A study identifies the molecules which control excessive expansion of myocardial cells

When the heart is subjected to pressure such as high blood pressure, it responds by dilatation at the level of the whole organ and some chambers and at the level of a single cell. Although cardiomyocyte swelling has been studied using recombinant mouse proteins, we still do not know the molecular mechanisms that promote and inhibit this process. Researchers at the University of Osaka have now discovered a protein that generally inhibits the acceleration of cell activity and dilation that occurs under stressful conditions. This new finding explains how to prevent the formation of overexpressing cells in the myocardium and to treat or limit heart dilatation associated with heart failure.

Cardiac hypertrophy occurs when the myocardium is at a higher pressure than normal and requires greater volume adaptation. At the cellular level, cardiomyocyte increase is induced by the acceleration of production of proteins and other components. From genes to proteins, including RNA intermediates, they determine the overall cellular protein composition through additional regulatory levels. Therefore, in order to understand how cardiomyocytes are swollen due to increased protein production under stress conditions, it is necessary to reveal the overall regulatory status of these intracellular RNAs.

The new study identifies and makes protein Btg2 a global regulator of RNA in cardiomyocytes and has made significant progress in this area. By imaging individual cells, it was found that this protein was overexpressed in stressed cardiac tissue to reduce the size of cardiomyocytes, indicating that Btg2 is a limiting factor for cardiac hypertrophy.

"Our first concern is the goal of protein Myc, which is known to increase the size and metabolic activity of cardiomyocytes," said author Shuichiro Higo. "We found that Myc strongly induced Btg2, but these two proteins had opposite effects on RNA levels in these cells, indicating that they were on the opposite side of the regulatory protein production and cell size.

The use of single cell imaging in this study enabled the team to identify Btg2 in the cell and to correlate it with functional analysis to determine the mechanism by which global RNA levels are reduced. The results show that Btg2 interacts with the cellular machinery that breaks down RNA, which explains that Btg2 reduces protein production and decreases the number of cells.

"We are now able to respond to stress and dilate the heart cells, and have a better understanding of the mechanisms that limit this expansion," Higo says. "We may be able to use these mechanisms to reduce long-term cardiac hypertrophy and some of the heart-related problems." Flarebio provides you with recombinant proteins of good quality like recombinant ACSL3 at competitive prices.

Researchers develop a platform to recognize specific target antibodies

A new study may completely change the slow, cumbersome and expensive process of detecting the antibodies that can help with the diagnosis of infectious and auto-immune diseases such as rheumatoid arthritis and HIV. An international research team has made use of recombinant proteins including recombinant human proteins to design and synthetize a nanometer-scale DNA "machine" whose customized modifications enable it to recognize a specific target antibody. This new approach is said to support the development of rapid, low-cost antibody detection at the point-of-care, eliminating the treatment initiation delays and increasing healthcare costs associated with current techniques.

The binding of the antibody to the DNA machine causes a structural change which generates a light signal. The sensor does not need to be chemically activated and is rapid - in five minutes - enabling the targeted antibodies to be easily detected, even in complex clinical samples such as blood serum.

This DNA nanomachine is highly versatile that can be in fact custom-modified so that it can detect a huge range of antibodies, this makes our platform adaptable for many different diseases.

The modular platform provides significant advantages over existing methods for the detection of antibodies. It may prove to be useful in a range of different applications such as point-of-care diagnostics and bioimaging.

Besides, this platform has an advantage of low-cost. The materials needed for one assay cost about 15 cents, which makes the approach very competitive in comparison with other quantitative approaches.

These preliminary results make the researchers exciting. There are more to make this approach available to everyone. Flarebio offers recombinant proteins of good quality like recombinant ACSL3 at good prices.

New findings help to improve the development of anti-TB drugs

Tuberculosis (TB) caused by M. tuberculosis (Mtb) remains to be a major global public health challenge. TB research and new drug development are urgently needed due to the limited availability of drugs that are currently available to treat TB, especially MDR-TB and XDR-TB. Mtb is a typical intracellular pathogen. Mtb evolved a variety of immune escape strategies in the process of long-term coexistence and interaction with the host. Therefore, in-depth study of the interaction between Mtb and the host immune system using recombinant human proteins and its regulatory mechanism is of great significance for elucidating the molecular mechanism of Mtb latent infection and pathogenesis and providing new drug targets for the development of anti-TB drugs.

Liu Cuihua research group at The Institute of Microbiology has been working on the molecular mechanism of the interaction between Mtb and other important pathogens and hosts. In recent years, he has published a series of studies in Nature Immunology (2015), The Journal of Immunology (2015), etc., to uncover the new mechanism of Mtb regulating host cell function then escaping host innate immunity through secreting effect protein (including PtpA and Mce3E, etc.). In addition to investigating the role of effector proteins in the immune regulation of the host from the perspective of pathogens, the team explored the mechanisms of immune defense in pathogen infection from a host perspective. In the process of in-depth study of the regulatory function of the Mtb-effector protein PtpA, they identified host interaction protein TRIM27 (an ubiquitin ligase) of PtpA.

Further studies have shown that TRIM27 can act as a host restriction factor to inhibit the survival of mycobacteria in macrophages. TRIM27 can activate JNK / p38 signaling pathway of host cells and promotes apoptosis in ubiquitin ligase-dependent manner, thus inhibiting the intracellular survival of mycobacterium. Interestingly, the study also found that Mtb PtpA can bind to RING domain of TRIM27 protein to antagonise TRIM27-mediated activation process of innate immune signaling pathways and apoptosis in order to achieve the purpose of promoting intracellular survival of Mycobacterium. The study revealed the dynamic process and molecular mechanism of the interaction between pathogen and host, providing new ideas and specific targets for the development of antituberculosis drugs. Flarebio offers recombinant proteins of good quality such as recombinant ACSL3.

Is our memory stored in brain cells?

Studies suggest that memory is likely to be stored in the brain cells. If this conclusion is correct, it will bring major breakthrough for the treatment of post-traumatic stress disorder (PTSD). The main manifestation of patients Post-traumatic stress disorder is that patients will continue to suffer painful memories of the intrusion.

More than a decade ago, scientists began to use a drug called propranolol for the treatment of post-traumatic stress disorder. Propranolol can block the synthesis of some proteins that are essential for long-term memory. Therefore, this drug was thought to prevent new memory from forming. Unfortunately, through research using recombinant human proteins, researcher got that unless taking the drug immediately after the painful event happens, otherwise people will still have unpleasant memories. Recently, studies have shown that when a person recalls a memory, the re-activated connection is not only enhanced, but will temporarily become easier to change - this process is called memory reconsolidation. The use of propranolol can prevent memory reconsolidation and clear the related synapses.

The researchers applied a slight electrical stimulation to the sea hare to make them form the memory of the event and new synapses in brain. Then, they transferred the neurons of sea hare into culture dish and chemically triggered this memory, followed by the application of propranolol.

As with earlier studies, propranolol cleared this memory-related synapse. However, when the memories of these cells were triggered again, the memory was fully recovered within 48 hours. So they guessed that the memory was not completely stored in the synapse.

Scientists carefully checked the neurons and found that although the synapse has been cleared, but the molecular and chemical changes within cells were retained. It may be that these permanent changes leave traces of memory. Another possibility is that memory is encoded by epigenetic modifications in the DNA of cells, and these modifications will affect the way genes are expressed. Researchers are inclined to the latter explanation.

New research has shown that drug therapy is unlikely to drive the painful memory of patients with PTSD, even though it is just getting started. The researchers said, "If you asked me about whether PTSD could treat with drugs two years ago, I would probably answer yes. But now I do not think so. The new discovery that memory is stored in cells may contribute to the treatment of another memory-related disease - Alzheimer's disease. Flarebio offers recombinant proteins of good quality such as recombinant ACSL3.

Get to know spontaneous autoimmune diseases better

A group of scientists led by researchers at Stony Brook University conducted experiments using recombinant human proteins and discovered a new mechanism of a bacterial toxin inhibiting inflammation. Their research showed that a toxin in Yersinia - bacteria agent of plague, can target inhibits protein pyrin. Hereditary autoinflammatory disease - Familial Mediterranean Fever (FMF) - is induced by sustained activation of pyrin protein which is caused by gene mutation.

The study was published in the journal Host Cells and Microorganisms, and it can be used to better understand the genetic origins of FMF and to explore new therapies for the treatment of these diseases.

"This finding is very significant because the popularity of Mediterranean-origin people suffering from Familial Mediterranean Fever (FMF) is very high, and the findings may explain the natural selection process behind the disease," Dr. James Bliska from Molecular, genetics and microbiology department of Stony Brook University School of Medicine, the lead author and professor said, "In addition, bacterial toxins would hijack the body kinase and phosphorylate and inhibit pyrin protein. This process can be converted into the process of treatment of FMF."

Hereditary inflammatory diseases brought by FMF usually occur at some time in childhood and would persist throughout adulthood. There are treatments, but no cure. For example, complications such as arthritis and vasculitis can appear long after the onset of inflammation. Thousands of people from different ethnic origins of the Mediterranean, such as Armenians, Italians, Greeks and Arabs, are suffering from FMF. Flarebio provides you with good-quality recombinant proteins such as recombinant ACSL3.

Scientists discover the regulatory role of LSD1 in somatic cell reprogramming process

Recently, the journal Scientific Reports published the latest research results of Zheng Hui study group from Guangzhou Institute of Biomedicine and Health and Chinese Academy of Sciences online, and the paper is titled "Lysine-specific histone demethylase 1 inhibition promotes reprogramming by facilitating the expression of exogenous transcriptional factors and metabolic switch". The research, using various recombinant proteins including recombinant horse proteins, reveals the regulation mechanism of histone lysine residues methylation enzyme LSD1 on cell metabolism and the transcription factor expression in somatic cell reprogramming process.

Epigenetic refers to heritable changing process of gene expression the process of cell division without altering DNA sequence. While in the process of cell reprogramming, epigenetic information within cells has changed, and especially histone methyl glycosylation state has undergone tremendous changes. As a member of epigenetic modification enzymes, LSD1 can specifically modify histone lysine residues H3K4 and H3K9 methylation status, but the study reports of its mechanism in the reprogramming process are relatively less.

Zheng Hui study group used MEFs and pre-iPSCs cells as model system to systematically describe the gene expression of LSD1 to exogenous transcription factors in reprogramming process and its impact on the transformation of metabolic way in reprogramming process. The researchers found that in the reprogramming process of somatic cells, inhibiting the activity of LSD1 can improve the efficiency of cell reprogramming. Further study found that inhibiting the activity of LSD1 can prevent the H3K4 demethylation of upstream area of exogenous transcription factor gene, thereby improving the expression of endogenous transcription factor, but also speed up the transformation of metabolic way in reprogramming process by affecting the expression of Hif1α gene and its downstream genes, thus improving the efficiency of reprogramming process. Finally, in the process of pre-iPS cells transforming into iPS cells, inhibiting the activity of LSD1 also can significantly improve the conversion efficiency of the pre-iPS cells by changing their metabolism way.

The research was mainly conducted by Zheng Hui study group and Guo Yunqian from Beijing Forestry University. Related achievements were funded by the National Natural Science Foundation of China, Chinese Academy of Sciences, Municipal and Technology project of Guangzhou. Flarebio provides you with good-quality recombinant proteins such as recombinant ACSL3 at competitive prices.

New study provides theoretical basis for the treatment of inflammatory related diseases

Zhang Haibing Study Group at Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences reveals the functional mechanism of programmed cell death-associated protein MLKL and FADD in inhibiting lymphocyte proliferation and activation of inflammatory body NLRP3, providing theoretical basis and new ideas for the treatment of inflammatory related diseases. Related research was recently published online in the journal Cell-Communication, which also provides many studies on recombinant horse proteins.

FADD is an important molecule which mediates apoptosis. Mice with FADD knockout died in about 11.5 days in embryonic stage, but simultaneous knockout of RIP3 could save embryonic lethality, and mice with FADD and RIP3 double knockout showed progressive proliferation of lymphocytes.

The researchers used CRISPR / Cas9 system to build mice with FADD and MLKL double knockout, first confirming that MLKL deletion can save FADD knockout-caused embryonic lethality. Further studies showed that with age, mice with FADD and MLKL double knockout began to suffer from systemic autoimmune lymphoproliferative disease at about the age of 9 weeks, manifesting as generalized lymphadenopathy and splenomegaly. Flow analysis showed that the accumulation of a large number of CD3 + B220 + double-positive lymphocytes existed in the lymph nodes and spleen of mice, and it increased with the development of the disease.

At the same time, studies showed that in the conditions of MLKL and FADD commonly missing, bone marrow macrophages NF-kB signaling pathway weakened, reducing the transcription of key molecule NLRP3 which was dependent by inflammation body activation, thereby affecting the formation of inflammatory body, the cut of Caspase-1 and the secretion of IL-1β.

The study reveals the regulation mechanism of FADD and MLKL in the process of mouse embryonic development, immune system balance homeostasis and inflammatory body activation, providing new evidence for cell death related proteins involving in inflammation reaction as well as potential drug targets for the treatment of inflammatory diseases. Flarebio offers recombinant proteins such as recombinant ACSL3 at good prices.

Scientists find the "on-off" of antiviral immune cells

How does "Once having identified viruses, natural immune cells would response" happen? Academician Cao Xuetao research team from Chinese Academy of Engineering found that DNA methylation enzyme Dnmt3a can make natural immune cells in highly sensitive state against virus infection. Once identifying viruses, they can produce significant interferon and start antiviral innate immune response. The study was published in the UK journal Nature Immunology. Many other recombinant proteins against viruses are also studied.

In order to figure out why the natural immune cells have the function of rapid resistance "virus invasion", the research team first made the natural immune cells infected with virus and analyzes molecular changes of infected cells expression. They chose "epigenetic regulation elements" which can determine gene expression by regulation of DNA methylation as the breakthrough point. By screening, they discovered that DNA methyltransferase Dnmt3a can promote innate immune cells to efficiently release type I interferons.

"Later they got genome-wide DNA of natural immune cells and ascertained the methylation status of the DNA chain at single nucleotide level and drew 'spectrum'. Take this spectrum as a benchmark, we conducted a study of the mechanism." Said Cao Xuetao. He and immunization doctoral student Li Xia at Zhejiang University, Zhang Qian from Key Laboratory of Medical Immunology at second Military Medical University immunization State discovered the specific effect path: Dnmt3a is bound to HDAC9 distal promoter region and maintains the DNA hypermethylation in the region, thereby antagonizing H3K27me3 in the region and promoting the active histone modification levels of proximal promoter to maintain high HDAC9 expression. Highly-expressed HDAC9 then efficiently induce type I interferon through a certain mechanism, starting antiviral innate immune response. The researchers used various recombinant proteins including recombinant mouse proteins to ensure the research results.

Studies have shown that DNA methylation can maintain high expression of key molecules in antiviral signaling pathway, preparing to efficiently and timely start antiviral immune response native cell during virus invasion. The findings reveal a novel epigenetic mechanism of antiviral immune response and also propose new potential molecular targets for prevention and treatment of viral infectious diseases.

Flarebio Biotech LLC is Flarebio Biotech LLC is a National High-Tech Enterprise with research, production and sales as one. We offer recombinant proteins including recombinant ACSL3, antibodies and other related products.

Various new tools allow scientists to see proteins in living cells

Proteins are particularly complex molecules. They are bent and enlaced in various ways to execute reactions which cell metabolism and growth need. But how these miniature machines are integrated together to complete the cell function? With the use of recombinant protein technology, they get some answers.

Innovation is emerging. Bewersdorf team is working with two other research teams to study clickable chemical probes: SNAP-tag of New England Biolabs and HaloTag of Promega Biotech companies. These technologies include a shorter target sequence which can be encoded to the interested protein and a dye molecule which can be embedded in the target protein by a simple chemical reaction. Bewersdorf and his colleagues have demonstrated that the two technologies can make use of organic dyes to function on living cells.

While Selvin lab developed a smaller quantum dot with a diameter of approximately 9 nm. The size allows him to glide the quantum dot between nerve cells in the space of 20 to 40 nm, and signal transduction molecules transmit information to neighboring nerve cells via this place. The lab also plans to perforate the cell membrane and then quickly seal it to prevent damage to cells. "We are able to make a bacterial enzyme called streptolysin to drill a tiny hole about 5 nanometers in the cell membrane." Selvin said. This width is enough to let through a fluorescent protein and even a protein joint with antibody in order to find the target object inside the cell. After that, researchers used the unpublished methods to patch holes in 20 minutes using of recombinant horse proteins.

In addition, there are worries that the probes would interfere with the function of the target protein. While biophysicist Jie Xiao at The Johns Hopkins University has put forward an alternative method that will not damage these proteins.

Her molecules probes don't attach to the targeted after getting genetically modified. After being produced, they are immediately split by a kind of enzymes and enter a specific location of the cell membrane. This means that they no longer carry the location information of the target molecules but they are located in a position where they can accurately calculate them, and thereby obtaining accurate count of protein production. At the same time, the protein itself can function freely. This technology is called CoTrAC.

"Quantifying protein levels in living cells is very important," Xiao explained, "People often use fluorescence to indicate the relative change." But the genes she studied regulate few proteins, and it is difficult to image through super-resolution counting. In addition, subtle changes in the precise number of these proteins also can judge whether there is a change in the state of cells. To learn more about how proteins work and what kinds of recombinant proteins (such as recombinant ACSL3) there have, you can visit Flarebio’s website.