GrandRhino
Founding Member
Tonight we tackle more science. Yes but not just any science...the latest, this one is based on yet another peer reviewed published paper from this year. A warning, it gets fairly scientifically funky...muster through it though, I'll try and make it as readable as possible. Bonus(es) at the end...
ACKNOWLEDGMENT
Like a professional deep sea master fisher type person, acknowledgement to my source from the West....thank you from all of us at HC PAR Land....because of your wonderful finds I can research and write these such posts.
No, this is not Scott I'm referring to...this is someone quite independent of any investment/brokerage firm.
Another sterling catch? Cast out that net far and wide Paradigmers, bring us new research so we can continuously test, understand and enjoy this wondrous little molecule we have and we will be better informed investors. We must be solidly educated at this early stage to have raw conviction to hold for not weeks....but years. (Not advice).
INTRO
Before I even get to what this newly published study is, we need an intro. on the role and function and even definition of a thing called Hepcidin.Hepcidin is a protein that regulates the entry of iron into the circulatory system of mammals.
Is it important?
Mate!
Now the trick is, at the end of the day, we don't want too much iron pumping...
No no, this isn't quite the iron pumping around I'm talking about....I mean iron in our blood...
Accumulation and hyper production of iron in the liver occurs when you are in an inflammatory state...
While Iron is an essential component for all living creatures, too much of it isn't good. So much so that too much can be a biohazard. 1
Hepcidin plays a critical role in regulation of Iron. We need a balance...not too much, but not too little.
One more thing I need to define before we get to juicy stuff, osteoclasts (referred to as OC for short)...these are the little cells that are responsible for breaking down bones. No, we do not want to eradicate all osteoclasts, we need some of them for sure. It's these guys that help to turn over bone which allows for growth of new bone...BUT we don't want too many of them.
When do we get too many of them? Well when OA prevails, when there is inflammation...Don't forget, some inflammation is good, well its vital, its this state that alerts the body into action to address the underlying problem. The 'bad' inflammation I'm talking about is the CONSTANT inflammation, the type of state we are in when we have OA for example.
Of course OA is just one of literally thousands of inflammatory type diseases/conditions.
Now that you know what an osteoclast is, we have to define another type of cell that kind of goes hand in hand but in an opposite way, the osteoblast. These guys pretty much do the opposite...they are responsible for bone formation.
How important are these guys? Here is a quote:
"All forms of acquired osteoporosis reflect increased osteoclast function relative to that of the osteoblast." 2
Ok so the next question is how does iPPS have anything to do with this?Ah, this is where this newest study comes into play:
THE STUDY
So the peer review was based on a study that set out to:
"... find out whether PPS is able to control the formation and function of hepcidin 1 treated OC and thereby intracellular iron concentration. To the best of our knowledge, the present study is the first attempt to identify the effect of PPS on hepcidin facilitated differentiation and intracellular iron concentration in bone marrow derived OC. "
So as I mentioned, we don't want too many of the Osteoclasts, we get too many when inflammatory conditions prevail:
"However, excessive activation of the immune mediators at the inflammatory conditions can enhance the OC production and eventually the severe bone erosion can be occurred. Therapeutic interventions targeting osteoclastogenesis might enable it to restore bone mass in arthritic patients ."
Read that last bit again....Therapeutic interventions targeting osteoclastogenesis might enable it to restore bone mass in arthritic patients.
So we know our you-beaut iPPS:
This is the DMOAD..this is the holy grail.. we should get more data on it in a number of months (008 top line read out). I know its a long time between drinks...but the science keeps churning out.
Ok so we have the scene set now...we have a problem....inflammation...this leads to too many OC's and this in turn leads to the bone degenerative processes. Lets now check out some more of the results the study found.
RESULTS
Ok some more background just before we can hit these results.... 'Wells' are simply the little dishes that the substances can be kept in. Here's a pic:
Examples of wells used in the lab.
Ok now lets have a sticky beak at the results:
Bar graphs show the number of OC cells/well. Data are representative of three independent experiments and expressed as means ± SE. Means with * are significantly different from 0 μg/mL of PPS ( *p < 0.05, **p < 0.01).
Just take a look at the above chart. Its charts like these that keeps me going. Irrefutable raw science. All this empirical data ain't coming from one team...multiple groups of researchers are finding novel ways in which PPS is working.
That chart is depicting our molecule, that we own, crushing the number of wells that contain higher levels of osteoclasts. Amazing.
How about some more quotes directly from the paper:
"PPS inhibits osteoclastogenesis. Effects of different concentrations of PPS were evaluated over the BMMs treated M-CSF and RANKL. Dose dependent inhibition of TRAP-stained multinucleated cells (3 nuclei) were detected significantly at all the concentrations of PPS from 1 (p < 0.001), 5, 10, 20 micro g/mL (p < 0.005)".
"Quantitative qPCR data showed that PPS at 5–10 μg/mL significantly downregulates the gene expression (p < 0.05) level of CTK while inhibiting expression level of MMP-9 and NFATc1 in concentration-dependant manner".
"Previous studies have indicated that OC development comprises high iron requirements. With that phenomenal statement, it further supplemented the inhibitory effect of PPS on osteoclastogenesis and their functional capability even at the presence of hepcidin. Outcome of this study confirms that PPS regulates hepcidin 1-facilitated formation and function of OC derived from canine bone marrow thereby inhibiting iron accumulation in the cells."
BONUS TIME
Want more than the above results? How about three bonuses:
BONUS 1
Getting a bit bogged down in all those scientific terminology?
How about a pic? Just before the pic, allow me just one explanation; Fluorescence (using Phen Green) is a process to highlight using UV light to detect levels of iron concentrations. Counterintuitively, the intensity of green is high when the concentration of iron is low.If you see a more darker snapshot then that's not as desirable.
Pic E) where there is no Hepcidin, its a good pic, not too much iron, thus we can see some of the Phen Green.
Pic F) A bad situation, the darker image indicates there is too much concentration of iron, bio hazard warning!
Pic G) PPS to the rescue, tackling the excess iron through regulation, now resulting in the image lighting up as we are back to more normalised levels of iron.
Ok how about another pic? Look at the stark difference PPS makes...from these over sized globules with zero PPS added (top left), to something resembling a more normal manageable distribution in the bottom right pic
BONUS 2
Bonus 2 refers to just how many people know about this science...not a lot...we are in the tiniest of subset of the mass population, yes right now...yes despite the sheer amount of data, all them SAS patients and even a handful of American Pro Footballers...the word is not at all out, at any sort of scale...
How do I know this?
Paradigmers, you me and the great peer review fisherman in the West are only a few that know about this stuff, lets hear it from the authors of this paper:
"To the author’s knowledge, no similar studies have previously been reported to determine a priori what the crucial pathways to address."
...and furthermore...
"The present study demonstrates for the first time that PPS is a novel inhibitor of hepcidin-facilitated OC formation and function from bone marrow-derived stem cells."
BONUS 3
We know our drug is valuable. We know it works...
To accelerate the sheer benefits of our drug we need one large puzzle piece to make our picture complete. DMOAD.
Forget about the actual number of patients now hearing about our drug as they realise that there is a chance of it reversing the course of the disease...forget about the Docs that now make us a priority for their patient lists. Forget about the AMA putting out new fresh recommendations that we should be front line treatment. JUST think about the revenue lift from circa $2500 to $6000 plus. A 2.4 increase without changing any other factor.
Why am I bringing the topic of DMOAD up now?
The researchers in this peer review mentioned it, welcome to Bonus 3:
"The present study demonstrates for the first time that PPS is a novel inhibitor of hepcidin-facilitated OC formation and function from bone marrow-derived stem cells. With the multiple facets of action of PPS, this novel finding would be upgraded the uses of DMOARs and specially, PPS for the betterment of OA and RA associated anemia and iron imbalance."
The evidence of the efficacy and the great capability of our molecule just keeps rolling in...
DYOR as per usual.
- Mozz
REFERENCES
MAIN REFERENCE
Pentosan polysulfate regulates hepcidin 1-facilitated formation and function of osteoclast derived from canine bone marrow
Hepcidin which is the crucial regulator of iron homeostasis, produced in the liver in response to anemia, hypoxia, or inflammation. Recent studies have suggested that hepcidin and iron metabolism are involved in osteoporosis by inhibiting osteoblast function and promoting osteoclastogenesis...
OTHER REFERENCES
1] https://www.frontiersin.org/articles/10.3389/fnut.2018.00103/full
2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1851862/
3] https://www.ncbi.nlm.nih.gov/books/...remove bone by,that produce white blood cells
