Ontology highlight
ABSTRACT:
PROVIDER: PRJNA661978 | ENA |
REPOSITORIES: ENA
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Project description:Sunflower (Helianthus annuus L.) calathide is becoming more well-known as a result of its anti-hyperuricemia bioactivity. Aiming at developing anti-hyperuricemic ingredients in sunflower calathide extract (SCE), we were fortunate to discover abietic acid (AA), identified from SCE, has the capacity to inhibit xanthine oxidase activity at low concentrations (IC50 = 10.60 µM and inhibition constant was 193.5 nM) that examined by inhibitor screening experiment in vitro and computer-simulated molecular docking. To further explore the anti-hyperuricemia effects, the UA-stimulated human embryonic kidney (HEK) 293T cells were evaluated as a conceivable model in the current study. The huge amounts of high-throughput sequencing data, which mapping to reference genome, were analyzed by bioinformatics approaches: Weighted Gene Co-Expression Network Analysis (WGCNA) along with Kyoto Encyclopedia of Genes and Genomes (KEGG). Interestingly, the purine metabolism-related genes expressed in the AA treatment were nearly opposite to that of the UA group, indicating negative feedback regulations that AA perhaps contributes to maintain urate homeostasis in the high UA-exposed kidney cellular environment. Here, we consider that HEK293T cells ought to be an achievable in vitro model for UA metabolism research because the PNPase, PRPS1, PRPS2, and RPIA, which participate in UA generation, widely expressed in the untreated 293T cells as well. And AA markedly suppressed the PNPase, PRPS2, and RPIA expressed in UA-stimulated 293T cells, implying inhibitions for UA biosynthesis. As a result, AA not only inhibited xanthine oxidase activity efficiently but also regulated genes PNPase, PRPS2, and RPIA. It is promising to be developed as an inhibitor against hyperuricemia. Therefore, abietic acid, which could be isolated from plants, has the potential for anti-hyperuricemia, and the current study provided a precedent for pharmacology analysis of natural ingredients.
2022-03-11 | GSE198133 | GEO
Project description:Uric acid (UA) is the final product of purine metabolism and plays an important role as a physiological antioxidant. In recent years, several different groups have reported a correlation between decreased UA in Parkinson’s disease (PD) and clinical progression and stage of PD. However, little is known about the molecular mechanisms of decreased UA under oxidative stress. We used our systematic functional annotation pipeline for silkworm genes to identify a novel UA metabolic pathway regulator under oxidative stress in a UA metabolism mutant silkworm Bombyx mori model.
2013-07-24 | GSE37735 | GEO
Project description:In this study, we repoort the protective effect of ursolic acid (UA) on vascular calcification in chronic kidney disease. To elucidate the molecular mechanism underlying the anti-vascular calcification effect of UA, we performed RNA-seq to identify the gene expresion under UA treatmment.
2024-09-13 | GSE276910 | GEO
Project description:Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with learning, memory, and cognitive deficits. Neuroinflammation and lysosomal dysfunction are thought to play key roles in the progression of AD pathology. Diverse measures have been applied to treat AD, but currently, there is no effective treatment. Urolithin A (UA) is a gut microbial metabolite of ellagic acid shown to stimulate mitophagy and acts as a potent anti-inflammatory and anti-oxidant agent. However, long-term safety and the potential role of UA in altering pathology of AD is still largely unclear. In this study, we investigated the underlying mechanisms for the beneficial effects of UA in multiple mouse models of AD. We report that long-term UA treatment significantly improves learning and memory, olfactory function, and synaptic function of neurons in AD transgenic mice. We demonstrate that UA decreases soluble and insoluble Ab1-42, total Tau, and Tau phosphorylation. Furthermore, alterations in lysosomal cathepsins, particularly upregulation of cathepsin Z, was observed in the AD mice brains and normalized by UA treatment. Notably, UA treatment also ameliorates neuroinflammation, DNA damage, mitochondrial dysfunction, and restores lysosomal functions in AD mice brains. Collectively, these results provide new insights into the role of UA in regulating lysosomal dysfunction, cathepsins, and suggests that UA may have a potential therapeutic application for AD.
2024-07-01 | GSE212972 | GEO
Project description:Natural compounds ursolic acid (UA) and digoxin isolated from fruits and other plants display potent anti-cancer effects in preclinical studies. UA and digoxin have been at clinical trials for treatment of different cancers including prostate cancer, pancreatic cancer and breast cancer. However, they displayed limited benefit to patients. Currently, a poor understanding of their direct targets and mechanisms of action (MOA) severely hinders their further development. We previously identified nuclear receptor RORγ as a novel therapeutic target for castration-resistant prostate cancer (CRPC) and triple-negative breast cancer (TNBC) and demonstrated that tumor cell RORγ directly activates gene programs such as androgen receptor (AR) signaling and cholesterol metabolism. Previous studies also demonstrated that UA and digoxin are potential RORγt antagonists in modulating the functions of immune cells such as Th17 cells. Here we showed that UA displays a strong activity in inhibition of RORγ-dependent transactivation function in cancer cells, while digoxin exhibits no effect at clinically relevant concentrations. In prostate cancer cells, UA down-regulates RORγ-stimulated AR expression and AR signaling, whereas digoxin up-regulates AR signaling pathway. In TNBC cells, UA but not digoxin alters RORγ-controlled gene programs of cell proliferation, apoptosis and cholesterol-biosynthesis.Together, our study reveals for the first-time that UA, but not digoxin, acts as a natural antagonist of RORγ in the cancer cells. Our finding that RORγ is a direct target of UA in cancer cells will help select patients with tumors that likely respond to UA treatment.
2023-05-17 | GSE230039 | GEO
Project description:Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with learning, memory, and cognitive deficits. Neuroinflammation and lysosomal dysfunction are thought to play key roles in the progression of AD pathology. Diverse measures have been applied to treat AD, but currently, there is no effective treatment. Urolithin A (UA) is a gut microbial metabolite of ellagic acid shown to stimulate mitophagy and acts as a potent anti-inflammatory and anti-oxidant agent. However, long-term safety and the potential role of UA in altering pathology of AD is still largely unclear. In this study, we investigated the underlying mechanisms for the beneficial effects of UA in multiple mouse models of AD. We report that long-term UA treatment significantly improves learning and memory, olfactory function, and synaptic function of neurons in AD transgenic mice. We demonstrate that UA decreases soluble and insoluble Ab1-42, total Tau, and Tau phosphorylation. Furthermore, alterations in lysosomal cathepsins, particularly upregulation of cathepsin Z, was observed in the AD mice brains and normalized by UA treatment. Notably, UA treatment also ameliorates neuroinflammation, DNA damage, mitochondrial dysfunction, and restores lysosomal functions in AD mice brains. Collectively, these results provide new insights into the role of UA in regulating lysosomal dysfunction, cathepsins, and suggests that UA may have a potential therapeutic application for AD. To understand what metabolism-related gene expression changes are induced by Urolithin A, WT (C57BL6/J), 3xTgAD and 3xTgAD/PolB+/- mice were treated with water or Urolithin A (200mg/kg/day) by oral gavage for 5 months starting when the mice were 12m of age, thereafter hippocampi tissues was collected from each mouse and subjected to RNA isolation.
2024-07-01 | GSE214416 | GEO
Project description:Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with learning, memory, and cognitive deficits. Neuroinflammation and lysosomal dysfunction are thought to play key roles in the progression of AD pathology. Diverse measures have been applied to treat AD, but currently, there is no effective treatment. Urolithin A (UA) is a gut microbial metabolite of ellagic acid shown to stimulate mitophagy and acts as a potent anti-inflammatory and anti-oxidant agent. However, long-term safety and the potential role of UA in altering pathology of AD is still largely unclear. In this study, we investigated the underlying mechanisms for the beneficial effects of UA in multiple mouse models of AD. We report that long-term UA treatment significantly improves learning and memory, olfactory function, and synaptic function of neurons in AD transgenic mice. We demonstrate that UA decreases soluble and insoluble Ab1-42, total Tau, and Tau phosphorylation. Furthermore, alterations in lysosomal cathepsins, particularly upregulation of cathepsin Z, was observed in the AD mice brains and normalized by UA treatment. Notably, UA treatment also ameliorates neuroinflammation, DNA damage, mitochondrial dysfunction, and restores lysosomal functions in AD mice brains. Collectively, these results provide new insights into the role of UA in regulating lysosomal dysfunction, cathepsins, and suggests that UA may have a potential therapeutic application for AD. To understand what gene expression changes are induced by Urolithin A, WT (C57BL6/J), 3xTgAD and 3xTgAD/PolB+/- mice were treated with water or Urolithin A (200mg/kg/day) by oral gavage for 5 months starting when the mice were 12m of age. Thereafter, hippocampi tissue was collected from each mouse and subjected to RNA isolation.
2024-07-01 | GSE214406 | GEO
Project description:This study describes a circulating miRNA signature of unstable angina (UA), which may be used as a novel biomarker for unstable coronary artery disease (CAD). The Taqman low-density miRNA array were used to identify distinct miRNA expression profiles in the plasma of patients with typical UA and angiographically documented CAD (UA group, n = 13) compared to individuals with non-cardiac chest pain (control group, n = 13).
2013-08-13 | GSE49823 | GEO
Project description:Uric acid (UA) is the final product of purine metabolism and plays an important role as a physiological antioxidant. In recent years, several different groups have reported a correlation between decreased UA in Parkinson’s disease (PD) and clinical progression and stage of PD. However, little is known about the molecular mechanisms of decreased UA under oxidative stress. We used our systematic functional annotation pipeline for silkworm genes to identify a novel UA metabolic pathway regulator under oxidative stress in a UA metabolism mutant silkworm Bombyx mori model. Gene expression was measured in 3day of fifth instar larvae of abnormal uric acid synthesis Bombyx mori mutant of op.
2013-07-24 | E-GEOD-37735 | biostudies-arrayexpress
Project description:Undifferentiated arthritis (UA) is the term used to cover all the cases of arthritis that do not fit a specific diagnosis. A high proportion of UA patients can progress to rheumatoid arthritis (RA) or a different definite rheumatic disease, while others undergo spontaneous remission. In this study, we performed DNA methylation profiling of a UA cohort, in which progression into RA occurs for a significant proportion of the patients.
2021-06-16 | GSE175364 | GEO