scholarly journals P144 Clock gene expression levels inversely correlate with disease activity in ulcerative colitis and Crohn’s disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S228-S228
Author(s):  
Y Weintraub ◽  
S Cohen ◽  
N Chapnik ◽  
A Anafy ◽  
A Yerushalmy-Feler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Disease Activity ◽  
Clock Gene ◽  
Clock Genes ◽  
Clinical Status ◽  
Expression Levels ◽  
Clock Gene Expression ◽  
Gene Expression Levels

Abstract Background Pathophysiological mechanisms active in inflammatory bowel disease (IBD), such as mucosal barrier repair, innate and adaptive immune responses, intestinal motility and gut microbiome, all exhibit diurnal variations. Chronic disruption of the molecular clock augment inflammatory response. We have shown that newly diagnosed, naïve to treatment, young IBD patients showed reduced clock gene expression in both inflamed and non-inflamed intestinal tissues and in peripheral White Blood Cells (WBC). This reduction correlated with disease activity. Our aim in this study was to determine whether certain clock genes correlate with disease activity scores or inflammatory markers in Crohn’s disease (CD) vs. ulcerative colitis (UC). Methods 17 patients with CD and 13 with UC, 8–22 years old, were recruited. Patients were evaluated upon diagnosis and during medical treatment. Disease activity scores, C-reactive protein (CRP) and fecal calprotectin (Fcal) levels were measured and WBC were analysed for clock gene (CLOCK, BMAL1, CRY1, CRY2, PER1 and PER2) expression. Clock gene expression levels were correlated to disease activity scores (clinically active vs. remission), CRP levels (<5 mg/l vs. >5 mg/l) and Fcal levels (< 250 μg/mg vs. >250 μg/mg) in CD (21 samples) and UC (20 samples). Results In UC, BMAL (p<0.008), CLOCK (p<0.02), CRY1 (p<0.002), CRY2 (p<0.0009), PER1 (p<0.003) and PER2 (p<0.003) showed decreased expression when Fcal levels were > 250 μg/mg. When compared with the clinical status and CRP levels, only BMAL1 showed reduced expression (p<0.003 and p<0.001, respectively). In CD, clinical status correlated with clock gene expression: CLOCK (p<0.035), PER1 (p<0.001) and CRY1 (p<0.028) were reduced in active disease. CRP and Fcal did not correlate with clock gene expression. Conclusion Altered levels of certain clock genes were demonstrated in young CD and UC patients in exacerbation vs. remission. In UC, Fcal levels inversely correlated with all major circadian genes and partially with clinical status and CRP levels. In CD patients clock gene expression inversely correlated with clinical status.

scholarly journals P124 Clock gene expression levels can differentially distinguish between ulcerative colitis and Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S198-S200
Author(s):  
Y Weintraub ◽  
S Cohen ◽  
N Chapnik ◽  
A Yerushalmy-Feler ◽  
A Ben-Tov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Disease Activity ◽  
Clock Gene ◽  
Clock Genes ◽  
Clinical Status ◽  
Expression Levels ◽  
Clock Gene Expression ◽  
Gene Expression Levels

Abstract Background Pathophysiological mechanisms active in inflammatory bowel disease (IBD), such as mucosal barrier repair, innate and adaptive immune responses, intestinal motility and gut microbiome, all exhibit diurnal variations. Chronic disruption of the molecular clock augments inflammatory response. We have shown that newly diagnosed, naïve to treatment, young IBD patients showed reduced clock gene expression in both inflamed and non-inflamed intestinal tissues and in peripheral White blood cells (WBCs). This reduction correlated with disease activity1. Our aim in the current study was to determine whether certain clock genes correlate with disease activity scores or inflammatory markers in Crohn’s disease (CD) vs. ulcerative colitis (UC). Methods Fourteen CD and 11 UC patients, 8–22 years old, were recruited. Patients were evaluated upon diagnosis and during medical treatment. Disease activity scores, C-reactive protein (CRP) and faecal calprotectin (Fcal) levels were measured and WBC were analysed for clock gene (CLOCK, BMAL1, CRY1, CRY2, PER1 and PER2) expression. Clock gene expression levels were correlated to disease activity scores (clinically active vs. remission), CRP levels (<5 mg/l vs. >5 mg/l) and Fcal levels (<250 μg/mg vs. >250 μg/mg) in CD (21 samples) and UC patients (20 samples). Results In UC, CLOCK (p < 0.025), CRY1 (p < 0.033) and PER1 (p < 0.038) showed decreased expression when Fcal levels were >>250 μg/mg. When compared with the clinical status only BMAL1 showed reduced expression (p < 0.019). CRP levels showed no correlation with clock gene expression. In CD, CRP as well as the clinical status correlated with clock gene expression. Whereas CLOCK was reduced (p < 0.019), PER2 was induced (p < 0.005) when CRP levels were >5 mg/dl. Furthermore, CLOCK (p < 0.0005), PER1 (0.017) and PER2 (0.044) were reduced in CD patients with an active disease. However, Fcal did not correlate with clock gene expression. Conclusion Altered levels of certain clock genes were demonstrated in young CD and UC patients in relapse vs. remission and correlated with Fcal in UC patients and clinical status as well as CRP levels in CD patients. Reference

scholarly journals Su1111 CLOCK GENE EXPRESSION LEVELS CAN DISTINGUISH BETWEEN ULCERATIVE COLITIS AND CROHN'S DISEASE

2020 ◽  
Vol 158 (6) ◽  
pp. S-511-S-512
Author(s):  
Yael Weintraub ◽  
Shlomi Cohen ◽  
Nava Chapnik ◽  
Anat Yerushalmy-Feler ◽  
Amir Ben Tov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clock Gene ◽  
Expression Levels ◽  
Clock Gene Expression ◽  
Gene Expression Levels

scholarly journals Clock gene expression is altered in veterans with sleep apnea

2019 ◽  
Vol 51 (3) ◽  
pp. 77-82 ◽  
Author(s):  
Muna T. Canales ◽  
Meaghan Holzworth ◽  
Shahab Bozorgmehri ◽  
Areef Ishani ◽  
I. David Weiner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sleep Apnea ◽  
Clock Gene ◽  
Clock Genes ◽  
Apnea Hypopnea Index ◽  
Blood Collection ◽  
Cross Sectional ◽  
Sleep Complaints ◽  
Clock Gene Expression ◽  
Metabolic Outcomes

Clock gene dysregulation has been shown to underlie various sleep disorders and may lead to negative cardio-metabolic outcomes. However, the association between sleep apnea (SA) and core clock gene expression is unclear. We performed a cross-sectional analysis of 49 Veterans enrolled in a study of SA outcomes in veterans with chronic kidney disease, not selected for SA or sleep complaints. All participants underwent full polysomnography and next morning whole blood collection for clock gene expression. We defined SA as an apnea-hypopnea index ≥15 events/h; nocturnal hypoxemia(NH) was defined as ≥10% of total sleep time spent at <90% oxygen saturation. We used quantitative real-time PCR to compare the relative gene expression of clock genes between those with and without SA or NH. Clock genes studied were Bmal1, Ck1δ, Ck1ε, Clock, Cry1, Cry2, NPAS2, Per1, Per2, Per3, Rev-Erb-α, RORα, and Timeless. Our cohort was 90% male, mean age was 71 yr (SD 11), mean body mass index was 30 kg/m2 (SD 5); 41% had SA, and 27% had NH. Compared with those without SA, Per3 expression was reduced by 35% in SA ( P = 0.027). Compared with those without NH, NPAS2, Per1, and Rev-Erb-α expression was reduced in NH (50.4%, P = 0.027; 28.7%, P = 0.014; 31%, P = 0.040, respectively). There was no statistical difference in expression of the remaining clock genes by SA or NH status. Our findings suggest that SA or related NH and clock gene expression may be interrelated. Future study of 24 h clock gene expression in SA is needed to establish the role of clock gene regulation on the pathway between SA and cardio-metabolic outcomes.

scholarly journals Differential Expression of Circadian Clock Genes in the Bovine Neuroendocrine Adrenal System

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A66-A67
Author(s):  
Audrey L Earnhardt ◽  
David G Riley ◽  
Noushin Ghaffari ◽  
Penny K Riggs ◽  
Charles R Long ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Clock Gene ◽  
Target Genes ◽  
Clock Genes ◽  
Expression Profiles ◽  
Primary Objective ◽  
Clock Gene Expression ◽  
Adrenal System ◽  
Circadian Clock Genes

Abstract The primary objective of this investigation was to determine whether circadian clock genes were differentially expressed within or among bovine hypothalamic paraventricular nucleus (PVN), anterior pituitary gland (AP), adrenocortical (AC) and adrenomedullary (AM) tissues. The PVN, AP, AC, and AM were isolated from 5-yr-old Brahman cows (n = 8) harvested humanely at an abattoir between 0800-1100 h. Expression of target genes in each sample was evaluated via RNA-sequencing analyses. Gene counts were normalized using the trimmed mean of M values (TMM) method in the edgeR Package from Bioconductor, R. The normalized gene counts of genes important for circadian rhythm were statistically analyzed using the GLM Procedure of SAS. The genes analyzed were circadian locomotor output cycles protein kaput (CLOCK), cryptochrome circadian regulator 1 and 2 (CRY1 and CRY2), aryl hydrocarbon receptor nuclear translocator like (ARNTL), period circadian regulator 1 and 2 (PER1 and PER2), neuronal PAS domain protein 2 (NPAS2), and nuclear receptor subfamily 1 group D member 1 (NR1D1). Overall, relative expression profiles of clock genes differed (P &lt; 0.01) within each tissue with PER1 having greater expression in all tissues (P &lt; 0.01). Within the PVN expression of CLOCK, CRY1, ARNTL, and PER2 was less than that of CRY2, NPAS2, and NR1D1 (P &lt; 0.01). In the AP, with the exception of PER1, no other clock gene differed in degree of expression. In the AC, expression of CLOCK and NPAS2 was greater than CRY1, ARNTL, PER2, and NR1D1 (P &lt; 0.05), whereas CRY2 expression exceeded only CRY1 (P &lt; 0.05). Within the AM, CLOCK and CRY2 expression was greater than CRY1 and ARNTL (P &lt; 0.05). Overall, clock gene expression among tissues differed (P &lt; 0.01) for each individual clock gene. The AC and AM had similar clock gene expression, except expression of CRY2 and PER2 was greater in AM (P &lt; 0.05). The AC and AM had greater expression of CLOCK than the PVN and AP (P &lt; 0.01), with PVN having greater expression than AP (P &lt; 0.01). The AP had greater expression of NPAS2, followed by PVN, with the least expression in the AC and AM (P &lt; 0.01). Both PVN and AP had greater CRY1 and NR1D1 expression than AC or AM (P &lt; 0.01). The AP had greater PER1 expression than PVN, AC, and AM (P &lt; 0.01), whereas PVN, AC, and AM had greater ARNTL expression than AP (P &lt; 0.05). Both AP and AM had greater expression of PER2 than PVN or AC (P &lt; 0.01). The PVN had greater expression of CRY2 than the AP, AC, and AM (P &lt; 0.01). These results indicated that within each tissue the various clock genes were expressed in different quantities. Also, the clock genes were expressed differentially among the tissues of the bovine neuroendocrine adrenal system. Temporal relationships of these genes with the primary endocrine products of these tissues should be investigated to define the roles of peripheral clock genes in regulation of metabolism and health.

scholarly journals Molecular Signature of Persistent Histological Inflammation in Ulcerative Colitis with Mucosal Healing

2020 ◽  
Vol 29 (2) ◽  
pp. 159-166
Author(s):  
Mircea Manuc ◽  
Elena Mirela Ionescu ◽  
Elena Milanesi ◽  
Maria Dobre ◽  
Ioana Tieranu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Pearson Correlation ◽  
Mucosal Healing ◽  
Formyl Peptide Receptor ◽  
Molecular Signature ◽  
Expression Levels ◽  
Endoscopic Remission ◽  
Formyl Peptide ◽  
Gene Expression Levels

Background and Aims: Therapeutic targets in ulcerative colitis (UC) have evolved over time from clinical remission to biological and endoscopic remission. Histologic remission remains a debatable outcome due to lack of data regarding its impact on long-term evolution. The development of histologic activity scores has brought standardization. We aimed to identify mucosal markers differentiating histological inflammation from histological remission in UC patients. Methods: The gene expression levels of 84 genes associated with inflammatory bowel diseases have been analyzed in 43 colonic mucosa samples from 30 patients with UC. The gene expression levels have been correlated with histological inflammation score of Geboes. Patients with endoscopic remission were divided by histological activity into two groups and molecular results were compared in order to identify differences in the mucosal gene expression. Results: We found a significant Pearson correlation (p<0.001 and r>0.5) between the Geboes score and the expression of 29 genes, whereas negative correlation (p<0.001 and r<-0.50) was observed with two genes in the entire UC cohort. In the subgroup of patients with endoscopic remission three transcripts: formyl-peptide receptor 1 (FPR1), matrix metalloproteinases 1 (MMP1) and mucine 1 (MUC1) were significantly up-regulated in patients with histological inflammation compared to patients with histologic remission. Conclusion: Our study further emphasizes the importance of histological assessment when endoscopic mucosal healing is present, as FPR1, MMP-1 and MUC1 were all significantly upregulated in patients with histological alterations.

scholarly journals Rhythms during the polar night: evidence of clock-gene oscillations in the Arctic scallop Chlamys islandica

2020 ◽  
Vol 287 (1933) ◽  
pp. 20201001
Author(s):  
Mickael Perrigault ◽  
Hector Andrade ◽  
Laure Bellec ◽  
Carl Ballantine ◽  
Lionel Camus ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clock Gene ◽  
Clock Genes ◽  
Biological Rhythms ◽  
The Arctic ◽  
Polar Night ◽  
Clock Gene Expression ◽  
Chlamys Islandica ◽  
Autumnal Equinox ◽  
Cyclic Variations

Arctic regions are highly impacted by climate change and are characterized by drastic seasonal changes in light intensity and duration with extended periods of permanent light or darkness. Organisms use cyclic variations in light to synchronize daily and seasonal biological rhythms to anticipate cyclic variations in the environment, to control phenology and to maintain fitness. In this study, we investigated the diel biological rhythms of the Arctic scallop, Chlamys islandica , during the autumnal equinox and polar night. Putative circadian clock genes and putative light perception genes were identified in the Arctic scallop. Clock gene expression oscillated in the three tissues studied (gills, muscle, mantle edge). The oscillation of some genes in some tissues shifted from daily to tidal periodicity between the equinox and polar night periods and was associated with valve behaviour. These results are the first evidence of the persistence of clock gene expression oscillations during the polar night and might suggest that functional clockwork could entrain rhythmic behaviours in polar environments.

Changes of the HSD17B10 Gene Expression Levels in Ulcerative Colitis

2013 ◽  
Vol 19 (2) ◽  
pp. E23-E24 ◽  
Author(s):  
Xue-Ying He ◽  
Yu-Xiao Yang ◽  
Song-Yu Yang
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Expression Levels ◽  
Gene Expression Levels
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