Cancer cells may spread faster due to fat metabolism

Hepatocarcinoma is the third leading cause of cancer-related death worldwide and is the fastest growing cancer in Australia. "Many people suspect that the fatal nature of liver cancer is the process of cell metabolism, which is thought to play an important role in helping cancer cells to proliferate," says Kyle Hoehn, associate professor at UNSW. The team led by Hoehn managed to successfully prevent the formation of fat in hepatocytes of transgenic mice with unintended consequences. Unlike the team predicted that the termination of the growth of cancer cells, blocking this metabolic pathway led to more than twice the emergence of the tumor. The surprising results were published this week in Nature Communications, which also publishes other studies on recombinant human proteins.

Hoehn said, "It is currently developing drugs to target and block this metabolic pathway, which is considered promising to treat the liver and other cancers. These results may cause some concern at least for liver cancer. Our findings are completely contrary to intuition. But it is clear that any use of these drugs in the treatment of liver cancer should be more cautious in the future because there may be unintended consequences."

When cells divide, they need to reconstruct all of their structural components including their protective film made of fat and promote the process through lipid production. "The fat generation is the hallmark of invasive liver cancer, and the survival rate of high-fat-producing tumors is the lowest," Hoehn said. "Before we start this experiment, we believe that if you can knock out fat-producing legs, then you can stop rapid formation or proliferation of cancer cells."

The team tested whether their genetically-modified mice could obtain cancer by exposure to DNA-damaging carcinogens and introducing high-fat diets. These injuries increase the risk of developing advanced tumors of life. At 9 months of age, they compared the tumor burden of genetically-modified mice and mice with normal liver fat production. The results were very surprising. In addition, the team found that cancer cells rapidly adapt to the loss of fat production: they began to remove more fat from the blood and burn more fat by burning less fat. Thus, by pulling out one leg of lipid metabolism, they got stronger.

Although it looks like a retrograde on the surface of cancer treatment, Hoehn said, "Cancer cells seem to always have a solution. They are smart little bastards. This finding has revealed valuable insights into the complex biology of cancer cells and also identifies possible new targets for future drugs: mechanisms that drive antioxidant defense systems or fat intake." By the way, Flarebio offers high-quality recombinant proteins such as recombinant NPP1 for your research.

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.

To better learn transcription factors through SMiLE-seq

EPFL scientists have developed a technique through recombinant rat proteins to make DNA-binding proteins faster, more accurate and more efficient. The results were published in the Jan. 16 issue of Nature-Methods.

The gene contains the DNA code used to produce all the proteins in the cell. To begin the process, the gene must first be transcribed from DNA into RNA. This requires a huge family of DNA-binding proteins called transcription factors, which are of great interest to biologists because of their importance in gene expression. However, due to their pure numbers, their ability to combine into pairs and the difficulty of studying their DNA binding properties in the lab, scientists have known little about transcription factors despite of much effort.

The Bart Deplancke lab at the EPLL Institute of Biotechnology has now invented a new technology called SMiLE-seq, which can greatly accelerate the process with a small amount of transcription factors. The technology uses microfluidics: the science of controlling minute liquids in the same tiny space. Microfluidics is fast becoming an outstanding area of ??EPFL, bringing together many different fields and disciplines.

SMiLE-seq works by adding a small amount of transcription factors (or factors when detecting heterodimers) in microfluidic devices that have microchannel-sized chips that allow liquid to flow therethrough. Once the transcription factor is attached to the surface of the chip, large libraries of random DNA are gently pumped into the chip and flow through them. This allows the transcription factor to recognize its corresponding DNA sequence. Thereafter, the transcription factor-DNA complex is physically captured by dropping the microfluidic control button, and the unbound DNA is simply washed off.

Next, the bound DNA is removed from the device and ready for sequencing to identify which portion is captured by the transcription factor. This information is input into specialized software that allows the researcher to determine the DNA binding properties of transcription factors or heterodimers. This, in turn, helps to better predict the in vivo DNA binding profile.

The use of microfluidics in SMiLE-seq offers three major advantages: First, it reduces the amount of transcription factor required for this type of experiment because it only requires their picogram. Second, it greatly accelerated the experimental process, from a few days to less than an hour. Finally, SMiLE-seq is not limited by the length of the DNA target sequence, nor is it biased towards a stronger affinity protein-DNA interaction. Flarebio provides you with high-quality recombinant proteins like recombinant NPP1 at competitive prices.

Nature Communications: new target of atherosclerosis has been found

Recently, a team from Yale University found a protein that plays an important role in intravascular deposition of low-density lipoprotein (LDL) cholesterol, which provides an innovative medical approach to block LDL deposition. To prevent or slow down blood vessel obstruction leading to heart disease. The research is published in the journal Nature Communications, which also publishes other studies on recombinant human proteins.

Cardiovascular disease caused by atherosclerosis is the world's first major cause of death. Atherosclerosis occurs because lipoproteins, especially LDL, bind to fat and cholesterol in the bloodstream and transport them through the endothelial cells that make up the inner walls of the blood vessels, whereas the deposition of fats and cholesterol in the subendothelial region results in Atherosclerosis of the important reasons.

At present, the most effective therapy to prevent such diseases is to lower the level of LDL in the blood, which reduces the likelihood that LDL lipoprotein particles enter and reside in the vessel wall. However, the molecular mechanisms by which LDL is transported across the vascular endothelium have not been fully elucidated. For a long time, scientists believe that LDL receptors are responsible for intracellular transport of LDL function. However, some people who don't have LDL receptors in the body still produce high levels of LDL deposition, which mechanism is still an unsolved mystery.

To find out the mechanism of LDL transport, researchers at Yale University used RNAi libraries to screen more than 18,000 genes. They focused on genes that affect the transport of LDL into endothelial cells. The results show that a protein called ALK1 can help LDL to the intracellular transfer. ALK1 binds directly to LDL and promotes LDL through endothelial cells into subendothelial tissue through a specific endocytic pathway, rather than introducing LDL into lysosomal degradation. If the ALK1 gene is specifically knocked out in the endothelial tissue of the mouse, the LDL level of the vascular endothelium is reduced.

"We found that ALK1 protein can bind to LDL, which means it may trigger early atherosclerosis," said William C. Sessa, professor of communication at the University of Yale. "If we find small molecules or antibodies that block ALK1 protein, then it may be used in conjunction with other lipid-lowering therapies to reduce the risk of atherosclerosis." By the way, Flarebio provides you with high-quality recombinant proteins like recombinant NPP1 at good prices.

This microprotein existing in P-body is also vital to our body

In the genome of human body, there is a large number of genes small open reading frame (smORF). They encode too small proteins that most of these genes have not been annotated, not to mention the function of the protein they translate. These "microproteins" are difficult to detect. Therefore, scientists at Yale University and the Salk Institute have adopted a set of special methods through recombinant mouse proteins. They first cleared the larger volume of protein in the cell and then analyzed the amino acid sequence of the remaining protein components using liquid chromatography-mass spectroscopy proteomics and designed the biology Information algorithm. The results identified more than 400 such microproteins and their genes. The results have been published in the recent issue of the journal Nature.

Among the microproteins over 400, the scientists have performed a functional study of a protein that is involved in mRNA degradation in the cell and recycling excess mRNA, preventing mRNA from continuing to produce specific proteins that are no longer needed. Thus, the process of gene expression in the cell regulation is very important. However, for this mechanism, we didn't know that there is a "little" protein which plays a key role.

The protein, called Nobody, is indeed "obscure" as its name looks like. However, Nobody's actual full name is non-annotated P-body dissociating polypeptide, which means "un-annotated P-body dissociation polypeptide" and has high evolutionary conservatism.

The researchers found that Nobody exists in the P-body and has interaction with a variety of protein components (such as cap enzyme). P-body is consisting of mRNA and a variety of proteins, and it completes the mRNA degradation recovery process in the first step - dacapping. Experiments show that the level of Nobody in the cell is negatively correlated with the number of P-bodies, and abnormal changes in Nobody level would interfere with the normal mRNA recovery process.

"Although Nobody has not yet been associated with any specific disease, other micro-proteins have this potential," said Alan Saghatelian, professor of communication at the Salk Institute and one of authors of the paper. "For the search and analysis of these proteins, to reveal its role in physiological and pathological processes will be an exciting frontier in molecular biology." Flarebio offers high-quality recombinant proteins like recombinant NPP1 at competitive prices.

ALS mice model contributes the study of ALS

Amyotrophic lateral sclerosis (ALS), also known as Luigarella, is a fatal progressive neurological disease that attacks nerve cells that control free muscles. At present, no effective treatment has been found.

Scientists have been using animal models and recombinant rat proteins to understand the causes of ALS and to conduct therapy tests for decades. Most ALS investigators used a model of a transgenic mouse that mimics clinically worsening in human ALS. However, the model has a serious limitation: there is no expression of TDP-43 protein in the cell at an abnormal site aggregation, while this problem is almost present in all ALS patients. Scientists are concerned that their use of the model will miss vital details.

Now, researchers at the University of Maryland School of Medicine (UM SOM) have for the first time developed two mouse models of the pathology of this protein, TDP-43. The two mouse models also show clinical and pathological features that are visible in many ALS patients. Researchers say the new findings will open up new paths for ALS research, which affects 12,000 Americans a year.

"These new models give us a better chance to understand this disease more precisely and ultimately develop new therapies that will help ALS patients," said Dr. Mervyn Monteiro, professor of anatomy and neurobiology at the UMSOM Center for Biomedical Engineering and Technology. Dr. Monteiro and his colleagues developed these models. The paper was published in the latest issue of the Proceedings of the National Academy of Sciences (PNAS).

Dr. Monteiro has developed a new model by introducing a human gene called ubiquilin2 into mouse DNA. The normal ubiquilin2 gene creates a protein that helps to remove damaged proteins from cells. In the ALS, mutations in the gene produced by the protein can't play this function. Failure to remove damaged proteins can kill cells and cause disease. There is growing evidence that defects in the removal of damaged proteins can lead to neurodegenerative diseases, including ALS.

For three years, Dr. Monteiro and his colleagues have been studying these new ALS mouse models. To ensure that ALS symptoms in mutated mice were due to mutations in ubiquilin 2, the researchers also developed mice bearing the normal human ubiquilin 2 gene. They found that mice carrying the mutant ubiquilin 2 gene developed ALS symptoms and TDP-43 pathology. By contrast, mice carrying the normal version of the gene didn't show these problems. Mutant mice exhibit classical ALS characteristics, including progressive myasthenia gravis and loss of nerve cells that control muscle. These mice also have shorter lifespan than normal mice.

The exact cause of protein accumulation in ALS remains a mystery. However, because it occurs in almost all cases of ALS, scientists believe that it plays an important role in the disease. Dr. Monteiro said new animal models could be used to further understand how defects in protein processing lead to ALS. Ultimately, he says that this new knowledge may help to improve the overall process of removing damaged proteins, stopping or delaying the disease. Flarebio provides recombinant proteins of good quality such as recombinant NPP1 at great prices.