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2. Aberrantly expressed hsa_circ_0060762 and CSE1L as potential peripheral blood biomarkers for ALSMetka Ravnik-Glavač, Massimo Mezzavilla, Ana Dolinar, Blaž Koritnik, Damjan Glavač, 2023, izvirni znanstveni članek Povzetek: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive adult-onset neurodegenerative disease that is often diagnosed with a delay due to initial non-specific symptoms. Therefore, reliable and easy-to-obtain biomarkers are an absolute necessity for earlier and more accurate diagnostics. Circular RNAs (circRNAs) have already been proposed as potential biomarkers for several neurodegenerative diseases. In this study, we further investigated the usefulness of circRNAs as potential biomarkers for ALS. We first performed a microarray analysis of circRNAs on peripheral blood mononuclear cells of a subset of ALS patients and controls. Among the differently expressed circRNA by microarray analysis, we selected only the ones with a host gene that harbors the highest level of conservation and genetic constraints. This selection was based on the hypothesis that genes under selective pressure and genetic constraints could have a major role in determining a trait or disease. Then we performed a linear regression between ALS cases and controls using each circRNA as a predictor variable. With a False Discovery Rate (FDR) threshold of 0.1, only six circRNAs passed the filtering and only one of them remained statistically significant after Bonferroni correction: hsa_circ_0060762 and its host gene CSE1L. Finally, we observed a significant difference in expression levels between larger sets of patients and healthy controls for both hsa_circ_0060762 and CSE1L. CSE1L is a member of the importin β family and mediates inhibition of TDP-43 aggregation; the central pathogenicity in ALS and hsa_circ_0060762 has binding sites for several miRNAs that have been already proposed as biomarkers for ALS. In addition, receiver operating characteristics curve analysis showed diagnostic potential for CSE1L and hsa_circ_0060762. Hsa_circ_0060762 and CSE1L thus represent novel potential peripheral blood biomarkers and therapeutic targets for ALS.
Ključne besede: amyotrophic lateral sclerosis, ALS, circRNA, biomarker, peripheral blood biomarker, hsa_circ_0060762, CSE1L, biomedicine
Objavljeno v DiRROS: 12.07.2024; Ogledov: 267; Prenosov: 218
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3. Genetic polymorphisms of xenobiotic metabolizing enzymes in human colorectal cancerVita Dolžan, Metka Ravnik-Glavač, Katja Breskvar, 1998, objavljeni znanstveni prispevek na konferenci Povzetek: It was proposed that both hereaditary and environmental factors contribute to the development of colorectal cancer (CRC). Carcinogenic polycyclic aromatic hydrocarbons (PAHs) from food or tobacco smoke can form DNA adducts and thus initiate carcinogenesis after metabolic activation via cytochrome P4501A1 (CYP1A1). Intermediate metabolites are detoxified by conjugation with glutathione S-transferases. Our aim was to look for inherited metabolic suceptibility to CRC. We used PCR-based genotyping approach to determine the frequencies of polymorphic alleles of two cytochromes P450 (CYP2D6 and CYP1A1)and two glutathione S-transferases (GSTM1 and GSTT1) in DNA samples from 31 sporadic, 25 familial CRC cases and 73 healthy controls. The difference in frequencies of poor metabolisers due to CYP2D6 gene polymorphismwas close to the limit of statistical significance between sporadiCRC and healthy control group (lambda 2=5.52, m=2, p=0.06) despite the small sample size. The frequencies of either CYP1A1 MspI, GST M1 or GST T1 genotypes were not significantly different in both CRC cases and in controls. Although our study suggests some difference in metabolic susceptibility between sporadic and familial CRC, further studies are needed to investigate the combined effect of polymorphic genes involved in carcinogen metabolism in a larger group of patients with defined exposure to dietary carcinogens and smoking.
Objavljeno v DiRROS: 19.01.2024; Ogledov: 569; Prenosov: 148
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