,25 recommends quercetin instead. Quercetin, also a zinc ionophore, is an over-the-counter alternative to HCQ and works much like HCQ does. According to Marik:26

"Experimental and early clinical data (published in high impact journals) suggests that this compound has broad antiviral properties (including against coronavirus) and acting at various steps in the viral life cycle. It also appears to be a potent inhibitor of heat shock proteins (HSP 40 and 70) which are required for viral assembly."
Ivermectin Continues To Be Censored, US on 'Media Lockdown'
In the video above, Hecker speaks with several recovered COVID-19 patients who received the MATH+ protocol. One, Manuel Espinoza, a urologist from Texas, was on a slow decline using the conventional COVID protocols. Then his wife found out about the MATH+ protocol online, and Espinoza was emergency airlifted to UMMC. "Within hours" of the treatment his health had turned around, he said, and "within days, just immense improvement."27

Yet, Varon said that every time he mentioned ivermectin on social media, "he went to Facebook jail." Reporters also told him, multiple times, that they were banned from reporting on certain COVID-19 drug treatments.28 Similar censorship was experienced by Dr. Pierre Kory, who was also a part of the group that formed FLCCC.

On December 8, 2020, Kory testified to the Senate Committee on Homeland Security and Governmental Affairs, which held a hearing on "Early Outpatient Treatment: An Essential Part of a COVID-19 Solution." He called on the NIH, CDC and FDA to review the expansive data on ivermectin to prevent COVID-19, keep those with early symptoms from progressing and help critically ill patients recover:29,30

Despite his impassioned pleas and astonishing science to back them up, the treatment was not only ignored by the committee but promptly eviscerated.31 Meanwhile, media reports claimed ivermectin was unproven and the World Health Organization also refused to endorse it.

YouTube removed Kory's testimony, which had nearly 9 million views, calling it a danger to the community.32 Kory says that while his research on ivermectin has gotten lots of attention worldwide, it's gotten zero in the U.S. — "U.S. is on a media lockdown," he said.33 Varon agreed, telling Hecker that "no one" is asking about the MATH+ protocol. "Right now everyone is interested in vaccination."34

MATH+ Protocol Is Available in 23 Languages
FLCCC's I-MASK+ protocol can be downloaded in full,35 giving you step-by-step instructions on how to prevent and treat the early symptoms of COVID-19. FLCCC also has protocols for at-home prevention and early treatment, called I-MASS, which involves ivermectin, vitamin D3, a multivitamin and a digital thermometer to watch your body temperature in the prevention phase and ivermectin, melatonin, aspirin and antiseptic mouthwash for early at-home treatment.

Household or close contacts of COVID-19 patients may take ivermectin (18 milligrams, then repeat the dose in 48 hours) for post-exposure prevention.36 FLCCC also has a management protocol — I-RECOVER37 — for long haul COVID-19 syndrome. The protocols are translated into 23 different languages to provide widespread, free access to this lifesaving information, including how to get ivermectin.38

FLCCC remains hopeful that ivermectin will be formally adopted into national or international COVID-19 treatment guidelines in the near future. But, as Hecker noted, the inexpensive medication faces a major hurdle:39

"Had there been an existing known, safe and effective treatment for COVID-19, Emergency Use Authorization of a vaccine for the virus would be prohibited by law. Could that have been part of the motivation for the strange censorship of certain COVID-19 treatments that we witnessed over the past year at news and social media corporations?"
 

anti-barabas-ite

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Del ahead of the curve.

Vandenbosch. Explaining how you make variants...yeah by vaxxing for symptoms instead of virus!!!!
 

CrackSmokeRepublican

An ancient story of Fhunter Xiden...and the pipe.
Cave Beast
🐸 Citizen of the Internet 🐸
⏰☕🚬🚽🚿🪒
if you get sick with a Flu toxicity event, there are things that you can and most likely should do.

first do not eat sugar! ha just kidding. but being a diabetic isn't going to help!

do everything to strengthen your mitochondrial health!
read GU for practical self help.

and be prepared in case you are skripal'ed by the ZOG terrorists in our midst.

be ready to inform your Dr. ahead of time with protocols other than a death Vent. IF you ever went to hospital.


STORY AT-A-GLANCE
  • Early in the pandemic, five critical care physicians formed the Front Line COVID-19 Critical Care Working Group (FLCCC), which developed the highly effective COVID-19 treatment protocol known as MATH+
  • MATH+ involves a combination of ivermectin, vitamin C, methylprednisolone, thiamine, vitamin D and other readily available substances to treat COVID-19
  • Other FLCCC protocols have been developed for COVID-19 prevention and early at-home treatment, as well as for long-haul symptoms
  • From March 20, 2021, to May 21, 2021, there were 1,293 hospitalized COVID-19 patients at United Memorial Medical Center. Eighty-six of them died, resulting in a 6.7% death rate; that’s about half the 12.5% death rate for hospitalized COVID-19 patients reported by the National Center for Health Statistics over the same period
  • One of the MATH+ creators, Dr. Joseph Varon, who leads the COVID-19 unit at United Memorial Medical Center (UMMC) in Houston, has been trying to get the word out about the success of MATH+, but has been censored by the media
  • The newest MATH+ protocol features ivermectin as a core drug and replaced hydroxychloroquine (HCQ) with quercetin

Have you heard of the MATH+ protocol to treat COVID-19? One of its creators, Dr. Joseph Varon, who leads the COVID-19 unit at United Memorial Medical Center (UMMC) in Houston, has been trying to get the word out about it since the start of the pandemic. "We have options for patients now. We just need to make those options available," he said, speaking with broadcast journalist Ivory Hecker.1

Hecker has a story in her own right, as she was fired from FOX 26 Houston in June 2021 after she interrupted a live news segment to tell viewers the station had prohibited her from sharing certain information, adding that she's "not the only reporter being subjected to this."2

Censorship is an ongoing problem that's reached unprecedented levels during the pandemic, and is the reason why you probably haven't heard of the MATH+ protocol, despite its immense success in saving lives over the last year. Varon has been at the frontlines throughout, marking his 366th consecutive day treating COVID-19 patients on March 20, 2021.3

From March 20, 2021, to May 21, 2021, there were 1,293 hospitalized COVID-19 patients at United Memorial Medical Center. Eighty-six of them died, resulting in a 6.7% death rate. That's about half the 12.5% death rate for hospitalized COVID-19 patients reported by the National Center for Health Statistics over the same period.4

MATH+ Protocol Saves Lives, but Media Is Ignoring It
Early on in the pandemic, five critical care physicians formed the Front Line COVID-19 Critical Care Working Group (FLCCC), which developed the highly effective COVID-19 treatment protocol known as MATH+. Varon was among them, as was Dr. Paul Marik, a critical care doctor at Sentara Norfolk General Hospital in East Virginia. The protocol for hospitalized patients was initially based on the following:

  • Intravenous Methylprednisolone
  • High-dose intravenous Ascorbic acid (vitamin C)
  • Plus optional treatments Thiamine, zinc and vitamin D
  • Full dose low molecular weight Heparin

In the beginning, only supportive care was offered to COVID-19 patients. Even today, people with COVID-19 are told to stay home and isolate until they're lacking oxygen, a recommendation that Marik believes is costing lives, since early treatment with MATH+ is so effective:5


The MATH+ protocol led to high survival rates. Out of more than 100 hospitalized COVID-19 patients treated with the MATH+ protocol as of mid-April 2020, only two died. Both were in their 80s and had advanced chronic medical conditions.6 But according to Varon, despite their unusual successes, reporters weren't interested in why the patients at his hospital were more likely to survive.7

The physicians behind MATH+ are clear that their protocols are fluid and change in response to the data. As such, there have been two major changes since MATH+ was first released, one involving ivermectin and another involving hydroxychloroquine (HCQ).


Ivermectin Added to MATH+
Ivermectin was added as a core medication in FLCCC's protocols for the prevention and treatment of COVID-19 in October 2020.8 Ivermectin — a broad-spectrum antiparasitic that also has anti-inflammatory activity — has been found to reduce COVID-19 mortality by 81%.9 The drug is also safe, inexpensive and widely available, with decades of clinical usage suggesting it has a "high margin of safety."10

By December 2020, FLCCC, noting the extreme success of the drug, called for widespread adoption of ivermectin, both as a prophylactic and for the treatment of all phases of COVID-19.11,12 In one prevention trial, 58 volunteers took 12 milligrams of ivermectin once per month for four months.

Only four (6.96%) came down with mild COVID-19 symptoms during the May through August 2020 trial period.13 In comparison, 44 of 60 health care workers (73.3%) who had declined the medication were diagnosed with COVID-19. In June 2021, Varon and colleagues published a review in the American Journal of Therapeutics, which included meta-analyses based on 18 randomized controlled treatment trials of ivermectin in COVID-19.14 The results were impressive, showing:15

  • Large, statistically significant reductions in mortality, time to clinical recovery and time to viral clearance when used for treatment
  • Significantly reduced risks of contractive COVID-19 with regular ivermectin use
The data are so strong that, at the India Institute of Medical Sciences, all health care workers now take two 0.3 mg/kg doses of ivermectin 72 hours apart, then repeat the dose monthly to prevent COVID-19.16 And in regions that have implemented ivermectin distribution campaigns, associated reductions in case fatality rates results.17 According to the review:18


Marik believes that a mass distribution program of ivermectin, together with melatonin, vitamin D and aspirin, could end the pandemic. By assuming everyone is infected and treating with this safe combination of inexpensive compounds, Marik says, "We'll eliminate SARS-CoV-2. It will be gone."19 This isn't likely to happen, though, due to "economic and political factors that benefit from the ongoing pandemic."20

HCQ Replaced With Quercetin
HCQ, a zinc ionophore, was part of the MATH+ protocol for the first six months of the pandemic. (They have recently swapped quercetin for HCQ.) At this time, the death rate for COVID-19 patients at Varon's UMMC was 4.4%, compared to a death rate of about 20% at other hospitals.21

Hecker first spoke with Varon about HCQ in August 2020, and he spoke favorably about using the controversial drug, noting that out of more than 300 COVID-19 patients treated at UMMC, they had a 95% success rate.22

Misinformation and outright lies were spun about HCQ, including fabricated research, in an apparent effort to suppress and prevent its widespread use. Other physicians, including Dr. Vladimir Zelenko, a practicing physician in a Jewish community in Monroe, New York, have had great success using HCQ for COVID-19.23

However, in June 2020, the National Institutes of Health halted a clinical trial of HCQ after stating that, while the drug wasn't harmful, it also wasn't beneficial to hospitalized patients.24

Backlash ensued following the NIH announcement, and FLCCC phased out the use of HCQ in its protocols. Their latest I-MASK+ protocol, updated June 30, 2021,25 recommends quercetin instead. Quercetin, also a zinc ionophore, is an over-the-counter alternative to HCQ and works much like HCQ does. According to Marik:26


Ivermectin Continues To Be Censored, US on 'Media Lockdown'
In the video above, Hecker speaks with several recovered COVID-19 patients who received the MATH+ protocol. One, Manuel Espinoza, a urologist from Texas, was on a slow decline using the conventional COVID protocols. Then his wife found out about the MATH+ protocol online, and Espinoza was emergency airlifted to UMMC. "Within hours" of the treatment his health had turned around, he said, and "within days, just immense improvement."27

Yet, Varon said that every time he mentioned ivermectin on social media, "he went to Facebook jail." Reporters also told him, multiple times, that they were banned from reporting on certain COVID-19 drug treatments.28 Similar censorship was experienced by Dr. Pierre Kory, who was also a part of the group that formed FLCCC.

On December 8, 2020, Kory testified to the Senate Committee on Homeland Security and Governmental Affairs, which held a hearing on "Early Outpatient Treatment: An Essential Part of a COVID-19 Solution." He called on the NIH, CDC and FDA to review the expansive data on ivermectin to prevent COVID-19, keep those with early symptoms from progressing and help critically ill patients recover:29,30

Despite his impassioned pleas and astonishing science to back them up, the treatment was not only ignored by the committee but promptly eviscerated.31 Meanwhile, media reports claimed ivermectin was unproven and the World Health Organization also refused to endorse it.

YouTube removed Kory's testimony, which had nearly 9 million views, calling it a danger to the community.32 Kory says that while his research on ivermectin has gotten lots of attention worldwide, it's gotten zero in the U.S. — "U.S. is on a media lockdown," he said.33 Varon agreed, telling Hecker that "no one" is asking about the MATH+ protocol. "Right now everyone is interested in vaccination."34

MATH+ Protocol Is Available in 23 Languages
FLCCC's I-MASK+ protocol can be downloaded in full,35 giving you step-by-step instructions on how to prevent and treat the early symptoms of COVID-19. FLCCC also has protocols for at-home prevention and early treatment, called I-MASS, which involves ivermectin, vitamin D3, a multivitamin and a digital thermometer to watch your body temperature in the prevention phase and ivermectin, melatonin, aspirin and antiseptic mouthwash for early at-home treatment.

Household or close contacts of COVID-19 patients may take ivermectin (18 milligrams, then repeat the dose in 48 hours) for post-exposure prevention.36 FLCCC also has a management protocol — I-RECOVER37 — for long haul COVID-19 syndrome. The protocols are translated into 23 different languages to provide widespread, free access to this lifesaving information, including how to get ivermectin.38

FLCCC remains hopeful that ivermectin will be formally adopted into national or international COVID-19 treatment guidelines in the near future. But, as Hecker noted, the inexpensive medication faces a major hurdle:39
Simple reliable treatments without the criminal Vaxxes is all that is needed. During the 1918 Flu pandemic they provided "sunlight" (Vitamin D, Ultraviolet light) to fight the Flu then and it generally worked. MATH+ looks like a proven formula to fight the Flu if it is acquired. The Vaxx is a Lab-Rat cocktail proven now in Israeli as not all that effective. Even non-Covid-19 flu infections have killed a lot of people for years. It is good they have a program now to stop a lot of idiot J-Track idiocy from getting implemented around this J-Sh*t. Anyone who says the "Vaxx" is safe, I want you to take 1,000 jabs for the rest of your dumb "Science" life. Is that too much to ask for a "Vaxx Believer"? Take the Challenge or STFU science dork and get natural immunity. Better MATH+ is a good calc. 1,000 vaxxes for Board Members first if MATH+ isn't involved.
 

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Time to break out the tin foil hat?
View attachment 60870
maybe a faraday cage or faraday hat


even if you don't "believe" there is a market for saving your goods...



Ken Cosgrove: (To client) I’m not telling you to listen to anyone, but this is a very fresh approach.

Don Draper: “It’s okay, Ken. I don’t think there’s much else to do here than to call it a day. Gentlemen, thank you for your time.

Client: (shrugs) Is that all?

Don Draper: You’re a non-believer. Why should we waste time on kabuki?

Client: I don’t know what that means.

Don Draper: It means that you’ve already tried your plan and you’re number four. You’ve enlisted my expertise and you’ve rejected it to go along the way you’ve been going. I’m not interested in that. You can understand.

Client: I don’t think your three months and however many thousands of dollars allows you to refocus the core of our business.

Don Draper: Listen, I’m not here to tell you about Jesus. You already know about Jesus. Either he lives in your heart or he doesn’t. Every woman wants choices. But in the end, none wants to be one of 100 in a box. She’s unique. She makes the choices and she’s chosen him. She wants to tell the world he’s mine. He belongs to me, not you. She marks her man with her lips. He is her possession. You’ve given every woman who wears your lipstick the gift of total ownership.

Client: (pause) Sit down.

Don Draper: No. Not till I know I’m not wasting my time.

Client: Sit down.
 

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Leaked Internal CDC Memo Shows They Knew COVID Vaccinated Can Spread the Virus


The Washington Post has secured an internal, confidential CDC document showing the CDC not only was aware that the COVID-19 vaccine wasn’t going to work in some people — coined “breakthrough cases” — but that they also knew that “primary vaccine failure” would occur among the immunocompromised and elderly.
Not only that, they also knew that “Delta variant vaccine breakthrough cases may be as transmissible as unvaccinated cases.”
The PDF documents, available on the Post’s website as a PDF slide presentation, also show that the CDC expected more vaccine-failure cases as more people were vaccinated. Even so, in boldface type, the CDC slide presentation said it was important to describe those cases as “rare” or a “small percentage” of the total cases — and to recommend universal masking to reduce as the answer to the breakthrough cases.
“At current incidence, 35,000 symptomatic infections per week among 162 million vaccinated Americans,” one slide with graphs says. Deaths in vaccinated individuals were also predicted to rise sharply, beginning in May 2021.
The documents are stamped “CONFIDENTIAL” in red capital letters.

SOURCES:
The Washington Post July 29, 2021
The Washington Post July 29, 2021
 

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More Canadians Under 65 Died From Lockdowns Than From COVID-19




The fallout numbers from the worldwide lockdowns are weighing heavily in Canada, with statisticians reporting that four times as many Canadians died from indirect causes of the lockdown than the number that died from COVID itself.
A government report, “Provisional Death Counts and Excess Mortality,” shows that 5,535 Canadians under the age of 65 died between January 2020 to April 2021 because of “indirect consequences” due to the pandemic. During that same time frame, the report says 1,380 Canadians in the same age group died because of COVID-19 itself. Indirect consequences include “delayed medical procedures, increased substance use or a decline in deaths attributable to other causes, such as influenza,” according to the report.
Shutdowns forced more Canadians to stay at home and the cancellation or postponement of medical procedures and vital support services, while many businesses were forced to close. During that time, Statistics Canada confirmed that substance abuse increased as did the mortality rate.
Most of the people who died from COVID-19 in Canada were over the age of 85 and had dementia, Alzheimer’s, chronic heart disease or other pre-existing “cardiovascular and respiratory conditions,” the report said.

SOURCES:
Statistics Canada July 18, 2021
Statistics Canada Provisional Death Counts and Excess Mortality report July 12, 2021
 

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Can I donate COVID-19 convalescent plasma if I have received the vaccination?
At this time individuals who have received a COVID-19 vaccine are not able to donate convalescent plasma with the Red Cross. The Red Cross is working as quickly as possible to evaluate this change – as it may involve complex system updates. Please know, the Red Cross is committed to building a readily available inventory of convalescent plasma to ensure patients battling COVID-19 have all treatment options available to them.


Because the vax kills antibodies that you would produce?
 

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Dr Andrew Kaufman hosted Alex Jones 4th hour on wednesday with a guest whistleblower?
Andrew Kaufman - On the Research!

anybody catch it? this "whistleblower" is making the rounds of
"alt medical communitay"

Karen Kingston:

back to graphene oxide as part of the lipid nano particles?



SDS of pfizer jab allegedly;



These nanoparticles promote the uptake of therapeutically effective nucleic acids such as oligonucleotides or mRNA both in vitro and in vivo.[3][4]


A61K48/0008 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition

At physiological pH, ALC-0315 becomes protonated at the nitrogen atom, yielding an ammonium cation that is attracted to the messenger RNA (mRNA), which is anionic.[


ALC-0315
1628156340771.png


Description
Description
ALC-0315 is a synthetic lipid. A colorless oily material, it has attracted attention as a component of the SARS-CoV-2 vaccine, BNT162b2, from BioNTech and Pfizer. Wikipedia
Formula: C48H95NO5
Molar mass: 766.29 g/mol

don't taint your blood with demons kids!
 

anti-barabas-ite

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Dr Andrew Kaufman hosted Alex Jones 4th hour on wednesday with a guest whistleblower?
Andrew Kaufman - On the Research!

anybody catch it? this "whistleblower" is making the rounds of
"alt medical communitay"

Karen Kingston:

back to graphene oxide as part of the lipid nano particles?



SDS of pfizer jab allegedly;



These nanoparticles promote the uptake of therapeutically effective nucleic acids such as oligonucleotides or mRNA both in vitro and in vivo.[3][4]


A61K48/0008 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition

At physiological pH, ALC-0315 becomes protonated at the nitrogen atom, yielding an ammonium cation that is attracted to the messenger RNA (mRNA), which is anionic.[


ALC-0315
View attachment 61363


Description
Description
ALC-0315 is a synthetic lipid. A colorless oily material, it has attracted attention as a component of the SARS-CoV-2 vaccine, BNT162b2, from BioNTech and Pfizer. Wikipedia
Formula: C48H95NO5
Molar mass: 766.29 g/mol

don't taint your blood with demons kids!
A - HUMAN NECESSITIES
A61 - MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
A61K48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
Narrower

A61K48/0016 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the nucleic acid is delivered as a 'naked' nucleic acid, i.e. not combined with an entity such as a cationic lipid
 

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A - HUMAN NECESSITIES
A61 - MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
A61K48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
Narrower

A61K48/0016 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the nucleic acid is delivered as a 'naked' nucleic acid, i.e. not combined with an entity such as a cationic lipid

Correlation of the cytotoxic effects of cationic lipids with their headgroups

remember kids, we are run by a light power, an electrical charge, positive and negative, when those are not in alignment, bad things can happen to your mitochondria and cells.

snip


However, cationic lipids still have the problem of toxicity, as they can activate several cellular pathways like pro-apoptotic and pro-inflammatory cascades, which has become one of the main bottlenecks for their applications.1416 Cationic lipids are positively charged amphiphiles consisting of three basic chemical functional domains: a hydrophilic headgroup, a hydrophobic domain, and a linker bond that tethers the cationic headgroup and hydrophobic tail domain.17 The cytotoxic effects are severely associated with the cationic nature of the vectors, which is mainly determined by the structure of its hydrophilic group. The hydrophilic headgroup exhibits positive charges which trigger their interaction with negatively charged DNA through electrostatic attractions, leading to the formation of complexes containing condensed DNA.18 However, the relationship between the cationic lipid headgroup structures and toxicity is rarely discussed, which greatly hinders the advancement of cationic lipids towards clinical trials. Our study showed that peptide headgroups were much superior to quaternary ammonium headgroups in terms of transfection efficiency and toxicity.1921 Therefore, we chose quaternary ammonium and peptides as headgroups of cationic lipids for studying their cytotoxic effects (Fig. 1). Herein, the correlation of cytotoxic effects of cationic lipids with their headgroups will be elucidated based on the research on the origin of apoptosis, by analyzing caspase-3,9 enzymatic activities, reactive oxidative stress (ROS), mitochondrial membrane potential (MMP) and cell cycle arrest. This study aims at providing the scientific basis for the development of safe and efficient cationic lipids.

end snip

light, water and magnetism.

anyone not watching the unparalleled introduction of non native EMF around the world is not really following along.

the science niggers are messing with your light water and magnetism, they don't "believe" in the quantum biology of human cells and mitochondrial functions.

virus niggers don't talk to light water andmagnetism niggers .

virus niggers "believe" in floaty shit from outer space? or at least outer wuhan and bats.
 

CrackSmokeRepublican

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Good points @anti-barabas-ite was looking at this recently. Found this article which helps show relationships. Some of this is years-ago findings. "Gain of Function" was around this:
----------------
Early on in the pandemic, Lee Makowski read an article about the condition of people’s bodies after dying of COVID-19, and he was shocked by what he learned—there was something very wrong with the patients’ blood.

The autopsy reports revealed COVID-19 patients were suffering from huge amounts of thick, coagulated blood, and dysfunctional blood vessels were tearing through body tissue instead of repairing it—highly uncommon side effects of respiratory disease

The postmortem evidence plus his own experience with something called “COVID toes”—an odd side effect of the disease that causes heightened blood vessel formation in the toes, turning them bright red—led Makowski to speculate that something about the virus might be causing abnormal blood-related complications.

“One of the most perplexing and devastating effects of this disease is the scenario where three or four weeks after being hospitalized with pneumonia, people under the age of 50 are back home, they feel fine, and then all of a sudden they have a stroke and die,” says Makowski, professor and chair of the bioengineering department at Northeastern.

Makowski, who recently published his hypothesis in the journal Viruses, believes the spike protein found on the surface of the virus might mimic proteins that regulate blood vessels and control the formation of blood clots, which could explain many of the non-respiratory complications of COVID-19.

The spike protein is an arm-like apparatus that the virus uses to attach to and enter healthy cells. At the tip of the spike protein rests a string of three amino acids called RGD. This structure is known for connecting cells to each other in the body.

William Olson-Sidford, who studies bioengineering, works on SARS-CoV-2 research in Lee Makowski's lab inside the the Interdisciplinary Science and Engineering Complex. Photos by Matthew Modoono/Northeastern University Researchers don’t know yet whether RGD is the culprit for COVID-19’s blood-related complications, but they do know that RGD can contribute to the formation of blood clots and the growth of new blood vessels when it interacts with cell receptors called integrins.“Other proteins that have RGD are known to cause complications. Our theory is that RGD is making it easier for the virus to bind to things that could cause these blood complications,” says William Olson-Sidford, a third-year bioengineering student and co-author of the paper who worked on this project as a co-op last fall.Right now, researchers know that the virus’s spike protein binds to cell receptors called ACE2. ACE2 is found in many cell types including in the lungs, heart, blood vessels, kidneys, liver, and gastrointestinal tract.“But our theory is that because [the virus] has an RGD, it may also be more likely to bind to other cells in the body that people aren’t thinking about,” Olson-Sidford says.Makowski hypothesizes that dysregulated blood vessel growth—which can disrupt lung tissue—is triggered by an increase of RGD during infection.As for COVID-19-related kidney failure, “it’s hard to know whether it’s caused by direct damage to the tissue by viral invasion or indirect damage through coagulation and blocked arteries,” Makowski says. But either way, a faulty connection between RGD and integrin could be the culprit.Recognizing that coagulation is a major problem has greatly improved the survival rate of people who are severely sick with COVID-19, Makowski says. “Now if you end up in the ICU, you almost always get an anticoagulant, and that saves a lot of lives.”Uncovering the cause of that coagulation is the next step. Makowski hopes his hypothesis will spur other researchers to investigate further.For media inquiries, please contact Shannon Nargi at s.nargi@northeastern.edu or 617-373-5718.



© 2021 Northeastern University

https://news.northeastern .edu/2021/02/08/covid-19-can-affect-the-blood-its-spike-protein-may-be-the-culprit/
 

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Detail on Ivermectin it works as an anti-coagulant and helps stop the Viral infection like other viruses (Dengue Fever)...basically it helps to stop the "spike" from binding on the cell wall?:

----------

J Antibiot (Tokyo) . 2020 Sep;73(9):593-602.
doi: 10.1038/s41429-020-0336-z. Epub 2020 Jun 12.
Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen

Fatemeh Heidary 1 , Reza Gharebaghi 2 3

Affiliations
Free PMC article

Abstract
Ivermectin proposes many potentials effects to treat a range of diseases, with its antimicrobial, antiviral, and anti-cancer properties as a wonder drug. It is highly effective against many microorganisms including some viruses. In this comprehensive systematic review, antiviral effects of ivermectin are summarized including in vitro and in vivo studies over the past 50 years. Several studies reported antiviral effects of ivermectin on RNA viruses such as Zika, dengue, yellow fever, West Nile, Hendra, Newcastle, Venezuelan equine encephalitis, chikungunya, Semliki Forest, Sindbis, Avian influenza A, Porcine Reproductive and Respiratory Syndrome, Human immunodeficiency virus type 1, and severe acute respiratory syndrome coronavirus 2. Furthermore, there are some studies showing antiviral effects of ivermectin against DNA viruses such as Equine herpes type 1, BK polyomavirus, pseudorabies, porcine circovirus 2, and bovine herpesvirus 1. Ivermectin plays a role in several biological mechanisms, therefore it could serve as a potential candidate in the treatment of a wide range of viruses including COVID-19 as well as other types of positive-sense single-stranded RNA viruses. In vivo studies of animal models revealed a broad range of antiviral effects of ivermectin, however, clinical trials are necessary to appraise the potential efficacy of ivermectin in clinical setting.

https://pubmed.ncbi.nlm.nih .gov/32533071/
https://pubmed.ncbi.nlm.nih .gov/32942671/
-------

Inhibits WNT Pathway


Dr Alice Melotti studied Ivermectin as an inhibitor of the WNT‐TCF pathway in cancer. Her report was published in 2014 EMBO molecular medicine. Dr Melotti used a transcriptional reporter assay for TCF activity driven by Beta-CATENIN to test a collection of 1,040 drugs and small molecules. Only one agent, Ivermectin, perfectly tracked the gene expression profile induced by blocking the TCF gene, and therefore inhibits the WNT pathway. This has profound significance for anti-cancer stem cell therapy, because blocking the WNT pathway is the key to killing cancer stem cells. (15-16) Blocking the WNT pathway in a breast cancer model killed cancer stem cells.(18) Similarly, blocking the WNT pathway in Mantle cell lymphoma preferentially killed the cancer stem cells.(16)


Other useful inhibitors of the WNT pathway which target cancer stem cells include dietary agents curcumin and the small molecule PKF118-310, a fungal product. (17) In addition to curcumin, other natural, dietary WNT- Inhibitors include sulforaphane, ECGC, resveratrol, retinoids and curcumin. (19)


Ivermectin Effective Against Triple Negative Breast Cancer Cells via modulation of P2X4/P2X7-gated Pannexin-1 channels



Dr Dragonov reported in Nov 2015, Scientific Reports on the mechanism of cancer cell killing by Ivermectin. (9) He notes that tumors have upregulated P2X7 receptors, which are involved with regulation of high ATP concentrations in the tumor micro-environment. The high ATP promotes tumor progression, and if the channels are sensitized by Ivermectin, cause cancer cell death. Dr Dragonov found that:


“Ivermectin kills mouse and human triple-negative breast cancer (TNBC) cells through augmented P2X7-dependent purinergic signaling associated with caspase-1 and caspase-3 activation.” (note caspase activation means apoptotic programmed cell death)(9)


In addition, Dr Dragonov hypothesized that Ivermectin kills cancer cells by enhancing receptor P2X7 sensitivity to extracellular ATP. In doing so, Ivermectin induces both an apoptotic and a non-apoptotic, inflammatory type of cell death. The inflammatory cell death stimulates the immune system, a beneficial effect, so that the patients own immune system will kill new cancer cells in the future.


Mouse and Human Triple Negative Breast Cancer Cells


Dr Dragonov reports that Mouse and human TNBC cells are sensitive to Ivermectin with IC50 values as low as 2 μM with 24 hr exposure time.(9)


Synergy with other Chemo Agents


Dr Dragonov reports Ivermectin cancer cell killing effects synergistic with chemotherapeutic agents such as doxorubicin (Adriamycin) and paclitaxel (Taxol) which induce ROS (reactive oxygen species).(9) One might speculate Ivermectin would synergize with Artemisinin compounds which induce ferroptosis, a form of oxidative cell death. One might also speculate on Ivermectin synergy with alpha lipoic acid (ALA) which increases electron flux through the mitochondrial electron transport chain.


Ivermectin Induces Immunogenic Cell Death


Dr Dragonov reports that beneficial long-term clinical response after chemotherapy involves stimulation of a robust anti-cancer immune response, also called induction of “immunogenic cell death (ICD)”. Ivermectin is one agent which induces ICD immunogenic cancer cell death, and therefore may induce long term or permanent remission after treatment.(9)


Ivermectin Approved for Pediatric Scabies


scabies Ivermectin NEJM


Left Image From NEJM showing life cycle of scabies parasite involving skin. Treatment with Ivermectin.


Ivermectin is a highly effective anti-parasitic drug, FDA approved for pediatric scabies (see left image) . Ivermectin has extensive veterinary use as an anti-parasitic drug for pets, horses and farm animals (See HeartGard header image)


Niclosamide (Niclide) Anti-Parasitic Blocks WNT pathway


Using a high-throughput screening method, Dr Chen identified niclosamide as a potent inhibitor of the Wnt/β-catenin pathway, also down regulating the Nuclear Factor Kappa Beta ( NF-κB), and potent anti-cancer stem cell agent .(20-21) Niclosamide was found effective against ovarian cancer cell lines, as monotherapy. Niclosamide was also effective in combination with conventional chemotherapy, enhancing the ovarian cancer cell killing effect.(22-23) Niclosamide was an effective anticancer agent when studied in breast cancer, leukemia and glioblastoma cell models. (25-31)


Using high-throughput drug screening of more than 1,200 clinically approved drugs, the antihelmintic niclosamide was identified as the most promising candidate, selectively targeting Ovarian cancer stem cells, in vitro and in vivo.(22)


Typical Niclosamide treatment dosage for dwarf tapeworm: Adults—2 grams a day for seven days. Treatment may be repeated in seven to fourteen days if needed.(24) The 2005 WHO safety report on niclosamide found no toxicities, and it was deemed generally safe for use in pregnant women and children.(32)


Unexpected Clinical Benefits of Anti-Parasitic Drugs


The anti-cancer effects of Ivermectin and Niclosamide were unexpected clinical benefits. Will Ivermectin and Niclosamide revolutionize cancer treatment, making chemotherapy and stem cell transplant obsolete relics for the medical museum?


Army MEdical Museum Jeffrey DaCh MDLeft Image Medical Museum courtesy of Army.


Ivermectin as Anti-Viral Drug



A number of studies over the years have shown ivermectin to have considerable broad spectrum anti-viral activity by targeting the host nuclear transport importin α/β1 heterodimer, thus inhibiting viral replication of dengue, HIV and covid-19 (corona virus). Recently there has been considerable interest in Ivermectin as drug treatment for Covid-19 (SARS Cov-2 Corona virus), especially in combination with azithromycin, doxycycline, hydroxychloroquine and Zinc. A recent study showed 40% reduction in mortality of hospitalized Covid 19 patients treated with Ivermectin. (48-66)

https://jeffreydachmd .com/2016/05/ivermectin-antiparasitic-anticancer-wonder-drug/
 
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CrackSmokeRepublican

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More detail on WNT pathways and COVID-19. It is working like a mini-Cancer on the lungs. Generally PPARγ's generally help stop Lung cancers but COVID-19 may assist Spike Protein residency (infection). Essentially it turns COVID-19 infected into something like Type-2 diabetics if the ACE2 is affected (brain fog from vaccines-infection alone):
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Interplay of Opposing Effects of the WNT/β-Catenin Pathway and PPARγ and Implications for SARS-CoV2 Treatment
Alexandre Vallée1*, Yves Lecarpentier2 and
Jean-Noël Vallée3,4
  • 1Department of Clinical Research and Innovation, Foch Hospital, Suresnes, France
  • 2Centre de Recherche Clinique, Grand Hôpital de l’Est Francilien (GHEF), Meaux, France
  • 3University Hospital Center (CHU) Amiens Picardie, University of Picardie Jules Verne (UPJV), Amiens, France
  • 4Laboratory of Mathematics and Applications (LMA), Unité Mixte de Recherche (UMR) Centre National de la Recherche Scientifique (CNRS) 7348, University of Poitiers, Poitiers, France
The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has quickly reached pandemic proportions. Cytokine profiles observed in COVID-19 patients have revealed increased levels of IL-1β, IL-2, IL-6, and TNF-α and increased NF-κB pathway activity. Recent evidence has shown that the upregulation of the WNT/β-catenin pathway is associated with inflammation, resulting in a cytokine storm in ARDS (acute respire distress syndrome) and especially in COVID-19 patients. Several studies have shown that the WNT/β-catenin pathway interacts with PPARγ in an opposing interplay in numerous diseases. Furthermore, recent studies have highlighted the interesting role of PPARγ agonists as modulators of inflammatory and immunomodulatory drugs through the targeting of the cytokine storm in COVID-19 patients. SARS-CoV2 infection presents a decrease in the angiotensin-converting enzyme 2 (ACE2) associated with the upregulation of the WNT/β-catenin pathway. SARS-Cov2 may invade human organs besides the lungs through the expression of ACE2. Evidence has highlighted the fact that PPARγ agonists can increase ACE2 expression, suggesting a possible role for PPARγ agonists in the treatment of COVID-19. This review therefore focuses on the opposing interplay between the canonical WNT/β-catenin pathway and PPARγ in SARS-CoV2 infection and the potential beneficial role of PPARγ agonists in this context.

Introduction
The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has quickly reached pandemic proportions. Like SARS-CoV, SARS-CoV-2 is a member of the Beta-coronavirus family. Although the majority of COVID-19 patients present mild to moderate clinical features (1, 2), some may develop severe pneumonia or suffer from the acute respiratory distress syndrome (ARDS) and multi-organ failure, leading to high death rates. Nevertheless, the pathophysiology of Corona Virus Disease-19 (COVID-19) remains unclear. Currently, in patients with life-threatening ARDS, there is growing evidence that virally-induced pro-inflammatory cytokines (such as Interleukin (IL)-6 and tumor necrosis factor-α (TNF-α)) enhance inflammation in the latter stages of this disease (35). Such findings are further corroborated by recent studies indicating that high levels of IL-6 are predictors of mortality (6). Cytokine profiles in COVID-19 patients have revealed increased levels of interleukin-1β (IL-1β), IL-2, IL-6 and tumor necrosis factor-alpha (TNFα) (7). TNF-α is one of the main activators of IL-6 expression and an increase in baseline plasma levels of IL-6 may predict that survival chances are poor (7). Moreover, an increase in the proportion of Th17 cells has been observed in COVID-19 patients, leading to the stimulation of IL-6 (8). Recent evidence has shown that the upregulation of the canonical WNT/β-catenin pathway is associated with inflammation and a cytokine storm in ARDS (9) and especially COVID-19 patients (10). Several studies have shown that, in numerous diseases (1114), the WNT/β-catenin pathway interacts with PPARγ (peroxisome proliferator-activated receptor gamma) in an opposing interplay, with the effects of one opposing those of the other. Recent studies have also highlighted the possible role of PPARγ agonists as modulators of inflammatory and immunomodulatory drugs by targeting the cytokine storm in COVID-19 patients (15, 16). This review focuses on the opposing interplay between WNT/β-catenin and PPARγ in SARS-CoV-2 infection and the potential role of PPARγ agonists in this context.

Inflammation and SARS-CoV-2 Infection
The severity of symptoms in SARS-CoV-2 infection depends on the viral infection and the host immune system. The COVID-19 cytokine profile of patients is closely associated with cytokine release, indicating macrophage activation, and an increase in the level of cytokines such as the TNFα, IL-6 and interferon-gamma (IFN-γ) (4).

The increased levels of these cytokines is a characteristic of ARDS, with a low level of oxygen in the blood and shortness of breath (17). The SARS-CoV-2 infection mainly damages the endothelial cells of the airway, alveoli, vascular system, and macrophages in the lungs. SARS-CoV-2 recruits the receptor of angiotensin-converting enzyme 2 (ACE2) for infection (18). The expression of the ACE2 receptor is decreased in the lungs in the SARS-CoV-2 infection, dysregulating the renin-angiotensin system, which damages the fluid and electrolyte balance, blood pressure levels, and increases the vascular permeability and inflammatory processes in the airway (1921).

SARS-CoV recruits several immune-suppressive proteins thereby increasing the immune response (22). SARS-CoV enhances several structural and non-structural proteins acting as antagonists of interferon signaling. Stopping interferon signaling could be a response to: a) prevent the recognition of viral RNA via the pattern recognition receptor (PRR), b) decrease the synthesis of type I interferon protein by interrupting the toll-like receptor-1 (TLR-1) and the retinoic acid-inducible gene I (RIG-I), and c) increase the STAT pathway activity (23).
The SARS-CoV-2 virus causes massive damage to the infected epithelial and endothelial cells, with an excessive release of cytokines and chemokines (18). In SARS-CoV-2, stimulation of the caspase-1 enhances the production of pro-inflammatory cytokines such as IL-1β and IL-6 (24). These cytokines bind with other immune cells, including T-lymphocytes and monocytes (8, 25). Severe COVID-19 patients show increased levels of the granulocyte colony-stimulating factor (G-CSF), IL-2, IL-6, IL-10, monocyte chemo-attractant peptide (MCP)-1), macrophage inflammatory protein 1α (MIP1α) and TNF-α (26).

The nuclear factor-κB (NF-κB) pathway is one of the main inflammation processes. NF-κB is a hetero-dimeric transcription factor belonging to the Rel protein family. Under physiological conditions, RelA/p50, the heterodimer’s predominant form of the NF-κB pathway, is inactivated in the cytoplasm by the IkB protein (27). SARS-CoV infection leads to a release of pro-inflammatory cytokines and growth factors to activate the IkB Kinase (IKK), which phosphorylates and degrades the IkB protein through an ubiquitination mechanism (28).
The NF-κB pathway can modulate the expression of pro-inflammatory genes responsible for the cytokine storm. SARS-CoV-2 can induce the nuclear translocation of the NF-κB pathway to stimulate IL-6 expression (28). Numerous studies have shown that SARS-CoV (2931), including SARS-Cov-2 (32), can activate the NF-κB pathway.

The Canonical WNT/β-Catenin Pathway
The name WNT is derived from Wingless drosophila melanogaster and its mouse homolog Int. The canonical WNT/β-catenin pathway is involved in several mechanisms, controlling signaling, including embryogenesis, cell proliferation, migration and polarity, apoptosis, and organogenesis (33). Nevertheless, the WNT/β-catenin pathway can be altered in several pathological diseases, such as inflammation, metabolic, neurological and psychiatric disorders, fibrosis and cancer processes (3442).
The WNT ligands belongs to the family of secreted lipid-modified glycoproteins (43). WNT ligands are produced by neurons and immune cells localized in the central nervous system (CNS) (44). WNT pathway dysfunction can affect numerous neurodegenerative pathologies (11, 4548). The canonical WNT pathway comprises the β-catenin, T-cell factor and lymphoid enhancer factor (TCF/LEF). Cytoplasmic accumulation of β-catenin is modulated by the destruction complex AXIN, tumor suppressor adenomatous polyposis coli (APC), and glycogen synthase kinase-3 (GSK-3β). In the absence of WNT ligands, the destruction complex has a role in the phosphorylation of the cytoplasmic β-catenin and leads to its proteasomal destruction. However, when they are present, WNT ligands bind with Frizzled (FZL) and LDL receptor-related protein 5/6 (LRP 5/6) to interrupt the destruction complex and prevent β-catenin degradation into the proteasome. β-catenin translocates to the nucleus to interact with the TCF/LEF. This stimulates the WNT target genes (4951).
Glycogen synthase kinase-3β (GSK-3β) is one of the major inhibitors of the WNT/β-catenin pathway (35, 36, 5255). As an intracellular serine-threonine kinase, GSK-3β is a major negative controller of WNT signaling (56). GSK-3β is involved in the control of numerous kinds of pathophysiological pathways, including cell membrane signaling, cell polarity, and inflammation (5759). GSK-3β interacts by downregulating the cytoplasmic β-catenin and stabilizing it to enhance its nuclear migration (60).
A positive interplay has been recently observed between the WNT/β-catenin pathway and inflammation, expressed by an activated NF-ϰB pathway (37). Over-stimulation of WNT/β-catenin leads to the enhancement of IϰB-α degradation and then NF-ϰB pathway transactivation (61). The WNT/β-catenin pathway increases COX expression, which then influences the inflammatory response (62). In addition, the NF-ϰB pathway downregulates GSK-3β and positively enhances β-catenin signaling (63, 64).
WNT/β-Catenin Pathway and SARS-CoV-2 Infection
Several studies have shown that WNT ligands, secreted by immune cells, can control inflammatory response and immune cell modulation (6568). Moreover, WNT ligands play major roles in tissue damage and repair (65). The WNT/β-catenin pathway is upregulated in severe sepsis-induced acute lung injury and sepsis mouse models (67, 69). The WNT pathway is damaged in sepsis or ARDS, and therefore plays a major role in fibrosis and inflammation (66, 70). In COVID-19 patients, the transforming growth factor (TGF-β) stimulates the WNT/β-catenin pathway, leading to an increased risk of pulmonary fibrosis (70) and pulmonary infection (10, 71) (Table 1). Several studies have shown that the TGF-β and WNT/β-catenin pathways upregulate each other in a positive feedback (54, 88).

TABLE 1
www.frontiersin.org
Table 1 Mechanisms by which the WNT/β-catenin pathway is modulated and the possible roles of PPARγ agonists in treating SARS-CoV-2 infection.

The TGF-β pathway is one of the main signaling pathways involved in fibrosis through the enhancement of EMT and fibroblast differentiation (89). Several inflammatory cytokines have a positive relationship with the TGF-β pathway (89). Interactions between the TGF-β pathway and Smad pathway are involved in pulmonary fibrosis (90). The TGF-β/Smad pathway has been shown to be a promotor of PAI-1 synthesis in SARS-CoV (91). Moreover, cytokines can activate the JAK/STAT pathway (92) to dysregulate cellular homeostasis, proliferation and apoptosis (93). IL-6 can activate the JAK/STAT pathway in T helper cells (4, 94) to induce several biological functions, such as immune regulation, lymphocyte differentiation and oxidative stress (72, 95). The increase in IL-6 observed in severe COVID-19 patients is associated with significantly lower survival rates (6, 96). COVID-19 patients present both dysregulated JAK/STAT pathway (97) and important role of TGF-β/Smad pathway (98).
In severe COVID-19 patients, serum IL-6 is significantly greater than in non COVID-19 subjects (99). The excessive production of inflammatory cytokines in the lungs of COVID-19 patients is associated with the increase in macrophage activation (100). In a mouse model of systemic inflammation, PAI-1 is involved in the regulation of host inflammatory responses through Toll- like Receptor-4 (TLR4)-mediated macrophage activation (101). Activation of the NF-κB pathway results in stimulating the TGF-β pathway in a vicious loop (73) and in concordance with PAI-1 (74). Thus, PAI-1 seems to be partly responsible for the excessive production of cytokines by macrophages in severe COVID-19 patients (75). PAI-1 expression is associated with increased IL-10 and an activated TGF-β pathway (102). Thus, the activated TGF-β pathway observed in COVID-19 patients may drive the pulmonary fibrosis process (102). In COVID-19 patients, ECM dysregulation could be one of the sources of stimulation of the TGF-β pathway (76, 103) (Table 1). This stimulation is responsible for the activation of integrin αvβ6 and thrombospondin induced by the STAT pathway (76, 104). In COVID-19 patients, a vicious loop is involved between the TGF-β pathway, the STAT pathway and PAI-1 (75). Furthermore, the targets involved in fibrosis, such as collagens, proteoglycans, integrins, the connective tissue growth factor, and matrix metalloproteinases (MMPs) are activated by the TGF-β pathway (105). SARS-CoV proteins may enhance the TGF-β-induced expression of PAI-1 and collagen I to induce lung fibrosis (106).

PPARγ
PPARs (peroxisome proliferator-activated receptors) are ligand-activated transcription factors that bind PPREs (PPAR-response elements). In the nucleus, PPARs form a heterodimer with the retinoid X receptor (RXR) (107). They are composed of a ligand-binding domain that interacts with a DNA-binding domain to modulate it (108). PPARs are involved in numerous pathophysiological processes, such as cell differentiation, protein metabolism, lipid metabolism, carcinogenesis (109, 110), adipocyte differentiation, insulin sensitivity and inflammation (111, 112). PPARs are subdivided into three isoforms: PPARα, PPARγ and PPARβ (113). PPARγ is highly expressed in adipose tissue and macrophages (114). PPARγ ligands can be synthetic or natural. PPARγ ligands have hypoglycemic and hypocholesterolemic roles. PPARγ agonists such as thiazolidinediones (TZDs) have been used to treat type 2 diabetes patients (115) and to decrease inflammatory activity (115). Natural ligands include prostaglandins and unsaturated fatty acids (116). Natural ligands include prostaglandins and unsaturated fatty acids. Moreover, PPARγ ligands, such as thiazolidinediones, can directly decrease inflammatory activity (12), fibrosis processes (117) and lung inflammation (118). In adipocyte mitochondria, pioglitazone (30–45 mg/day for three months) can reduce the expression of cytokines, including IL-6 and TNFα in humans (119). In patients with impaired glucose tolerance, four months (45 mg/day) of treatment with pioglitazone is associated with a reduction of monocyte IL-1, IL-6, IL-8 and lymphocyte IL-2, IL-6 and IL-8 (120). Pioglitazone has also shown a potential for decreasing ferritin in a rat model of angiotensin II-induced hypertension (121). Moreover, pioglitazone can decrease the secretion of pro-inflammatory cytokines (IL-1b, IL-6, and IL-8) and increase the anti-inflammatory ones (e.g. IL-4 and IL-10) in astrocytes stimulated by lipopolysaccharide (122). Pioglitazone (treatment for 7 days) could decrease TNFα and IL-6 mRNA expression in the peritoneal lavage fluid (15, 123). Furthermore, pioglitazone is a well-known inhibitor of lung inflammation and fibrosis (118), through normalization of the expression of TNF-α (124). Pioglitazone and rosiglitazone use can reduce both the increase in inflammatory markers and the decrease in the glutamate transporter (GLT-1) expression, in a primary mixed culture of astrocytes and microglia caused by exposure to in vitro viral proteins (HIVADA gp120) and in vivo models (125). Pioglitazone can decrease the neuro-inflammation and maintain mitochondrial respiration (126). The use of pioglitazone has also produced encouraging results in the form of decreasing CRP and IL-6 levels (127). In animal studies, pioglitazone has been shown to decrease mortality from sepsis and lung injury by reducing inflammatory cytokine production in omental tissue (123).

Opposing Interplay Between the WNT/β-Catenin Pathway and PPARγ
Several studies have shown that the canonical WNT/β-catenin pathway and PPARγ act in an opposing manner in numerous disorders, including cancers, neurodegenerative diseases, psychiatric disorders and fibrosis processes (47, 117, 128). In many diseases, PPARγ expression is downregulated by β-catenin signaling over-activation (12, 13, 48, 129131). PPARγ agonists are considered to offer promising treatment through this crosstalk process (13, 132, 133). Indeed, PPARγ is considered to be a negative β-catenin target gene (134, 135). The WNT/β-catenin pathway and PPARγ interact through a TCF/LEF domain of β-catenin and a catenin-binding domain within PPARγ (77, 136). Through this link, a decrease in WNT/β-catenin pathway activity enhances the activation of PPARγ (78), while PPARγ over-expression inhibits β-catenin signaling (79).

Opposing Interplay Between the WNT/β-Catenin Pathway and PPARγ in SARS-CoV-2 Infection: The ACE2 Hypothesis

SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) as a main cell receptor to infect humans (80, 137139) (Table 1). ACE2 plays a leading role in the regulation of cardiovascular and renal functions (140) and has also been shown to have a major role in SARS-CoV-2 infection (80, 138). SARS-CoV-2 may invade human organs besides the lungs through the expression of ACE2 (141). Recent findings have revealed that ACE2 is downregulated in SARS-CoV-2-infected lung tissue (142). Evidence from studies has shown that SARS-CoV-2 gains direct access to cells through ACE2 receptors (80, 143), as happens with SARS-CoV (144). SARS-CoV-2 infection leads to the downregulation of the expression of ACE2 by binding with the spike (S) viral protein – 1273 amino acid long protein (145). The pivotal role of ACE2 is its degradation of angiotensin II into angiotensin1-7 (146). This degradation mechanism is blocked by a selective ACE2 inhibitor, such as MLN-4760 (147). A recent study focusing on SARS-CoV-2 has shown that angiotensin II accumulation leads to fibrosis, endothelial dysfunction, increased inflammation and oxidative stress (81). Moreover, angiotensin II is associated with macrophage activation and both IL-6 and TNF-α overexpression (148). Furthermore, the deficiency in ACE2 could exacerbate outcomes in COVID-19 patients (148). In COVID-19 patients, ACE2 expression is inversely associated with the WNT/β-catenin and TGF-β pathways (141). ACE2 presents a positive association with PD-L1, a predictive marker for active response to immune inhibitors (142). The stimulation of ACE2 allows it to play a major protective role in the treatment of hypertension, heart disease, cancer and COVID-19 (141), which are all disorders that show an upregulation of the WNT/β-catenin pathway. Rats with renal ischemia/reperfusion-induced injury treated by pioglitazone have shown a downregulated WNT/β-catenin pathway and increased ACE2 expression (82). Even though very few studies have so far highlighted the possible role of PPARγ agonists in treating COVID-19 patients, rosiglitazone has been shown to increase ACE2 expression in animal models (81) and it could also potentially be used in diabetic patients with COVID-19 (85).

PPARγ Agonists in SARS-CoV-2 Infection
To date, few studies have focused on the potentially interesting link between PPARγ agonists and the development of COVID-19. The role of these agonists in SARS-CoV-2 infection therefore remains hypothetical (15, 16) (Table 1). Currently, no clinical and randomized trials have been investigated. However, in a recent research review article it was hypothesized that pioglitazone could play a role in attenuating lung injury in COVID-19 patients (15). Pioglitazone is another available thiazolidinedione that may inhibit the activation of NF-kB and MAPK pathways by reducing the expression of CARD9 in COVID-19 patients (15, 86). Several reports have indicated that PPARγ agonists could be candidates for modulating the cytokine storm in the COVID-19 disease (87, 149, 150). A possible therapeutic role for pioglitazone has been identified with respect to the SARS-CoV-2 infection (16). Pioglitazone can act as a 3CL-Pro inhibitor to downregulate SARS-CoV-2 RNA synthesis and replication (151). More specifically, PPARγ agonists can decrease the secretion of several pro-inflammatory cytokines, including TNF-α, IL-1, and IL-6, in both the monocytes and macrophages (152).
Recent studies have shown that numerous COVID-19 patients present hypertension and diabetes, whereas few patients present chronic obstructive-pulmonary diseases (153, 154). Moreover, a recent meta-analysis showed that hypertension and diabetes were highly associated with comorbidities in COVID-19 patients (155). One of the major roles of PPARγ agonists is to decrease TNF-α expression, the proportion of Th17 cells and NF-κB activity in order to repress inflammation (12). Numerous inflammatory cytokines, chemokines, or intracellular pathways, such as TNF-α and IL-6, can downregulate PPARγ expression, whereas in adipocytes, adiponectin increases PPARγ expression and then downregulates the LPS-induced NF-ϰB expression and IL-6 production (156). Pioglitazone suppresses inflammation by reducing TNF-α and MCP-1 expression, two important mediators of inflammation (157). However, the use of PPARγ agonists may have some side effects, even though newer molecules now have fewer disadvantages. The use of PPARγ agonists may therefore increase cardiovascular events, despite numerous studies showing no significant increase in side effects (14).
Conclusion
In the rapidly evolving situation surrounding the COVID-19 pandemic, it is essential to better understand the different pathways involved in the disease. In the SARS-CoV-2 infection, the canonical WNT/β-catenin pathway seems to be upregulated in association with the TGF-β and STAT pathways, whereas both ACE2 and PPARγ expression is downregulated, coupled with an increased number of pro-inflammatory markers. Since increased WNT/β-catenin pathway activity is associated with the increase of immune signaling and fibrosis processes, the inhibition of this pathway could result in the negative modulation of the SARS-CoV-2 infection. PPARγ agonists provide inexpensive treatments that are commonly used around the globe. By directly targeting inflammation, ACE2 and the WNT/β-catenin pathway, PPARγ agonists may well be prospective candidates for delivering SARS-CoV-2 therapy in clinical settings.

https://www.frontiersin .org/articles/10.3389/fimmu.2021.666693/full
 
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CrackSmokeRepublican

An ancient story of Fhunter Xiden...and the pipe.
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Something to keep in mind... Syrian Rue seeds (Harmine) was the Aryan "Soma" (stopped viral infections, increased muscle mass and improved intelligence in the forebrain). All documented. Kills SARS-Covid 19 as well as many other parasitics. Pregnant women should not take it. It fights most cancers very effectively btw and documented. This is ancient Aryan "tech" that can be used today. Red Blood cells radiate "UV-Light" in-vivo with it. UV light (sunlight) kills most viral pathogens.

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The Small Molecule Harmine Is an Antidiabetic Cell-Type-Specific Regulator of PPARγ Expression
Author links open overlay panelHironoriWaki1Kye WonPark1NicoMitro4LimingPei1RobertDamoiseaux2Damien C.Wilpitz1KarenReue3EnriqueSaez4PeterTontonoz1


https://doi.org/10.1016/j.cmet.2007.03.010Get rights and content
Under an Elsevier user license
open archive

Summary
PPARγ is the master regulator of adipogenesis and the molecular target of the thiazolidinedione antidiabetic drugs. By screening for compounds that promote adipogenesis, we identified a small molecule that targets the PPARγ pathway by a distinct mechanism. This molecule, harmine, is not a ligand for the receptor; rather, it acts as a cell-type-specific regulator of PPARγ expression. Administration of harmine to diabetic mice mimics the effects of PPARγ ligands on adipocyte gene expression and insulin sensitivity. Unlike thiazolidinediones, however, harmine does not cause significant weight gain or hepatic lipid accumulation. Molecular studies indicate that harmine controls PPARγ expression through inhibition of the Wnt signaling pathway. This work validates phenotypic screening of adipocytes as a promising strategy for the identification of bioactive small molecules and suggests that regulators of PPARγ expression may represent a complementary approach to PPARγ ligands in the treatment of insulin resistance.
https://www.sciencedirect .com/science/article/pii/S1550413107000733
 
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anti-barabas-ite

Work stuff through in your brain...UNVAXXED
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This is ancient Aryan "tech" that can be used today. Red Blood cells radiate "UV-Light" in-vivo with it. UV light (sunlight) kills most viral pathogens.
now we are getting somewhere!

early on plandemic you may remember, hotels in japan were using a robot that flashes a uv light in hotel rooms to allegedly kill "pathogens" on surfaces as a faster more effective method of action to help restore confidence in the hygiene at shared spaces.
what frequency of light they use I don't recall.

where I work they spray a chemical agent every few hours on surfaces, never wiping it off, and creating a sludge on the surfaces. its disgusting.
the custodial teams use $1500.00 spray guns after donning hazmat suits and breathing apparatus to do the spraying.


Also recall that recent findings of patients that have contracted an illness allegedly a "virus" low levels of vitamin d in thier systems, vitamin d receptors are in lots of cells, the best source of vitamin d is from the sun via melenopsin in the skin and opsins in the eye.
the creation of these receptors was precisely for regulating light frequencies into chemical and enzyme reactions.
once your light gathering abilities are deregulated, your systems will begin to fail.
the charges on different chemical bonds, cells structures reactions in producing enzymes becomes diss-regulated or interrupted, your systems are going to try and adapt and adjust to the new source or lack of source to what's being input.
humans are adapting to a change in electrical energy all the time. how we individually adapt can be regulated by outside forces and hard to pinpoint the causes.
how you choose to regulate the interaction with these outside forces should be up to you, regardless the "greater good".
nobody knows if the greater good is going to adapt to kill you and your phenotype.
bolshevism is no way to regulate your human bodily adaptions.


diabetics and mitochondrial dysfunctioning humans are not getting the sun in thier eyes or on thier skin.
is fixing plandemic911 as easy as sitting in the sun and eating licorice root? probably, can Montgomery burns make 6 billion dollars a quarter on it and the world be reshaped in a noahide image? probably not.

Jesus
light
water
magnetism
Amen
 
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