Novel mutations of the PAX6, FOXC1, and PITX2 genes cause abnormal development of the iris in Vietnamese individuals.

Purpose: Congenital iris abnormality is a feature of several genetic conditions, such as aniridia syndrome and anterior segment degeneration (ASD) disorders. Aniridia syndrome is caused by mutations in the PAX6 gene or its regulatory elements in the locus 11p13 or deletions of contiguous genes, while ASDs are the result of mutations in various genes, such as PAX6, FOXC1, PITX2, and CYP1B1. This study aims to identify pathogenic mutations in Vietnamese individuals with congenital anomalies of the iris. Methods: Genomic DNA was extracted from peripheral blood of 24 patients belonging to 15 unrelated families and their available family members. Multiplex ligation-dependent probe amplification (MLPA) was used to detect the deletions or duplications in the 11p13-14 region, including the PAX6 gene and its neighboring genes. Direct PCR sequencing was used to screen mutations in 13 exons and flanking sequences of the PAX6 gene. The patients without mutation in the PAX6 locus were further analyzed with whole exome sequencing (WES). Identified mutations were tested with segregation analysis in proband family members. Results: We identified a total of 8 novel and 4 recurrent mutations in 20 of 24 affected individuals from 12 families. Among these mutations, one large deletion of the whole PAX6 gene and another deletion of the PAX6 downstream region containing the DCDC1 and ELP4 genes were identified. Eight mutations were detected in PAX6, including four nonsense, three frameshift, and one splice site. In addition, two point mutations were identified in the FOXC1 and PITX2 genes in patients without mutation in PAX6. Some of the mutations segregated in an autosomal dominant pattern where family members were available. Conclusions: This study provides new data on causative mutations in individuals with abnormal development of iris tissue in Vietnam. These results contribute to clinical management and genetic counseling for affected people and their families.

The Association Between Femoral Artery Intima-Media Thickness and Serum Glucagon-Like Peptide-1 Levels Among Newly Diagnosed Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: Endothelium dysfunction and decrease of incretin effects occur early in type 2 diabetes mellitus and these changes contribute to diabetic cardiovascular complications such as atherosclerosis, thick intima-media, coronary, and peripheral arterial diseases. In patients with diabetes, the femoral artery is a site of a high incidence of injury in peripheral vascular diseases, and atherosclerotic changes may appear earlier in the femoral artery compared to the carotid artery. This study was conducted to determine the prevalence of increased femoral artery intima-media thickness (IMT) and atherosclerotic plaque and their correlation with serum glucagon-like peptide-1 (GLP-1) levels in newly-diagnosed patients with type 2 diabetes mellitus. MATERIALS AND METHODS: A cross-sectional study was conducted on 332 patients with nT2D in the National Endocrinology Hospital, Vietnam from January 2015 to May 2018. IMT was measured by Doppler ultrasound and GLP-1 by enzyme-linked immunosorbent assay (ELISA). All data were analyzed with SPSS version 26 for Windows (SPSS Inc, Chicago, IL). RESULTS: Prevalence of thick femoral artery IMT and atherosclerotic plaque was 38.2 and 22.3%, respectively. There was a relationship between IMT and age, waist to hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting GLP-1, high sensitive CRP (hsCRP) and 24-hour microalbuminuria secretion (24-h MAUS). The fasting serum GLP-1 (fGLP-1) levels were reduced significantly in patients with thickness and atherosclerosis femoral artery (p = 0.001). After adjusting with other related factors, namely, DBP and estimated glomerular filtration rate (eGFR), whilst hsCRP and 24-h MAUS showed a significantly positive correlation to IMT (Standardized B and p of 0.242, 0.004 and 0.178, 0.043, respectively), fGLP-1 showed a significantly negative correlation to IMT (Standardized B = -0.288, p = 0.001). CONCLUSION: Among n2TD, the percentage for femoral artery thick IMT and atherosclerosis was 38.2% and 22.3% respectively, and serum GLP-1 was negatively correlated with thick IMT and atherosclerosis.

Geranyl dihydrochalcones from Artocarpus altilis and their antiausteric activity.

Human pancreatic cancer cell lines have remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. The search for agents that preferentially inhibit the survival of cancer cells under low nutrient conditions is a novel antiausterity strategy in anticancer drug discovery. In this study, the methanolic extract of the leaves of Artocarpus altilis showed 100 % preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions at a concentration of 50 µg/mL. Further investigation of this extract led to the isolation of eight new geranylated dihydrochalcones named sakenins A-H (1-8) together with four known compounds (9-12). Among them, sakenins F (6) and H (8) were identified as potent preferentially cytotoxic candidates with PC50 values of 8.0 µM and 11.1 µM, respectively.