Protein in hake's eyes becomes new hope for people with corneal blindness

Corneal blindness is a visual impairment which affects about 10 million people in the worldwide. It occurs from the cornea becoming clouded, scarred or any other infection that ultimately affects the transparency of cornea, finally making a person blind. It includes a range of eye diseases, injuries or infections that damage the corneal tissues and lead to permanent blindness. Due to shortage of cornea donation, only 100,000 can receive transplantation each year. Now researchers have new findings in research using recombinant human proteins.

A recent study at the University of Auckland in New Zealand found that they can make use of a kind of protein in the eyes of hake to make alternatives of human cornea. The study is expected to solve the shortage of donated corneas.

Researchers from Auckland University said they can get rich protein from the eyes of hake and use them to create biological materials for "corneal tissue engineering" of human beings, namely manufacturing cornea alternatives.

Medical director and leading ophthalmologist from Focus London clinic Alam said, "This news brings new hope for thousands of people who are at the risk of blindness. In a recent trial in UK, doctors first used IOL (intraocular lens) to conduct transplantation. This is really encouraging news. However, the synthesis technology is still in its infancy, and the operation is expected to begin in 2017. If the eye crystals of the fish prove to be effective, it can change the fate of thousands of people in this country and around the world."

Biological Sciences researchers from University of Auckland said that the possibility of such transplant having rejection is very small. Flarebio Biotech LLC offers good-quality recombinant proteins including recombinant LARGE at good prices.

Cancer cells: the new discovery of PITPNC1 protein

Researchers from Rockefeller University at New York and the University of Bergen at Norway published their discovery of a protein called PITPNC1 on the journal Cancer. Molecular biologist at the University of Bergen, first author Dr. Nils Halberg who is interested in producing recombinant proteins like recombinant dog proteins said, "We found that invasive cancer cells spreading in colon, breast and skin cancer have higher content of PITPNC1 protein than non-invasive cancer cells."

More than 90% of cancer deaths are due to metastasis, namely so-called new tumor lesions caused by the condition that invasive cells leave the primary tumor and metastases to other parts of the body. Any discoveries about the metastasis process of cancer cells all help us step further on the way of saving millions of lives.

The name of metastatic cancer cells is the same with that of the cancer cells it comes from. For example, lung metastatic cancer forming by a kind of breast tumor metastasis is known as metastatic breast cancer, instead of lung cancer. Under a microscope, metastatic tumor cells generally look very similar to primary cancer cells. Moreover, metastasis cancer cells and primary cancer cells often have some similar molecular features, such as the expression of certain proteins. It can be proved by many recombinant proteins such as recombinant rat proteins.

Dr. Halberg explained that there are many different kinds of cells inside a tumor cell. Some of the cells are benign and will not cause any troubles, while some cells become invasive and are ready to spread at any time. And it is difficult to predict which cells are about to become invasive cells.

In their paper, the team describes how they separated invasive cells from the metastatic breast cancer, melanoma and colon cancer and how they found that the invasive cells all express a kind of genes more highly than cells without proliferation. The gene encodes the protein PITPNC1. Dr. Halberg said, "This means that we can make a forecast about which tumor cells are easy to become invasive and spread at an earlier stage than what we can do currently."

He and his colleagues also found that this protein also has a very specific function in the process of cancer spread. It can make of blood vessels to metastase tumor cells to new sites in vivo. In order to be able to leave the tumor and enter blood vessels and then adhere to a new organ, invasive cells need to penetrate tissue. Dr. Halberg said that they cut matrix proteins around cells by releasing a kind of molecules like scissors, while it is PITPNC1 protein which regulates this process.

The team hopes that the results would help to find treatment to reduce the risk of proliferation of cancer - for example, after surgery. Halberg concluded, "If we can provide a personalized treatment targeting at this protein, we can prevent the spread of it."

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Nature: toremifene is expected to be an anti-Ebola drug

Fatal infections caused by Ebola virus (EBOV) break out frequently in recent years, and Ebola outbreak in West Africa caused a large number of deaths. There are no approved effective drugs or vaccines against EBOV. Since 2013, scientists have adopted a large number of small molecules and marketed drugs in vitro mouse model tests and computer virtual screening to find compounds of anti EBOV. In 2013, Johansen, LM et al., conducted experiments on a series of selective estrogen receptor modulators including anticancer drug toremifene, finding that they have potential inhibitory effect on EBOV virus. But they did not clarify the mechanism.

Recently, David I. Stuart and other researchers from the University of Oxford took EBOV outer membrane glycoprotein (GP) as the study object and found that toremifene can combine GP and reduce its stability, thereby blocking viral fusion with the endosomal membrane and playing anti-viral effect. They also resolved the crystal structure of GP protein and the complex of GP protein, toremifene and ibuprofen, clarifying the action mechanism of toremifene.

EBOV outer membrane has a three-glycoproteins (GP, furin protein is cut into two subunits GP1 and GP2), which is solely responsible for host cell attachment, fusion kernel entry and film. Thus, GP is the primary target for the development of antiviral drugs. The researchers used recombinant protein - recombinant EBOV outer membrane glycoprotein (GP) to test whether the nine compounds would bind directly to proteins through the method of protein thermal transfer. Experimental results showed that when the dose of toremifene was 100 μM and pH value was 5.2, it can significantly reduce the melting temperature (Tm) of EBOV GP to 14 ℃. This is opposite to the previously-reported research result that inhibitors reducing the melting temperature of proteins will increase the stability of protein structure. In contrast, ibuprofen showed only a very critical effect (Tm decrease rate was less than 2 ℃), lacking for potential virus inhibition.

The researchers also first reported EBOV GP protein with no ligand and high-resolution crystal structure of the GP and toremifene and ibuprofen complex. Surprisingly, toremifene and ibuprofen all combined in a hole between the subunits GP1 and GP2. This hole is located in a huge tunnel entrance, and this big tunnel can be connected with other similar tunnels. The interactions of drug and GP1, GP2 are mainly hydrophobic effect. In filamentous virus, amino acid residues which combine with these drugs are highly conserved, excepting Marburg virus (MARV), indicating that the Marburg virus probably will not be combined with these drugs. This work illustrates the suppression mechanism of drugs on viruses, providing a viable direction for the development of more anti-EBOV drugs. Flarebio Biotech LLC is a National High-Tech Enterprise with research, production and sales as one. And high-quality recombinant proteins such as recombinant NRG3 are offered 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.

The study of female germline stem cells has achieved new progress

Researchers from School of Biomedical Engineering of Shanghai Jiaotong University and Bio-X Institute conducted the research of epigenetic spectrum of female mouse reproductive stem cells and found the epigenetic regulation mechanism which decides basic biological characteristics of the cells. Related study was recently published online in the journal Genome Biology, which also published a lot of studies about recombinant proteins such as recombinant mouse proteins.

Conventional wisdom holds that the produce of oocytes of vast majority of female mammals occurs only in the fetal period, and the number of oocytes doesn't increase after birth but decreases by years, which means that there are no germline stem cells in ovarian after birth. Do female mammals have germ stem cells? If so, what is the molecular mechanism that decides stem cell characteristics of development unipotency and undifferentiation?

Zhao Xiaodong study group from Shanghai Jiaotong University and Wu Ji study group from Bio-X Institutes Jiaotong University conducted collaboration and discovered female reproductive stem cell-specific histone modifications label of mark enhancer; more importantly, this study reveals DNA methylation determines developmental unipotent of female reproductive cells as a major epigenetic regulatory mechanism by inhibiting the development process of somatic cells. And it also involves in the maintenance of their female gender identity. At the same time, the researchers also found that germ cell-related factor PRMT5 also plays an important role in maintaining undifferentiated state of female reproductive stem cells. Flarebio also provides recombinant proteins such as recombinant Cdh9 at good prices.

The great advantages of prokaryotic expression system for recombinant proteins

Prokaryotic expression system is developing well and the process is simple and fast. It has the advantages of low cost and high yield and is worthy trying for most proteins. It is especially suitable for eukaryotic proteins which express prokaryotic sources and don't require post-translational modification.

The necessary host bacteria of prokaryotic expression system include E.coli, Bacillus and the like. Wherein the Gram-positive Bacillus is more suitable to secrete and express recombinant proteins such as recombinant human proteins in its periplasmic space; gram-negative E.coli is capable of expressing heterologous proteins at broad spectrum.

E. coli expression system is currently the most developed recombinant protein expression system. Common strains of E. coli include BL21 (DE3), BL21 (DE3) Star, and B834 (DE3) and so on. All these strains were knocked out protease and are lysogenic to phage DE3. DE3 is a derivative λ phage with a phage resistance zone 21 and / ac / gene, / acUV5 promoter and T7 RNA polymerase gene. This section is inserted into the int gene, thus preventing DE3 from integrating into the chromosome or being excised from the chromosome in the absence of helper phage. Once forming DE3 lysogen state, only /acUV5 promoter induced by IPTG guides T7 RNA polymerase gene transcription. Add IPTG-induced T7 RNA polymerase production in lysogen culture system and then target DNA on plasmid begins to transcribe.

At the same time, there are some specially-designed strains expressing recombinant proteins with special needs. For example, methionine auxotroph expresses selenomethionine proteins; strains with enhancement of solubility express toxic protein expression strains; strains supplemented with rare codons express eukaryotic proteins. And here I would recommend a biocompany named Flarebio which produces and provides superior recombinant proteins including recombinant Cdh10 at competitive prices.

A new gene is found to be a factor of judgment for Alzheimer's disease

Alzheimer's disease researchers at the US University of Wisconsin found a group of biomarkers, which can help to identify which older people are more likely to suffer from Alzheimer's disease before showing the symptom of dementia. The study was published in the journal Brain, which also published some studies on recombinant human proteins.

"The Association of Alzheimer's Disease estimates that if we have the precautionary approach five years before the appearance of clinical symptoms, then half of the patients who develop dementia would survive from the disease," lead author of the study Annie Racine said. "In other words, we can save millions of lives and save billions of dollars."

Doctor Sterling Johnson who is senior author of the study said, "Changes in the brain - such as the emergence β- amyloid plaques and interlacing with tau proteins - are biomarker of Alzheimer's disease. Not every who have such changes in brain will show Alzheimer's disease. The study found that biomarkers can predict who will develop the disease.

The study included 175 elderly people who have the risk of Alzheimer's disease. According to brain scans and pathologic features of these participants, researchers divided the participants into four groups. The researchers conducted 10 years of follow-up to the participants to monitor changes in cognitive abilities of participants in different groups.

The results showed that the performance of the biomarkers of one group of participants acted well and had a good prediction role on Alzheimer's. In the group of 22 participants, in the group of 22 participants, APOE4 gene of two-thirds of participants were positive, this biomarker is the biggest risk factor for sporadic Alzheimer's disease.

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