How do undifferentiated cells affect biological fate

From the light-sensitive cones of the retina to the filtering cycle of the kidneys, the body is made up of hundreds of cells that are dedicated to doing their jobs precisely. However, this delicate work may seem complicated, but in fact each of the cells involved starts as a single primitive cell. How do these primitive, undifferentiated cells decide to do something themselves? This question has long been the focus of the biological community.
Now, scientists from the university of California medical center and other institutions have discovered new clues about the molecular logic of cells that could explain how this works. The findings, based on studies of neuronal tissue in mice, suggest that cells face multiple choices as they grow, and that they work together as a team until they reach their final target organ.
"A mother cell can be anything, but how does that selection work?"Sanne Boersma, a senior researcher in biomedical sciences at the university of California medical research center. "Our study represents an attempt to define the molecular logic behind cell selection. "We believe our results will help us understand how cells perform their specific roles and what may go wrong in the process of cell differentiation."
The researchers say their results are related only to neurons, and it is unclear whether other tissues, organs and organisms follow similar cellular differentiation mechanisms. But the same approach can be used to understand cell differentiation in other tissues.

USP21 Enzyme Promotes Basal-like breast cancer

Basal-like breast cancer (BLBC) is the most aggressive subtype of breast cancer, and this disease overlaps with the triple negative classification. There is an urgent need for new treatments of these types of breast cancer.
In cancer cells, the transcription factor controls the rate at which genetic information is replicated from DNA to intracellular messenger RNA. Transcription is critical for the correct completion of the cell cycle and cell proliferation. One of these transcription factors is FOXM1, a large amount of FOXM1 was found in basal-like breast cancer. Although this factor is important in normal and cancer cell cycles, scientists have not fully understood the mechanisms in FOXM1 regulation.
In a recent study by researchers from the University of North Carolina and the Lineberger Comprehensive Cancer Center, researchers found that the USP21 enzyme protects the protein FOXM1, which occurs with basal-like breast cancer, metastasis, and poor patient prognosis. There is a close connection.
Using RNA interference screening techniques, the researchers found that the regulatory factor that determines the abundance of FOXM1, the USP21 enzyme, increases the abundance and stability of FOXM1. The more USP21 in the cells, the more protection FOXM1 receives in the cell cycle. When the researchers depleted USP21, they found a significant reduction in protein in the FOXM1 transcriptional network and a significant delay in cell cycle progression.
"We found that USP21 is generally expressed in basal-like, triple-negative breast cancer. We believe that in the future, a drug can be developed to inhibit USP21, which induces cancer cells to destroy FOXM1 and prevent cancer cells from continuing to grow and proliferate," the researchers said. "We believe that USP21 it is not only drives basal-like breast cancer in patients, but also it is a new target for therapeutic intervention."
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New target for the treatment of inflammatory bowel disease

Researchers at Washington University School of Medicine analyzed gene expression patterns in colon tissue from patients with ulcerative colitis and Crohn's disease. They found that the activity of the coagulation-related protein PAI-1 was elevated in patients with severe inflammatory bowel disease.
The researchers performed transcriptome analysis on colon biopsies. They found that more than 1,770 genes in IBD patients were dysregulated compared to controls. This group of genes focuses on genes involved in blood clotting or hemostasis. The researchers pointed out that this may also be the cause of increased risk of thrombosis in patients with IBD.
Later, they further narrowed the target range through network analysis and biological pathway analysis. They focused on the SERPINE1 gene because it is associated with inflammation and intestinal epithelium. This gene encodes the PAI-1 protein, a key protein responsible for blood clotting.
The researchers found that the expression of SERPINE1 was increased in the IBD colon tissue collected at the inflamed site compared to the site of remission or unaffected sites. They further identified a group of 380 genes whose expression is related to SERPINE1. In a mouse model of colitis, they found that the expression of PAI-1 exacerbated the symptoms of the disease.
For patients with severe disease and those who are resistant to anti-TNF therapy, researchers have found that elevated levels of PAI-1 are more common.
Through more mouse studies, they found that PAI-1 promotes inflammation through interaction with tissue plasminogen activator (tPA) protein, which typically prevents colitis and mucosal damage. PAI-1 aggravates mucosal damage by blocking tPA-mediated cleavage and activation of anti-inflammatory TGF-β.
The researchers reported that inhibition of PAI-1 reduces mucosal damage and inflammation. In mice they used small molecule MDI-2268 to block PAI-1, a reduction in mucosal damage and infl......

Molecular chaperone and p53 can stimulate the anti-tumor activity of cells

The p53 protein can determine whether a cell lives or dies. If genetic damage is detected, the protein promotes apoptosis. New research from the University of California medical school shows that this cancer defense only works in the presence of special proteins called molecular chaperones.
In many cancer treatments, not only do they attack cancer cells, they also damage normal cells. So finding a healthier way is a medical dream.P53 can be studied as a naturally harmless therapeutic direction. The presence of p53 serves as a monitoring function, and when severe genomic damage is detected, the cell initiates a process of apoptosis, which prevents tumor cell growth.
But how does this regulatory mechanism work？To answer this question, the scientists tagged p53 with a fluorescent dye to monitor the structure of individual p53 molecules. In an isolated state, p53 presents a folding pattern and is fully unfolded under the influence of Hsp70, consuming energy in this process. When Hsp90 is added, the expanded p53 returns to its folded form again.
"Molecular chaperones play a significant role in the morphology and function of p53," the researchers lamented. "Cells have an extremely complex regulatory mechanism, and molecular chaperones play a guiding role in the correct alignment of tumor suppressor proteins."
Molecular chaperones on the one hand keep p53 unfolded and bioactive. But if the cell is stressed, the chaperone causes p53 to fold, bind to the DNA, and even cause the cell itself to die.
The researchers believe this pattern of molecular interactions could lead to a better understanding of how proteins work and could lead to new targets for cancer treatment.

Did tumor regression represent cure?

If your doctor tells a cancer patient that your cancer is "in remission. "Does this mean you're cured？For cancer patients, the word "cured" can only be used as an afterthought. Often, cancer that has been in remission for many years is considered cured if there is no recurrence. However, if the same conditions are present that caused the first cancer, the cancer will return. It can only be cured if it kills all the cancer cells. But because of technical limitations, it is impossible to detect small Numbers of cancer cells, so it is hard to tell whether cancer will still be detected. A medical CT scan can detect small cancers within a few millimeters, but a cancer of one millimeter, which doesn't show up on the scan, is a cancer tissue that contains about 100,000 cancer cells. So even if the cancer no longer causes symptoms, there may still be cancer cells left. They can continue to divide and eventually relapse again.
In cases where it is not clear whether remission means that cancer is cured, the possibility of cure should be considered in the treatment of cancer. If a cancer is being treated, measures should be taken to minimize residual cancer. For example, in breast cancer, there is no visible disease after surgery, but some cells still exist near the site of surgery, so additional treatment should be given. Radiation therapy is usually given after surgery to remove the tumor. The aim is to kill the remaining cells in the breast.
Five-year survival rates are common when reporting cancer results. Five-year survival is the percentage of patients who survive five years after diagnosis. But with many cancers in remission, surviving five years means they may be cured. But different types of cancer are different. A person diagnosed with an invasive hemangioma is more likely to be cured if the cancer does not return within two years. In breast cancer, the opposite is true. The chance of recurrence after complete remission was the greatest in the first two ......