2016年11月17日星期四

Science: Amyloid protein lesion also can be the bane of tumor

Scientists at the Flanders Institute for Biotechnology (FIB) in Belgium have published a study releasing a patent called Pept-in in the world-renowned scientific journal Science. This patent was developed through recombinant human proteins and can simulate Alzheimer's disease Amyloid formation mechanism and make use of amyloid polymerization properties to make the disease protein of tumor and other diseases assemble and lose function, thus achieving therapeutic purposes. This represents a new idea of drug development and may be able to bring targeted new treatment of a variety of diseases including cancer.

Amyloid protein is a ubiquitous protein found in our daily foods, such as boiled eggs and beer foams. It has also been shown to be associated with Alzheimer's disease, multiple sclerosis, Parkinson's disease, glaucoma and other diseases. In particular, a typical pathological change of Alzheimer's disease is amyloidogenic amyloidosis in the brain to form amyloid plaques. With regard to amyloidosis related to medical research and drug development, the current mainstream idea is to inhibit the protein to treat diseases, rather than the use of this protein. There has been a significant capital injection into the development of new drugs that target amyloidogenic targets such as beta amyloidosis and Tau protein.

Amyloid formation seems to imply a negative pathogenic signal. However, research teams led by Prof. Frederic Rousseau and Professor Joost Schymkowitz of the VIB Institute have used these substances to form tumors and attack many diseases.

They used their own development of Pept-in patented technology to design and synthesize a vascin called amyloidogenic material (a characteristic amyloid protein structure of short-chain peptide sequence). The molecule has to promote amyloidosis which can rapidly penetrate the tumor cell membrane and promote the tumor cells on the vascular endothelial growth factor receptor 2 (VEGFR2) protein cohesive degeneration and lose their function. VEGFR2 is an important molecule to promote the survival of tumor growth. It means that the inactivation of cancer can inhibit the therapeutic effect.

"This method allows the surface protein of the tumor to condense. It is just like a tumor-like spider web-like dragnet traps tumor to limit its growth," Professor Rousseau said. He is convinced that using of Pept-in patented technology and aimed at the key disease for many diseases protein, they can design and synthesize the corresponding polymer molecules (amyloid protein structure of the characteristics of short-chain peptide sequence) to promote the pathogenic target protein to enhance cohesion and then fight many diseases. Because Pept-in patented technology makes use of the principle of amyloid formation to apply it to almost any target protein aggregation process. In the future, it can’t only be used to develop anti-cancer therapy, but also can be used against drug-resistant bacterial infection.

"In the next few years, our team will focus on using this technology to benefit more patients," Professor Schymkowitz said at the press conference. Flarebio offers recombinant proteins of good quality such as recombinant PIGR at great prices.

2016年11月16日星期三

Scientists uncover how plants respond to drought at the molecular level

The sagging and drying of plant leaves suggests that we should water them, but how do plants respond to drought at the molecular level? Scientists at the Salk Institute have recently made a major breakthrough on this issue. This finding might help agricultural production adapt to adverse climates such as drought. The study was published in the Nov. 4 issue of Science. Studies have shown that in the face of unfavorable natural conditions, a small part of the plant proteins would act as a "command" to regulate the complex stress response. These experimental results were conducted using recombinant dog proteins and are expected to contribute to the development of new technologies for improving the use efficiency of plant water.

"At the molecular level, the response of plant to stress is a complex process involving hundreds of genes," said Joseph Ecker, author of the paper. "We have discovered a class of regulatory proteins that play a key role in plant responses to stresses such as drought. And if we can control a regulator protein, it's the equivalent of controlling all the genes it regulates."

Plant roots and leaves would secrete abscisic acid when water is scarce or salinity is high. "Only twenty or several regulatory proteins control the expression of hundreds or even thousands of genes," said Liang Song, the first author of the paper. "By identifying key regulatory proteins and studying their mechanisms of action, we can gain a deeper understanding and even regulate plant responses to stress."

In the experiments, the team at the Salk Institute tracked real-time changes in gene expression during plant secretion of abscisic acid and identified key regulatory proteins. These proteins control plant response to drought stress conditions such as stress response. By locating the binding sites of these regulatory proteins to DNA, they identified key proteins that can regulate gene expression networks, which can efficiently elicit a stressful response to environmental changes. This group focused on studying some of the known regulatory proteins that respond to abscisic acid.

During the experiment, they obtained 122 data sets containing 33,602 genes, of which 3061 genes had at least one time point of change in the expression intensity. Data analysis revealed a multi-level regulatory mechanism, in which regulatory proteins play a key role in gene expression regulation. Interestingly, the binding pattern of a protein at a particular time in DNA can explain much of the expression of a gene over a longer period of time. These kinetic properties together reveal that plant responses to environmental stimuli are a genome-wide synergistic response.

"Based on the understanding of the network structure, we found that a single key regulatory protein can control multiple components, which means that gene regulation is an accurate and interrelated process." Song said. "This is important for agriculture because it suggests that the control of one gene can activate or inhibit another set of genes, making it possible to design a human intervention program as a whole." This study suggests that this multi-level synergistic gene activity may be widespread in flower plants. Flarebio offers good-quality recombinant proteins such as recombinant CDH15 at good prices.

A new small molecule that can drive an extracellular-controlled hypoxic response

An international team has found through recombinant human proteins that a new small molecule called VH298 that can drive an extracellular-controlled hypoxic response.

The new study, led by Dundee University researcher Alessio Ciulli, is a new clinical approach that is critically important in the field of ischemic injury research due to brain and heart problems, as well as chronic kidney disease or chemotherapy-induced cardiovascular damage and anemia.

The use of small molecules in recent years is one of the research hot spots in new drug development, because it allows for the selective validation of new pharmacological targets and the rapid development of new compounds. However, the identification of these molecules is indeed more difficult.

According to the researchers, VH298 can inhibit the protein-protein interaction between the ubiquitin E3 ligase VHL and the HIF-1alpha transcription factor, a process similar to the selective control pathway that results in hypoxia in vivo. This work demonstrated for the first time that VHL protein as a drug intervention target. VH298 can stimulate erythropoietin (EPO) levels and resist hypoxia-induced injury.

Researcher Carles Galdeano, a member of the Computational Biology and Drug Design Research Group, graduated from the University of Barcelona School of Pharmacy with a PhD, and his previous research focused on neurodegenerative drug intervention.

Galdeano now focuses his research efforts on small molecule identification with biomedical roles in the proteasome ubiquitin system and is currently doing postdoctoral research. Flarebio offers recombinant proteins of good quality such as recombinant PIGR at great prices.

2016年11月15日星期二

High-protein diet is good to your body and helpful to losing weight

Previous studies have shown that high-protein diet can help to lose weight - researchers now believe that they find the principle in it. Some studies have shown using recombinant mouse proteins that high-protein diet is good for you and also helps you lose weight. Researchers at the Imperial College in London have discovered the esoteric. Protein in the digestion process will produce an amino acid called phenylalanine. It will raise a hormone level, telling us that we've been full and we should reduce food intake.

The key to the problem is appetite. The release of phenylalanine from high-protein foods suppresses hunger. There are two sets of mechanisms. First of all, it will stimulate the body to create a hormone called GLP-1, which will inhibit your appetite, so you do not overeat. Second, it reduces the secretion of a hormone known as gastrin. The combination of both makes you feel fuller and hungrier.

The researchers did experiments in rats, injecting only one dose of phenylalanine and comparing them with mice that did not inject any material. They found that both hormonal levels were changed. When they gave obese mice a high-protein diet, these changes affect the body - mice eat less and began to lose weight.

In the final experiment, scientists used phenylalanine in human intestinal cells in culture dishes and observed the same process. Of course, the mouse and petri dish cells with the human body are huge, but this is still very convincing evidence. Mariana Norton, the first author of the paper, will present the study at this week's Congress of Endocrinology, which will then be peer reviewed and published.

Meat is a good source of protein, but not the only source. Other animal products (milk and eggs, etc.) and plants (spinach, tofu, amaranth, etc.) are excellent sources of protein. Flarebio provides superior recombinant proteins like recombinant Aoc3 at competitive prices.

Scientists discover new-type rearrangement mutations of B-ALL

Analysis of B-ALL carcinogenic mutations through recombinant horse proteins is of great significance for prognosis and treatment options. However, it is still not possible to identify the genetic basis of nearly 30% of B-ALL cases.

Researchers at institutions such as St Jude Children's Research Hospital recently conducted a transcriptome analysis of samples from more than a thousand B-ALL patients and found a new class of oncogenic rearrangements. These rearrangements all involve the MEF2D gene, the latter one may combine with at least six other genes (the BCL9 gene is the largest) after rearrangement, resulting in a fusion protein. The average age of patients with these mutations was 14, and the five-year disease-free survival rate was 71.6%. The researchers speculated that 5.3% of the currently unknown B-ALL cases in 30% of those carcinogenic mutations actually showed MEF2D gene rearrangement mutations. The findings are published in the recent issue of journal Nature Communications.

Panobinostat (Farydak) is an inhibitor of histone deacetylase (HDAC) and was approved by FDA in February 2015 for use in combination with bortezomib and dexamethasone to treat multiple myeloma. The researchers found that the HDAC expression levels of B-ALL cancer cells with MEF2D gene rearrangement mutations were significantly higher, and once it was administered panobinostat, its growth will be effectively curbed.

"In the past few decades, we have gained an in-depth understanding of the genetic changes that have led to ALL," said Dr. Stephen P. Hunger, Ph.D., author of The Children's Hospital of Philadelphia. "However, this study shows that we are still discovering new-type ALL subtypes. Gene mutations that occur in these ALL cancer cells will provide important information about therapeutic efficacy and accurate medical planning."

In addition to MEF2D gene, the researchers also found 20 patients with ZNF384 gene rearrangement mutations. ZNF384 protein is also a transcription factor. Among them, ZNF384 can recombine with other six genes to produce fusion protein. Analysis showed that B-ALL cancer cells carrying MEF2D and ZNF384 gene rearrangement mutations had a unique gene expression pattern. This suggests that the above fusion proteins are likely to be the key factors leading to cancer.

In the colony-forming experiments, the researchers also found that the MEF2D-BCL9 fusion protein could significantly enhance the proliferation of mouse lineage negative bone marrow cells by viral vectors, while the normal MEF2D or BCL9 protein did not.

"This suggests that the formation of MEF2D fusion proteins is a critical step in the transformation of leukocytes with limited longevity into infinitely proliferating leukemic cancer cells," said Dr. Charles G. Mullighan. Flarebio provides you with good-quality recombinant proteins such as recombinant TLR2 at great prices.

2016年11月14日星期一

Scientists find the link between DNA and chronic joint pain

Scientists at King's College London have discovered a link between DNA modification and chronic generalized joint pain, one of the main symptoms of fibromyalgia, and the study is funded by the Arthritis Research Foundation. Fibromyalgia is a common chronic condition that causes muscle and bone fatigue and widespread pain. Although fibromyalgia is very popular, the etiology is little understood, and the treatments are limited. What's worse, fibromyalgia can't be detected using routine tests such as scanning or X-ray detection. The disease affects 4% of the world. The study, published in the journal PLOS ONE which also has other studies on recombinant dog proteins, will help scientists develop a diagnosis of fibromyalgia through blood tests.

"Fibromyalgia is affected by genetic factors, but there are a number of complex intermediate processes between genes and diseases," said Frances Williams, Ph.D., one of the authors of the article from the Department of Twin and Genetic Epidemiology. "Identifying measurable epigenetic associations is an important step. What's more, these results will provide information on future studies of fibromyalgia and other chronic pain syndromes, such as irritable bowel syndrome."

Stephen Simpson, director of the British Arthritis Institute, commented on the study, "Millions of people in the UK suffer from fibromyalgia, and this exciting study has helped us understand how individuals' epigenetic differences affect fiber Myalgia and chronic extensive musculoskeletal pain. For people with long-standing fibromyalgia, they have been struggling to diagnose their pain symptoms. This study will help to better understand, manage and treatment joint pain."

The researchers used twins to study whether DNA methylation affects the way genes start up when they produce a particular protein and to observe whether there are differences between musculoskeletal pain patients and non-patients. Scientists have determined that patients with chronic extensive pain and non-patients have different levels of DNA methylation in the three genes. Preliminary indications suggest that people may have different methylation patterns in their DNA and that this may affect the initiation of some genes and may lead to a variety of conditions. Flarebio offers superior recombinant proteins including recombinant Ptpra at good prices.

These antibiotics can also be cheaper and easier to treat tuberculosis!

Scientists have taken an important step in designing a new antibiotic to fight resistant bacterial infections, such as tuberculosis. In the study of natural chemical biology using recombinant mouse proteins, they described these new compounds to attack previous non-targeted enzymes, which are important for building and sustaining the cell wall of bacteria. The team said that these antibiotics can also be cheaper and easier to treat tuberculosis (TB).

The treatment of MDR-TB is costly. In addition, the treatment takes a long time and do harm to human body, and it has potentially life-threatening side effects. "One of the reasons for the new study is that more than half of the antibiotics given to patients today are of the β-lactam class," said Gyanu Lamichhane, associate professor of medicine at the Johns Hopkins University School of Medicine in Baltimore. These drugs paly their role by destroying DD-transpeptidase enzyme, while this enzyme is essential for the construction and maintenance of bacterial cell walls. Without enzymes, the bacteria die quickly.

However, about 10 years ago, the researchers discovered another enzyme called LD-transpeptidase - also important for the cell wall - is an antibiotic that allows bacteria such as TB to survive. In new research - in a complex imaging system, with the help of a protein called X-ray crystallography, the team investigated the detailed molecular structure of the LD-transpeptidase extracted from various bacteria.

With knowledge about the structure of the new enzyme, the researchers then tested the molecules that might work on it. They tested new compounds from beta-lactam antibiotic subclasses that specifically bind to new enzymes. By using live bacterial cultures, they show that compounds called carbapenems block wall-building enzymes. This also suggests that CDC, called the ESKAPE pathogen, works in a group of bacteria and is considered a particular threat because of its ability to resist drug resistance.

The team also tested two carbapenems in different groups of TB-infected mice. They found that even without the use of classical tuberculosis antibiotics, new compounds - especially ibuprofen - had a better therapeutic effect on tuberculosis in mice. "Our data show that carbapenem successfully treats tuberculosis infection by attacking enzymes," said Professor Lamichhane. The team is now planning clinical trials to test the safety and efficacy of some of these new compounds. Flarebio provides good-quality recombinant proteins like recombinant Itgb1 at competitive prices.