Noninvasive, Blood-Based Biomarkers as Screening Tools for Hepatic Fibrosis in People With Type 2 Diabetes.

Nonalcoholic fatty liver disease (NAFLD) is dramatically increasing in parallel with the pandemic of type 2 diabetes. Here, the authors aimed to assess the performance of the most commonly used noninvasive, blood-based biomarkers for liver fibrosis (FibroTest, NAFLD fibrosis score, BARD score, and FIB-4 Index) in subjects with type 2 diabetes. Liver stiffness measurement was estimated by two-dimensional shear wave elastography. Finally, the authors assessed the diagnostic role of ActiTest and NashTest 2 in liver fibrosis in the examined population.

PNPLA3 rs 738409 and Other Nongenetic Factors Associated with Hepatic Steatosis Estimated by Magnetic Resonance Imaging Proton Density Fat Fraction in Adult Greek Subjects with Type 2 Diabetes Mellitus.

Objectives: Nonalcoholic fatty liver disease is dramatically increasing in parallel with the pandemic of type 2 diabetes mellitus. We investigated factors associated with hepatic steatosis (HS) in adult Greek individuals with established type 2 diabetes mellitus. Materials and Methods: We investigated 120 consecutive people with type 2 diabetes attending the Diabetic Outpatient Clinic at an Academic Hospital in Athens, Greece. All of them had demographic, clinical, and biochemical data recorded. HS was estimated by magnetic resonance imaging determined by proton density fat fraction software and defined as the percentage of total liver fat divided by the liver volume. HS of >5% was considered abnormal. The PNPLA3 (I148M) variant was evaluated as a genetic factor by standard molecular techniques. FibroMax™ was also calculated. Results: Of the 120 participants, median age was 61.7, 46% were females, diabetes duration was 10 years, and HbA1c (glycated hemoglobin) was 6.7%. The median value of HS was 7.8. The PNPLA3 rs738409 CC/CG/GG genotype frequencies were 54.2%, 35%, and 10.8%, respectively. In multivariate analysis, PNPLA3 rs738409 (ß = 0.425, P = 0.001), waist circumference (ß = 2.448, P = 0.001), and female sex (ß = 0.419, P = 0.002) had a direct association with HS, while duration of diabetes (ß = -0.179, P = 0.011) had an inverse association with HS. Conclusions: HS in type 2 diabetes is the sum of interplay of various factors exerting a direct or an inverse association, the most prominent among them being abdominal obesity and PNPLA3 molecular variability.

Clock genes: their role in colorectal cancer.

Clock genes create a complicated molecular time-keeping system consisting of multiple positive and negative feedback loops at transcriptional and translational levels. This circadian system coordinates and regulates multiple cellular procedures implicated in cancer development such as metabolism, cell cycle and DNA damage response. Recent data support that molecules such as CLOCK1, BMAL1 and PER and CRY proteins have various effects on c-Myc/p21 and Wnt/ß-catenin pathways and influence multiple steps of DNA damage response playing a critical role in the preservation of genomic integrity in normal and cancer cells. Notably, all these events have already been related to the development and progression of colorectal cancer (CRC). Recent data highlight critical correlations between clock genes' expression and pathogenesis, progression, aggressiveness and prognosis of CRC. Increased expression of positive regulators of this circadian system such as BMAL1 has been related to decrease overall survival while decreased expression of negative regulators such as PER2 and PER3 is connected with poorer differentiation, increased aggressiveness and worse prognosis. The implications of these molecules in DNA repair systems explain their involvement in the development of CRC but at the same time provide us with novel targets for modern therapeutic approaches for patients with advanced CRC.

Expression of clock genes in patients with colorectal cancer.

Recent studies have demonstrated the influence of clock genes in cell cycle regulation, cell proliferation, apoptosis and DNA damage recognition and repair. There is evidence suggesting the implication of clock genes in colorectal cancer (CRC) development and progression. The aim of this study is to evaluate the expression levels of clock genes in CRC and correlate them with patients' prognosis. Forty-two CRC samples (from 24 males and 18 females), their paired noncancerous tissues and 8 biopsies from healthy individuals were included. Quantitative real-time PCR was used to examine the expression levels of CLOCK1, BMAL1, PER1, PER2 and PER3 genes in all the samples. In the cancerous tissues CLOCK1 (p<0.0001) and BMAL1 (p<0.0001) expression levels were higher, while PER1 (p<0.0024) and PER3 (p<0.0001) expression levels were lower compared to matched healthy tissues. No difference was observed in the expression levels of PER2 (p=0.99). No correlation was found between clock gene expression and patients' clinicopathological characteristics or prognosis. The results suggest abnormal expression of CLOCK1, BMAL1, PER1 and PER3 genes in CRC but no correlation with patients' prognosis.