Mild Ulcerative Colitis Patients Research Articles

The significance of PD-1/PD-L1 imbalance in ulcerative colitis.

To investigate the expression and significance of programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1) in the mucosal tissues and peripheral blood of patients with ulcerative colitis (UC). Eighty patients with UC were recruited from January 2021 to August 2022 from the Shanxi Province People's Hospital. PD-1 and PD-L1 expression was assessed by immunohistochemistry in mucosal tissues. An enzyme-linked immunosorbent assay was used to measure soluble PD-1 and PD-L1 levels in peripheral blood serum, and the membrane-bound forms of PD-1 (mPD-1), (T-helper cell) Th1 and Th17, in peripheral blood were determined by flow cytometry. PD-1 expression was observed only in the monocytes of the mucosal lamina propria of UC patients, while PD-L1 was mainly located in both epithelial cells and monocytes on the cell membrane. The expression level of PD-1/PD-L1 in the monocytes and epithelial cells of mucosal lamina propria increased with disease activity (P < 0.05). The percentages of PD-1/T and PD-1/CD4+T in the peripheral blood of moderate UC patients (PD-1/T 12.83 ± 6.15% and PD-1/CD4+T 19.67 ± 9.95%) and severe UC patients (PD-1/T 14.29 ± 5.71% and PD-1/CD4+T 21.63 ± 11.44%) were higher than in mild UC patients (PD-1/T 8.17 ± 2.80% and PD-1/CD4+T 12.44 ± 4.73%; P < 0.05). There were no significant differences in PD-1/CD8+T cells between mild and severe UC patients (P > 0.05). There was a statistically significant difference in the expression level of sPD-L1 between the UC groups and healthy controls, and the expression level of sPD-L1 increased with disease severity (P < 0.05); however, there was no statistically significant difference in sPD-1 expression levels between the UC groups and healthy controls (P > 0.05). The correlation coefficients between Th1 and sPD-L1, PD-1/T, PD-1/CD4+T and PD-1/CD8+T were 0.427, 0.589, 0.486, and 0.329, respectively (P < 0.001). The correlation coefficients between Th17 and sPD-L1, PD-1/T, PD-1/CD4+T and PD-1/CD8+T were 0.323, 0.452, 0.320, and 0.250, respectively (P < 0.05). The expression level of PD-1/PD-L1 was correlated with UC disease activity, and two forms of PD-1 and PD-L1 may be used as a potential marker for predicting UC and assessing disease progression in UC patients. PD-1/PD-L1 imbalance was a significant phenomenon of UC immune dysfunction. Future research should focus on two forms of PD-1/PD-L1 signaling molecules to better understand the pathogenesis of UC and to identify potential drug therapies.

Gut Microbiome and Metabonomic Profile Predict Early Remission to Anti-Integrin Therapy in Patients with Moderate to Severe Ulcerative Colitis.

Patients with ulcerative colitis (UC) have low response rates to anti-integrin medications, necessitating the identification of noninvasive biomarkers for predicting remission to anti-integrin therapy. In this study, patients with moderate to severe UC commencing anti-integrin therapy (n = 29), inactive to mild UC patients (n = 13), and healthy controls (n = 11) were selected. Besides clinical evaluation, fecal samples were collected at baseline and week 14 from moderate to severe UC patients. The clinical remission was defined based on the Mayo score. Fecal samples were assessed with 16S rRNA gene sequencing, liquid chromatography-tandem mass spectrometry, and gas chromatography-mass spectrometry (GC-MS). We identified that Verrucomicrobiota was significantly more abundant in the remission group (P < 0.001) than that of nonremission group at phylum level for patients commencing vedolizumab. GC-MS analysis revealed that the concentrations of butyric acid (P = 0.024) and isobutyric acid (P = 0.042) were significantly higher in the remission group compared to the nonremission group at baseline. Finally, the combination of Verrucomicrobiota, butyric acid, and isobutyric acid improved the diagnosis of early remission to anti-integrin therapy (area under the concentration-time curve = 0.961). We identified significantly higher phylum level diversity of Verrucomicrobiota in remission than the nonremission groups at baseline. Notably, the combination of gut microbiome and metabonomic profiles improved the diagnosis of early remission to anti-integrin therapy. IMPORTANCE It is reported that patients with ulcerative colitis (UC) have low response rates to anti-integrin medications in the latest VARSITY study. Therefore, our primary goals were to discover differences in the gut microbiome and metabonomics patterns between early remission and nonremission patients and to explore the diagnostic value in predicting clinical remission to anti-integrin therapy accurately. In this study, we found that Verrucomicrobiota was significantly more abundant in the remission group (P < 0.001) than that of nonremission group at phylum level for patients commencing vedolizumab. Gas chromatography-mass spectrometry analysis revealed that the concentrations of butyric acid (P = 0.024) and isobutyric acid (P = 0.042) were significantly higher in the remission group compared with the nonremission group at baseline. Notably, the combination of Verrucomicrobiota, butyric acid, and isobutyric acid improved the diagnosis of early remission to anti-integrin therapy (area under the concentration-time curve = 0.961).

Spread of Mesalazine Rectal Foam after Single Dose in Mild Ulcer Patients

Background: The rectal foam enemas were used for ulcerative colitis of distal regions due to its desired efficacy and less side effects. The spread and persistence of the drug plays a key role in the treatment. Therefore, the objective of the present study is to study the spread and persistence of Salofalk (Mesalazine foam Enema), manufactured by Dr. Falk Pharma GmbH (mesalazine) rectal foam in mild ulcerative colitis patients.&#x0D; Methods: This is an open label, uncontrolled prospective study in ulcerative colitis patients. The patients received 2 g of mesalazine rectal foam (labelled with Tcm99) in two actuations (30 mL). The spread of the radiolabeled formulation was assessed over a period of 4 h by gamma scintigraphy.&#x0D; Results: The formulation was retained by the patients till 4 h imaging period. The foam spread in rectum, sigmoid colon and descending colon. The percentage radioactive dose exposed is more in sigmoid colon compared to rectum and descending colon in 4 h imaging period. The spread of the foam extended till descending colon for two out of 4 patients.&#x0D; Conclusion: The study results are consistent with the previous studies, and it supports the label indication. The obtained data of the present study provides in vivo evidence of the spread of formulation in the desired site of action.

The expression analysis of Fra-1 gene and IL-11 protein in Iranian patients with ulcerative colitis

BackgroundFra-1 (fosl1) belongs to the activator protein1 (AP-1) family inducing IL-11 expression in oxidative stress condition. IL-11 plays a pivotal role in protecting epithelial barriers integrity. In this study, we investigated the Fra-1 gene expression in the inflamed mucosa of patients with ulcerative colitis (UC) as well as its relation to IL-11 expression.Materials and methodsWe enrolled 20 patients and 20 healthy controls with definite UC based on the clinical criteria. Fra-1 gene expression in inflamed and non-inflamed colonic biopsies was determined by real-time polymerase chain reaction (RT-PCR). The IL-11 protein concentration was measured by Enzyme-Linked Immunosorbent Assay (ELISA) method. Pearson correlation was applied to calculate the relation between Fra-1 and IL-11.ResultsAn increased level of Fra-1 gene expression was observed in patients with mild ulcerative colitis. The protein concentration of IL-11 was also increased in mild UC patients. Conversely, a significant decrease of IL-11 protein level was detected in severe UC patients compared to control group.ConclusionOxidative stress in inflamed intestinal biopsies can induce fra-1 gene expression. Our findings suggest that Fra-1 transcription factor leads to the production of IL-11 protein in UC patients.

Initial study on the relationship between Clostridium difficile and inflammatory bowel disease

Objective Through the examination of Clostridium difficile (Cd) in the stool of inflammatory bowel disease (IBD) patients to investigate its infection status in IBD patients and the relationship with IBD.Methods From December 2009 to January 2011,a total of 130 diagnosed IBD patients were collected in the Department of Gastroenterology,Ruijin Hospital,Shanghai Jiaotong University School of medicine,including 60 ulcerative colitis (UC) patients and 70 Crohn's disease (CD) patients.At same time.60 irritable bowel syndrome patients and 60 healthy volunteers were collected as control.Stool samples were tested by PCR and Cd toxin A/B test kit (CDTK).SPSS statistical software was used for statistical analysis.Results In 130 enrolled IBD patients,16 cases (12.3％) were Cd infected,of which 10 were UC cases (16.7％) and 6 were CD cases (8.6％).No Cd infection was found positive in control group (x2 =15.779,P=0.000).The infection rate of Cd in the patients of active stage was higher than that in the patients of inactive stage (x2 =10.092,P=0.001).The infection rate of coion-type CD patients was 4/14,which was significantly higher than those of other types CD patients (x2 =13.125,P=0.001).The infection rate of Cd was 4.5％ in mild UC patients,14.3％ in moderate and 6/17 in severe (x2 =6.667,P=0.037) ; the infection rate were 0％ in mild CD patients,4.2％ in moderate and 5/16 in severe.The infection rate increased along with the increase of The disease severity (x2 =13.907,P=0.000).There was no significant difference in the infection rate of Cd between broad-spectrum antibiotics used and not used patients (x2 =1.414,P =0.378), or between patients with broad-spectrum antibiotics used alone and combined with immunosuppressant (x2 =0.330,P=0.962).Conclusions There was certain infection rate of Cd in IBD patients,especially the patients in active stage. The infection rate increased along with the increase of the IBD severity. Key words: Bacillus; Colitis,ulcerative; Crohn disease; Irritable bowel syndrome; Polymerase chain reaction; Feces

Evaluation of QT and P Wave Dispersion and Mean Platelet Volume among Inflammatory Bowel Disease Patients

In inflammatory bowel disease (IBD) number of thromboembolic events are increased due to hypercoagulupathy and platelet activation. Increases in mean platelet volume (MPV) can lead to platelet activation, this leads to thromboembolic events and can cause acute coronary syndromes. In IBD patients, QT-dispersion and P-wave dispersion are predictors of ventricular arrhythmias and atrial fibrilation; MPV is accepted as a risk factor for acute coronary syndromes, we aimed at evaluating the correlations of these with the duration of disease, its localization and activity. The study group consisted of 69 IBD (Ulcerative colitis n: 54, Crohn's Disease n: 15) patients and the control group included 38 healthy individuals. Disease activity was evaluated both endoscopically and clinically. Patients with existing cardiac conditions, those using QT prolonging medications and having systemic diseases, anemia and electrolyte imbalances were excluded from the study. QT-dispersion, P-wave dispersion and MPV values of both groups were compared with disease activity, its localization, duration of disease and the antibiotics used. The P-wave dispersion values of the study group were significantly higher than those of the control group. Duration of the disease was not associated with QT-dispersion, and MPV levels. QT-dispersion, P-wave dispersion, MPV and platelet count levels were similar between the active and in mild ulcerative colitis patients. QT-dispersion levels were similar between IBD patients and the control group. No difference was observed between P-wave dispersion, QT-dispersion and MPV values; with regards to disease duration, disease activity, and localization in the study group (p>0.05). P-wave dispersion which is accepted as a risk factor for the development of atrial fibirilation was found to be high in our IBD patients. This demonstrates us that the risk of developing atrial fibrillation may be high in patients with IBD. No significant difference was found in the QT-dispersion, and in the MPV values when compared to the control group.