阿尔茨海默氏症,萎缩脑细胞 z-bo 2020-09-23 381

　　The unexpected results of the Salmonella test led to research showing that conventional chemotherapy can more easily cure drug-resistant cancer cells. Scientists at the University of Massachusetts Medical School have discovered that the Salmonella protein SipA can naturally reduce the well-known drug-resistant molecules found in many different types of cancer cells. By providing gold nanoparticles attached to proteins, researchers can significantly increase the sensitivity of tumors to certain chemotherapy and shrink colon and breast cancer tumors in mice.

　　Professor and Deputy Director of the Department of Microbiology and Physiology, University of Massachusetts Medical School. Dr. McCormick and Dr. Ganhan, assistant professors of biochemistry and molecular pharmacology and nanomedicine experts, are co-authors of this article. \r\n McCormick said: "Given the amazing clinical potential of this research to treat certain drug-resistant cancers, this is very interesting. Based on these findings, we are in the preclinical development stage. It has a history of more than 150 years. During this period, scientists have observed a variety of bacteria that can reduce cancer tumors. Recently, researchers have discovered that Salmonella and other bacteria can be used to fight cancer cells. He suggested that they can directly stimulate the immune response. The researchers also found that, Similar to other treatments, certain bacteria can selectively grow in tumors. Due to multiple reasons related to immune-related reactions and concerns about potential infections, Salmonella or other infections, the mechanisms that control these different effects are still unknown. In the family, Dr. McCormick has been researching biological tools to overcome the natural defenses of Salmonella-infected cells, especially testing the effects of SipA on specific transporters in human intestinal cells. He said that SipA may upregulate proteins and cause inflammation. It is believed that McCormick has used the common transporter P-gp as a control to complete a series of experiments. She was surprised, although she did not expect to find any abnormalities, she found that the bacterial product almost completely eliminated the P-gp transporter. P-gp is usually found on the surface of cells and is outdated.

　　McCormick believes that Salmonella needs to remove foreign bodies, debris and toxins from the cells, so Salmonella needs to inactivate the P-gp protein and promote cell infection to prevent cancer recurrence. Excess P-gp in these cells may lead to the development of drug resistance. The role of P-gp in these cells is that chemotherapeutic drugs and anticancer drugs are excreted from the cells before they are accumulated and killed. If you want to know the importance of -gp, then this new evidence shows that SipA alone can eliminate the P-gp protein that causes multidrug resistance cancer and can be used as an anticancer drug, but this protein exists in the body. Must be sent to the tumor McCormick has worked with Gangan to develop a Salmonella nanoparticle mimic of SipA. In addition to bacteria, SipA protein is a highly unstable potential patient. But it cannot be purely injected. Instead of using whole bacteria, it can simulate and stabilize bacteria. And we have developed a nanoparticle scaffold for transportation. One of them is called "nanoworm". \r\nDue to its inertness and unique three-dimensional scaffold, Han Gang chose gold and developed nanoparticles small enough to invade tumors, but they were too big. It is absorbed by most biological tissues. Regino Mercadorbo, a postdoctoral researcher in McCormick’s laboratory, said: “This tumor is different from normal people. We expect our nanobacteria to invade tumors instead of accumulating in other tissues because of tumors. It is easy to invade.”\R \nSipA-nanobug and the widely used chemotherapy drug doxorubicin are used in mouse models of colon cancer and humanized breast cancer. Mercado-Lubo said: "The results are very good. Very few tumors were found within 30 days. This is unusual. In some cases, the tumors are smaller than the thin part of the tissue."

　　It is also important that gold nanoparticles cannot accumulate in lung, heart and brain tissue. \r\nNext, McCormick, Gang Han and colleagues conducted further research on preclinical development. This helps to determine the safety, toxicity and dosage levels of this nanobacteria in patient studies. \r\n McCormick also said: "In the past two decades, scientists have been hoping to reverse the drug resistance of cancer cells by screening thousands of small P-gp inhibitor molecules. These attempts are clinically The above is still variable. Well, we proved that we can use SipA to achieve natural priority and 2 million years of co-evolution, and effectively eliminate intracellular P-gp without causing immune responses. Hanban is: a mimic It can stabilize certain therapeutic proteins and can be used in combination with various clinical chemotherapies to overcome multidrug resistance in different tumors.\R\nFor the first time, scientists have discovered a mysterious atrophic cell in the human brain, and It turns out that it seems to be related to Alzheimer's disease. I don't know," said Marie Evetranbre of Laval University in Quebec, Canada. She recently presented this discovery at the Translational Neuroimmunology Conference in Montana. These cells appear to be atrophied forms of microglia. Microglia keep the brain in order and protect it from infection. This is usually achieved by establishing unwanted brain connections or destroying abnormally infected brain cells.

　　However, the cells Tramble found looked darker and more destructive under the electron microscope. Tramble said: "It took a long time to identify them." He said that these contracted cells did not show the colored chemicals that are normally seen in microglia under a microscope. Compared with normal microglia, these dark cells seem to surround neurons and the synapses that tightly connect them. Trumbull said: "They are very active near the synapses," where these microglia appear, the synapses are usually atrophied and are degenerating. Tremblay discovered these dark microglia in mice for the first time, and found that their number increased as the mice got older. At the same time, these cells seem to be involved in many things, including stress, neurodegenerative diseases-Huntington's disease and Alzheimer's disease mouse models. Tremblay said: "Alzheimer's mice have 10 times more dark microglia than control mice."

　　Now she has detected these cells in the human body for the first time. Tramble analyzed the brains of Alzheimer's disease patients who died at the age of 45 and found that the dark microglia in them were about twice as large as the brains of healthy people at the same age.