It is likely to find a way to prevent disease recurrence

In a study published in the journal New England Journal of Medicine, researchers from US and Dutch found mutations of genes related to immune system in metastatic melanoma patients. These patients initially responded to the treatment against PD-1, but the disease relapsed after six months.

Research team from University of California at Los Angeles (UCLA), Jonsson Comprehensive Cancer Center and Netherlands Cancer Institute conducted exon sequencing for the tumor samples of four patients with metastatic melanoma before they received pembrolizumab drug therapy. The researchers also analyzed the protein coding sequence of tumor samples through recombinant mouse proteins after late recurrence. By comparing sequencing results of tumor samples before treatment and after relapse, they found the mutations associated with checkpoint blocking resistance.

The researchers found suspected mutations in three patients. In the body of one of them, they found truncation mutations which affected β-2-microglobulin (B2M) encoding gene. This mutation causes the expression of type I major histocompatibility complex (MHC) molecules, and the molecules can be recognized by CD8T cells immune system. Another two recurrent tumors showed function mutations of gene functions of JAK1 or JAK2 genes, and these two gene encodings interfere related kinases.

First author of the study, doctoral Jesse Zaretsky from Antoni Ribas Laboratory at the University of California at Los Angeles said, "These mutations make the tumor produce resistance to the way of immune system killing tumors. For example, JAK mutations are associated with interferon receptors and make tumors become insensitive to the signals of slowing down tumor growth and killing tumors."

The team established cell lines of recurrent tumor patients with JAK2 function-loss mutations. Making used of nCounter expression system of NanoString Technologies company, they found that JAK2 protein expression deletion after treatment, decrease of interferon-γ activity and protein yield reduction are all associated with antigen presentation and T cell activity. The researchers plan to focus on the study of JAK2 protein using recombinant dog proteins, as JAK2 protein becomes the new key of treating cancer.

Zaretsky said that more large-scale studies are needed to observe whether this kind of mutations identified in patients with recrudescent metastatic melanoma is common in patients receiving other disease checkpoint blocking therapy and to look for other potential resistance-associated mutations. Researchers are now creating cell line models to study the pathogenesis of these resistance mutations, hoping to find a way to prevent disease recurrence. Flarebio provides you with good-quality recombinant proteins including recombinant CDH12 at good prices.

Japanese scientists develop a new technology to analyze secondary structures of protein

The Joint Study Group of RIKEN and Japanese electronics companies announced on August 1st, 2016 that they successfully developed a nuclear magnetic resonance method (NMR method) which it is possible to analyze the secondary structure of protein without the use of isotopic label. The research involves many kinds of recombinant proteins like recombinant horse proteins.

Secondary structure of protein means that polypeptide chain of a protein has a conformation which repeated regulation, and it is the basis of overall shape of a protein. The representative secondary structure of protein is β-sheet which is composed of extended polypeptide chain and can be divided into two types: parallel and antiparallel type.

It has been demonstrated in previous studies that the abnormal deposition of β-amyloid is one of the pathogenesis of Alzheimer's disease, while the β-amyloid protein is rich in β- sheet configuration. Because β- sheet configuration is very messy, it is difficult to use X-ray diffraction and cryo-electron microsocopy to analyze. Further, since the β-amyloid is not insoluble in water, so it can't use the NMR assay solution. In order to analyze these types of proteins such as β-amyloid protein, it is needed to artificially increase the isotope-labeled sample of carbon isotope 13C and nitrogen isotope 15N to conduct solid MAS NMR. But because the natural existing rates of 13C and 15N are only 1.1% and 0.36%, so the range of use is very limited.

The research team previously used to develop ultra-small NMtR sample tube which can rotate sample at a high speed. The researchers also successfully developed 14N/14N-related NMR testing method which can obtain the space information among nitrogen isotope 14N atoms which have the isotopic abundance of 99.64%.

In this study, the team members developed two tripeptide alanine (Alanine tripeptide) microcrystalline sample which respectively had parallel formula β- sheet and antiparallel β- sheet structure. They used 1 mg of the sample to conduct 14N / 14N-related NMR method. It was found that only in alanine tripeptide with antiparallel β- sheet structure, 14N / 14N-related signal could be detected in the space of the β-strand. This also proves that the method can identify the type of parallel β-sheet and antiparallel β- sheet. Flarebio provides you with superior recombinant proteins such as recombinant Nrg2 at good prices.

New-type of small molecule switch can control the activity of proteins

According to recent report of the American University of Pittsburgh website, the school research team developed a new technology that using small molecule phosphine as a "switch" to control the activity of the protein. The technology was developed using various recombinant proteins such as recombinant mouse proteins, and it provides a powerful tool for people to better study the biological processes of molecular behavior.

Protein is a kind of elements with the most species in vivo, and it is also one of the most important elements. The growth of teeth, bones, skin and organs and the generation of enzymes and hormones all are inseparable from the proteins. But for living cells which have been completely specialized, the use of proteins varies, and the way of interaction among the systems is different. For scientists, it is a great challenge to determine how they work.

Protein is consisting of long chains of amino acids. In the experiment, the researchers applied a non-natural amino acid in a particular position of certain proteins to make them lose activity, which is called "protection". When they treated the cells with a phosphine reagent to make them to express "protected" proteins, unnatural amino acids could be converted back to natural amino acids, which were out of protection back to active natural type proteins.

The research team used the small molecular switch in relevant processes of four kinds of cells: opening the luciferase activity to trigger cell bioluminescence; activating a protein initially found in jellyfish to cause enhance of fluorescence reaction and converting blue light into green; In the process of protein translocation, they used the small molecular switch to assist proteins to move among cells; In gene editing and DNA recombination, they used the switch to control the insertion and removal of genetic information.

This technology allows researchers to observe the activities of the protein and also helps protein separate from cellular activities. It helps researchers better understand their role and the interaction relationship between it and other ingredients components.

Chemistry Professor Alexander Dai Tesi of the school said that using a drug-like small molecule as external trigger to precisely control the cell-specific protein functions contributes to revealing the activities related to a single protein. A switch which can rapidly activate proteins allows us to learn more about their behavior and function."

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Proteins modified by ELP can effectively improve the circulating half-life

Compared with small molecule drugs, protein drugs have the advantages of high specificity, high activity, low toxicity and so on. There many recombinant human proteins drugs in the market. However, the circulating half-life of most protein drugs in vivo is short with low bioavailability and great side effects. Using modified protein drugs (PEG-based) or employing source albumin (HSA) fusion protein drug (HSA fusion) with polyethylene glycol (PEG) is a common way to improve the above problems, but there are obvious shortcomings, such as: biological activity of the outcomes is significantly reduced; complex process of production; low yield; high cost. Therefore, how to improve the efficiency of circulating half-life of proteins in vivo and the treatment is a very challenging biomedical problem.

Gao Weiping Study Group at Tsinghua University takes the lead to come up with a new, universal, simple and efficient method of elastin-like polypeptide fusion (ELP fusion) to design for precise protein - polymer conjugate. By fusing elastin-like polypeptide with interferon -α and using Escherichia coli to produce IFN-ELP fusion protein can get high yield and low cost, and it also keeps the biological activity of IFN-α. Model tests in mice found that proteins modified by ELP can effectively improve the circulating half-life in vivo and residence condition of tumor, eventually significantly improving the outcomes of patients and improving the survival rate of mice.

This method is expected to become a new strategy for protein modification drugs, improving drug stability, improving drug half-life and enhancing the therapeutic efficacy.

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New function of proteins has been found

Researchers at UT Southwestern Medical Center have discovered new uses of RNA binding proteins through the research of recombinant dog proteins, and the findings reveal the potential treatment options for neurological diseases and related disorders (such as autism, epilepsy, and certain types of cancer). "This discovery enables us to think from the other side: whether our newly-discovered RNA binding protein dysfunction leads to these deficiencies?" said Dr. Michael Buszczak, author of the study and an associate professor of molecular biology.

The research article was published in the journal Developmental Cell, and the results showed that: Rbfox oversees the regulation role of mRNA in the synthesis of protein engineering. Taking Drosophila as the study target, the researchers found that Rbfox1 protein has a regulatory role in the process.

Gene encoding process, i.e. the process of splicing exon into mRNA, Rbfox1 protein plays a key role. Good transcription process makes the translation success rate of protein doubled. Splicing occurs mainly in the nucleus site - the study found that the nucleus contains many Rbfox1 proteins. But mutating Rbfox1 proteins were also found in the cytoplasm, and the function of this part of protein was not previously known. "We found that cytoplasmic Rbfox1 inhibits the synthesis of certain proteins," Dr. Buszczak said.

The first author of the study, molecular biology graduate student Arnaldo Carreira-Rosario at UT Southwest found that Rbfox1 can bind to specific mRNA molecules to prevent them to be translated into proteins. He is also very good at producing recombinant proteins such recombinant horse proteins. If Rbfox1 protein is lost, then the mRNA molecules would no longer be suppressed, leading to abnormal cell growth and even cancer.

The researchers found that cytoplasmic Rbfox1 proteins are necessary for the development of germ cells of Drosophila. "Without this protein, the differentiation of germ cells is blocked in a special stage and will not go down. They can't differentiate into mature eggs," Dr. Buszczak said. Not being able to form mature eggs will result in sterile of fruit fly. In other cases, it will lead to inappropriate cell proliferation, which formed a cancer.

Dr. Mani Ramaswami says that the study finds the link among Rbfox1 protein function and neuronal development and function. Rbfox1 protein may be important in the development of program of neurological disorders. "We believe that after Rbfox1 protein is inactivated, it will affect the expression of certain proteins and ultimately cause disease, but it does not affect the process of RNA splicing," Dr. Buszczak representation. "If this interpretation is correct, then it will partly affect the treatment regimen of some diseases."

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ZMYND8 protein is able to inhibit the expression of tumor metastasis-related genes

Although this protein reads like a license plate number in European countries very much, ZMYND8 protein has been shown to have the effect of inhibiting metastasis of prostate cancer-related genes. The findings mainly came from the research on cell study and recombinant mouse proteins, and they were published online on July 28th in the journal Molecular Cell.

"These findings are quite important because metastasis is a complex process, and studying tumor metastasis is a big challenge for doctors." Dr. Min Gyu Lee is an associate professor of molecular and cellular oncology. He said, "Tumor metastasis is very important. We need to know the key of how tumor cells obtaining the ability of metastasis and invasion. Understanding how this process happens is crucial for doctors to prevent tumor metastasis. We believe that this study could help medical researchers better know and understand the process."

Dr. Lee's research focuses on the modification of proteins using recombinant proteins, and this step is crucial for gene regulation; wherein the acetylation and methylation of tumor development is the most common. Dr. Lee's research group believed that ZMYND8 is the "reader" of histone. Identifying histone modifications is likely to affect gene expression.

"The effect of histone acetylation and methylation on gene expression may receive the impact of specific binding proteins," said Dr. Lee. They found that ZMYND8 is the "reader" of histone marker H3K4mel and H3K14ac, and both of them are related to tumor metastasis-related genes.

The research team also noted that ZMYND8 also has synergy with another type of tumor marker "Eraser" JARID1D. Mutual cooperation between them can inhibit tumor metastasis-related genes. "These findings reveal an unknown mechanism of tumor metastasis suppressor, i.e. ZMYND8 genes can inhibit the expression of tumor metastasis-related genes through reading histone markers H3K4mel and H3K14ad its synergy with JARID1D."

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A novel therapy: to decrease antioxidants to tumor cells

A new study shows that reducing levels of antioxidants in pancreatic cancer cells would help to kill cancer cells, providing a new strategy for the treatment of this infamous fatal disease. The Leng Quangang research team was led by Professor David Tuveson who is very interested in producing recombinant proteins such as recombinant horse proteins.

Each cell would produce oxides and antioxidants: when the cell is healthy, both of them would stay in balance. What the treatment of Leng Quangang research team hopes to develop is to make cell die in malignant stage or before by increasing intracellular levels of oxides.

When the cell finds the oxide is superabundant, it will follow an established principle which is called apoptosis to commit suicide. One of the methods of increasing oxide levels in cancer is to reduce the levels of antioxidants therein. How to do this to best without harming healthy cells? The researchers focused mostly on a protein called NRF2, which can destroy the balance between the oxide and antioxidants within the cell.

When NRF2 is activated, a compound called glutathione would be synthesized in the cells. It is an important antioxidant. So, reducing the activity of NRS or knocking it becomes a matter of course. However, due to two reasons, it is difficult to be done. One of the reasons is that it is a transcription factor, a protein that regulates other genes. The researchers used to use recombinant dog proteins to conduct part of the experiment. Transcription factors are notoriously difficult to be regulated by target drugs. "But in any case you might not want to knock it, because NRF also regulate hundreds of different genes in addition to promoting the synthesis of glutathione." Chio said. No one can knock out a gene which affects many cellular processes.

Tuveson, Chio and other colleagues proposed alternative strategies after conducting experiments on pancreatic cancer cells of animal model in the laboratory and tried out several therapeutic measures. Making use of a class of pancreas organs, they observed the situation after NRF2 was knocked out. The experiment was divided into normal group, pre-cancerous cell group and cancer cell group. Pre-cancerous cell group showed kras mutations. This gene is mutated in almost all human pancreatic cancer cells. In addition to gene mutation, a gene which made p53 gene inactivating in cancer cell group also showed mutation. p53 gene is a powerful tumor suppressor gene. In most human malignancies, these two genes would have mutated.

These experiments give an important clue: when NRF2 is lost, the translation mechanism within the cell becomes very sensitive to the balance between oxide and antioxidants. Translation is the process of cells creating proteins according to genes. What is essential is that normal cells are unaffected. This means that as long as reducing the levels of antioxidants, the protein synthesis in pre-cancerous cells and cancer cells are affected, while normal cells are not affected. This could become a powerful therapeutic tool. Flarebio provides high-quality recombinant proteins such as recombinant APP.