Versatile Role of Prokineticins and Prokineticin Receptors in Neuroinflammation

Prokineticins are a new class of chemokine-like peptides involved in a wide range of biological and pathological activities. In particular, prokineticin 2 (PK2), prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2) play a central role in modulating neuroinflammatory processes. PK2 and PKRs, which are physiologically expressed at very low levels, are strongly upregulated during inflammation and regulate neuronal-glial interaction. PKR2 is mainly overexpressed in neurons, whereas PKR1 and PK2 are mainly overexpressed in astrocytes. Once PK2 is released in inflamed tissue, it is involved in both innate and adaptive responses: it triggers macrophage recruitment, production of pro-inflammatory cytokines, and reduction of anti-inflammatory cytokines. Moreover, it modulates the function of T cells through the activation of PKR1 and directs them towards a pro-inflammatory Th1 phenotype. Since the prokineticin system appears to be upregulated following a series of pathological insults leading to neuroinflammation, we will focus here on the involvement of PK2 and PKRs in those pathologies that have a strong underlying inflammatory component, such as: inflammatory and neuropathic pain, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, stroke, obesity, diabetes, and gastrointestinal inflammation.

Histopathological study of gastrointestinal endoscopic biopsies in pediatric patients

Background Non neoplastic GI lesions in pediatrics are variable and differ in types and prevalence among each pediatric age group. Helicobacter pylori is an important pathogen that can cause gastritis and peptic ulcers in adults as well as in children. Celiac disease is a gluten-dependent autoimmune disorder which affects individuals having genetic susceptibility. Eosinophilic gastrointestinal diseases are disorders that primarily affect the gastrointestinal tract with eosinophil-rich inflammation in the absence of known causes for eosinophilia. Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, mainly affecting the gastrointestinal tract with extraintestinal manifestations and associated immune disorders. It seems that it is one of the most common gastrointestinal diseases affecting children in the developed countries. Aim of the work To study different types of paediatric non neoplastic gastrointestinal lesions from gastrointestinal endoscopic biopsies received at the Pathology Department in Ain Shams University hospital during a period of 2 years (2017-2018), and to correlate them with the clinicopathological presentations and endoscopic findings. Patients and Methods A cross sectional study was conducted on all pediatric gastrointestinal biopsies received at Pathology Department in Ain Shams University Hospital during the period of two years (2017- 2018). Only cases with information for all the covariates (n = 580) were selected and the results were statistically analyzed. Results Total 580 pediatric cases were enrolled according to inclusion criteria. Nonspecific gastrointestinal inflammation represented (47.1%), Helicobacter pylori associated gastrointestinal inflammation represented (43.5%), Eosinophilic gastrointestinal disease represented (3.8%), Inflammatory bowel disease (IBD) represented (3.7%), Celiac disease represented (1.9%). Conclusion This is the first study conducted in Ain Shams University Hospitals to assess the different types of pediatric non neoplastic gastrointestinal lesions received with clinicopathological and endoscopic correlation. The most common pediatric non neoplastic GI lesion is Helicobacter pylori infection. The diagnosis of pediatric non neoplastic GI disorder necessitates interdepartmental teamwork between GI pediatricians and pathologists.

Timing of Tributyrin Supplementation Differentially Modulates Gastrointestinal Inflammation and Gut Microbial Recolonization Following Murine Ileocecal Resection

Background: Gastrointestinal surgery imparts dramatic and lasting imbalances, or dysbiosis, to the composition of finely tuned microbial ecosystems. The aim of the present study was to use a mouse ileocecal resection (ICR) model to determine if tributyrin (TBT) supplementation could prevent the onset of microbial dysbiosis or alternatively enhance the recovery of the gut microbiota and reduce gastrointestinal inflammation. Methods: Male wild-type (129 s1/SvlmJ) mice aged 8–15 weeks were separated into single cages and randomized 1:1:1:1 to each of the four experimental groups: control (CTR), preoperative TBT supplementation (PRE), postoperative TBT supplementation (POS), and combined pre- and postoperative supplementation (TOT). ICR was performed one week from baseline assessment with mice assessed at 1, 2, 3, and 4 weeks postoperatively. Primary outcomes included evaluating changes to gut microbial communities occurring from ICR to 4 weeks. Results: A total of 34 mice that underwent ICR (CTR n = 9; PRE n = 10; POS n = 9; TOT n = 6) and reached the primary endpoint were included in the analysis. Postoperative TBT supplementation was associated with an increased recolonization and abundance of anaerobic taxa including Bacteroides thetaiotomicorn, Bacteroides caecimuris, Parabacteroides distasonis, and Clostridia. The microbial recolonization of PRE mice was characterized by a bloom of aerotolerant organisms including Staphylococcus, Lactobacillus, Enteroccaceae, and Peptostreptococcacea. PRE mice had a trend towards decreased ileal inflammation as evidenced by decreased levels of IL-1β (p = 0.09), IL-6 (p = 0.03), and TNF-α (p < 0.05) compared with mice receiving TBT postoperatively. In contrast, POS mice had trends towards reduced colonic inflammation demonstrated by decreased levels of IL-6 (p = 0.07) and TNF-α (p = 0.07). These changes occurred in the absence of changes to fecal short-chain fatty acid concentrations or histologic injury scoring. Conclusions: Taken together, the results of our work demonstrate that the timing of tributyrin supplementation differentially modulates gastrointestinal inflammation and gut microbial recolonization following murine ICR.

Chemically-Induced Colitis Models in Animal

Ulcerative colitis is a chronic inflammation that can affect the distal part of the colon, submucosa and rectal mucosa, and can affect the entire colon even to the terminal ileum. There are several factors that can cause this disease, such as genetics, environment, intestinal microbiota and the presence of enteric infectious agents. Chemical induction in experimental animals for research on gastrointestinal inflammation has been frequently used due to the similarity of the anatomical and physiological structures of experimental animals with the human digestive tract. This review focuses on recent understanding of the chemicals that used as induction agents in animals

Anti-Inflammatory Effect of Phytoncide in an Animal Model of Gastrointestinal Inflammation

Background: Phytoncide is known to have antimicrobial and anti-inflammatory properties. Purpose: This study was carried out to confirm the anti-inflammatory activity of two types of phytoncide extracts from pinecone waste. Methods: We made two types of animal models to evaluate the efficacy, an indomethacin-induced gastroenteritis rat model and a dextran sulfate sodium-induced colitis mouse model. Result: In the gastroenteritis experiment, the expression of induced-nitric oxide synthase (iNOS), a marker for inflammation, decreased in the phytoncide-supplemented groups, and gastric ulcer development was significantly inhibited (p < 0.05). In the colitis experiment, the shortening of the colon length and the iNOS expression were significantly suppressed in the phytoncide-supplemented group (p < 0.05). Conclusions: Through this study, we confirmed that phytoncide can directly inhibit inflammation in digestive organs. Although further research is needed, we conclude that phytoncide has potential anti-inflammatory properties in the digestive tract and can be developed as a functional agent.