scholarly journals Reduced Colonic Mucosal Injury in 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Poly ADP-Ribose Polymerase (TIPARP/PARP7)-Deficient Mice

2022 ◽  
Vol 23 (2) ◽  
pp. 920
Author(s):  
David Hutin ◽  
Karoline Alvik Hagen ◽  
Peng Shao ◽  
Kim Sugamori ◽  
Denis M. Grant ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Body Weight Loss ◽  
Mucosal Injury ◽  
Type I ◽  
Lipocalin 2 ◽  
Cytochrome P450 1A1 ◽  
Microbial Composition ◽  
Aryl Hydrocarbon ◽  
Significant Difference ◽  
Chemokine Ligand

Poly-ADP-ribose polymerases (PARPs) are important regulators of the immune system, including TCDD-inducible poly-ADP-ribose polymerase (TIPARP), also known as poly-ADP-ribose polymerase 7 (PARP7). PARP7 negatively regulates aryl hydrocarbon receptor (AHR) and type I interferon (IFN-I) signaling, both of which have been implicated in intestinal homeostasis and immunity. Since the loss of PARP7 expression increases AHR and IFN-I signaling, we used a murine dextran sulfate sodium (DSS)-induced colitis model to investigate the effect of PARP7 loss on DSS-induced intestinal inflammation. DSS-exposed Parp7−/− mice had less body weight loss, lower disease index scores, and reduced expression of several inflammation genes, including interleukin IL-6, C-x-c motif chemokine ligand 1 (Cxcl1), and lipocalin-2, when compared with wild-type mice. However, no significant difference was observed between genotypes in the colonic expression of the AHR target gene cytochrome P450 1A1 (Cyp1a1). Moreover, no significant differences in microbial composition were observed between the genotypes. Our findings demonstrate that the absence of PARP7 protein results in an impaired immune response to colonic inflammation and suggests that PARP7 may participate in the recruitment of immune cells to the inflammation site, which may be due to its role in IFN-I signaling rather than AHR signaling.

scholarly journals A37 ENTERIC MICROBIOTA CONTRIBUTE TO BEHAVIORAL ALTERATIONS OBSERVED IN MICE WITH COLITIS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 44-45
Author(s):  
F Vicentini ◽  
L Griffin ◽  
C Keenan ◽  
J Cavin ◽  
K Nieves ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Body Weight Loss ◽  
Sickness Behavior ◽  
Behavioral Changes ◽  
Brain Inflammation ◽  
Anxiety And Depression ◽  
Lipocalin 2 ◽  
Microbial Composition ◽  
Fecal Microbiota Transplant ◽  
Brain Physiology

Abstract Background The enteric microbiota has been recognized as an essential regulator of both gut and brain physiology, a complex interaction generally termed the microbiota-gut-brain axis. Disturbances to gastrointestinal physiology lead to alterations in the composition of the enteric microbiota, whereas dysbiosis can also contribute to pathophysiology. Inflammatory bowel diseases (IBD) are chronic, relapsing inflammatory conditions of the gastrointestinal tract, associated with microbial dysbiosis. Interestingly, IBD patients exhibit an increased incidence of mental illness (i.e. anxiety and depression), often termed “sickness behavior”, even during the remitting phase of their disease. Nevertheless, it is unclear if alterations in the enteric microbiota associated with IBD are responsible for the observed modification in brain function and behavior. Here, we hypothesized that sickness behavior is driven by alterations in microbial composition, which occur in the context of intestinal inflammation. Aims We sought to determine whether transfer of the microbiota from colitic mice, exhibiting sickness behaviour, into healthy counterparts would induce behavioral changes. Methods Male mice (C57Bl/6J; 8 weeks old) were used in all experiments. Colitis was induced by administration of 2.5% dextran sodium sulfate (DSS) in the drinking water for 5 days. Colonic inflammation was assessed by measuring fecal lipocalin-2 and the expression of pro-inflammatory mediators via qPCR. Cecal matter from donor mice (control or DSS treated) were collected for fecal microbiota transplant (FMT). FMT was performed via oral gavage in antibiotic-treated recipient mice. Gut bacteria were evaluated by 16S rRNA sequencing in cecal samples. Anxiety- and depression-like behavior were assessed by elevated plus maze and tail suspension test, respectively. Results DSS-treated mice exhibited clinical disease, reflected by body weight loss, increased fecal lipocalin-2 and elevated colonic pro-inflammatory cytokine transcripts. An increase in anxiety-like behavior was observed in mice with colitis, although no alterations in depression-like behavior were detected. Colitic mice exhibited a unique microbial community. Transferring cecal material from colitic mice into recipient, antibiotic-treated mice, recapitulated alterations in behavior seen in colitic donors, as shown by increased anxiety-like behavior and unexpectedly, increased depression-like behavior. These behavioral changes occurred in the absence of colonic or brain inflammation in the recipient mice, but were associated with changes in stress-related gene expression (i.e. Crh). Conclusions Colitis-associated sickness behavior can be transmitted to antibiotic-treated recipient mice via FMT, which occurs in the absence of overt intestinal or brain inflammation. Funding Agencies CIHRNational Council for Scientific and Technological Development (CNPq-Brazil)

scholarly journals Aryl Hydrocarbon Receptor Activation Ameliorates Experimental Colitis by Modulating the Tolerogenic Dendritic and Regulatory T Cell Formation

2020 ◽  
Author(s):  
Xiufang Cui ◽  
Jiajia Li ◽  
Di Wang ◽  
Yan Yang ◽  
Chunhua Jiao ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cell ◽  
Aryl Hydrocarbon Receptor ◽  
Intestinal Inflammation ◽  
Experimental Colitis ◽  
Treg Cells ◽  
Receptor Activation ◽  
Surface Markers ◽  
Cytochrome P450 1A1 ◽  
Aryl Hydrocarbon

Abstract Background Intestinal immune dysfunction is involved in the onset of Crohn's disease (CD). The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor widely expressed in various immune cells, including DCs. Although AhR plays an important role in immune tolerance, its role in the DCs is unclear. The purpose of this study was to investigate whether the activation of AhR can induce tolerogenic DCs (tolDCs) and the differentiation of regulatory T (Treg) cells, as well as ameliorate experimental colitis. Methods Bone marrow derived DCs were incubated with or without FICZ(100 nM) which was a kind of AhR for 12 hours, subsequently the cells were stimulated to mature. Scanning electron microscope (SEM) was used to observe dendritic formation on DC surface. Proliferation of T lymphocytes was evaluated by proliferation experiment. The expression of surface markers in DCs were detected by flow cytometry and the gene expression levels of cytokines were measured using RT-qPCR. The levels of cytokines in cell supernatants were determined by ELISA. The expression of cytochrome P450 1A1(CYP1A1) and forkhead box P3 (Foxp3) were measured by Western blotting. TolDCs were transferred to murine colitis model and the intestinal inflammation were evaluated. T-helper (Th) 17 cells and Treg in spleens and mesenteric lymph nodes (MLNs) were analyzed by flow cytometry. Results AhR activation in the DCs resulted in a lower expression of surface markers such as CD80, CD83, CD86, and pro-inflammatory cytokine production, and higher anti-inflammatory production (IL-1β, IL-23, and IL-12) compared to the control DCs. The surface dendrites in DCs were significantly reduced following AhR activation by FICZ. Such DCs with FICZ-mediated activation of AhR, namely tolDCs, inhibited CD4+ T cell proliferation and promoted Treg cell differentiation. Adoptive transfer of tolDCs to a TNBS-induced colitis mouse model significantly alleviated the severity of inflammation by decreasing the frequency of Th17 cells and increasing the frequency of Treg cells. Conclusions Activation of AhR in the DCs could induce tolDCs, and the transplantation of tolDCs may help in relieving intestinal inflammation and maintaining the Th17/Treg differentiation balance. Thus, our data suggest that AhR may be a potential therapeutic target for CD.

scholarly journals Functional Anatomical Changes in Ulcerative Colitis Patients Determine Their Gut Microbiota Composition and Consequently the Possible Treatment Outcome

2020 ◽  
Vol 13 (11) ◽  
pp. 346
Author(s):  
Anita Bálint ◽  
Klaudia Farkas ◽  
Orsolya Méhi ◽  
Bálint Kintses ◽  
Bálint Márk Vásárhelyi ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Bacterial Community Composition ◽  
Hypervariable Region ◽  
Intestinal Microbiome ◽  
Total Proctocolectomy ◽  
Rrna Gene ◽  
Microbial Composition ◽  
Faecal Samples ◽  
Significant Difference ◽  
Distinct Separation

Gut microbial composition alters in some special situations, such as in ulcerative colits (UC) after total proctocolectomy and ileal pouch-anal anastomosis (IPAA) surgery. The aim of our study was to determine the composition of the intestinal microbiome in UC patients after IPAA surgery, compared with UC patients, familial adenomatous polyposis (FAP) patients after IPAA surgery and healthy controls. Clinical data of patients, blood and faecal samples were collected. Faecal microbiota structure was determined by sequencing the V4 hypervariable region of the 16S rRNA gene. Overall, 56 patients were enrolled. Compared to the Healthy group, both the Pouch active and UC active groups had higher Enterobacteriaceae, Enterococcaceae and Pasteurellaceae abundance. The Pouch and UC groups showed distinct separation based on their alpha and beta bacterial diversities. The UC group had higher Prevotellaceae, Rikenellaceae, Ruminococcaceae abundance compared to the Pouch active group. Pouch and FAP participants showed similar bacterial community composition. There was no significant difference in the bacterial abundance between the active and inactive subgroups of the Pouch or UC groups. Gut microbiome and anatomical status together construct a functional unit that has influence on diversity, in addition to intestinal inflammation that is a part of the pathomechanism in UC.

scholarly journals Diversity, Composition and Functional Inference of Gut Microbiota in Indian Cabbage white Pieris canidia (Lepidoptera: Pieridae)

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 254
Author(s):  
Ying Wang ◽  
Jianqing Zhu ◽  
Jie Fang ◽  
Li Shen ◽  
Shuojia Ma ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
16S Rrna Gene Sequencing ◽  
Adult Survival ◽  
Rrna Gene ◽  
Life Stages ◽  
Microbial Composition ◽  
Significant Difference ◽  
Functional Inference ◽  
Rrna Gene Sequencing ◽  
Insect Fitness

We characterized the gut microbial composition and relative abundance of gut bacteria in the larvae and adults of Pieris canidia by 16S rRNA gene sequencing. The gut microbiota structure was similar across the life stages and sexes. The comparative functional analysis on P. canidia bacterial communities with PICRUSt showed the enrichment of several pathways including those for energy metabolism, immune system, digestive system, xenobiotics biodegradation, transport, cell growth and death. The parameters often used as a proxy of insect fitness (development time, pupation rate, emergence rate, adult survival rate and weight of 5th instars larvae) showed a significant difference between treatment group and untreated group and point to potential fitness advantages with the gut microbiomes in P. canidia. These data provide an overall view of the bacterial community across the life stages and sexes in P. canidia.

scholarly journals Analysis of sagittal profile and radiographic parameters in symptomatic thoracolumbar disc herniation patients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ang Gao ◽  
Yongqiang Wang ◽  
Miao Yu ◽  
Xiaoguang Liu
Keyword(s):  
Disc Herniation ◽  
Thoracic Spine ◽  
Normal Population ◽  
Sagittal Profile ◽  
Sacral Slope ◽  
Type I ◽  
Type Ii ◽  
Radiographic Parameters ◽  
Significant Difference ◽  
Thoracolumbar Region

Abstract Background Few studies describe thoracolumbar disc herniation (TLDH) as an isolated category, it is frequently classified as the lower thoracic spine or upper lumbar spine. Thus, less is known about the morphology and aetiology of TLDH compared to lumbar disc herniation (LDH). The aim of study is to investigate sagittal alignment in TLDH and analyze sagittal profile with radiographic parameters. Methods Data from 70 patients diagnosed with TLDH were retrospectively reviewed. The thoracic-lumbar alignment was depicted by description of curvatures (the apex of lumbar curvature, the apex of thoracic curvature, and inflexion point of the two curvatures) and radiographic parameters from complete standing long-cassette spine radiographs. The rank sum test was utilised to compare radiographic parameter values in each subtype. Results We found two subtypes differentiated by the apex of thoracic kyphotic curves. The sagittal profile was similar to that of the normal population in type I, presenting the apex of the thoracic kyphotic curve located in the middle thoracic spine. The well aligned thoracic-lumbar curve was disrupted in type II, presenting the apex of the thoracic kyphotic curve located in the thoracolumbar region in type II patients. Thirty-six patients were classified as type I, and 34 patients were classified as type II. The mean sagittal vertical axis, T1 pelvic angle and L1 pelvic angle were 27.9 ± 24.8°, 8.2 ± 7.3° and 6.2 ± 4.9°, respectively. There was significant difference (p < 0.001) of thoracolumbar angle between type I (14.9 ± 7.9°) and type II patients (29.1 ± 13.7°). Conclusions We presented two distinctive sagittal profiles in TLDH patients, and a regional kyphotic deformity with a balanced spine was validated in both subtypes. In type I patients, disc degeneration was accelerated by regional kyphosis in the thoracolumbar junction and eventually caused disc herniation. In type II patients, excessive mechanical stress was directly loaded at the top of the curve (thoracolumbar apex region) rather than being diverted by an arc as in a normal population or type I patients. Mismatch between shape and sacral slope value was observed, and better agreement was found in Type II patients.

Efficiency of diffusion-weighted MRI for differentiating radiologically similar simple and type I hydatid cysts of the liver

2021 ◽  
pp. 028418512098813
Author(s):  
Ilyas Dundar ◽  
Mesut Ozgokce ◽  
Fatma Durmaz ◽  
Sercan Ozkacmaz ◽  
Saim Turkoglu ◽  
...  
Keyword(s):  
Treatment Options ◽  
Type I ◽  
Hydatid Cysts ◽  
Liver Cysts ◽  
Diffusion Weighted ◽  
Significant Difference ◽  
Mean Diameter ◽  
Apparent Diffusion ◽  
Adc Values ◽  
Hepatic Lesions

Background Determining the nature of purely cystic hepatic lesions is essential because different kinds have different follow-ups, treatment options, and complications. Purpose To explore the potential of apparent diffusion coefficient (ADC) values of diffusion-weighted imaging (DWI) for the differentiation of type I hydatid cysts (HC) and simple liver cysts (SLC), which have similar radiological appearances. Material and Methods This single-center prospective study was conducted during 2016–2019. Round, homogenous, anechoic liver cysts >1 cm were classified according to at least two years of imaging follow-up, radiological features, serology, as well as puncture aspiration injection reaspiration procedure and pathology results. ADC values of 95 cysts (50 type I HCs and 45 SLCs) were calculated on DWI. The differences in ADC values were analyzed by independent t-test. Results Of 51 patients, 28 were female, 23 were male (mean age 32.07 ± 22.95 years; age range 5–82 years). Mean diameter of 45 SLCs was 2.59 ± 1.23 cm (range 1.2–7.6 cm) and ADCmean value was 3.03 ± 0.47 (range 2.64–5.85) while mean diameter of 50 type I HCs was 7.49 ± 2.95 cm (range 2.8–14 cm) and ADCmean value was 2.99 ± 0.29 (range 2.36–3.83). There was no statistically significant difference in ADC values between type I HCs and SLCs Conclusion Some studies report that ADC values of type I HCs are statistically significantly lower than those of SLCs. Others suggest no significant difference. In our study with a higher number of cases, using ADC parameters similar to those in previous studies, we did not find any statistically significant difference.

scholarly journals THU0521 EVALUATION OF LIVER FIBROSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS UNDER METHOTREXATE TREATMENT. UTILITY OF FIBROSCAN AND BIOMARKERS IN ROUTINE CLINICAL PRACTICE.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 499.2-500
Author(s):  
A. De Diego Sola ◽  
M. Vaamonde Lorenzo ◽  
A. Castiella Eguzkiza ◽  
M. J. Sánchez Iturri ◽  
N. Alcorta Lorenzo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Metabolic Syndrome ◽  
Liver Fibrosis ◽  
Controlled Study ◽  
Type I ◽  
Concomitant Treatment ◽  
Duration Of Treatment ◽  
Significant Difference ◽  
Apri Score ◽  
The Mean

Background:Despite therapeutic advances in recent years, methotrexate (MTX) remains the gold standard for the treatment of rheumatoid arthritis (RA). Among the side effects that have been blamed on it are liver fibrosis (LF) and cirrhosis, although late studies have failed to show such a relation1,2. The only validated test in the diagnosis of LF is biopsy. Given the relevance of MTX in the treatment of RA, it is important to evaluate non-invasive diagnostic options for LF such as transitional elastography (FibroScan, FS).Objectives:To evaluate the percentage of LF in RA patients treated with MTX. Secondly, to assess the correlation between altered liver function, RA activity, and LF. To determine whether dose and/or duration of treatment with MTX may affect the development of LF in such patients.Methods:We did a prospective study between February 2019 and January 2020. Patients affected of RA treated with MTX were included. Patients with basal liver disease (hepatitis B, hepatitis C and steatohepatitis), alcohol consumption, type I diabetes mellitus, chronic renal failure, heart failure, obesity and concomitant treatment with leflunomide or antiretrovirals were excluded. Demographic, clinical, analytical and therapeutic variables were collected. Liver fibrosis was assessed by FS in kilopascals (kpa) and using the APRI score. RA activity was assessed by DAS28 score. Continuous variables are described with mean and standard deviation (SD), and qualitative variables are shown with absolute value and percentage. Spearman’s and Mann-Whitney’s U tests were used for the bivariate analysis.Results:Fifty patients were included (Table 1 and 2). Of these, 38 were women (76%) with mean age of 61.8 years (SD 11.7) and mean RA evolution time of 13.7 years (SD 8.2). The mean DAS28 at the visit was 2.39 (SD 1.1). The FS showed an average of 4.8 kpa (SD 2). The mean duration of treatment with MTX was 85.8 months (SD 93.3) and that of AD-MTX was 5414.6mg (SD 5011). Patients were divided into those with DA-MTX greater than 4000mg (21, 42%) and less than 4000mg (29, 58%) and no significant differences were found in terms of LF in FS (p 0.637) or APRI scale (p 0.806). No significant differences were found in terms of treatment duration either. Six patients (12%) had elevated aspartate aminotransferase (AST) and 9 (18%) had elevated alanine aminotransferase (ALT). No significant difference was found in FS values in relation to ALT, but it was with elevated AST (p 0.021). Similarly, differences were found in APRI based on AST (p 0.045). Metabolic syndrome was collected in 4 patients (8%) without significant differences with FS or APRI values. There were no significant differences in LF depending on gamma-glutamyl transpeptidase (GGT) values.Conclusion:FS and APRI score are useful for the determination of LF in RA patients treated with MTX. There is no evidence of a relationship between AD-MTX and LF by FS or APRI. AST values may be related to the presence of fibrosis as determined by FS or APRI. and the presence of the metabolic syndrome are not.References:[1]G.L. Erre, et al. Methotrexate therapy is not associated with increased liver stiffness and significant liver fibrosis in rheumatoid arthritis patients: A cross-sectional controlled study with real-time two-dimensional shear wave elastography. European Journal of Internal Medicine 69 (2019) 57–63. Internet.[2]R. Conway et al. Risk of liver injury among methotrexate users: a meta-analysis of randomised controlled trials. Semin Arthritis Rheum 2015 Oct;45(2):156–62. Internet.Disclosure of Interests:None declared

scholarly journals Perioperative Outcomes Following Kidney-Pancreas Transplantation in Alberta, Canada: Research Letter

2021 ◽  
Vol 8 ◽  
pp. 205435812110293
Author(s):  
Danielle E. Fox ◽  
Robert R. Quinn ◽  
Paul E. Ronksley ◽  
Tyrone G. Harrison ◽  
Hude Quan ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Postoperative Care ◽  
Pancreas Transplantation ◽  
Type I Diabetes ◽  
Small Sample Size ◽  
Small Sample ◽  
Perioperative Outcomes ◽  
Type I ◽  
Patient Safety Indicators ◽  
Significant Difference

Background: Simultaneous kidney-pancreas transplantation (SPK) has benefits for patients with kidney failure and type I diabetes mellitus, but is associated with greater perioperative risk compared with kidney-alone transplantation. Postoperative care settings for SPK recipients vary across Canada and may have implications for patient outcomes and hospital resource use. Objective: To compare outcomes following SPK transplantation between patients receiving postoperative care in the intensive care unit (ICU) compared with the ward. Design: Retrospective cohort study using administrative health data. Setting: In Alberta, the 2 transplant centers (Calgary and Edmonton) have different protocols for routine postoperative care of SPK recipients. In Edmonton, SPK recipients are routinely transferred to the ICU, whereas in Calgary, SPK recipients are transferred to the ward. Patients: 129 adult SPK recipients (2002-2019). Measurements: Data from the Canadian Institute for Health Information Discharge Abstract Database (CIHI-DAD) were used to identify SPK recipients (procedure codes) and the outcomes of inpatient mortality, length of initial hospital stay (LOS), and the occurrence of 16 different patient safety indicators (PSIs). Methods: We followed SPK recipients from the admission date of their transplant hospitalization until the first of hospital discharge or death. Unadjusted quantile regression was used to determine differences in LOS, and age- and sex-adjusted marginal probabilities were used to determine differences in PSIs between centers. Results: There were no perioperative deaths and no major differences in the demographic characteristics between the centers. The majority of the SPK transplants were performed in Edmonton (n = 82, 64%). All SPK recipients in Edmonton were admitted to the ICU postoperatively, compared with only 11% in Calgary. There was no statistically significant difference in the LOS or probability of a PSI between the 2 centers (LOS for Edmonton vs Calgary:16 vs 13 days, P = .12; PSIs for Edmonton vs Calgary: 60%, 95% confidence interval [CI] = 0.50-0.71 vs 44%, 95% CI = 0.29-0.59, P = .08). Limitations: This study was conducted using administrative data and is limited by variable availability. The small sample size limited precision of estimated differences between type of postoperative care. Conclusions: Following SPK transplantation, we found no difference in inpatient outcomes for recipients who received routine postoperative ICU care compared with ward care. Further research using larger data sets and interventional study designs is needed to better understand the implications of postoperative care settings on patient outcomes and health care resource utilization.

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