Project description:Regulatory T cells (Tregs) are known to maintain survival and suppressive function in the presence of high levels of extracellular lactic acid. However, the effect of lactic acid on Treg induction is not known. We therfore evaluated the effect of lactic acid on Treg induction and observed an increased induction of Tregs in the presence of lactic acid. This increase occurred in a glycolysis-independent, acidity-dependent manner.
Project description:D-lactic acid is a three-carbon organic acid with a chiral structure and can improve the thermostability of polylactic acid. Microorganisms such as the methylotrophic yeast Pichia pastoris, which lack the natural ability to produce or accumulate high amounts of D-lactic acid, have been engineered to produce it in high titers. However, tolerance to D-lactic acid remains a challenge. In this study, we demonstrate that cell flocculation improves tolerance to D-lactic acid and leads to increased D-lactic acid production in Pichia pastoris. By incorporating a flocculation gene from Saccharomyces cerevisiae (ScFLO1) into P. pastoris KM71, we created a strain (KM71-ScFlo1) that demonstrated up to a 1.6-fold improvement in specific growth rate at high D-lactic acid concentrations. Furthermore, integrating a D-lactate dehydrogenase gene from Leuconostoc pseudomesenteroides (LpDLDH) into KM71-ScFlo1 resulted in an engineered strain (KM71-ScFlo1-LpDLDH) that can produce D-lactic acid at a titer of 5.12 0.35 g/L in 48 hours , a 2.6-fold improvement over the control strain lacking ScFLO1 expression. Transcriptomics analysis of this strain provided insights into the mechanism of increased tolerance to D-lactic acid including the upregulations of genes involved in lactate transport and iron metabolism. Overall, our work represents an advancement in the efficient microbial production of D-lactic acid by manipulating yeast flocculation.
Project description:Glioblastoma is the most common primary malignant brain tumor with an unfavorable prognosis and a reprogrammed metabolism. In order to define the role of lactic acid in the context of glioblastoma epigenetic remodeling, pediatric GBM cells, KNS42, were growth for 24h in different media conditions (starvation media -0.5mM Glucose; 0.5mM Glutamate or physiological media -5mM Glucose; 0mM Glutamate) with or without L-lactic acid for 24h. Thereafter, cells were harvested and samples were subjected to ChIP isolation using H3K27ac and H3K9ac antibodies. DNA was subsequently processed for CHIP sequencing to assess epigenetic changes mediated by lactic acid.
Project description:Raw expression values (CHP data) for transcriptional profiling of the response of Saccharomyces cerevisiae to challenges with lactic acid at pH 3 and pH 5. Keywords: response to lactic acid
Project description:To characterize the effect of lactic acid on the L. plantarum growth and adaptation, we investigated the transcriptome under hydrochloride (HCl) or lactic acid at the early stage of the growth.
Project description:Via aerobic glycolysis-Warnburg effect, cancer cells can convert 85-90% of glucose they acquire to lactic acid, which is thus ubiquitously abundant in solid tumor environment. We also observed that lactic acid effectively rescues cancer cells from glucose staration. In order to understand the biological function of lacitc acid, we did the microarrays. murine breast cancer 4T1 cells were incubated in RPMI-1640 containing 3mM glucose and 20mM lactic acid for 1 day, 3 days, 4 days, 5 days, 7 days, 9 days and 11 days. 4T1 cells were incubated in RPMI-1640 containing 3mM glucose as control. We extracted the RNA and hybridized on the microarrays. We sought to obtain temporal genes that prolonged the cell life with lactic acid during the glucose starvation.
Project description:Lactic acid is used to check skin sensitivity of human. However transcriptional profiling has not been done yet. This study was targeted to understand the transcriptional changes occur in human skin upon treatment with lactic acid.
Project description:Via aerobic glycolysis-Warnburg effect, cancer cells can convert 85-90% of glucose they acquire to lactic acid, which is thus ubiquitously abundant in solid tumor environment. We also observed that lactic acid effectively rescues cancer cells from glucose staration. In order to understand the biological function of lacitc acid, we did the microarrays.
