RESUMEN
Tumor acidosis is associated with increased invasiveness and drug resistance. Here, we take an unbiased approach to identify vulnerabilities of acid-exposed cancer cells by combining pH-dependent flow cytometry cell sorting from 3D colorectal tumor spheroids and transcriptomic profiling. Besides metabolic rewiring, we identify an increase in tetraploid cell frequency and DNA damage response as consistent hallmarks of acid-exposed cancer cells, supported by the activation of ATM and ATR signaling pathways. We find that regardless of the cell replication error status, both ATM and ATR inhibitors exert preferential growth inhibitory effects on acid-exposed cancer cells. The efficacy of a combination of these drugs with 5-FU is further documented in 3D spheroids as well as in patient-derived colorectal tumor organoids. These data position tumor acidosis as a revelator of the therapeutic potential of DNA repair blockers and as an attractive clinical biomarker to predict the response to a combination with chemotherapy.
Asunto(s)
Neoplasias Colorrectales , Tetraploidía , Humanos , Proteínas de la Ataxia Telangiectasia Mutada/genética , Transducción de Señal , Daño del ADN , Reparación del ADN , Inhibidores de Proteínas Quinasas/farmacologíaRESUMEN
The objective of this study was to determine the effects of some minor components such as squalene and mono- and diglycerides (MDG) on the frying stability of olive pomace oil. Refined olive pomace oil was distilled using a falling film type short-path distillation unit at 230 °C under a pressure of 0.02 mbar to remove minor components. Distilled olive pomace oil was introduced with approximately 10,000 mg/kg of squalene and 2.5% of MDG. Fryings were performed 8 times/day at 180 °C for 3 min. Whole frying procedure proceeded for 5 days. Total polar compounds, polymerized triglycerides (PTG), free fatty acids, viscosity, color index, p-anisidine value, smoke point, fatty acid composition and iodine values of the oils were monitored. Results indicated that all criteria except smoke point and iodine value increased in all fractions during fryings. The lowest total polar compound was obtained in distilled olive pomace oil while PTG was the lowest in the MDG added fraction. Lower increases in viscosity and color indexes were recorded in squalene incorporated samples. It was observed that squalene and MDG were not effective on the oxidation rate of unsaturated fatty acids during frying.
RESUMEN
In this study, pigmented pectin (grape pectin, GP) was extracted from the peels of black Isabel grapes. This highly methoxylated GP was composed mainly of galacturonic acid, arabinose, and other neutral monosaccharides. Its red color was ascribed to the anthocyanin content, and the main contribution was from malvidin-3-O-glucoside. To improve the yield and color properties of spray-dried Isabel grape juice powders, maltodextrin (MD) was substituted with this colored GP. When 25% of MD was substituted with GP, the powder yield increased from 46.0% to 60.4%, but it decreased to 21% when the substitution was 40%. GP inclusion increased the encapsulation efficiency of total anthocyanin in powders from 55.70% to 88.66%. When this spray-dried grape juice powder containing GP was utilized in a jelly recipe (4%-10%), a higher level of inclusion yielded stronger and more brittle jellies. When the jellies containing varying amounts of GP were subjected to in vitro digestion, the formulation with a higher amount of GP yielded a higher recovery of anthocyanins. In addition to being utilized as a carrier agent for spray-drying applications, this pigmented GP can also be tailored for a variety of applications, such as the development of pH-sensitive edible films and functional beverage formulations.
Asunto(s)
Vitis , Antocianinas/análisis , Pectinas , Polvos , Jugos de Frutas y VegetalesRESUMEN
Ethanol has been widely used for the extraction of propolis. Due to its certain disadvantages, there has been an ongoing search to find alternative non-ethanolic extraction solvents. This study aimed to compare the phenolics, antioxidant, and antibacterial activity of propolis extracts prepared with 70% ethanol (EWE), propylene glycol (PGE), and L-arginine solution (BE). All extracts were subjected to an in vitro simulated digestion procedure, and the phenolic profile of non-digested and digested samples was determined by using LC-MS/MS. Additionally, the change in total phenolic (TPC), total flavonoid content (TFC), and antioxidant capacities were determined at each digestion phase. TPC and TFC of non-digested propolis extracts had similar values, although BE showed higher antioxidant capacity (p < .05). The amount of TPC reached or transformed at the intestinal stage was higher for BE and PG compared to EWE. BE also provided the highest antioxidant capacity assay in digested samples. The most common phenolics were pinocembrin, pinobanskin, galangin, and CAPE in non-digested extracts. However, their concentration was drastically reduced by digestion, and their recovery (R%) ranged from 0% to 9.38% of the initial amount detected in the non-digested extracts. Chrysin was the most bioaccessible flavonoid in all extracts. Among phenolic acids, the highest R% was determined for trans-cinnamic acid (22.14%) from BE. All extracts showed in vitro inhibitory activity against Escherichia coli and Staphylococcus aureus. This study suggests that an L-arginine solution could be used as an alternative solvent to ethanol and propylene glycol for propolis extraction.
RESUMEN
Although the Med-Diet is a healthy diet model, it is affected by current dietary habits. Therefore, new foods with improved nutritional value should be developed to respond to the needs of people following the Med-Diet. This study was focused on developing high-ß-glucan flat bread (bazlama) with a relatively lower GI. A bread wheat (cv. Tosunbey) flour was enriched with the flour of a high-ß-glucan-content hull-less barley (cv. Chifaa) flour (15, 30, 45 and 60%) to develop a functional bazlama. The nutritional and technological properties of bazlama samples enriched with barley flour were compared with the ones produced from bread wheat. All of the barley flour-enriched bazlama samples had higher yellowness values (b*) than the control (both crumb and crust), which is generally preferred by the consumers. Texture results indicated that bazlama samples became harder with the increase in barley flour supplementation level. The results showed that 3 g of ß-glucan can be provided from the barley flour-enriched bazlama samples (at 45 and 60% levels), and this is the limit to carry health claims. The bazlama samples enriched with barley flour were richer in Mg, K, Mn, Fe, and Zn minerals than the control (100% Tosunbey flour). While the glycemic index (GI) of commercial bread wheat and Tosunbey bazlama samples were high (88.60% and 79.20%, respectively), GI values of the bazlama samples enriched with 60% (64.73) and 45% barley flour (68.65) were medium. The lower GI values of barley flour-enriched bazlama samples are probably due to the higher ß-glucan contents of the bazlama samples. Additionally, as the barley flour supplementation level of the bazlama samples increased, the phenolics and antioxidant capacities of free and bound extracts increased compared to bread wheat bazlama. The results indicated that hull-less barley (cv. Chifaa) with high ß-glucan content may be utilized at relatively higher levels (45 and 60%) to produce bazlama with improved nutritional properties.