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Medical Bulletin 20/ August/ 2024
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Overview
Here are the top medical news for the day:
New Nanobody Treatment Reduces Lung Metastases in Breast Cancer
In a recent study published in oncotarget proposes that a nanobody that targets a specific part of the V-ATPase on the surface of cells can block the activity of this protein in 4T1-12B breast cancer cells. This nanobody not only stops these cancer cells from invading other tissues in lab tests but also prevents them from spreading to the lungs when the cells are implanted in the mammary fat pad of mice.
Researchers suggest that selective inhibition of plasma membrane V-ATPases in breast tumor cells inhibits the invasion of these cells in vitro. They have now developed a nanobody directed against an extracellular epitope of the mouse V-ATPase c subunit.
The vacuolar H+-ATPase (V-ATPase) is an ATP-driven proton pump responsible for regulating the acidity levels within intracellular compartments. It achieves this by transporting protons across the plasma membrane of different cell types, including cancer cells, which helps maintain proper pH balance and supports various cellular functions.
Breast cancer is among the most frequently diagnosed cancers, making up nearly one-third (30%) of all new cases in women in 2022. When first diagnosed with early-stage breast cancer, 20–30% of patients will eventually develop metastatic breast cancer. Additionally, 6–10% of all breast cancer cases are diagnosed at stage IV, known as de novo metastatic breast cancer. Metastasis is often linked to a worse prognosis compared to non-metastatic breast cancer, with a median survival of just 2–3 years. The most common sites where breast cancer spreads include the bone, liver, lung, and brain.
Reference: Li Z., Alshagawi M. A., Oot R. A., Alamoudi M. K., Su K., Li W., Collins M. P., Wilkens S., Forgac M. A nanobody against the V-ATPase c subunit inhibits metastasis of 4T1-12B breast tumour cells to lung in mice. Oncotarget. 2024; 15: 575-587.
How Omega-3 Fatty Acids May Help Prevent Heart Arrhythmias ?
In a recent study published in International Journal of Molecular Sciences, researchers found that Omega-3 polyunsaturated fatty acids appear to offer significant benefits for cardiovascular health. Specifically, eicosapentaenoic acid (EPA), a component of fish oil, not only helps relax blood vessels and reduce blood clotting but also plays a role in preventing atrial fibrillation and other types of arrhythmias.
Researchers investigated the role of eicosapentaenoic acid in inducing long-term electrical changes in cultured mouse cardiomyocytes using a variety of bioanalytical techniques.
This study primarily investigated how a mixture of oleic acid and palmitic acid (OAPA), two commonly studied saturated fats, affects calcium balance in cardiomyocytes by altering Ca2+ ion channels, and whether eicosapentaenoic acid (EPA) can reverse these effects and restore normal function.
The researchers first used real-time PCR to show that oleic acid and palmitic acid significantly reduced the mRNA levels of Cav1.2 L-type Ca2+ channels. Live cell imaging further revealed that oleic acid and palmitic acid decreased the spontaneous beating rate of cardiomyocytes.
However, these effects were countered when even a small amount of eicosapentaenoic acid was introduced alongside oleic acid and palmitic acid, leading to the restoration of both mRNA and protein levels of Cav1.2. Electrophysiological tests also demonstrated that eicosapentaenoic acid prevented the decrease in Cav1.2 channel current caused by oleic acid and palmitic acid.
Our study indicates that eicosapentaenoic acid has a protective effect on cardiomyocytes by correcting the disruptions caused by excessive consumption of saturated fatty acids, commonly associated with high-fat diets
Reference: Morishima M, Wang P, Horii K, Horikawa K, Ono K. Eicosapentaenoic Acid Rescues Cav1.2-L-Type Ca2+ Channel Decline Caused by Saturated Fatty Acids via Both Free Fatty Acid Receptor 4-Dependent and -Independent Pathways in Cardiomyocytes. International Journal of Molecular Sciences. 2024; 25(14):7570. https://doi.org/10.3390/ijms25147570
Role of Sex Hormones in Weight Gain and Cardiometabolic Health
A decrease in estrogen during menopause leads to alterations in body fat distribution and an increased risk of cardiovascular and metabolic diseases. However, a recent study has uncovered potential treatments that could eventually reverse these adverse changes.
Study published in Natures Communications suggest that blocking a receptor known as Cxcr4 in mice decreases the likelihood of fat stem cells becoming white fat, or white adipose tissue. This approach could be used alongside low doses of estrogen therapy to help manage changes in body fat distribution in menopausal women and reduce the risk of cardiometabolic diseases. Typically, effective estrogen therapy requires higher doses, which increases the risk of breast cancer.
Researchers have long understood that sex hormones like testosterone and estrogen influence fat development. Estrogen typically promotes the accumulation of beneficial subcutaneous fat, which offers metabolic protection. However, when estrogen levels drop, such as during menopause, women lose this protective fat and instead gain unhealthy white fat, which stores excess calories. This shift often leads to an increased risk of cardiometabolic diseases in women as they reach their 50s.
This discovery opens up exciting possibilities for exploring how healthy and unhealthy fat tissues form stem cells, potentially aiding efforts to combat obesity. It also suggests a strategy for reducing unhealthy white fat in postmenopausal women by blocking Cxcr4 and then using low-dose estrogen therapy, which could minimize the risk of breast cancer. Such an approach might also help prevent cardiovascular and metabolic diseases linked to excess white fat.
Reference: Steiner, B.M., Benvie, A.M., Lee, D. et al. Cxcr4 regulates a pool of adipocyte progenitors and contributes to adiposity in a sex-dependent manner. Nat Commun 15, 6622 (2024). https://doi.org/10.1038/s41467-024-50985-8
Speakers
Dr. Garima Soni
BDS, MDS(orthodontics)
Dr. Garima Soni holds a BDS (Bachelor of Dental Surgery) from Government Dental College, Raipur, Chhattisgarh, and an MDS (Master of Dental Surgery) specializing in Orthodontics and Dentofacial Orthopedics from Maitri College of Dentistry and Research Centre. With 2 years of dedicated clinical experience, she brings a blend of academic excellence and practical expertise to the field of dentistry, ensuring high-quality care and innovative solutions for patients.