Search

Background and aims: Monocyte recruitment in the lamina propria and inflammatory phenotype driven by the mucosal microenvironment is critical for the pathogenesis of inflammatory bowel disease. However, the stimuli responsible remain largely unknown. Recent works have focused on stromal cells, the main steady-state cellular component in tissue, as they produce pro-inflammatory chemokines that contribute to the treatment-resistant nature of IBD. Methods: We studied the regulation of these processes by examining the communication patterns between stromal and myeloid cells in ileal Crohn's disease (CD) using a complete single-cell whole tissue sequencing analysis pipeline and in vitro experimentation in mesenchymal cells. Results: We report expansion of S4 stromal cells and monocyte-like inflammatory macrophages in the inflamed mucosa and describe interactions that may establish sustained local inflammation. These include expression of CCL2 by S1 fibroblasts to recruit and retain monocytes and macrophages in the mucosa, where they receive signals for proliferation, survival, and differentiation to inflammatory macrophages from S4 stromal cells through molecules such as MIF, IFNγ, and FN1. The overexpression of CCL2 in ileal CD and its stromal origin was further demonstrated in vitro by cultured mesenchymal cells and intestinal organoids in the context of an inflammatory milieu. Conclusions: Our findings outline an extensive cross-talk between stromal and myeloid cells, which may contribute to the onset and progression of inflammation in ileal Crohn's disease. Understanding the mechanisms underlying monocyte recruitment and polarization, as well as the role of stromal cells in sustaining inflammation, can provide new avenues for developing targeted therapies to treat IBD. [ABSTRACT FROM AUTHOR]

Crohn's disease is a relapsing chronic inflammatory condition of the intestine with increasing prevalence around the world. Biologic therapies are currently widely used and have proved safe and effective in treating moderate to severe Crohn's disease. However, contemporary bibliography contains little information about the use of these drugs in patients with end‐stage renal disease undergoing hemodialysis. Here we present a case of a 47‐year‐old female patient with treatment‐refractory Crohn's disease on hemodialysis. In this patient, treatment with the anti‐IL‐12/23 receptor antibody ustekinumab was effective in inducing and maintaining remission while being safe in administering throughout hemodialysis. [ABSTRACT FROM AUTHOR]

Introduction Th17 cells play a crucial role in neutrophilic inflammation and tissue injury in non-cystic fibrosis (non-CF) bronchiectasis. Clarithromycin demonstrates anti-inflammatory and immunomodulatory properties but the effect of long-term clarithromycin prophylaxis on the Th17 response in non-CF bronchiectasis is still unexplored. Methods Th17 response was studied in 22 patients with stable non-CF bronchiectasis receiving daily 500-mg clarithromycin for 12 weeks. We analysed IL-17 concentrations in exhaled breath condensate (EBC) and peripheral blood Th17 cells, whereas functional parameters and clinical data were recorded in parallel. Results Both, post-treatment absolute counts of CD4+IL17+ cells in peripheral blood and IL-17 levels in EBC decreased significantly (post-treatment CD4+IL17+ mean 2.418 ± 0.414 cells/[mu]l versus pre-treatment 3.202 ± 0.507 cells/[mu]l, p = 0.036 and post-treatment IL-17 mean levels 7.16 ± 0.47 pg/ml versus pre-treatment 9.32 ± 0.47 pg/ml, p < 0.001, respectively). Post-treatment EBC IL-17 levels decreased significantly in both patients who exhibited exacerbations and those who remained stable during the study period (mean 6.72 ± 0.37 versus 9.12 ± 0.64 pg/ml, p = 0.01 and 7.69 ± 0.9 versus 9.53 ± 0.72 pg/ml, p = 0.042, respectively), while pre-treatment and post-treatment levels did not differ between the two groups (p = 0.665 and p = 0.465, respectively). PaO.sub.2 improved significantly (post-treatment mean 77.73 ± 2.23 mmHg versus pre-treatment 73.18 ± 2.22 mmHg, p = 0.025), while PaCO.sub.2, post-bronchodilation FEV1, and post-bronchodilation FVC remained unaltered. Conclusions Our results argue for a reduction of both systemic and local Th17 response after prophylactic, low-dose clarithromycin administration in patients with non-CF bronchiectasis, suggestive of a potential anti-inflammatory and/or immunomodulatory action., Author(s): Evangelia Fouka[sup.1] [sup.6] , Eleftheria Lamprianidou[sup.2] , Konstantinos Arvanitidis[sup.3] , Eirini Filidou[sup.3] , George Kolios[sup.3] , Paraskevi Miltiades[sup.2] , Emmanouil Paraskakis[sup.4] , Antonios Antoniadis[sup.5] , Ioannis Kotsianidis[sup.2] , Demosthenes [...]

Objective: The aim of this study was to examine the role of growth factors associated with angiogenesis and oxidative stress in the pathogenesis of spontaneous miscarriage. Methods: We performed a comparative mRNA expression analysis of VEGF, PlGF, Flt-1, Angiogenin and Endoglin using Real-Time PCR, in the placenta and decidua collected from 12 patients presenting with spontaneous abortion and from 14 women undergoing induced abortion, during the first and second trimester of pregnancy. Results: The mRNA expression of Flt-1 was significantly upregulated in the placenta of spontaneous abortions (5.17-fold, IQR: 2.72–9.11, p < 0.01). The placental expression of the soluble isoforms of Flt-1, sFlt-1 e15a and sFlt-1 i13, was also significantly upregulated in spontaneous abortions (sFlt-1 e15a: 2.35-fold, IQR: 0.98–2.83, p < 0.01; sFlt-1 i13: 3.47-fold, IQR: 2.37–5.08, p < 0,05). Placental tmFlt-1, PlGF and Endoglin showed a tendency of higher expression levels in spontaneous abortions, although they did not reach statistical significance (tmFlt-1: 7.42-fold, IQR: 3.58–14.32; PlGF: 2.36-fold, IQR: 0.90–4.12; Endoglin: 1.97-fold, IQR: 1.18–2.43). VEGF and Angiogenin mRNA expression in induced, as well as in spontaneous abortions, did not convey any statistically significant difference. In the decidua, the expression levels of Flt-1 and its splice variants sFlt-1 e15a, sFlt-1 i13 and tmFlt-1 did not show any statistically significant differences, as was the case for the rest of the herein examined growth factors. Conclusions: In this study, we observed higher levels of sFlt-1 mRNA expression in the placenta of spontaneous abortions, while expression of other growth factors in placenta and decidua remained constant. This suggests that an imbalance of sFlt-1 expression in the placenta might contribute to the pathogenesis of spontaneous abortion, probably via oxidative stress, providing a possible biomarker for prompt identification of this condition. [ABSTRACT FROM AUTHOR]

Bifidobacterium lactis, Lactobacillus acidophilus, Lactiplantibacillus plantarum and Saccharomyces boulardii are common probiotic supplements. Colonic subepithelial myofibroblasts (cSEMFs) are actively involved in mucosal wound healing and inflammation. cSEMFs, isolated from healthy individuals, were stimulated with 102 or 104 cfu/mL of these probiotic strains alone and in combination, and their effect on chemokine and wound healing factor expression was assessed by qRT-PCR, ELISA and Sircol Assay, and on cSEMFs migration, by Wound Healing Assay. These strains remained viable and altered cSEMFs' inflammatory and wound healing behavior, depending on the strain and concentration. cSEMFs treated with a combination of the four probiotics had a moderate, but statistically significant, increase in the mRNA and/or protein expression of chemokines CXCL1, CXCL2, CXCL4, CXCL8, CXCL10, CCL2 and CCL5, and healing factors, collagen type I and III, fibronectin and tissue factor. In contrast, when each strain was administered alone, different effects were observed, with greater increase or decrease in chemokine and healing factor expression, which was balanced by the mixture. Overall, this study highlights that the use of multiple probiotic strains can potentially alert the gut mucosal immune system and promote wound healing, having a better effect on mucosal immunity than the use of single probiotics. [ABSTRACT FROM AUTHOR]

Post-inflammatory scarring is the end-result of excessive extracellular matrix (ECM) accumulation and tissue architectural destruction. It represents a failure to effectively remodel ECM and achieve proper reinstitution and healing during chronic relapsing inflammatory processes. Scarring may affect the functionality of any organ, and in the case of inflammatory bowel disease (IBD)- associated fibrosis leads to stricture formation and often surgery to remove the affected bowel. The activated myofibroblast is the final effector cell that overproduces ECM under the influence of various mediators generated by an intense interplay of classic and non-classic immune cells. This review focuses on how proinflammatory mediators from various sources produced in different stages of intestinal inflammation can form profibrotic pathways that eventually lead to tissue scarring through sustained activation of myofibroblasts. [ABSTRACT FROM AUTHOR]

Regenerative medicine is a novel scientific field that employs the use of stem cells as cell-based therapy for the regeneration and functional restoration of damaged tissues and organs. Stem cells bear characteristics such as the capacity for self-renewal and differentiation towards specific lineages and, therefore, serve as a backup reservoir in case of tissue injuries. Therapeutically, they can be autologously or allogeneically transplanted for tissue regeneration; however, allogeneic stem cell transplantation can provoke host immune responses leading to a host-versus-transplant reaction. A probable solution to this problem is stem cell encapsulation, a technique that utilizes various biomaterials for the creation of a semi-permeable membrane that encases the stem cells. Stem cell encapsulation can be accomplished by employing a great variety of natural and/or synthetic hydrogels and offers many benefits in regenerative medicine, including protection from the host's immune system and mechanical stress, improved cell viability, proliferation and differentiation, cryopreservation and controlled and continuous delivery of the stem-cell-secreted therapeutic agents. Here, in this review, we report and discuss almost all natural and synthetic hydrogels used in stem cell encapsulation, along with the benefits that these materials, alone or in combination, could offer to cell therapy through functional cell encapsulation. [ABSTRACT FROM AUTHOR]