Researchers conduct research new treatment of cancer stem cells

Many cancer patients enter the remission after chemotherapy, but they will continue to relapse after the treatment. More and more evidence suggests that this is due to the infinite reproduction of cancer stem cells may grow new tumors. A team from Milan, Italy, designed a program specifically targeted to cancer stem cells in certain cancers and reduced their tumorigenic potential. The study was published in the EMBO Molecular Medicine, which has published many studies on various recombinant proteins like recombinant rat proteins.

Each of our bodies has stem cells that are constantly splitting and renewing cells in the body. The team led by Pier Paolo Di Fiore and Salvatore Pece explored the role of Numb protein in maintaining stem cells in normal mammary gland development and found that Numb protein is necessary to maintain balance before stem cell and gland differentiation. Numb upregulates p53, a protein that blocks cell division. When Numb is deleted, p53 is also reduced, leading to increased self-replication of stem cells, which may lead to tumor formation.

In many breast cancers, Numb concentrations are lower, which is associated with poor prognosis. In this study, the role of Numb in these tumors was observed and found to be deficient in Numb's tumors, and the number of cancer stem cells increased, thus providing higher proliferation and growth potential for tumors. In addition, the researchers found that p53 plays an important role in it. When the concentration of Numb decreases, the concentration of p53 will also decrease. However, when p53 levels are recovered by blocking the degradation of Nutlin-3, the tumor is less aggressive and has fewer cancer stem cells. Many drugs targeting p53 pathways, such as Nutlin-3, are currently in clinical development.

Finally, the researchers examined the potential for the combination of Nutlin-3 and paclitaxel (a common chemotherapeutic agent). Although paclitaxel alone can reduce the tumor, the risk of recurrence is great once terminating the treatment. The combination of paclitaxel and Nutlin-3 not only enhances the response of paclitaxel to tumors, but also prevents Numb-deficient tumors from proliferating after treatment has ceased. This indicates that Nutlin-3 or similar drugs have the potential to fight against chemical resistance caused by cancer stem cells.

In the context of current research, researchers have developed preclinical model systems that specifically capture the effects on cancer stem cell therapy. All results were based on transplanting the patient's tumor cells into mice and then studying the presence of stem cells or the invasive nature of the cancer by a variety of methods. The system of testing different effects of different compounds on cancer stem cells may be a valuable tool in future experiments.

These preclinical findings suggest that patients with breast cancer with a defective expression of Numb may be eligible for the use of the currently clinically developed Nutlin-3 similar drugs. Using the same preclinical model, researchers are testing the efficacy of this candidate drug for cancer stem cells, as well as the possibility of minimal toxicity of standard chemotherapy regimens in the treatment of human breast cancer. By the way, Flarebio provides you with high-quality recombinant proteins such as recombinant ITGB2 at good prices.

A potential drug target for obesity and related metabolic diseases

Guo Fumin Research team at Chinese Academy of Sciences, Shanghai Institute of Health revealed that the new function of hypothalamic aorticoprine (POMC) neurons activating transcription factor 4 (ATF4) to regulate energy balance and lipid metabolism of the body, providing a potential drug target for obesity and related metabolic diseases. Related research results have been published online recently in the journal Diabetes. By the way, this journal is also famous for its studies involving recombinant rat proteins.

The obesity of body is caused by imbalance of energy intake and energy consumption, and it plays a key regulatory role for body energy balance in central nervous system. In the hypothalamic arcuate nucleus, there are two types of neurons that regulate energy metabolism: one is the brain-related protein neurons that promote appetite; the other is the appetite-suppressing POMC neurons. POMC neurons inhibit the appetite by releasing the melanogenesis of the melanocortin, which on the other hand affects the energy dissipation of the body by regulating the excitability of the sympathetic nervous system.

The researchers specifically knocked out the ATF4 gene in mouse POMC neurons. Analysis showed that these knockout mice became thinner, the insulin sensitivity, leptin sensitivity and energy dissipation of the body increased and they could resist obesity induced by high-fat diet, insulin resistance and leptin resistance. Further study showed that ATF4 can bind to the promoter of the ATG5 gene to directly regulate its expression. The researchers also constructed double-knock mice of the ATF4 gene and the ATG5 gene in POMC neurons. Through its phenotypic analysis, it showed that double-knock mice can reverse the phenotype of ATF4 single-knockout mice. By the way, Flarebio provides you with recombinant proteins of good quality such as recombinant ITGB2.

Phosphorylation affects the tumor growth and development

Scientists from VIB-KU Leuven have identified new mechanism that affects tumor growth through recombinant mouse proteins. Typical hypoxia in the tumor not only stimulates proliferation, but also counteracts the important role of protein PHD2 as a "cancer cell killer". The possible solution is to block the enzyme PP2A / B55 which recover the function of PHD2 to slow down cancer growth. The study was led by Massimiliano Mazzone (VIB-KU Leuven) and published in the leading scientific journal Cell Reports.

Poor prognosis in cancer is usually associated with hypoxia, which is interference to the oxygen supply to tumor cells. The protein PHD2 is called a "hypoxic sensor", which is highly dependent on the amount of oxygen. At the VIB-KU Center for Cancer Biology in Leuven, the study was led by Dr. Giusy Di Conza and his colleagues. Massimiliano Mazzone focuses on the study of phosphorylation.

When phosphorylated, PHD2 is more active and promotes the death of cancer cells in the hypoxic region of the tumor. However, tumors tend to overexpress phosphatase PP2A / B55, an enzyme that removes phosphate groups ("dephosphorylated") from PHD2. Thus, PHD2 is partially inactivated, which counteracts the positive effects of this "killer cancer cell".

Massimiliano Mazzone (VIB-KU Leuven) said, "Surprisingly, we have found that PHD2 phosphorylation is regulated by a pathway such as mTOR. mTOR is the primary sensor for metabolic stress in tumors and normal cells, such as lack of nutrients. Thus, our findings are applicable not only to cancer but also to other diseases such as inflammation or metabolic diseases."

During the study period, Mazzone's lab worked closely with several domestic and foreign researchers. In particular, the German ISAS Laboratories (Dortmund) and the University of Leuven Hospital play a decisive role in providing the human cancer samples needed for research. In these samples, the researchers found that PP2A / B55 were highly expressed in tumors compared with healthy tissues.

Prof. Massimiliano Mazzone (VIB-KU Leuven) said, "This leads us to conclude that PP2A / B55 are a potential target for promising cancer treatment, which is why we are starting to study the potential of specific drugs. The ultimate goal is to design this phosphatase function of the molecules, which targeted to fight cancer."

In addition to new insights into cancer treatment, these findings may also produce new biomarkers: PHD2 phosphorylation status may help to understand the process of tumor transformation and therefore choose appropriate treatment.

Professor Massimiliano Mazzone (VIB-KU Leuven) said, "In order to fully understand all the progress of these processes, we also need to carefully study the tumor microenvironment and immune system. After all, they strongly affect tumor growth." Flarebio offers high-quality recombinant proteins like recombinant Itgb2 at competitive prices.

SPOP: new treatment target for renal cancer

In recent years, the incidence of renal cancer increased the rate of malignant tumors in the first place. Clinical treatment shows that renal cancer is not sensitive to radiotherapy and chemotherapy. VEGFR inhibitors such as sorafenib and sunitinib are the first-line drugs for advanced renal cell carcinoma. Although FDA-approved drugs for kidney cancer treatment has been up to ten, these drugs are very limited efficacy of metastatic renal cell carcinoma, and susceptible to drug resistance. According to previous research using recombinant mouse proteins, it is a very important and urgent task to discover and confirm the new drug targets for the treatment of RCC-specifics.

Liu Jiang, a researcher at the Beijing Genomics Institute of the Chinese Academy of Sciences, discovered early that the SPP of the ubiquitin ligase E3 family member Cul3-binding substrate protein was overexpressed in 99% of clear-cell renal cell carcinoma tissues and was expressed in normal renal tissue SPOP and is still a biomarker of clear cell renal cell carcinoma. SPOP is still overexpressed in metastatic clear cell renal carcinoma. Liu Jiang group further study showed that SPOP is incorrectly positioned in the cytoplasm cell renal cell carcinoma. Overexpression of hypoxia-inducible factor HIF transcription enhances SPOP overexpression and hypoxic microenvironment drives the accumulation of overexpressed SPOP proteins in the cytoplasm of renal carcinoma and ultimately promotes the formation of renal carcinoma.

The above fundamental research in biology poses a key scientific question whether small molecule compounds can targetly interfere with SPOP-mediated protein interactions to achieve specific treatment of clear cell renal cell carcinoma. In order to study the interaction between SPOP and protein, SPROP was used to identify the crystal structure of the substrate polypeptide complex, and the structure-based screening strategy was used in combination with drug Chemical synthesis optimization and other technical means. The successful acquisition of SPOP can be combined with small molecule compounds. The compound can inhibit the binding of SPOP to substrate protein, interfering with the SPOP-mediated regulation of ubiquitination of PTEN, DUSP7 and other ubiquitination-modified signal transduction pathway, and ultimately inhibiting the growth of clear cell renal carcinoma cells in vitro and in vivo. This important result is published in the journal Cancer Cell. This study provides evidence for the pharmacological function of SPOP as a target for clear-cell renal cell carcinoma, as well as a new direction for the discovery of SPOP inhibitors and for the treatment of renal cell carcinoma, unlike kinase inhibitors. Almost at the same time, Nature has published two reports on the hypoxia-inducible factor HIF-2α inhibitor PT2399 (analogue PT2385 has entered the clinical stage), suggesting that the HIF pathway for the Small molecule inhibitors will also become a new target for renal cancer treatment. Flarebio offers recombinant proteins of good quality such as recombinant Itgb2 for your research.

Scientists have found new drugs that can be used to prevent spread of breast tumor

A new study has found that drugs approved for the treatment of estrogen receptor-positive breast cancer have the potential to prevent the spread of refractory triple-negative breast cancer. The study using recombinant horse proteins and published in Nature Communications shows that the drug blocks triple-negative breast cancer in many models by blocking an enzyme pathway called CDK4 / 6 - the CDK4 / 6 inhibitor.

Estrogen Receptor Positive (ER Positive) Breast cancer is one of the most common forms of breast cancer, which contains estrogen receptors. When these receptors receive the hormone signal, it will promote cancer cell growth. Similarly, in progesterone receptor-positive (PR-positive) breast cancer, cancer cells containing progesterone receptors can promote cancer cell growth, whereas HER2-positive breast cancer cells on the HER2 gene receptor may exacerbate the condition. Fortunately, there are some hormones for the treatment of breast cancer and other drugs that can target the role of estrogen, progesterone and HER2 receptors, and CDK4 / 6 inhibitors belong to this category. These drugs have been approved for the treatment of ER and HER2-positive breast cancer.

Now, co-author of the study Dr. Matthew Goetz and colleagues from the Rochester Mayo Clinic Women's Cancer Program believe that the use of CDK4 / 6 inhibitors in the treatment of triple negative breast cancer may be effective. Triple-negative breast cancer cells lack estrogen, progesterone and HER2 receptors. Thus, the cancer does not respond to the treatment of the target targeting these receptors, which makes treatment more difficult. However, the team found that CDK4 / 6 inhibitors can effectively prevent triple-negative breast cancer cells spread to other parts - that is, cancer metastasis.

The study found that CDK4 / 6 inhibitors do not triple negative breast cancer cell growth. These drugs can be targeted by acting on a protein known as SNAIL to significantly reduce the spread of cancer cells to distant organs, and SNAIL can promote cancer Cell transfer. According to the researchers, their findings suggest that CDK4 / 6 inhibitors may be beneficial in triple-negative breast cancer patients.

"These findings may provide a new treatment for preventing cancer metastasis. Meo Clinic is carrying out a new study focusing on the role of CDK4 / 6 inhibitors and may inhibit the presence of women with triple negative breast cancer," Dr. Matthew Goetz says. By the way, Flarebio provides recombinant proteins of high quality including recombinant ITGB2.

Some apolipoproteins are associated with type 2 diabetes

The proportion of apolipoprotein (apo) CIII and apoCIII to apoA1 is associated with type 2 diabetes (T2D), according to a study published in the December 28 issue of Diabetes Care, which also has some other studies on recombinant human proteins.

Dr. Adela Brahimaj and colleagues from the Erasmus University Medical Center in Rotterdam, the Netherlands, and used data from 971 individuals from the population-based Rotterdam study to examine the role of apolipoprotein in the risk of type 2 diabetes. They examined the association of high-density lipoprotein cholesterol (HDL-C), apoA1, apoCIII, apoD and apoE, and the ratio of apolipoprotein to apoA1 and T2D risk.

The researchers found that at a median follow-up of 13.5 years, 110 people developed diabetes. Apolipoprotein E, apoA / apoA1 ratio, apoE to apoA1 ratio and apolipoprotein score remained significant after adjusting for age, sex, body mass index, diabetes maternal history, hypertension, alcohol use, smoking, diabetes mellitus. The prevalence of cardiovascular disease was associated with a serum lipid-lowering agent (odds ratios of 0.74, 1.65, 1.36, 1.72, 1.88 and 1.6 for each standard deviation of natural logarithmic conversion). After adjustment for triglycerides in the final model, only apoCIII and apoCIII-to-apoA1 ratios remained significant (hazard ratios, 1.42 and 1.56, respectively).

"Serum apoCIII levels and apoCIII-to-apoA1 ratios are associated with incident type 2 diabetes," the authors write. They are independent of known risk factors and are stronger than HDL-C levels. Flarbio provides high-quality recombinant proteins like recombinant Itgb2 at competitive prices.

Piezo2 is clearly an important part of the respiratory process

A team of members of several US research institutions has found evidence that a protein has some control over the respiration process in mice through recombinant horse proteins. In their paper published in the journal Nature, the team described their study of protein Piezo2 and its multifaceted effects on regulating respiration. In France, Christo Goridis and the French Institute for Biological Products provided a report on the team's work in the same issue, outlining what the team was looking for and how they experimented and what they found.

As Goridis points out, previous studies have shown that many animals including humans have so-called Hering-Breuer reflections. This is an automatic mechanism that stops breathing when the lungs are filled and prevents damage caused by overfilling. But so far, little is known about the mechanisms involved in this process. To learn more, the team began by observing the vagal sensory neurons in the airway of mice, and previous studies have shown its role in breathing - they convey information about the condition of the lungs to the brain. Previous studies have also shown that the Piezo2 protein does participate in the process, although it is unclear how it works. In this new effort, researchers have learned more about protein expression in the lung system and their role.

The team examined all parts of the mice that were involved in respiration, which showed Piezo2 expression in nodular and jugular ganglia, some spinal sensory neurons and lung tissues. In order to find out the role of the protein in different regions, the team disabled the gene responsible for the expression of the protein. They found that the absence of Piezo2 in the jugular and dorsal root neurons resulted in neonatal death from respiratory distress. The production of proteins in nodular neurons shut down mice to adulthood but prevented the activation of Hering-Breuer reflexes - mice that inhale an unusual amount of air during normal respiration. The researchers also designed some of the light involved in the neural response, allowing the activation and inactivation of Piezo2 expression. This allowed the researchers to cause Hering-Breuer reflections only by turning on the light.

The researchers summed up their findings that Piezo2 is clearly an important part of the respiratory process. They noted that more work needs to be done to get a clearer picture of how the entire respiration process works. By the way, Flarebio provides you with superior recombinant proteins including recombinant ITGB2 for your research.

New method of anti-cancer method: taking advantage of drug resistance of cancer cells

Due to the resistance of cancer cells, the function of proteasome inhibitors in the treatment of cancer is limited. According to this study using recombinant mouse proteins, researchers at the Whitehead Institute have found a mechanism of resistance that occurs naturally in a variety of cancers that expose the fragility of drugs and stimulate natural cell death.

The finding, published in the Proceedings of the National Academy of Sciences, is titled "Inhibition of 19 s proteasome unit labeling of cell changes in various cancer states".

Hydrolases are large protein complexes that play an important role in regulating degradation and maintaining intracellular protein balance. When the cells become cancerous and produce tremendous pressure and are responsible for maintaining the protein balance. This goal is called proteasome inhibitors. Although proteasome inhibitors are effective in killing cancer cells in culture dishes (in vitro), they are severely limited in clinical use because of their resistance.

"At the moment, we have discovered an intuitive mechanism by which cells can obtain proteasome inhibitors in vitro," explains the team leader. "In our report, we describe in detail the effects of this mechanism on a variety of human cancers. In addition, we have determined that this mechanism is widely present in cells in a wide variety of states and can be combined with existing drugs."

By analyzing thousands of cancer cells and tumors, the researchers found that those cells resistant to proteasome inhibitors were inhibited.

In addition to resistance to proteasome inhibitors, the researchers report that inhibition of the expression of the proteasome subunit reflects a wide range of cellular genetic alterations. This facilitates treatment with biomarker methods.

"Resistance to cancer stems from multiple mechanisms, genetic or epigenetics. With this finding, we can develop new strategies and new compounds as arrays and make use of their drug-resistant properties which are more susceptible to effectively treat a variety of cancer types," said the research team leader. Flarebio provides you with high-quality recombinant proteins like recombinant ITGB2 at good prices.

Whether the treatment of amyloid protein hypothesis loses the scientific basis?

Eli Lilly and Company recently announced the results of its Phase 3 clinical trial of Alzheimer's disease (AD) drug candidate, solanezumab. Although the results using recombinant mouse proteins are not satisfactory, this doesn't mean that the treatment of amyloid protein hypothesis lost the scientific basis.

Amyloid hypothesis began in the 1980s and is an important theory which has the most research evidence to support the interpretation of AD causes. AD is the most important form of Alzheimer's disease. The deposition of amyloid protein (β-Amyloid, Aβ) is one of the important markers of AD. Amyloid Hypothesis think that Aβ levels in AD patients are abnormally elevated due to imbalance between production and degradation, leading to the deposition of Aβ in the brain and leading to neuronal damage and death in the brain. It is the root cause of memory and cognitive decline.

Based on this theory, different therapies targeting Aβ have been developed. Some of them attempt to target Aβ-producing proteases to prevent Aβ production, while others hope to bind free Aβ monomers in the blood, preventing them from entering the brain to produce deposits. The current trial results show that these therapies are not yet effective in preventing cognitive decline.

"This may be related to the characteristics of some of the therapies," says Christian Haass, MD, head of the Munich-based Neurodegenerative Disease Research." For example, some drugs can only bind to Aβ monomers, but not to deposited Aβ fibers; In addition, drugs injected into the patient's body may bind to Aβ monomers in the bloodstream, resulting in insufficient drug to enter brain, reducing Aβ monomer in the brain."

Other drugs with different mechanisms are expected to bring about a turn for the better. Aducanumab, which can target Aβ deposition in the brain, is one of them. In early clinical trials, this antibody can eliminate Aβ deposition in the brain and reduce memory loss. Its Phase 3 clinical trial is expected to end in 2020. The researchers believe that the different modes of action of Aβ may be the key to alleviating symptoms.

In summary, the current clinical trials in the setbacks encountered in progress, but it does not necessarily explain the amyloid hypothesis is wrong. New drug development is a long and thorny road. We hope that the new drug development of AD can find the direction of progress and ultimately bring new treatment for patients. Flarebio provides good-quality recombinant proteins such as recombinant Itgb2 for your research.

The role of tau protein and phosphate in Alzheimer's disease

Alzheimer's disease is the most common form of dementia, and it is characterized by a gradual loss of cognitive ability, namely the ability to learn, memorize and plan. More than 35 million people worldwide are diagnosed with Alzheimer's disease. The figure continues to increase due to the aging population. Unfortunately, we have no way to cure this disease. The current treatment is effective, but it can only reduce the symptoms to a very low level. Therefore, understanding how Alzheimer's disease is formed and its hidden processes through recombinant human proteins is important for effective treatment of this disease.

Researchers have recently discovered a new and surprising clue about the role of tau and phosphate in Alzheimer's disease. The first evidence comes from genes. They unexpectedly found a gene that protects mice from Alzheimer's disease. The study also found that the protein formed by this gene will gradually decrease with the onset of Alzheimer's disease.

In conjunction with the use of cultured mouse neurons, the researchers carefully studied how this gene works and found that this gene affects the manner in which phosphate groups attach to tau proteins. This gene plays a protective role by establishing a special tau phosphorylation model.

The researchers also found that when mice were given a specific mode of attachment of phosphate groups, they were protected from Alzheimer's disease. The study changed our thinking about molecular events in Alzheimer's disease. Researchers have found that a specific tau phosphorylation pattern can prevent neuronal death in mice with this disease model. In other words, a phosphorylated tau that protects the brain from Alzheimer's disease can form in the brain. This challenges the conventional wisdom of researchers that tau phosphorylation only causes toxic effects and is "sinful" in the development of Alzheimer's disease. Flarebio provides you with good-quality recombinant proteins like recombinant Itgb2 at great prices.

APOL1 gene can induce kidney disease

According to an article published in the November 18 issue of the American Journal of Nephrology, the National Institutes of Health System for Children has discovered a gene, APOL1, which induces kidney disease. The new form of the mutated APOL1 gene increases the risk of chronic kidney disease among people of African descent. Using a powerful genetic approach and recombinant horse proteins, national researcher of children was able to mimic APOL1 in Drosophila renal cell pathology. It opens the door to identifying other proteins that interact with APOL1, which is an important first step in identifying kidney disease that is currently drug-free.

The advantages of Drosophila in biomedical research include its rapid generation time and unparalleled ability to explore the basic biological processes of human underlying diseases through rich, complex genetic tools. People of African descent usually inherit APOL1 mutant genes to protect Africans from sleeping sickness in Africa, but this gene increases the odds of developing certain types of kidney disease by 17 to 30 times or more. Individuals are at higher risk of being infected with human immunodeficiency Viruses (HIV). Drosophila kidney cells, called kidney cells, accurately mimic the pathological features of human kidney cells in APOL1-associated kidney disease.

"Kidney cells have striking structural and functional similarities to mammalian podocytes and proximal tubule cells," says Zhe Han, an advanced Drosophila expert and associate professor of cancer and immunology at the Center for Cancer and Immunology. "This provides us with a simple kidney disease model system."

In a recent study, Han's team cloned the mutated APOL1 gene in cells from podocytes cultured in patients with HIV-associated nephropathy. They created transgenic Drosophila, similar to human APOL1 kidney cells, and observed that the initial transgene caused an increase in cellular functional activity. However, as the flies age, APOL1 leads to decreased cell function, increased cell size, abnormal vesicular acidification and accelerated cell death.

"The main function of kidney cells is to filter proteins, remove toxins from flowing blood, reabsorb protein components and chelate harmful toxins. Surprisingly, these cells begin to become more active and play a temporary role at a higher level. The cells become bigger and stronger, but they can't sustain this enhancement," said Han. "Cells die and cell hypertrophy is the way the human heart responds to stress overload after swelling to twice its normal size. We think that kidney cells may use the same coping mechanism."

The Children's Research Group is a multidisciplinary team of members from the Cancer and Immunology Research Center, the Center for Genetic Medicine Research and the Department of Nephrology. The group also characterizes flies phenotypes associated with APOL1 gene expression, which will facilitate the design and implementation of Drosophila gene screening methods to identify proteins that interact with APOL1 and contribute to disease mechanisms. Such proteins represent potential therapeutic targeting targets. Transplantation is currently the only option for patients with kidney disease associated with APOL1.

"It's just the beginning," Han said. "Now that we have an ideal preclinical model, we plan to start testing out-of-the-box therapeutic compounds, such as different kinase inhibitors, to determine if they block any steps leading to kidney cell disease." Flarebio offers recombinant proteins such as recombinant Itgb2 at competitive prices.

It's promising to treat Alzheimer's disease using gene therapy

Recently, a study from the Imperial College of Technology in London, England, has provided new possibilities for the treatment of Alzheimer's disease through recombinant human proteins. The researchers said their mice experiments showed that gene therapy may be successful in the treatment of Alzheimer's disease. The study was published in the Proceedings of the National Academy of Sciences.

Researcher Magdalena Sasite participating in the study of Imperial College London said that they used the modified lentiviral vector to inject a gene called PGC1-α into the memory region of the mouse brain. These mice just began to develop early symptoms of Alzheimer's disease. The results showed that this therapy prevented the accumulation of β-amyloid in the brain of mice, which is thought to cause brain cell death and was closely related to the pathogenesis of Alzheimer's disease.

The researchers said that after treatment with gene therapy for 4 months, few amyloid plaques of Alzheimer's disease existed in these mice brain. In the task-testing of memory, these treated mice behaved as well as healthy mice. In addition, their brain memory region also showed no loss of brain cells.

Genetic factors play an important role in the pathogenesis of Alzheimer's disease. Preston Estepp, director of Gerontology Research of "Personal Genome Project" of Harvard University School of Medicine and the author of the book Longevity of the Gene, said, "There are two most significant genes. They are apolipoprotein E (APOE) and amyloid precursor protein (APP)."

"More and more research evidence suggests that APOE is responsible for transporting iron into the brain. With the increase in iron accumulation, APP protein is also increasing to protect the brain cells and tissues. Then, the special cells that function as cleaners begin to work. A small portion of the APP will be cut off and discarded, and the abandoned part is β-amyloid protein, which is the culprit of formation of brain age spots. The enzymes which play cutting role play other roles in the cells, but the APP cut on the human body does not make any sense and may even cause collateral damage to the human body. With the accumulation of β-amyloid, functional brain cells will be killed and replaced," Estepp made the above explanation for the interaction of APOE and APP genes with iron.

Estepp suggested that we should pay more attention to the iron content of food. "For normal women, 18mg of iron can provide them with 100% of the daily intake. For other adults, the general daily 8mg of iron can be met," Estepp also said, "There are individual differences in iron uptake efficiency. In addition to the iron content of the food and the reasonable control of the intake, we can also monitor the key biomarkers for iron, including serum iron, serum ferritin, hemoglobin and so on.” Flarebio offers recombinant proteins of good quality such as recombinant Itgb2 at great prices.

Nature: MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models

Medical research scientists have been trying to find a new type of "generic" drugs or methods that can effectively kill tumor cells and can be used for the treatment of acute myeloid leukemia, lymphoma and multiple myeloma and other blood type cancer and can also be used in melanoma, Lung cancer and breast cancer. Achieving this ideal seems to be gaining momentum. A related international collaborative study appears in the recent top journal, Nature, and it is entitled "The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models". The journal also publishes other studies on recombinant rat proteins.

This "miracle" compound is called S63845 and it targets the BCL2 family of proteins, MCL1 (pro-survival bone marrow cell leukemia 1), which is essential for cancer cell survival.

Professor Guillaume Lessene from the Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia, Professor Andrew Wei, a hematologist from Melbourne Alfred Hospital and Dr. Donia Moujalled from the Servier Research Institute of Medicinal Chemistry, Hungary, led their team to collaborate on the study, The results showed that S63845 is not only effective for several types of cancer, but also has good tolerance for normal cells.

Tumor cells develop and sustain their growth by avoiding programmed cell death. MCL1 is overexpressed in many cancers, but targeting the small molecules of the proteins has been challenging in clinical trials. The small molecule described in this study, S63845, can bind to the BH3 binding domain of the MCL1 protein with high affinity and specificity. Mechanistically, the scientists have shown that S63845 effectively kills MCL1-dependent cancer cells, including multiple myeloma, leukemia, and lymphoma cells by activating the BAX / BAK-dependent mitochondrial pathway. In vivo, S63845 exhibits potent antitumor activity with an acceptable safety factor as a single agent for a variety of cancers. In addition, through alone or in combination with other anti-cancer drugs, the researchers found that inhibition of MCL1 function can also be effective for several solid cancer-derived cell lines.

Professor Guillaume Lessene believes that this work provides the first clear preclinical evidence that inhibition of MCL1 is effective against a wide range of cancer types. "MCL1 is important for many cancers because it is a pro-survival protein that allows cancer cells to escape programmed cell death - a process that normally acts to remove cancer cells from the body, which is currently being carried out in a variety of cancer models. Extensive studies have shown that S63845 effectively targets survival of MCL1-dependent cancer cells, "Professor Lessene said.

Olivier Geneste, Ph.D., director of oncology at Servier, said that MCL1 was considered a valuable yet highly challenging target for preclinical studies and could be used to design drugs for this target important basis. "S63845 was discovered in collaboration with Vernalis and based on the discovery technology of fragments and structures," he said. "Servier and Novartis are collaborating on such targets. As part of the project, the clinical development of MCL1 inhibitors is expected to be launched in the near future. Flarebio provides you with good-quality recombinant proteins such as recombinant ITGB2 at good prices.

Alzheimer's disease of experimental mice is curable now!

Molecular biologists have successfully created and tested the first reverse transcriptase therapy for Alzheimer's disease by use of recombinant mouse proteins, which protects mice from disease. The study was published in the Proceedings of the National Academy of Sciences (PNAS).

"Our results show that gene therapy can be used to treat Alzheimer's disease, although it is too early to talk about this. Therefore, we must overcome a large number of obstacles. In addition to direct injection of brain, we can't induce this gene therapy through other methods," said Magdalena Sastre at the Imperial College in London, UK.

In the last two years, biologists have gained a better understanding of the causes of Alzheimer's disease and the definition of the disease. For example, recently scientists have found that Alzheimer's disease may be transmitted; β-amyloid plaques may be an important part of the innate immune system; and some therapies that are expected to treat the disease.

One approach - forcing the PPARGC1A protein associated with cell self-purification systems and cellular metabolic work to actively counteract beta-amyloid plaques. Sastre and colleagues believe that this process can be achieved by gene therapy (embedding other copies of the gene in hippocampal cells, storage centers, and the cerebral cortex). To test this idea, the scientists grew a population of mice with Alzheimer's disease and introduced a special retrovirus that contained other copies of the PPARGC1A protein in their brains. Another group of uninfected rodents was the control group.

Four months later, scientists compared the state change of the two groups of rats. It was found that the presence of a copy of the PPARGC1A protein had a very positive effect on rodent status, significantly reducing the amount of beta-amyloid protein entanglement in the rat nerve cells and preventing the negative effects produced by the development of Alzheimer's disease.

According to scientists, these mice have good memory, and they complete the task of finding a maze outlet and the ability to deal with other cognitive problems as much as not suffering from Alzheimer's disease in healthy rodents. The fact that rodents are healed proves that almost no cell survives in the hippocampus and cortex. When Alzheimer's disease enters the final stage, neurons usually die in large numbers.

Scientists hope their research will serve as the basis for the development of retroviral vaccines that can be adapted to humans without the need to inject potentially lethal drugs directly into the brain. According to scientists, this gene therapy can not only adapt to the existing Alzheimer's disease, but also can be used as a special vaccine to prevent disease development. Flarebio offers good-quality recombinant proteins such as recombinant ITGB2 at good prices.

This herbal ingredient is effective on a certain kind of leukemia

An international study group led by the University of Hong Kong reported in a new issue of the journal Science Translational Medicine that the effect was significant when homoharringtonine extracted from the genus Cephalotaxus was used to treat acute myeloid leukemia patients with FLT3-ITD gene mutations. Acute myeloid leukemia is a common cancer of the adult human blood system, and nearly 30% of patients with acute myeloid leukemia carry FLT3-ITD gene mutations.

Liang Ruhong, vice president of the Li Ka-shing School of Medicine of the University of Hong Kong said that the standard chemotherapy regimen and drug sorafenib were not effective in patients with acute myeloid leukemia carrying the gene mutations. In order to find a better treatment, they made use of leukemia cells of patients and recombinant rat proteins to conduct drug screening in vitro and found that homoharringtonine has significant inhibition function on it.

According to Liang Ruhong, homoharringtonine is a bio-ester base derived from the Cephalotaxus plant. In China, homoharringtonine is commonly used in the treatment of acute myeloid leukemia but not for a specific type of leukemia, so the effect is not so significant.

Liang Ruhong and his colleagues recruited 24 acute myeloid leukemia patients who showed relapse or are refractory with FLT3-ITD gene mutations to conduct clinical trials. They used homoharringtonine and sorafenib to conduct combination therapy, and finally 20 patients Leukemia cells in vivo were removed, and the overall survival was significantly longer.

Liang Ruhong said, "Homoharringtonine can inhibit cell protein synthesis so that cancer cells can't produce important proteins, leading to cancer cell apoptosis. Relative to the current approach, the side effects of combination therapy are small and can be applied to frail or elderly patients." Liang Ruhong thought that this study provides an effective treatment strategy for FLT3-ITD acute myeloid leukemia. Flarebio offers superior recombinant proteins such as recombinant ITGB2 at great prices.

Abnormal protein deposition is linked with incidence of cognitive dysfunction disease

IPS Cell Research Institute of Kyoto University, Japan, announced that they successfully used cells from patients with frontal lobe degeneration and recombinant human proteins to produce iPS cells (induced pluripotent stem cells), confirming the abnormal protein deposition is associated with the incidence of cognitive dysfunction disease.

The team led by Prof. Inoue Takeuchi, director of the Institute of iPS Cell Research, completed the experiment. The results were published in Scientific Reports in UK on October 10, 2016.

Frontotemporal lobar degeneration (FTLD) is a disease caused by social disorders and language disorders due to focal cerebral frontal and temporal lobar degeneration and atrophy. Experts generally believe that Tau gene mutation is the cause of frontotemporal lobe degeneration, but the specific mechanism has not been proven.

The researchers used the cells of two patients with two different types of Tau gene mutations to produce iPS cells and then used gene editing technology to modify the gene mutation of iPS cells. They transformed the iPS cells of these two people into neurons cells and compared them, finding that Tau gene mutations may cause the deposition of abnormal proteins.

In addition, the researchers also found that in iPS cells of Tau gene mutations, the calcium content increased. If inhibiting calcium ions into the cells, then the amount of abnormal protein can be reduced and cell survival rate can increase. Professor Inoue Haruhisa said, "This achievement is an important step towards new drug research and development." Flarebio offers recombinant proteins of good quality such as recombinant ITGB2 at great prices.

Scientists find a gene variation that can increase the mortality of smokers

Previous studies involving recombinant dog proteins have shown that the clustering genetic variation of the nicotinic acetylcholine receptor subunit (CHRNA5-CHRNA3-CHRNB4) on chromosome 15 has a strong association with smoking and the risk of smoking-related disease. CHRNA5-CHRNA3-CHRNB4 includes chronic obstructive pulmonary disease (COPD), peripheral arterial disease and lung cancer.

As multivariate label of CHRNA5-CHRNA3-CHRNB3 cluster, whether rs1051730 (C/T) is associated with changes in incidence and morbidity of smoking-related diseases? In this regard, we analyzed a population-based prospective cohort study (Malmö diet and cancer study).

At baseline, participants were divided into three groups: current smokers (n = 6951), former smokers (n = 8426), and never smokers (n = 9417). They used Cox proportional hazards model to assess the association of rs1051730 and first-time COPD, smoking-related cancers, other cancers and cardiovascular diseases. They also followed the association between rs1051730 and the overall mortality risk from these diseases in the next nearly 14 years.

Data shows that among current smokers, the first COPD, smoking-related cancer, other cancers and cardiovascular diseases respectively showed 480 cases, 852 cases, 810 cases and 1022 cases. There were a total of 1,508 deaths, among which cardiovascular disease, respiratory disease and cancer were respectively 500, 102 and 677 deaths.

The analysis showed that with the increase in the number of T alleles, the overall mortality, COPD and incidence of tobacco-related cancers increased. The association remained after adjustment for smoking. But for people who never smoked, they did not show this connection.

Our data showed that the genetic variation of the CHRNA5-CHRNA3-CHRNB3 cluster is associated with the increase of mortality of smokers, COPD and incidence of tobacco-related cancers. Flarebio provides good-quality recombinant proteins like recombinant ITGB2 at competitive prices.

New hope for developing new breast cancer drugs

Australian National University announced on 10th that researchers of the school have new findings of a group of proteins which helps to turn on or off some gene expression in the blood cell generation process, which helps to develop new and more effective breast cancer drugs.

Through a lot of studies using recombinant proteins such as recombinant horse proteins, researchers reveal the working mechanism of a group of specific proteins - chromatin helicase DNA binding protein (CHD). The group of proteins consists of the nucleosome remodeling deacetylase. This enzyme can turn on or off certain gene expression in the replication process of blood cells and stem cells. One of the proteins, CHD4, is associated with breast cancer, while there are no drugs specifically for this protein among existing drugs to treat breast cancer.

Dr. Daniel Ryan from Medical Research Centre of John Curtin at the Australian National University said that some currently-used breast cancer treatments are effective, but their mechanisms are not clear. While the research he is undertaking reveals the working mechanism of CHD4, which would make it possible to specifically develop super drugs of this protein for the treatment of breast cancer later. More precisely targeted therapies will reduce the toxicity of the drug and reduce resistance.

He said the researchers still need to break down this enzyme in order to explore how different proteins work with each other and to learn how complex molecular structures operate. Flarebio Biotech LLC is a National High-Tech Enterprise with research, production and sales as one. It provides you with superior recombinant proteins like recombinant ITGB2 at good prices.

Researchers unexpectedly find new vaccine which is effective to hepatitis B

A new anti-grass pollen allergy vaccine (BM32) also can be effective against hepatitis B virus infection. The study used a lot of recombinant proteins such as recombinant horse proteins and was conducted by the Institute of Physiology, Medical University of Vienna pathology experts, published in the journals EBioMedicine.

BM32 vaccine is developed based on innovative recombinant peptide - carrier technology. Compared with other immunotherapies, the technology shows fewer side effects on allergy sufferers. The technology was conducted under the dominant of Rudolf Valenta from Medical University of Vienna.

In a IIb Phase trial led by the research institution, Carolin Cornelius found that BM32 can also resist hepatitis B virus infection when it prevent grass pollen allergy at the same time. Cornelius said, "We can prove that for those people who weren’t vaccinated with hepatitis B vaccine previously, the effective resistance rate against hepatitis B virus would reach 80% after taking BM32 vaccine." Related researchers said that the concept of peptide - carrier fusion proteins perhaps would provide new ideas for the development of immunotherapy which can improve hepatitis B infection in the future.

Cornelius continued, "We are currently researching on whether the vaccine is able to specifically resist hepatitis B virus. Hepatitis B virus infection is very common nowadays. About 350 million people worldwide carry the hepatitis B virus in the blood. For people who have taken hepatitis B vaccine, there is also 5-10% of them may respond to the virus." Flarebio provides you with good-quality recombinant proteins like recombinant ITGB2.

New hope for patients with Alzheimer's disease

A new therapy of Alzheimer's disease brings new hope for people to cure this incurable disease. This therapy seems to be able to reduce the major pathogenic factor protein deposits in the brains of patients. According to research published by American and Swiss researchers in the journal Nature, the researchers used recombinant human proteins to conduct research and found that the new treatment also slows down the decline of brain processes.

The researchers divided 165 patients with Alzheimer's disease into two groups to conduct research. A group of patients took placebo, and the other group took Aducanumab antibody once a month. Such antibodies can reduce the typical protein deposits in brains of patients with Alzheimer's disease. Before typical features of Alzheimer's disease such as memory loss, thought and language barriers occur, the brains of patients have deposited amyloid plaques. We can call them β-amyloid plaques.

After a year of observation, a group of patients showed significant reduce of protein deposits. Moreover, the decline rate of cognitive function in patients was significantly slower than patients who took placebo. But the researchers believed that the positive role of the new antibody on cognitive function needs further investigation. However, scientists' findings confirm the hypothesis of amyloid protein and correctness of continuing to study the antibody which treats Alzheimer's disease.

Alzheimer's disease specialist Christian Haass at Neurodegenerative Disease Center Germany (DZNE) said previous studies also found the possibility of removing brain protein deposits, but it can't restore lost memories or stable memory. In contrast, the biggest difference in this research result is that we can confirm that reducing the protein deposits and memory stability is closely related. This is of course the main goal we want to achieve.

Haas said that this is undoubtly a very great progress that has been ever made in this area. Because the results of this study clearly indicate that antibody therapy is effective for the treatment of Alzheimer's disease. Antibody therapy can maintain memory. Haas believes, however, it is too early to refer it as "breakthrough". This is a small-scale test, but it is definitely the first to have some positive impacts on the memory of Alzheimer's patients at least.

Previous multiple tests showed that Alzheimer's disease has already develops long before memory loss, because protein deposits have been formed at an earlier time. Patients must be treated early if they want to prevent progression of the disease. It will be too late for most patients if they go to the doctor when the memory is fading. Flarebio provides you with good-quality recombinant proteins such as recombinant ITGB2 at good prices.