April 2020

Bio-Synthesis Newsletter - April 2020

Is 8-oxo-7,8-dihydroguanosine a biomarker for aging?

8-oxo-7,8-dihydroguanosineIncreasing levels of oxidized nucleosides in human cerebrospinal fluids have been reported in Alzheimer patients. New research now suggests that the oxidation product 8-oxo-7,8-dihydroguanosine (8oxoG) is a biomarker of aging and possibly lung cancer.  8-oxo-7,8-dihydroguanine is one of the most studied oxidative DNA products generated in cells by reactive oxygen species (ROS). If oxidized guanine in DNA is left unpaired, a D-to-T mutation can occur. A similar mismatch of 8oxoG in RNA to adenine (A) leads to transcriptional errors and the production of abnormal proteins. However, in human cells, oxidized DNA can be repaired by repair enzymes. Therefore synthetic oligonucleotides modified with 8oxoG are useful for the study of DNA repair pathways and mechanisms. 8oxoG, if present in urine, can be detected using modern UPLC instruments, often coupled to DAD or mass detectors.

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FISH and RT-PCR allows detection of RET

gene rearrangmentsRET (rearranged during transfection) variants are mostly observed in tumors of neural crest origin. The RET proto-oncogene codes for a receptor tyrosine kinase, a member of the glial cell line-derived neurotrophic factor (GDNF) family of extracellular signaling molecules. RET mutations are associated with the development of diseases including cancer. Kim et al. in 2020 reported that FISH, as well as RT-PCR, can be clinically used for the analysis of RET variants. EGFR mutations and a KIF5B-RET fusion gene have been detected in lung cancer and the expression of RET-associated signaling molecules varied in RET variant-positive groups. These findings suggest that RET and ERK inhibitors may be combined to treat lung adenocarcinoma with RET variants.

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Xanthohumol may prevent cancer

Xanthohumol may prevent cancerXanthohumol is a natural product found in hops. Gerhauser et al. in 2002 reported that Xanthohumol has anticarcinogenic properties. Xanthohumol is a scavenger for reactive oxidative species (ROS), including hydroxyl- and peroxyl radicals, and also inhibits superoxide anion radical and nitric oxide production. At nanomolar concentration, xanthohumol prevents carcinogen-induced preneoplastic lesions in mouse mammary gland organ cultures. Because of the health-promoting properties of xanthohumol, a beer enriched in this substance would be a very beneficial beverage.

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Aspirin may not inhibit amyloid formation in type 2 diabetes

AspirinThe treatment of type 2 diabetes with aspirin is controversial. However, scientists have now recognized that in type 2 diabetes β-cell death and β-cell dysfunction play important roles in the disease. Beta-cells (β-cells) are found in the pancreas where they store and release insulin. The peptide hormone insulin regulates the metabolism of carbohydrates, fats, and proteins via the absorption of glucose from the blood into cells. Among other factors, the deposition of amyloid in the islets of Langerhans leads to islet graft failure. A new study now showed that aspirin did not disaggregate preformed amylin amyloid fibrils under the conditions of these studies, at 25 °C and pH 7.4. Also, ketoprofen was similarly ineffective at inhibiting amylin amyloid formation. 

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