MicroRNAs and chronic inflammation contribution to gastrointestinal integrity

Recent studies have revealed that chronic inflammation represents a major basis for different forms of human malignancies. Chronic inflammations are involved in the pathogenesis of 15-25% of human malignancies. Gastrointestinal (GI) cancer is one of the most common causes of mortality in the European Union. The mechanisms leading to cancer development and its progression are not completely understood. Advances are required both in early detection and therapy of GI cancers. There are many factors connecting inflammation and cancer. Cytokines that are small protein molecules regulating growth, differentiation, development and immune response mechanisms in cells. Overexpression of cyclooxynenase-2 is associated with decreased apoptosis, cell to cell adhesion, increased proliferation and angiogenesis contributes to the increased immunosuppresion and mediates carcinogenetic effects. MicroRNAs are regarded as a novel class of gene expression regulators. They are gene-silencing RNAs which negatively regulate gene expression. After binding to target mRNAs they lead either to mRNA destruction or inhibition of translation. Hence, they can play an important role in carcinogenesis. Currently, almost all of the miRNA-related studies on cancers based on the different expression profile of miRNAs in cancer cells compared to normal cells. In summary, miRNAs, proinflammatory cytokines and other factors, may be involved in cancer development based on chronic inflammation by controlling cell differentiation and apoptosis. Assessing the role of miRNAs will provide the new insights on their contribution to the link between chronic inflammation and subsequent cancer, and new markers for cancer diagnoses and cancer therapy

Genetic immunization of ducks for production of antibodies specific to Helicobacter pylori UreB in egg yolks

Following genetic immunization of laying ducks with a plasmid expressing Helicobacter pylori UreB (large subunit of urease), IgY against UreB were obtained from egg yolks. These polyclonal and monospecific IgY antibodies are of higher-titer and specifically recognize recombinant H. pylori urease purified from Escherichia coli. To our knowledge this is the first report describing generation of IgY antibodies directed against antigens of H. pylori by DNA-based immunization

Long-term Helicobacter pylori infection switches gastric epithelium reprogramming towards cancer stem cell-related differentiation program in Hp-activated gastric fibroblast-TGFβTGF\beta dependent manner

Helicobacter pylori (Hp)-induced inflammatory reaction leads to a persistent disturbance of gastric mucosa and chronic gastritis evidenced by deregulation of tissue self-renewal and local fibrosis with the crucial role of epithelial-mesenchymal transition (EMT) in this process. As we reported before, Hp activated gastric fibroblasts into cells possessing cancer-associated fibroblast properties (CAFs), which secreted factors responsible for EMT process initiation in normal gastric epithelial RGM1 cells. Here, we showed that the long-term incubation of RGM1 cells in the presence of Hp-activated gastric fibroblast (Hp-AGF) secretome induced their shift towards plastic LGR5+/Oct4$^{high}$/Sox-2$^{high}$/c-Myc$^{high}$/Klf4$^{low}$ phenotype (l.t.EMT+RGM1 cells), while Hp-non-infected gastric fibroblast (GF) secretome prompted a permanent epithelial-myofibroblast transition (EMyoT) of RGM1 cells favoring LGR−/Oct4$^{high}$/Sox2$^{low}$/c-Myc$^{low}$/Klf4$^{high}$ phenotype (l.t.EMT-RGM1 cells). TGFβ1 rich secretome from Hp-reprogrammed fibroblasts prompted phenotypic plasticity and EMT of gastric epithelium, inducing pro-neoplastic expansion of post-EMT cells in the presence of low TGFβR1 and TGFβR2 activity. In turn, TGFβR1 activity along with GF-induced TGFβR2 activation in l.t.EMT-RGM1 cells prompted their stromal phenotype. Collectively, our data show that infected and non-infected gastric fibroblast secretome induces alternative differentiation programs in gastric epithelium at least partially dependent on TGFβ signaling. Hp infection-activated fibroblasts can switch gastric epithelium microevolution towards cancer stem cell-related differentiation program that can potentially initiate gastric neoplasm

Application of the clustering technique to multiple nutritional factors related to inflammation and disease progression in patients with inflammatory bowel disease

Diet and nutritional status affect intestinal inflammation in patients with inflammatory bowel disease (IBD). The aim of this study was to use a cluster analysis to assess structural similarity between different groups of parameters including short-chain fatty acid (SCFA) levels in stool as well as hematological and inflammatory parameters (such as serum C-reactive protein (CRP) and proinflammatory and anti-inflammatory cytokines). We also assessed similarity between IBD patients in terms of various biochemical features of disease activity and nutritional status. A total of 48 participants were enrolled, including 36 patients with IBD and 12 controls. We identified four main meaningful clusters of parameters. The first cluster included all SCFAs with strong mutual correlations. The second cluster contained red blood cell parameters and albumin levels. The third cluster included proinflammatory parameters such as tumor necrosis factor-α, CRP, platelets, and phosphoric, succinic, and lactic acids. The final cluster revealed an association between zonulin and interleukins IL-10, IL-17, and IL-22. Moreover, we observed an inverse correlation between IL-6 and body mass index. Our findings suggest a link between nutritional status, diet, and inflammatory parameters in patients with IBD, which contribute to a better adjustment of the nutritional treatment

The level of leptin in blood among patients with infective diarrhoea

Wprowadzenie: Biegunka infekcyjna jest zespołem chorobowym, który charakteryzuje się wystąpieniem licznych stolców lub stolców ze zwiększoną ilością wody powstających na skutek zadziałania czynnika zakaźnego. Leptynę zalicza się do rodziny helikalnych cytokin klasy I, a jej wydzielanie zależy od wielkości tkanki tłuszczowej. Wzrost ilości zgromadzonej tkanki tłuszczowej powoduje nasilenie wydzielania tego związku hamującego ośrodek sytości. Stężenie leptyny zwiększa się po posiłku i zmniejsza kilka godzin po nim. Jej wytwarzanie nasilają niektóre cytokiny, a sama wpływa na komórki układu immunologicznego. Cel: Porównanie stężenia leptyny we krwi chorych na biegunkę infekcyjną na początku objawów oraz po wyleczeniu, 8 tyg. później, a także ocena korelacji stężenia tej cytokiny ze wskaźnikami biochemicznymi krwi chorych. Materiał i metody: Badania prospektywne przeprowadzono w grupie 30 chorych. Oznaczano im morfologię krwi obwodowej, stężenie białka C-reaktywnego (C-reactive protein - CRP) i leptyny w surowicy metodą ELISA. Wyniki: Stwierdzono różnice w stężeniach leptyny - większe jej stężenie w okresie biegunki infekcyjnej niż w okresie zdrowia, ale różnice te nie były istotne statystycznie. U chorych z biegunką infekcyjną odnotowano istotną zależność między liczbą płytek krwi, leukocytów i stężeniem CRP a stężeniem leptyny. Wnioski: Wyniki te wskazują na korelację, jaka istnieje między aktywnością stanu zapalnego, wyrażoną poziomem wskaźników zapalnych, i stężeniem cytokin prozapalnych a stężeniem leptyny u chorych z biegunką infekcyjną.Introduction: Infective diarrhoea is a disease which is characterized by the presence of frequent, watery stools caused by an infective agent. Leptin belongs to the family of class I helical cytokines. It is secreted mainly by adipocytes. Increased amounts of adipose tissue result in increased secretion of leptin, which inhibits the satiety centres. The level of leptin increases after a meal and decreases a few hours later. Leptin production is stimulated by some cytokines and also leptin acts on immunological system cells. Aim: To compare the level of leptin in the blood of patients with infective diarrhoea at the beginning of symptoms and after recovery, 8 weeks later and to correlate the level of leptin in the blood with biochemical parameters measured in the blood. Material and methods: A prospective study was done with 30 patients. Blood morphology, C-reactive protein and the level of leptin in the blood using the ELISA method were performed in all patients at the beginning of symptoms and after recovery, 8 weeks later. Results: We observed differences between the leptin level in the blood at the beginning of the infective diarrhoea and after recovery, 8 weeks later, but they were not statistically significant. We observed among patients with infective diarrhoea at the beginning of symptoms positive correlations between leptin and white blood cells, CRP and thrombocytes in blood. Conclusions: These results suggest a correlation between the activity of inflammation measured by blood inflammatory markers and the level of leptin among patients with infective diarrhoea

The importance of nutritional aspects in the assessment of inflammation and intestinal barrier in patients with inflammatory bowel disease

Intestinal inflammation in inflammatory bowel disease (IBD) is closely linked to nutrition. This study aimed to evaluate associations between nutritional, inflammatory, and intestinal barrier parameters in patients with IBD. We assessed nutritional status, fecal short-chain fatty acid profile, serum cytokine levels, and mRNA expression of enzymes and tight junction proteins in intestinal biopsies obtained from 35 patients, including 11 patients with inactive IBD, 18 patients with active IBD, and six controls. Patients with active IBD were characterized by hypoalbuminemia, fluctuations in body weight, and restriction of fiber-containing foods. In addition, they had significantly reduced levels of isovaleric acid and tended to have lower levels of butyric, acetic, and propionic acids. Patients with active IBD had higher mRNA expression of peroxisome proliferator-activated receptor γ and inducible nitric oxide synthase, and lower mRNA expression of claudin-2 and zonula occludens-1, compared with patients with inactive IBD. Moreover, patients with a body mass index (BMI) of ≥25 kg/m(2) had higher median tumor necrosis factor-α levels that those with a lower BMI. We comprehensively evaluated inflammatory parameters in relation to IBD activity and nutritional status. The discrepancies between proinflammatory and anti-inflammatory parameters depending on IBD activity may be related to nutritional factors, including diet and abnormal body weight