Evgen Pharma Share Discussion Threads

[moneymunch] 12/1/2021 17:03

Looks like it has....Gl ;-)

[amaretto1] 12/1/2021 17:01

Val up today ... DDDD .. ready to ! EVG needs to wake up ..

[peanut100] 12/1/2021 11:07

https://www.independent.co.uk/voices/vaccine-covid-treatments-coronavirus-b1783955.html?amp

[moneymunch] 12/1/2021 10:53

Very wise, potential news on multiple disease targets stacking UP!!! Gl :-)

[nobbygnome] 12/1/2021 09:36

VAL has taken off this morning and they are valued more than EVG already. When on earth is it going to be EVG's turn to attract the herd to a ridiculously undervalued company....

I am buying a few more!

[moneymunch] 12/1/2021 07:25

Compelling documented research that highlights exactly why SFX-01 was selected for Covid patient trials from over 130 drug candidates, including the STAT3 and Nrf2 pathways influence over ACE2 expression. Gla ;-)

[moneymunch] 12/1/2021 07:21

STAT3

19/9/20

J Cell Mol Med. 2020 Sep 19. doi:

10.1111/jcmm.15838. Online ahead of print.

ABSTRACT

The SARS-coronavirus 2 is the aetiologic agent COVID-19. ACE2 has been identified as a cell entry receptor for the virus. Therefore, trying to understand how the gene is controlled has become a major goal. We silenced the expression of STAT3α and STAT3β, and found that while silencing STAT3α causes an increase in ACE2 expression, silencing STAT3β causes the opposite effect. Studying the role of STAT3 in ACE2 expression will shed light on the molecular events that contribute to the progression of the disease and that the different roles of STAT3α and STAT3β in that context must be taken in consideration. Our results place STAT3 in line with additional potential therapeutic targets for treating COVID-19 patients.




Published: 09 October 2020

An aberrant STAT pathway is central to COVID-19

Toshifumi Matsuyama, Shawn P. Kubli, Steven K. Yoshinaga, Klaus Pfeffer & Tak W. Mak

Cell Death & Differentiation (2020)Cite this article



Abstract

COVID-19 is caused by SARS-CoV-2 infection and characterized by diverse clinical symptoms. Type I interferon (IFN-I) production is impaired and severe cases lead to ARDS and widespread coagulopathy. We propose that COVID-19 pathophysiology is initiated by SARS-CoV-2 gene products, the NSP1 and ORF6 proteins, leading to a catastrophic cascade of failures. These viral components induce signal transducer and activator of transcription 1 (STAT1) dysfunction and compensatory hyperactivation of STAT3. In SARS-CoV-2-infected cells, a positive feedback loop established between STAT3 and plasminogen activator inhibitor-1 (PAI-1) may lead to an escalating cycle of activation in common with the interdependent signaling networks affected in COVID-19. Specifically, PAI-1 upregulation leads to coagulopathy characterized by intravascular thrombi. Overproduced PAI-1 binds to TLR4 on macrophages, inducing the secretion of proinflammatory cytokines and chemokines. The recruitment and subsequent activation of innate immune cells within an infected lung drives the destruction of lung architecture, which leads to the infection of regional endothelial cells and produces a hypoxic environment that further stimulates PAI-1 production. Acute lung injury also activates EGFR and leads to the phosphorylation of STAT3. COVID-19 patients’ autopsies frequently exhibit diffuse alveolar damage (DAD) and increased hyaluronan (HA) production which also leads to higher levels of PAI-1. COVID-19 risk factors are consistent with this scenario, as PAI-1 levels are increased in hypertension, obesity, diabetes, cardiovascular diseases, and old age. We discuss the possibility of using various approved drugs, or drugs currently in clinical development, to treat COVID-19. This perspective suggests to enhance STAT1 activity and/or inhibit STAT3 functions for COVID-19 treatment. This might derail the escalating STAT3/PAI-1 cycle central to COVID-19.

.................

Concluding remarks

The SARS-CoV-2 virus has evolved multiple tools to escape immune detection and destruction, and thus has become the most formidable virus in over 100 years. Our survey of the current literature reveals that severe cases of COVID-19 are commonly dependent on the over-stimulation of the STAT3/PAI-1 signaling network. We believe that this shared node may be the Achilles’ Heel of COVID-19 and a vulnerable point of the disease. We therefore urge the immediate investigation and application of STAT therapy as a treatment for this perplexing disorder, and hope that our article provides a sound foundation for doing so.

A final note: during our analysis of the literature on COVID-19 and related topics, we noticed many similarities in the pathogenesis of COVID-19 and cancers. In fact, both STAT3 and PAI-1 have been separately implicated in cancer development and are the subjects of extensive clinical investigations. A shared node of STAT3 and PAI-1 activities may also function in some pSTAT3-positive cancers, creating a cascade of harmful responses comparable to those of COVID-19. Any STAT-related agents developed to treat COVID-19 may therefore eventually enjoy much wider clinical use.

[moneymunch] 12/1/2021 07:15

SARS-CoV-2 Biology and Potential Crosstalk with NRF2

The SARS-CoV-2 genome encodes non-structural proteins (nsp) that are required for replication, structural proteins including spike (S), envelope (E), membrane (M), and nucleocapsid (N), and accessory proteins ORF3, 6, 7a, 7b, 8, and 9b that interact with the host cells [38].

The receptor-binding domain (RBD) located in the S protein of SARS-CoV-2 interacts with the angiotensin-converting enzyme 2 (ACE2) of host cells to allow viral entry (Figure 1) [39].

The use of ACE inhibitors/angiotensin-receptor blockers, which are widely prescribed to patients with cardiovascular pathologies [40], is currently being considered for COVID-19 (clinical trial numbersi NCT04311177 and NCT04312009 for the use of losartan) because angiotensin II, the target of ACE inhibitors, has vasoconstrictive, proinflammatory, pro-oxidative, and prothrombotic effects [41].

However, these inhibitors alter the balance ACE/ACE2 and increase ACE2 levels, thus potentially increasing the number of docking sites for viral entry [42].

NRF2 deficiency is known to upregulate ACE2, whereas its activator oltipraz reduces ACE2 levels [43], suggesting that NRF2 activation might reduce the availability of ACE2 for SARS-CoV-2 entry into the cell (Figure 1).

..................

Sulforaphane

The isothiocyanate sulforaphane (SFN), originally isolated from broccoli, a cruciferous vegetable, as an inducer of the classical NRF2 target, NAD(P)H:quinone oxidoreductase 1 (NQO1) [76], is the most potent naturally occurring NRF2 activator, with well-documented antioxidant and anti-inflammatory effects [77].

The high bioavailability of SFN and its stabilized α-cyclodextrin-encapsulated version sulforadex (SFX-01) makes it an excellent candidate for alleviating excessive anti-inflammatory responses and protecting the lungs.

SFN has been found to be protective in animal models of respiratory disease, including an ARDS model in rabbits [78] and a hyperoxia-induced pulmonary injury model in mice [79].

It also limits RSV replication and virus-induced inflammation in the lungs of wild-type, but not NRF2-null, mice [80].

In HIV-1 transgenic rats, SFN increased GSH levels and the expression of NQO1, and restored the tight junctions between the alveolar epithelial cells [81].

In an in vitro model of influenza A infection, SFN reduced both viral cell entry and replication [82].

In addition, SFN suppresses HCV replication [83] and reduces HSV-1 virion production [29].

Interestingly, SFN inhibits nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)-, and pyrin domain-containing protein (NLRP) 1 and 3 inflammasomes (crucial innate immune components that shape host immune homeostasis) as well as pyroptosis, partly in an NRF2-independent manner [84].

Moreover, an interesting study conducted in smokers (a patient cohort with higher risk of lung infections, damage etc.) showed that SFN increased the expression of NQO1 in cells of nasal lavage fluid and, upon infection with live attenuated influenza virus, lowered the levels of IL-6 and viral load [85].

Sources of sulforaphane, including standardized broccoli extracts, dietary supplements, and encapsulated stabilized sulforaphane (Prostaphane and SFX-01) have been in numerous clinical trials for indications that range from lung disease to inflammatory diseases which are closely related to COVID-19 pathophysiology.

These include chronic obstructive pulmonary disease (COPD), asthma, allergy, rhinitis, aging, diabetes mellitus, Helicobacter pylori infection, and subarachnoid hemorrhage (Table 1). The clinical trials provide extensive pharmacokinetics, pharmacodynamics, safety, and efficacy information [77] that can be extrapolated to COVID-19.

Notably, most of these trials have recommended cruciferous-free diets during the study period to minimize baseline noise and accurately detect the plasma and urinary levels of sulforaphane and its metabolites [86].

[moneymunch] 12/1/2021 07:02

That's interesting, i never knew that there had been "a major shadow hanging over SNG's results" ????? Gla ;-)





Research
Synairgen's inhaled interferon for COVID-19 enhances short, harmless version of virus entry point: study
by Arlene Weintraub | Jan 11, 2021 11:00am

Last summer, shares of Synairgen skyrocketed 300% on a study showing its inhaled form of interferon beta-1a being developed to treat COVID-19 lessened the chance that patients would progress to a severe form of the virus.

But there was a major shadow hanging over the results: Interferon is known to increase levels of the cell surface protein ACE2, which serves as the entry point for SARS-CoV-2, the virus that causes COVID-19. That sparked fears that interferon-based treatments would ultimately fail in the treatment of the coronavirus.

Now, researchers led by the University of Southampton, which is collaborating with Synairgen in the development of its drug, have discovered that interferon raises levels of a short form of ACE2 that doesn’t allow SARS-CoV-2 to enter cells. In fact, it may have a protective effect, the team reported in the journal Nature Genetics.

[riggerbeautz] 11/1/2021 10:33

LOL never thought you’d be holding company with me ;) patience is a virtue, that’s how we get our 5,10,20 baggers over the years. Can always trade a few around the fringe bringing the averages down.

That said be good to get a positive update here.

[bumpa33] 11/1/2021 09:47

I know how you love a snail Rb, you’re in the right place :) !

[brasso3] 10/1/2021 23:12

Copper thing? PXC?

[riggerbeautz] 10/1/2021 23:06

Bumpa as ever thanks. I’m not daft, it gets too noisy in there for me some days and I lose focus so go quiet.

The copper thing everyone talks about, I let go 50k Friday, play every spike there. Oh and yes there is a lot of bullish exuberance on all those crypto related plays but trading opportunities too, even for me and you know I like snail stocks, that’s why I’m here ;)

Keep up the good posts here, enjoy reading this board.

[moneymunch] 10/1/2021 22:17

Hopefully not too long to find out Bumpa, I've been searching for patent filings related to SFN, but easier said than done, but Huw's excitement he expressed in his recent interview suggests that disclosure of the collaboration could be close, and one would assume that given the rate of new Covid-19 cases, the recruitment of the first 100 patients to SFX-01's Covid trial could be well advanced. Gl :-)

Ps Surrey has just been confirmed the highest rate for new Covid cases in the UK.:-(

[bumpa33] 10/1/2021 18:59

If I were to a take an educated guess on this ‘exciting hard to treat solid tumor pre-clinical data’ I’d go for liver cancer, the predominant form being Hepatocellular carcinoma (HCC), as the target. Wikipedia has primary liver cancer as the 6th most prevalent cancer worldwide, but the 2nd biggest killer - I’d assume behind lung cancer? The liver is the primary site of detoxification and subject to high levels of oxidative stress, there’s that phrase again...

[johnwise] 09/1/2021 18:51

Brilliantly Explain The Shocking Truth About Modern Day Eating Habits And Amazing Benefits Of A Ketogenic Diet.

VIDEO: Ketogenic Diet & Cancer by Dr. Mike Vanderschelden

[saint in exile] 09/1/2021 18:38

Has he got 3 eyes?

[bumpa33] 09/1/2021 18:30

p.p.s Rb - MODE was offered all week, I’m guessing some of the placing money happy to get out, probably muted the rise though mm’s were still pushing it. If it gets sticky could move sharper. But I’d always keep a picture of Rowland in my minds eye.

[bumpa33] 09/1/2021 18:22

Pacific Media, now that’s a blast from the past mm...!

Durlacher was one of the darlings I remember well, Infobank another. There were so many though - and 90% of them were junk.

[bumpa33] 09/1/2021 18:17

You too Rb. Had a quick look in on the other thread out of interest, the Italian thing they’re talking about IS a con job - 100%, the copper thing that everyone seems excited about, well they’ve yet to show they’ve got anything of substance - well worded RNS’s aside - and why I still think it’s a heavy promo job from a stable well versed in the art over the years. Maybe in time it’ll prove me wrong. Keep these to yourself, one of the reasons I stay clear from posting/reading over there now is I can’t be bothered with the arguments I’d cause from speaking out.