“Do you need to do cell experiments in Chinese medicine research?†If you change this question, “Do you need to do cell experiments for clinical disease research?†What is your answer? Looking at the article on disease research on the CNS, everyone is very clear.
Let's talk about why disease research requires cell experiments. This is related to the history of disease research, or the degree of development of disease research.
1, the discovery of any disease, there is a clinical phenotype, where is uncomfortable, and called disease.
2. In the history of disease research, where is uncomfortable, the first research is that what organs and tissues have problems, leading to this clinical phenotype. Therefore, the current division of the hospital, most of them are divided according to organs, cardiology, cardiac surgery, liver and gallbladder and so on. The emergence of anatomy has facilitated the development of this step of research. Of course, we can also say that the emergence of anatomy has been promoted because of the need for in-depth research from clinical phenotypes to organ tissues. Da Vinci is the master.
3. Determine what organs and tissues are in question and what further research is going on. The smallest functional unit of organ tissue is the cell. Further in-depth research is that what cells in the tissue change are different from normal cells, which causes the normal function of the tissues and organs to change, resulting in a clinical phenotype. The advent of the microscope has contributed to the rapid development of this step. Pathology has emerged, and the pathology department is called "the foundation of medicine" by William Osler, the father of modern medicine. From here on, medical research entered the microscopic era.
4. Pathological research has made disease research fine into the smallest functional unit in the organization, which has played a huge role in the diagnosis of clinical diseases. But for treatment, why the cells change, how to reverse their changes, it seems powerless. After the emergence of molecular biology, people began to explore this issue again. One of the main substances in life activity in cells is protein, and protein technology is also developed first. People began looking for disease-related proteins in the cells. However, at the molecular level, protein is actually a result, which is the result of gene coding. When DNA is found and proved to be genetic material in cells, it guides the expression of intracellular proteins, and the disease research really enters. The molecular stage. At present, we are still at this stage, looking for disease-related genes that change what functions of cells in the tissue, leading to disease development.
5. The disease has reached the end of the molecular level of genes. The enthusiasm of human exploration is the source of human development, and exploration has not stopped. After finding the functional gene of this disease, I began to explore why this gene changes in the cells of the disease, and who makes him change. This discussion is the upstream regulation mechanism of functional genes. Or explore how this gene changes the function of cells. This is the downstream mechanism of functional genes. Disease function genes, whether to promote disease through EMT. Whether autophagy affects the development of disease. Whether metabolism affects the development of disease (tumor immune checkpoint treatment is now a hot spot in tumor immunotherapy research, on March 16th nature, our Chinese study found that cholesterol esterification can enhance the anti-tumor activity of CD8+ T cells).
Clinical phenotype - organ tissue - cell - gene - mechanism. Be sure to pay attention to this complete process in our own research. The description of Jibo in the lecture is whether the completion of a topic depends on whether the history of disease research has been repeated in this research, whether there are genes, the correlation between genes and clinical samples, the function of genes on cells, and the mechanism by which genes function. . The clinical phenotype, written in the first paragraph, is published in the first paragraph.
Talk about the history of the development of disease research. We started talking about medicine.
The development of western medicine begins with the disease function gene. If a gene changes its development and promotes the development of the disease, this functional gene is a candidate drug target for the disease. If we can find a substance that can reverse the functional changes caused by the gene, if the last substance passes the preclinical experiment, the clinical phase I phase III phase IV phase IV test is the drug. As for what this substance is, is it a small molecule compound, a protein, or a nucleic acid. Yes. The development of western medicine is that there is a drug target first, and then there is a medicine.
Chinese medicine, Chinese medicine is the product of clinical experience and is summarized in clinical practice. It is the first drug, the post-study mechanism. The theoretical system of Chinese medicine appears very early. It is different from the theoretical system of Western medicine, but everyone pays attention to the explanation of the "pathological medical theory" of the disease. There is no difference between good and bad, only the angle is different. But in terms of drugs, the two have the same.
At present, people who are suspicious of Chinese medicine, in summary, have three questions.
1. What is the ingredient? That is, the ingredients are unclear, or what is the active ingredient. The quality control of medicinal materials begins with the active ingredients, which is one of the work of modernization of traditional Chinese medicine.
2. Is it effective? The effective here refers to what medicine is used by the patient and whether it is standardized. What is the preclinical data? Although traditional Chinese medicine has been used clinically for many years, has it done statistical analysis to summarize the rules and standardization. For the people we do research, the key is the preclinical data.
3. Mechanism. That is, the mechanism by which the drug is effective, and who is the downstream drug target. Linked to Western medicine, it is the disease function gene that this drug works.
At present, in the field of traditional Chinese medicine research, many teachers who are doing drugization are doing the separation and purification of pharmaceutical ingredients and solving the first problem. There are also many teachers who are going deeper and do not know which of these ingredients are active ingredients. The second problem is solved.
Everyone noticed that there is a misunderstanding here. Many people think that Chinese medicine is a group operation. If you separate a single component, it is likely to be ineffective. Chinese medicine research cannot do this. OK. For example, to treat a disease, it is necessary to solve 5 points. The Chinese medicine contains 5 ingredients corresponding to these 5 points, so that a Chinese medicine containing 5 ingredients cures the disease. However, if there are only 4 components in this drug, and 4 points are solved, the treatment effect is not good or invalid. This is what is often seen in the clinical practice of traditional Chinese medicine. Without a single drug, it has no effect. Then there is a problem. In the end, it takes a few points and several components, and each component is responsible for what. Why do you want to do this?
1, drug material control. The active ingredients are clear. The drug material control is based on the active ingredient. (Effective here refers to the function of this component, not to the final clinical treatment effect of the group. The drug itself has no therapeutic effect, but it can promote other ingredients to play a therapeutic role.)
2. Reduce side effects. Three-drug. In fact, in many traditional Chinese medicine compounds, many drugs are tonic and play a protective role. One purpose is to improve the body's resistance, and the other is to eliminate the harmful effects of side-effect substances in the medicine. Because the medicine is not purified, the beneficial substances are inside, and the harmful ones are also inside. Through careful research, the goal is to find beneficial substances and remove harmful substances. It may also be said that the same substance is beneficial and harmful, yes, research has shown that this is the case, such as pi shuang. Note that it was discovered after the study, and the research data was taken out rather than speculated. In this way, we can strictly control it in actual use, and play a beneficial role in the effective concentration to reduce its toxic effects. And what is the substance in the medicinal materials we use, whether it is beneficial or harmful, or both. How to control to increase its beneficial side reduces its harmful side. All of us need to study in depth.
3, precise treatment. Because the effective ingredients are clear and their functions are clear, then we can adjust the medication according to the actual situation of the patient to achieve precise treatment.
In fact, the current treatment of Western medicine is also going in the direction of joint operations, multi-drug use. The cocktail therapy for AIDS is a compound. Now with tumor immunotherapy, antibody therapy for PD-1 is also clinically used in combination with other drugs. The same road is the same. However, Western medicine is to first understand each component, the function of each component, and then put it together. The traditional Chinese medicine is already combined. Now it is to understand the functions of the ingredients and each ingredient. The purpose is to "know the truth and know why", improve the efficacy, reduce side effects, and precision medicine.
Whether the drug is effective or whether the ingredients are effective. Is it OK to do animal experiments? Comparing the history of disease research, animal models only simulate clinical, but they do not represent clinical. The current requirement for drug research is to provide more in-depth evidence if it is to be proven effective. That is, the mechanism of drug research, through which downstream disease function genes. That is the third question, the mechanism. This issue is currently the most cutting-edge area in traditional Chinese medicine research. The effective downstream mechanism of the drug, who is the downstream drug target. In this regard, Western medicine, whether it is an effective mechanism or a mechanism of side effects, is relatively clear. Our Chinese medicine research is still in its infancy.
To find the downstream drug target of the drug, find the disease function gene from the differential gene downstream of the drug. There are hundreds of different genes downstream of the drug. The search for disease function genes from these genes must be done on the cells. Because it is necessary to prove whether the gene changed downstream of the drug is a functional gene of the disease, the gene must be manipulated separately to observe its function. If done with animals, the cost of performing genetic manipulation on animals is many times higher than on-cell operations, especially cycles. The gene cycle on animals is too long. So the best path is to find this functional gene on the cell model of the disease and then verify it on the animal.
What is the cell used for? Going back to the history of disease research, this disease, the study believes that the disease has evolved and what cells have changed. What kind of cells do we use?
What is the detection indicator? Still returning to the research history of this disease, this cell is involved in the development of the disease, how does it change to participate in the development of the disease, whether it is proliferating, or is it apoptotic or differentiated. These are our test indicators.
Note that there are many, many diseases related to a disease. Which cell we use as my cell model in the design of the subject. From the perspective of the feasibility and success rate of the project, it is recommended to use cells that are genetically manipulated. This will do more with less.
PS: I hope that friends who have more exchanges with Jibo in learning and experimentation can pay attention to Jikai Gene WeChat and reply to the word "Jibo". 
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