I can see the status bar

Chapter 746
Unless through gene therapy, doctors have no way to directly interfere with the expression of AQP4 protein.That is to say, there is no solution to directly treat the insufficient expression of AQP4 protein.But... this does not stop the doctors from developing some bold and experimental ideas.

Just like in the early days of coronary artery bypass grafting, when doctors deal with the shortage of certain tissues in the body, one of them is a "borrower".They have been doing this method of tearing down the east wall to make up for the west wall for hundreds of years-since the earliest black slave teeth were transplanted to the president of the United States, this method has been widely used by doctors.

However, when the method of tearing down the east wall to make up for the west wall cannot be effective, the doctors will consider using certain methods to stimulate the human body, so that the west wall that has been toppled can be... effect.

After all, the human body is a living system, not like industrially produced equipment - once it fails, there is no choice but to replace it.If the original organ can be maintained, it is very likely to rely on repair at the cellular level to complete the troubleshooting.

For other enzyme or protein deficiencies, it is often difficult for doctors to intervene.For example, Chen Tianyi, who was diagnosed with ornithine formyltransferase deficiency (OTCD) before.The reason why it is treated by liver transplantation instead of simply supplementing ornithine formyltransferase is because there is no reliable way to deliver drugs-ornithine formyltransferase is essentially a protein.Oral administration is not possible due to protein digestion in the gastrointestinal tract.It is also useless to administer ornithine formyltransferase through veins—the main working position of these transferases is in the mitochondria of liver cells. No matter how many transferases are floating in the blood, they cannot enter the mitochondria of liver cells to play a role .

Therefore, when treating OTCD, doctors mainly use various means to remove and reduce ammonia that cannot be converted by ornithine formyltransferase from the human body.

When dealing with insufficient expression of AQP4 protein, doctors can take similar measures to intervene in OTCD.Supplementing the body with AQP4 protein directly will have no effect - the protein may be digested and stored in the body as excess protein.For the AQP4 protein to function, it must appear on the cell membrane.

But for the research on AQP4, Sun Lien had a new idea.If there aren't enough AQP4 proteins to do what they're supposed to do...stimulate them to do more than they did before.

As a highly specific protein, AQP4 itself is a very efficient water channel.But the lack of quantity caused Tang Min to suffer from severe interstitial cell edema.Quantity cannot be intervened, at least with current medical methods.Then, protein phosphorylation has become the most likely effective method that Sun Lien can take now.

Protein phosphorylation is the most fundamental, common, and most important mechanism for regulating and controlling protein activity and function.According to the current research results, both PKA (protein kinase A) and PKC (protein kinase C) are possible effective substances to phosphorylate AQP4 and greatly increase water permeability.

Although the specific mechanism and process of action cannot be determined, in some cases, PKA can catalyze the phosphorylation of serine on aquaporin.PCK is the regulator of AQP4 expression.As an activator of PKC, phorbol sodium diphosphate can act on AQP4 and regulate AQP4 activity by catalyzing the phosphorylation of AQP4 protein.

What Sun Lien aimed at at the beginning was the strange-sounding name "phorbol sodium diphosphate".But... During the few minutes of waiting for the colleague to reply, he found painfully... this way might not work.

Although I have never heard of this drug, according to the information obtained by Sun Lien, phorbol, also known as phorbol ester, is a T lymphocyte activator and is highly carcinogenic.Its main purpose is to act on HL-60 cells and induce such cells to secrete TNF-α (Tumor Necrosis Factor α).

HL-60 cells are an important cell line for basic medical research, just like the famous HeLa cells, which were isolated from a human with cancer.The patient had acute promyelocytic leukemia, and the isolated cells could differentiate spontaneously and be induced to differentiate by certain substances.And phorbol is one such substance.

In other words, phorbol sodium diphosphate is a highly carcinogenic chemical agent used to induce HL-60 cells to secrete TNF-α, which is only used on certain cells in vitro in experiments.It is a dangerous tool in the field of medical research.This also means that Sun Lien is unlikely to regulate Tang Min's AQP4 activity through phorbol sodium diphosphate—unless he intends to risk being convicted of murder and illegal medical practice, and causing Tang Min to develop cancer.

The thesis didn't stop there, though.Probably because of the close association between AQP4 protein and hydrocephalus, there are not few studies on stimulating AQP4.While Sun Lien rejected phorbol sodium diphosphate, he found a way that seemed obviously safer.

AQP4 potency in brain cells may be activated by arginine vasopressin (AVP). AVP can activate two types of receptors, V1 and V2, while V1 can activate PLC (phospholipase C), and V2 receptor can activate the activity of AC (adenylate cyclase).Subsequently, phosphatase C and adenylate cyclase can activate protein kinase A and protein kinase C, respectively, so as to achieve the purpose of phosphorylating AQP4 protein.

Arginine vasopressin is much more familiar to Sun Lien.

Arginine vasopressin, also known as vasopressin, is an antidiuretic hormone.Clinically, doctors often use this injection to treat central diabetes insipidus and temporary diabetes insipidus caused by cranial trauma or surgery.It can also be used in the differential diagnosis of diabetes insipidus, in the treatment of nocturnal enuresis in patients six years of age or older, etc.

And the most wonderful thing is that, as a hormone, it can easily pass through the brain-blood barrier, and its safety is dozens of orders of magnitude stronger than that of the highly carcinogenic phorbol sodium diphosphate.Except for skin allergies and anaphylaxis reported in individual cases, this drug has almost no serious side effects and adverse reactions.

The only thing worthy of Sun Lien's reconsideration are two main points.

As an antidiuretic, arginine vasopressin inherently increases intracranial water and may cause water intoxication due to excess fluid intake.Therefore, it should be used with caution in patients at risk of increased intracranial pressure.Secondly, it is assumed that arginine vasopressin successfully entered Tang Min's body and entered her brain tissue through the brain-blood barrier.To successfully phosphorylate AQP4 protein, it also needs to go through the conversion process of V1V2 receptors and PCL and AC.It is unknown how this conversion process affects the body, nor is it known how much arginine vasopressin is required to achieve the desired level of phosphorylation.

But at least it's a direction.

Just when Sun Lien straightened out his thinking and was about to share his "unique and bold idea" with Yuan Pingan, Yuan Pingan suddenly jumped up from his seat.

He waved the mobile phone in his hand towards Sun Lien, and Sun Lien could only roughly recognize that the screen of the mobile phone was a WeChat chat interface.But he couldn't even recognize a word of what was written on it.

"The Tongxie still keeps the samples, and they are starting to measure mRNA!" After being excited for a while, Yuan Pingan realized that Sun Lien didn't know what he was getting excited about.So he quickly put the phone into Sun Lien's hand and said, "The paraffin samples are stored in a freezer at minus [-] degrees, we don't need to do another biopsy!"

(End of this chapter)