RESUMO
BACKGROUND: Lymphatic valves are specialized structures in collecting lymphatic vessels and are crucial for preventing retrograde lymph flow. Mutations in valve-forming genes have been clinically implicated in the pathology of congenital lymphedema. Lymphatic valves form when oscillatory shear stress from lymph flow signals through the PI3K/AKT pathway to promote the transcription of valve-forming genes that trigger the growth and maintenance of lymphatic valves. Conventionally, in many cell types, AKT is phosphorylated at Ser473 by the mTORC2 (mammalian target of rapamycin complex 2). However, mTORC2 has not yet been implicated in lymphatic valve formation. METHODS: In vivo and in vitro techniques were used to investigate the role of Rictor, a critical component of mTORC2, in lymphatic endothelium. RESULTS: Here, we showed that embryonic and postnatal lymphatic deletion of Rictor, a critical component of mTORC2, led to a significant decrease in lymphatic valves and prevented the maturation of collecting lymphatic vessels. RICTOR knockdown in human dermal lymphatic endothelial cells not only reduced the level of activated AKT and the expression of valve-forming genes under no-flow conditions but also abolished the upregulation of AKT activity and valve-forming genes in response to oscillatory shear stress. We further showed that the AKT target, FOXO1 (forkhead box protein O1), a repressor of lymphatic valve formation, had increased nuclear activity in Rictor knockout mesenteric lymphatic endothelial cells in vivo. Deletion of Foxo1 in Rictor knockout mice restored the number of valves to control levels in lymphatic vessels of the ear and mesentery. CONCLUSIONS: Our work identifies a novel role for RICTOR in the mechanotransduction signaling pathway, wherein it activates AKT and prevents the nuclear accumulation of the valve repressor, FOXO1, which ultimately enables the formation and maintenance of lymphatic valves.
RESUMO
The consumption of fruit and vegetable juices is widely recognized as a healthy choice across all age groups. Orange, carrot, and aloe vera are renowned for their functional properties and health benefits. In this study, we investigated the potential incorporation of aloe vera gel into blended orange and carrot juices. We also evaluated the resulting mixed probiotic juices (chemical, microbiological, and sensory aspects) during a 14-day storage period at refrigerator temperature. The chemical composition and phytochemical structure of aloe vera gel were examined, followed by an assessment of the biological effects of these healthy juices on diabetic albino rats. The results indicated improvements in total soluble solids, reducing sugars, and total sugars with increasing storage duration. Furthermore, the study demonstrated that incorporating aloe vera into the natural mixed juices enhanced their phytochemical quality. The treatment supplemented with aloe vera gel gave the highest total content of phenolic and flavonoid substances, which were 310 mg of GAE/100 g and 175 mg of quercetin/100 g, respectively. Probiotic strains (Bifidobacterium animalis subsp lactis Bb12, Lactiplantibacillus plantarum 299V, and Lactobacillus acidophilus L10) exhibited good viable cell counts in orange and mixed orange and carrot probiotics juices with viable counts of 7.42-8.07 log CFU/mL. Regarding sensory attributes, the study found that increasing the ratio of orange juice improved the taste while increasing the ratio of carrot juice enhanced the color in juice mixtures. Incorporation of aloe vera into mixed natural juices also enhanced the reduction of blood glucose, triglyceride, cholesterol, LDL, creatinine, ALT, AST, and urea levels while increasing total protein and HDL levels in diabetic rats. Based on these findings, oranges, carrots, and aloe vera offer the potential to produce new, flavorful, nutritious, and appealing juices. Moreover, this study determined that a functional juice with favorable sensory properties can be created by blending 75% orange juice, 20% carrot juice, and 5% aloe vera gel. Additionally, aloe vera demonstrated greater efficacy as an antidiabetic agent in rats. Further research is suggested to explore the potential advantages of aloe vera gel and probiotic juices in mitigating diabetes and other metabolic syndromes.
