scholarly journals Expression of Inflammation-Related Genes Is Altered in Gastric Tissue of Patients with Advanced Stages of NAFLD

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Rohini Mehta ◽  
Aybike Birerdinc ◽  
Arpan Neupane ◽  
Amirhossein Shamsaddini ◽  
Arian Afendy ◽  
...  

Obesity is associated with chronic low-grade inflammation perpetuated by visceral adipose. Other organs, particularly stomach and intestine, may also overproduce proinflammatory molecules. We examined the gene expression patterns in gastric tissue of morbidly obese patients with nonalcoholic fatty liver disease (NAFLD) and compared the changes in gene expression in different histological forms of NAFLD. Stomach tissue samples from 20 morbidly obese NAFLD patients who were undergoing sleeve gastrectomy were profiled using qPCR for 84 genes encoding inflammatory cytokines, chemokines, their receptors, and other components of inflammatory cascades. Interleukin 8 receptor-beta (IL8RB) gene overexpression in gastric tissue was correlated with the presence of hepatic steatosis, hepatic fibrosis, and histologic diagnosis of nonalcoholic steatohepatitis (NASH). Expression levels of soluble interleukin 1 receptor antagonist (IL1RN) were correlated with the presence of NASH and hepatic fibrosis. mRNA levels of interleukin 8 (IL8), chemokine (C-C motif) ligand 4 (CCL4), and its receptor chemokine (C-C motif) receptor type 5 (CCR5) showed a significant increase in patients with advanced hepatic inflammation and were correlated with the severity of the hepatic inflammation. The results of our study suggest that changes in expression patterns for inflammatory molecule encoding genes within gastric tissue may contribute to the pathogenesis of obesity-related NAFLD.

2004 ◽  
Vol 16 (8) ◽  
pp. 763 ◽  
Author(s):  
Han-Seung Kang ◽  
Chae-Kwan Lee ◽  
Ju-Ran Kim ◽  
Seong-Jin Yu ◽  
Sung-Goo Kang ◽  
...  

In the present study, differential gene expression in the uteri of ovariectomised (OVX) and pro-oestrous rats (OVX v. pro-oestrus pair) was investigated using cDNA expression array analysis. Differential uterine gene expression in OVX rats and progesterone (P4)-injected OVX rats (OVX v. OVX + P4 pair) was also examined. The uterine gene expression profiles of these two sets of animals were also compared for the effects of P4 treatment. RNA samples were extracted from uterine tissues and reverse transcribed in the presence of [α32P]-dATP. Membrane sets of rat arrays were hybridised with cDNA probe sets. Northern blot analysis was used to validate the relative gene expression patterns obtained from the cDNA array. Of the 1176 cDNAs examined, 23 genes showed significant (>two-fold) changes in expression in the OVX v. pro-oestrus pair. Twenty of these genes were upregulated during pro-oestrus compared with their expression in the OVX rat uterus. In the OVX v. OVX + P4 pair, 22 genes showed significant (>two-fold) changes in gene expression. Twenty of these genes were upregulated in the OVX + P4 animals. The genes for nuclear factor I–XI, afadin, neuroligin 2, semaphorin Z, calpain 4, cyclase-associated protein homologue, thymosin β-4X and p8 were significantly upregulated in the uteri of the pro-oestrus and OVX + P4 rats of both experimental pairs compared with the OVX rat uteri. These genes appear to be under the control of P4. One of the most interesting findings of the present study is the unexpected and marked expression of the neuroligin 2 gene in the rat uterus. This gene is expressed at high levels in the central nervous system and acts as a nerve cell adhesion factor. According to Northern blot analysis, neuroligin 2 gene expression was higher during the pro-oestrus and metoestrus stages than during the oestrus and dioestrus stages of the oestrous cycle. In addition, neuroligin 2 mRNA levels were increased by both 17β-oestradiol (E2) and P4, although P4 administration upregulated gene expression to a greater extent than injection of E2. These results indicate that neuroligin 2 gene expression in the rat uterus is under the control of both E2 and P4, which are secreted periodically during the oestrous cycle.


2021 ◽  
Author(s):  
Graham L. Cromar ◽  
Jonathan Epp ◽  
Ana Popovic ◽  
Yusing Gu ◽  
Violet Ha ◽  
...  

ABSTRACTToxoplasma gondii is a single celled parasite thought to infect 1 in 3 worldwide. During chronic infection, T. gondii can migrate to the brain where it promotes low-grade neuroinflammation with the capacity to induce changes in brain morphology and behavior. Consequently, infection with T. gondii has been linked with a number of neurocognitive disorders including schizophrenia (SZ), dementia, and Parkinson’s disease. Beyond neuroinflammation, infection with T. gondii can modulate the production of neurotransmitters, such as dopamine. To further dissect these pathways and examine the impact of altered dopaminergic sensitivity in T. gondii-infected mice on both behavior and gene expression, we developed a novel mouse model, based on stimulant-induced (cocaine) hyperactivity. Employing this model, we found that infection with T. gondii did not alter fear behavior but did impact motor activity and neuropsychiatric-related behaviurs. While both behaviors may help reduce predator avoidance, consistent with previous studies, the latter finding is reminiscent of neurocognitive disorders. Applying RNASeq to two relevant brain regions, striatum and hippocampus, we identified a broad upregulation of immune responses. However, we also noted significant associations with more meaningful neurologically relevant terms were masked due to the sheer number of terms incorporated in multiple testing correction. We therefore performed a more focused analysis using a curated set of neurologically relevant terms revealing significant associations across multiple pathways. We also found that T. gondii and cocaine treatments impacted the expression of similar functional pathways in the hippocampus and striatum although, as indicated by the low overlap among differentially expressed genes, largely via different proteins. Furthermore, while most differentially expressed genes reacted to a single condition and were mostly upregulated, we identified gene expression patterns indicating unexpected interactions between T. gondii infection and cocaine exposure. These include sets of genes which responded to cocaine exposure but not upon cocaine exposure in the context of T. gondii infection, suggestive of a neuroprotective effect advantageous to parasite persistence. Given its ability to uncover such complex relationships, we propose this novel model offers a new perspective to dissect the molecular pathways by which T. gondii infection contributes to neuropsychiatric disorders such as schizophrenia.


Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 462 ◽  
Author(s):  
George Ramirez ◽  
Jaime Palomino ◽  
Karla Aspee ◽  
Monica De los Reyes

The competence to undergo expansion is a characteristic of cumulus cells (CCs). The aim was to investigate the expression of GDF-9 and BMP-15 mRNA in canine cumulus cells in relation to cumulus expansion and meiotic development over the estrous cycle. CCs were recovered from nonmatured and in vitro-matured (IVM) dog cumulus oocyte complexes (COCs), which were obtained from antral follicles at different phases of the estrous cycle. Quantitative real-time polymerase chain reaction (q-PCR) was used to evaluate the relative abundance of GDF-9 and BMP-15 transcripts from the CCs with or without signs of expansion. The results were evaluated by ANOVA and logistic regression. The maturity of the oocyte and the expansion process affected the mRNA levels in CCs. There were differences (p < 0.05) in GDF-9 and BMP-15 gene expression in CCs isolated from nonmatured COCs when comparing the reproductive phases. Lower mRNA levels (p < 0.05) were observed in anestrus and proestrus in comparison to those in estrus and diestrus. In contrast, when comparing GDF-9 mRNA levels in IVM COCs, no differences were found among the phases of the estrous cycle in expanded and nonexpanded CCs (p < 0.05). However, the highest (p < 0.05) BMP-15 gene expression in CCs that did not undergo expansion was exhibited in anestrus and the lowest (p < 0.05) expression was observed in estrus in expanded CCs. Although the stage of the estrous cycle did not affect the second metaphase (MII )rates, the expanded CCs obtained at estrus coexisted with higher percentages of MII (p < 0.05). In conclusion, the differential expression patterns of GDF-9 and BMP-15 mRNA transcripts might be related to cumulus expansion and maturation processes, suggesting specific regulation and temporal changes in their expression.


Blood ◽  
1992 ◽  
Vol 80 (8) ◽  
pp. 1880-1884 ◽  
Author(s):  
G Magrinat ◽  
SN Mason ◽  
PJ Shami ◽  
JB Weinberg

Abstract Nitric oxide (NO) functions as an intercellular messenger molecule in such varied contexts as neurotransmission, immune regulation, and the control of vascular tone. We report that NO, delivered as purified gas or released from the pharmacologic NO donors sodium nitroprusside or 6- morpholino-sydnonimine, caused monocytic differentiation of cells of the human myeloid leukemia cell line HL-60 and altered gene expression. The treated cells stopped proliferating, became spread and vacuolated, had increased expression of nonspecific esterase and the monocyte marker CD14, and displayed increased capacity to produce hydrogen peroxide. Furthermore, these treated cells had increased steady-state expression of messenger RNA (mRNA) for tumor necrosis factor-alpha (TNF- alpha) and interleukin-1 beta (IL-1 beta), but decreased expression of mRNA for the proto-oncogenes c-myc and c-myb. The increase in TNF-alpha and IL-1 beta mRNA levels was due (at least in part) to a new transcription of these specific mRNAs. NO elaborated in the bone marrow microenvironment may have a role in normal and malignant hematopoietic cell growth and differentiation.


2017 ◽  
Vol 313 (2) ◽  
pp. E107-E120 ◽  
Author(s):  
Mathilde Guerville ◽  
Anaïs Leroy ◽  
Annaëlle Sinquin ◽  
Fabienne Laugerette ◽  
Marie-Caroline Michalski ◽  
...  

Obesity and its related disorders have been associated with the presence in the blood of gut bacteria-derived lipopolysaccharides (LPS). However, the factors underlying this low-grade elevation in plasma LPS, so-called metabolic endotoxemia, are not fully elucidated. We aimed to investigate the effects of Western diet (WD) feeding on intestinal and hepatic LPS handling mechanisms in a rat model of diet-induced obesity (DIO). Rats were fed either a standard chow diet (C) or a Western Diet (WD, 45% fat) for 6 wk. They were either fed ad libitum or pair-fed to match the caloric intake of C rats for the first week, then fed ad libitum for the remaining 5 wk. Six-week WD feeding led to a mild obese phenotype with increased adiposity and elevated serum LPS-binding protein (LBP) levels relative to C rats, irrespective of initial energy intake. Serum LPS was not different between dietary groups but exhibited strong variability. Disrupted ileal mucus secretion and decreased ileal Reg3-γ and -β gene expression along with high ileal permeability to LPS were observed in WD compared with C-fed rats. Ileal and cecal intestinal alkaline phosphatase (IAP) activity as well as Verrucomicrobia and Bifidobacterium cecal levels were increased in WD-fed rats compared with C-fed rats. WD consumption did not impact mRNA levels of LPS-handling hepatic enzymes. Correlation analysis revealed that ileal passage of LPS, IAP activity, Proteobacteria levels and hepatic aoah gene expression correlated with serum LPS and LBP, suggesting that ileal mucosal defense impairment induced by WD feeding contribute to metabolic endotoxemia.


2020 ◽  
Vol 9 (5) ◽  
pp. 1276
Author(s):  
Pedro Martínez-Paz ◽  
Marta Aragón-Camino ◽  
Esther Gómez-Sánchez ◽  
Mario Lorenzo-López ◽  
Estefanía Gómez-Pesquera ◽  
...  

Nowadays, mortality rates in intensive care units are the highest of all hospital units. However, there is not a reliable prognostic system to predict the likelihood of death in patients with postsurgical shock. Thus, the aim of the present work is to obtain a gene expression signature to distinguish the low and high risk of death in postsurgical shock patients. In this sense, mRNA levels were evaluated by microarray on a discovery cohort to select the most differentially expressed genes between surviving and non-surviving groups 30 days after the operation. Selected genes were evaluated by quantitative real-time polymerase chain reaction (qPCR) in a validation cohort to validate the reliability of data. A receiver-operating characteristic analysis with the area under the curve was performed to quantify the sensitivity and specificity for gene expression levels, which were compared with predictions by established risk scales, such as acute physiology and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA). IL1R2, CD177, RETN, and OLFM4 genes were upregulated in the non-surviving group of the discovery cohort, and their predictive power was confirmed in the validation cohort. This work offers new biomarkers based on transcriptional patterns to classify the postsurgical shock patients according to low and high risk of death. The results present more accuracy than other mortality risk scores.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 383-383
Author(s):  
Martin K. H. Maus ◽  
Craig Stephens ◽  
Stephanie H. Astrow ◽  
Peter Philipp Grimminger ◽  
Dongyun Yang ◽  
...  

383 Background: Gene expression levels of ERCC1, TS, EGFR and VEGFR2 may have predictive value for the personalized use of standard chemotherapeutics as well as agents targeting the EGFR and VEGF pathways and the efficacy of EGFR directed monoclonal antibodies like panitumumab and cetuximab has been confirmed to be dependent on wt KRAS and wt BRAF in patients with advanced colorectal cancer. We investigated the correlations between KRAS/BRAF mutational status and the mRNA expression levels of these genes. Methods: Formalin-fixed paraffin-embedded tumor specimens from 600 patients with advanced colorectal adenocarcinoma were microdissected and DNA and RNA was extracted. Specifically designed primers and probes were used to detect 7 different base substitutions in codon 12 and 13 of KRAS, V600E mutations in BRAF and the expression levels of ERCC1, TS, EGFR and VEGFR2 by RT-PCR. Results: Mt KRAS tumors had significantly lower TS and EGFR gene expression levels compared with wt KRAS (p<0,001), whereas mt BRAF tumors showed significantly increased TS and EGFR mRNA levels compared to wt BRAF (p<0,001). Mt BRAF tumors showed significantly higher mRNA levels than mt KRAS tumors (p<0,001). ERCC1 and VEGFR2 mRNA levels were significantly down-regulated in mt KRAS specimen (p<0,001), but showed no significant correlation with BRAF mutational status. Conclusions: KRAS and BRAF mutations are associated with opposite mRNA expression levels for TS and EGFR. Recently, resistance to BRAF inhibition in mt BRAF colorectal tumors has been shown in preclinical models to be associated with up-regulation of EGFR. Our data suggests that BRAF mutants are associated with high EGFR levels at the time of diagnosis, and not necessarily part of an acquired mechanism of resistance. Significantly lower mRNA expression levels of VEGFR2 in mt KRAS tumors may explain lower response to angiogenesis inhibition seen in the TML study.


2011 ◽  
Vol 6 ◽  
pp. BMI.S6487 ◽  
Author(s):  
ZhongFa Zhang ◽  
See-Tong Pang ◽  
Katherine A. Kasper ◽  
Chunyan Luan ◽  
Bill Wondergem ◽  
...  

Objective Urothelial carcinoma (UC) of the kidney is a relatively rare but aggressive form of kidney cancer. Differential diagnosis of renal UC from renal cell carcinoma (RCC) can be difficult, but is critical for correct patient management. We aimed to use global gene expression profiling to identify genes specifically expressed in urothelial carcinoma (UC) of the kidney, with purpose of finding new biomarkers for differential diagnosis of UC of both upper and lower tract from normal tissues. Materials and Methods Microarray gene expression profiling was performed on a variety of human kidney tumor samples, including clear cell, papillary, chromophobe, oncocytoma, renal UC and normal kidney controls. Differentially expressed mRNAs in various kidney tumor subtypes were thus identified. Protein expression in human UC tumor samples from both upper and lower urinary tract was evaluated by immunohistochemistry. Results FXYD3 (MAT-8) mRNA was specifically expressed in UC of the kidney and not in normal kidney tissue or in any RCC tumor subtypes. FXYD3 mRNA levels displayed equal or better prediction rate for the detection of renal UC than the mRNA levels of selected known UC markers as p63, vimentin, S100P, KRT20 and KRT7. Finally, immunohistochemical staining of clinical UC samples showed that FXYD3 protein is overexpressed in majority of UC of the upper genitourinary tract (encompassing the kidney, ~90%) and in majority of high grade bladder UC (~84%, it's < 40% in low grade tumors, P < 0.001) compared to normal kidney and bladder tissues. Conclusion FXYD3 may be a promising novel biomarker for the differential diagnosis of renal UC and a promising prognosis marker of UC from bladder. Because it was identified genome-widely, FXYD3 may have important biological ramifications for the genetic study of UC.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 303-303
Author(s):  
Mikayla Chen ◽  
Neil Shay

Abstract Objectives Watermelon is a nutrient-dense fruit known to contain high levels or arginine and citrulline; these two compounds may influence the nitric oxide pathway, vasodilation, and thus be hypotensive. We tested the hypothesis that when C57BL/6J male mice fed a high-fat diet (HF) had additions to the HF diet of either watermelon flesh (WF), arginine (ARG) or citrulline (CIT), changes in gene expression patterns would occur vs. those seen in HF. Further, we hypothesize that patterns of expression seen in WF, ARG, and CIT groups would be somewhat similar based on increased dietary levels of ARG and CIT in all three groups. Methods Following prior work (Becraft et al.; 2018, Egea et al. 2020), groups of mice were provided either a low-fat diet (LF, 10% kcal fat), high-fat diet (HF, 45% kcal fat), HF plus Watermelon Flesh (WF), HF plus 1% (w/w) arginine (ARG) or 1% (w/w citrulline (CIT) for 10 weeks. Watermelon flesh was provided at 10% of total energy. After ten weeks, animals were euthanized, and liver total RNA was isolated using Trizol. Total RNA was then used for gene expression analysis (N = 4 per group) using Clariom S microarrays and TAC analysis software (ThermoFisher). Results Mice fed WF, ARG, and CIT had several shared canonical pathways of gene expression, including eicosanoid metabolism via cytochrome P450 monooxygenases and exercise-induced circadian rhythm (All P &lt; 0.05). Intake of WF and ARG significantly up-regulated both Cyp2c9 and Cyp2c38 mRNA levels (P &lt; 0.05). The Bst2 gene was significantly down-regulated in all three groups compared to HF mice (P &lt; 0.05). The Cyp2b9 gene was upregulated ∼10.7 fold in WF, and &gt; 1000-fold in ARG mice (P &lt; 0.05). Conclusions We demonstrated that when added to a HF diet, WF, ARG, and CIT all produced a change in hepatic gene expression in male mice. Possibly due to the close relationship of ARG and CIT metabolism, and high content of ARG and CIT in WF, expression patterns observed in all three groups demonstrated a high degree of similarity. Several genes, including Cyp2c9, Cyp2c38, and Elvol5 were up-regulated; these genes may be involved in modifying steroids and arachidonic acid and other long-chain fatty acids. Funding Sources National Watermelon Promotion Board.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sofie Ahlin ◽  
Consuelo Cefalo ◽  
Isabel Bondia-Pons ◽  
Kajetan Trošt ◽  
Esmeralda Capristo ◽  
...  

AimsTo test the hypothesis that adipose tissue gene expression patterns would be affected by metabolic surgery and we aimed to identify genes and metabolic pathways as well as metabolites correlating with metabolic changes following metabolic surgery.Materials and MethodsThis observational study was conducted at the Obesity Unit at the Catholic University Hospital of the Sacred Heart in Rome, Italy. Fifteen patients, of which six patients underwent Roux-en-Y gastric bypass and nine patients underwent biliopancreatic diversion, were included. The participants underwent an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Small polar metabolites were analyzed with a two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS). Gene expression analysis of genes related to metabolism of amino acids and fatty acids were analyzed in subcutaneous adipose tissue. All procedures were performed at study start and at follow-up (after 185.3 ± 72.9 days).ResultsTwelve metabolites were significantly changed after metabolic surgery. Six metabolites were identified as 3-indoleacetic acid, 2-hydroxybutyric acid, valine, glutamic acid, 4-hydroxybenzeneacetic acid and alpha-tocopherol. The branched chain amino acids displayed a significant decrease together with a decrease in BCAT1 adipose tissue mRNA levels. Changes in the identified metabolites were associated to changes in lipid, insulin and glucose levels.ConclusionsOur study has identified metabolites and metabolic pathways that are altered by metabolic surgery and may be used as biomarkers for metabolic improvement.


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