The molecular mechanism of SF3B1 mutations leading to RNA splicing disorder

As a key step in the RNA processing process, the accuracy of RNA splicing is one of the prerequisites for the normal expression of a gene. The disorder of gene expression caused by RNA splicing is an important reason for the occurrence of multiple diseases. In recent years, high-throughput sequencing technology has detected a variety of splicing factor mutations in various tumor cells. These mutations have different effects on RNA splicing, leading to abnormal expression of downstream genes. SF3B1 / Hsh155 are a key factor in the early splicing assembly, and a high frequency mutation occurs in a variety of tumor cells with most significant in patients with myelodysplastic syndrome (MDS) and chronic lymphocytic leukemia (CLL). The studies through recombinant horse proteins have shown that these SF3B1 / Hsh155 mutations can lead to changes in the splicing pattern of specific genes, but its molecular mechanism of RNA splicing is not clear.

Recently, the Shanghai Institute of Plant Physiology and Ecology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and the Charles Query Laboratory of Einstein College of Medicine in the United States have published research papers in the International Journal of Genetics and Development, and the study is titled "SF3B1 / Hsh155 HEAT motif mutations using interaction with the spliceosomal ATPase Prp5, resulting in tangential branch site selectivity in pre-mRNA splicing". According to the high conservativeness of SF3B1 / Hsh155 protein and the advantages of the genetic system of budding yeast, it was found that these SF3B1 / Hsh155 high frequency mutants could only specifically change the accuracy of splice recognition of intron frontal region sequences. The accuracy of the identification of other areas of the child is not affected. This feature is very similar to the mutant phenotype of RNA helicase Prp5, which has been studied by Xu Yongzhen team for a long time.

The results of protein interaction showed that SF3B1 / Hsh155 had a direct interaction with Prp5. Further studies showed that the high frequency mutation of SF3B1 / Hsh155 significantly changed the intensity of its interaction with Prp5. It is important that the change in the intensity of this interaction is closely related to the recognition accuracy of the intron fulcrum region. Subsequent mutant studies have shown that enhancing the interaction of SF3B1 / Hsh155-Prp5 facilitates the formation of early splice complexes and accelerates the dissociation of Prp5. Conversely, weakening the interaction between SF3B1 and Hsh155-Prp5 will prevent early splice complex and inhibit the dissociation of Prp5. This progress not only reveals the molecular mechanism of SF3B1 / Hsh155 high frequency mutation leading to RNA splicing disorder and improved the assembly model of early splicing body, but also provided important clues for the further study of related diseases. Flarebio provides recombinant proteins of good quality such as recombinant TLR2 at reasonable prices.

Methylation deficiencies can be important causes of cancer

Every human cell contains a complete DNA gene that contains not only the genetic information of the human body, and the so-called methyl group in the gene is an essential component of human tissue. Researchers at the Jena Institute of Aging in Germany have confirmed for the first time that DNA errors and methylation deficiencies are an important cause of cancer. The results of the study were published in the latest issue of Nature which also publishes other studies on recombinant rat proteins.

Each tissue of the human body consists of tissue-specific cells of a particular attribute. Gene selection is very strict, such as in the intestinal cells only the corresponding gene directory activation into intestinal cells. What plays an important role in gene regulation is the so-called methyl group, which activates the gene by the action of the enzyme, and the process is called DNA methylation. When the human body develops cancer or suffer from aging diseases, the activity of normal gene fragments will be wrong. The exact process and the role of DNA methylation have not been fully studied.

The function of DNA methylation as a gene to start the "switch" (promoter) has been known, but why a single gene has methyl groups (the so-called gene body) is unclear so far. The team led by Francis Nari at the Leibniz Institute for Human Aging for the first time confirmed that the gene would go wrong when the promoter in the gene contained methyl groups. The result is the generation of abnormal proteins that interfere with the composition of normal cells, causing cell function and identity to undergo large-scale destruction, cell variation and may lead to cancer, which is a mysterious process of DNA methylation.

"The results of this study are exciting because we are now finally able to understand why many of the DNA in cancer cells is rarely methylated," Dr. Francis Nari says in a research note. "It is a lack of genes that cause the gene to be abnormal active state, producing abnormal proteins and spreading cancer cells." Unlike the natural degeneration in the DNA life cycle, changes in DNA methylation deletions can in principle be regulated by so-called chemical messenger substances. Dr. Francis Nari added, "There is no DNA methylation in the genome, and there may be a protein mutation, which is a completely new understanding and will provide a new way to treat cancer. If we find a way to make a methyl group transfer to the exposed cancer cell DNA sequence, it is possible to prevent cancer cells from breeding." Flarebio provides you with superior recombinant proteins like recombinant TLR2 at good prices.

Gene editing technology helps tomatoes flower and mature two weeks in advance

Research team at Cold Spring Harbor Laboratory (CSHL) made use of CRISPR gene editing technology to make tomatoes flowering and maturing two weeks more in advance and to expand the scope of this important crop cultivation. The study was published in the journal Nature Genetics which has also publishes other studies on recombinant dog proteins.

"We show the strong ability of CRISPR to rapidly enhance crop traits," said Zachary Lippman, associate professor of CSHL. The technology is not only suitable for tomatoes, but also can be used for corn, soybeans, wheat and other major crops.

Lippman and his colleagues studied a wild tomato in the Galapagos Islands. The Galapagos Islands are located near the equator, and the day and night time are nearly 12 hours a year.

The wild tomatoes of the Galapagos Islands go to the place with long summer, and it will be very late to flower and bear fruit. Studies have shown that this tomato is extremely sensitive to sunshine length. The longer the daytime, the longer the flowering time; the shorter the daytime, the shorter the flowering time.

Flowering time is regulated by a hormone system, and florigen and anti-florigen SP (SELF PRUNING) to work together. Researchers have found that domesticated tomatoes are not as sensitive as wild tomatoes to day length because of the SP5G mutations that have been acclimated to tomatoes. When wild tomatoes on the Galapagos Islands grow in New York, the SP5G gene-coded anti-florigen show rapid increase in the level of expression and activity, resulted in the flowering of the plants for a long time. In contrast, this increase in anti-florigen in domesticated tomatoes is much weaker.

Researchers use gene editing tool CRISPR to induce SP5G gene mutations that do not produce any anti-chaperonin proteins. Studies have shown that such editors make the common tomato varieties earlier. In addition, manipulating another chlamydia gene will make the tomato grow as dense as the shrubs and show precocity fruiting. By the way, Flarebio offers recombinant proteins of good quality like recombinant Itgb5 at competitive prices.

Researchers from the Shanghai Institute of Health Sciences, Shanghai Jiaotong University School of Medicine recently used the human genome-wide transcription factor siRNA library to screen transcription factors which participate in the ESC self-renewal and found that a series of important genes which are important for maintaining human ESC, particularly the great importance and mechanism of PHB as a new member of HIRA complex in the regulation of human embryonic stem cells (embryonic stem cells, ESC) self-renewal. The study was published in the December 8 issue of Cell Stem Cell which also has other studies on recombinant human proteins, and the author of the article is Professor Jin Ying from Shanghai Jiaotong University School of Medicine.

In this study, the researchers used the human genome-wide transcription factor siRNA library to screen participants in the ESC self-renewal transcription factor and found a series of genes that play an important role in maintaining human ESC properties. They studied the PHB gene in particular. Previous studies have learned that PHB is involved in a variety of important life processes in mammalian cells. However, the function of the gene in the ESC has not been reported. The study of the Jinying group found that PHB plays an important role in maintaining human ESC self-renewal and promoting the reprogramming of human adult cells, especially PHB plays a unique role in maintaining the correct histone methylation of human ESC effect. Further studies have shown that PHBs interact with the HIRA complex of the chaperone protein H3.3 and maintain the protein stability of the HIRA complex.

In addition, the researchers found that PHB and HIRA jointly regulate the enrichment of H3.3 in the whole genome of chromatin, especially in the regulation of H3.3 in isocitrate dehydrogenases (IDHs) Gene promoter region and the expression of IDH gene to control the production of a-ketoglutarate (a-KG), a key metabolite that plays an important role in the fate of ESC, to shape the correct histones Methylation levels, maintenance of human hESC self-renewal and epigenetic characteristics.

This study reveals the key role of PHB in pluripotency regulation through genome-wide, large-scale siRNA screening, and it reported that PHB interacts with HIRA complex to regulate the enrichment of H3.3 on chromatin. This study also revealed the important regulation of HIRA complex and H3.3 on IDH gene expression and key metabolite a-KG, and proposed an apparent-metabolic regulatory loop maintained by human ESC. Flarebio provides you with good-quality recombinant proteins like recombinant ECEL1 at competitive prices.

Scientists have developed lower-cost therapy for uncommon genetic diseases

Scientists from an international research group suggested in Nature on Feb. 22 that blocking the molecules which cause Gauchers disease (GD) and other lysosomal storage disease (LSD) inflammation and organ damage can be used as a treatment, and this method is lower than the current treatment costs. More research through recombinant human proteins will be conducted.

Through the study of laboratory mouse models and human cells, the team showed that C5aR1 is a key molecular pathway in driving the inflammatory process of Goie disease. The process of inflammation of Geshe disease is initiated by the mutation of GBA1 gene. GBA1 encodes lysosomal enzyme glucocerebrosidase (GCase), which degrades the adipose molecule glucoamate (GC). C5aR1 is a small peptide (protein component) receptor from a complement system known as C5a (part of the immune system) that drives inflammation in several different types of immune cells.

Dr. Manoj Pandey, a scientist at the Syndicate Children's Human Genetics Division, and his colleagues showed that inflammatory glucose enamel accumulation in the spleen, liver, lung and bone marrow immune cells drives the self-expression of the glucose-ceramide that forms the immune complex antibody induction. These immune complexes promote the production of C5a and the activation of its receptor C5aR1.

Based on the evidence that C5aR1 participates in the process of Goie's disease, the researchers decided to test targeted molecular pharmacology in laboratory mouse models. Using C5aR antagonists (C5aRA) developed by K?hl, scientists injected C5aRA into the peritoneal cavity of mice. In the lung, liver and spleen of mice, the infiltration of proinflammatory immune cells (macrophages) is substantially reduced, and the accumulation of glucose-ceramide is almost completely eliminated.

Because the current project was carried out in mouse models and human blood cells, Pandey and his colleagues stressed the need for additional research before determining whether C5aR1 is effective and safe enough to be tested in human patients.

Pandey said the researchers will continue to test the C5aRA molecules used in mouse studies that are effective in targeting human and mouse C5aR. They will also test commercially available anti-C5 monoclonal antibodies called eculizumab and produced by Alexion Pharmaceuticals, which helped finance this study. This will allow researchers to test these compounds as a neoadjuvant therapy for human patients with Gaucher and other lysosomal storage diseases. Flarebio provides you with high-quality recombinant proteins such as recombinant Nrg2 at competitive prices.

Nat Commun: the smallest gene scissors

The Institute of Basic Sciences (IBS) in collaboration with KIM Eunji (ToolGen Inc.) and KIM Jeong Hun (Seoul National University) designed the smallest CRISPR-Cas9 to date and delivered it to myocytes and mouse eyes through adeno-associated virus (AAV) and used it to modify the blinding genes. This CRISPR-Cas9 system is derived from Campylobacter jejuni (CjCas9) and is expected to be an effective "non-exclusion" disease treatment tool. The study has been published in Nature Communications, which also publishes other studies on recombinant mouse proteins.

In this study, the team found that CjCas9 was both efficient and small enough. It has 984 amino acids, which can be packaged in AAV with multiple directed RNAs and fluorescent reporter proteins. In order to use bacterial proteins for gene editing, scientists had to optimize some aspects of the technology. They designed a short DNA sequence followed by targeting the DNA sequence by Cas9, known as the Protospacer Adjacent Motif (PAM). Each of the different Cas9 requires a specific PAM sequence; otherwise the target DNA sequence will not be bound and cleaved. Secondly, they had to modify the length of the wizard RNA.

Subsequently, IBS scientists packaged the new CRISPR-Cas9 complex with two guide RNAs and fluorescent reporter proteins into AAV to modify the genes in mouse muscle and eyes. They focused on two genes involved in age-related macular degeneration (AMD), because these two genes are one of the main causes of adult blindness. A gene is a common therapeutic target for ADM, known as vascular endothelial growth factor A (VEGF A), and the other gene is a transcription factor that activates VEGF A transcription, known as HIF-1a. Unlike VEGF A, HIF-1a is not considered a drug target. The so-called "miscarriage" genes, such as the usual transcription factors, can't be targeted directly by antibodies and other biological or chemical agents. In this study, the team demonstrated that CjCas9 was efficiently delivered to the retina through AAV to inactivate Hif1a and VEGF A in mice and reduce the area of choroidal neovascularization (CNV).

Intraocular injection of AAV-packaged CRISPR-CjCas9 can be beneficial in the treatment of various retinal diseases and systemic diseases. KIM Jin-Soo explains that CjCas9 is highly specific and does not cause off-target mutations in the genome.

The mouse and human Hif1a gene target sequences are identical, so the method proposed in this study will be useful in the treatment of ADM in human patients. By paving the way in which CjCas9 is applied to "unavoidable" genes or non-coding sequences, this technology broadens the scope of therapeutic targets so that the entire human genome is potentially drugizable. By the way, Flarebio offers recombinant proteins of good quality like recombinant COLEC12.

IRS-1 is essential for smooth muscle cells that make up veins and arteries

Diabetic patients have a high risk of heart disease. In spite of knowing this, scientists are still trying to use recombinant mouse proteins to track the specific biological causes behind this risk or to find ways to intervene. Researchers at the UNC School of Medicine are now searching for a possible culprit - a protein called IRS-1, which is essential for smooth muscle cells that make up veins and arteries.

According to a study published in the Journal of Biochemistry, too little IRS-1 causes cells to revert to "dedifferentiation" or stem cell-like states, and this may form plaques in the heart arteries, a disease known as atherosclerosis. The disease increases the risk of heart attack, stroke and other forms of heart disease. "When diabetes is under mismanagement, your blood sugar rises and the amount of this protein decreases, so the cells show abnormal proliferation."

The study focused on the formation of venous and arterial wall cells called vascular smooth muscle cells. The main function of these cells is to shrink each time the heart beats, helping to push oxygen-enriched blood to the body's tissues. When the plaques accumulate along the arterial wall, these cells gradually lose their ability to contract.

In the new study, the team found that IRS-1 was an inhibitor of abnormal signaling pathways, thereby maintaining vascular smooth muscle cell differentiation or localization. In the absence of IRS-1, the cells return to the stem cell-like state, which in turn activates abnormal signaling pathways and promotes cell proliferation.

In diabetic patients, the presence of IRS-1 is affected by the effectiveness of blood glucose levels or blood glucose levels. Previous studies have shown that IRS-1 is significantly reduced in patients with frequent or persistent hyperglycemia. The new study is the first to link this reduction with heart disease.

The next step, Clemmons Lab will look for substances that can stimulate this protein synthesis even in the presence of hyperglycemia. The results suggest that drugs that promote the promotion of IRS-1 can counteract the deleterious effects of hyperglycemia on atherosclerosis.

Clemmons said that the activity of IRS-1 may also play a role in other diabetic complications, such as eye and kidney diseases. Researchers plan to study these potential links. By the way, Flarebio provides you with recombinant proteins of good quality such as recombinant CDH2.

It is promising to find radical cure of inflammatory diseases

Scientists from institute have revealed that dead cells release effective inflammatory molecules that trigger inflammation in necrotic disease. The discovery can produce new and existing drugs that target molecules to be studied as a way of treating inflammatory diseases such as psoriasis and inflammatory bowel disease. The results are published in the Journal of the National Academy of Sciences, which also has other studies on recombinant human proteins.

The studies led by Dr. Lisa Lindqvist, Dr. Kate Lawlor, Dr. James Vince and Dr. Stephanie Conos have shown that interleukin-1β (IL-1) triggers inflammation during necrotic death. Death is important to protect us from infection by sacrificing infected or diseased cells for greater benefit. However, necrosis becomes inappropriate, triggering a damaging inflammation that causes an inflammatory disease.

Dr. Lindqvist said the discovery challenged a long dogmatic that inflammation caused by necrosis was a byproduct of dead cell debris. "Our study has determined that death cells release IL-1, a strong inflammatory signal in the autopsy process. Now we have found that IL-1 is the 'root cause' of necrosis-related inflammation," Dr. Lindqvist said. "We speculate that targeting this molecule may be an effective way to treat inflammatory diseases."

The results suggest that targeting IL-1 can inhibit inflammation associated with a variety of inflammatory diseases, including multiple sclerosis, ischemia-reperfusion injury, atherosclerosis, liver disease, pancreatitis, psoriasis, inflammatory bowel disease and infectious disease. "Our research suggests that the existing drugs that prevent IL-1 may help to treat these diseases," Dr. Lindqvist said. "We are also exploring how IL-1 is secreted by autopsy so that we can create new drugs to prevent its release and reduce inflammation to treat inflammatory diseases." Flarebio offers high-quality recombinant proteins like recombinant CDH2 at competitive prices.

New cancer immunotherapy can kill target cancer cells

Researchers have developed a manual structure that can mimic cell membranes which can "open" immune cells and let it attack and destroy a specified target. According to research using recombinant horse proteins, this approach may be used as a cancer immunotherapy in the future, and it also provides a more in-depth understanding about how immune cells are activated to find and kill cancer cells. The results of the study were published recently at a joint meeting between the UK and the Dutch Society of Immunology. The meeting was held in Liverpool, England.

Immunotherapy is to make the body's own immune system attack cancer cells, and it is the most promising new form of cancer treatment. For this effective immunotherapy, we need to understand how the immune system recognizes cancer cells and reacts to cancer cells. This requires antigen presenting cells (APCs) to present proteins (or antigens) on tumor cells. Antigen-presenting cells are a group of immune cells that are responsible for coordinating the immune response.

PhD student Loek Eggermont and research team from the figdor lab at the Radboud University Medical Center in the Netherlands have solved this problem by developing artificial antigen presenting cells. They developed a filamentous polymer scaffold that possesses a specific structure that mimics the antigen presenting cells of the cell membrane. This kind of stent is embedded with a variety of different T cell activating proteins. In vitro studies, they found that this artificial antigen - presenting cells were able to activate the effects of human T cells on their proliferation and differentiation. They also found that different receptors on T cells must pass through their artificial antigens close to each other, and T cells can achieve optimal activation.

These findings help us better understand the mechanism of T cell activation, that is, what signals these cells need to start attacking cancer cells, and it provides a promising way to study the development of more effective immunotherapy. The group's goal now is to make this polymer more specific to cancer proteins, making it possible to induce T cells to attack cancer cells. After that, the system needs to be tested. The mouse model as a first assessment to assess whether it can be used to effectively treat cancer in the body.

"Immunotherapy is largely dependent on the proper activation of immune cells, such as T cells, to detect and destroy tumor cells. Currently, immunotherapy against cancer mainly relies on activation of non-specific immune systems," said a researcher at the Radboud University Medical Center.

"We have demonstrated in-vitro studies that artificial antigen-presenting cells are effective in activating T cells and our findings also help us to better understand the mechanisms underlying this T cell activation. Although more research is needed to find out whether the system works in animal models, we hope that one day it will bring new development to cancer immunotherapy." Flarebio provides superior recombinant proteins including recombinant ECE1 at competitive prices.

Future treatment method of inflammatory bowel disease and colon cancer

Can inflammatory bowel disease and colon cancer be prevented by changing the shape of a single protein?

There is a close link between uncontrolled intestinal inflammation and inflammatory bowel disease, and they would develop into colon cancer in the end. This uncontrolled inflammation is associated with changes in the number of intestinal bacteria, which can invade the mucosal tissue after damage to the protective protective cell barrier.

The team from the Virginia Tech University conducted research through recombinant mouse proteins and found that the shape of the protein IRAK-M, which modifies inflammation, can significantly reduce the clinical progression of both diseases.

Changes in the protein make the immune system more effective and destroy the bacteria before they begin to do harm. The complete report has been published in the journal Biomedical. "We changed the IRAK-M protein of the mice and found that the inflammation was significantly reduced and the cancer was naturally reduced," the researchers said.

He said that the next step will be conducted in conjunction with the Caroline Clinic and Duke University, a clinical trial of human patients. "Ultimately, if we were able to design a therapy for the IRAK-M target, we thought it might be a viable strategy of preventing inflammatory bowel disease."

According to data from the Centers for Disease Control and Prevention, colon cancer is a major disease related to life and death and the third largest cancer killer in the United States. At present, research team from Virginia Tech is in full swing to study. They said, "When our finding has a potential clinical significance, we feel really excited. We can sincerely hope that our research results can contribute to the future treatment of inflammatory bowel disease and colon cancer and other diseases." By the way, Flarebio offers high-quality recombinant proteins like recombinant CDH15 at competitive prices.

A convincing scientific evidence for the Zika virus leading to microcephaly

In recent years, Brazil and other countries in the Americas frequently show microcephaly. According to studies on recombinant human proteins, the scientific community has confirmed that the Zika virus infection shows some association with the incidence of microcephaly, but they don't know how the virus impacts fetal brain development. German researchers have said that they have found the scientific evidence of Zika virus that causes microcephaly.

Researchers at the University of Cologne, Germany, and other institutions reported in a new issue of Cell-Stem Cells that they "reprogrammed" healthy human skin cells into cultured pluripotent stem cells to culture neural precursor cells. Neural precursor cells can differentiate a variety of nerve cells and can be described as the "starting point" of brain development.

Under specific experimental conditions, the researchers gathered many neural precursor cells into brain organs, that is, a few millimeters in size with three-dimensional structure of the brain tissue fragments. The process of embryonic brain simulates the early development and observes the virus effect of infection on embryonic brain development.

The results showed that Zika virus allows cells to involve in cell division - the central body shows failure so that nerve precursor cells prematurely differentiate into mature nerve cells. This "precocious" seems to be of no harm, but it will make a lot of nerve precursor cells no longer involve in brain organ growth into a complete brain process, leading to microcephaly.

Researchers said that they used Zika virus strains isolated from the small head deformed embryos in the experiment, and the experimental results provide a convincing scientific evidence for the Zika virus leading to microcephaly.

Zika virus spreads mainly through Aedes aegypti, but it is also sexually transmitted. People infected with Zika virus may show fever, rash, joint pain and other symptoms similar to dengue fever. The vast majority of infected patients are mild, but pregnant women need to be careful. Once infected, it may lead to fetal malformations. Flarebio provides you with good-quality recombinant proteins including recombinant TLR2 at competitive prices.

A new development in CRISPR has been made by the father of gene editing

The father of gene editing Zhang Feng made a new development in CRISPR, and his research team identified two class II CRISPR-Cas systems (subtype VI-B) that lack Cas1 and Cas2 through recombinant rat proteins, which contain a single large effector, Cas13b and two previously-unidentified related proteins: Csx27 and Csx28.

The microbial adaptive immune system CRISPR-Cas (regular intervals of short palindromic repeat and CRISPR-related proteins) helps bacteria and archaea resist exogenous nucleic acid invasion. CRISPR-Cas system is divided into two categories: Category 1 CRISPR-Cas system is the use of a variety of Cas protein and crRNA to form a complex; 2 type CRISPR-Cas system is a large single component of the Cas protein co-crRNA.

Scientists studied the most highly-conserved cas genes involved in the CRISPR immunization phase and analyzed the microbial genome sequences of their loci and carried out a diversified CRISPR-Cas system to calculate the sequence database. Using this method, a class 2 subtype VI-A system targeting the RNA of Cas13a (formerly C2c2) was found.

In this study, Zhang Feng team used the computer database mining method and found two subtypes VI-B CRISPR-Cas system which can achieve heterologous expression of RNA interference. Cas13b treats its own CRISPR array with short or long repeats, excising the target RNA with ribonuclease activity. In addition, they also analyzed the RNA secondary structure required for the target. The discovery of these systems has helped to develop new tools for manipulating and monitoring cellular transcription processes.

The results of this study have been published in the journal Molecular Cell on February 16, and Zhang Feng is the author of this article. Zhang Feng is one of the pioneers of genomic editing technology CRISPR and has played a key role in applying the CRISPR / Cas system to human cells. In recent years, he has won many awards and has been called as "the father of gene editing" by the media. By the way, Flarebio offers high-quality recombinant proteins like recombinant TLR2 at good prices.

Injecting synthetic mRNAs that encode viral proteins into mice

Vaccine developers have used recombinant rat proteins and succeeded in protecting mice against Zika viruses by injecting synthetic mRNAs that encode viral proteins into animals. The mouse cells are then constructed as part of the virus that stimulates the immune system to produce antibodies to identify future infections. When the body again exposed to the pathogen, the immune system will follow its original memory to create more protective substances to prevent pathogen damage. The study, published on February 17 in Cell, followed the February 2 issue in Nature, shows that Zika's mRNA vaccine has similar positive results in both mice and monkeys. Richner and Himansu et al. have found that the modified mRNA vaccine induces immunity to the Zika virus and minimizes the cross-immune response enhancement of the Zika virus and dengue infection.

"We measured the virus in mouse blood, brain, spleen, and female mice in the uterus, and 95% of our mice did not find viral replication in our group of vaccines." said Michael Diamond, the article's senior author and an infectious disease researcher from St. Louis Washington University School of Medicine.

Rather than using a weakened virus or viral fragment to stimulate the immune system to produce an immune response, RNA vaccine induced cells to build part of the virus, and largely this part of the virus forced cells to establish more virus model. "The Zika virus injects their RNA into the cytoplasm and then hijacks the cell's own translation mechanism to produce the Zika virus antigens," said Giuseppe Ciaramella, co-senior author of the study, who is also the chief scientific officer of the modern venture capital firm Valera and specializes in infectious disease treatment Expand. "Using our vaccine, we can lead the cells to do exactly the same."

Although RNA is directed by injecting RNA to construct a complete virus, the vaccine contains RNA to direct two Zika proteins. When the vaccine RNA enters the mouse cells, it binds to the ribosome and is translated into a protein and released. These two viral proteins are not infected with any other cells, but they are sufficient to allow the immune system to recognize the Zika virus and produce an immune response.

Because the Zika virus can enter the brain, the researchers have been hesitant to use Zika's weakened virus to produce immunity. Even with the weakened Zika virus, some scientists still focus on these attenuated Zika viruses that could still cause some damage in the brain. However, using RNA vaccines, cells can quickly take RNA before the virus reaches the brain.

Another key advantage of using RNA vaccines is its adaptability. Biologists have a lot of practical ways to change the RNA chain, making it easier to customize the vaccine. Flarebio offers high-quality recombinant proteins like recombinant ITGB5 at competitive prices.

Diabetics with early kidney disease lack protective "anti-aging" hormones Klotho

A new study by King's College London showed that diabetics with early kidney disease lack protective "anti-aging" hormones Klotho. Klotho protein is a new type of anti-aging-related proteins that play an important role in resisting body aging. Klotho is secreted by the kidneys. Studies using recombinant dog proteins have shown that secreted Klotho protein can inhibit the aging of the body, play the role of anti-oxidation, anti-apoptotic and protect the cardiovascular, kidney and other systems so as to regulate a variety of aging-related diseases.

A study published on Feb. 13 in the European Diabetes Research Association journal Diabetologia shows that Klotho may play an important role in the development of common kidney disease in diabetic patients. This means that Klotho's expression level may serve as a potential marker for predicting the risk of kidney disease, as well as developing new targets for the treatment and prevention of kidney disease in patients with type 1 diabetes. The preliminary work of the research team also shows that Klotho protects the vascular system from changes associated with abnormal aging, such as arterial wall thickening (atherosclerosis), which characterizes age-related diseases such as diabetes, heart disease and hypertension.

In this study, scientists studied blood and urine samples from 78 patients with type 1 diabetes, 33 of which showed signs of early stage of diabetic nephropathy (known as microalbuminuria). The researchers found that Klotho levels in the blood of patients with microalbuminuria were lower in patients with microalbuminuria than those without microalbuminuria. Klotho levels in patients without microalbuminuria were the same as those for healthy adults.

"This is the first time that Klotho has been associated with type 1 diabetic nephropathy," said Dr. Giuseppe Maltese of the first author of the study at the King's College London. "This finding means that new disease markers and potential treatments can be developed."

"With further research, through the larger type 1 and type 2 diabetes patients, we hope to expand the scope of this study in order to identify early high-risk patients in the progress of kidney disease and cardiovascular disease," said Dr. Janaka Karalliedde, senior author.

Researchers say the study will help scientists better understand how this hormone contributes to healthy aging and how Klotho's flaws lead to age-related illnesses. As part of the ARK (King Academy Aging Research) research program, they are further researching Klotho's role in aging and longevity.

The limitations of this study include its relatively small sample size and selectivity, making it impossible for researchers to determine the causal relationship between Klotho and kidney disease progression. By the way, Flarebio provides you with recombinant proteins of good quality such as recombinant Ptpra.

Adipocytes play an important role in human body

Adipocytes are not simply large in the presence of large amounts of lipids in the body, whereas they emit hormones and other signaling proteins that affect many other types of tissues. In a new study in the United States, scientists have determined through research using recombinant human proteins that adipocytes can deliver microRNAs through the exosomes pathway and regulate other organs. This suggests that fat cells are promising in the use of gene therapy for metabolic diseases such as fatty liver disease.

Professor Ronald Kahn from the Joslin Diabetes Center published a study on Nature on Feb. 15 that revealed that the mechanism which could provide a potential for new treatments to develop the possibility of using adipocytes to develop gene therapy to help treating the liver or other organ metabolic diseases, cancer and so on.

MicroRNAs are not translated into proteins but can regulate other RNA to produce proteins. All cells of our body can produce microRNAs, and some of these microRNAs are known to be released from the cells into the bloodstream. However, once they enter the blood, what they have done is what scientists have been arguing about.

Joslin scientists have focused on microRNAs from adipocytes that are released into the blood through the "exosomes" pathway. Researchers have constructed a genetically modified mouse model that prevents adipocytes from producing microRNAs. Joslin researchers later found that the number of circulating microRNAs in the exosomes decreased significantly in mice that did not originate from adipocyte microRNAs. This reduction in the number of circulating microRNAs can be restored when the investigator transplanted normal fat into these mice, indicating that most of the circulating microRNAs were from fat.

Next, the scientists studied two forms of fat malnutrition: fat loss or hereditary fat metabolism. In both groups, they found that circulating microRNA levels in exosomes were below normal levels. "This suggests that these circulating microRNAs produced by fat may help diagnose metabolic diseases such as obesity, type 2 diabetes and fatty liver disease," Kahn said. Flarebio provides you with good-quality recombinant proteins including recombinant COLEC12 at reasonable prices.

New theoretical basis for prevention and treatment of liver disease

Zhejiang University researchers found that iron content is too high and hereditary hemochromatosis can induce liver cells and macrophages "iron death", while "cystine glutamate transporter" can inhibit liver death. The discovery will provide new ideas for liver iron damage and prevention and treatment of hemochromatosis. Related papers have been published recently in the Liver Disease and completed by the Zhejiang University School of Public Health, Zhejiang University, Institute of Transformation Medicine and Zhengzhou University. The researchers conducted the research using various recombinant rat proteins.

Iron death is a cell death pathway that is different from traditional cell death, such as apoptosis, necrosis, and it is mainly caused by iron-dependent oxidative damage, involving a series of complex biochemical reactions, gene expression and signal transduction. Take hereditary hemochromatosis as an example, too much iron stored in the liver, heart and pancreas and other substantive cells can ultimately lead to tissue and organ disease, and it is the most important cause of liver disease, diabetes, heart disease and other chronic diseases.

Dr. Wang Hao and other researchers from Zhejiang University School of Public Health used a variety of mouse models to conduct the study and found that hereditary hemochromatosis mice significantly increased the level of iron death. Feeding iron deficiency diet or iron death inhibitor can significantly improve the liver fibrosis and other iron overload caused by pathological damage. Researchers further screened by gene chip that cysteine glutamate transporters are key genes that regulate iron death due to iron overload.

This study reveals a new pattern of iron death in liver injury, which targets liver disease caused by diseases such as hereditary hemochromatosis targeting the key genes and provides an important theoretical basis for the prevention and treatment of major diseases such as liver disease and hemochromatosis. By the way, Flarebio offers high-quality recombinant proteins like recombinant NPP1 at competitive prices.

The molecule which can inhibits activity of the protein related to pancreatic cancer

Early diagnosis of pancreatic cancer is difficult and lacks specific drugs. Recently, according to research through recombinant horse proteins, researchers from France and Spain have found a substance that has been used to treat anxiety can interfere with the development of pancreatic cancer.

Pancreatic cancer is one of the deadliest tumors. At present, it is generally treated through chemotherapy program. Nupr1 protein belongs to the "intrinsic disorder protein". As early as the 20th century, 90 scientists have pointed out that it is involved in the development of pancreatic cancer. Now, scientists have discovered molecules that can inhibit the activity of this protein.

Experts have shown that this study has been selected from among more than 1,000 drugs that have been approved for the treatment of various diseases to screen for the effective inhibition of Nupr1 activity. Through the combination of computer simulation and pharmacological test, it can be seen that this molecule can interact with Nupr1 protein. In-vitro experiments show that it can reduce the ability of tumor cells to activate and transfer and completely inhibit the possibility of colony formation. The active compound has been tested for efficacy in animals and has been shown to prevent the development of the disease. This compound is trifluoperazine.

Trifluoperazine was previously used only as an antipsychotic in clinical practice, demonstrating its excellent anti-tumor effect. The study has a new shift in the direction of treatment of pancreatic cancer. Inhibition of Nupr1 may become a new treatment device for the treatment of the pancreatic cancer. By the way, Flarebio provides you with recombinant proteins of good quality like recombinant CDH2.

Phosphorylation affects the tumor growth and development

Scientists from VIB-KU Leuven have identified new mechanism that affects tumor growth through recombinant mouse proteins. Typical hypoxia in the tumor not only stimulates proliferation, but also counteracts the important role of protein PHD2 as a "cancer cell killer". The possible solution is to block the enzyme PP2A / B55 which recover the function of PHD2 to slow down cancer growth. The study was led by Massimiliano Mazzone (VIB-KU Leuven) and published in the leading scientific journal Cell Reports.

Poor prognosis in cancer is usually associated with hypoxia, which is interference to the oxygen supply to tumor cells. The protein PHD2 is called a "hypoxic sensor", which is highly dependent on the amount of oxygen. At the VIB-KU Center for Cancer Biology in Leuven, the study was led by Dr. Giusy Di Conza and his colleagues. Massimiliano Mazzone focuses on the study of phosphorylation.

When phosphorylated, PHD2 is more active and promotes the death of cancer cells in the hypoxic region of the tumor. However, tumors tend to overexpress phosphatase PP2A / B55, an enzyme that removes phosphate groups ("dephosphorylated") from PHD2. Thus, PHD2 is partially inactivated, which counteracts the positive effects of this "killer cancer cell".

Massimiliano Mazzone (VIB-KU Leuven) said, "Surprisingly, we have found that PHD2 phosphorylation is regulated by a pathway such as mTOR. mTOR is the primary sensor for metabolic stress in tumors and normal cells, such as lack of nutrients. Thus, our findings are applicable not only to cancer but also to other diseases such as inflammation or metabolic diseases."

During the study period, Mazzone's lab worked closely with several domestic and foreign researchers. In particular, the German ISAS Laboratories (Dortmund) and the University of Leuven Hospital play a decisive role in providing the human cancer samples needed for research. In these samples, the researchers found that PP2A / B55 were highly expressed in tumors compared with healthy tissues.

Prof. Massimiliano Mazzone (VIB-KU Leuven) said, "This leads us to conclude that PP2A / B55 are a potential target for promising cancer treatment, which is why we are starting to study the potential of specific drugs. The ultimate goal is to design this phosphatase function of the molecules, which targeted to fight cancer."

In addition to new insights into cancer treatment, these findings may also produce new biomarkers: PHD2 phosphorylation status may help to understand the process of tumor transformation and therefore choose appropriate treatment.

Professor Massimiliano Mazzone (VIB-KU Leuven) said, "In order to fully understand all the progress of these processes, we also need to carefully study the tumor microenvironment and immune system. After all, they strongly affect tumor growth." Flarebio offers high-quality recombinant proteins like recombinant Itgb2 at competitive prices.

Scientists have analyzed the crystal structure of MFN1 fragment

It is reported that Professor Gao Song research group from the Zhongshan University Cancer Center center analyzed the crystal structure of MFN1 fragment in different triphosphate guanosine (GTP) hydrolysis condition and clarified the mechanism of MFN1 hydrolysis GTP and proposed MFN1 mitochondrial outer membrane embolization mediated model. Recently, the relevant research has been published online in the journal Nature, which also publishes other studies on recombinant human proteins.

The body consists of tens to hundreds of trillion cells, of which the vast majority of cells contain an important "organ" called "mitochondria" (organelle), which is the "energy plant" of cells. Mitochondrial fusion relies on a protein "machine" implementation called mitofusin. This machine is anchored on the surface of the mitochondria to achieve docking and fusion of different mitochondria by using a small molecule compound "fuel" called GTP. Mitofusin machines sometimes suffer from a "part" failure due to genetic mutations, leading to mitochondrial fusion disorders and the associated human disease.

Researchers use "X-ray crystal diffraction" and other technologies to make mitofusin form as sugar and salt-like crystals (volume only one thousandth of a million) for diffraction experiments. They finally observed microstructure of mitofusin machine and found it can adjust their own structure through the consumption of GTP fuel and can adsorb each other.

The study reveals an important process of basic life activities that has important guiding roles for people to explore the causes of related diseases and to develop appropriate clinical approaches. By the way, Flarebio offers good-quality recombinant proteins like recombinant App at good prices.

The guarding proteins that prevent worsening of pancreatic cancer cells

Researchers at the MD Anderson Cancer Center at the University of Texas have identified guarding proteins that prevent the worsening of pancreatic cancer cells, and they also found treatments that prevent these cells from worsening when these helper proteins are depleted. Related articles have been published online in Nature in February. The journal also publishes other studies on recombinant horse proteins. They developed a series of preclinical experiments using tumor xenografts from patients and mouse models. The findings are beneficial to develop a potential treatment for patients with rapidly-worsening and treatment-resistant pancreatic cancer cell subsets.

Dr. Giannicola Genovese, one of the authors of the paper, said, "Cancer cells have significant plasticity that makes it very difficult to treat." Genovese and colleagues found that after primary cancer-driven gene KRAS disappears, the elimination of the SMARCB1 gene would make a small part of the pancreatic cancer cells change into a mesenchymal state, that is, a removable invasive cell state. They also found the fragility of mesenchymal cells: these cells are extremely dependent on protein production to meet the increased metabolic needs. Genovese said, "Inhibition of protein homeostasis combined with standard chemotherapy can be highly effective in killing these most aggressive pancreatic cancer cell subsets." Protein steady state refers to a balanced state which is achieved by the processes of protein synthesis, folding, modification and degradation.

This led the Genovese team to study a drug called AUY922. AUY922 is an inhibitor of heat shock protein 90 that blocks protein homeostasis. Whether used as a single reagent or in combination with a chemotherapeutic agent gemcitabine, AUY922 increases the response rate and prolongs their survival in mice presenting with key features of human pancreatic cancer.

"We are analyzing cell populations within the pancreas, trying to understand the functional weakness of each cell population. And then we plan to develop a more rational combination of therapy," said Dr. Giulio Draetta, director of the Institute of Cancer Science at the Anderson Cancer Center.

Draetta noted the identification of invasive subpopulations and the determination of their sensitivity to protein homeostasis, allowing the treatment of specific cell types to be matched. "This is the real function of the definition of personalized therapy," said Draetta. By the way, Flarebio offers recombinant proteins of good quality such as recombinant ECE1.

Researchers have discovered the potential target of early-stage Parkinson's disease

The team led by Patrik Verstreken (VIB-KU Leuven) has identified the underlying mechanisms of early Parkinson's disease. Making use of flies, mice and patient cell models, the team focused on cardiolipin which is combined by glycerol C1 and C3 and two molecules of phosphatidic acid and is an important component of mitochondrial inner membrane and bacterial membrane. They demonstrated that reducing the role of protein FASN which affects mitochondria can lead to an increase in cardiolipin levels and a decrease in Parkinson's symptoms. These results may pave the way for the treatment of lipid-based Parkinson's disease. The team's research was published in the Journal of Cell Biology with other articles on recombinant mouse proteins.

In this study, Verstreken and his team of collaborators from Belgium, Germany and Portugal observed the protein FASN responsible for lipid generation in cells, bypassing the genetic defects of mitochondria. "Several drugs that block FASN are already present because this protein is important for cancer research and treatment, and many drugs have been used in clinical trials. Through this study, we can now have the background of Parkinson's," said Professor Verstreken.

In their research process, the researchers encountered an unexpected phenomenon. Using flies, mice and human cell models, they saw that FASN has a direct effect on mitochondria. Mitochondria have their own independent genome and acts as an energy generating machine in their cells.

"The PINK1 gene encodes the PINK1 protein, and one of the mutations leads to lower levels of mitochondria in the mitochondria," said Professor Verstreken. "Surprisingly, blocking FASN, which is not limited to mitochondria, actually avoids the PINK1 mutant mitochondria effect, thus blocking FASN increases the amount of specific type of lipid in the mitochondria and reduces the degradation of neurons.

Professor Verstreken has identified several goals for future research projects seeking a deeper understanding of the linkages between specific levels of lipid in neurons and Parkinson's disease. "Before developing new treatments, we need to answer questions such as "whether there is a link between early Parkinson's prevalence and progress and lipid content, "Professor Verstreken said. “Although we have successfully demonstrated that cardiolipin can improve the function of mitochondria in flies, mouse models and human cells, we still need to explore its effect on actual patients." By the way, Flarebio provides you with high-quality recombinant proteins including recombinant TLR2 for your research.

Many autoimmune diseases have common susceptibility genes

Shanghai Jiaotong University School of Medicine was informed that Shen Nan research team from its affiliated Yan Chai Hospital collaborated with the United States South Carolina Medical University and other institutions to find susceptibility genes associated with a variety of autoimmune diseases, finding new targets for the intervention treatment of systemic lupus erythematosus, rheumatoid arthritis, primary Sjogren's syndrome and other autoimmune diseases. Related results have been published online in the journal Natural – Genetics, which also publishes other studies on recombinant human proteins.

To carry out the mechanism research on autoimmune diseases from the gene level and then to find an effective target for intervention has been the focus of the study in recent years for Chinese and foreign rheumatoid immunologists. Shen Nan research team joint includes the Chinese Academy of Sciences Shanghai Institute of Health Sciences Institute of Health Science, Peking University People's Hospital, Nanjing Medical University, South Carolina Medical University and other research units. They made use of immune chip and found a significant susceptibility site which is significantly related to systemic lupus erythematosus. Since this site is located in the genomic noncoding region, gene expression correlation analysis suggests that this locus is not a functional site. However, the site is located near the complex region of the repeatable multi-copy region and can't be used to find a functional site of disease linked to this site using high-throughput second-generation sequencing (NGS). Thus, the researchers are never able to lock the pathogenesis of intervention, nor are they able to study the function change mechanism of pathogenic sites.

The researchers used a specific long fragment gene amplification sequencing method in the complex gene region and found another functional genetic susceptibility site. The mutation type of susceptibility this site would cause NCF1 protein amino acid changes, resulting in the reduction of NAPDH oxidase reactive oxygen production, thus participating in the development of the disease.

"More importantly, the site is also associated with the genetic susceptibility of patients with rheumatoid arthritis and primary Sjogren's syndrome," said Shen Nan. In the research method, this study used the first generation of sequencing method to find functional pathogenesis site, making up for the second generation of sequencing technology loopholes and providing a new way of thinking for the future discovery of functional pathogenic multi-gene complex genetic diseases. Flarebio offers recombinant proteins of good quality such as recombinant TLR2 at competitive prices.

New drugs for the treatment of multiple myeloma patients

Multiple myeloma is a cancer of bone marrow plasma cells. Plasma cells produce certain proteins that establish the immune system. According to research using recombinant dog proteins, when the number shows abnormalities, these proteins damage the body and the immune system.

"We are now able to diagnose and treat myeloma earlier before it begins to damage the body, thus effectively controlling myeloma, and any irreversible damage to the body may be significantly delayed," said Dr. Sikander Ailawadhi, haematologist and oncologist from Jacksonville Mayo Clinic Cancer Center.

In 2015, the US Food and Drug Administration approved three new drugs for the treatment of multiple myeloma in two weeks. "The approval of these drugs for the treatment of diseases that are considered to be incurable in such a short period of time is unprecedented," Ailawadhi said. "Most patients showed symptom relief, and their survival rate has been improved."

"We can almost guarantee that every patient who has been diagnosed with newly diagnosed myeloma has a certain degree of reaction," he added.

"Some of the most exciting things are the development of new drugs," Ailawadhi explained. "Specifically, we can use the currently available drugs to observe what resistance to drive myeloma cells and to isolate those pathways and then to develop new drugs that specifically target those resistance mechanisms."

Ailawadhi says that more drugs are coming soon. At present, the Mayo Clinic has more than 50 active clinical trials. Flarebio offers recombinant proteins of good quality such as recombinant ECEL1.

To prevent and treat cancer cachexia with MEK inhibitor

Tumor cachexia is a multifactorial syndrome characterized by progressive skeletal muscle atrophy and weight loss, and this condition can’t be fully reversed by conventional nutritional support, leading to progressive organ dysfunction. Cachexia not only reduces the sensitivity of drug treatment and increases the incidence of complications, affecting the implementation of patients with comprehensive treatment programs, but also leads to decreased quality of life and survival of patients significantly to be reduced. Clinically, with the lack of cachexia drugs with effective prevention and treatment, new ideas based on the understanding of the new breakthrough of pathogenesis in the treatment of cachexia have been the hot spots in domestic and foreign research in recent years. More research through recombinant mouse proteins is needed.

Skeletal muscle atrophy is the most important clinical features of cachexia. Clinical and basic research has always been taking skeletal muscle atrophy as a prognostic indicator of clinical cancer patients with reduced quality of life and shortening life expectancy. When the weight of the cachexia was 30%, the reserve of skeletal muscle protein decreased by 75% and the survival time was significantly shortened. The journal Cell reported that the quality of animal skeletal muscle was not only able to effectively reverse the decline in cachexia and significantly prolong the survival of model animals without affecting the rate of tumor growth. These results suggest that slowing the cachexia skeletal muscle atrophy is an important goal of its prevention and treatment. But there is no clinical intervention in the current cachexia skeletal muscle atrophy drugs.

MEK / ERK signaling pathway is not only important in tumor cell proliferation and differentiation, but also in regulating skeletal muscle energy metabolism and protein synthesis. A clinical study of advanced cholangiocarcinoma showed that the specific adverse effect of the first generation MEK inhibitor siMedidine was an increase in skeletal muscle mass, but the mechanism was unknown. To this end, the animal experimental results of Dr. Yang Quanjun from Shanghai Jiaotong University Affiliated Sixth People's Hospital Guo Cheng Task Force showed that the preventive and therapeutic administration of sixtemidine can effectively prevent and interfere with tumor cachexia animal weight and skeletal muscle, and it also can reduce the expression of E3 ubiquitination ligase MuRF1 and MAFbx (skeletal muscle protein degradation mainly by the two ubiquitin ligated ligands) and reduce the food intake and serum cytokines. Further studies on MyHC and MEK / ERK-related signaling pathways in the gastrocnemius muscle showed that siemetilib could inhibit the activation of ERK and increase the phosphorylation of AKT, leading to a decrease in the phosphorylation of FoXO3α and GSK3β downstream and increase of phosphorylation of mTOR.

The results of the Gregory B. Lesinski team from the Winship Cancer Institute in Emory University show that the second-generation MEK inhibitor, Binimetinib, also increases skeletal muscle mass and the function is gained through promoting skeletal muscle fibers synthesis and inhibition of skeletal muscle protein ubiquitination degradation. These results suggest that antineoplastic MEK inhibitors may be used for the prophylaxis and treatment of certain advanced stages of the disease in the future. By the way, Flarebio provides you with superior recombinant proteins including recombinant ITGB5 at good prices.

New insights into further treatment options of cancer

A team from Yale University found through recombinant rat proteins that melanoma cells and white blood cells fuse to form a metastatic mixture. This finding further explains the spread of melanoma and other cancers, providing new insights into further treatment options.

When the malignant cells from a primary tumor spread to other tissues and organs, the cancer becomes deadly. The team analyzed tumor biopsies in patients with malignant melanoma who had undergone bone marrow transplants prior to cancer, comparing DNA from primary melanoma to lymph node DNA after cancer spread. In both cases, they found a mixture of the patient's own DNA and the donor's DNA.

The presence of this hybrid DNA is intense on the surface, which generally attacks cancer cells rather than fused leukocytes, forming a genetic mixture after diffusion.

These findings can serve as new cancer treatment targets. "We need to focus on how leukocytes and cancer cells fuse, and this process involves many steps. These steps are our goals. Future therapy can be designed to prevent bone marrow-derived fusion cells. These studies are focused on the new technology pathways of discovery of targeted metastasis itself," the researchers conclude. Flarebio offers high-quality recombinant proteins including recombinant Nrg2 at competitive prices.

S6K1 gene is closely related to obesity and aging

S6K1 plays a role in many key metabolic processes, and previous studies have shown that S6K1 is closely related to obesity. On Feb. 8, Spanish scientists published a report in the journal Nature, where they identified downstream effectors of mTORC1-S6K1. S6K1 kinase mediates obesity and aging in mice by affecting metabolic pathways by EPRS and FATP1. This research using recombinant human proteins will promote the development of biomarkers and promote targeted therapies for obesity and aging.

S6K1 gene can determine the number of adipocytes in our childhood, and adipose cells are differentiated from stem cells. The authors of the study, Dr. George Thomas and Dr. Sara Kozma, were heads of the Metabolic and Cancer Research Group. Their previous work has shown that S6K1 differentiates into adipocytes through transcriptional regulation of mesenchymal stem cells (MSC) and plays a key role in the expansion of adipose tissue. S6K1 can determine the number of fat cells. S6K1 tends to be active in the process of stem cell differentiation. It will inhibit the differentiation of WNT signaling in adipocytes, and ultimately promoting the differentiation of adipocytes.

The researchers found that glutamylprolyl tRNA synthetase (EPRS) can serve as a target for mTORC1-S6K1, promoting obesity and aging. MTORCl-S6Kl induces the phosphorylation of EPRS, which is released from the aminoacyl tRNA multiple synthetase complex. It is necessary to perform the unconventional function of EPRS outside of protein synthesis.

To investigate the physiological role of EPRS phosphorylation, the researchers constructed knock-in mutant mice carrying Eprs-deficient phosphate. Homozygous Eprs knock-in mutant mice showed low weight, reduced adipose tissue and prolonged lifespan, similar to the phenotype of S6K1-deficient mice and adipose tissue-deficient mice.

EPRS phosphorylation mediates S6K1-dependent metabolic reactions. In adipocytes, insulin stimulates the release of S6K1-dependent EPRS phosphorylation from multiple complex enzyme complexes. Furthermore, screening by interaction showed that phosphorylation of EPRS combined with fatty acid transporter 1 (FATP1) induced its localization on the cell membrane and stimulated the uptake of long chain fatty acids. EPRS and FATP1 are downstream effectors of mTORC1-S6K1 and are essential for the metabolic phenotype.

These findings provide further evidence that S6K1 can serve as a predictor of obesity or as a drug target for obesity suppression. Flarebio offers high-quality recombinant proteins like recombinant COLEC12 at good prices.

Scientists have found new target of treating blood cancer

A proteoglycan molecule called CD99 is frequently found in stem cells from patients with blood cancer, including acute myeloid leukemia (AML) and associated myelodysplastic syndrome (MDS). The detailed report was published in the January 25 issue of the journal Science Translational Medicine. Based on this finding, the researchers designed an antibody that recognizes and disrupts CD99-coated leukemic cells, which have now been demonstrated in human and mouse cells. Antibodies are immune proteins that attach to specific targets, just like proteins that invade viral surfaces. In recent years, researchers have been able to control antibodies so they can target pathogenic molecules by conducting research involving recombinant horse proteins.

"Our findings not only confirm new stem cell molecules that drive human malignancies, but also show that these antibodies can kill human AML stem cells directly," the researchers said.

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are caused by abnormal stem cells in the bone marrow, and patients show anemia, an increased risk of infection and bleeding. The findings are based on an understanding of cancer. Just as normal tissue, including stem cells causing other cells, this "cancer stem cell", is a major factor in many types of cancer. In AML, a small percentage of leukemic stem cells can't grow into mature red or white blood cells. Most of the initial treatment of leukemia is significant, but it often relapses.

The researchers were interested in CD99 in the observation of AML and MDS cells. Previously, CD99 was crucial for the rare bone tumor of Ewing's sarcoma, so the researchers wanted to find out the effect of CD99 on blood cancer. After comparing 79 AML patients and 24 MDS patients, the researchers found that about 85% of the patients showed high levels of CD99. High levels of CD99 were able to separate diseased stem cells from normal stem cells. The researchers then designed the antibody and bound it to CD99. It was found that when the antibody binds to CD99 on the surface of cancer cells, it sends a signal to the inside of the cell to increase the activity of SRC-family kinase.

"With the appropriate support, we believe we can quickly identify the best antibodies for patients and begin clinical trials," the researchers concluded. By the way, Flarebio provides you with superior recombinant proteins like recombinant CDH2 at good prices.

SPOP: new treatment target for renal cancer

In recent years, the incidence of renal cancer increased the rate of malignant tumors in the first place. Clinical treatment shows that renal cancer is not sensitive to radiotherapy and chemotherapy. VEGFR inhibitors such as sorafenib and sunitinib are the first-line drugs for advanced renal cell carcinoma. Although FDA-approved drugs for kidney cancer treatment has been up to ten, these drugs are very limited efficacy of metastatic renal cell carcinoma, and susceptible to drug resistance. According to previous research using recombinant mouse proteins, it is a very important and urgent task to discover and confirm the new drug targets for the treatment of RCC-specifics.

Liu Jiang, a researcher at the Beijing Genomics Institute of the Chinese Academy of Sciences, discovered early that the SPP of the ubiquitin ligase E3 family member Cul3-binding substrate protein was overexpressed in 99% of clear-cell renal cell carcinoma tissues and was expressed in normal renal tissue SPOP and is still a biomarker of clear cell renal cell carcinoma. SPOP is still overexpressed in metastatic clear cell renal carcinoma. Liu Jiang group further study showed that SPOP is incorrectly positioned in the cytoplasm cell renal cell carcinoma. Overexpression of hypoxia-inducible factor HIF transcription enhances SPOP overexpression and hypoxic microenvironment drives the accumulation of overexpressed SPOP proteins in the cytoplasm of renal carcinoma and ultimately promotes the formation of renal carcinoma.

The above fundamental research in biology poses a key scientific question whether small molecule compounds can targetly interfere with SPOP-mediated protein interactions to achieve specific treatment of clear cell renal cell carcinoma. In order to study the interaction between SPOP and protein, SPROP was used to identify the crystal structure of the substrate polypeptide complex, and the structure-based screening strategy was used in combination with drug Chemical synthesis optimization and other technical means. The successful acquisition of SPOP can be combined with small molecule compounds. The compound can inhibit the binding of SPOP to substrate protein, interfering with the SPOP-mediated regulation of ubiquitination of PTEN, DUSP7 and other ubiquitination-modified signal transduction pathway, and ultimately inhibiting the growth of clear cell renal carcinoma cells in vitro and in vivo. This important result is published in the journal Cancer Cell. This study provides evidence for the pharmacological function of SPOP as a target for clear-cell renal cell carcinoma, as well as a new direction for the discovery of SPOP inhibitors and for the treatment of renal cell carcinoma, unlike kinase inhibitors. Almost at the same time, Nature has published two reports on the hypoxia-inducible factor HIF-2α inhibitor PT2399 (analogue PT2385 has entered the clinical stage), suggesting that the HIF pathway for the Small molecule inhibitors will also become a new target for renal cancer treatment. Flarebio offers recombinant proteins of good quality such as recombinant Itgb2 for your research.

Scientists have new breakthrough in motor proteins

Researchers at Penn State suggest that motor proteins which pause at the ends of microtubules and produce pushing forces can also stimulate their growth. The function of the proteins is a critical component in understanding cell division and nerve branching and growth, according to research using recombinant horse proteins.

Kinesins are found in multicellular organisms. They are a family of motor proteins. They act as little engines within the cells and transport molecular cargo along microtubules. The microtubules are hollow cylinders of the protein tubulin. They are dynamic and can grow and shrink when the cell change shape.

The researchers are trying to understand more about the motor and what makes the sequences unique since they carry out so many vital functions in the cells.

There are forty-five different kinesin motor proteins in human body in all. The researchers tracked the movements of each one and found that motor pauses at the end of the microtubules. Later it produces pushing forces to slide the microtubules apart and allow the motor to grow the microtubules. Their findings are reported in Nature Communications recently.

They bound microtubules to a microscope slide and added free tubulin subunits together with modified kinesin-5 motor proteins. The results showed that the motor proteins added improve the rate and persistence of microtubule growth.

In conclusion, if we can terminate cancer cell division, new approaches in treatment will come into being. Therefore, understanding more about how kinesin-5 influences microtubule dynamics and its importance in properly segregating genetic material in cell division is of great concern. Flarebio provides you with recombinant proteins of good quality including recombinant Dpp4.

To locate and surveil immune cell of human body with new technology

The immunotherapy of using human immune cells to attack cancer cells is the current international scientific research focus, but how immune cells specifically functions in vivo has always been a mystery. US researchers have recently developed a new method for the first time through recombinant rat proteins to achieve location and surveillance of immune cell of human body.

At this stage, immunotherapy still has its limitations. The effect of immune cells finding and killing cancer cells is sometimes better than conventional cancer therapy, but sometimes does not work. Doctors often have to wait a few months to check whether the tumor shrinks to know whether the immune cells attack cancer cells. If immunotherapy does not work, then the cancer cells may have spread or become more difficult to deal with.

Researchers at Stanford University and other researchers in the United States reported online on the academic journal Science Translational Medicine that they have spent 10 years and have found a way to track immune cells.

They have genetically engineered immune cells from patients and added a "reporter gene", a gene that directs the synthesis of a protein that can be detected by positron emission tomography. After the genetically-modified immune cells being injected back to the human body, by detecting the relevant protein, we can know the location of immune cells, the number of information, and we can analyse whether they are close to the tumor and attack.

The researchers successfully tested this technique in glioblastoma patients. They say that new technologies can also be used to track immune cells against other cancers. "The technique, which can show how the living body's immune system works without removing any human tissue, is unprecedented," says research director, Professor Sanjee Gambier from Stanford University. Flarebio offers superior recombinant proteins such as recombinant Dpp4 at good prices.

A new leap forward the prevention and treatment of fatty liver treatment

Researchers from the Institute of Biomedical Sciences (Barcelona Biomedical Research Institute) and IDIBAPS Biomedical Research Institute published their research using recombinant mouse proteins in the journal Nature Cell Biology. The researchers hope that this discovery will lead to a new leap forward the prevention and treatment of fatty liver treatment. One of the co-leaders of the study, IDIBAPS group leader Dr. Mercedes Fernández, said that it laid a good foundation for subsequent applied sciences.

Fatty liver is caused by depletion of CPEB4 in mice, and no one knows exactly what causes fatty liver, although we do know that people who are obese or overweight, or those with diabetes, high cholesterol or high triglycerides are more likely to suffer from fatty liver. In addition, rapid weight loss and poor eating habits can also lead to fatty liver. However, NAFLD may also occur in some populations without these risk factors.

Dr. Fernández and his colleagues noted that some large genomics studies have found that gene variants that encode CPEB4 are associated with dyslipidemia. In their study, the murine liver of CPEB4 was lowly expressed in the study. They found that with age, mice gradually developed fatty liver. They also found that feeding a high-fat diet to young mice deficient in CPEB4 resulted in a more pronounced fatty liver.

Further studies on the expression of CPEB4 at the molecular level suggest that this protein plays a key role in the liver stress response. For example, placing a liver cell in a stressful state caused by a high-fat diet can disturb the balance of a cell component called endoplasmic reticulum (ER). When lacking for CPEB4, ER shows less response on the stress. ER has many functions, including the production of protein and lipid and the removal of excess waste.

The researchers found that ER regains its balance by releasing CPEB4 to adapt to stress - for example, removing excess waste. They also found that circadian rhythms affected the release of CPEB4; it was more active during the day (the liver had a lot of work to do) and was quietest at night. The team believes that without CPEB4, ER can not fully restore the balance of stress, which will lead to fat accumulation, forming fatty liver. Flarebio offers high-quality recombinant proteins like recombinant TLR2 for your research.

To study protein dynamics in a new way

Researchers have developed the first computational method based on evolutionary principles to predict protein dynamics. These researchers are from the Structural Biology Computational Group of the Spanish National Cancer Research Centre (CNIO), led by Alfonso Valencia, together with a group led by Francesco Gervasio at the University College London (UK). Protein dynamics can explain the changes in the shape or dimensional structure that they experience in order to interact with other compounds or speed up chemical reactions. This study push the development of the computational study of protein dynamics, and it is helpful for the design of drugs and for the research about genetic disease. It is published in the journal Proceedings of the National Academy of Sciences (PNAS), which also publishes other studies on recombinant dog proteins.

As we know, proteins are crucial to the thousands of cellular functions which work in a living organism. It is chains of smaller molecules which are called amino acids that form the protein - a three-dimensional structure. By studying the co-evolution of amino acids, we can reconstruct the form or structure of these biological compounds in their natural surroundings. We can also predict physical contacts between amino acids with higher accuracy and in sufficient number by analyzing the sequences of a given family of proteins, to reconstruct the folding and structure of a protein accurately.

Nevertheless, the structure won't remain changeless. It interacts with other biological compounds or with drugs, which is called protein dynamics. The study about it turns out to be extremely difficult no matter through experimental observations or computational tools.

"We developed a model in which the amino acids that have a strong co-evolutionary relationship attracted each other, without further additional data," says Simone Marsili, researcher who has also participated in the project. "First, we simulate the folding process and then we can see how the simulations were able to predict the changes in shape of the proteins at different levels of complexity, including those required for kinases to function." Flarebio offers superior recombinant proteins like recombinant TLR2 at competitive prices.

Scientists are trying to push Porcn inhibitor as a regenerative agent for heart disease

Anticancer agents which are under development can promote the regeneration of damaged myocardium , and they may help to prevent congestive heart failure in the future. The results of the study have been published in the Proceedings of the National Academy of Sciences, which also publishes other studies on recombinant human proteins.

Dr. Lawrence Lum, associate professor of cell biology at UT Southwestern Medical Center, has been developing cancer drugs for Wnt signaling molecules for many years. These molecules are essential for tissue regeneration, but also often lead to cancer. What's crucially important for the production of the human Wnt protein is the porcupine (Porcn) enzyme, because Drosophila embryo lacking this gene is similar to Porcn. They were curious when testing Porcn inhibitors developed by the researchers.

"We saw a lot of predictable adverse effects in bone and hair, but one unexpected result was a slight increase in the number of split myocytes (cardiomyocytes)," said senior author Dr Lum. "In addition to a strong interest in Porcn inhibitors in anticancer agents, this study suggests that this agent can be used in regenerative medicine."

Based on their preliminary results, the researchers induced heart attacks in mice and then treated with Porcn inhibitors. Compared with untreated animals, their blood pumping capacity of the heart increased nearly twice. Dr. Rhonda Bassel-Duby, director of the Center for Regenerative Sciences and Medicine, professor of molecular biology and molecular biology, said, "Our laboratory has been studying cardiac repair for a few years. Surprisingly, the administration of Wnt inhibitors significantly improved mice Cardiac function after a heart attack."

Importantly, in addition to improving pumping capacity in mouse hearts, the researchers also noted a reduction in cardiac fibrosis or scarring. Collagen load scars that occur after a heart attack can lead to an undue increase in the size of the heart and lead to heart failure. "Although fibrotic reactions may be immediately beneficial, they may overwhelm the ability of the heart to regenerate over a long period of time, and we believe that we have a drug that can modulate this fibrosis response, thereby improving wound healing in the heart," said Dr. Murchison Linthicum, Harold C. Simmons Comprehensive Cancer Center, deputy director of basic research and a medical researcher.

In addition, Professor Lum said preliminary experiments showed that Porcn inhibitors only need to be used within a short time after a heart attack, suggesting that the unpleasant side effects which are usually caused by cancer drugs can be avoided. "We hope to push the Porcn inhibitor into clinical trials within the next year as a regenerative agent for heart disease," Dr. Lum said. Flarebio provides you with high-quality recombinant proteins including recombinant ITGB5.

To find a new and effective anticancer drug target

Cancer is a heterogeneous disease, and signaling pathways plays an important role in the occurrence and progress of cancer. According to research through recombinant horse proteins, different gene mutations can cause different signal pathway abnormalities, resulting in the performance of different clinical subtypes. Different subtypes of various anti-cancer drug reactivity will be quite different. Complex signaling pathways affect the survival of cancer patients rate and prognosis. It is a difficult problem to find a new and effective anticancer drug target to regulate the corresponding signal pathway.

Ras gene is a kind of oncogene, including K-ras, H-ras and N-ras. They can promote cell proliferation and growth in normal cells. When it shows mutation activation, Ras signaling pathway promotes cell proliferation and then malignant transformation of cells happens. In February, the electronic edition of Cell published an article by Tim wang from the University of Cambridge, Massachusetts. Under the mentoring guidance of Whitehead Institute and the Cambridge broad Institute, the researchers conducted gene sequencing on 14 acute lymphatic Cell leukemia patients and compared the main gene map and the known genomic data and found that the genotype of cancer patients will be divided into different subtypes, contributing to the development of new treatment and application.

This article tittled Major Gene Analysis Reveals the Roles of Oncogene Ras and Lethal Interactions in Gene Network Synthesis focuses on the role of genes and proteins in Ras signaling pathways in the treatment of acute lymphoblastic leukemia and other malignant diseases. The study found that, once Ras protein occurs, the disease will develop and drug therapy can be said to have been "powerless". Only from the gene level inhibition of Ras signaling pathway can effectively prevent the occurrence of malignant tumors.

With the development of genetic engineering technology, by knocking out 18,000 protein-coding genes one by one in the human genome through CRISPR-based gene editing technology, we can find the regulatory role of the Ras signaling pathway genes so as to find new anti-cancer gene target and to promote individualized treatment of cancer. It is believed that in the near future, the target drug acting on the Ras signal pathway can be applied to the clinical treatment of malignant diseases. Flarebio offers suprior recombinant proteins such as recombinant ITGB5 at good prices.