AD: Shocked! The peak value of plasma Aβ42/Aβ40 began to decline 41 years before the deposition of brain Aβ! Alzheimer's diseases: New discovery on plasma Aβ42/Aβ40. AD: Shocked! The peak value of plasma Aβ42/Aβ40 began to decline 41 years before the deposition of brain Aβ! Amyloid β (Aβ) plaque deposition and phosphorylated tau (p-tau) protein tangles are two important pathological features of Alzheimer's disease (AD), and there are many kinds of AD biomarkers derived around them, Knowledge of the longitudinal trajectories of key markers could not only help improve the selection and monitoring of participants in clinical trials, but also help identify those at high risk for neurodegenerative changes and cognitive impairment. Although research on AD biomarkers has increased substantially in recent years, research on longitudinal changes in biomarkers is relatively limited. Studies have shown that the levels of plasma Aβ 42 /Aβ 40 , p-tau181 and glial fibrillary acidic...
bioRxiv: Scientists have identified a new potential target for the treatment of lung cancer
In cancer research, personalized medicine therapy often uses special genetic changes in a single tumor to find its weakness and attack it. Many tumors carry high levels of mutations, perhaps because of a special antiviral defense Mechanism-APOBEC system, which can accidentally damage DNA and induce mutations.
The analysis of cancer mutation characteristics often provides researchers with a large amount of information on the source of mutations, and can guide the use of clinical therapies, including immunotherapy, etc.; in particular, APOBEC3A (A3A, apolipoprotein B mRNA editing enzyme catalyzed polypeptide-like protein 3A, apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3A) has now become the main driver of mutations in cancer cells. Its expression can cause DNA damage and become sensitive to ATR and CHK1 checkpoint kinase inhibitor therapy.
Image source: https://www.biorxiv.org/content/10.1101/2021.02.05.429803v1
Recently, in a research report titled "Loss of HMCES is synthetic lethal with APOBEC activity in cancer cell" published on the pre-printed platform bioRxiv, scientists from the Barcelona Institute of Science and Technology and other institutions found through research, called HMCES The special enzymes may be the Achilles heel of some lung tumors, especially lung tumors with high-level mutations induced by the APOBEC system. HMCES is a protein related to abasic site protection, and it can also serve as a central protein that is resistant to A3A expression.
Researcher Dr. Supek pointed out that blocking the enzyme HMCES may have a strong destructive effect on cells with an active APOBEC system (such as many lung cancer cells), but it has no effect on cells that are not activated by the system, as in health. As observed in the cell. In addition to showing specificity to cancer cells, HMCES can also potentially be targeted by drugs, which makes it a promising candidate for future scientists to develop lung cancer therapies.
Image source: Josep Biayna, et al.bioRxiv (2021). DOI: 10.1101/2021.02.05.429803
In this study, the researchers used computer and experimental methods in collaboration with scientists from two different disciplines. The researchers used CRISPR/Cas9 technology to perform genetic screening experiments on various types of human lung adenocarcinoma cell lines. These experiments can analyze the effects of removing each gene from cancer cells. Based on this, the researchers wanted to see if the cancer would be tolerant to these changes. At the same time, they also performed statistical analysis on the data obtained from the CRISPR genetic screening conducted in other laboratories and confirmed the experimental results in this article.
The researchers said that when a cell senses a DNA mismatch, it will perform a DNA repair reaction to preserve the cell's genetic information. It is worth noting that this reaction will also be coupled with the APOBEC enzyme. APOBEC is usually used by human cells to resist viral infections. It also plays a key role in helping the body resist hepatitis and HIV infection. Previously, researchers worked on the genome. The data science laboratory described this mechanism, and they also found that in some cases, when APOBEC enzyme and DNA repair process are active at the same time, APOBEC can intercept the DNA repair process, thereby creating a mutation mystery.
Image source: Josep Biayna, et al.bioRxiv (2021). DOI: 10.1101/2021.02.05.429803
Advanced cancers tend to accumulate a large number of DNA mutations, which will make the cancer more aggressive and better resistant to drugs; many of these mutations are caused by APOBEC, which can accelerate tumor evolution. Therefore, killing can activate the APOBEC system Cancer cells may be able to slow the evolution of tumors and prevent them from acquiring new dangerous mutations. In summary, the researchers revealed that the destruction of HMCES and the expression of A3A will increase the sensitivity of cancer cells to ionizing radiation, oxidative stress and ATR inhibition. These strategies are often used in the process of tumor treatment; therefore, HMCES or It can be used as a very attractive target for the development of selective therapies for A3A-expressing tumors.