miRNA controls the noise of protein expression

It is well known that some microRNAs can downregulate particular genes. However, for a more extensive use of these small non-coding RNAs, people are still not too clear. A new study shows that miRNA can act as a damper of genomic noise to control the changes of protein expression. The results are published in the journal Science on April 3. There are also other studies about recombinant proteins published in the same journal.

The universality and conservatism of miRNA and its tendency of slightly inhibiting the vast majority of their targets make some people speculate that the function of miRNA is precisely controlling of gene expression among cell populations. In this study, researchers from the Massachusetts Institute of Technology (MIT) and the Humboldt University used mathematical modeling and synthesis of genetics to prove miRNA does provides this type of noise control.

To test the function of the endogenous miRNA, researchers used dual fluorescent protein reporter system to quantify the protein levels and volatility of mouse embryonic stem cells, in which two different reporter genes (ZsGreen and mCherry) are transcribed by a common bidirectional promoter. And recombinant horse proteins and recombinant dog proteins are used. On mCherry reporter gene 3'UTR contains some variation and multiple miRNA binding sites, and researchers used flow cytometry to quantify single-cell fluorescence.

They studied the effects of miR-20a on designing target site in reporter gene. Compared with the control, in cells with low expression of the reporter gene, the noise reduced; while in cells of high expression, the noise increased. It is noteworthy that when the reporter gene of miR-20a target site is ideal or there are multiple sites in the 3'UTR, the change of this noise is particularly evident.

To explore these mechanisms which seem to have opposing effects to each other, the researchers created a mathematical model to decompose the total noise into intrinsic noise (i.e. changes of protein expression produced the random process of protein production as well as external noise (i.e. the changes produced by fluctuations of external factors).

This model predicted the effects of miRNA regulation on different types of noise, compared with the genes which were not regulated, intrinsic noise of genes which were regulated by miRNA reduced. Meanwhile, miRNA regulation was expected to increase the external noise. Taken together, this model predicted that the net effect of inherent noise reduction and external noise increase will result in the reduction of low-expressed total noise, while the total noise of high expression increased.

To test this prediction experimentally, the researchers changed the reporting system by making the two reporter genes contain the same 3'UTR, while their expression difference only came from the processing of each gene, namely the inherent noise. They found that the regulation of miR-20a reduced the intrinsic noise, which was consistent with the prediction of mathematical model. Further experiments showed that genes regulated by multiple miRNAs experienced a more pronounced noise reduction. Flarebio provides different recombinant proteins such as recombinant CDH10 for your research.

The researchers believed that these results indicated miRNA make sure of the accuracy of protein expression and explained the phenomenon that is commonly observed that endogenous gene is targeted by a plurality of miRNA combinations as well as preferential of genes with low expression.

Denosumab may prevent women carrying BRCA1 mutation from suffering from breast cancer

Recently, a study published by Australian researchers in the journal Nature Medicine indicated that a drug called denosumab may prevent women carrying BRCA1 mutation from suffering from breast cancer. The real effect of it still needs more research using recombinant horse proteins and recombinant dog proteins.

Women carrying the BRCA1 gene mutation have a very high health risk, because the mutation can significantly increase the risk of suffering from invasive breast cancer and ovarian cancer. Currently, many of such women choose to have surgery to remove breast and ovarian tissue in order to fundamentally eliminate the cancer. The famous American actress Angelina Jolie is one of them. However, if we can prevent the occurrence of cancer in these high-risk women without surgery, it will undoubtedly bring a significant improvement in their quality of life.

Australian researchers precisely identified the tumor precursor cells which may be cancerous in the future by analyzing the breast tissue of BRCA1 gene mutation carriers. These pre-tumor cells are very similar to the real tumor cells. They can proliferate rapidly, and it is easy to accumulate DNA damage; these characteristics make them easy to become cancerous.

The researchers found that these tumor precursor cells all express a protein called RANKL. Then recombinant protein found its role. This discovery is an important breakthrough, because drugs which inhibit RANKL protein signaling pathway have been used in clinical practice, such as monoclonal antibody drug denosumab. Denosumab has been approved for the treatment of osteoporosis and unresectable giant cell tumor of bone. Therefore, the researchers examined the impact of this RANKL inhibitor on tumor precursor cells in breast tissue carrying BRCA1 mutation.

The results suggest that inhibition of RANKL signaling pathway can close the proliferation of tumor precursor cells in breast tissue carrying BRCA1 mutation. Meanwhile, in the mouse model, this inhibitor can slow down the occurrence of breast cancer.

"We believe that this strategy can delay or prevent the BRCA1 gene mutation carriers from suffering from breast cancer," corresponding author Professor Geoffrey Lindeman at Australia Walter and Eliza Hall Institute of Medical Research who are also interested in the development of various recombinant proteins such as recombinant Cdh26 said, "We have begun a clinical trial to further study the role of denosumab in preventing breast cancer."

A key enzyme plays an important role in the development of Parkinson's disease

Researchers from Johns Hopkins say they found two important new clues in the process of battling with Parkinson's disease: blocking an enzyme called c-Abl can protect specially-bred mice from suffering the disease, while the chemical marker of the second protein may indicate the presence of the disease and its severity. Their work not only provides a promising target for the drug development but also provides tools to more broadly accelerate Parkinson's disease research. The research results were published online on June 27 in the Journal of Clinical Research. This journal also published some other studies on recombinant mouse proteins and recombinant horse proteins.

Parkinson's disease is a progressive neurological disease which affects movement. Autopsies showed the c-Abl was very active in the brain of patients with the disease. In addition, in the study of specially-bred mice which were prone to the disease, the researchers found that the drugs which blocked the c-Abl may play a role in preventing or delaying the disease. However, assistant professor of neurology Dr Han Seok Ko at John Hopkins said, "Those drugs used in the study may also block other similar proteins, so we're not sure blocking c-Abl is the reason that prevent animals from showing symptoms or affect the disease progression."

The researchers' new experiment began from the condition that the mice were genetically modified so that they got the disease. If "knocking out" the gene carrying c-Abl, the symptoms of the disease will be reduced. Conversely, if changing the genes and increasing levels of c-Abl, the symptoms of the disease in mice will increase and the deterioration will accelerate. The researchers said the increase in the number of c-Abl also make normal mice suffering from Parkinson's disease.

To understand more about the mechanisms of disease, the researchers inspected the interaction between c-Abl protein and another protein α- synuclein. We all knew that α- synuclein clump in brain is a hallmark of Parkinson's disease. Researchers from Johns Hopkins found that the c-Abl adds a molecule called phosphate group to a specific site on the α- synuclein, while the continuous increase of c-Abl levels will lead to more α- synuclein aggregation and worsening of symptoms.

"We plan to study whether α- synuclein protein carrying a phosphate group at the site where c-Abl targeted on can be used to measure the severity of Parkinson's disease. There is no such biochemical measurements exist, and it hinders research on potential therapies of the disease," Dawson represented. More research would be done using recombinant Cdh2.

New breakthrough of cancer is expected to provide new therapy

Dr. Stéphanie Kermorgant from Barts Cancer Institute of Queen Mary College, London, UK (QMUL) and colleagues started to study what would happen to cancer cells without cell culturing from zebrafish and mouse. They found that the "integration" - protein that the cell surface and the surrounding tissues combine and have communication - plays an important role in the process of primary tumor remaining viable. The team explained that the known integrins participate in the "outside-in" and "inside-out" signaling, which helps cancer cells combine with surrounding tissues. Researchers got the results with the use of recombinant rat proteins and recombinant dog proteins.

However, they found that in the process of metastasis, the way the integrin takes is the signaling of "from the inside-in", which a signaling defense form is happening in cells. Integrin β1 and a protein known as c-Met accompanied each other in cancer cells during metastasis, the authors explained. Then, these two proteins move to a specific site within the cell, usually the parts of degrading and recycling cellular components. However, these two proteins make use of this site to send signal to other sites of cancer cells, triggering defense mechanisms of cell death. The researchers said it was the first time to identify the specific process of cancer metastasis. Various recombinant proteins such as recombinant Folh1 play their roles.

Next, the research team began to study what would happen if blocking β1 and c-Met two proteins into cells or transferred to a desired site of the anti-signal. In the test process of breast and lung cancer cells, the researcher found that the cells are less likely to metastasis, suggesting that β1 and c-Met played a vital role in the development of breast cancer. Dr. Kermorgant and his colleagues believed that their findings suggested that, preventing β1 from entering the cancer cells at the very start may be an effective way to fight cancer metastasis.

Integrin inhibitors have been used as a method of cancer therapy and have been tested. At present, the drug can be targeted to the function of integrin signaling activity of the surface of cancer cells. The research team said that this may explain why the efficacy of these drugs is so poor.

"Cancer metastasis is currently no cure and it is still one of the main goals of cancer research. Our research updates relevant knowledge on how the two key molecules communicate and survive and play their role together in cancer metastasis. "We hope this research can develop new drugs for preventing the spread of cancer in the body." Dr. Stéphanie Kermorgant says.

Expression levels of CD38 and CIP can significantly affect daratumumab sensitivity

Related studies have shown that anti CD38 monoclonal antibody daratumumab can treat severe relapsed / refractory multiple myeloma (MM). This antibody is well tolerated and has high single-agent activity. However, not all patients will respond to the drug, and even some patients eventually have more disease progression. A recent study published in the journal Blood was designed to investigate the effect of CD38 and the level of expression of complement regulatory protein (CIPs) before treatment on the response and whether this protein expression can lead to drug resistance. Recombinant dog proteins are used in the research.

The study included 102 MM patients who had received daratumumab monotherapy (16 mg / kg). The researchers found that at least a majority of patients with response (PR) before treatment had significantly higher levels of CD38 expression in MM cells, while patients who had no PR showed lower levels of CD38 expression. However, the cellular surface expression of CIPs, CD46, CD55 and CD59 was independent to clinical response.

In addition, after injecting daratumumab for the first time, CD38 expression of bone marrow and circulating MM cells decreased; after withdrawal of daratumumab, CD38 expression levels of MM cells rise again. In contrast, only at the time of disease progression, CD55 and CD59 expression of MM cells will increase. All-trans retinoic acid increased the MM cells CD38 levels of patients with resistance to daratumumab and reduced the expression of CD55 and CD59, which makes daratumumab mediated complement-dependent cytotoxicity significantly enhanced.

Together, these data demonstrate that the expression levels of CD38 and CIP can significantly affect daratumumab sensitivity. This reminds us that the next step should be to explore to MM combination therapy strategies which can change the expression levels of CD38 and CIP. For more information about proteins like recombinant App, you can visit Cusabio’s website.

High antibody levels can reduce the risk of heart disease

Can strong immune system resist a heart attack? The research team of patients with high blood pressure found that for those patients with higher antibody levels, regardless of other risk factors, they have lower risk of heart attack. They recommended that a blood test which measures antibody levels would help to assess a person's risk of heart attack. The study found an antibody which is called IgG in blood in hypertensive patients can reduce the risk of heart attack. Some recombinant human proteins also can reduce certain heart disease.

The study from Imperial College London in the UK has been published in the journal EbioMedicine. It describes how the team found the link between blood immunoglobulin G (IgG) antibody levels and the reduced risk of heart attack. Cardiology consultant physician and clinical researcher director Dr. Ramsay Khamis said, "It is a very exciting discovery that connecting a more stronger and powerful immune system to prevent a heart attack. At the same time, when giving a heart attack patient proper treatment, we have a new way to follow."

In their study, Dr. Khamis and his colleagues conducted a survey on patients with heart disease. The researchers analyzed the total IgG in the blood and another antibody which is called immunoglobulin M (IgM). They also examined oxidized low density lipoprotein (LDL) cholesterol or "bad" cholesterol in the blood LDL, which will promote antibody levels of atherosclerosis. The results showed that people with higher antibody levels were at lower risk of heart attack. The team was surprised to find that the strongest link of reducing the risk of heart attack was higher level of antibodies, and this is independent of other risk factors such as cholesterol and blood pressure.

This study focuses on the patients with hypertension. Previous studies also use recombinant dog proteins and recombinant horse proteins to conduct similar research. The research team now wants to find out whether there are links in other high-risk populations. The researchers pointed out that measuring blood IgG is relatively simple and inexpensive and yet to be further study. Their findings may show easier way for doctors to determine the patient's risk of heart attack. "We hope to protect humans from a heart trouble through improving the immune system." Some other recombinant proteins like recombinant Adam19 are offered by Cusabio.

The RNA-cutting method which is similar to the method of gene cutting

Researchers who found the molecular "scissors" which cut genes now have developed a similar method for targeting and cutting RNA. The new cutting tools should help researchers better understand the role of RNA in cells and disease. Some people think that it might be used to treat many diseases from Huntington's disease to heart disease one day. Various recombinant proteins have achieved their goal.

In order to develop the "Blade" aimed at this process, Zhang Feng from the Broad Institute in the United States led researchers to make use of CRISPR (clustered, short palindromic repeats at regular intervals), namely the system evolved by bacteria for confrontation pathogen. CRISPR had previously been used to edit DNA, but theoretically it should also be effective for RNA. The study was published in the journal Science. Zhang Feng said that his latest method - making use of C2c2 enzymes to target RNA -relies on existing natural systems, thus it may be more effective than approaches which need more control. Studies have not confirmed that C2c2 system plays a role in mammalian cells, but Zhang Feng said that the results which had not been released make him maintain an optimistic attitude. The application of recombinant human proteins also used to experience some tests.

Professor cellular and molecular medicine Gene Yeo at the University of California, San Diego said, "A large number of such tools will allow us to monitor and study the RNA. This will help us to treat RNA not only as an intermediate molecule between DNA and proteins, but also a tool for the treatment of diseases and developmental problems."

Gene contains double-stranded DNA which produces single-stranded RNA, while single-stranded RNA in turn produces necessary proteins for life. Many diseases are due to too much or too little protein. Theoretically, effects on RNA could help to push the levels of these proteins up or down, and therefore providing methods of treatment. For example, the levels of recombinant INSRR can lead to different health condition.

Compared with "tinkering" basic DNA, manipulating RNA would create fewer ethical concerns. Zhang Feng said that he has always been very interested on the development of RNA system. New research shows that C2c2 is originally a system targeted to RNA. And the same to Cas9 system targeted to specific RNA, C2c2 can be directly "targeted" to the expected RNA sequence, so it was less likely to show off-target effects.

PI3K protein inhibitor has great therapeutic effect for PanNET

Recently, researchers from Bellvitge Institute for Biomedical Research found an inhibitor of PI3K protein has a good therapeutic effect in pancreatic neuroendocrine tumors (PanNET). The study was published in the journal Clinical Cancer Research. More studies about recombinant proteins like recombinant dog proteins and recombinant horse proteins can be found in it. The research results greatly enhanced scientists' understanding of the role of PI3K signaling pathway in cancer and provide a new way for pancreatic endocrine tumor treatment of neurological and other tumors.

Pancreatic neuroendocrine tumor is also called islet cell tumors, and this type of pancreatic cancer accounts for about 2% of all newly diagnosed cases of pancreatic cancer. In the past 20 years, almost no better ways to treat this type of cancer, and PanNET heterogeneity also make the design of targeted therapies very complicated. Research shows that 16 percent of PanNET patients carrying mutations of PI3K signaling pathway and the researchers evaluated the activity of PI3K pathway tumor of samples of 40 cases.

The researchers found that no matter by genetic means or by means of pharmacological inhibition of specific PI3K isoform (also known as p110α), the effects all are sufficient to induce tumor cell death and inhibiting angiogenesis, thereby preventing tumor progression and metastasis. Compared with general inhibitors, this inhibitor with configuration specificity has a lower the toxicity to human body. The human body can accept higher doses to achieve the role of complete closure of PI3K signaling pathway.

PI3K inhibitors have been used in clinical practice. These findings all indicated that this new inhibitor is promising to become the treatment way of this vicious disease. The study also reveals new role of PI3K protein in cancer biology with the use of recombinant Cdh1.

The folding mechanism is a part of the genetic code

Theoretical physicists have recently identified biological sensational news: our body's genetic information is not only stored in the nucleotide sequence of the DNA and it partly depends on the way DNA folds into chromosomes. Specifically, the three-dimensional structure of DNA will determine gene expression. In fact, the biologists are already aware of the things above and with the use of recombinant proteins, and they even have found the proteins which assist to fold DNA. But now it is a bunch of physicists who for the first time reveal the true mystery and what they use are computer simulation tools.

Watson and Crick discovered the double helix structure of DNA in 1953 and determined our genetic information is stored in the base pairs composed of four basic groups - G, A, C, T. These sequences will determine which kind of protein will be produced in which cell. Some DNA in all the cells in our body is the same at first, but why they can differentiate different proteins to meet so many different organ functional needs? Our stomach cells may not produce proteins that can make the eyes brown, but they need to produce digestive enzymes. Then how does such a division mechanism work? It is a complex question which needs a lot of experiments using the technology of recombinant protein to solve out.

In the 80's, scientists found that the mechanism was controlled by the folding way of DNA inside the cells. Besides, environmental factors are also significant. For example, environmental stress can activate and silence some genes. DNA folding way determines which genes can be "read" in the cells. To make it simple, the genes folded in the most remote corner are "unreadable" and genes on the outside can be "read". In this way, different cells can determine which protein that should be synthesized to meet different needs. Prior studies have shown that the mutation ways of DNA are more than one: in addition to changing the DNA nucleotide sequence, changing DNA folding is another way. Changing the shape and the folding of DNA bases and the "read" nature, the final protein synthesis will also be affected. Recombinant KEL can show the process.

More and more scientists are doing research in this area. With the understanding of controllable DNA folding, the possibility that we can finally take advantage of it is getting a little bit larger. Related articles have been published in the academic journal PLOS ONE.

Intake of probiotics may be effective for the prevention and treatment of depression

Japan's National Medical Center compared intestinal bacteria of 43 severe depressed patients and 57 healthy people and found that the number of beneficial bacteria bifidobacteria and lactobacilli of patients with depression was significantly less than that of healthy people. The study results show that people who have less beneficial bacteria are at a higher risk of depression.

The current number of patients receiving treatment for depression is about 700,000 in Japan, and it is supposed that patients who do not receive the treatment presumably exceed the number of 3-4 times, and it is one of the main diseases which threat much to the health state of Japanese. It is generally believed that depression is caused by biological reasons such as neurotransmitter abnormalities, endocrine abnormalities and chronic inflammation, but depression is still not more understood. There are 1,000 kinds of human gut bacteria and the number is more than 100 trillion; the total weight is about 1 to 1.5 kg. These bacteria absorb nutrients, vitamins and protein synthesis from food to prevent outside pathogenic bacteria invade the body, bearing a very important task. Scientists can use the technology of recombinant protein to realize it.

The team took 43 patients with severe depression and 57 healthy people as the object of study. They gathered bifidobacteria and lactobacilli from the stool test personnel and used 16 s rRNA genes quantitative reverse transcription polymerase chain reaction (PCR) to analyze and found that the number of bifidobacteria in patients with severe depression was significantly lower than that of healthy subjects; the total number of bacteria of lactobacillus was also low. In related analysis, the percentage of patients with severe depression who were below critical value of bifidobacterium (109.53 in per gram of feces) was 49% (21/43 people), and that of healthy groups was 23% (13/57 people). The team also found that in tested subjects, the ratio of concurrent irritable bowel syndrome in patients with severe depression was significantly higher.

The research results which were published in the online edition of the journal Affective Disorder first report that a small number of bacteria may easily lead to an increased risk of depression. And the study also finds that stress-induced mental illness such as irritable bowel syndrome is also related with beneficial bacteria. Intake of probiotics such as yogurt and lactic acid drinks may be effective for the prevention and treatment of depression. Then whether some recombinant proteins such as recombinant Lrfn1 also can do some help?

Jardiance can both reduce cardiovascular events and relieve renal dysfunction

Eli Lilly and BI today announced that their type 2 diabetes drug SGLT2 inhibitor Jardiance also can alleviate renal dysfunction besides displaying the cardiovascular benefits. This is the secondary endpoint of prospective clinical trial called EMPA-REG. The primary end point of this four-stage clinical trial involved in 7,000 people is cardiovascular events. After tracking for average 3.1 years, the results showed that compared with placebo, the combination of standard therapy and Jardiance were more capable to reduce myocardial infarction, death from heart disease and stroke risk. What is announced today at ADA and published in the NEJM this experiment is the secondary endpoint. And the combination of standard therapy and Jardiance reduced 39% of renal injury or worsening of renal impairment (urine protein / creatinine ratio> 300, creatinine doubling) compared with placebo. More importantly, Jardiance reduced the number of patients who started dialysis by55%. Jardiance becomes the first hypoglycemic drug which can both reduce cardiovascular events and relieve renal dysfunction after a lot of research with different recombinant proteins.

Although this is the first hypoglycemic drug that can relieve renal dysfunction, there are a few precautions. First, these observations are secondary endpoint of EMPA-REG but not the main outcome indexes of the trial; second, these indexes of renal function are also indexes of blood glucose, so they just have no great distinction. Delay of kidney dialysis is the real index for patients' living. Although Jardiance reduces the risk by 55%, the absolute risk is not great from 0.6% to 0.3%. The main reason is that the majority of them are patients with early kidney damage and the tracking time is only 3.1 years which was much shorter.

However, this is still an important progress. 35% of people with diabetes would have kidney dysfunction, which is a major complication of diabetes. Renal dysfunction is a great market and it is estimated that 10% of Americans have varying degrees of renal dysfunction. There are no drugs which are very effective to treat renal dysfunction except some traditional antihypertensive drugs, so drug with new mechanism is an important contribution to this population.

Now there are two types of drugs which can improve cardiovascular event and Jardiance has been shown to improve renal dysfunction. Although the efficacy of these drugs to improve the prognosis is still relatively minor, this undoubtedly establishes a higher standard for future hypoglycemic drugs. Later, hypoglycemic drugs which only lower blood glucose may be not enough. That's why Merck recently doubled safety trials into efficacy test and stopped the long-term development of DPP4 inhibitor.

Before people are not optimistic about SGLT as hypoglycemic mechanism and think that cannot be alone to treat diabetes glucosuria out. Diabetes is not just glucose, but SGLT would not just inhibit glucose reabsorption. With our in-depth understanding of diabetes, we would know that diabetes will prove to be the same as and cancer which is a combination of a variety of diseases. In the future, the pre-clinical studies need more complex scientific hypotheses and optimization methods, and clinical development needs to draw precise medical experience of the tumor. With the help of recombinant mouse proteins like recombinant Cdh8, we can find the real beneficiaries according to the mechanism tags, and not all people with glucose abnormality can use.

Bacteria have complex enzyme as early as 3.4 billion years ago

A study recently published in the journal Cell Biology Chemistry reveals that 3.4 billion years ago, the ancestors of all bacteria may have enzyme complex, which is only 600 million years later than the origin of life on Earth. This discovery is amazing because scientists used to conclude that the bacteria didn't evolve until much later even 1 billion years after the origin of life. There are also other studies on expressions of recombinant mouse proteins.

Modern enzyme and molecules which they interact with are in correspondence like a lock and key. They usually only "work" for one reaction, but they can get the job done very well. Instead, Michael Harms from the University of Oregon of the United States said that earlier enzymes are "very sloppy" and don't have a relationship of lock and key with the molecules. There are many "pocket" in their structure which can seize a variety of different chemical substances and control many reactions, but none of the tasks can be well executed.

In order to study when modern enzyme appeared, Reinhard Sterner and colleagues from the University of Regensburg, Germany rebuilt a kind of enzyme consists of 4 parts in accordance with the appearance they may seem prior to isolation of modern bacteria and archaea bacteria. This enzyme called tryptophan synthase, aided the generation of a kind of amino acids which are essential to bacteria, archaea, plants and fungi. First, before importing the sequence into the computer program which finds similarities among them, the researchers analyzed the genes that encode this enzyme in modern bacteria and archaea. They then conducted thousands of simulations on the possible appearance of ancient DNA sequence which generated modern genes.

Based on the way that major bacterial populations separated from each other, the program locks one of the most-likely sequences. The team members inserted this "redivious" gene into modern E. coli cells. The gene can copy a large number of genes which were much like the modern version of enzymes. Harms said that this indicates that the time when the bacteria lost their "sloppy" protein was much earlier than people had expected. Meanwhile, DNA residue from billions of years ago does not exist, so this rebuilding experimental study is the only way to study ancient genes. Researchers also can produce some recombinant rat proteins to simulate the process.

However, Mathieu Groussin from the Massachusetts Institute of Technology thought that if researchers can reconstruct some of the other possible protein rather than the most-likely proteins, they would have more confidence in their results. In this case, they will know whether other possible sequences also had a functional protein. More kinds of recombinant proteins such as recombinant CDH12 can be found at Cusabio’s website.

The drug inotuzumab ozogamicin make most ALL patients be able to receive stem cell transplantation

The randomized three phase clinical trials of the drug inotuzumab ozogamicin showed the majority of statistically significant acute lymphoblastic leukemia (ALL) patients relapsed after receiving standard therapy are eligible to receive stem cell transplantation. Inotuzumab ozogamicin, also known as CMC-544, can bond with antibody targeted at CD22. This antibody is a protein that can be found in the surface of 90% of ALL cells. Once drugs are connected to CD22, ALL cells will attract it to human body and ultimately die. There are also other research about in-vivo effect of recombinant proteins in ALL.

This study shows that the complete remission rate of drugs is up to 81%. Compared with standard therapy, its disease progression-free period was significantly prolonged and overall survival was improved significantly. The research was conducted in MD Anderson Cancer Center at the University of Texas. The findings have been published in the June 12 online edition of the New England Journal of Medicine.

Dr. Hagop Kantarjian at Leukemia Group said 41% of ALL patients in the study can continue to receive a transplant after taking inotuzumab ozogamicin, while only 11% of patients can receive a transplant after taking the conventional standard therapy. Taking into account that stem cell transplant is the only hope of cure, the ability of Hagop Kantarjian increasing the probability of a patient to receive a transplant is very encouraging.

Donor stem cell transplantation is generally considered to be a cure for this vicious leukemia, and there will be 6500 people diagnosed with the disease in the United States in 2016. However, patients must complete remission to accept the post-transplant. The existing complete remission (CR) rate of patients who are just diagnosed with B-cell ALL is 60-90%. However, most of these patients will relapse, and only 30-50% of patients can achieve long-term disease-free survival in more than three years.

Dr. Kantarjian said that the complete remission rate of standard chemotherapy in patients with early relapse program was only 31-41%, while it was only 18-25% for patients with late recurrence. The complete remission rate of inotuzumab ozogamicin clinical trials in patients is 58%, which was higher than previously reported, and it may because the patients received treatment in later period.

Moderate side effects were found in the trials. The most common side effect is reduction of blood cells, which leads to a decrease in blood cell abnormalities. And liver toxicity all existed. The study was funded by Pfizer. Cusabio also provides other products such as recombinant CDH2 to support more accurate research results.

High-sensitivity cardiac troponin I assay is beneficial to rule out acute myocardial infarction

A recent study published in the journal JAMA Cardiology shows that detection of high-sensitivity cardiac troponin I can help to identify or rule out whether a patient with chest pain emergency has suffered from myocardial infarction. Although the current US guidelines haven't recommended the application of high-sensitivity cardiac troponin I testing, the technology can indeed rule out acute myocardial infarction more quickly. The journal also published some other famous studies on the development of different recombinant proteins, such as recombinant human proteins, recombinant dog proteins, recombinant rat proteins and recombinant horse proteins.

Johannes Tobias Neumann from the University Heart Center in Hamburg of Germany and other researchers analyzed three queues (BACC, ADAPT and APACE) and found an optimal troponin I threshold for the diagnosis of NSTEMI. They developed and verified a more accurate method of diagnosis and exclusion of acute myocardial infarction.

First, the researchers used the data of BACC queue and found the optimal threshold 6ng / L and developed a fast approach of diagnosis of acute myocardial infarction. European Society of Cardiology guidelines suggest emergency physician conduct high-sensitivity cardiac troponin I tests after the patient reaches the hospital and three hours later. The results show that using the critical value of troponin diagnostic applications resulting type 1 NSTEMI negative predictive value is 99.8% (95% CI, 98.6-100), only one false-negative findings; negative predictive value of all NSTEMI patients is 99% (95% CI, 97.5-99.7) and four false-negative cases were found.

When using 1 hour diagnostic method to measure levels of cardiac troponin I, the negative predictive value 1 type NSTEM was 99.8% (95% CI, 98.6-100)1 hour later; 3 hours later it came to 100% (95% CI, 98.5- 100). In all NSTEMI patients, 406 cases (39%) of patients can be discharged, among which four patients were false-negative (negative predictive value 99%; 95% CI, 97.5-99.7). The results were very precise and recombinant APP played an important role.

When using threshold troponin diagnosis of myocardial infarction, the positive predictive value of one hour diagnosis of Type 1 NSTEMI I was 82.8% (95% CI, 73.2-90), and 3 hours later it came to 78.6% (95% CI, 69.8- 85.8). In all NSTEMI patients, the positive predictive value of 1 hour 87.1% (95% CI, 79.6-92.6), 3 hours of 84.6% (95% CI, 78-89.9).

The researchers identified the method in ADAPT and APACE queue. In ADAPT queue, 1748 patients received two hours of law verification and 249 cases of NSTEMI were found. Admission negative predictive value was 99.6% (95% CI, 99.1-99.9), and 2 hours later it was 99.7% (95% CI, 99.2-99.4). In the diagnostic process, the positive predictive value was 81.5% (95% CI, 75.3-86.3). APACE queue used a similar method of one hour and three hours. In the queue, negative predictive value on admission was 98.6% (95% CI, 98.6-99.2), and 1 hour later it was 99.2% (95% CI, 98.4-99.2 ) and 99.1% (95% CI, 97.1-99.8) after 3 hours; 1 hour later the positive predictive value was 80.4% (95% CI, 75.1-84.9) and 3 hours later it was 68.8% (95% CI, 59.2- 77.3). Transmembrane protein plays an important role in basic physiological processes, including molecule transport, signal transduction, energy utilization and so on. Cusabio offers recombinant proteins of good quality.

Get to know what cytokine recombinant protein is

Cytokine (CK) refers to a class of small molecular proteins which are synthesized and secreted by immune cells (e.g. mononuclear - phagocytic cells, T cells, B cells, NK cells, etc.) and certain non-immune cells (e.g. vascular endothelial cells, epidermal cells, fibroblasts, etc.) via being stimulated and it has a wide range of biological activity. It belongs to recombinant protein with high purity, high activity and low endotoxin features, and it includes recombinant human protein, recombinant mouse protein and recombinant dog protein.

Cytokines can be divided into the following categories by function:

1. Interleukin (IL)

This is a class of cytokines produced by a variety of cells and acts on a variety of cells. It originally got the name because it is produced by white blood cells and plays a role in leukocytes and now it continues to use this name.

2.Interferon (IFN)

It is named because of its ability of interfering with viral replication. It has a very wide range of biological activity and plays an important role in the immune response and immune regulation. It is one of the major pro-inflammatory cytokines. Interferon is divided into: I type (seven kinds, such as IFN-α and IFN-β) and type II (only IFN-Y).

3. Tumor necrosis factor (TNF)

It is named because it can both directly kill tumor cells in vitro and in vivo. There are about 30 members in his family. Its main members include: TNF-α, a single-core factor mainly by monocytes and macrophages; TNF-β, one kind of lymphokines and it is mainly produced by lymphocytes and NK cells produce, and its biological activity is similar to TNF -α.

4. Colony stimulating factor (CSF)

A group of cytokines in vivo and can selectively stimulate hematopoietic progenitor cells to proliferate, differentiate and form a cytokine lineage cell colonies, including macrophages CSF, granulocyte CSF, macrophage / granulocyte CSF and stem cell factor.

5. Growth factor (GF)

A class of cytokines which can mediate different types of cell growth and differentiation. According to their function and different the cellular effects, they are named as transforming growth factor (TGF), nerve growth factor (NGF), epidermal growth factor (EGF), vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF) and the like.

6. Chemokine

A class of cytokine family which has different target cells chemotactic effect and can be secreted by certain white blood cells and tissue cells. It is a family of proteins including more than 60 members. Most members contain four conserved cysteine (C). According to its N-terminal cysteine arrangement, it can be divided into four subfamilies: CXC, CC, C and CX3C.

You can visit Cusabio’s website to find more recombinant proteins.

A protein "switch" that can cut off the blood supply pathway

A recent British study found that regulating a signaling protein can prevent the formation of new blood vessels around the cancerous tissue of prostate cancer, thereby cutting off the supply pathway of nutrients for cancer and inhibiting tumor growth and cancerous proliferation.

Researchers from the University of Nottingham, Bristol University and other institutions said in a report which was published in the journal Oncogene on the 10th that they had studied vascular endothelial growth factor, which is a signaling protein. It can exist in two forms and play two roles which can both promote the growth of new blood vessels and inhibit their growth.

Through making use of recombinant mouse proteins and recombinant horse proteins, the researchers found that prostate cancer cells will produce such factors which promote the growth of blood vessels. They make new blood vessels to generate new cancerous tissues about around for transporting oxygen and other essential nutrients.

Based on this finding, the researchers developed a compound which can "switch" the "switch" formed by vascular endothelial growth factor so that all the factors exist in the forms of inhibiting blood vessel growth. In animal experiments, the researchers injected the compound to mice with prostate cancer three times a week, and the tumors stopped growing and gradually began to shrink, while the mice didn't show obvious discomfort. This is how recombinant proteins plays their role in the experiment.

The researchers said the next step they will test whether the therapy are valid on a human patient and confirm the therapeutic effect on other types of cancer. If all goes well, a biotechnology company affiliated to the University of Nottingham would set out to develop oral or injectable drugs and take them as a new long-term maintenance treatment for cancer patients to control growth of cancer cells and inhibit its spread to other organs.

The present developing situation of CRISPR/Cas9 gene editing technology

The development of genetic editing technology CRISPR / Cas9 is just like the advent of PCR technologies. It not only opened a new door for the academic community, but also be continuously concerned by the mass media. CRISPR / Cas9 gene technology can conduct modifications, knock, knock and the like at fixed point. More importantly, CRISPR can complete genetic editing with the method of high throughput. What's more, the operation is simple and the cost is low. These features make the CRISPR / Cas9 a good choice for gene editing. Therefore, MIT Technology Review called CRISPR / Cas9 technology "century invention".

The subversive role of CRISPR / Cas9 technology in the biological and medical fields naturally is sought after by the investment community, and the massive influx of capital was invested into the startup projects related to this technology. Currently, there are three companies in leading position on the market, namely Editas Medicine, Intellia Therapeutics and CRISPR Therapeutics. Over the past three years, the three companies had financed a total of more than 660 million US dollars. In addition, they also obtained more than 500 million US dollars in revenue through cooperation with Novartis, Bayer and other well-known pharmaceutical companies.

Speaking of CRISPR / Cas9, we should also mention the controversy regarding its intellectual property ownership. Relevant legal proceedings are still in progress, but no one can place a stake in the ground. Ownership of intellectual property rights in the field of high technology has never been a black or white thing. In IT industry, Apple and Samsung all accused each other of violating its intellectual property rights from each other. Similarly in the field of biotechnology, the attribution of intellectual property rights has also been accompanied by controversy. For example, to obtain the ownership of EPO (a treatment for anemia drug), Amgen and Genetics Institute went to the court in the late 1980s to compete for intellectual property rights related to recombinant protein expression. In 1989, the federal district court in Boston judged that both sides had the patent and both of them violated intellectual property rights of each other; while in 1991, the first federal appeals court overturned the judgment of the Federal District Court in Boston and granted the intellectual property rights to Amagen. Likewise, MedImmune and Genetech had also played a lawsuit for their intellectual property related to mAb (monoclonal antibody) for many years.

Scientists uncover the important role of bone marrow pluripotent progenitor cells in genetic disease

Recently, key laboratory researcher Wang Qianfei from Beijing Institute of Genomics, Chinese Academy of Medical accurate genome and professor Yang Fengchun of the University of Miami Miller School of Medicine cooperated to reveal the critical role of germline newborn Bohring-Opitz syndrome mutations ASXL1 multipotent progenitor cells in the bone marrow stromal function bone development and maintenance, and the research was published in the journal Stem Cell Reports. There are also some other studies about recombinant proteins that were published in the famous journal.

Bone marrow stromal multipotent progenitor cell (BMSC) is a kind of multipotent progenitor cells with self-renewal and multi-lineage differentiation potential. The relationship between ostosis and fat cells in BMSC is crucial for normal bone homeostasis and the differentiation fate of these cells causes the abnormalities of body. Bohring-Opitz syndrome (BOS) is heterogeneity of genetic disease which causes death of young children, and it is characterized by severe growth retardation, upper fixed contractures, abnormal posture, feeding difficulties and severe mental disorders. Previous studies have found that the patients showed germline mutations ASXL1 gene BOS newborn, resulting in loss of function protein ASXL1. However, as enhancer of transcriptional activation / inhibition key regulator PcG and TrxG protein, the cellular and molecular mechanisms of ASXL1 causing gene mutation and inducing BOS still remains unclear.

The researchers found in Asxl1-targeted mouse model that Asxl1 gene complete knockout and conditional knockout of osteoblast progenitor cells cause severe bone loss and reduction of the number of bone marrow stromal multipotent progenitor cells; Asxl1-knockout bone marrow stromal multipotent progenitor cells showed self-renewal ability damage and change of differentiation tend. Transcriptome sequencing and bioinformatics analysis showed that some gene expression related to cell proliferation, bone development and morphogenesis changed; moreover, imprinted gene enrichment analysis of gene expression down-regulation of self-renewal of stem cells, suggesting that Asxl1 has regulation function on the dryness of bone marrow stromal multipotent progenitor cells. The researchers further found that the re-expression of Asxl1 makes the expression of the dry genes NANOG and OCT4 normalized, restoring the self-renewal capacity of bone marrow stromal Asxl1 knockout pluripotent progenitor cells. Besides, taking suitable recombinant rat proteins or recombinant mouse proteins is very important.

ASXL1 somatic mutations occur in myeloid malignancies, including myelodysplastic syndrome, chronic myelomonocytic leukemia and acute myeloid leukemia. The study reveals that ASXL1 plays an important role in Bohring-Opitz Syndrome by affecting the bone marrow stromal multipotent progenitor cell function and bone development, providing new opportunities for metabolic bone disease and clinical treatment of cancer.

New genome project raises the possibility of the emergence of costumed genetically-modified human

25 US scientists announced that they would raise one hundred million of US dollars this year to start the preparation of the Human Genome plans, and their objectives include synthesing a complete human genome in 10 years. There is report pointing out that the program is bound to lead to heated ethical arguments whether human life can be artificially synthesized. The genome of an organism refers to the complete DNA sequence in a set of chromosomes, i.e., the genetic blueprint. Synthesizing a complete human genome, in theory, would help to create humans of no parents with biological significance, and it also raises the possibility of the emergence of costumed genetically-modified human. At the same time, the research of recombinant human proteins should also be continued.

However, scientists say that their purpose is not here. They pointed out that synthetic human genome can be used in various ways, including developing portable bred human organs, giving cellular immunity to the virus re-encoded by the genome, giving the cells ability to fight through cell engineering technology, accelerating vaccines and drugs R & D process and so on.

Scientists from Harvard University, Massachusetts Institute of Technology, New York University and other leading academic institutions announced to carry out the project entitled "Human Genome Project-Write" after a meeting at Harvard University. Scientists admitted that this plan is controversial. They noted that the Human Genome Project had also been considered controversial, but now it is considered one of the greatest feats of exploration, which leads to revolution in the field of science and medicine.

The Human Genome Project lasts from 1990 to 2003, and it was focused on gene sequencing, allowing scientists to "read" the genome. Human Genome Project-Write is focused on the preparation of the plan to build the gene so that scientists can "write" genome. The primary objective of the human genome project is to reduce the cost of synthesis of large genomes to one thousandth of now in 10 years. According to reports, there are about 3 billion base pairs in the human genome. Constructing a complete human genome is extremely high at the cost of today's prices.

Scientists hope to raise one hundred million US dollars of fund this year to carry out this plan; funding the whole project is expected to require not more than three billion US dollars of the Human Genome Project. Cusabio also can provide its good quality of recombinant proteins for research support.

Japanese researchers find new mechanism of Lypd8 protein preventing inflammation

Japanese researchers discovered a mechanism - a protein called Lypd8 defends the body against inflammation - it is attached to the tail of the bacteria to stop its process. The findings were published in journal Nature.

Dysfunction of intestinal barrier is usually considered to be the main cause of inflammatory bowel disease. In mice with intestinal mucosal barrier injury caused by genetic changes, the bacteria invade the colonic mucosa and lead to a high susceptibility of intestinal inflammation. It has been clear that this mucosal barrier layer provides protection, but the mechanism of inhibition of bacterial invasion is not yet clear.

The research team, led by Dr. Ryu Okumura and Professor Kiyoshi Takeda from the Institute of Medicine, Osaka University, was specialized in Ly6/Plaur domain containing 8 (Lypd8), a highly glycosylated glycosyl phosphatidylinositol immobilized protein, which specific expresses and embeds into intestine in colonic epithelial cells.

Ulcers in patients with type colitis colonic epithelial cells have lower Lypd8 expression. In mice withLypd8 missing, flagellated bacteria such as Proteus mirabilis and Escherichia coli can frequently invade the intestinal mucosa. When exposed to dextran sulfate sodium (DSS), a compound that stimulates infectious inflammation, mice with Lypd8 deletion showed more severe DSS- excitation enteritis compared with those wild-type mice.

In laboratory studies with recombinant mouse proteins and recombinant rat proteins, Lypd8 protein bonds to bacterial flagellum which grows in semi-solid agar dish. This mechanism is about how Lypd8 inhibit bacterial movement and how the bacteria invade colonic epithelial cells of human host.

Chinese anti-tumor drug APG-115 is approved to enter US clinical use

Designed and developed by enterprises with a global intellectual property rights and functioning on the new target MDM2-p53, anticancer drug APG-115 of precision was approved to enter into the US clinic. The project is the fifth product that has entered the clinic of Ascentage Pharma products in the pipeline, and it is also the company's second product that has entered the US clinical-stage.

APG-115 is a small molecule inhibitor which is orally active with highly-selective targeting MDM2-p53 protein bindings. Preclinical data suggest that APG-115 can form a highly efficient suppression to sarcoma, primary liver cancer, primary gastric tumors, and animals test administration can allow tumor to disappear completely. Another study showed that APG-115 has a significant therapeutic effect on dry senile macular disease. Later, Ascentage Pharma will accelerate the progress of APG-115 clinical research for the early project into the market, providing more efficient and safe new treatments for clinical cancer and dry senile macular lesions.

Here is some introduction of Ascentage Pharma. Ascentage Pharma is a clinical-stage biopharmaceutical research and development company based in Chinese medicine and globally oriented. Ascentage Pharma mainly aims at international novel small molecule anticancer drugs targeted development and research and development trends to design, optimize and develop a series of original small molecule targeted anticancer drugs with global proprietary for the treatment of cancer, hepatitis B and anti-diseases of aging. It fills the domestic market of such technology research and product gaps and enters the international market of high-end medicine. Ascentage Pharma has developed a number of core technologies based on drug design and optimization areas targeting protein structure and has nearly dozens of international patents. Cusabio is also a biocompany which is engaged the development production of high-level recombinant human proteins. Up to now, there are five Ascentage Pharma products entered into the United States, Australia and Chinese clinical stage I-II stage. It has been focused on clinically validated cancer targets, and its main R & D product critical path pipeline apoptosis inhibitors of protein restart tumor cells apoptotic program by inhibiting IAP, Bcl-2 / Bcl-xL and MDM2-p53 and so on; the second and third generation inhibitor for the treatment of cancer appears kinase mutation body.

The protein regulation to stem cell division

Stem cells themseves have many regulatory factors that may react to signals from outside world so as to adjust their proliferation and differentiation, including regulation of proteins with cell asymmetric division and control of gene expression of nuclear factor. In addition, the number of stem cell division before terminal differentiation of stem cells is also constrainted by intracellular regulatory factors. This is called endogenous regulation.

1. Intracellular protein regulation of stem cell division:

The differentiation of Stem cells can produce new stem cells or differentiated functional cells. This differentiation asymmetry is due to the unequal distribution of the cell's own components and other surroundings. Structural proteins of cells, in particular cytoskeletal component, is very important for the cell development. As in Drosophila ovary, the regulation of asymmetric stem cell division is a organelle called shrink body containing many regulatory proteins such as membrane contractile protein and cyclin A. The combination of the shrink body and spindle body determines the part of cell differentiation, thereby making the essential ingredients that maintain the stem cell traits remain in the progeny of stem cells.

2. The regulation of transcription factor:

In vertebrates, the regulation of transcription factors to stem cell differentiation is very important. For example, in the occurrence of embryonic stem cells, the transcription factor Oct4 is required. Oct4 is a transcription factor of mammalian early embryonic cell expression, and it induces the expression of the target gene product FGF-4 and other growth factors. It can regulate the further differentiation of stem cells and the surrounding trophoblast through making use of paracrine function of growth factor. If Oct4 deleted, mutant embryos only can develop to the blastocyst stage, while the internal cells can't develop into the inner cell mass. Besides, leukemia inhibitory factor (LIF) can promote cultured mouse ES cell self-renewal, but it has no effect on human adult stem cells, indicating that transcriptional regulation between different species is not entirely consistent. Another example is that the Tcf / Lef family of transcription factors is very important for the differentiation of epithelial stem cells. Tcf / Lef is intermediate medium of the Wnt signaling pathway. When formating transcriptional complex with the β-Catenin, Tcf / Lef can promote skin cells to turn into a pluripotent state and to differentiate into hair follicles. In the industry of biology, recombinant human protein technology is developing prosperously due to the findings above.

Ten most popular databases of protein research

Previously/Before then, GEN website made a list of the most popular databases of protein research. See detailed list of the following:

1. BioGRID database was established in 2003. It is a database about protein - protein interactions and gene interaction database. Some wonderful studies on recombinant mouse protein also come from here.

2. DDBJ database was established in 1984. It is one of the world's three major DNA databases. Together with the NCBI's GenBank and EBI EMBL database, they compose of international DNA databases which updates daily exchange of data and information.

3. Database of Interacting Proteins is a database records protein - protein interactions which have been experimentally determined. This database is intended to provide a comprehensive and integrated tool for the scientific community to browse and efficiently extract protein interactions related to biological processes for network information interaction. In addition to details of cataloging protein - protein interactions, DIP is also useful for understanding protein function and protein - protein relationship, studying the properties of protein interaction networks, predicting benchmarking protein - protein interaction and studying the evolutionary of protein - protein interactions.

4. ExPasy database collects a lot of information, providing a range of tools and links for biologists to solve the puzzle of the information age.

5. Gepasi database is a modeling software about biochemical systems. It simulates the kinetics systems of biochemical reactions and provides a number of tools to model data to perform metabolic control analysis and linear stability analysis.

6. IntAct database provides a free, open-source analysis tool for intermolecular interactions.

7. KEGG database is an utilities repository with advanced features which helps to understand biological systems.

8. MINT is a database about molecular interactions. Data sources are mainly from scientific literature related to verification of protein - protein relatio.

9. SWISS-PROT is annotated protein sequence database and maintained by the European Bioinformatics Institute (EBI).

10. Uniprot database provides comprehensive and high-quality information of protein sequence and protein functions for the scientific community and it also offers them with some technologies of recombinant proteins.

TOR protein complex's unique architecture has just been revealed

We have always know for a long time that the protein TOR (Target of Rapamycin) - can control the cell growth, and it takes part in the development of cancer, diabetes and other types of diseases. Now there are also other studies on recombinant rat proteins show great progress.

Researchers from the University of Basel's Biozentrum cooperated with other scientists at ETH Zurich to examine the structure of mammalian TOR complex 1 (mTORC1) more detailedly and deeply. In the latest publication in the journal Science, these scientists just revealed the TOR protein's unique architecture.

Professor Michael Hall found the protein TOR about 25 years ago at the Biozentrum. This protein belongs to one of the most studied proteins in the whole protein kinase family, which is an important family of regulatory proteins controlling a lot of cellular processes. In mammals, TOR is called mTOR. It is of great importance for cellular signaling and involves in different diseases like diabetes, cancer and even neurodegeneration. There have many mTOR inhibitors been approved to be applied in therapeutic use, particularly for the treatment of allograft rejection and cancer.

However, although researchers have conducted extensive research on TOR in the past decades, their desire of uncovering detailed structure of the protein kinase and its partners has not been satisfied. Combining cryo-electron microscopy with crystallographic methods, the research team of Professor Timm Maier together with researchers from ETH Zurich now can provide new and novel insight into the protein complex mTORC1’s architecture and production of other recombinant human proteins.

Chinese scientists release new findings of mTORC1 protein complex

Cells would strictly control their metabolic processes to reconcile their growth and nutritional status according to nutrient levels in the environment. mTORC1 (mammalian target of rapamycin complex) is responsible for the integration of environmental and intracellular signaling and is responsible for the regulation of cell growth. mTORC1 is similar to the generation of recombinant human protein. mTORC1 dysregulation is very common in cancer, diabetes and other human diseases.

Amino acids will make mTORC1 transfer to the lysosome and activate there. People used to think that this activation is dependent on the amino acid Rag small GTPase, Ragulator complexes and v-ATPase (vacuolar H + -adenosine triphosphatase).

Research team from Fudan University and the University of California recently found that different amino acids on the regulation of mTORC1 are not the same. Leucine mTORC1 activation requires Rag GTPase, but activation of glutamine does not depend on Rag GTPase. The results were published in journal Science on January 7, and the paper's corresponding author is famous scholar professor Kun-Liang Guan.

Professor Kun-Liang Guan is mainly engaged in signal transduction regulating cell growth and tumor cell biology. He has been awarded many honors including the "MacArthur Genius Award" in United States. He is now currently a professor at the University of California, San Diego (UCSD) Department of Pharmacy, Institute of Life Sciences, Zhejiang University jointly Dean, Fudan University Biomedical Institute for Genomic Research laboratory of molecular cell Biology and PI.

The researchers knocked out cells RagA and RagB, but glutamine still allows mTORC1 to transfer to lysosomes. The study shows that this process requires v-ATPase but not Ragulator. In addition, the researchers also found that glutamine-induced activation of mTORC1 needs Arf1 GTPase to play a role.

This study reveals an mTORC1 activation cascade which is not dependent on Rag GTPase, showing the specific amino acid differences in the regulation of mTORC1. The article points out that leucine needs RagA and RagB to activate mTORC1, while glutamine doesn't need them. This difference appears to be an evolutionarily conserved regulation.

There are many cancer cell lines show increase of mTORC1 activity, and the growth of cancer cells is highly dependent on glutamine. It can be seen that mTORC1 activation induced by glutamine plays an important role in the growth of normal cells and tumor cells, was also occupied in the study and development of recombinant mouse protein.