Mutations in the p53 gene in cancer patients offer clues to new research

P53 is a tumor suppressor and one of the most widely studied genes in cancer. It senses cell damage and activates mechanisms that stop cells dividing or start apoptosis, preventing damaged cells from entering the normal cell cycle. Mutations in the p53 gene can cause cell protection mechanisms to fail, possibly leading to cancer. Researchers at the University of Edinburgh School of medicine studied mutations in p53 to fully understand how the gene deactivates. The new findings may help predict clinical prospects.
Camille Bonneaud, a professor at the University of Edinburgh School of medicine, used big data to reveal that mutations in p53 were more frequent in patients with lower survival rates among all cancer types studied. At the same time, at the chromosome level, the research found that the p53 gene deletion obvious pattern. Studies have also shown that p53 mutations are closely related to genomic instability, suggesting that normal proteins play an important role in monitoring chromosome integrity. Meanwhile, in most patients with tumors caused by p53 mutations, other tumor suppressor genes were deleted and oncogenes amplified.
"P53 is one of the most important gatekeepers in cancer prevention, and understanding this gene will allow us to understand the pathogenesis of cancer, which will lead to better treatment of cancer," said professor Camille Bonneaud. The research could open up new avenues for cancer caused by mutations in the p53 gene.

Long-term latency of HIV is highly correlated with cognitive impairment

A team of British researchers reported in the journal Nature that they detected HIV DNA in the cerebrospinal fluid of patients with AIDS and found that these patients were more likely to have cognitive impairment than those without HIV.
For AIDS treatment, the most commonly used method is combination antiretroviral therapy (cART), which only inhibits HIV replication, but cannot eliminate it from the patient's body. Once the treatment is stopped, the virus replicates again. Clearing all HIV from the body of AIDS patients has long been the key to treating HIV, but in the central nervous system the effects of HIV are not fully understood.
In the new study, a team of researchers from several institutions, including the University of Cambridge, examined the cerebrospinal fluid of 49 AIDS patients. The vast majority of these patients were middle-aged women who received cART therapy for 5 years. The results showed that 46 percent of the patients had HIV DNA in their CSF cells, more than 40 percent had some degree of cognitive impairment, and 8 percent of those without HIV DNA in CSF cells had cognitive impairment. The researchers detected HIV DNA in the cerebrospinal fluid of most HIV patients, suggesting that cART could not kill the virus lurking in the central nervous system. Although there are many factors causing cognitive impairment in AIDS patients, such as age, inflammation, vascular dysfunction, etc., there is a close correlation between latent HIV DNA in CSF cells and cognitive impairment. The mechanism is unclear, but the findings have potential clinical value. The cognitive interference of HIV is another reminder of the complexity of the brain environment. In the future, we will associate more neurological diseases with brain pathogens.

Angiogenin

Angiogenin is the first cytokine identified to have a pro-Angiogenic effect from human tumor tissue. The family consists of four members, Ang1、2、3、4. Ang1 is synthesized by pericytes, vascular smooth muscle cells and tumor cells. Under the action of paracrine, Ang1 binds to receptors on adjacent endothelial cell membranes, phosphorylates the receptors, and then initiates signal transmission. But the exact process remains unclear. It is clear that Ang1 plays an important role in inhibiting endothelial cell apoptosis, reducing vascular atrophy and degrading cell life activities. According to the mechanism of Ang1, the researchers took
Ang1 is associated with tumor development. Studies have shown that Ang1 can promote tumor angiogenesis. Although the mechanism is not clear, it is an indisputable fact that Ang1 is involved in tumor angiogenesis. The possible mechanism of Ang1 in tumor angiogenesis is inhibition of endothelial cell apoptosis. The anti - apoptosis effect of Ang1 is a series of complex biochemical reactions. After Ang1 binds to the receptor, the subunit of PI3K linked to the receptor is phosphorylated to activate PI3K. PI3K ACTS on inositol phosphate to increase the contents of inositol 1, 4 and 5 triphosphate and inositol 3, 4 and 5 triphosphate, which positively regulate Ser/Thr kinase. Phosphorylation sites are Thr308 and Ser473. Survivin expression after Ang1 inhibits the phosphorylation of caspase7 and caspase9. Therefore, Ang1 may promote tumor angiogenesis in the process of tumor development, but this mechanism still needs to be further studied.
E0008m is a ready-to-use microwell, strip plate ELISA (enzyme-linked immunosorbent assay) Kit for analyzing the presence of the A Disintegrin and Metalloprotease 30 (Angiopoietin-1) ELISA Kit target analytes in biological samples. The concentration gradients of the kit standards or positive controls render a theoretical kit detection range in biological research samples containing......

New mechanisms that prevent cancer cells from killing healthy cells

Cancer cells in the face of the body's natural defense system cannot be killed, one of the main reason is the cancer was actually a kind of peculiar to human cells, they have a natural mechanism, can not only avoid the body's defense and tracking system, can even turn into our part of the defense system, so as to speed up the transfer and diffusion. So finding out how cancer cells respond to defense systems is key to fighting cancer.
Lead researcher Filippo Giancotti of the University of Edinburgh has taken an important step in this direction by identifying a cellular competitive mechanism that he calls "health fingerprints".
Filippo and his team found that the cells next to each other in the body are constantly evaluating each other's fitness levels through special markers on their surfaces. "We found that the cells themselves have two markers: one that tells them they're young and healthy, and the other that tells them they're old or damaged," Filippo explains. If a cell is healthier than its neighbors, that means it will destroy its neighbors, ensuring the health and integrity of the entire tissue."
Filippo and his team found that this process plays an important role in cell development, tissue regeneration and preventing aging, but it also gives cancer cells a chance to grow further. Cancer cells use their markers to disguise themselves as healthy cells, which can multiply without aging. In contrast, normal cells around cancer cells appear less healthy. Through a cellular competition mechanism, cancer cells grow, allowing neighboring normal cells to be devoured, destroying tissue and making room for tumors to spread. "But at the same time it makes the tumor more aggressive. The results are acceptable for mice, but too dangerous for humans, "Filippo points out. But the human immune system is also a double-edged sword and cannot allow destructive cancer cells to grow freely. This mechanism could be a potential new way to treat cancer.
Filipp......

Neuronal aging inhibits protein degradation

Autophagy is the process of dealing with the body's harmful "garbage". The body produces many wastes every day, such as some accumulated proteins. In order to make the structure and function of human cells normal, these "garbage" needs a mechanism to eliminate. If this mechanism is blocked, waste products accumulate in the cells, eventually leading to disease in the body. As cells age, their ability to expel harmful waste decreases, according to a new study from Duke University's institute of medical research. The findings suggest that the deterioration of autophagy in older neurons may be a risk factor for a range of neurodegenerative diseases, such as Alzheimer's and Parkinson's.
"Reduced autophagy makes neurons more susceptible to genetic or environmental risks," holtzbauer says. "Neurodegenerative diseases associated with worsening autophagy, such as Alzheimer's, Huntington's and Parkinson's, are the main areas of interest."
The mechanism of autophagy is that the autophagosome first binds to misfolded proteins and processes these wastes in the first step. Then, the autophagosomes that contain human waste bind to lysosomes, and the enzymes in the lysosomes degrade the waste. This degradation mechanism is the main way to keep neurons healthy, without which they eventually die from the accumulation of waste.
Through a series of studies of mice, the team showed that while the early stages of autophagosome formation were unaffected, they found that older mice had defects in their autophagosomes that could allow garbage to accumulate at synapses, causing neurons to receive or transmit signals that were interrupted or stopped. Holtzbauer points out that in other studies of the same type, researchers have found defective autophagosomes in the tissues of dead people with neurodegenerative diseases.
This provides further evidence that autophagosomes may play an important role in human neurodegenerative diseases, a finding that needs to be confirmed ......