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New treatment target of insulin resistance in type 2 diabetes
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A team led by researchers at the University of California School of Medicine was able to reverse diabetes insulin resistance and impaired glucose tolerance by eliminating protein galectin-3 (Gal3) in obese diabetic mouse models.

By binding to the insulin receptor on the cell, Gal3 prevents insulin from binding to the receptor-induced insulin resistance. A team led by Professor Jerrold Olefsky, professor of endocrine and metabolic medicine from the University of California, San Diego School of Medicine, showed that by gene deletion Gal3 or using a drug inhibitor, insulin sensitivity and glucose tolerance can be restored even in older mice normal. However, obese mice remained unchanged.

"This study used Gal3 as a program target for insulin resistance and diabetes in the mouse model," said Olefsky, senior director of the study, a deputy director of scientific research. "Our findings suggest that Gal3 inhibition in the human body may be an effective treatment for diabetes."

Olefsky and other researchers have been studying how chronic tissue inflammation leads to type 2 diabetes insulin resistance. In an article published in a cell journal on November 3, the researchers explained that inflammation needs to disrupt the specific exclusive macrophages of target cells. For example, in obese adipose tissue (fat), 40% of the cells are macrophages. Macrophages also secrete lactose lectin - 3, and then as a signal protein to attract more macrophages, resulting in more Gal3 production.

In addition, the researchers identified the source of bone marrow macrophages that are the source of insulin resistance that leads to insulin resistance. More importantly, the researchers found that Gal3 is secreted by macrophages and can lead to insulin resistance independent of inflammation in the liver, adipocytes and muscle cells.

Gal3 has been linked to other diseases. Olefsky would continue to study Gal3 depletion that may serve as a target for nonalcoholic steatohepatitis and heart and liver fibrosis.
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The small molecule inhibitors of some biogenic enzymes are effective for gliomas
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A paper published in the Journal of Cancer Research lists the results of studies on gliomas: 1) identification of biogenic enzymes associated with gliomas; 2) a mechanism for the regulation of such enzymes; 3) by using a mouse model of gliomas, it is shown that the small molecule inhibitors they develop are effective for gliomas.

Such GA11 inhibitors retain a core structure similar to that of natural inhibitors of biological enzymes; however, such inhibitors have been modified to allow them to pass through the blood-brain barrier.

"In principle, these features make GA11 a candidate for treatment of gliomas," Dr. Ichiro Nakano said.

Nakano is a professor of neurosurgery at the University of Alabama at Birmingham, and he and other researchers are further pre-clinical evaluation of GA11 and its analogues.

"Polymorphic glioblastoma (GBM) is a class of highly lethal tumors. Over the past 30 years, little progress has been made to increase the average survival of patients from five months to 15 to 16 months," Nakano said.

GBM tumors are a class of mixed cell tumors. A small amount of gliomas stem cells induce GBM tumorigenicity, so these stem cells become the primary goal of treatment. Nakano and colleagues infer that determining the regulatory mechanism of bone marrow mesenchymal stem cells activity may develop new and effective treatments.
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Scientists have discovered anti-Zika virus protein
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Recently, the Chinese Academy of Medical Sciences Institute of System Medicine, Suzhou Institute of System Medicine (referred to as "the system") has published a research result with the University of California, Los Angeles and other institutions. The researchers found that protein Cholesterol-25-Hydroxylase (CH25H) and its enzymatic reaction product, 25-hydroxycholesterol (25HC), had a definitive protective effect on the disease caused by Zika virus infection and was expected to inhibit Ebola Viruses, HIV and so on. The results have been published by the internationally renowned journal Immunity.

Zika virus broke out in Brazil and other countries in the United States from 2015 and is still a global threat to human health. China has also reported dozens of cases of imported Zika cases. Once pregnant women infected with Zika virus, it may lead to fetal development abnormalities, neonatal head disease and other neurological diseases. There is currently no effective therapy for the Zika virus, nor through the clinical trial of the vaccine.

According to Dr. Li Chunfeng, who participated in the research system, as early as in 2013, Chinese and American scientists discovered the broad-spectrum antiviral effect of 25-hydroxycholesterol. After the outbreak of the Zika virus, the system responded to the national call and the Institute of Microbiology and Epidemiology of the Academy of Military Medical Sciences, Chinese Academy of Sciences Institute of Genetics and Development and the University of California, Los Angeles and other institutions carried out joint research on the cholesterol-25-hydroxy.

Cholesterol-25-hydroxylase is an interferon-stimulating gene whose gene expression product allows the cholesterol to be oxidized to produce 25-hydroxycholesterol. Through the experiment, the researchers found that 25-hydroxy cholesterol can directly block the virus into the cell process, including a variety of insect vector yellow viruses have a broad spectrum of antiviral activity including Zika virus. Researchers used the mouse model of the Zika virus infection and rhesus animal model and found that 25-hydroxy cholesterol treatment can significantly inhibit the virus in vivo replication and can effectively prevent the occurrence of microcephaly.

Professor Cheng Genhong, who participated in the study, said that 25-hydroxycholesterol was the first small molecule to be found in the monkey to inhibit the replication of the Zika virus and was the first compound to prevent the microcephaly caused by infection of the virus.

"Theoretically, it may have the same effect on the human body. Our next step is to begin clinical trials to verify the effectiveness of 25-hydroxy cholesterol on the human body," Cheng Genhong said. The system will also examine the antiviral effect of 25-hydroxycholesterol derivatives and look for substances that are more effective in suppressing Zika virus infection.

In addition, based on 25-hydroxy-cholesterol broad-spectrum antiviral effect, Chinese and American scientists have experimentally confirmed that 25-hydroxy cholesterol can inhibit Ebola virus, AIDS and so on. The two sides will continue to cooperate to apply it to the prevention and treatment of new viral diseases, which will provide new programs for effective prevention and treatment of viral infectious diseases.
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To develop cancer drugs by synthesizing proteins which not exist in nature
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Protein structure almost has unlimited possibilities. According to our needs to design and manufacture of proteins, it is possible to achieve a variety of magical functions.

Protein is the "labor" of all living creatures, carrying out various orders from DNA. It also has a variety of complex structures to achieve all the important functions of humans and all organisms, including digestive food, tissue growth, blood oxygen transmission, cell division, neuronal activation, muscle supply and so on. Surprisingly, the function of such a diversity of proteins comes only from the combined sequence of 20 amino acid molecules in the region. Until now, the researchers have just begun to understand how these linetypes are folded into complex structures.

Even more surprising is that nature seems to use only a small part of all possible protein structures, although the latter is large in number. Therefore, the use of existing amino acid design with a special structure of the unconventional protein, that is, nature has never had synthetic protein, having a very attractive application prospects. Synthetic protein method is: to genetic transform bacteria to make its DNA control produce a specific amino acid sequence and then synthesize proteins. It is important to be able to produce and study synthetic proteins at the atomic level for the development of new areas of basic research and for practical applications in more areas.

At the beginning of the design process, supposing a new protein structure that resolves a particular problem or implements a function, and then in turn determines a candidate amino acid sequence that can be folded into such a structure. The Roseetta protein model design software identifies the most promising candidates: the amino acid sequence that folds the lowest energy state of the target structure. Next, these sequences are transferred from the computer to the laboratory, producing synthetic proteins and testing.

At present, there is no technology comparable to the wonderful function of protein implementation. The infinite possibilities of synthetic proteins allow protein design to greatly expand the ability of protein technology.
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Scientists have discovered new treatment method of hemophilia
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A small-scale gene therapy trial involving several Canadian patients provides new hope for hemophiliacs. Hemophilia is a fatal hereditary rare disease. Due to lack of coagulation factors or protein, hemophilia patients would suffer from long-term uncontrollable bleeding, and even mild trauma would cause bleeding.

A new gene therapy developed by Philadelphia Children's Hospital has produced very encouraging results. Preliminary studies have shown that single therapy of experimental therapy may be able to help patients with type B hemophilia lacking clotting factor IX. The therapy involves the use of a designed gene to replace the wrong gene of hemophiliacs. The designed gene is placed into an inactivated virus and then injected into the liver, where it helps the patient produce clotting factors and prevent bleeding. "This brings the potential for a one - time treatment to change the patient's life," said Dr. Lindsey George, Ph.D., of the Philadelphia Children's Hospital.

Scientists have found that after only one dose of treatment, nine patients who participated in the trial did not show any bleeding for up to a year. Although more and more studies are needed to confirm the benefits of the therapy, the researchers are encouraged. "It's really exciting from my point of view as a clinical researcher," Dr. George said.

Among the nine patients treated, four were Canadian. One of them is the 52-year-old Ontario Cambridge Bakery owner, John Konduros. As a lifelong hemophilia patient, he has been living in any fear of any collision, cuts or scratches that may cause internal bleeding, disability or even death.

"It affects every part of my life from I'm a child until now," he told CTV News, "If you've ever seen my childhood, you'll find that I have never been in a group with other kids together. I'm always hiding aside," Konduros said. If another child happens to hurt his legs when playing, then he would be absent in 2 or 3 weeks. Konduros has not had any risk of bleeding since it received experimental treatment about eight months ago. So far, the immune system of the two trial patients has responded to the treatment, but the scientists said there was no serious side effect. Konduros did not have any problems.

Dr. Jerry Teitel, MD, director of the hemophilia treatment center at St. Michael's Hospital in Toronto, collaborated with Philadelphia researchers as "a revolutionary therapy". Dr. Teitel said, "In the development of drugs to help more hemophilia in the process, the scientists have a long way to go. We need to show that the results are reliable in a large number of patients. And we need to show that the results can last for a long time, but not sure whether they are for a lifetime."
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CD28 protein is the key factor to response of PD-1 inhibitor
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Opdivo, Keytruda and other immunological check point inhibitors mainly lift the body's T cells in the "immune suppression" state by blocking the PD-1 / PD-L1 signaling pathway so that T cells are activated to kill tumor cells. The problem is that these drugs are not effective for all cancer patients, and the reasons are not yet fully elucidated.

Scientists at Emory University in the United States recently published in Science and said, "To make the immune suppression of T cells activated and a large number of proliferation response, in addition to the need for Opdivo, Keytruda and other immunological check point inhibitors, but also need other 'fuel'. In the mouse experiment, if the use of genetic engineering technology to knock out the CD28 expression gene or the use of antibodies to block the expression of CD28, T cells couldn't respond to PD-1 inhibitors and achieve substantial amplification."

In order to verify the effect of this finding on the human body, the scientists at Emory University contacted the oncologists of the Winship Cancer Institute to analyze tumor tissue samples from NSCLC patients who received PD-1 inhibitor therapy. In these T cells, the proportion of CD28-positive cells was poor, ranging from 20% to 90%, suggesting that only a small fraction of T cells responded to PD-1 and amplified.

The FDA-approved immunoassay inhibitor is only effective for a small number of patients, and many biopharmaceutical companies see the "more effective inhibition of immunological checkpoint signaling pathways" as the highest priority research and development direction, and therefore they carried out a variety of immunotherapy drugs and other drugs combined with the study, such as Opdivo and Johnson & Johnson JNJ-64041757 combined treatment of NSCLC, Keytruda and Anjin the oncolytic virus Imlygic combined treatment of melanoma.

Emory University's research team is currently leading the way to improve the efficacy of CD28 to improve the effectiveness of cancer immunotherapy. The strategy is to take CD28 as a precursor molecular marker to screen the most appropriate cancer patients to enhance the efficacy of tumor immunotherapy.
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The key protein of leukemia has been discovered
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Scientists have found that regulatory protein ENL can promote the occurrence of leukemia. This has deepened the academic understanding of transcriptional regulation and suggests a potential leukemia therapy.

The cause of blood tumors is usually chromosome translocation, resulting in two proteins connected to the formation of fusion protein, and ultimately causing disease. Recombinant protein in regulatory protein mixed lineage leukemia (MLL) is also commonly found in invasive childhood leukemia and is associated with poor prognosis. Therefore, it is necessary to develop a leukemia treatment strategy based on MLL rearranged (MLL-r) fusion protein. In the journal Nature, Erb et al. and He et al., point out that ENL protein is a key factor in the survival of MLL-r cells in leukemia. Erb et al. and Wan et al. have shown that this "read" ability of ENL to acetylated histones is critical to induction of MLL-r leukemia.

Erb et al. and Wan et al. found another complementary mechanism for SEC and DotCom stability. They found that the inactivation of ENL weakened the function of SEC and DotCom in MLL-r cells. The ability of ENL to bind to SEC and DotCom suggests a model that recognizes the acetylated H3 through the YEATS domain, enhancing the stability of the SEC and DotCom complexes with DNA binding and regulating the activity of the genomic abnormalities.

Protein ENL is essential for MLL-r leukemia. Some leukemias are found in some of the MLL protein and another part of the protein mixture of protein. The second protein is usually part of the SEC (super elongation complex) protein complex or the DotCom (DOT1L-containing complex). Both of these protein complexes regulate gene transcription procedures in MLL-r leukemia (complete and partially fused SEC / DotCom complexes). The ENL protein binds to two complexes, while the complex is fused to the MLL in the cell. ENL interacts with the fused SEC / DotCom and interacts with the fused SEC / DotCom. ENL contains a YEATS domain that recognizes a specific acetyl (Ac) on histone H3. Erb et al. and Wan et al. demonstrated that the YEATS domain of the ENL protein helps to stabilize the binding of SEC and DotCom to DNA and promote gene expression that drives leukemia.

This new model suggests a possibility that drugs such as small molecule inhibitors targeting the ENL YEATS domain can selectively kill leukemia MLL-r cells. Other cell types appear to be able to tolerate ENL loss to a large extent, but the SEC, DotCom and ENL are expressed in a variety of cells, so it is important to understand this tolerance when developing such drugs on the difference.

The effect of these combination therapies suggests that multiple histone-modified signals act together to form a specific epigenetic state of MLL-r leukemia. Thus, long-targeted therapy is more effective and can reduce the emergence of drug resistance - which is one of the risks of single drug therapy. Thus, Erb et al. and Wan et al.'s findings on ENL not only deepen our understanding of how cells integrate transcription-related signals, but also provide new insights into the treatment of complex diseases.
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Protein Myb helps to prevent the development of immune and inflammatory diseases
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Researchers have found that protein Myb plays a vital role in maintaining the health of our immune system and preventing the development of immune and inflammatory diseases. Preclinical studies have shown that Myb gives immune cells known as regulatory T (Treg) cells "authority" to control the intensity of immune responses. The study was published on Immunity and was led by Dr. Shelia Dias and Professor Stephen Nutt in collaboration with immunologists and bioinformatics teams at the Walter and Eliza Hall Institutes.

Dr. Dias said it was the first sign that Myb had an impact on the immune system. "For decades, Myb has been associated with the formation of multiple types of cancer," Dr. Dias said. "Our study shows that Myb is also important for the function of Treg cells, and we find that at the site where Myb is absent, the ability of Treg cells controlling immune response is also weak, and the immune system continues to respond to a range of threats from mild infections to life-threatening disease. Researchers around the world are investigating how the immune system coordinates and controls health."

"There are many different cell types in the immune system, each with a specific obligation. And when these cells fail to perform their duties, there is a risk of health," Dr. Dias said.

Professor Nutt said, "Increasing the knowledge of the mechanisms that control the immune response is critical to understand how immunization and inflammatory illness occurs and to ultimately develop more effective treatment. If we can figure out how Myb affects Treg cells in the immune system, we may be able to manipulate this activity."

"In the long run, we would like to extend this study to the clinic in order to understand whether our findings can be applied to human immunology," he said.
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Scientists have discovered a specific protein associated with drug resistance
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The article published in the EMBO journal states that scientists have discovered a specific protein associated with drug resistance that could lead to new chemotherapy tools. Researchers have pointed out the role of f FOXO1 in chemotherapeutic resistance. In addition, they have identified a potential chemotherapy tool that is, constructing a short segment of amino acids: peptides.

There are many forms of cancer drugs. Among them, taxane chemicals are used for the treatment of advanced cancer. However, as time goes by, the taxane becomes less effective. Cancer cells communicate through other pathways. In this study, the researchers focused on how cancer cells develop other pathways and how to produce drug resistance.

Cells need energy functions. Kinases help chemicals react back and forth in specific molecules, usually in proteins. This activity will burn cell function. The scientists studied the serine / threonine kinase AKT. AKT helps cells survive, playing a very important role in many kinds of cancer. It can close the AKT drugs to improve the effectiveness of chemotherapy. However, due to the inherent complexity of cell communication, this therapy itself may allow tumor survival.

In this study, scientists used taxanes on cancer cells to block or inhibit AKT action, and they found that taxanes prevented FOXO1 protein from migrating cells to the nucleus. FOXO1 stays in the nucleus. In another protein, it becomes signal of active and improperly begins, helping cancer survive and produce drug resistance. "This is why AKT inhibitors are not approved by clinical trials. However, when FOXO1 migrates out of the nucleus, it binds to a protein called IQGAP1 scaffold. Binding action will prevent chemotherapy resistance. "We also found that the combination of taxane and FOXO1-derived inhibitors can inhibit cancer growth."
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