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Mutations and ectopic FAT1 cadherin expression are implicated in a broad spectrum of diseases ranging from developmental disorders to cancer. The regulation of FAT1 and its downstream signalling pathways remain incompletely understood. We hypothesized that identification of additional proteins interacting with the FAT1 cytoplasmic tail would further delineate its regulation and function. A yeast two-hybrid library screen carried out against the juxtamembrane region of the cytoplasmic tail of FAT1 identified the E3 ubiquitin-protein ligase SH3RF1 as the most frequently recovered protein-binding partner. Ablating SH3RF1 using siRNA increased cellular FAT1 protein levels and stabilized expression at the cell surface, while overexpression of SH3RF1 reduced FAT1 levels. We conclude that SH3RF1 acts as a negative post-translational regulator of FAT1 levels.

Olea europaea L. leaves are an agricultural waste product with a high concentration of phenolic compounds, especially oleuropein. Oleuropein has been shown to exhibit anti-proliferative activity against a number of cancer types. However, they have not been tested against pancreatic cancer, the fifth leading cause of cancer related death in Western countries. Therefore, water, 50% ethanol and 50% methanol extracts of Corregiola and Frantoio variety Olea europaea L. leaves were investigated for their total phenolic compounds, total flavonoids and oleuropein content, antioxidant capacity and anti-proliferative activity against MiaPaCa-2 pancreatic cancer cells. The extracts only had slight differences in their phytochemical properties, and at 100 and 200 μg/mL, all decreased the viability of the pancreatic cancer cells relative to controls. At 50 μg/mL, the water extract from the Corregiola leaves exhibited the highest anti-proliferative activity with the effect possibly due to early eluting HPLC peaks. For this reason, olive leaf extracts warrant further investigation into their potential anti-pancreatic cancer benefits.

Euphol identified in Euphorbia tirucalli (E. tirucalli) has been linked with various health benefits. This study aimed to optimize ultrasonic extraction conditions for euphol from E. tirucalli leaf. Different solvents were tested to determine the most effective solvent for extraction of euphol. Then, response surface methodology (RSM) was employed to optimize ultrasound-assisted extraction conditions including temperature, time and power for maximal extraction of euphol. Our results showed that ethyl acetate:ethanol (4:1, v/v) was the most effective solvent for the extraction of euphol. Ultrasonic temperature and time had a positive impact, whereas, ultrasonic power had a negative effect on the extraction efficiency of euphol. The optimum ultrasonic extraction conditions for euphol were identified as: solvent-to-fresh sample ratio of 100:32 mL/g; ultrasonic temperature of 60 °C; ultrasonic time of 75 min and ultrasonic power of 60% (150 W). Under these optimum conditions, approximately 4.06 mg of euphol could be obtained from one gram of fresh E. tirucalli leaf. This extract also contained phenolic compounds (2.5 mg GAE/g FW) and possessed potent antioxidant capacity. These optimal conditions are applicable for a larger scale to extract and isolate euphol for potential utilization in the pharmaceutical industry.

BackgroundZinc deficiency is one of the most preva- lent micronutrient deficiencies in developing countries, including Iran. The main direct causes of zinc deficiency are insufficient zinc intake, absorption or metabolic disorder, and increase in need during acute growth periods.ObjectiveTo determine the prevalence of zinc defi- ciency in preschool boys and girls in urban and rural populations in order to assist policy makers. Children of preschool age (i. e., 6 years old in Iran) were studied because interventions in this age group are believed to result in greater improvement in learning skills once these children enter school.MethodsA national cross-sectional study was carried out on 4,374 randomly selected healthy preschool children from Iranian families in 2001. Serum zinc concentration was measured by atomic absorption spectrometry. The cutoff point for zinc deficiency was set at a serum level of 10 μmol/L (65 μg/dL).ResultsThe prevalence of zinc deficiency was esti- mated at approximately 19.3%. The highest preva- lence was seen in the region that includes Sistan and Baluchistan, South Khorasan, and the southeast area of Kerman and the lowest in the region of Boushehr, Hor- mozgan, and South Khoozestan. The prevalence of zinc deficiency was significantly higher in rural areas than in urban areas. No significant difference in prevalence was seen between boys and girls.ConclusionsIn the long run, nutritional security and increased access to and intake of foods with high levels of zinc are the most sustainable strategies to overcome zinc deficiency. Fortification of staple foods, improved qual- ity of traditional bread, and supplementation for at-risk population groups are considered short- and mid-term nterventions. Nutrition education and behavioral change may be long-term strategies.

Scaevola spinescens (Goodeniaceae) has been traditionally used by indigenous Australians to treat various ailments including cancer, thus it is necessary to identify optimum extraction conditions for bioactive components from this plant. This study investigated the effects of different extraction conditions on Total Phenolic Content (TPC), antioxidant capacity (ABTS, DPPH, CUPRAC, FRAP assays) and anti-cancer activity (MTT assay) of S. spinescens. The results showed that optimal extraction conditions for TPC using water were 80°C, 15 min and ratio of 20:1 mL/g. However, the aqueous extract prepared under optimal conditions had lower TPC and less antioxidant capacity than those of the organic solvent extracts. The acetone extract displayed the greatest TPC as well as the highest antioxidant capacity and anti-cancer activity against a panel of cancer cell lines, including cancers of the pancreas, breast, lung, brain, skin, colon and ovary. Therefore, further investigations should be conducted to identify key bioactive compounds as potential anti-cancer agents.

Euphorbia tirucalli (E. tirucalli) is now widely distributed around the world and is well known as a source of traditional medicine in many countries. This study aimed to utilise response surface methodology (RSM) to optimise ultrasonic-assisted extraction (UAE) conditions for total phenolic compounds (TPC) and antioxidant capacity from E. tirucalli leaf. The results showed that ultrasonic temperature, time and power effected TPC and antioxidant capacity; however, the effects varied. Ultrasonic power had the strongest influence on TPC; whereas ultrasonic temperature had the greatest impact on antioxidant capacity. Ultrasonic time had the least impact on both TPC and antioxidant capacity. The optimum UAE conditions were determined to be 50 °C, 90 min. and 200 W. Under these conditions, the E. tirucalli leaf extract yielded 2.93 mg GAE/g FW of TPC and exhibited potent antioxidant capacity. These conditions can be utilised for further isolation and purification of phenolic compounds from E. tirucalli leaf.

The interaction between the Drosophila cadherins fat and dachsous is regulated by phosphorylation of their respective ectodomains, a process catalysed by the atypical kinase four-jointed. Given that many signalling functions are conserved between Drosophila and vertebrate Fat cadherins, we sought to determine whether ectodomain phosphorylation is conserved in FAT1 cadherin, and also whether FJX1, the vertebrate orthologue of four-jointed, was involved in such phosphorylation events. Potential Fj consensus phosphorylation motifs were identified in FAT1 and biochemical experiments revealed the presence of phosphoserine and phosphothreonine residues in its extracellular domain. However, silencing FJX1 did not influence the levels of FAT1 ectodomain phosphorylation, indicating that other mechanisms are likely responsible.