THERAPIES FOR CROHN'S DISEASE: a clinical update

Sobrado, Carlos Walter; Leal, Raquel Franco; Sobrado, Lucas Faraco

doi:10.1590/s0004-28032016000300016

Cited by 11 publications

(21 citation statements)

References 51 publications

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“…In addition, more than 1/3 of CD patients need at least one intestinal operation in their lives, while 70% of the CD patients with fibrosis strictures need partial resection of the intestinal tract within 10 years of disease progression, and 70%-90% patients will have a recurrence of anastomotic strictures and over 50% patients will form new strictures[ 6 , 7 ]. Moreover, a large number of clinical and experimental results have confirmed that the main drugs for treatment of CD, such as glucocorticoids, immune agents and biological agents, can effectively inhibit intestinal inflammation, but do not have positive activity in preventing the further progress of intestinal fibrosis[ 8 , 9 ]. Thus, there is still a lack of drugs that can effectively inhibit or reverse CD intestinal fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn’s disease intestinal fibrosis

Yang¹,

Zhu²,

Li³

et al. 2018

WJG

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AIMTo explore the role and mechanism of total flavone of Abelmoschus manihot (TFA) on epithelial-mesenchymal transition (EMT) progress of Crohn’s disease (CD) intestinal fibrosis.METHODSFirst, CCK-8 assay was performed to assess TFA on the viability of intestinal epithelial (IEC-6) cells and select the optimal concentrations of TFA for our further studies. Then cell morphology, wound healing and transwell assays were performed to examine the effect of TFA on morphology, migration and invasion of IEC-6 cells treated with TGF-β1. In addition, immunofluorescence, real-time PCR analysis (qRT-PCR) and western blotting assays were carried out to detect the impact of TFA on EMT progress. Moreover, western blotting assay was performed to evaluate the function of TFA on the Smad and MAPK signaling pathways. Further, the role of co-treatment of TFA and si-Smad or MAPK inhibitors has been examined by qRT-PCR, western blotting, morphology, wound healing and transwell assays.RESULTSIn this study, TFA promoted transforming growth factor-β1 (TGF-β1)-induced (IEC-6) morphological change, migration and invasion, and increased the expression of epithelial markers and reduced the levels of mesenchymal markers, along with the inactivation of Smad and MAPK signaling pathways. Moreover, we revealed that si-Smad and MAPK inhibitors effectively attenuated TGF-β1-induced EMT in IEC-6 cells. Importantly, co-treatment of TFA and si-Smad or MAPK inhibitors had better inhibitory effects on TGF-β1-induced EMT in IEC-6 cells than either one of them.CONCLUSIONThese findings could provide new insight into the molecular mechanisms of TFA on TGF-β1-induced EMT in IEC-6 cells and TFA is expected to advance as a new therapy to treat CD intestinal fibrosis.

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Section: Introductionmentioning

confidence: 99%

Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn’s disease intestinal fibrosis

Yang¹,

Zhu²,

Li³

et al. 2018

WJG

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“…IBD is prevalent in the western world, and in European countries, the incidence rates for CD and UC are 0.5–10.6 and 0.9–24.3/10,000 individuals, respectively (3). Traditional drugs such as glucocorticoids, sulfasalazine and immunosuppressants are used for the treatment and maintenance of UC, and drugs such as aminosalicylates, antibiotics, corticosteroids and immunosuppressants are used for the treatment of CD, though these are limited by their incomplete clinical efficacy and side effects (4,5). …”

Section: Introductionmentioning

confidence: 99%

Berberine alleviates dextran sodium sulfate-induced colitis by improving intestinal barrier function and reducing inflammation and oxidative stress

Zhang

Wang

Tong

et al. 2017

Experimental and Therapeutic Medicine

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Berberine has demonstrated efficacy in alleviating experimental colitis in vivo and in vitro. However, the anti-colitis mechanisms of berberine that enable it to promote intestinal barrier function in vivo remain unclear. The present study aimed to evaluate the effect of berberine on intestinal epithelial barrier function, expression of tight junction proteins and the levels of inflammatory and oxidative stress factors in the intestinal mucosa of dextran sulfate sodium (DSS)-induced colitis mice. Berberine (100 mg/kg) was administered for five days to mice with established colitis, induced by administration of DSS (3% w/v) for six days. Intestinal barrier function and the presence of proinflammatory factors, oxidative stress and active signaling pathways in the colon were determined principally by western blotting and reverse transcription-quantitative polymerase chain reaction. It was observed that berberine reduced weight loss, shortening of the colon and colon damage in DSS-colitis mice. In addition, berberine significantly inhibited the increase of fluorescein isothiocyanate-dextran in serum and the decrease of zonula occluden-1 (also known as tight junction protein-1), occludin and epithelial cadherin expression in colonic tissue, relative to a DSS-treated control group. Berberine also significantly inhibited the expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α mRNA and phosphorylation of signal transducer and activator of transcription 3. Furthermore, berberine reduced the levels of myeloperoxidase and increased the levels of superoxide dismutase and catalase in colon and serum samples relative to the control group. The expression of cluster of differentiation 68 in the colon of colitis mice was also reduced by berberine. Collectively, these data suggest that berberine alleviates colitis principally by improving intestinal barrier function and promoting anti-inflammatory and antioxidative stress responses. In turn these effects inhibit macrophage infiltration into the colon and thus may be central to the anti-colitis activity of berberine.

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“…The need for treatment monitoring, employing and quantitatively identifying the serum concentration of IFX and antibodies is extremely relevant for clinical practice (2,3) .…”

Section: Resultsmentioning

confidence: 99%

“…Immunogenicity was not the main factor for the loss of response to the drug, because the minority (10%) had high levels of ATIs. The introduction of drug monitoring for anti-TNFs, including drug level and detection of ATIs, allow more personalized therapeutic management with better dose adjustment and possibly greater economy (2,3) .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of infliximabe through levels and detection of anti-infliximabe antibodies in Crohn's disease patients

Ricci¹,

Leal²,

Miani³

2019

Rev. Trab. Iniciaç. Cient. UNICAMP

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We studied 40 patients with Crohn's disease (CD), 18 to 60 years of age, of both genders, who were followed up at the IBD outpatient clinic, Gastrocenter - UNICAMP, and who were under continuous and regular use of Infliximab (IFX). The peripheral blood collection was performed before the IFX application. Quantification of serum IFX levels and presence of anti-IFX antibody (ATIs) were performed by the ELISA method - Promonitor®. The endoscopic activity of the disease was defined as CDEIS> 5 or the presence of deep ulcers in at least one intestinal segment analyzed and according to the radiological activity. The study has been approved by the UNICAMP Research Committee CAAE 53097116.2.0000.5404.

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THERAPIES FOR CROHN'S DISEASE: a clinical update

Cited by 11 publications

References 51 publications

Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn’s disease intestinal fibrosis

Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn’s disease intestinal fibrosis

Berberine alleviates dextran sodium sulfate-induced colitis by improving intestinal barrier function and reducing inflammation and oxidative stress

Evaluation of infliximabe through levels and detection of anti-infliximabe antibodies in Crohn's disease patients

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