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Purpose: The solid tumor microenvironment promotes T cell dysfunction and reduces the effectiveness of immunotherapies such as chimeric antigen receptor-based T cell cells. In preclinical models, early results have shown that T cell metabolism modulation can improve intratumoral T cell function. Experimental design: We investigated GPC3 expression in human normal and tumor tissue specimens. Both in vitro and in vivo, we developed and evaluated BOXR1030, a novel CAR T therapeutic co-expression that targets CAR T cell function and exogenous glutamic-oxaloacetic transaminase 2 with CAR T cell function both in vitro and in vivo. Result: Cellular deposition of tumor antigen GPC3 was detected by immunohistochemical staining in tumor biopsies from hepatocellular carcinoma, liposarcoma, squamous lung cancer, and Merkel cell carcinoma patients. Conclusions: These results show that co-expression of GOT2 can greatly raise the overall antitumor activity of CAR T cells by inducing broad changes in cellular structure and phenotype.
Source link: https://doi.org/10.1371/journal.pone.0266980
Positive correlations have been found between circulating Serum amyloid A levels and obesity in several studies in the past. SAA1. 1, SAA2. 1, and SAA3 are among the three inducible forms of SAA: SAA1. 1, SAA2. 1, and SAA3. We have investigated the role of SAA in the formation of obesity and its associated metabolic disorders in vivo using mice lacking for all three inducible forms of SAA: SAA1. 1, SAA2. 1, and SAA3. Male and female mice were made obese by a high fat, high sucrose diet with added cholesterol, and control mice were fed rodent chow diets.
Source link: https://doi.org/10.1371/journal.pone.0266688
Using a lipidomic analysis technique, we aimed to investigate the effects of elevated-altitude persistent hypoxia on lipid metabolism in rats' adipose tissue as hypoxia affects lipid metabolism. Visceral adipose tissues from rats housed in a high-altitude hypoxia environment with 14. 7 percent oxygen and 20. 9 percent oxygen were determined in a low-altitude normoxia environment housing 41 m with 20. 9 percent oxygen and a low-altitude normoxia atmosphere of 42 m with 20. 9 percent oxygen for eight weeks, using ultra-performance liquid chromatography-Orbitrap mass spectrometry system. The hypoxia group's body weight and visceral adipose tissue mass dropped by 8 weeks after eight weeks, compared to those of the normoxia group. Cells in the hypoxia group's visceral adipose cells were significantly smaller than those of visceral adipose cells in the normoxia group. In the hypoxia group, concentrations of diacylglycerols and triacylglycerols were significantly lower than those in the normoxia group.
Source link: https://doi.org/10.1371/journal.pone.0267513
The transfusion of refrigerated WB to treat acute bleeding in military fields was largely influenced by the widespread use of cold-storing type-O whole blood. In this research, we compared the effects of room temperature and refrigeration up to 24 hours on WB's coagulation properties. In cold-stored WB compared to that in RT-stored WB, the preservation of platelet aggregation response induced by arachidonic acid and adenosine diphosphate was much higher than that in RT-stored WB. In all samples after 24 hours of storage, the platelet aggregation response induced by thrombin receptor-activating peptide 6 was significantly reduced in all samples after 24 hours of storage, compared to that at baseline. After 6 hours of storage compared to those of frozen-stored samples, the lactate levels in WB stored at RT increased sharply. WB for ANH stored in the refrigerator had improved metabolic stability after 6 hours of storage and faster aggregation response after 12 hours of storage than WB stored at RT.
Source link: https://doi.org/10.1371/journal.pone.0267980
Long-term obesity in zebrafish has metabolic endpoints similar to mammals, including increased adiposity, weight, hepatic steatosis, and hepatic lesions, but there are no signs of glucose dysregulation or variations in metabolic rate or mitochondrial function. Malnutrition in early life has been linked to an increased risk of disease and exacerbation of metabolic syndrome, but fish that were restricted from five days after fertilization to nine months old showed no signs of an exacerbated phenotype.
Source link: https://doi.org/10.1371/journal.pone.0267933
These pathway diagrams show pertinent links between biological entities and domain knowledge in a graphic form that makes it easier for humans to comprehend. These pathway diagrams illustrate common connections between biological species and domain knowledge that are easy to comprehend for humans. However, while humans are adept at interpreting the messages of diagram designers, algorithms become more difficult to use as the number of drawing approaches increases. WikiPathways supports many drawing styles that must harmonize to provide semantically enhanced access. We explore how the graphically-modelled biological knowledge in diagrams can be manipulated and harmonized, as well as exemplify how the collected data can be used to programmatically answer biological questions. We find that we can convert graphically modelled knowledge to a sufficient degree into a semantic model and address some of the current drawbacks. Our findings show that the bulk of WikiPathways' graphical biological knowledge is modelled into the semantic layer, with the semantic data intact and connectivity information preserved.
Source link: https://doi.org/10.1371/journal.pone.0263057
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