scholarly journals P039 New molecular markers of the development of ulcerative colitis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S151-S151
Author(s):  
A A Iakovlev ◽  
A Volkov ◽  
G Tarasova ◽  
A Zubova

Abstract Background The mechanisms of ulcerative colitis (UC) progression require detailed study. Modern achievements of proteomic methods of analysis are ideal for research that is free from hypotheses and allows us to define molecular characteristics of inflammation in colon mucosa of UC patients. Methods The study was comparative cohort with parallel design and included 88 patients (range from 22 to 35 years, 37 men and 51 women): 53 (60.2%) pancolitis and 35 (39.8%) left-sided UC, mild and moderate activity. The control group included 30 healthy individuals. Biosamples of colon mucosa in patients with UC in the active stage and in healthy persons were received by ileocolonoscopy with colon mucosa biopsy. The separation of individual proteins of colon mucosa was based on technologies of IEF, SDS-PAGE, 2DPAGE, by standard sets (MB-HIC C8 Kit, MB-IMAC Cu, MB-Wax Kit, «Bruker», USA). Automated mass spectrometry imaging was performed by MALDI-TOF-MS/MS, Ultraflex II, «Bruker», USA). The data of the molecular interactions and functional features of proteins were received with STRING 10.0 database. Results We identified following functional groups of peptides and proteins in molecular patterns of colon mucosa in UC patients: SMAD family member 2 (SMAD2) activates the transcription of TFG1β, that leads to specific regulation of the CCN2 gene in cells and the development of fibrosis in colon submucosa in UC patients; the stimulation of the expression of apoС-III in affected colon mucosa in UC is associated with the activation of the FOXO1 signaling pathway that supports inflammatory processes in colon mucosa; the second small heat shock protein (HSP2) controls the apoptosis of colonocytes, is also responsible for the mucosa resistance to therapeutic strategies; caspase 8 protects colonocytes from TNFα-induced cell death through a necroptosis mechanism via the blockade of the RIP3 expression; the expression of prohibitin maintains optimal activity of the electronic transport chain through the activity of transcription factor STAT3 and the decrease in the TNFα expression; significant decrease of the PPARγ expression promotes the activation of STAT and AP-1 signaling pathways, which promotes the activity of immune and inflamation processes in colon mucosa and a significant increase in the NF-kB expression in colon mucosa is associated with the activation of TNFα and IL-1, which promotes the increase of immune processes in colon mucosa. Conclusion Bioinformatics analysis revealed the presence of molecules that are the participants in the universal pathways of UC in the active stage, and the molecular interactions involved. This information may provide new avenues for the development of novel diagnostic tests for UC.

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S174-S174
Author(s):  
G Tarasova ◽  
A Volkov ◽  
A Iakovlev ◽  
T Ghazudin ◽  
I Shcherbakova

Abstract Background Success was made in the study of TLR in congenital and adaptive immunity, which determined a new look at immune processes at ulcerative colitis (UC). Modern achievements of proteomic methods of analysis research allow to define molecular characteristics of the inflammation in colon mucosa of patients with UC. Methods The study included 86 patients with UC, an average age of 39.0 ± 1.4 years. Groups: 1–15 (17.4%) patients with distal form of UC, 2–42 (48%) left-sided form, 3–29 (33.7%) patients with total UC. The expression of TLR on peripheral blood monocytes was determined in the immunofluorescence test. Two-colour analysis was performed on a flow-through laser cytofluorimeter (Cytomics FC500, Beckman Coulte). The percentage of monocytes (CD14 + cells) carrying TLR2, TLR4, TLR6 on their surface was assessed. The separation of proteins of colon mucosa was based on technologies of IEF, SDS–PAGE, 2DPAGE (Bruker, USA). The getting of mass spectrogram was determined by matrix-assisted laser desorption-ionisation time-of-flight mass spectrometry (MALDI-TOF-MS/MS, Ultraflex II, Bruker, USA). Statistical analysis was performed using the software Statistica 10.0 (Statsoft). Results The direct average relationship was established between the number of monocytes expressing CD14 + CD282 +, CD14 + CD284 +, CD14 + CD286 + and the area of inflammation (r = 0.49, r = 0.55, r = 0.42, p < 0.05). The nonlinear regression equation was used. Calculation example: the risk of recurrence UC = exp (−26.1 + (0.4) × TLR 2)/(1 + exp (−26.1 + (0.4) × TLR 2)), χ2 = 130, 59, p < 0.0001. Thus, when the number of monocytes expressing TLR2 is not more than 60%, the risk of recurrence of the UC is not more than 11%, with values above 70%, the probability of recurrence exceeds 80%. We identified potentially new molecular markers of the early relapse of ulcerative colitis: SMAD2 activates the transcription of TFG1β and leads to development of fibrosis in colon submucosa in patients with UC; significant decrease of the expression of PPARγ promotes the activation of STAT and AP-1 signalling pathways that promotes the increase of the synthesis of IL-2,6,8,12,TNFα, the activity of immune and inflammation processes in colon mucosa; the reduction of expression of β-defensin-1 in cells of colon mucosa are accompanied with increased expression of CCR6, that promotes the formation of inflammatory infiltrates in colonic submucosa in UC. Conclusion Expression of TLR 2,4,6 in blood monocytes (the risk of recurrence UC ratio) and new protein molecular markers of colon mucosa (SMAD2, PPARγ and apoС-III) can be used as a tool for prediction of early relapse UC.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Guohua Li ◽  
Sheng Zeng ◽  
Wangdi Liao ◽  
Nonghua Lv

Objective. To study effect and its mechanism of Bifid Triple Viable for initially treating ulcerative colitis with 5-aminosalicylic acid.Methods. 82 patients, who were firstly diagnosed as ulcerative colitis, were randomized into experiment group (41 cases, treated with Bifid Triple Viable and Etiasa) and control group (41 cases, treated with Etiasa). The clinic symptom score, colon mucosa inflammation score, and some immune indices were detected and compared between two groups before and two months after treatment.Results. Two months after treatment, the clinical symptom score, colon mucosa inflammation score, and IL-1βexpression in colon mucosa decreased significantly (P<0.01), and IL-10 and IgA expressions in colon mucosa increased significantly (P<0.01). Those differences were more marked in experiment group than control group (P<0.05). However, peripheral blood T cell subgroup, immunoglobulins, and complements had no significant difference between two groups two months after treatment, but the ratio of peripheral blood CD4+ T cell to CD8+ T cell in experiment group increased more than that in control group (P<0.05).Conclusion. Bifid Triple Viable contributed to Etiasa to treat ulcerative colitis in inducing remission period, which was perhaps related to affecting the patient’s immune function.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Wenli You ◽  
Zitong Xu ◽  
Aiting Di ◽  
Penglin Liu ◽  
Chengjian Pang ◽  
...  

Objective. Tong Xie Yao Fang (TXYF) is a classic and effective prescription in traditional Chinese medicine which is used to treat ulcerative colitis (UC). Our study investigated the effect of TXYF on Hippo pathway activation in UC-induced intestinal mucosa injury and explored the possible mechanism. Method. After ulcerative colitis was successfully induced by trinitrobenzene sulfonic acid (TNBS), 48 Sprague Dawley (SD) rats were randomly divided into a control group, model group, TXYF group, and sulfasalazine group and treated with the corresponding drugs for 28 days. The parameters including body weight, colon length, spleen index, and disease activity index (DAI) and histopathological characteristics were assessed. The myeloperoxidase (MPO) activity and IL-6 level in the colon mucosa were determined with the corresponding commercial kits. The expressions of the Hippo pathway components YAP1, TAZ, P-YAP, and LATS1 were detected in the colon mucosa of each group on different stages by quantitative real-time PCR (qRT-PCR) and western blotting. Immunohistochemical staining was used to evaluate the growth and apoptosis of the colon epithelium. Result. TXYF significantly improved the weight loss, colonic shortening, DAI, spleen enlargement, and histopathological score of the rats with TNBS-induced UC. TXYF also reduced the MPO activity and expression of IL-6 in the colon mucosa. Furthermore, treatment with TXYF significantly increased YAP1 expression in the early stage (3–7 days) and significantly decreased YAP1 expression in the late stage (14–28 days). In the early stage, TXYF inhibited Hippo pathway activity, which promoted proliferation and regeneration of the intestinal mucosa. In the late stage, the Hippo pathway was activated, thereby inhibiting apoptosis and promoting intestinal mucosal differentiation. Conclusion. TXYF alleviated the inflammatory response and promoted mucosal healing in rats with UC, which was probably achieved through the Hippo pathway. These results indicated that TXYF was a potential therapy for treating UC.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S138-S138
Author(s):  
G Tarasova ◽  
A Volkov ◽  
A Iakovlev ◽  
T Ghazudin ◽  
I Shcherbakova

Abstract Background Success was made in the study of TLR in congenital and adaptive immunity, which determined a new look at immune processes at ulcerative colitis (UC). Modern achievements of proteomic methods of analysis research allow to define molecular characteristics of the inflammation in colon mucosa of patients with UC. Methods The study included 86 patients with UC, an average age of 39.0 ± 1.4 years. Groups: 1–15 (17.4%) patients with distal form of UC, 2–42 (48%) left-sided form, 3–29 (33.7%) patients with total UC. The expression of TLR on peripheral blood monocytes was determined in the immunofluorescence test. Two-colour analysis was performed on a flowthrough laser cytofluorimeter (Cytomics FC500, Beckman Coulte). The percentage of monocytes (CD14 + cells) carrying TLR2, TLR4, and TLR6 on their surface was assessed. The separation of proteins of colon mucosa was based on technologies of IEF, SDS–PAGE, 2DPAGE, by standard sets (MB-HIC C8 Kit, MB-IMAC Cu, MB-Wax Kit, Bruker, USA). The getting of mass spectrogram was determined by matrix-assisted laser desorption-ionisation time-of-flight mass spectrometry (MALDI-TOF-MS/MS, Ultraflex II, Bruker, USA). Statistical analysis was performed using the software Statistica 10.0 (Statsoft). Results The direct average relationship was established between the number of monocytes expressing CD14 + CD282 +, CD14 + CD284 +, CD14 + CD286 + and the area of inflammation (r = 0.49, r = 0.55, r = 0.42, p &lt; 0.05). The nonlinear regression equation was used. Calculation example: the risk of recurrence UC = exp (−26.1 + (0.4) × TLR 2)/(1 + exp (−26.1 + (0.4) × TLR 2)), χ2 = 130, 59, p &lt; 0.0001. Thus, when the number of monocytes expressing TLR2 is not more than 60%, the risk of recurrence of the UC is not more than 11%, with values above 70%, the probability of recurrence exceeds 80%. We identified potentially new molecular markers of the early relapse of ulcerative colitis: SMAD2 activates the transcription of TFG1β and leads to development of fibrosis in colon submucosa in patients with UC; significant decrease of the expression of PPARγ promotes the activation of STAT and AP-1 signalling pathways that promotes the increase of the synthesis of IL-2, 6, 8, 12, TNFα, the activity of immune and inflammation processes in colon mucosa; the reduction of expression of β-defensin-1 in cells of colon mucosa is accompanied with increased expression of CCR6 that promotes the formation of inflammatory infiltrates in colonic submucosa in UC. Conclusion Expression of TLR 2, 4, 6 in blood monocytes (the risk of recurrence UC ratio) and new protein molecular markers of colon mucosa (SMAD2, PPARγ, and apoС-III) can be used as a tool for prediction of early relapse UC.


2016 ◽  
Vol 1 (4) ◽  
Author(s):  
Hartini Tiono

Ulcerative colitis is a chronic inflammatory disease mainly affects sigmoid colon and rectum. The inflammation process will activate NF-κB and leads to proinflamatory cytokine release such as Interleukin-6 (IL-6). Fig leaves contain a high level of flavonoid which can prevent NF-κB activation, and further inhibits IL-6 secretion. This research aims to see the preventive effect of methanolic extract of fig leaves towards colon histopathological feature and IL-6 serum level on ulcerative colitis induced mice. Balb/C male mice were randomly assigned into 5 groups (n=5). The treatment groups were dextran suphate sodium (DSS) control group (group I), methanolic extract of Fig leaves dose 28 mg/ day control group (group II), and methanolic extract of Fig leaves dose 7 mg/ day (group III), 14 mg/ day (group IV), and 28 mg/ day (group V) for 14 days, which at the 8th till 14th day were given DSS to induce colitis. The results showed that both of colon mucosal damage and IL-6 serum level of group I were significantly different from other groups (p=0,029). In  conclusion, the methanolic extract of Fig leaves can improve colon mucous damage and decrease IL-6 serum level on ulcerative colitis-induced mice. Keywords: ulcerative colitis, fig leaves, colon mucousal damage, interleukin-6


2021 ◽  
Vol 93 (8) ◽  
pp. 869-875
Author(s):  
Irina V. Kozlova ◽  
Anna P. Bykova

Aim. To determine clinical features and some mechanisms of osteosarcopenia development in patients with chronic pancreatitis (CP). Materials and methods. A casecontrol study was conducted on the basis of the Saratov State Clinical Hospital 5 in 20152018 of patients with CP. In a study of 161 patients with CP included, the control group 30 healthy individuals. Patients were divided into groups according to the etiology of CP: 79 with toxic-metabolic CP, 82 with biliary CP. To determine the risks of low-energy fractures, 154 patients were tested with the Fracture risk assessment tool (FRAX). Along with the standard examination, 30 patients with CP dual-energy X-ray absorptiometry was performed. To assess the state of skeletal muscles, body mass index was determined, hand-held dynamometry was performed, and a set of Short Physical Performance Battery (SPPB) tests was used. Along with the assessment of traditional risk factors for osteosarcopenia gender, age, state of reproductive function in women, body mass index, functional state of the pancreas (pancreas) the quantitative content of interleukins (IL)-2, 6, 8 in in colonic biopsies was analyzed by enzyme-linked immunosorbent assay (ELISA). Results. Bone disorders, according to densitometry, was detected in 70.0% of patients with CP, in 13.3% of the control group. Presarcopenia was detected in 62 (38.5%) patients with CP, sarcopenia in 34 (21.1%), in the control group presarcopenia and sarcopenia were not detected. Sarcopenia was statistically significantly more common in toxic-metabolic CP than in biliary CP (2=11.6; p0.001). Correlations of the lumbar spine T-score and IL-6 (r=-0.29; p=0.03), IL-8 (r=-0.29; p=0.04) were revealed. Correlations between sarcopenia and the concentration of cytokines in the in the colon mucosa in CP were determined (IL-2: r=0.44; p0.001; IL-6: r=0.48; p0.001; IL-8: r=0.42; p0.001). Conclusion. The development of osteopenia and sarcopenia syndromes in CP is interrelated and associated with both traditional risk factors and an increased concentration of cytokines in the in the colon mucosa.


2019 ◽  
Vol 10 (4) ◽  
pp. 71-79
Author(s):  
I. F. Shlyk ◽  
L. P. Sizyakina ◽  
R. V. Sidorov ◽  
S. V. Shlyk

Objective: to study the functional characteristics of innate immunity in the formation of postpericardial syndrome (PPS) in patients undergoing coronary artery bypass graft ing (CABG).Materials and methods: the study involved 60 people, 40 of them made up the main group of patients with coronary artery disease, which retrospectively aft er 1 month of observation was divided into 2 groups. Group I CABG and PPS, group II CABG without PPS. The control group consisted of 20 patients without IHD. Before surgery, aft er 5, 14 days and 1 month, the expression of toll-like receptors (TLRs) 2, 4, 9, the content of CD16+ and Granzyme B lymphocytes, the HCT test and serum α-defensin were evaluated in blood cells. Statistical analysis of the results of the study was carried out using the program Statistica 12.0 (StatSoft , USA). The difference in mean values between groups was evaluated by the Mann-Whitney test. Statistical signifi cance was considered signifi cant at p ≤ 0.05.Results: when comparing the initial indices of the main groups and the control group, an increase in the expression of TLRs 2, 4, 9 was revealed. An increase in the content of CD16+, as well as an increase in the cytotoxic activity of natural killers and an increase in the production of α-defensin.Conclusions: on the basis of the study, activation of the cellular link of innate immunity, an increase in the cytotoxic potential of natural killers and a signifi cantly high level of α-defensin both before and aft er CABG were revealed, which can play an important role in the development of PPS. 


2005 ◽  
Vol 11 (3) ◽  
pp. 177-180 ◽  
Author(s):  
L. A. Lohankova ◽  
Yu. V. Kotovskaya ◽  
A. S. Milto ◽  
Zh. D. Kobalava

The structural and functional features of the microcirculatory heel (MCB) were studied in patients with arterial hypertension (AH) in relation to the presence or absence of type 1 diabetes mellitus (DM). Two hundred and twelve patients were examined. These included 110 patients with grades 1 and 2 arterial hypertension (AH) and type 2 DM, 82 patients with AH without type 2 DM, and 20 apparently healthy individuals. Laser Doppler flowmetry (LDF) was used to estimate basal blood flow, the loading test parameters characterizing the structural and functional status of MCB, and the incidence of hemodynamic types of microcirculation. Patients with AH concurrent with type 1 DM were found to have the following microcirculatory features: an increase in perfusion blood flow (microcirculation index, 8,8±1,8 perf. units versus 4,9±0,8 perf, units in patients with AH without DM and 6,7±0,9 perf. units in the control group), a drastic reduction in myogenic activity to 13,2±5,7 % versus 16,7±6,8 and 25,2±6,4 %, respectively, a decrease in vascular resistance, impairment of autoregulation, and low reserve capacities (reserve capillary blood flow was 197,8±31,6 % versus 429,9±82,01 % in the group of AH without DM and 302,8±50,1 % in the control group), a predominance of the hyperemic hemodynamic type (58,8 % in patients with AH and DM, 20,9 % in those with AH without DM, and 20,0 % in the controls). The specific features of the altered microcirculatory bed in patients with AH concurrent with type 2 DM were ascertained. These included the predominance of hyperemic microcirculation, impaired autoregulation. diminished microvascular resistance, and the low reserve capacities of the microcirculatory bed.


2021 ◽  
Vol 15 (7) ◽  
pp. 2343-2347
Author(s):  
YU. S. Ivanchuk ◽  
L.V. Tribuntсeva ◽  
A.V. Budnevsky ◽  
N.I. Ostroushko ◽  
YA. S. Shkatova ◽  
...  

Background. Physical activity is associated with better asthma control and life quality in asthma. Osteoarthritis is one of the less studied comorbidities in asthmatic patients. Methods. The study included 38 patients diagnosed with asthma, 65 patients with asthma and osteoarthritis, and 40 volunteers who did not suffer from asthma and osteoarthritis. During the study, 3 groups were formed: Group 1 consisted of patients with asthma; Group 2 included patients with both asthma and osteoarthritis, Control group consisted of volunteers. Spirometry, Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Test (АСТ) were used in asthmatic patients. International Physical Activity Questionnaire (IPAQ) in its short from was filled by all the participants. Results. Both Group 1 and Group 2 did not engage in vigorous physical activity. Median of MET-min/week total (1825) was significantly less in Group 2 compared with Control and Group 1 (p=0.0000 and p=0.0169, respectively). MET-min/week total had positive correlations with ACT (r=0.50, p<0.05), AQLQ(S) total (r=0.58, p<0.05), AQLQ(S) activity domain (r=0.28, p<0.05), AQLQ(S) emotions domain (r=0.24, p<0.05), AQLQ (S) symptoms domain (r=0.34, p<0.05), FVC (r=0,28, p<0.05), FEV1 (r=0,37, p<0.05), Index Tiffno (r=0,18, p<0.05). Minutes/week sitting time had a negative correlation with ACT values (r=-0.33, p<0.05), AQLQ(S) total values (r=-0.39, p<0.05). Conclusion. Patients with asthma and osteoarthritis spend significantly less time on moderate activity, walking compared with asthmatics not suffering from osteoarthritis; they avoid vigorous activity. Higher physical activity is associated with better life quality, asthma control and lung function, thus paying attention to osteoarthritis in asthmatic patients is crucial. Key words: life quality, physical activity, asthma, osteoarthritis


2021 ◽  
Vol 93 (8) ◽  
pp. 975-981
Author(s):  
Oleg V. Knyazev ◽  
Anna V. Kagramanova ◽  
Sergei G. Khomeriki ◽  
Asfold I. Parfenov

Current conception of deep remission in patients with ulcerative colitis (UC) consists of clinical remission, endoscopic mucosal healing and normalization of laboratory markers. Histological remission should not be used as a primary end point for therapeutic efficacy, but instead should be considered as a marker of deep remission. The main goal of UC treatment should be focused on endoscopic healing of colon mucosa, decrease of inflammation activity, prolonged remission, absence of disease recurrence, and also histologic remission. Nevertheless, the term histologic remission has not yet been fully validated and no histologic indexes have been standardized. We need single unified definition for remission, based on multicentral studies analysis. One of important challenge is restoration of normal colon mucosal and results of multiple studies showed contradictory tests for assessing histologic remission, thus remaining an issue for further discussion.


Sign in / Sign up

Export Citation Format

Share Document