Ischemia, or a lack of blood flow to an area of the body, is a major cause of tissue damage and cell death. Many cell types die when deprived of oxygen and nutrients, but some, such as progenitor cells, can survive and even proliferate. The paper "Let-7i inhibition enhances progesterone-induced functional recovery in a mouse model of ischemia" by Dr. Meharvan Singh, and colleagues show that inhibiting the let-7i microRNA can enhance progesterone-induced recovery from ischemia in a mouse model. Progesterone is a hormone known to protect against cell death and promote cell proliferation. It does this by activating specific genes that promote cell survival and inhibiting other genes that promote cell death. Let-7i is a microRNA that is known to inhibit the expression of genes involved in cell proliferation. Inhibiting let-7i allows more progesterone-induced cell proliferation and survival, leading to enhanced tissue repair after ischemia. The authors first induced ischemia in the mouse hindlimb by ligating the femoral artery. This caused tissue damage and cell death in the limb. The mice were then treated with progesterone or a control vehicle. Mice treated with progesterone had significantly less tissue damage and cell death than mice treated with the control vehicle. The authors then looked at the expression of let-7i in the ischemic tissue. They found that progesterone treatment led to a decrease in let-7i expression. Inhibition of let-7i enhanced progesterone-induced cell proliferation and migration, leading to enhanced tissue repair. This study shows that inhibiting let-7i can enhance progesterone-induced tissue repair after ischemia. This study also indicates that Let-7i increased the levels of several essential genes involved in cell proliferation, migration, and angiogenesis in the ischemic mouse brain; they found that Let-7i enhanced the production of the neurotrophic factor BDNF in the ischemic mouse brain. This could potentially be used to improve outcomes in patients with ischemic diseases.
Another study that links the role of microRNA let-7i in post-stroke recovery is "MicroRNA Let-7i Is a Promising Serum Biomarker for Post-stroke Cognitive Impairment and Alleviated OGD-Induced Cell Damage in vitro by Regulating Bcl-2" the authors of this paper discussed the role of the microRNA let-7i in post-stroke cognitive impairment (PSCI), microRNA let-7i is a promising serum biomarker that has the potential to alleviate cell damage caused by oxygen-glucose deprivation (OGD) in vitro. This is achieved by let-7i regulating the level of the cell death protein Bcl-2. In PSCI, there is an increase in microRNA let-7i in the serum. This upregulation of let-7i is thought to contribute to the development of PSCI. In vitro, microRNA let-7i can alleviate cell damage caused by OGD. This is achieved by let-7i regulating the level of the cell death protein Bcl-2. Bcl-2 is a protein that is involved in the control of cell death. When the level of Bcl-2 is high, cell death is prevented. When the level of Bcl-2 is low, cell death is promoted. In OGD-induced cell damage, the level of Bcl-2 is low. This leads to cell death. However, when microRNA let-7i is present, the level of Bcl-2 is increased. This leads to cell survival. The reason why microRNA let-7i is a promising serum biomarker for PSCI is that it can modulate Bcl-2 levels. This leads to the prevention of cell death, which is a crucial feature of PSCI. In conclusion, microRNA let-7i is a promising serum biomarker for PSCI. It can prevent cell death, which is a vital feature of PSCI.
These two studies were both fascinating to read. The connection between the two studies is that microRNA let-7i is a promising serum biomarker for post-stroke cognitive impairment and alleviates OGD-induced cell damage in vitro by regulating Bcl-2, and let-7i inhibition enhances progesterone-induced functional recovery in a mouse model of ischemia. I hope to see future studies that expand on these results with human clinical trials to come soon.
Works cited:
Nguyen T, Su C, Singh M. Let-7i inhibition enhances progesterone-induced functional recovery in a mouse model of ischemia. Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):E9668-E9677. doi: 10.1073/pnas.1803384115. Epub 2018 Sep 20. PMID: 30237284; PMCID: PMC6187141.
Wang ZQ, Li K, Huang J, Huo TT, Lv PY. MicroRNA Let-7i Is a Promising Serum Biomarker for Post-stroke Cognitive Impairment and Alleviated OGD-Induced Cell Damage in vitro by Regulating Bcl-2. Front Neurosci. 2020 Mar 24;14:215. doi: 10.3389/fnins.2020.00215. Erratum in: Front Neurosci. 2021 Jan 29;15:648121. PMID: 32265630; PMCID: PMC7105869.
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