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PROVIDER: PRJNA701784 | ENA |
REPOSITORIES: ENA
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Project description:Ramulus Mori (Sangzhi) alkaloids (SZ-A) improves lipid metabolism and adipose tissue inflammation in HFD-induced obese mice.This study compares transcriptome profiling (RNA-seq) in the epididymal adipose tissue of normal chow, high-fat diet (HFD) control and SZ-A-treated HFD mice to verify the regulatory mechanisms of SZ-A. These results demonstrated that SZ-A regulates lipid metabolism and inflammation.
2022-11-20 | GSE214618 | GEO
Project description:Ramulus Mori (Sangzhi) alkaloids (SZ-A) alleviates nonalcoholic fatty liver disease in mice. This study compares transcriptome profiling (RNA-seq) in the liver of normal chow, high-fat diet (HFD) control and SZ-A-treated HFD mice to verify the regulatory mechanisms of SZ-A. These results demonstrated that SZ-A regulates lipid metabolism and metabolic stress-induced inflammation and fibrosis.
2022-03-23 | GSE199105 | GEO
Project description:The novel Traditional Chinese Medicine Ramulus Mori (Sangzhi) alkaloid tablets (SZ-A) are approved by The China National Medical Products Administration for the treatment of type 2 diabetes mellitus (T2DM). However, the extensive pharmacological characteristics and the underlying mechanism are unknown. This study investigated the mechanisms by which SZ-A ameliorates glucose metabolism in KKAy mice, an animal model of T2DM. Diabetic KKAy mice were treated intragastrically with SZ-A once daily for 8 weeks, after which glucose levels, lipid metabolism, gut microbiome, systemic inflammatory factors, luminal concentrations of short-chain fatty acids (fecal samples), and ileal proteomic changes were evaluated. The ileum tissues were collected, and the effects of SZ-A on pathological inflammatory damage were evaluated by hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry. The mRNA and protein expression levels of various inflammatory markers, including monocyte chemoattractant protein-1 and phosphorylated nuclear factor kappa B p65, were detected in the ileum tissues. SZ-A improved glucose metabolism with enhanced insulin response and elevated glucagon-like peptide 1 (GLP-1) during the glucose tolerance test in diabetic KKAy mice. Gut microbiota analysis demonstrated that SZ-A administration elevated the abundance of Bacteroidaceae and Verrucomicrobia, reduced the levels of Rikenellaceae and Desulfovibrionaceae; and increased the concentrations of fecal acetic and propionic acids compared to the diabetic model group. Additionally, SZ-A markedly improved ileal inflammatory injury and pro-inflammatory macrophage infiltration and improved intestinal mucosal barrier function in diabetic KKAy mice. SZ-A also attenuated the levels of circulating endotoxin, pro-inflammatory cytokines, and chemokines in the mice sera. Collectively, SZ-A ameliorated the overall metabolic profile including glucose and lipid metabolism in KKAy mice, which may be associated with an improvement in GLP-1 and insulin secretion, at least in part by modulating the gut microbiome and relieving the degree of ileal and systemic inflammation.
2021-09-10 | PXD024241 | Pride
Project description:Chronic kidney disease (CKD) has emerged as a significant global public health issue due to its rising prevalence. The co-morbidity of CKD and diabetes is becoming increasingly severe, with diabetes being a primary cause of CKD leading to end-stage kidney disease (ESKD). Therefore, there is an urgent need to develop drugs that offer comprehensive benefits for patients with diabetes and CKD. This has also become a trend in the development of new hypoglycemic drugs. SZ-A is a natural drug approved by the National Medical Products Administration (NMPA) for treating type 2 diabetes mellitus. It has been shown to have good hypoglycemic effects and excellent safety. Subsequent in-depth studies have confirmed that it also has multiple pharmacological effects, including inhibiting colon inflammation, reducing body weight, alleviating non-alcoholic fatty liver disease, and improving insulin resistance. Our team's preliminary research found that SZ-A has the potential to significantly improve the progression of diabetic nephropathy and has a wide distribution in renal tissues. However, the mechanism by which SZ-A exerts its renoprotective effects has not been fully elucidated. It is unclear whether its effect on renal function is dependent on its glucose-lowering effect or if it acts directly on the kidney. The objective of this study was to evaluate the effect of SZ-A on non-diabetic chronic kidney disease by constructing an adenine-induced chronic kidney disease model. The study aimed to explore the mechanism of action of SZ-A in depth, both in vivo and ex vivo, and to elucidate the effect and mechanism of action of SZ-A and its components on renal function. The study results indicate that SZ-A can alleviate adenine-induced renal function decline in a dose-dependent manner. This therapeutic effect does not depend on the glucose-lowering effect. The SZ-A treatment group exhibited improvements in renal fibrosis, inflammation, and oxidative stress compared to the model group. Renal transcriptome analysis revealed that the protective effect of SZ-A was associated with enhanced fatty acid oxidation and decreased inflammation. Both the animal and cellular levels confirmed SZ-A's ameliorative effect on these factors, with DNJ playing a significant role. This study presents an innovative finding on the molecular mechanism through which SZ-A enhances renal function in patients with type 2 diabetes mellitus and concurrent CKD. The study reveals that SZ-A regulates energy metabolism, protects mitochondria, and identifies the single component that plays a major role. These findings provide scientific support for expanding therapeutic options and promoting the rationalization of drug use in clinical settings.
2024-03-14 | GSE261354 | GEO
Project description:Skeletal muscle plays a central role in the control of metabolism and exercise tolerance. Analysis of muscle enhancers activated after exercise in mice revealed the orphan nuclear receptor NURR1/NR4A2 as a prominent component of exercise-responsive enhancers. We show that exercise enhances the expression of NURR1 and transgenic overexpression of NURR1 in skeletal muscle confers an endurance phenotype in mice. NURR1 expression in skeletal muscle is also sufficient to prevent hyperglycemia and hepatic steatosis by enhancing muscle glucose uptake and storage as glycogen. Furthermore, treatment of obese mice with putative NURR1 agonists increases energy expenditure, improves glucose tolerance, and confers a lean phenotype, mimicking the effects of exercise. These findings identify a key role for NURR1 in governance of skeletal muscle glucose metabolism and reveal a transcriptional link between exercise and metabolism. Our findings also identify NURR1 agonists as possible exercise mimetics with the potential to ameliorate obesity and other metabolic abnormalities.
2019-08-01 | GSE130839 | GEO
Project description:Light is a major environmental factor that affects metabolic pathways and stimulates the production of secondary metabolites in potato. However, adaptive changes in potato metabolic pathways and physiological functions triggered by light are partly explained by gene expression changes. Regulation of secondary metabolic pathways in potato has been extensively studied at transcriptional level, but little is known about the mechanisms of post-transcriptional regulation by miRNAs. To identify light-responsive miRNAs/mRNAs and construct putative metabolism pathways regulated by the miRNA-mRNA pairs, an integrated omics (sRNAome and transcriptome) analysis was performed to potato under light stimulus. A total of 31 and 48 miRNAs were identified to be differentially expressed in the leaves and tubers, respectively. Among the DEGs, 1353 genes in the leaves and 1841 genes in the tubers were upregulated, while 1595 genes in the leaves and 897 genes in the tubers were downregulated by light. Mapman enrichment analyses showed that genes related to MVA pathway, alkaloids-like, phenlypropanoids, flavonoids, and carotenoids metabolism were significantly upregulated, while genes associated with major CHO metabolism were repressed in the leaves and tubers. Integrated miRNA and mRNA profiles revealed that light-responsive miRNAs are important regulators in alkaloids metabolism, UMP-salvage, lipid biosynthesis, and cellulose catabolism. Moreover, several miRNAs may participate in glycoalkaloids metabolism via JA signaling pathway, UDP-glucose biosynthesis and hydroxylation reaction. This study provides a global view of transcriptome response in potato response to light, our results suggest that miRNAs might play important roles in secondary metabolic pathways, especially in glycoalkaloid biosynthesis. The findings will enlighten us on the genetic regulation of secondary metabolite pathways and pave the way for future application of genetically engineered potato.
2016-09-28 | GSE79984 | GEO
Project description:Schizophrenia (SZ) is a devastating psychiatric illness affecting 1% of the world population. In addition to genetic predisposition, environmental factors contribute to the risk for developing SZ. Such genome environment interactions frequently activate epigenetic and epitranscriptomic mechansims. There are emerging evidence that genetic and environmental risk factors merge at the level of microRNA expression, which are discussed as biomarker and therapeutic target in various disorders including neuropsychiatric diseases. In this study we analyzed the blood microRNAome of healthy individuals and SZ patients via small RNA sequencing. By combining these data with a corresponding analysis of post-mortem human brain tissue, we identify one candidate microRNA that is down-regulated in patients. Moreover, its expression is significantly correlated to disease phenotypes. Manipulation of this microRNAs in mouse prefrontal cortex causes schizophrenia-like phenotypes. Functional analysis revealed the cellular processes affected by this microRNA and allowed us to develop an arsenal of RNA-based therapeutic approaches that are able to ameliorate molecular disease phenotypes in mouse and human-based cellular systems as well as the behavioral phenotypes. In conclusion, we identify a novel microRNA as target for stratified RNA-therapeutics in schizophrenia.
2024-03-26 | GSE224142 | 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:Skeletal muscle plays a central role in the control of metabolism and exercise tolerance. Analysis of muscle enhancers activated after exercise in mice revealed the orphan nuclear receptor NURR1/NR4A2 as a prominent component of exercise-responsive enhancers. We show that exercise enhances the expression of NURR1 and transgenic overexpression of NURR1 in skeletal muscle confers an endurance phenotype in mice. NURR1 expression in skeletal muscle is also sufficient to prevent hyperglycemia and hepatic steatosis by enhancing muscle glucose uptake and storage as glycogen. Furthermore, treatment of obese mice with putative NURR1 agonists increases energy expenditure, improves glucose tolerance, and confers a lean phenotype, mimicking the effects of exercise. These findings identify a key role for NURR1 in governance of skeletal muscle glucose metabolism and reveal a transcriptional link between exercise and metabolism. Our findings also identify NURR1 agonists as possible exercise mimetics with the potential to ameliorate obesity and other metabolic abnormalities.
2019-08-01 | GSE130838 | GEO
Project description:Light is a major environmental factor that affects metabolic pathways and stimulates the production of secondary metabolites in potato. However, adaptive changes in potato metabolic pathways and physiological functions triggered by light are partly explained by gene expression changes. Regulation of secondary metabolic pathways in potato has been extensively studied at transcriptional level, but little is known about the mechanisms of post-transcriptional regulation by miRNAs. To identify light-responsive miRNAs/mRNAs and construct putative metabolism pathways regulated by the miRNA-mRNA pairs, an integrated omics (sRNAome and transcriptome) analysis was performed to potato under light stimulus. A total of 31 and 48 miRNAs were identified to be differentially expressed in the leaves and tubers, respectively. Among the DEGs, 1353 genes in the leaves and 1841 genes in the tubers were upregulated, while 1595 genes in the leaves and 897 genes in the tubers were downregulated by light. Mapman enrichment analyses showed that genes related to MVA pathway, alkaloids-like, phenlypropanoids, flavonoids, and carotenoids metabolism were significantly upregulated, while genes associated with major CHO metabolism were repressed in the leaves and tubers. Integrated miRNA and mRNA profiles revealed that light-responsive miRNAs are important regulators in alkaloids metabolism, UMP-salvage, lipid biosynthesis, and cellulose catabolism. Moreover, several miRNAs may participate in glycoalkaloids metabolism via JA signaling pathway, UDP-glucose biosynthesis and hydroxylation reaction. This study provides a global view of transcriptome response in potato response to light, our results suggest that miRNAs might play important roles in secondary metabolic pathways, especially in glycoalkaloid biosynthesis. The findings will enlighten us on the genetic regulation of secondary metabolite pathways and pave the way for future application of genetically engineered potato.
2016-09-28 | GSE79985 | GEO