DIA-SWATH analysis of the effect of cysteamine in cystinotic fibroblasts
Ontology highlight
ABSTRACT:
INSTRUMENT(S): ZenoTOF 7600
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Jesus Mateos
PROVIDER: MSV000095020 | MassIVE | Thu Jun 13 05:51:00 BST 2024
REPOSITORIES: MassIVE
Similar Datasets
Project description:Mathematical modeling of regulatory T cell effects on renal cell carcinoma treatment
Lisette dePillis 1, , Trevor Caldwell 2, , Elizabeth Sarapata 2, and Heather Williams 2,
1.
Department of Mathematics, Harvey Mudd College, Claremont, CA 91711
2.
Harvey Mudd College, Claremont, CA 91711, United States, United States, United States
Abstract
We present a mathematical model to study the effects of the regulatory T cells (Treg) on Renal Cell Carcinoma (RCC) treatment with sunitinib. The drug sunitinib inhibits the natural self-regulation of the immune system, allowing the effector components of the immune system to function for longer periods of time. This mathematical model builds upon our non-linear ODE model by de Pillis et al. (2009) [13] to incorporate sunitinib treatment, regulatory T cell dynamics, and RCC-specific parameters. The model also elucidates the roles of certain RCC-specific parameters in determining key differences between in silico patients whose immune profiles allowed them to respond well to sunitinib treatment, and those whose profiles did not.
Simulations from our model are able to produce results that reflect clinical outcomes to sunitinib treatment such as: (1) sunitinib treatments following standard protocols led to improved tumor control (over no treatment) in about 40% of patients; (2) sunitinib treatments at double the standard dose led to a greater response rate in about 15% the patient population; (3) simulations of patient response indicated improved responses to sunitinib treatment when the patient's immune strength scaling and the immune system strength coefficients parameters were low, allowing for a slightly stronger natural immune response.
Keywords: Renal cell carcinoma, mathematical modeling., sunitinib, immune system, regulatory T cells.
2024-09-02 | BIOMD0000000908 | BioModels
Project description:Defects in nephrogenesis can have detrimental effects on cardiovascular and renal health in adult life. This is confirmed by observations in the Munich Wistar Frömter (MWF) rat that exhibits a congenital nephron deficit and renal failure with age. We performed genome-wide transcriptome analysis in embryonic kidneys to identify candidate genes for the reduced nephron number in MWF. We compared MWF E15.5 with stage-matched spontaneously hypertensive rats (SHR) at E16. Microarray analysis revealed 311 transcripts representing 253 known genes with differential expression between MWF and SHR (FC >+1.5 or <-1.5, FDR<0.05). 8 samples were analyzed, n=4 per group
2015-07-01 | E-GEOD-66079 | biostudies-arrayexpress
Project description:26 limb-girdle muscular dystrophy patients from Latvia and 34 patients from Lithuania with clinical symptoms of limb-girdle muscular dystrophies, along with 204 healthy unrelated controls were genotyped for 96 most frequent known limb-girdle muscular dystrophies causing mutations for the region, using VeraCode GoldenGate system. More information can be found in article Robust genotyping tool for autosomal recessive type of limb-girdle muscular dystrophies in BMC Musculoskeletal Disorders by I. Inashkina et al.
2016-04-28 | E-MTAB-4662 | biostudies-arrayexpress
Project description:<p><strong>OBJECTIVE:</strong> Patients with renal failure suffer from symptoms caused by uraemic toxins, possibly of gut microbial origin, as deduced from studies in animals. The aim of the study is to characterise relationships between the intestinal microbiome composition, uraemic toxins and renal failure symptoms in human end-stage renal disease (ESRD).</p><p><strong>DESIGN:</strong> Characterisation of gut microbiome, serum and faecal metabolome and human phenotypes in a cohort of 223 patients with ESRD and 69 healthy controls. Multidimensional data integration to reveal links between these datasets and the use of chronic kidney disease (CKD) rodent models to test the effects of intestinal microbiome on toxin accumulation and disease severity.</p><p><strong>RESULTS:</strong> A group of microbial species enriched in ESRD correlates tightly to patient clinical variables and encode functions involved in toxin and secondary bile acids synthesis; the relative abundance of the microbial functions correlates with the serum or faecal concentrations of these metabolites. Microbiota from patients transplanted to renal injured germ-free mice or antibiotic-treated rats induce higher production of serum uraemic toxins and aggravated renal fibrosis and oxidative stress more than microbiota from controls. Two of the species, Eggerthella lenta and Fusobacterium nucleatum, increase uraemic toxins production and promote renal disease development in a CKD rat model. A probiotic Bifidobacterium animalis decreases abundance of these species, reduces levels of toxins and the severity of the disease in rats.</p><p><strong>CONCLUSION:</strong> Aberrant gut microbiota in patients with ESRD sculpts a detrimental metabolome aggravating clinical outcomes, suggesting that the gut microbiota will be a promising target for diminishing uraemic toxicity in those patients.</p>
2020-10-20 | MTBLS700 | MetaboLights
Project description:Defects in nephrogenesis can have detrimental effects on cardiovascular and renal health in adult life. This is confirmed by observations in the Munich Wistar Frömter (MWF) rat that exhibits a congenital nephron deficit and renal failure with age. We performed genome-wide transcriptome analysis in embryonic kidneys to identify candidate genes for the reduced nephron number in MWF. We compared MWF E15.5 with stage-matched spontaneously hypertensive rats (SHR) at E16. Microarray analysis revealed 311 transcripts representing 253 known genes with differential expression between MWF and SHR (FC >+1.5 or <-1.5, FDR<0.05).
2015-07-01 | GSE66079 | GEO
Project description:Chronic kidney disease (CKD) has become one of the greatest threats to public health, characterized by renal fibrosis. However, no treatment targeting renal fibrosis is available so far. Several natural diterpene compounds exhibit extraordinary inhibitory effects on TGF-β1-induced renal fibroblast activation and renal fibrosis in UUO mouse model. RNA-sequencing reveals the signaling pathways affected by these compounds. The direct target of the compounds are explored via quantitative mass spectrometry. Besides, the efficacies of the compounds are compared with pirfenidone, an FDA-approved drug for idiopathic pulmonary fibrosis, which is under clinical trials for treating CKD patients. Moreover, these compounds exhibit more potent anti-fibrotic activities than conventional CKD medications such as valsartan and enalapril. Taken together, our study discovered that these diterpeniods alleviate kidney fibrosis by blocking the pro-fibrotic signaling pathway, which has great potential for the treatment of CKD.
2023-10-20 | GSE243694 | GEO
Project description:Statin play an important role in the treatment of diabetic nephropathy (DN). In recent years, increasing attention has been given to the relationship between statin and insulin resistance, but many randomized controlled trial (RCT) studies confirm that the therapeutic effect of statin on DN is more beneficial than harmful. However, further confirmation of whether the beneficial effects of long-term statin administration on DN still outweigh the detrimental effects is needed. In the current study, we found that long-term statin administration may exacerbate insulin resistance, interfere with glucose and lipid metabolism, lead to renal cell apoptosis, inflammation and severe renal fibrosis, and ultimately decrease renal function. Mechanistically,Through RNA seq analysis, we found that long-term statin administration affects lipid metabolism and exacerbates inflammation and fibrosis.
2022-05-15 | GSE196701 | GEO
Project description:Attention deficit hyperactivity disorder (ADHD) is a common psychiatric condition of children with a prevalence of 5-10% worldwide. Up to 30% of adults with a history of childhood ADHD maintain symptoms in later life; these adult ADHD patients are severely impaired in social and professional life due to persistence of ADHD core symptoms like impulsivity, attention deficit and hyperactivity as well as frequently observed co-morbidities like alcohol and drug abuse, major depression, bipolar and personality disorders. Pharmaceutical treatment options include methylphenidate (MPH), which is amongst others an inhibitor of the dopamine transporter and therefore increases dopamine levels in the brain. However, not all ADHD patients are MPH responders with clinical features to distinguish responders and non-responders being not at hand so far. Likewise, neurobiological reasons for drug response are still elusive. Here, we examined the global transcriptional response of MPH on lymphoblastoid cell lines (LCLs) derived from ADHD patients and unaffected controls.
2014-09-05 | E-GEOD-52889 | biostudies-arrayexpress
Project description:This is the reduced kidney metabolic network described in the article
Drug off-target effects predicted using structural analysis in the context of a metabolic network model.
Chang RL, Xie L, Xie L, Bourne PE, Palsson BØ. PLoS Comput Biol.
2010 Sep 23;6(9):e1000938. PMID: 20957118
, DOI: 10.1371/journal.pcbi.1000938
Abstract:
Recent advances in structural bioinformatics have enabled the prediction of protein-drug off-targets based on their ligand binding sites. Concurrent developments in systems biology allow for prediction of the functional effects of system perturbations using large-scale network models. Integration of these two capabilities provides a framework for evaluating metabolic drug response phenotypes in silico. This combined approach was applied to investigate the hypertensive side effect of the cholesteryl ester transfer protein inhibitor torcetrapib in the context of human renal function. A metabolic kidney model was generated in which to simulate drug treatment. Causal drug off-targets were predicted that have previously been observed to impact renal function in gene-deficient patients and may play a role in the adverse side effects observed in clinical trials. Genetic risk factors for drug treatment were also predicted that correspond to both characterized and unknown renal metabolic disorders as well as cryptic genetic deficiencies that are not expected to exhibit a renal disorder phenotype except under drug treatment. This study represents a novel integration of structural and systems biology and a first step towards computational systems medicine. The methodology introduced herein has important implications for drug development and personalized medicine.
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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1011080004 | BioModels
Project description:Duchenne muscular dystrophy (DMD) is a genetic disease that results in the death of affected boys by early adulthood.The genetic defect responsible for DMD has been known for over 25 years, yet at present there is neither cure nor effective treatment for DMD. During early disease onset, the mdx mouse has been validated as an animal model for DMD and use of this model has led to valuable but incomplete insights into the disease process. For example, immune cells are thought to be responsible for a significant portion of muscle cell death in the mdx mouse; however, the role and time course of the immune response in the dystrophic process have not been well described. In this paper we constructed a simple mathematical model to investigate the role of the immune response in muscle degeneration and subsequent regeneration in the mdx mouse model of Duchenne muscular dystrophy. Our model suggests that the immune response contributes substantially to the muscle degeneration and regeneration processes. Furthermore, the analysis of the model predicts that the immune system response oscillates throughout the life of the mice, and the damaged fibers are never completely cleared.
2024-09-02 | BIOMD0000001015 | BioModels