Find early markers for Steatosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER:
PROVIDER: S-DIXA-089 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description: Not available
| S-DIXA-088 | biostudies-other
Project description: Not available
| S-DIXA-090 | biostudies-other
Project description:BACKGROUND: Despite the impressive growth of sequence databases, the limited availability of nuclear markers that are sufficiently polymorphic for population genetics and phylogeography and applicable across various phyla restricts many potential studies, particularly in non-model organisms. Numerous introns have invariant positions among kingdoms, providing a potential source for such markers. Unfortunately, most of the few known EPIC (Exon Primed Intron Crossing) loci are restricted to vertebrates or belong to multigenic families. RESULTS: In order to develop markers with broad applicability, we designed a bioinformatic approach aimed at avoiding multigenic families while identifying intron positions conserved across metazoan phyla. We developed a program facilitating the identification of EPIC loci which allowed slight variation in intron position. From the Homolens databases we selected 29 gene families which contained 52 promising introns for which we designed 93 primer pairs. PCR tests were performed on several ascidians, echinoderms, bivalves and cnidarians. On average, 24 different introns per genus were amplified in bilaterians. Remarkably, five of the introns successfully amplified in all of the metazoan genera tested (a dozen genera, including cnidarians). The influence of several factors on amplification success was investigated. Success rate was not related to the phylogenetic relatedness of a taxon to the groups that most influenced primer design, showing that these EPIC markers are extremely conserved in animals. CONCLUSIONS: Our new method now makes it possible to (i) rapidly isolate a set of EPIC markers for any phylum, even outside the animal kingdom, and thus, (ii) compare genetic diversity at potentially homologous polymorphic loci between divergent taxa.
| S-EPMC2949868 | biostudies-literature
Project description:Correlative evidence indicates that apoptosis is associated with the progression of alcoholic liver disease. If apoptosis contributes to ethanol (EtOH)-induced steatohepatitis and/or fibrosis, then mice deficient in Bid, a key pro-apoptotic Bcl-2 family member, or mice treated with a pan-caspase inhibitor (VX166) should be resistant to EtOH-induced liver injury.This hypothesis was tested in mice using a model of chronic, heavy EtOH-induced liver injury, as well as in a model in which moderate EtOH feeding accelerated the appearance of early markers of hepatic fibrosis in response to acute carbon tetrachloride (CCl(4) ) exposure.Chronic EtOH feeding to mice increased TUNEL- and cytokeratin-18-positive cells in the liver, as well as the expression of receptor-interacting protein kinase 3 (RIP3), a marker of necroptosis. In this model, Bid-/- mice or wild-type mice treated with VX166 were protected from EtOH-induced apoptosis, but not EtOH-induced RIP3 expression. Bid deficiency or inhibition of caspase activity did not protect mice from EtOH-induced increases in plasma alanine and aspartate amino transferase activity, steatosis, or mRNA expression of some inflammatory cytokines. Moderate EtOH feeding to mice enhanced the response of mice to acute CCl(4) exposure, resulting in increased expression of ?-smooth muscle actin and accumulation of extracellular matrix protein. VX166-treatment attenuated EtOH-mediated acceleration of these early indicators of CCl(4) -induced hepatic fibrosis, decreasing the expression of ?-smooth muscle actin, and the accumulation of extracellular matrix protein.EtOH-induced apoptosis of hepatocytes was mediated by Bid. Apoptosis played a critical role in the accelerating the appearance of early markers of CCl(4) -induced fibrosis by moderate EtOH but did not contribute to EtOH-induced hepatocyte injury, steatosis, or expression of mRNA for some inflammatory cytokines.
| S-EPMC3337974 | biostudies-literature
Project description:Data acquisition in (pre)clinical studies is often based on a hypothesis. Numerical algorithms, however, may help to find biomarkers from existing data without formulating any hypothesis. By simply assessing whether a statistical relationship exists between two parameters from a (unlimited) database, every (in)conceivable combination of data becomes a hypothesis. The aim was to create an unbiased and highly automated approach for secondary analysis of (pre)clinical research, including the possibility of a non-linear functional relationship. In our example, an almost homogeneous database was formed by overall 45 parameters (vital, blood and plasma parameters) measured in 11 individual experimental studies at 6 different time points using 57 rats without and 63 rats with systemic inflammation following lipopolysaccharide infusion. For each rat, four group classifiers (treatment, survival, study, ID) were used to get valid samples by a later filtering of the statistical base. Any information about the hypothesis leading to the respective studies was suppressed. In order to assess whether a statistical relationship exists, a total of six different functional prototypes (linear and non-linear) were postulated and examined for their regression. Regression quality, correlation and significance were obtained in form of matrices. In our example, ultimately 510 300 regressions were optimized, automatically evaluated and filtered. The developed algorithm is able to reveal statistical relationships from a nearly crude database with low effort by systematic and unbiased analysis. The finding of well-known correlations proves its reliability, whose validity could be increased by clean aggregation of different studies. In addition, new interesting hints for future research could be gained. Thus, unknown markers can be found which are associated with an increased risk of death during systemic inflammation and sepsis. A further development of the program is planned including multiple regressions (more than two parameters could be related to each other) or cluster analysis.
| S-EPMC6859257 | biostudies-literature
Project description:A non-invasive diagnostic test does not exist for acute graft versus host disease (aGVHD). We therefore sought to identify biomarkers for aGVHD using antibody microarrays (Schleicher and Schuell Serum Biomarker Chips, Whatman) that simultaneously assayed 120 plasma proteins. We measured these proteins in a set of 42 patient plasma samples following an allogeneic bone marrow transplant (BMT): 21 patients with a diagnosis of aGVHD grade II-IV (+GVHD) and 21 patients without aGVHD (–GVHD) at similar times after transplant. We excluded data from 2 hybridizations that had very bright dots and appeared as outliers in preliminary principal components analysis, so that we finally compared 20 +GVHD to 20 -GVHD samples. Keywords: disease state analysis, antibody microarray
2008-10-31 | GSE9791 | GEO
Project description:Evidence suggests that advanced fibrosis, as determined by the noninvasive NAFLD fibrosis score (NFS), is a predictor of cardiovascular mortality in individuals with ultrasonography-diagnosed NAFLD. Whether the severity of histology (i.e., fibrosis stage) is associated with more pronounced cardiovascular organ damage is unsettled. In this study, we analyzed the clinical utility of NFS in assessing increased carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI). In this cross-sectional study NFS, cIMT and LVMI were assessed in 400 individuals with ultrasonography-diagnosed steatosis. As compared with individuals at low probability of liver fibrosis, individuals both at high and at intermediate probability of fibrosis showed an unfavorable cardio-metabolic risk profile having significantly higher values of waist circumference, insulin resistance, high sensitivity C-reactive protein (hsCRP), fibrinogen, cIMT, and LVMI, and lower insulin-like growth factor-1 (IGF-1) levels. The differences in cIMT and LVMI remained significant after adjustment for smoking and metabolic syndrome. In a logistic regression model adjusted for age, gender, smoking, and diagnosis of metabolic syndrome, individuals at high probability of fibrosis had a 3.9-fold increased risk of vascular atherosclerosis, defined as cIMT>0.9 mm, (OR 3.95, 95% CI 1.12-13.87) as compared with individuals at low probability of fibrosis. Individuals at high probability of fibrosis had a 3.5-fold increased risk of left ventricular hypertrophy (LVH) (OR 3.55, 95% CI 1.22-10.34) as compared with individuals at low probability of fibrosis. In conclusion, advanced fibrosis, determined by noninvasive fibrosis markers, is associated with cardiovascular organ damage independent of other known factors.
| S-EPMC4128729 | biostudies-other
Project description:BACKGROUND & AIMS:De novo lipogenesis is increased in livers of patients with nonalcoholic steatohepatitis (NASH). Acetyl-coenzyme carboxylase catalyzes the rate-limiting step in this process. We evaluated the safety and efficacy of GS-0976, an inhibitor of acetyl-coenzyme A carboxylase in liver, in a phase 2 randomized placebo-controlled trial of patients with NASH. METHODS:We analyzed data from 126 patients with hepatic steatosis of at least 8%, based on the magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF), and liver stiffness of at least 2.5 kPa, based on magnetic resonance elastography measurement or historical biopsy result consistent with NASH and F1-F3 fibrosis. Patients were randomly assigned (2:2:1) to groups given GS-0976 20 mg, GS-0976 5 mg, or placebo daily for 12 weeks, from August 8, 2016 through July 18, 2017. Measures of hepatic steatosis, stiffness, serum markers of fibrosis, and plasma metabolomics were evaluated. The primary aims were to confirm previous findings and evaluate the relation between dose and efficacy. RESULTS:A relative decrease of at least 30% from baseline in MRI-PDFF (PDFF response) occurred in 48% of patients given GS-0976 20 mg (P = .004 vs placebo), 23% given GS-0976 5 mg (P = .43 vs placebo), and 15% given placebo. Median relative decreases in MRI-PDFF were greater in patients given GS-0976 20 mg (decrease of 29%) than those given placebo (decrease of 8%; P = .002). Changes in magnetic resonance elastography-measured stiffness did not differ among groups, but a dose-dependent decrease in the fibrosis marker tissue inhibitor of metalloproteinase 1 was observed in patients given GS-0976 20 mg. Plasma levels of acylcarnitine species also decreased in patients with a PDFF response given GS-0976 20 mg. GS-0976 was safe, but median relative increases of 11% and 13% in serum levels of triglycerides were observed in patients given GS-0976. CONCLUSIONS:In a randomized placebo-controlled trial of patients with NASH, we found 12-week administration of GS-0976 20 mg decreased hepatic steatosis, selected markers of fibrosis, and liver biochemistry. ClinicalTrials.gov ID NCT02856555.
| S-EPMC6318218 | biostudies-literature
Project description:Steatosis is the accumulation of triglycerides in hepatic cells wherein fats exceed 5% of the entire liver weight. Although steatotic liver damage is reversible due to the liver's regenerative capability, protracted damage often and typically leads to irreversible conditions such as cirrhosis and hepatocellular carcinoma (HCC). Therefore, early steatotic detection is critical for preventing progression to advanced liver diseases. This also becomes particularly important given the higher prevalence of drug usage, as drugs are a frequent cause of liver damage. Currently, the recommendation to diagnose steatosis is using liver enzymes and performing a liver biopsy. Liver biopsy remains the gold standard method of detection, but the procedure is invasive and an unreliable diagnostic tool. Non-invasive, specific and sensitive diagnostic solutions such as biomarkers are therefore needed for the early detection of steatosis. Our aim is to identify changes in urinary metabolites in tetracycline-induced hepatic steatotic rats at different stages of the diseases using metabolomic-based techniques. Sprague Dawley male rats are treated by intraperitoneal injection (I.P.) with either 62.5 mg kg-1 or 125 mg kg-1 tetracycline, an antibiotic previously known to induce steatosis. We analyse the metabolic profile of the urinary tetracycline induced hepatic steatotic rats using 1H nuclear magnetic resonance (NMR), 2D 1H-1H TOCSY (total correlation spectroscopy) and electrospray liquid chromatography-mass spectrometry (ESI-LC-MS/MS) based metabolomics. The combined analysis of haematoxylin & eosin (H&E), oil red O (ORO) and direct measurement of triglyceride content in the liver tissues of the control samples against 125 mg kg-1 and 62.5 mg kg-1 treated samples, reveals that 125 mg kg-1 tetracycline exposure potentially induces steatosis. The combination of 1H NMR, 2D 1H-1H TOCSY and ESI-LC-MS/MS alongside multivariate statistical analysis, detected a total of 6 urinary metabolites changes, across 6 metabolic pathways. Furthermore, lysine concentration correlates with liver damage as tetracycline dose concentration increases, whilst both H&E and ORO fail to detect hepatocellular damage at the lowest dose concentration. We conclude that the combination of 1H NMR and ESI-LC-MS/MS suggests that these are suitable platforms for studying the pathogenesis of steatosis development, prior to morphological alterations observed in staining techniques and offer a more detailed description of the severity of the steatotic disease.
| S-EPMC9057704 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a major liver tumor (~80%), besides hepatoblastomas, angiosarcomas, and cholangiocarcinomas. In this study, we used a systems biology approach to construct protein-protein interaction networks (PPINs) for early-stage and late-stage liver cancer. By comparing the networks of these two stages, we found that the two networks showed some common mechanisms and some significantly different mechanisms. To obtain differential network structures between cancer and noncancer PPINs, we constructed cancer PPIN and noncancer PPIN network structures for the two stages of liver cancer by systems biology method using NGS data from cancer cells and adjacent noncancer cells. Using carcinogenesis relevance values (CRVs), we identified 43 and 80 significant proteins and their PPINs (network markers) for early-stage and late-stage liver cancer. To investigate the evolution of network biomarkers in the carcinogenesis process, a primary pathway analysis showed that common pathways of the early and late stages were those related to ordinary cancer mechanisms. A pathway specific to the early stage was the mismatch repair pathway, while pathways specific to the late stage were the spliceosome pathway, lysine degradation pathway, and progesterone-mediated oocyte maturation pathway. This study provides a new direction for cancer-targeted therapies at different stages.
| S-EPMC4558430 | biostudies-literature