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Metabolism - PLOS

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Last Updated: 15 May 2022

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BOXR1030, an anti-GPC3 CAR with exogenous GOT2 expression, shows enhanced T cell metabolism and improved anti-cell line derived tumor xenograft activity

Purpose: The solid tumor microenvironment promotes T cell dysfunction and reduces the absorption of immunotherapies such as chimeric antigen receptor-based T cell cells. In preclinical models, early findings have shown that T cell metabolism modulation can improve intratumoral T cell function. Experimental design: We analyzed GPC3 expression in human normal and tumor tissue samples. In vitro and in vivo, we developed and evaluated BOXR1030, a novel CAR T therapeutic co-expressing glypican-3-targeted CAR and exogenous glutamic-oxaloacetic transaminase 2 in terms of CAR T cell function, both in vitro and in vivo. Cellular carcinoma, liposarcoma, squamous lung cancer, and Merkel cell carcinoma patients were shown by immunohistochemical staining in tumor biopsies from hepatocellular carcinoma, liposarcoma, squamous lung cancer, and Merkel cell carcinoma patients. Conclusions: These findings, combined, showed that co-expression of GOT2 can significantly raise the overall antitumor activity of CAR T cells by inducing broad variations in cell function and phenotype.

Source link: https://doi.org/10.1371/journal.pone.0266980


Serum Amyloid A is not obligatory for high-fat, high-sucrose, cholesterol-fed diet-induced obesity and its metabolic and inflammatory complications

Positive correlations have been found between circulating Serum amyloid A levels and obesity in previous studies. We have investigated the role of SAA in the formation of obesity and its associated metabolic disorders in vivo using mice lacking all three inducible 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


Comprehensive lipidomic analysis reveals regulation of glyceride metabolism in rat visceral adipose tissue by high-altitude chronic hypoxia

Using a lipidomic analysis method, we aimed to investigate the effects of high-altitude persistent hypoxia on lipid metabolism in rats' adipose tissue as hypoxia affects lipid metabolism in adipose tissue. The hypoxia group's body weight and visceral adipose tissue mass weight had dramatically decreased after 8 weeks relative to those of the normoxia group. paraphrasedoutput cells in the hypoxia group were significantly smaller than those of visceral adipose cells in the normoxia group. The hypoxia group's total lipid concentration was lower than that in the normoxia group. In the hypoxia group, diacylglycerols and triacylglycerols were significantly lower than those in the normoxia group.

Source link: https://doi.org/10.1371/journal.pone.0267513


Elucidation of host and symbiont contributions to peptidoglycan metabolism based on comparative genomics of eight aphid subfamilies and their Buchnera

Despite genome deletion associated with endosymbiosis, Pea aphid Buchnera maintains genes for PGN synthesy, synthesis of PGN, while Buchneras of many other aphid species also lacks or completely lacking these genes. We sequenced genomes from four closely related lineages to investigate how host and symbiont genes influence PGN production, as well as eight subfamilies. We now have 17 species from four remarkably different lineages, including eight subfamilies in order to investigate how host and symbiont genes influence PGN production. Although four aphid rlpA gene subfamilies have no connection to the symbiont PGN gene bank, the absence of aphid amiD and ldcA HTGs coincides with the loss of symbiont PGN metabolism genes. Horizontically-transferred genes for certain insects that carry bacterial symbionts can enable hosts to control symbiosis by modulating symbiosis by controlling symbiosis and cell wall metabolism. Although mealybug horizontally-transferred genes work together to synthesize the symbiont cell wall, the role of aphid horizontally-transferred genes in symbiont cell wall metabolism remains unclear. We investigated whether different aphid horizontally-transferred genes co-occur with symbiont genes that support cell wall metabolism in different aphid lineages, indicating linked function. In addition, we found that symbiont cell wall synthesis is maintained in a single aphid lineage despite a lack of genes that is considered essential for building the cell wall, implying that other adaptations maintain the cell wall in aphid species with incomplete cell wall synthesis pathways.

Source link: https://doi.org/10.1371/journal.pgen.1010195


Understanding signaling and metabolic paths using semantified and harmonized information about biological interactions

These pathway diagrams show key links between biological species and domain knowledge in a visual style that makes it easier for humans to comprehend. However, while humans are skilled at interpreting the diagrams' message, algorithms become more difficult when the number of drawing approaches increases. The relationships between the biological entities that underlie the biological causality are particularly challenging, here. Diagrams can be interpreted and harmonized by diagrams, and we can show how the resulting data can be used to programmatically answer biological questions. We then use this to demonstrate that reproducible notebooks can be used to investigate MECP2's up- and downstream targets and to investigate sphingolipid metabolism. Our findings show that the bulk of WikiPathways' graphical biological data is modelled into the semantic layer, with the semantic information intact and connectivity information preserved.

Source link: https://doi.org/10.1371/journal.pone.0263057

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions