scholarly journals Serum exosomal pregnancy zone protein as a promising biomarker in inflammatory bowel disease

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Jing Shao ◽  
Yan Jin ◽  
Chunhong Shao ◽  
Hui Fan ◽  
Xiaorui Wang ◽  
...  

Abstract Background Inflammatory bowel disease (IBD) is a kind of intestinal immune dysfunction disease, and its occurrence and prevalence are on the rise worldwide. As a chronic gastrointestinal disease, its pathogenesis is still unknown. Exosomes are vesicles in various body fluids that carry a variety of substances. They can mediate intercellular communication and long-distance transport of multiple media. In this study, we investigated the protein profile of serum exosomes from healthy people and IBD patients to explore a new serological biomarker for IBD. Methods Initially, exosomes were extracted from serum samples, and the proteins within the exosomes were identified by label-free liquid chromatography/mass spectrometry (LC-MS/MS). Western blot and ELISA were used to assess the identified protein. To further analyze the target protein, an acute colitis mouse model was established, and exosomes in colonic tissue and serum were extracted to investigate the protein in them. Results Firstly, serum exosomes were extracted from samples, and proteins in exosomes were identified by LC-MS/MS. Through statistical analysis, we identified 633 proteins. Among these proteins, pregnancy zone protein (PZP) showed a marked difference between patients with IBD and healthy people, in that its expression level was much higher in the IBD patients This exosomal protein was associated with immunosuppressive effects. Also, the level of PZP in colon tissue exosomes and serum exosomes of acute colitis mice was significantly higher than that of the control group. Conclusions Our findings indicated that serum exosome PZP was present at a high level in the IBD patients. Hence it might be a promising biomarker and enhance auxiliary diagnosis of IBD.

2021 ◽  
Vol 58 (4) ◽  
pp. 495-503
Author(s):  
Maraci RODRIGUES ◽  
Cleonice BUENO ◽  
Elizete Aparecida LOMAZI ◽  
Maria Inez Machado FERNANDES ◽  
Clarice Blaj NEUFELD ◽  
...  

ABSTRACT BACKGROUND: Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCAs) have long been used to differentiate between Crohn’s disease (CD) and ulcerative colitis (UC), more recently having been used as prognostic indicators. OBJECTIVE: To determine the diagnostic accuracy of serological markers in the identification of pediatric CD and UC in Sao Paulo, Brazil, as well as to correlate those markers with characteristics demographic and clinical of these two diseases. METHODS: Retrospective cross-sectional multi-center study involving pediatric patients with inflammatory bowel disease (IBD). We identified ASCAs serological markers and p-ANCA, correlating their presence with demographic and clinical data, not only in the patients with IBD but also in a group of age-matched gastrointestinal disease-free controls. RESULTS: A total of 122 patients, 74 with IBD (46% males), treated at four pediatric gastroenterology referral centers, the mean age of 13±7 years, 49 (66%) with CD, and 25 (34%) with UC. The control Group comprised 48 patients (54% males). The proportion of patients testing positive for p-ANCA was significantly higher in the UC group (69.9%) compared to the CD group (30.4%), as well as being significantly higher in the CD group versus the control Group (P<0.001 for both). The proportion of patients testing positive for ASCA IgA (76.2%) and ASCA IgG (94.4%) markers was also significantly higher in the CD group than in the control Group (P<0.001), and such positivity correlated significantly with the use of immunomodulatory medications such as azathioprine and anti-tumor necrosis factor agents (azathioprine 38.9%, anti-TNF 55.6%; P=0.002). In the CD group, the proportion of patients testing positive for the ASCA IgA was significantly higher among those who underwent surgery than among those who did not (26.86±17.99; P=0.032). CONCLUSION: In pediatric patients with IBD in Sao Paulo, Brazil, serological tests proving to be highly specific, although not very sensitive, for the diagnosis of IBD. However, the serological markers showed a positive correlation with the severity of the disease.


2020 ◽  
Vol 22 (1) ◽  
pp. 364
Author(s):  
Qiyuan Han ◽  
Thomas J. Y. Kono ◽  
Charles G. Knutson ◽  
Nicola M. Parry ◽  
Christopher L. Seiler ◽  
...  

Epigenetic dysregulation is hypothesized to play a role in the observed association between inflammatory bowel disease (IBD) and colon tumor development. In the present work, DNA methylome, hydroxymethylome, and transcriptome analyses were conducted in proximal colon tissues harvested from the Helicobacter hepaticus (H. hepaticus)-infected murine model of IBD. Reduced representation bisulfite sequencing (RRBS) and oxidative RRBS (oxRRBS) analyses identified 1606 differentially methylated regions (DMR) and 3011 differentially hydroxymethylated regions (DhMR). These DMR/DhMR overlapped with genes that are associated with gastrointestinal disease, inflammatory disease, and cancer. RNA-seq revealed pronounced expression changes of a number of genes associated with inflammation and cancer. Several genes including Duox2, Tgm2, Cdhr5, and Hk2 exhibited changes in both DNA methylation/hydroxymethylation and gene expression levels. Overall, our results suggest that chronic inflammation triggers changes in methylation and hydroxymethylation patterns in the genome, altering the expression of key tumorigenesis genes and potentially contributing to the initiation of colorectal cancer.


Author(s):  
Christopher X. W. Tan ◽  
Henk S. Brand ◽  
Bilgin Kalender ◽  
Nanne K. H. De Boer ◽  
Tymour Forouzanfar ◽  
...  

Abstract Objectives Although bowel symptoms are often predominant, inflammatory bowel disease (IBD) patients can have several oral manifestations. The aim of this study was to investigate the prevalence of dental caries and periodontal disease in patients with Crohn’s disease (CD) and ulcerative colitis (UC) compared to an age and gender-matched control group of patients without IBD. Material and methods The DMFT (Decayed, Missing, Filled Teeth) scores and the DPSI (Dutch Periodontal Screening Index) of 229 IBD patients were retrieved from the electronic health record patient database axiUm at the Academic Centre for Dentistry Amsterdam (ACTA) and were compared to the DMFT scores and DPSI from age and gender-matched non-IBD patients from the same database. Results The total DMFT index was significantly higher in the IBD group compared to the control group. When CD and UC were analyzed separately, a statistically significant increased DMFT index was observed in CD patients but not in UC patients. The DPSI did not differ significantly between the IBD and non-IBD groups for each of the sextants. However, in every sextant, IBD patients were more frequently edentulous compared to the control patients. Conclusion CD patients have significantly more dental health problems compared to a control group. Periodontal disease did not differ significantly between IBD and non-IBD groups as determined by the DPSI. Clinical relevance It is important that IBD patients and physicians are instructed about the correlation between their disease and oral health problems. Strict oral hygiene and preventive dental care such as more frequent checkups should be emphasized by dental clinicians.


2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Tian Tian ◽  
Ziling Wang ◽  
Jinhua Zhang

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease whose incidence has risen worldwide in recent years. Accumulating evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of IBD. This review highlights the generation of reactive oxygen species (ROS) and antioxidant defense mechanisms in the gastrointestinal (GI) tract, the involvement of oxidative stress signaling in the initiation and progression of IBD and its relationships with genetic susceptibility and the mucosal immune response. In addition, potential therapeutic strategies for IBD that target oxidative stress signaling are reviewed and discussed. Though substantial progress has been made in understanding the role of oxidative stress in IBD in humans and experimental animals, the underlying mechanisms are still not well defined. Thus, further studies are needed to validate how oxidative stress signaling is involved in and contributes to the development of IBD.


2021 ◽  
Author(s):  
Christian Hundhausen ◽  
Rebekka Schneckmann ◽  
Yanina Ostendorf ◽  
Jacqueline Rimpler ◽  
Anette von Glinski ◽  
...  

2015 ◽  
Vol 81 (21) ◽  
pp. 7582-7592 ◽  
Author(s):  
Mireia Lopez-Siles ◽  
Margarita Martinez-Medina ◽  
Carles Abellà ◽  
David Busquets ◽  
Miriam Sabat-Mir ◽  
...  

ABSTRACTFaecalibacterium prausnitziidepletion in intestinal diseases has been extensively reported, but little is known about intraspecies variability. This work aims to determine if subjects with gastrointestinal disease host mucosa-associatedF. prausnitziipopulations different from those hosted by healthy individuals. A new species-specific PCR-denaturing gradient gel electrophoresis (PCR-DGGE) method targeting the 16S rRNA gene was developed to fingerprintF. prausnitziipopulations in biopsy specimens from 31 healthy control (H) subjects and 36 Crohn's disease (CD), 23 ulcerative colitis (UC), 6 irritable bowel syndrome (IBS), and 22 colorectal cancer (CRC) patients. The richness ofF. prausnitziisubtypes was lower in inflammatory bowel disease (IBD) patients than in H subjects. The most prevalent operational taxonomic units (OTUs) consisted of four phylotypes (OTUs with a 99% 16S rRNA gene sequence similarity [OTU99]), which were shared by all groups of patients. Their distribution and the presence of some disease-specificF. prausnitziiphylotypes allowed us to differentiate the populations in IBD and CRC patients from that in H subjects. At the level of a minimum similarity of 97% (OTU97), two phylogroups accounted for 98% of the sequences. Phylogroup I was found in 87% of H subjects but in under 50% of IBD patients (P= 0.003). In contrast, phylogroup II was detected in >75% of IBD patients and in only 52% of H subjects (P= 0.005). This study reveals that even though the main members of theF. prausnitziipopulation are present in both H subjects and individuals with gut diseases, richness is reduced in the latter and an altered phylotype distribution exists between diseases. This approach may serve as a basis for addressing the suitability ofF. prausnitziiphylotypes to be quantified as a putative biomarker of disease and depicting the importance of the loss of these subtypes in disease pathogenesis.


2021 ◽  
Vol 162 (12) ◽  
pp. 443-448
Author(s):  
Gábor Xantus ◽  
V. Anna Gyarmathy

Összefoglaló. Gyulladásos bélbetegségben (IBD) a fájdalomérzés komplex szomatikus és pszichés jelenség. Ez utóbbi komponens pontosabb megértése segíthet a megfelelő kezelési stratégia megállapításában. A szorongásos hangulati zavarok és egyes maladaptív viselkedési minták (dohányzás és alkoholfogyasztás) előfordulási gyakorisága jól dokumentált IBD-ben, a kannabiszhasználat hatása ugyanakkor kevésbé ismert. A szerzők szisztematikus áttekintést végeztek annak megértéséhez, hogy vajon magasabb-e a marihuánahasználat gyakorisága felnőtt IBD-s betegek között egészséges kontrollpopulációhoz viszonyítva, és ha igen, akkor melyek a szerhasználat legfontosabb jellemzői. A kutatási periódust szándékosan az elmúlt 7 évre korlátoztuk, ugyanis 2013-tól jelentős változások álltak be a kannabinoidok jogi és orvosi megítélésében az USA-ban. Öt elsődleges és több másodlagos adatbázisban kutattunk előre meghatározott kulcsszavak segítségével 2013 óta teljes szöveggel megjelent, angol nyelvű felnőtt IBD-s populációt vizsgáló epidemiológiai tanulmányok vonatkozásában. 143 rekord közül 7 cikk felelt meg a beválogatási kritériumoknak. Eredményeink szerint a kannabiszhasználat gyakorisága IBD-ben szenvedő felnőtt betegek körében valószínűleg magasabb, mint a kontrollpopulációban: a „valaha, bármikor” használók aránya 54–70% között változott (szemben a 46–60% gyakorisággal a kontrollcsoportban), míg az „aktív használók” esetén a gyakoriság 6,8–25% között változott (vs. a kontrollcsoportban tapasztalt 8,6–14%-kal). A prevalenciaadatok széles variabilitása arra utal, hogy a beválogatott epidemiológiai tanulmányok valószínűleg vagy nem voltak megfelelően tervezve, vagy jelentős heterogenitással bírtak. A pszichés tényezők ellentmondásos mintája azt sugallja, hogy a kannabinoidok egyes esetekben ronthatták, más esetben valószínűleg javították bizonyos prominens tünetek megélését. Javasoljuk ezért, hogy a valós prevalencia megállapítása érdekében a keresztmetszeti vizsgálatok mellé ismételt pszichometriai vizsgálatokon alapuló vizsgálatok is bekerüljenek a további kutatásba. Orv Hetil. 2021; 162(12): 443–448. Summary. Pain perception in inflammatory bowel disease (IBD) is beyond a purely somatic process. In-depth understanding of psychologic elements might enable more effective management in this patient group. Anxiety disorders and certain maladaptive coping strategies like smoking and alcohol consumption are well-documented in IBD, unlike the scarcely researched cannabis use. The authors designed a systematic review, to investigate if the prevalence of cannabis use is higher in IBD that in unselected controls. The research window was intentionally set to cover for the past 7 years, as in 2013 major legislative changes took place in the cannabis decriminalisation process in the United States. 5 primary and several secondary databases were researched with a pre-formulated algorithm registered at PROSPERO for full text epidemiological studies published in English language involving adult IBD patients. Out of 143 records, 7 articles met the in/exclusion criteria. Our results suggest that cannabis use among adult patients with IBD is likely to be higher than in the unselected control population. The proportion of “ever” users varied from 54% to 70% (vs. 46–60% in the control group); and for ‘active users’, the prevalence ranged between 6.8% to 25% (vs. 8.6–14% in the control group). The wide variability in prevalence data suggests that the selected epidemiological studies were either inappropriately designed or were too heterogeneous (or both). The contradictory pattern of psychological factors suggests that cannabinoids might improve or worsen IBD depending on case by case basis. We therefore opine that in addition to cross-sectional papers, studies based on repeated psychometric analysis are needed to establish the real prevalence and inform cannabinoid prescription and holistic management in inflammatory bowel disease. Orv Hetil. 2021; 162(12): 443–448.


2020 ◽  
Vol 36 (7) ◽  
pp. 799-807
Author(s):  
Shigeki Ishioka ◽  
Takashi Hosokawa ◽  
Taro Ikeda ◽  
Noriyoshi Konuma ◽  
Hide Kaneda ◽  
...  

Abstract Purpose Our previous studies demonstrated that mature adipocyte-derived dedifferentiated fat (DFAT) cells possess similar multipotency as mesenchymal stem cells. Here, we examined the immunoregulatory potential of DFAT cells in vitro and the therapeutic effect of DFAT cell transplantation in a mouse inflammatory bowel disease (IBD) model. Methods The effect of DFAT cell co-culture on T cell proliferation and expression of immunosuppression-related genes in DFAT cells were evaluated. To create IBD, CD4+CD45RBhigh T cells were intraperitoneally injected into SCID mice. One week later, DFAT cells (1 × 105, DFAT group) or saline (Control group) were intraperitoneally injected. Subsequently bodyweight was measured every week and IBD clinical and histological scores were evaluated at 5 weeks after T cell administration. Results The T cell proliferation was inhibited by co-cultured DFAT cells in a cell density-dependent manner. Gene expression of TRAIL, IDO1, and NOS2 in DFAT cells was upregulated by TNFα stimulation. DFAT group improved IBD-associated weight loss, IBD clinical and histological scores compared to Control group. Conclusion DFAT cells possess immunoregulatory potential and the cell transplantation promoted recovery from colon damage and improved clinical symptoms in the IBD model. DFAT cells could play an important role in the treatment of IBD.


Diagnostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1037
Author(s):  
Giuseppe Losurdo ◽  
Andrea Iannone ◽  
Antonella Contaldo ◽  
Michele Barone ◽  
Enzo Ierardi ◽  
...  

Concomitant inflammatory bowel disease (IBD) and hepatitis C virus (HCV) infection is a relevant comorbidity since IBD itself exposes to a high risk of liver damage. We aimed to evaluate liver stiffness (LS) in IBD-HCV after antiviral treatment. We enrolled IBD patients with HCV. All patients at baseline underwent LS measurement by elastography. Patients who were eligible for antiviral therapy received direct antiviral agents (DAAs) and sustained viral response was evaluated at the 12th week. A control group was selected within IBD patients without HCV. One year later, all IBD-HCV patients and controls repeated LS measurement. Twenty-four IBD-HCV patients and 24 IBD controls entered the study. Only twelve out of 24 received DAAs and all achieved sustained viral response (SVR). All IBD subjects were in remission at enrollment and maintained remission for one year. After one year, IBD patients who eradicated HCV passed from a liver stiffness of 8.5 ± 6.2 kPa to 7.1 ± 3.9, p = 0.13. IBD patients who did not eradicate HCV worsened liver stiffness: from 7.6 ± 4.4 to 8.6 ± 4.6, p = 0.01. In the IBD control group, stiffness decreased from 7.8 ± 4.4 to 6.0 ± 3.1, p < 0.001. In conclusion, HCV eradication is able to stop the evolution of liver fibrosis in IBD, while failure to treat may lead to its progression. A stable IBD remission may improve LS even in non-infected subjects.


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