scholarly journals Moxibustion and Acupuncture Ameliorate Crohn’s Disease by Regulating the Balance between Th17 and Treg Cells in the Intestinal Mucosa

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Chen Zhao ◽  
Chunhui Bao ◽  
Jing Li ◽  
Yifang Zhu ◽  
Siyao Wang ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Molecular Markers ◽  
Treatment Group ◽  
Crohn's Disease ◽  
Intestinal Mucosa ◽  
Immune Cell ◽  
Treg Cells ◽  
Control Group ◽  
Therapeutic Effects ◽  
Immune Cell Subsets

Previous studies have demonstrated that acupuncture is beneficial to patients with Crohn’s disease (CD), but the mechanism underlying its therapeutic effects remains unclear. To identify the mechanism by which acupuncture treats CD, the balance between Th17 and Treg cells was assessed in CD patients. In this study, Ninety-two CD patients were randomly and equally assigned to a treatment group that were treated with herb-partitioned moxibustion and acupuncture or a control group with wheat bran-partitioned moxibustion and superficial acupuncture. The effect of these treatments on Th17 and Treg cells and their related molecular markers in the intestinal mucosa were detected before (week 0) and after (week 12) treatment. The results suggested that the ratio of Th17 and Treg cells was significantly decreased after treatment and that the levels of IL-17 and RORγt in the intestinal mucosa were obviously reduced, while the expression of FOXP3 was increased after treatment in both groups. In the treatment group, the expression of these molecules was more markedly regulated than the control group. In conclusion, moxibustion and acupuncture have been shown to regulate the ratio of Th17 and Treg cells in the intestinal mucosa of CD patients and restore the balance between these immune cell subsets.

scholarly journals The Polymorphism rs17525495 of LTA4H Is Associated with Susceptibility of Crohn’s Disease instead of Intestinal Tuberculosis in a Chinese Han Population

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Zi-qi Yu ◽  
Wen-fei Wang ◽  
Chuan-zhi Zhu ◽  
Ke-hong Zhang ◽  
Xin-chun Chen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Extrapulmonary Tuberculosis ◽  
Intestinal Tuberculosis ◽  
Taqman Assay ◽  
Jiangxi Province ◽  
Control Group ◽  
Healthy Population ◽  
Therapeutic Effects ◽  
Chinese Han

Background. Because of the similarity of intestinal tuberculosis and Crohn’s disease in disease phenotype, differential diagnosis has always been a clinical problem. Arachidonic acid metabolites play an important role in the inflammatory response of intestinal tuberculosis and Crohn’s disease. Recent studies have shown that the polymorphism locus in the promoter region of LTA4H gene affects LTB4 expression level and the susceptibility to extrapulmonary tuberculosis. Thus, we identified a total of 148 patients with intestinal tuberculosis, 145 with Crohn’s disease, and 700 normal controls in this study. Methods. All the study participants were local Han people from Jiangxi Province in the past eleven years. DNA was extracted from the paraffin-embedded specimens or the whole blood. The LTA4H promoter SNP (rs17525495) was genotyped with TaqMan assay. Results. The T-alleles frequency was not significantly increased in patients with intestinal tuberculosis compared with healthy control group (p=0.630; OR=1.07; 95%CI=0.81-1.41), while patients with Crohn’s disease have significantly increased T allele frequency compared with healthy population (p=0.032; OR=1.34; 95%CI=1.03-1.75). During treatment, the presence of the T allele significantly increased the proportion of Crohn’s patients requiring glucocorticoids (p<0.05). Conclusions. The T allele of LTA4H gene SNP (rs17525495) is a risk factor for Crohn’s disease instead of intestinal tuberculosis. More importantly, there may be a potential association of the different genotypes of rs17525495 with the treatment efficacy of 5-ASA and glucocorticoids in patients with Crohn’s disease. The association between LTA4H polymorphism and drugs therapeutic effects might contribute to the practice of precision medicine and the prediction of clinical outcomes.

scholarly journals P025 Evaluation of endoplasmic reticulum stress in intestinal mucosa from patients with Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S143-S144
Author(s):  
B Rodrigues ◽  
L B Pascoal ◽  
A Coope ◽  
M L S Ayrizono ◽  
M G Camargo ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Er Stress ◽  
Inflammatory Cytokines ◽  
Intestinal Mucosa ◽  
Inflammatory Process ◽  
Explant Culture ◽  
Control Group ◽  
Significant Difference

Abstract Background The endoplasmic reticulum (ER) is responsible for the synthesis and processing of secretory and membrane proteins. In some cases, proteins cannot reach their final conformation and they remain unfolded in the ER lumen. The accumulation of unfolded proteins leads to a state of stress in the ER (ER stress) that is considered toxic to the cells. As a result, cells may respond by driving the proteins to degradation, pausing the transcription process, or even inducing apoptosis.1 ER stress has recently been linked to the exacerbation of the inflammatory process in the pathogenesis of Crohn’s disease (CD).2 Therefore, our aim was to evaluate the effect of a chemical inhibitor on the activation of ER stress pathways and its modulation of pro-inflammatory cytokines. Methods After approval of a local Ethics Committee, biopsies of intestinal mucosa were collected by colonoscopy from patients with CD (CD group) and from patients without inflammatory bowel diseases (control group). Explant culture was performed to evaluate the occurrence of ER stress and was treated with a chemical ER stress inhibitor. Non-parametric tests were performed for statistical analysis adopting p &lt; 0.05 as significant value. Results Samples were collected from 10 patients with active CD (CDEIS ≥5) and six control patients. After cell culture, a significant difference was observed in the activation of the main ER stress pathway in the CD group when compared with control group. After treatment with a chemical inhibitor, there was significant decrease in the expression of genes responsible for the activation of ER stress. In addition, a decrease in the expression of inflammatory cytokines was observed after treatment. Conclusion The use of a chemical inhibitor has been shown to be effective in significantly decreasing the activation of ER stress and to modulate the inflammation in CD. The activation of the main ER stress pathways may contribute to the inflammatory process in CD, and its blockade suggests a potential new target in the treatment of CD. References

scholarly journals P081 Resolvin D2 attenuates colonic inflammation of Crohn’s disease patients

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S182-S182
Author(s):  
L B Pascoal ◽  
B B Palma ◽  
F H Chaim ◽  
G Nogueira ◽  
B L Rodrigues ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Mucosa ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Lipid Mediators ◽  
Control Group ◽  
Inflammatory Disorder ◽  
Tertiary Referral Hospital ◽  
Colonic Inflammation

Abstract Background Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. Usually, the clinical management are based on sulphasalazine, corticosteroid, immunomodulators, biologics therapy and bioactive small molecules. However, new therapeutic strategies involving the inflammatory process are being proposed as the use of pro-resolution lipid mediators. This study aimed to investigate the potential therapeutical role of Resolvin D2 (RvD2) in the intestinal mucosa of CD patients and its therapeutic potential. Methods The study included 16 CD patients, 8 patients in remission (CDR) and 8 with active disease (CDA) and 6 healthy subjects in the control group (CTR); all were followed up in tertiary referral hospital. Blood sample and colonic biopsies were collected during colonoscopy. Disease activity was determined by the Crohn’s Disease Endoscopic Index of Severity (CDEIS). The serum blood level of RvD2 was determined by enzymatic immunosorption assay (ELISA). Intestinal biopsies were submitted to cell culture and treated with Infliximab (IFX) or RvD2. The expression of inflammatory cytokines was evaluated by real-time PCR and RvD2 levels through the ELISA. A nonparametric test was used for statistical analysis, with adopted p&lt;0.05. The study was approved by the University of Campinas research ethics committee. Results The intestinal mucosa of the CDA group showed higher levels of pro-inflammatory markers, such as, IL1β (p=0.008 and p=0.01), IL6 (p=0.002), IL23 (p=0.03) and S100A8 (p=0.004 and p=0.01), compared to CTR and CDR groups, respectively. Although serum RvD2 levels of CDA (p=0.002) and CDR (p=0.004) groups were increased when compared to the CTR group, there is no differences between CDA and CDR groups (p&gt;0.05). However, intestinal explants of the CDA group treated with RvD2 showed a significantly decrease of IL1β expression (p&lt;0.05) when compared to the non-treated biopsies in the ex vivo culture experiments, similar to what was as verified by IFX treatment (p&lt;0.05). Conclusion The results suggest the participation of RvD2 in the modulation of colonic inflammation associated with CD. RvD2 showed to be as effective as IFX in attenuating the pro-inflammatory response present in the intestinal mucosa of patients with CD and provide insights into pro-resolution lipid mediators approaches to modulate chronic inflammation.

scholarly journals Comparative study on the antituberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiaoHe extract and JieHeWan

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Li-Yao Duan ◽  
Yan Liang ◽  
Wen-Ping Gong ◽  
Yong Xue ◽  
Jie Mi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chinese Medicine ◽  
Treatment Group ◽  
Mechanism Of Action ◽  
Cell Damage ◽  
Control Group ◽  
Therapeutic Effects ◽  
Model Group ◽  
Lung Histopathology ◽  
Th17 Cytokines

Abstract Background The traditional Chinese medicine NiuBeiXiaoHe (NBXH) extract and Chinese medicine preparation JieHeWan (JHW) exhibit anti-tuberculosis effects. The anti- tuberculosis effect of NBXH was compared with that of JHW to elucidate the mechanism of action of NBXH. Methods BALB/c mice aged 6-8 weeks were randomly divided into a normal control group, Tuberculosis (TB) model group, JHW treatment group, and NBXH treatment group. After 3 and 13 weeks of treatment, the therapeutic effect in each group was evaluated by comparing lung histopathology, lung and liver colony counts, the number of spots representing effector T cells secreting IFN-γ in an ELISPOT, and the levels of Th1, Th2, and Th17 cytokines, which were measured by a cytometric bead array (CBA). Mouse RNA samples were subjected to transcriptome sequencing. Results After 13 weeks of treatment, the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group (P < 0.05). Compared with those in the TB model group, the lung colony counts in the JHW and NBXH groups were significantly decreased (P < 0.05), and the IL-2 and IL-4 levels in the NBXH group were significantly increased (P < 0.05). NBXH partly restored significant changes in gene expression caused by Mycobacterium tuberculosis (M. tuberculosis) infection. According to GO and KEGG analyses, the changes in biological process (BP), cell composition (CC) and molecular function (MF) terms and in signaling pathways caused by NBXH and JHW treatment were not completely consistent, but they were mainly related to the immune response and inflammatory response in the mouse TB model. Conclusions NBXH had therapeutic effects similar to those of JHW in improving lung histopathology, reducing lung colony counts, and regulating the levels of cytokines. NBXH restored significant changes in gene expression and repaired cell damage caused by M. tuberculosis infection by regulating immune-related pathways, which clarified the mechanism of action of NBXH.

scholarly journals Extracellular vesicles package dsDNA to aggravate Crohn’s disease by activating the STING pathway

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Fan Zhao ◽  
Tao Zheng ◽  
Wenbin Gong ◽  
Jie Wu ◽  
Haohao Xie ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Extracellular Vesicles ◽  
Intestinal Inflammation ◽  
Therapeutic Effects ◽  
Murine Colitis ◽  
Sting Pathway ◽  
Deficient Mice

AbstractCrohn’s disease (CD) is an intestinal immune-dysfunctional disease. Extracellular vesicles (EVs) are membrane-enclosed particles full of functional molecules, e.g., nuclear acids. Recently, EVs have been shown to participate in the development of CD by realizing intercellular communication among intestinal cells. However, the role of EVs carrying double-strand DNA (dsDNA) shed from sites of intestinal inflammation in CD has not been investigated. Here we isolated EVs from the plasma or colon lavage of murine colitis and CD patients. The level of exosomal dsDNA, including mtDNA and nDNA, significantly increased in murine colitis and active human CD, and was positively correlated with the disease activity. Moreover, the activation of the STING pathway was verified in CD. EVs from the plasma of active human CD triggered STING activation in macrophages in vitro. EVs from LPS-damaged colon epithelial cells were also shown to raise inflammation in macrophages via activating the STING pathway, but the effect disappeared after the removal of exosomal dsDNA. These findings were further confirmed in STING-deficient mice and macrophages. STING deficiency significantly ameliorated colitis. Besides, potential therapeutic effects of GW4869, an inhibitor of EVs release were assessed. The application of GW4869 successfully ameliorated murine colitis by inhibiting STING activation. In conclusion, exosomal dsDNA was found to promote intestinal inflammation via activating the STING pathway in macrophages and act as a potential mechanistic biomarker and therapeutic target of CD.

scholarly journals Analysis of Crohn’s Disease-Related CARD15 Polymorphisms in Spanish Patients with Idiopathic Uveitis

2008 ◽  
Vol 24 (2) ◽  
pp. 111-117 ◽  
Author(s):  
N. Rodríguez-Pérez ◽  
A. Aguinaga-Barrilero ◽  
Marina B. Gorroño-Echebarría ◽  
Mercedes Pérez-Blas ◽  
J. M. Martín-Villa
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Dna Sequencing ◽  
Healthy Subjects ◽  
Gene Frequency ◽  
Spanish Population ◽  
Control Group ◽  
Accession Number ◽  
Direct Dna Sequencing ◽  
Exon 11

We wished to analyse the frequency of Crohn’s disease-linked CARD15 polymorphisms (P268S, R702W, G908R and 1007fs) in a group of Spanish patients with idiopathic uveitis. To this aim, DNA samples were obtained from 111 unrelated patients. P268S, R702W and G908R polymorphisms were detected using TaqMan Genotyping kits (Applied Biosystems), and the 1007fs variation by direct DNA sequencing. Control group consisted of 105 healthy subjects.None of the polymorphisms studied revealed a significant increase in the groups of patients, when compared to the control group. Thus, P268S is found in 50% of patients (gene frequency 0.284) vs 44% of control individuals (gene frequency 0.245); R702W in 7% of patients (0.036) vs 7% (0.033); G908R in 2% of patients (0.009) vs 4% (0.019) and, finally, 1007fsin 2% of uveitis patients (0.008) vs 4% (0.021). Moreover, DNA sequencing has allowed us to define two new intronic polymorphisms in phase, in the 5' and 3' boundaries of the exon 11 (GenBank accession number #DQ 869189).Altogether, our results suggest that the Crohn’s disease-linked CARD15 polymorphisms do not seem to predispose to idiopathic uveitis in the Spanish population.

scholarly journals Clinical Study of Acupotomy Trinity Lysis on Cervical Spondylotic Myelopathy with Liver and Kidney Deficiency Syndrome

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Jianyong Gao ◽  
Yi Zhao ◽  
Tinglan Sun ◽  
Weike Liu ◽  
Zhenguo Wang
Keyword(s):  
Treatment Group ◽  
Cervical Spondylotic Myelopathy ◽  
Deficiency Syndrome ◽  
Control Group ◽  
Therapeutic Effects ◽  
Kidney Deficiency ◽  
Significant Difference ◽  
Before And After ◽  
Liver And Kidney ◽  
Experimental Group

Objective: To compare the therapeutic effects of acupotomy trinity lysis and traditional acupotomy on cervical spondylotic myelopathy. Methods: A total of 205 patients with cervical spondylotic myelopathy of liver and kidney deficiency syndrome were randomly divided into the experimental group (105 cases) and the control group (100 cases). The experimental group was relaxed with acupotomy in three positions: Heaven (tian), Human (ren) and Earth (di). Traditional acupotomy was used to relax Ashi acupoints of the affected vertebra in the control group. One treatment was conducted in one week, and the duration of one course of treatment was three weeks. The VAS, JOA score and NDI index were observed after treatment.  Results: Before and after treatment, the total treatment efficiency of the treatment group was 95.23%, and that of the control group was 80.00%, there was significant difference between the two groups, P<0.05; Before operation, there was no significant difference in JOA score, NDI index score, and VAS score between the treatment group and the control group (P>0.05); there was no significant difference after 1 week (P>0.05), but there were significant differences between the two groups 2 weeks and 3 weeks after operation (P<0.05). Conclusion: Acupotomy trinity lysis is a safe, effective and economical treatment for cervical spondylotic myelopathy.

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