Snake Meat......source of chinese virus

[badger2]

We'll link Trump's oleandrin to turtle soup at Wuhan. We're still not buying that there existed a lab strain of COVID-19.

Oleandrin

Retraction: Oleandrin: A Cardiac Glycosides with Potent Cytotoxicity - PubMed

[This retracts the article on p. 131 in vol. 7, PMID: 24347921.].

www.ncbi.nlm.nih.gov

'....Oleandrin inhibits activity of nuclear factor kappa-light-chain-enhancer of activated B chain (NF-kappaB).'

Blumberg (NASA Astrobiology) discovered the Australian antigen of hepatitis B virus. HBV physically attaches to NF-kappa B.

These facts link to Baruch S. Blumberg Foundation study for GILT and the Wuhan connection to GILT and Pelodiscus sinensis, a suspected COVID-19 intermediate host, a turtle whose soup was fed to already quarantined patients in Wuhan. These connections were posted on page 39 of this thread, especially post #771, on 19 Jul 2020.

Snake Meat......source of chinese virus

ACE (angiotensin-converting enzyme) blockade was mentioned in post #756 for maximakinin from the Chinese Red Belly toad, Bombina maxima. Ace blockade is also from the venom of Bothrops jararaca, which interesting history is here: Snakes and Hypertension...

www.usmessageboard.com

 

[badger2]

In the controversial Trump-related article of post #903, one of the contributing authors, Weaver, dismisses hydroxychloroquine while comparing it to oleandrin (in vitro [italics]). Weaver seemingly has nothing to say about the synergy of the Raoult-Zelenko tripartite protocol (hydroxychloroquine, azithromycin, zinc, of previous messages). From the evidence of cumulative posts in this thread, especially oleandrin's impressive EC50, one would choose its use in hamsters as a COVID-19 animal model, without delay.

 

[badger2]

We link Trump's oleandrin to a Czech-Polish study, showing the connection to toads:

Bufadienolide

Bufadienolide - Wikipedia

en.wikipedia.org

'....toad genus Bufo....'

We have mentioned in this thread the amphibian bradykinin homologue, maximakinin, and this was the Rab link we were following due to the Rab study at Wuhan, Mar 2020:

Characterization of Zika Virus Endocytic Pathways in Human Glioblastoma Cells - PubMed

Zika virus (ZIKV) infections can cause microcephaly and neurological disorders. However, the early infection events of ZIKV in neural cells remain to be characterized. Here, by using a combination of pharmacological and molecular approaches and the human glioblastoma cell T98G as a model, we...

www.ncbi.nlm.nih.gov

'....Wuhan Institute of Virology....'

Sept 2020 Czech-Polish Oleandrigenin / Bufatalin / Bufadienolide

Synthesis and evaluation of Na+/K+-ATP-ase inhibiting and cytotoxic in vitro activities of oleandrigenin and its selected 17β-(butenolidyl)- and 17β-(3-furyl)- analogues - PubMed

Natural cardiac-active principles built upon the 14,16β-dihydroxy-5β,14β-androstane core and bearing a heterocyclic substituent at 17β, in particular, a cardenolide - oleandrin and a bufadienolide - bufotalin, are receiving a great deal of attention as potential anticancer drugs. The densely...

www.ncbi.nlm.nih.gov

'....Furthermore, selected 17beta-(4-butenolidyl)- and 17beta-(3-furyl)-14,16beta-dihydroxy-androstane derivatives were en route synthesized and examined for their Na+/K+-ATPase inhibitory properties, as well as cytotoxic activities in normal and cancer cell lines. It was found that the furyl- analogue of oleandrigenin/bufatalin and some related 17-(3-furyl)-derivatives show remarkably high activity.'

On 17 Jun 2020 we mentioned salmon androsterone and methylcyclohexanone in post #613 for the COVID-19 found on cutting boards, apparently from imported Scandinavian salmon.

There are two more studies by these Czech-Polish authors:

Synthetic Approach to the Core Structure of Oleandrin and Related Cardiac Glycosides with Highly Functionalized Ring D - PubMed

The first synthetic approach to the core structure of cardiac glycoside oleandrin exhibiting a potent cytotoxic activity, starting from a common androstane derivative, has been accomplished. The synthesis is focused on stereoselective transformations in the densely substituted and sterically...

www.ncbi.nlm.nih.gov

Synthesis and evaluation of cytotoxic and Na+/K+-ATP-ase inhibitory activity of selected 5α-oleandrigenin derivatives - PubMed

Oleandrin, the major biologically active constituent of shrub Nerium oleander preparations of which have been used in traditional Mediterranean and Asian medicine, attracts a great deal of attention due to its pronounced anticancer activity. The synthesis of oleandrigenin model...

www.ncbi.nlm.nih.gov

Maximakinin (aka bombakinin M), linking our trajectory to Rab genes and Zika virus (Wuhan Institute of Virology, et al), is from the Chinese Red Belly Toad, Bombina maxima.

 

[badger2]

Androstane derivatives mentioned in post #923, link to Trump's hydroxychloroquine and ebola, due to lysosomes/endosomes (hcq changes pH of endosomes):

Jul 2020 COVID-19 / Nieman-Pick Type C / Ebola / Hydroxychloroquine

Potential COVID-19 therapeutics from a rare disease: weaponizing lipid dysregulation to combat viral infectivity - PubMed

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has resulted in the death of more than 328,000 persons worldwide in the first 5 months of 2020. Herculean efforts to rapidly design and produce vaccines and other antiviral...

www.ncbi.nlm.nih.gov

 

[badger2]

17 Aug 2020 COVID-19 in Utah Mink

https://www.washingtonpost.com/science/2020/08/17/coronavirus-mink-first-us-cases/?hpid=hp_hp-top-table-main_virusminks-630pm%3Ahomepage%2Fstory_ans

Minks were mentioned in post #619, #653 (Denmark), #755 (for ACE2 and TGEV), and #754 (Spain) .

 

[badger2]

The report doesn't seem to state the locations by county, though does say there are 38 mink farms in the state.

 

[badger2]

This report states two mink farms:

Coronavirus detected at Utah mink farms

Mink are already known to be susceptible to the virus and tests done in Utah, Washington and Iowa, where the national lab is located, have proven infection. Early investigations point to human-to-animal transmission, though, the reverse is highly unlikely, the national lab reports.

www.deseret.com

'....two to three mink are dying every day in Utah....'

 

[badger2]

This study mentions arbidol, which is a Russian-made small indole compound for prophylaxis and treatment of influenza. It's also known as umifenovir. For COVID-19, the article uses TCM (Traditional Chinese Medicine). We will be taking a closer look at the constituents:

Jul 2020 COVID-19 / Qingfei Paidu Decoction

Clinical retrospective study on the efficacy of Qingfei Paidu decoction combined with Western medicine for COVID-19 treatment - PubMed

The combination of QPD with Western medicine demonstrated significant anti-inflammatory effects compared with those of only Western medicine in patients with mild and moderate COVID-19; however, neither mortality nor length of hospitalization was affected. Moreover, the combined treatment tended...

www.ncbi.nlm.nih.gov

'....QPD contains 948 different chemical compounds, which affect 790 potential target proteins....'

 

[badger2]

Before investigating Qingfei Paidu against COVID-19, there is some interesting plant chemistry that links Trump's oleandrin to Shenzhen (previous messages).

Nerium oleander (Apocynaceae) is the source of oleandrin. Nerium belongs to the Tribe Nerieae, which has 6 genera: Adenium, Alafia, Farquharia, Isonema, Nerium and Strophanthus. The cardiac glycosides from this tribe also occur in Strophanthus, though oleandrin proper does not.

URL functions if typed in the spacebar:

https://szdaily.sznews.com/attachment/pdf/201803/16/6a29637e-c129-48e7-96fa-d66214db34bc.pdf

'....The exhibition features extremely poisonous plants in Shenzhen, such as Gelsemium elegans, Strophanthus divaricatus, Strychnos angustifolia, devil's trumpet (Datura metel) and Upas Tree (Antiaris toxicaria).'

It was very likely the 1918 volume of JAMA that mentioned Gelsemium for influenza.

 

[badger2]

Ovarian cancer and PI3k were linked to Trump's oleandrin in post #899. Strophanthus from Madagascar is anti-ovarian cancer:

Roupellina (Strophanthus) boivinii / Ovarian Cancer

Cytotoxic cardenolide glycosides of Roupellina (Strophanthus) boivinii from the Madagascar rainforest - PubMed

Bioassay-guided fractionation of an ethanol extract of Roupellina (Strophanthus) boivinii from the rainforest of Madagascar afforded the six new cardenolide glycosides boivinides 1-6, as well as the four known cardenolide glycosides digitoxigenin 3-O-[beta-D-glucopyrananosyl-(1-->4)-alpha-L-acofr …

www.ncbi.nlm.nih.gov

Jul 2020 Oleandrin-PI3k Anti-HIV

Oleandrin: A bioactive phytochemical and potential cancer killer via multiple cellular signaling pathways - PubMed

Nerium oleander, a member of family Apocynaceae, is commonly known as Kaner in various countries of Asia and Mediterranean region. This plant has been renowned to possess significant therapeutic potential due to its various bioactive compounds which have been isolated from this plant e.g...

www.ncbi.nlm.nih.gov

In previous messages, Thai use of anti-HIV meds against COVID-19 were reported. Qingfei paidu treatment for COVID-19 also uses several anti-HIV plants in its decoction. We list the decoction:

Ephedra

Glycyrrhiza uralensis

Amygdalus communis

Atractylodes macrocephala Koidz

Radix bupleuri

Scutellaria baicalensis

Pinellia ternata

Asteris radix et rhizoma

Farfarae flos

Belamcanda chinensis

Asarum

Dioscorea polystachya

Citrus aurantium

Agastache rugosus

Zingiber officinale Rosc.

Wolfiporia cocos

Pericarpium citri Reticulatae

Raw gypsum

Cinnamomum cassia Presl

Alismatis

Polyporus umbellatus

Glycyrrhiza uralensis and Scutellaria baicalensis were the precise species used to show the first ever report that HIV-AIDS was a reversible disease, in a 49-month Chinese study of eight HIV-infected Tanzanians.

The Cinnamomum links to USMB thread, where on 13 May 2017, Rodishi posts (post #8) on procyanidins, which we have already mentioned in this thread:

Huckabee's Diabetes cure contract comes to an end.

Mike Huckabee Cures Diabetes With Snake Oil - The Daily Beast From the organization that paid Huckabee to tell other Christians cinnamon cures diabetes, there are some other doozies besides these: Cinnamon rolls contain a secret, diabetes-fighting ingredient! Your spice cabinet holds still...

www.usmessageboard.com

Cinnamomi cortex / procyanidins of the Japanese study were posted on 7 Jul 2020 (post #688):

Procyanidins and butanol extract of Cinnamomi Cortex inhibit SARS-CoV infection - PubMed

We found that the butanol fraction of Cinnamomi Cortex (CC/Fr.2) showed moderate inhibitory activity in wild-type severe acute respiratory syndrome coronavirus (wtSARS-CoV) and HIV/SARS-CoV S pseudovirus infections. The inhibition on pseudovirus was also seen in cells pretreated with the CC and...

www.ncbi.nlm.nih.gov

 

[badger2]

Further evidence that Trump's oleandrin is successful against COVID-19, rather than most of the other constituents of Nerium, is here:

Na+/Ka+-ATPase Inhibition

The Antiviral Effects of Na,K-ATPase Inhibition: A Minireview - PubMed

Since being first described more than 60 years ago, Na,K-ATPase has been extensively studied, while novel concepts about its structure, physiology, and biological roles continue to be elucidated. Cardiac glycosides not only inhibit the pump function of Na,K-ATPase but also activate intracellular...

www.ncbi.nlm.nih.gov

'....coronavirus: ouabain, digitoxin: inhibition of scr pathway....herpes simplex virus: strophanthin: inhibition of viral gene expression.'

Glycosylation of Cardenolide Aglycones in Leaves of Nerium

https://www.ncbi.nlm.nih.gov/pubmed/172662251

'....digitoxigenin....oleandrigenin....'

 

[badger2]

Oleandrigenin and digitoxigenin in Nerium play important roles in the synthesis of oleandrin. Digitoxin inhibits the src pathway.

Saracatinib / MERS / Src Pathway

Saracatinib Inhibits Middle East Respiratory Syndrome-Coronavirus Replication In Vitro - PubMed

The Middle East respiratory syndrome-coronavirus (MERS-CoV), first identified in Saudi Arabia, is an emerging zoonotic pathogen that causes severe acute respiratory illness in humans with a high fatality rate. Since its emergence, MERS-CoV continues to spread to countries outside of the Arabian...

www.ncbi.nlm.nih.gov

'....a potent inhibitor of src-family of tyrosine kinases.'

Src-Mediated Regulation of PI3K / Thyroid Cancer

Src-mediated regulation of the PI3K pathway in advanced papillary and anaplastic thyroid cancer - PubMed

Advanced stages of papillary and anaplastic thyroid cancer continue to be plagued by a dismal prognosis, which is a result of limited effective therapies for these cancers. Due to the high proportion of thyroid cancers harboring mutations in the MAPK pathway, the MAPK pathway has become a focal...

www.ncbi.nlm.nih.gov

'....Targeting src results in inhibition of growth, invasion, and migration....enhanced through a combined inhibition of src and the MAPK pathway.'

 

[badger2]

These reports show that BDNF links to oleandrin's anti-cancer/antiviral properties:

(2017) Oleandrin Reduces Glioma Growth

The Glycoside Oleandrin Reduces Glioma Growth with Direct and Indirect Effects on Tumor Cells - PubMed

Oleandrin is a glycoside that inhibits the ubiquitous enzyme Na⁺/K⁺-ATPase. In addition to its known effects on cardiac muscle, recent <i>in vitro</i> and <i>in vivo</i> evidence highlighted its potential for anticancer properties. Here, we evaluated for the first time the...

www.ncbi.nlm.nih.gov

'....We demonstrated that oleandrin does the following: enhances the brain-derived neurotrophic factor (BDNF) level in brain; reduces both microglia and macrophage infiltration and CD68 immunoreactivity in the tumor mass; reduces astrogliosis in peritumoral area; reduces glioma cell infiltration in healthy parenchyma. In BDNF-deficient mice and in glioma cells silenced for TrkB receptor expression, oleandrin was not effective, indicating a crucial role for BDNF in olandrin's protective and antitumor functions.'

Sept 2020 Recovery from SARS-CoV-2 Infection is Associated with Serum BDNF Restoration

Recovery from SARS-CoV-2 infection is associated with serum BDNF restoration - PubMed

Recovery from SARS-CoV-2 infection is associated with serum BDNF restoration

www.ncbi.nlm.nih.gov

 

[badger2]

The Israeli report above, "Recovery from SARS-CoV-2 Infection is Associated with Serum BDNF Restoration," states:

'In this study we provide the first data on serum BDNF levels in SARS-CoV-2 patients and their correlations with clinical and laboratory indices of disease severity. The contribution of lymphocytes BDNF secretion to the circulating pool, demonstrated in our earlier work, may link between the lymphopenia and the low BDNF observed in patients with severe disease....The kinetics of BDNF in this study may be explained by previous reports indicating the suppressive effect of pro-inflammatory states on BDNF levels and function....Further studies are needed to verify the interplay between ferritin and BDNF, and the potential of using BDNF as a biomarker in SARS-CoV-2 patients.'

 

[badger2]

Amongst Pubmed entries for oleandrin is one for the Notch gene. Here is linked Notch to BDNF of the Israeli study:

Notch Inhibition from Nerium / Oleandrin

The Notch Inhibitors Isolated from Nerium indicum - PubMed

Notch signaling plays a crucial role in differentiation and cell maintenance, but once aberrantly activated, it contributes to cancer progression. Notch inhibitors were isolated from plant extracts and tested using an originally constructed cell-based assay system. We isolated eight compounds...

www.ncbi.nlm.nih.gov

'....We isolated eight compounds from N. indicum that showed inhibition of Notch signaling pathway.'

Chinese Moxibustion Improves Learning Ability in Vascular Dementia (VD) Rats / BDNF / Notch / Vascular Dementia

[Moxibustion Improves Learning Ability by Regulating Hippocampal Neurotrophic Factor Expression and Notch Signaling in Vascular Dementia Rats] - PubMed

Moxibustion can improve learning ability in VD rats, which may be associated with its effects in up-regulating the expression of neurotrophic factors and in potentiating Notch signaling.

www.ncbi.nlm.nih.gov

'....The expression levels of BDNF, NGF, GFAP, Hes3, Notch1 genes and proteins were significantly upregulated in the model group relevant to the sham operation group.'

We think that the smoking moxibustion should be contraindicated, for this approach to dementia treatment could be dangerous to those with the ApoE3 allele (and[italics]) simultaneous COVID-19 infection:

Vascular Dementia / Smoking / Alzheimer's

Possibilities of Dementia Prevention - It is Never Too Early to Start - PubMed

Dementia represents one of the greatest global challenges for health and social care in this century. More than 50 million people worldwide suffer from dementia, and this number is predicted to triple by 2050. Ageing is often associated with cognitive impairment. Therefore, prevention of...

www.ncbi.nlm.nih.gov

'....Most cardiovascular risk factors such as hypertension, diabetes mellitus, hypercholesterolemia, atrial fibrillation and smoking are not exclusive risk factors for vascular dementia but also for Alzheimer's disease.'

 

[badger2]

Notch in COVID-19 infection is upregulated as is Notch in moxibustion-dementia:

6 Aug 2020 Notch Gene / Coronavirus

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection - PubMed

The novel virus SARS-CoV-2 has infected more than 14 million people worldwide resulting in the Coronavirus disease 2019 (COVID-19). Limited information on the underlying immune mechanisms that drive disease or protection during COVID-19 severely hamper development of therapeutics and vaccines...

www.ncbi.nlm.nih.gov

'....We demonstrate that Type I interferon (IFN) and Notch signaling pathways are significantly upregulated in lungs of juvenile infected macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease.'

 

[badger2]

As in the macaques (post #936) so too in humans:

21 Aug 2020 Inflammation in COVID-19

Inflammation: the key factor that explains vulnerability to severe COVID

Abnormal functioning of the immune system is what characterises severe COVID, and can be driven by diabetes, obesity, sex and age.

www.yahoo.com

'....many older people have fewer lymphocytes.'

 

[badger2]

This from Imperial College, London, links to post #621 of this thread for COVID-19 and glycosylation:

18 Aug 2020 Coronavirus Could Be Linked to Type 1 Diabetes in Children

Coronavirus could be linked to type-1 diabetes in children, study suggests

The autoimmune disease inhibits the body’s ability to produce insulin

www.independent.co.uk

'....around 70% of the children diagnosed with diabetes presented with diabetic ketoacidosis (DKA) -- a serious complication....50% of DKA cases were observed to be "severe" -- a much higher rate than usual.'

Glycosylation / Why a Fast Blood Glucose Control Should Be Necessary

Snake Meat......source of chinese virus

Early on in this thread, we pointed to the ethnic link to varying amounts of ACE2 receptors relative to COVID-19 susceptibility. Recently, another ACE2 factor has come to light. COVID-19 Glycosylation / Chloroquine https://www.ncbi.nlm.nih.gov/pubmed/32293710 'Hyperglycemia, Hydroxychloroquine...

www.usmessageboard.com

 

[badger2]

The report for UK diabetic children was posted today at Avian Flu Talk, though they don't seem to make the historical connections that would clarify the pediatric COVID-19/diabetes assemblage. The 18 Jun 2020 post #621 includes a report (Brufsky A, UPMC Hillman Cancer Center, Magee Women's Hospital, University of Pittsburgh) that does:

'Hyperglycemia, Hydroxychloroquine, and COVID-19 Infection.

A known history of diabetes and ambient hyperglycemia were found to be independent risk factors for morbidity and mortality in SARS (Diabet. Med. [2006] 23:623-8)....Diabetes was found in 7.4% of a cohort of hospitalized COVID-19 patients and appeared to be a risk factor for disease severity (NEJM [Feb 2020]: NEJMoa 2002032). A history of diabetes was associated with 22.5% of COVID-19 intensive care unit (ICU) admissions vs. 5.9% of non-ICU admissions in one case series (JAMA [2020] 323: 1061-9), and another recent ICU case series reported 14 of 24 (58%) with a history of diabetes.
....
A possible explanation for a link between hyperglycemia and ACE2 levels in the severity of COVID-19 disease could be explained by several clinical observations in SARS and preclinical observations in the NOD diabetic mouse model....potential changes in glycosylation of the ACE2, as well as glycosylation of the viral spike protein both possibly induced by uncontrolled hyperglycemia mat alter both the binding of the viral spike protein to ACE2 and the degree of the immune response, to the virus.
....
Autopsy of an untreated individual revealed high levels of ACE2 expression in the alveolar tissue of the lung, the islet cells of the pancreas, the heart, and the kidney. This suggested a mechanism of transient hyperglycemia induced by a transient inflammation of the islet cells by SARS-CoV through binding of the SARS-CoV to the ACE2 present on islet cells, resulting in a transient insulin-dependent diabetes mellitus, which resolves with the resolution of the disease.

In a study of NOD mice, ACE2 protein levels in the lung were putatively elevated when compared with control mice and returned to control levels when insulin was administered....This also suggests a possible paracrine loop hypothesis for COVID-19 infection where the virus infects the pancreas and lung, leading to hyperglycemia and upregulation of glycosylated ACE2 in the lung and further virus binding and inflammation. Poor glycemic control could therefore make the disease more severe....glucocorticoid use made hyperglycemia and possible clinical symptoms, more severe.
....
Interestingly, high ACE2 has a protective effect in varioous organs (J. Med. Virol [2020] 10.1002/jmv.25785). ACE2 gene expression is increased by estrogen in a mouse model, a potential protective factor for SARS-CoV infection and pathogenicity, as men are more likely than women to both acquire COVID-19 and have more severe disease. Recent survey studies found that ACE2 expression was higher in tissue of women and in younger adults, an inverse correlation to disease severity. A possible explanation for this discrepancy is that gene expression experiments cannot measure posttranslational modifications such as protein glycosylation. In the NOD diabetic mouse, ACE2 activity in the lung did not rise and fall with insulin administration, but the amount of ACE2 protein apparently did. This is consistent with a rise in glycosylated ACE2, as opposed to total ACE2, since antibody binding to proteins as measured by Western blot analysis could be affected by glycosylation. Therefore, it is likely that it is the amount of glycosylated ACE2 receptor, and not simply the amount of ACE2 alone, that is responsible for virus binding and fusion.'

 

[badger2]

The following report is half true. Oleandrin has been tested on COVID-19, though not in humans. The media thinks the cup is half empty rather than half full, which is the pathology:

Trump Strategy on COVID-19 Continues to Rely on Miracles

Trump strategy on COVID-19 continues to rely on miracles

After months of insisting the coronavirus would disappear to no success, the White House has continued that strategy in the lead-up to next week's Republican National Convention.

news.yahoo.com