Scientists find new target to treat chronic kidney disease

Renal fibrosis is a common pathophysiological change of chronic kidney disease. It can lead to renal failure, and there is no better treatment. Dr. Ian Logan from the University of Newcastle, UK, and his colleagues conducted a study of epigenetic modulators through recombinant human proteins, including SETD7, to determine whether epigenetically modulating factors are potential therapeutic targets for chronic kidney disease. The results were published in the Lancet.

The researchers used human kidney fibroblasts, mesangial cells, and mouse embryonic fibroblasts to analyze fibroblast transformation, extracellular matrix protein expression (immunofluorescence, wound healing), and whole-gene expression (whole genome chip technology) levels. The interaction of the lysine methyltransferase SETD7 with SMAD3 (immunoprecipitation), SMAD3 stability, and SMAD3 nuclear import was analyzed using renal tubular epithelial cells.

The results show that Transforming growth factor β1 (TGFβ1) -induced myofibroblast transformation was not found in SETD7-deficient cells. In addition, SETD7 lacks fibroblast collagen concentration and fibronectin - 1 concentration was lower than SETD7 normal cells, and wound healing slowed down. TGFβ1 can promote the interaction of SMAD3 with SETD7, thus increasing the stability of SMAD3 in cells. Immunofluorescence and subcellular separation revealed that SMAD3 nuclear input was dependent on SETD7. SETD7 overexpression increased the SMAD3 transcriptional activity of cis-regulatory elements (plasminogen activator inhibitor 1 and CAGA), while SETD7 deficiency can reduce SMAD3 transcriptional activity. Gene Ontology analysis showed that SETD7 regulates the expression of fibrogenic genes.

The study shows that SETD7 plays an important role in fibrogenesis - a major feature of chronic kidney disease and other fibrotic diseases. In view of the results of this study, drug inhibition of epigenetic regulators is expected to be a novel therapeutic approach for chronic kidney disease. Flarebio offers recombinant proteins of good quality such as recombinant ECE1 at competitive prices.

A protein that plays an important role in the development and progression of cancer

Researchers at the Sylvestre Cancer Research Center in the United States have discovered a protein that plays an important role in the development and progression of cancer through research using recombinant dog proteins, and this protein accumulates in dormant cancer cells and forms amyloid small body. Once this amyloid decomposition, cancer cells will be re-active. The study was published in the journal Developmental Cell.

We know that these amyloid bodies are related to the occurrence and development of Alzheimer's disease and Parkinson's disease, the relation of deposition of starch bodies and cancer is not clear. This study suggests that we can apply the knowledge of neuroscience to cancer so as to obtain a variety of types of cancer treatment.

"We found that these proteins are abundantly present in dormant cancer cell bodies, while the heat shock pathway breaks down the amyloid bodies formed by this protein deposition, which in turn restores dormant cancer cells," the experts said.

The study also found that ribosomal non-coding genes control the formation of amyloid bodies in cancer cells, so we can also take this gene as a target to produce drugs. If we can prevent the decomposition of amyloid in cancer cells, then we may be able to keep the cancer cells dormant indefinitely. In addition, we can also try to find another way for cancer cells to produce such amyloid bodies, thus making the active state of cancer cells to dormant state.

Through this study, we can imagine in the future that we may not have to completely remove the cancer cells. We can just keep it in a dormant state. Experts say that they are confident they can develop a new kind of cancer drugs. These drugs take related genes and pathways as targets, and some related drugs have been put into the market, while other drugs are still in the research process. Flarebio provides good-quality recombinant proteins such as recombinant NRG3 at competitive 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.

Low-density lipoprotein may be related to risk of diabetes

According to a study published in the Journal of the American Medical Association on Oct 4th, LDL lowering gene variants are associated with an increased risk of type 2 diabetes. The research was conducted using recombinant proteins such as recombinant mouse proteins.

Dr. Luca A. Lotta from the University of Cambridge, UK and his colleagues conducted heredity-associated meta-analysis to examine the association between low-density lipoprotein (LDL) reduced genetic variants and type 2 diabetes and coronary artery disease. The data included 50,775 patients with type 2 diabetes and 270,269 controls as well as 60,801 patients with coronary artery disease and 123,504 controls.

The researchers observed an inverse association between LDL-lowering of NPC1L1 gene variants and coronary artery disease (a predicted odds ratio of 0.61 for the gene predicts a reduction in LDL per 1 mmol / L), and they also discovered a direct association between type 2 diabetes mellitus (the predicted odds ratio of the gene for the reduction of LDL per 1 mmol / L was 2.42). For PCSK9 gene variation, the odds ratio for type 2 diabetes was 1.19 for every 1 mmol / L reduction in LDL. For a given reduction in LDL, the risk of coronary artery disease has similar reductions with gene mutation; type 2 diabetes mellitus isomer correlation was observed.

"In this meta-analysis, the presence of LDL-lowering NPC1L1 or nearby gene mutations was associated with a higher risk of type 2 diabetes," the study authors write. Flarebio provides you with good-quality recombinant proteins like recombinant Lrp3 at good prices.

The pathogenic protein of senile dementia may be used to treat cancer

For Alzheimer's disease, the existence of amyloid protein is often a bad predictor, because β-amyloid is a major constituent of senile plaques in the brain and is one of the most important indicators of disease severity, and it is also the key target for dementia immunotherapy.

However, as early as the end of May, in an article published in Science Translational Medicine, scientists conducted research using recombinant human proteins and speculated that β-amyloid may also carry an ancient evolution "mission": to protect brain from pathogen invasion and its function is similar to antimicrobial peptides.

In early October, scientists discovered "good" point for amyloid. The research team at the University of Miami Miller School of Medicine has revealed that amyloid allows can make cells including cancer cells to enter dormant state. This may bring new paradigm for cancer treatment. The related research results were published in the Cell sub-publication Developmental Cell on October 6th.

Dr. Stephen Lee led the research team to discover the formation mechanism of amyloid. Motif is the structural level of protein between the secondary structure and tertiary structure. Amyloidogenic motifs (ACMs) are able to direct amyloid production by interacting with non-coding ribosomal RNA (rIGSRNA). Β-amyloid peptide has a function similar to ACM, for it can mediate intracellular deposition of amyloid protein. In the signal pathway of heat shock, the key elements can degrade amyloid protein.

The researchers believe that this mechanism is one of the ways that cells respond to stress, allowing cells to store large amounts of proteins and enter the dormant state. Amyloid production allows cells to remain active under stress for extended periods of time. Dormant cancer cells would store large amounts of amyloid proteins, and heat shock signaling pathways will degrade the deposition of amyloid, making cancer cells "wake up", thereby promoting its proliferation and proliferation.

"If we can stop the degradation of amyloid in cancer cells, we will have the ability to keep the cancer cells dormant forever," Dr. Lee said. "In addition, we might be able to induce active cancer cells to store amyloid, thus making them dormant." Although this new idea can't eliminate cancer cells, it can block the deterioration of cancer. Flarebio offers recombinant proteins of good quality such as recombinant LRP3 at competitive prices.

A certain protein may be the starting factor for Alzheimer's disease

Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis all are likely to be related to structural collapse of the accumulation of proteins and brain inflammatory response. However, although there are many studies on recombinant rat proteins, the specific causes and mechanisms are unclear.

Researchers at the University of Louisville School of Medicine have found that proteins produced by intestinal bacteria can cause structural protein folding errors in the brain and inflammation of the brain. Their study found that intestinal bacteria can produce a protein has structure similar to the brain protein, and this protein will lead to an increase in the number of α-synuclein in the brain. In the brains of patients with Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, structural abnormalities of alpha-synuclein and associated amyloid accumulation can be found.

α-Synuclein is a protein existing in the brain of normal humans. In the brain of patients with Alzheimer's disease and Parkinson's disease, the protein will accumulate and form amyloid substances, thereby impairing brain function. Experts suspected that intestinal bacteria can produce a protein which can bring structural folding abnormalities of proteins in brain, and those brain proteins with abnormal structure will deposite in the brain. In addition, experts also suspected that the protein secreted by intestinal bacteria will promote the inflammatory response of brain.

A study implanted E. coli which can produce this protein in the intestine of experimental mice, while the other group of control mice was implanted with E. coli that could not produce the protein. The results showed that the experimental group mice brain produced more α-synuclein, and the brain inflammation was also stronger than the control group. There was a similar study on nematode also showed a similar result.

The expert said, "These two similar studies on different animals suggest that certain protein secreted by enteric bacilli may be the starting factor for Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Understanding this is very important, because many of these factors are not genetically determined. While coliform bacteria are part of our body, and we have many possible ways to influence the number of these bacteria, thereby treating the disease.

Colorectal bacteria play an important role in age-related brain degenerative diseases. Finally, experts said, "We are continuing our efforts to explore this mechanism, thus exploring further possible therapies." Flarebio offers good-quality recombinant proteins like recombinant CDH12 at competitive prices.

Yoshinori Ohsumi finds the real autophagy mechanism

The Nobel Prize in Physiology or Medicine in 2016 was awarded to Yoshinori Ohsumi who is interested in recombinant human proteins, because he discovered the autophagy mechanism. This is an evolutionarily conserved process in which eukaryotic cells can be partly recirculated through transporting double membrane vesicle to lysosome. Unlike other mechanisms of cellular degeneration, autophagy can remove aged or damaged proteins, macromolecular complexes and organelles, leaving place for participation in new physiological processes. In addition, autophagy is also a key cellular process for the removal of invading microbes and toxic protein aggregates, which plays a key role in the fight against infection, aging, and many human diseases.

Although autophagy has been confirmed in the 1960s, scientists still have little knowledge of its mechanisms and physiological significance over the next few decades. The work of Yoshinori Ohsumi significantly changes the understanding of this important cellular process.

In 1993, Yoshinori Ohsumi published his groundbreaking in fifteen genes in the yeast. Subsequently, he cloned these genes in yeast and mammalian cells and elucidated the function of the coded protein. Based on the pioneering discovery of Yoshinori Ohsumi, the importance of autophagy in human physiology and diseases is now widely recognized. Flarebio offers recombinant proteins of good quality such as recombinant Nrg2.