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ABSTRACT:
PROVIDER: PRJNA198764 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:compare of microRNA expression between IA and MMA
| PRJNA198766 | ENA
Project description:To exploring the difference of microRNA expression between IA and MMA, we have employed microRNA array expression profiling as a discovery platform to identify genes between the IA and MMA. Futher functional analyses were performed based on the data.
2013-04-25 | GSE46336 | GEO
Project description:To exploring the difference of microRNA expression between IA and MMA, we have employed microRNA array expression profiling as a discovery platform to identify genes between the IA and MMA. Futher functional analyses were performed based on the data. 3 IA and 3 MMA were used for the microarray.
2013-04-25 | E-GEOD-46336 | biostudies-arrayexpress
Project description:To exploring the difference of mRNA expression between IA and MMA, we have employed mRNA array expression profiling as a discovery platform to identify genes between the IA and MMA. It's a compensate experiment after microRNA array, we paired the mRNA data with miRNA targets, finally, these data were used for the functional analysis. 2 IA and 2 MMA tissue were used for the microarray
2013-04-25 | E-GEOD-46337 | biostudies-arrayexpress
Project description:To exploring the difference of mRNA expression between IA and MMA, we have employed mRNA array expression profiling as a discovery platform to identify genes between the IA and MMA. It's a compensate experiment after microRNA array, we paired the mRNA data with miRNA targets, finally, these data were used for the functional analysis.
2013-04-25 | GSE46337 | GEO
Project description:Systemic levels of methylmalonic acid (MMA), a byproduct of propionate metabolism, increase with age and MMA promotes tumor progression via its direct effects in tumor cells. However, the role of MMA in modulating the tumor ecosystem remains to be investigated. The proliferation and function of CD8+ T cells, key anti-tumor immune cells, declines with age and in conditions of vitamin B12 deficiency, which are the two most well-established conditions that lead to increased systemic levels of MMA. Thus, we hypothesized that increased circulatory levels of MMA would lead to a suppression of CD8+ T cell immunity. Treatment of primary CD8+ T cells with MMA induced a dysfunctional phenotype characterized by robust immunosuppressive transcriptional reprogramming and marked increases in the expression of the exhaustion regulator, TOX. Accordingly, MMA treatment upregulated exhaustion markers in CD8+ T cells and decreased their effector functions, which drove the suppression of anti-tumor immunity in vitro and in vivo. Mechanistically, MMA-induced CD8+ T cell exhaustion was associated with a suppression of NADH-regenerating reactions in the TCA cycle and concomitant defects in mitochondrial function. Thus, MMA has immunomodulatory roles, thereby highlighting MMA as an important link between aging, immune dysfunction, and cancer.
2024-10-17 | GSE256487 | GEO
Project description:Objective: To investigate the independent and interactive effects of circulating folate and methylmalonic acid (MMA) status on cardiovascular disease (CVD) mortality. Methods: This study included 22,487 individuals from the U.S. National Health and Nutrition Examination Survey (NHANES) between 1999 and 2014. Kaplan-Meier and weighted Cox proportional hazards models were used to assess the associations of folate and MMA with CVD mortality. Restricted cubic splines (RCS) evaluated nonlinear relationships. Additive interaction method explored interactive effects. Sensitivity analysis tested the robustness of the findings. In vitro, CCK-8 assays were performed to assess the combined effects of folate and MMA on H9c2 cardiomyocyte viability. Transcriptomic analysis identified differentially expressed genes (DEGs) and their enriched pathways. Results: During 12.1 years of median follow-up, 1,510 cardiovascular deaths (4.4%) were recorded. RCS analysis demonstrated a U-shaped association between folate levels and CVD mortality, and a linear association for MMA. When MMA ≤ 182 nmol/L, folate levels were not associated with CVD mortality. However, among individuals with MMA > 182 nmol/L, both low and high folate levels were significantly associated with higher CVD mortality, with adjusted hazard ratios (aHRs) of 1.43 (95% CI: 1.19-1.71) and 2.36 (95% CI: 1.85-3.00), respectively (both P < 0.001). An additive interaction between folate and MMA on CVD mortality (RERI: 0.82 [95% CI: 0.06-1.58], API: 0.35 [95% CI: 0.03-0.67]; SI: 1.57 [95% CI: 1.27-2.00]). Sensitivity analyses confirmed these findings. In vitro, MMA (8 mM) significantly enhanced folate-induced (1.6 mM) cytotoxicity, reducing cell viability to 49.26% (P < 0.001). Transcriptomic analysis revealed 53 DEGs under combined treatment, enriched in inflammation-related pathways. Conclusions: Both population-based and experimental evidence suggest that elevated folate and MMA levels independently increase CVD mortality risk, with their interaction synergistically exacerbating cardiovascular outcomes.
2025-11-02 | GSE307146 | GEO
Project description:Isolated methylmalonic acidemia (MMA) is a pleiotropic enzymatic defect of branched-chain amino acid oxidation most commonly caused by deficiency of methylmalonyl-CoA mutase (MUT). End stage renal disease (ESRD) is emerging as an inevitable disease-related complication, recalcitrant to conventional therapies and liver transplantation. To establish a viable model of MMA-associated renal disease, methylmalonyl-CoA mutase (Mut) was expressed in the liver of Mut -/- mice as a stable transgene under the control of an albumin (INS-Alb-Mut) promoter. Mut -/- ;TgINS-Alb-Mut mice were rescued from the neonatal lethality displayed by Mut -/- mice and manifested a decreased glomerular filtration rate (GFR), chronic tubulointerstital nephritis (CTIN) and prominent ultrastructural changes in the proximal tubular mitochondria, replicating precisely the renal manifestations seen in a large MMA patient cohort. To explore the pathophysiological changes that underlie the renal disease of MMA, we compared gene expression profiles of whole kidney mRNA samples between 4 female Mut +/+, Mut +/- and Mut -/- ;TgINS-Alb-Mut mice after they ingested a HP diet for 2 months. Females were used because more survived the dietary challenge, whereas the histology, ultrastructure and GFR effects were identical between sexes
2013-05-01 | E-GEOD-41044 | biostudies-arrayexpress