The protective effect of Jangkanghwan (Korean traditional food) on lipopolysaccharide-induced disruption of the colonic epithelial barrier

Jangkanghwan (JKH) is a Korean traditional food that is a mixture of food ingredients and traditional Korean medicine ingredients, and it has been observed to produce satisfactory anti-inflammatory, antioxidant, and antibacterial effects. In the current study, JKH was administered by gavage to BALB/C mice with lipopolysaccharide (LPS)-induced colonic epithelial dysfunction, and mouse body weight and food intake were recorded. Indexes such as colonic paracellular permeability, serum inflammatory cytokines, and bacterial translocation were used to comprehensively evaluate the regulatory effect of JKH on mouse colonic epithelial function, and qPCR and Western blot were also used to analyze the expression of tight junction (TJ)-related genes, such as occludin, claudin, zonula occludens (ZOs) proteins, and junction adhesion molecules (JAM) in the colonic epithelial tissue. The experimental results indicated that JKH relieved the edema of the liver, spleen, and mesenteric lymph node tissues, and reduced the loss of appetite and diarrhea caused by LPS injection in mice. It increased the amount of mice food intake from 3.7 g/day in the LPS group to 4.7 g per day; the water content in the feces of mice in the JKH group was 13.86% less than that in the LPS group. JKH reduced the inflammatory response in mice caused by LPS, protected the integrity of the colon, the permeability of fluorescent macromolecules was one-fourth of the LPS group, and enhanced the mRNA and protein expression of TJ-related proteins in colon tissue. Our findings highlight that JKH has benefits in intestinal health and relieving systemic inflammation, relevant aspects of its use as a functional food.

Pre-Clinical Application of Functional Human Induced Pluripotent Stem Cell-Derived Airway Epithelial Grafts

Airway pathologies including cancer, trauma and stenosis lack effective treatments, meanwhile airway transplantation and available tissue engineering approaches fail due to epithelial dysfunction. Autologous progenitors do not meet the clinical need for regeneration due to their insufficient expansion and differentiation, for which human induced pluripotent stem cells (hiPSCs) are promising alternatives. Airway epithelial grafts are engineered by differentiating hiPSC-derived airway progenitors into physiological proportions of ciliated (73.9+/-5.5%) and goblet (2.1 +/-1.4%) cells on a Silk Fibroin-Collagen Vitrigel Membrane (SF-CVM) composite biomaterial for transplantation in porcine tracheal defects ex vivo and in vivo. Evaluation of ex vivo tracheal repair using hiPSC-derived SF-CVM grafts demonstrate native-like tracheal epithelial metabolism and maintenance of mucociliary epithelium to day 3. In vivo studies reveal SF-CVM integration, maintenance of airway patency, showing 80.8+/-3.6% graft coverage with an hiPSC-derived pseudostratified epithelium and 70.7+/-2.3% coverage with viable cells, 3 days post-operatively. We demonstrate the utility of bioengineered, hiPSC-derived epithelial grafts for airway repair in a pre-clinical survival model, providing a significant leap for airway reconstruction approaches.

Interleukin-11 signaling underlies fibrosis, parenchymal dysfunction, and chronic inflammation of the airway

Interleukin (IL)-11 evolved as part of the innate immune response. In the human lung, IL-11 upregulation has been associated with viral infections and a range of fibroinflammatory diseases, including idiopathic pulmonary fibrosis. Transforming growth factor-beta (TGFβ) and other disease factors can initiate an autocrine loop of IL-11 signaling in pulmonary fibroblasts, which, in a largely ERK-dependent manner, triggers the translation of profibrotic proteins. Lung epithelial cells also express the IL-11 receptor and transition into a mesenchymal-like state in response to IL-11 exposure. In mice, therapeutic targeting of IL-11 with antibodies can arrest and reverse bleomycin-induced pulmonary fibrosis and inflammation. Intriguingly, fibroblast-specific blockade of IL-11 signaling has anti-inflammatory effects, which suggests that lung inflammation is sustained, in part, through IL-11 activity in the stroma. Proinflammatory fibroblasts and their interaction with the damaged epithelium may represent an important but overlooked driver of lung disease. Initially thought of as a protective cytokine, IL-11 is now increasingly recognized as an important determinant of lung fibrosis, inflammation, and epithelial dysfunction.

Alkaline phosphatase in pulmonary inflammation—a translational study in ventilated critically ill patients and rats

Background Alkaline phosphatase (AP), a dephosphorylating enzyme, is involved in various physiological processes and has been shown to have anti-inflammatory effects. Aim To determine the correlation between pulmonary AP activity and markers of inflammation in invasively ventilated critically ill patients with or without acute respiratory distress syndrome (ARDS), and to investigate the effect of administration of recombinant AP on pulmonary inflammation in a well-established lung injury model in rats Methods AP activity was determined and compared with levels of various inflammatory mediators in bronchoalveolar lavage fluid (BALF) samples obtained from critically ill patients within 2 days of start of invasive ventilation. The endpoints of this part of the study were the correlations between AP activity and markers of inflammation, i.e., interleukin (IL)-6 levels in BALF. In RccHan Wistar rats, lung injury was induced by intravenous administration of 10 mg/kg lipopolysaccharide, followed by ventilation with a high tidal volume for 4 h. Rats received either an intravenous bolus of 1500 IU/kg recombinant AP or normal saline 2 h after intravenous LPS administration, right before start of ventilation. Endpoints of this part of the study were pulmonary levels of markers of inflammation, including IL-6, and markers of endothelial and epithelial dysfunction. Results BALF was collected from 83 patients; 10 patients had mild ARDS, and 15 had moderate to severe ARDS. AP activity correlated well with levels of IL-6 (r = 0.70), as well as with levels of other inflammatory mediators. Pulmonary AP activity between patients with and without ARDS was comparable (0.33 [0.14–1.20] vs 0.55 [0.21–1.42] U/L; p = 0.37). Animals with acute lung injury had markedly elevated pulmonary AP activity compared to healthy controls (2.58 [2.18–3.59] vs 1.01 [0.80–1.46] U/L; p < 0.01). Intravenous administration of recombinant AP did neither affect pulmonary inflammation nor endothelial and epithelial dysfunction. Conclusions In ventilated critically ill patients, pulmonary AP activity correlates well with markers of pulmonary inflammation, such as IL-6 and IL-8. In animals with lung injury, pulmonary AP activity is elevated. Administration of recombinant AP does not alter pulmonary inflammation and endothelial or epithelial dysfunction in the acute phase of a murine lung injury model.

Plasma Soluble CD146 as a Potential Diagnostic Marker of Acute Rejection in Kidney Transplantation

Previous studies have implicated the role of CD146 and its soluble form (sCD146) in the pathogenesis of inflammatory diseases. However, the association between CD146 and acute rejection in kidney transplant patients remains unexplored. In this study, fifty-six patients with biopsy-proved rejection or non-rejection and 11 stable allograft function patients were retrospectively analyzed. Soluble CD146 in plasma was detected in peripheral blood by enzyme linked immunosorbent assay (ELISA), and local CD146 expression in graft biopsy was detected by immunohistochemistry. We found that plasma soluble CD146 in acute rejection recipients was significantly higher than in stable patients without rejection, and the biopsy CD146 staining in the rejection group was higher than that of the non-rejection group. Multivariate analysis demonstrated soluble CD146 as an independent risk factor of acute rejection. The area under the receiver operating characteristic curve (AUC) of sCD146 for AR diagnosis was 0.895, and the optimal cut-off value was 75.64 ng/ml, with a sensitivity of 87.8% and a specificity of 80.8%, which was better than eGFR alone (P = 0.02496). Immunohistochemistry showed CD146 expression in glomeruli was positively correlated with the Banff-g score, and its expression in tubules also had a positive relationship with the Banff-t score. Therefore, soluble CD146 may be a potential biomarker of acute rejection. Increased CD146 expression in the endothelial or tubular epithelial cells may imply that endothelial/epithelial dysfunction is involved in the pathogenesis of immune injury.