MDM2 proto-oncogene has an alarming and important function that promotes MYCN proto-oncogene expression

Scientists at the Sabang Institute at the Children's Hospital of California have recently discovered that the MDM2 proto-oncogene has an alarming and important function that promotes MYCN proto-oncogene expression. The study was published on October 17 on Oncogene, which also published some other studies on recombinant human proteins.

Retinoblastoma is a retinal neoplasm in children 1 to 2 years old. Although the incidence is low, if not treated, it can cause fatal or blinding serious consequences. This tumor also plays a special role in the study of cancer because its lesion progression is found to be associated with mutations or deletions of a single gene, RB1.

The MDM2 gene has been thought to be involved in the development of tumors because it promotes the transformation of normal cells into cancer cells. This function is thought to be associated with a tumor suppressor protein p53 that inhibits apoptosis which leads to aberrant proliferation.

MDM2 also plays an important role in other p53-independent signaling pathways. This protein, called MYCN, is regulated by MDM2 and plays an important role in cell proliferation. In the presence of this protein, retinoblastoma can grow by 20% to 25%, leading to secondary disease and poor prognosis. Although MYCN has the potential to be a therapeutic target, it is difficult to be blocked by a single small molecule. The findings of this study provide the theoretical support for the regulation of MYCN expression by targeting MDM2.

This study first elucidates that retinoblastoma is more dependent on MDM2 than on MDM4 which is another member of this family. Flarebio offers recombinant proteins of good quality such as recombinant CDH4 at competitive prices.

Newly-developed technology can directly detect Ebola virus

Ebola virus is such a deadly disease that found in 1976 in Africa. It is an unusual disease and after being discovered, it caused widespread concern and attention within the medical profession. Since 2014, Ebola virus in West Africa has killed over 11,000 people. Recently there are new cases found in Guinea and Sierra Leone.

A group form researchers at UC Santa Cruz has developed chip-based technology for reliable detection of Ebola virus and other viral pathogens. The system used recombinant rat proteins and can be integrated into a simple, portable device to quickly detect Ebola infections and control outbreaks since it uses direct optical detection of vital molecules. Tests have been done and the results show that the system has the sensitivity and specificity needed to provide a viable clinical assay. The results paper was published September 25 in Nature Scientific Reports.

The current Ebola virus detection relies on a method called polymerase chain reaction (PCR) to amplify the virus's genetic material for detection. Because PCR works on DNA molecules and Ebola is an RNA virus, the reverse transcriptase enzyme is used to make DNA copies of the viral RNA prior to PCR amplification and detection. This PCR detection seems to be more complex compared with the new-developed system, and it requires a laboratory setting. The system would detect the nucleic acids directly and achieve a comparable limit of detection to PCR and excellent specificity.

The system combines two small chips, one microfluidic chip for sample preparation and one optofluidic chip for optical detection. Senior author Holger Schmidt, the Kapany Professor of Optoelectronics at UC Santa Cruz and his collaborators have been developing optofluidic chip technology for optical analysis of single molecules as they pass through a tiny fluid-filled channel on the chip for the last ten years. The microfluidic chip for sample processing can be integrated as a second layer next to or on top of the optofluidic chip.

Although the team has not yet able to test the system starting with raw blood samples due to lack of additional sample preparation steps, it is a great step in the process. The scientists are devoting to make the system to detect less dangerous pathogens and do more useful analysis for other diseases. Flarebio provides recombinant proteins of good quality such as recombinant Cdh4.

Bowel inflammation patients can be saved by this protein

A group of researchers first demonstrated the role of stomach cancer-associated protein tyrosine phosphatase (SAP)-1 in the pathogenesis and prevention of Crohn's disease, ulcerative colitis, and other inflammatory bowel disorders. The group was led by Prof. MATOZAKI Takashi and Associate Prof. MURATA Yoji who're interested in study of recombinant human proteins at the Kobe University Graduate School of Medicine Division of Molecular and Cellular Signaling.

Inflammatory bowel diseases are disorders of unknown etiology that are often characterized by abdominal pain, diarrhea, bloody stool, fever, and weight loss. These diseases include Crohn's disease and ulcerative colitis. These symptoms effect too much on patients' daily life and the patients will be pushed at an elevated risk of mortality. And these patients are more likely to be linked with colorectal cancer.

A lot of studies published recently have demonstrated that intestinal epithelial cells are important in regulating bowel inflammation, but the underlying mechanism remains unknown. Before this, the scientists found that SAP-1 localizes to the microvilli of the brush border in gastrointestinal epithelial cells. The transmembrane-type tyrosine phosphatase SAP-1 has an extracellular domain that protrudes into the intestinal lumen and a cytoplasmic domain that mediates tyrosine dephosphorylation of proteins. They showed that SAP-1 ablation in a mouse model of inflammatory bowel disease resulted in a marked increase in the incidence and severity of bowel inflammation, which suggests that SAP-1 plays a protective role against colitis. What's more, carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 20, an intestinal microvillus-specific membrane protein, was identified as the target of SAP-1 tyrosine dephosphorylation. Suppression of CEACAM20 functions via dephosphorylation contributes to preventing colitis. They believe that their findings will drive the development of drugs that target SAP-1 and CEACAM20 to overcome intractable inflammatory bowel diseases by unlocking the anti-inflammatory mechanism of the intestinal epithelial cells.

The future researches of these scientists will be concentrated on taking advantage of the understanding of SAP-1 and CEACAM20 functions to develop new therapeutics for inflammatory bowel disease. Flarebio offers recombinant proteins such as recombinant CDH4 at competitive prices.

HRG replacement therapy may provide a new strategy for the treatment of sepsis

When suffering from sepsis, controlling the shape and activity of key proteins of a group of white blood cells and raising the levels can improve the chance of survival and recovery, according some studies using recombinant proteins. Blood poisoning after injury or infection is called sepsis, and it is a major reason of death worldwide. When suffering from sepsis, the body's immune system would over operate, leading to blood insufficiency of its own tissues and organs and thus causing damages. However, the exact molecular mechanisms of sepsis and its processes are unclear.

Now, Professor Masahiro Horie West in Japan and his colleagues from Okayama University, Shujitsu University and Kinki University have shown that a natural protein called histidine-rich glycoprotein (HRG) plays a significant role in the prevention of sepsis. They found that HRG controls the shape and activities of leukocyte which is called neutrophil to make them flow freely and show right response in the fight against sepsis.

Nishibori team intended to verify the role of HRG, because when sepsis happens, HRG levels in patients drop dramatically. HRG protein is produced and secreted by the liver. It is known that HRG is involved in regulating the immune response as well as the promotion of antibacterial and antifungal activity. The research team induced sepsis in a group of mice and took the healthy group as a control group. They purified human plasma HRG and made use of a dose of HRG protein to treat certain sepsis mice.

The researchers found that mice given HRG rapidly showed spontaneous activity and began to recover from sepsis. Further investigation showed that inflammation of the lungs of the treated mice was much less than the untreated mice. The shape of neutrophils of mice given HRG was more rounded and spherical, which made them more freely to go through micro-capillaries and veins. While the neutrophils of sepsis mice showed irregular cell shapes. This in turn triggers unwanted activity, because metamorphotic neutrophil will attach to other cells and establish cell mass, restricting blood flow.

"The reduce of plasma HRG is a fundamental way of incidence of sepsis," the authors stated in their paper published in the journal eBioMedicine (2016) , "HRG replacement therapy may provide a new strategy for the treatment of sepsis."

Further research is needed in healthy subjects and patients with sepsis, upstream signaling processes involved in HRG action. Further research will also determine whether HRG dose may be a valuable method for the treatment of patients with sepsis. Flarebio provides you with high-quality recombinant proteins such as recombinant CDH4 at reasonable prices.

The action mechanism of Alzheimer's disease has been revealed

Alzheimer's is the most common form of dementia globally and affects so many people in the world. It is the fourth leading cause of death in individuals over the age of 65. It is the only cause of death among the top ten that cannot be prevented, cured or even slowed down. A lot of research using recombinant mouse proteins have been conducted to study the disease.

However, there is good news. Scientists at Trinity College Dublin have figured out a fundamental mechanism underlying the development of Alzheimer's disease. It may lead to new forms of therapy for those living with the condition.

Alzheimer's disease is characterized, in part, by the build-up of a small protein ('amyloid-beta') in the brains of patients. Impaired clearance of this protein appears to be a major factor in the build-up of plaques, and then in the disease process itself. While the mode by which amyloid-beta is cleared remains unclear, it is evident that it needs to be removed from the brain via the bloodstream.

Those in the brain have properties that strictly regulate what gets in and out of the delicate tissue. It is what is known as the blood-brain barrier (BBB). The BBB functions as a tightly regulated site of energy and metabolite exchange between the brain tissue and the bloodstream.

The research shows that distinct components of these blood vessels termed tight junctions are altered in Alzheimer's disease. This alteration is thought to be an entrained mechanism to allow for the clearance of toxic amyloid-beta from the brain in those living with Alzheimer's disease. The research also highlights the importance of understanding diseases at the molecular level. The concept of periodic clearance of brain amyloid-beta across the BBB could hold tremendous potential for Alzheimer's patients in the future. What remains to be done is figure out how to achieve this. Flarebio provides superior recombinant proteins such as recombinant CDH4 at good prices.

Optimized gene therapy of Parkinson's disease shows great success

Levodopa is a commonly-used drug to alleviate the symptoms of Parkinson's disease. However, patients taking the drug mostly feel disappointed as the final outcome. When initially taking levodopa, the patient's symptoms in the tremor and balance would be mitigated and controlled. But as time goes on, the effect of drugs will become increasingly worse. They may have to use ultra-high doses of the drug, and some patients may spend several hours in a paralyzed state in almost every day.

Today, Voyager Therapeutics Company located in Cambridge, Massachusetts thought that gene therapy can prolong the efficacy of the drug levodopa. Currently, the company's gene therapy has entered clinical trials with the aid of recombinant proteins such as recombinant mouse proteins.

Parkinson's disease is due to the death of neuron which produces dopamine in brain, resulting in difficulties of patients in athletic ability. People plagued by this disease include the famous boxer Muhammad Ali and actor Michael Fox. Although the reason leading to the death of brain dopamine neuron is still not fully understood by scientists, the reason for the failure of the drug levodopa has been found. Levodopa is the precursor of dopamine. It can be turned into dopamine under the disposal of aromatic L- amino acid decarboxylase (AADC) in the brain. However, in the brain of patients with Parkinson's disease, with the passage of time, AADC levels are decreasing. This results the condition that L-dopa can't be sufficiently converted to dopamine.

The strategy of Voyager wishes to inject adeno-associated virus (AAV) which expresses AADC into the patient's brain through gene therapy, thereby restoring AADC levels in the brains of patients and prolonging the efficacy of levodopa. "We have spent 60 years to study the pharmacology of dopamine," said Steven Paul, CEO of Voyager. "If we can put genes into the right brain tissues at the right time, then there is no reason that we don't succeed."

However, to put the correct gene into the right brain tissue to ensure a sufficient number of expressions is not an easy task. In order to ensure that AADC can express in the correct tissue, Voyager specially designed an injection system which can put the virus carrying AADC gene into the brain. In recent clinical trials, the patients will lie on the MRI machine to accept injection of the virus. Thus, brain surgeon can see the position of the putamen in the brain, thus ensuring the injected virus can cover this important area which needs AADC protein expression. Meanwhile, Voyager Company adds a chemical marker on AADC protein so that the doctor can see the position of proteins which express in the brain after surgery. In ongoing clinical trials, the gene therapy of Voyager has shown a significant effect on some patients.

Dr. Krystof Bankiewicz, one of the co-founders of Voyager said, "We think the failure of previous gene therapy of Parkinson's disease is that the method of gene transfer has not been optimized." Whether the optimized gene therapy of Voyager Company would succeed? We look forward to seeing the results of their clinical trials. Flatebio offers recombinant proteins of good quality like recombinant Cdh4 at competitive prices.

New breakthrough has been made in the study of breast cancer targeted treatment

Dr. Xu Lingzhi and his research team from the Second Affiliated Hospital of Medical University in Dalian have made new achievements in the field of breast cancer stem cell properties and targeted therapy. The achievements describes the key regulating effect of p62 / SQSTM1-let-7a / b-MYC signaling pathway on breast cancer stem cell properties for the first time and indicates that signaling hub protein p62 / SQSTM1 can be an effective target for intervention, providing new thoughts for overcoming the recurrence, metastasis and drug resistance of breast cancer. Related research papers are recently published online in the journal Cancer Gene, which also publishes some other studies on recombinant human proteins.

Currently, the clinical treatment of breast cancer has been improved greatly, but the phenomenon of recurrence and drug resistance is becoming more serious. More and more evidence suggests that tumor stem cells are highly correlated with drug resistance, relapse and metastasis during tumor treatment. However, because of the dynamic evolution and high-degree heterogeneity of tumor stem cells, therapies aimed at cancer stem cells still lacks for effective targets and intervention mechanisms.

As a "signal hub" within the cell, p62 / SQSTM1 protein combines with a variety of signaling molecules through its own series of functional domains to be involved in the regulation of various signaling pathways. In the study, researchers took breast cancer as an example. By in-vitro and in-vivo animal experiments of cell lines, the researchers reveal the signaling protein p62 / SQSTM1 highly express in cancer stem cell enriched population for the first time, and it plays positive regulation role to "dry” character of tumor stem cells. Intervention of the expression of the gene can significantly reduce the "dry" character of tumor stem cells. The research team also found that the signaling protein p62 / SQSTM1 can promote mRNA stability after oncogene MYC transcription by reducing the expression of a small RNA-let-7a / b, thus mediating "dry" phenotype of tumor stem cells. Subsequent analysis of clinical samples further validated that the high expression of signaling protein p62 / SQSTM1 was negatively correlated with PFS and OS in breast cancer patients. Flarebio provides high-quality recombinant proteins such as recombinant CDH4 at good prices.

Developing more effective and tailored therapeutic approaches for managing IBD

Theresa Alenghat, VMD, PhD, from Cincinnati Children's Hospital Medical Center, OH, was awarded with the 2015 AGA-CCFA-Janssen Research Award in Inflammatory Bowel Disease (IBD) Epigenetics Research, which means that Dr. Alenghat who are interested in producing recombinant proteins including recombinant horse proteins, as the inaugural recipient of this award, will receive $100,000 per year for three years to study the role of epigenetics in the development of IBD.

Epigenetics -- referring to modifications of DNA and DNA-associated proteins due to any number of patient and environmental factors -- is an active area of research in IBD and a wide range of other diseases. The promise of epigenetics comes from the knowledge that epigenomic changes regulate gene expression in response to environmental triggers without altering the genetic sequence. Therefore, epigenetics represent an important, potentially reversible, target for IBD treatments.

With the grant, Dr. Alenghat will have the resources to conduct both basic and translational research initiatives to test how bacteria trigger changes in the epigenome during the development of IBD. Dr. Alenghat serves as assistant professor in the division of immunobiology at Cincinnati Children's Hospital Medical Center. "These novel insights may guide the development of more effective and tailored therapeutic approaches for managing IBD," said Dr. Alenghat.

Specifically, Dr. Alenghat will be testing the hypothesis that dysregulation of epigenomic modifications, in combination with alterations in the microbiota, drive the development and progression of IBD.

Crohn's disease and ulcerative colitis are painful and medically incurable illnesses that attack the digestive system. The former one may attack anywhere along the digestive tract (mouth to anus), while the other one only occurs in the large intestine (colon). Symptoms may include abdominal pain, persistent diarrhea, rectal bleeding, fever, fatigue and weight loss. More than 1.6 million Americans live with Crohn's disease and ulcerative colitis, the two diseases that fall under the IBD umbrella. Many of them require hospitalization and surgery. What's worse, these illnesses can cause severe complications, including colon cancer in patients with long-term disease.

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Proteins modified by ELP can effectively improve the circulating half-life

Compared with small molecule drugs, protein drugs have the advantages of high specificity, high activity, low toxicity and so on. There many recombinant human proteins drugs in the market. However, the circulating half-life of most protein drugs in vivo is short with low bioavailability and great side effects. Using modified protein drugs (PEG-based) or employing source albumin (HSA) fusion protein drug (HSA fusion) with polyethylene glycol (PEG) is a common way to improve the above problems, but there are obvious shortcomings, such as: biological activity of the outcomes is significantly reduced; complex process of production; low yield; high cost. Therefore, how to improve the efficiency of circulating half-life of proteins in vivo and the treatment is a very challenging biomedical problem.

Gao Weiping Study Group at Tsinghua University takes the lead to come up with a new, universal, simple and efficient method of elastin-like polypeptide fusion (ELP fusion) to design for precise protein - polymer conjugate. By fusing elastin-like polypeptide with interferon -α and using Escherichia coli to produce IFN-ELP fusion protein can get high yield and low cost, and it also keeps the biological activity of IFN-α. Model tests in mice found that proteins modified by ELP can effectively improve the circulating half-life in vivo and residence condition of tumor, eventually significantly improving the outcomes of patients and improving the survival rate of mice.

This method is expected to become a new strategy for protein modification drugs, improving drug stability, improving drug half-life and enhancing the therapeutic efficacy.

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Same DNA fragments can match with each other without the help of other molecules

A new study results show that without the help of other molecules, same DNA fragments can match with each other. Genes (genetic factors) are DNA fragments with genetic effect. The results showed that each encoding gene has specific properties, no matter biological properties or biological functions. However, a gene can't always keep intact. It would often show damages and need diagnosis and repair.

The repair process of encoding genes is called homologous recombination. In this process, a broken or damaged gene can be replaced as the complete DNA sequence of the same gene. Wrong interchange of genes would lead to a variety of genetic diseases such as condition progeria, an accelerated symptom of aging.

Gene repair and homologous recombination is the key to reproduction and evolution, because this restructuring process would recombine the genes we obtain from our parents together. Recombinant protein are involved in replication and gene substitution process. However, in the genetic recombination process, the protein will react spontaneously. But the researchers didn't know how homologous genes found each other at that time. In the human genome, after coiling, DNA strand forms complex gene beam, i.e. chromosome. On the chromosome, there are more than 20,000 genes. Therefore, for different DNA strands, it is not easy to find homologous genes.

Imperial College London and the US National Institutes of Health (NIH) carried out a DNA molecule experiment in 2008, and the results showed that without any outside help (i.e. without any guidance of other proteins and molecules), DNA molecules which have the same genetic code can find their pair fragment.

These results show that two relatively- short double-stranded DNA fragments would spontaneously match with the same types of DNA after being mixed randomly in a container. Professor Mara Prentiss from Harvard University also confirmed in the subsequent study that homologous double-stranded DNA can spontaneously match. Flarebio provides you with high-quality recombinant proteins including recombinant CDH4 at a competitive price.

Gene analysis of chromatin can identify the origin of cancer

Researchers from The Jackson Laboratory (JAX) United States have developed a new method to determine the cell type which causes a given type of leukemia through whole genome analysis on open chromatin. This method plays an important role in diagnosis and treatment of leukemia. The study was published in the journal Natural Communication, which also has many other studies on recombinant proteins.

Each cancer begins with a single cell mutation. Having knowing the origin of cancer cells, researchers can analyze cancer subtypes, thus developing new means of treatment. But the existing methods are difficult to identify its original cells from a large number of tumor cell samples.

Chromatin is an important component within the nucleus and is composed of DNA, histones and RNA. It will converge into chromosome at the special stage when cells divide. Each type of cells has a unique chromatin structure: closed chromatin would tightly wrap around the nucleosome which is relatively inactive; the contact degree between open chromatin and nucleosome is relatively loose, but it is more active. Assistant Professor Dr. Jennifer Trowbridge from Jackson Laboratory, who also likes to conduct research on recombinant human proteins, improved the present method of identifying originated cells of tumor cells through analysis of the open chromatin of tumor cells.

Trowbridge led colleagues in the laboratory to build a mouse model with acute myeloid leukemia (AML). They found five kinds of cells from the bone marrow of humans and mice: long-term hematopoietic stem cells, short-term hematopoietic stem cells, multipotent progenitor cells, common myeloid progenitors and granulocyte-macrophage progenitor cells. The AML caused by different origins showed different invasiveness in mice: lesions induced by stem cells were more intrusive, while lesions induced by progenitor cells were much smaller. The occurrence frequency of different invasive cells of leukemia was different: stem cells were higher and progenitor cells were lower.

Researchers analyzed open chromatin of different AML cell samples and compared them with open chromatin pattern of normal cells, and then they determined the features and gene expression patterns of open chromatin in AML cell samples, which allowed them to be able to distinguish AML induced by stem cells and AML induced by progenitor cells.

The researchers said that by further study on open chromatin of stem cells and progenitor cells of healthy populations and AML patient populations, they can more accurately determine cancer biomarker based on cell origin, which is important for the diagnosis and treatment of cancer. Flarebio provides various recombinant proteins (including recombinant CDH4) of good quality.

New findings on WNT10B gene mutations help to achieve precise treatment of congenital oligodontia

Wenzhou Medical College in China recently announced that the Genome Institute of Medicine school of this school united with Peking University School of Stomatology, Zhengzhou University School of Stomatology, Beijing Anzhen Hospital, Chinese Academy of Sciences Beijing Institute of Life Sciences, American National Institutes of Maxillofacial and Oral to first discovered that WNT10B gene mutations can lead to congenital or hereditary oligodontia. The study was recently published online in the journal Human Genetics, which is a sub-Journal of the American journal Cell. The journal also published some other studies about recombinant human proteins.

The morbidity of congenital hypodontia is 1.6% -9.6%. Oligodontia means hypodontia of six or more teeth, and it is the more serious disorders of tooth agenesis. It may be associated with abnormal development of other ectodermal body tissues, which seriously affects masticatory function and maxillofacial development in patients. It is one of the most difficult clinical oral diseases.

Currently, research on the pathogenic mechanism of oligodontia is still incomplete. The research team used technologies including the technology of recombinant protein and exome sequencing technology - namely detection of the relevant part of the whole genome encodes proteins - to conduct molecular genetic analysis on more than 150 cases of patients with oligodontia. They found that about 5% of patients showed WNT10B gene mutations, which is related to oligodontia especially lateral incisors and premolars missing, including patients with autosomal dominant inheritance and sporadic oligodontia. On this basis, the researchers explained the possible mechanisms of Wnt/beta-catenin signaling pathway the WNT10B genes involve in tooth development and oligodontia. The study found that the mutations which impact WNT10B gene function damaged the regulative ability of Wnt / beta-catenin signaling pathway to downstream TCF transcription factors, significantly reducing the ability of Wnt pathway inducing teeth embryonic stem cells to differentiate into vascular endothelial cells.

It is reported that the research results expand the gene mutation spectrum of human congenital oligodontia, providing a new basis for clinical diagnosis of congenital oligodontia, improving the pathogenesis of the disease and ultimately achieving precise treatment. Flarebio also offers recombinant CDH4 of good quality.