Schistosoma japonicum-derived peptide SJMHE1 ameliorates allergic symptoms and responses in mice with allergic rhinitis.

Helminth derived excretory/secretory molecules have shown efficacy in the treatment of allergic asthma in mice, but their roles in allergic rhinitis (AR) are little known. In this study, we aimed to determine the intervention effect of SJMHE1, a Schistosoma japonicum derived small molecular peptide, on ovalbumin (OVA)-induced AR mice and investigate its possible mechanism. AR was induced in BALB/c mice, following which the mice were treated with phosphate-buffered saline (PBS), OVA323-339 and SJMHE1 respectively. SJMHE1 treatment improved clinical symptoms (rubbing and sneezing), suppressed infiltrates of inflammatory cells and eosinophils in nasal mucosa, modulated the production of type-2 (IL-4 and IL-13) and anti-inflammatory (IL-10) cytokines in the nasal lavage fluids (NLF), spleen, and serum. To investigate the underlying mechanism, fluorescein isothiocyanate (FITC)-labeled SJMHE1 was subcutaneously injected into AR mice, and we found that the FITC-SJMHE1 could accumulate in spleen, but not in nasal mucosa. FITC-SJMHE1 mainly bound to CD19 positive cells (B cells), and the SJMHE1 treatment significantly increased the proportion of regulatory B cells (Bregs) and B10 cells, along with the enhancement of PR domain containing protein 1 (Prdm1) protein levels. SJMHE1 may alleviate AR by upregulating Bregs, and has great potential as a new avenue for the AR treatment.

A non-invasive strategy for suppressing asthmatic airway inflammation and remodeling: Inhalation of nebulized hypoxic hUCMSC-derived extracellular vesicles.

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are extremely promising nanoscale cell-free therapeutic agents. We previously identified that intravenous administration (IV) of human umbilical cord MSC-EVs (hUCMSC-EVs), especially hypoxic hUCMSC-EVs (Hypo-EVs), could suppress allergic airway inflammation and remodeling. Here, we further investigated the therapeutic effects of Hypo-EVs administration by atomizing inhalation (INH), which is a non-invasive and efficient drug delivery method for lung diseases. We found that nebulized Hypo-EVs produced by the atomization system (medical/household air compressor and nebulizer) maintained excellent structural integrity. Nebulized Dir-labeled Hypo-EVs inhaled by mice were mainly restricted to lungs. INH administration of Hypo-EVs significantly reduced the airway inflammatory infiltration, decreased the levels of IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluid (BALF), declined the content of OVA-specific IgE in serum, attenuated the goblet cell metaplasia, and the expressions of subepithelial collagen-1 and α-smooth muscle actin (α-SMA). Notably, Hypo-EV INH administration was generally more potent than Hypo-EV IV in suppressing IL-13 levels and collagen-1 and α-SMA expressions. RNA sequencing revealed that various biological processes, such as cell adhesion, innate immune response, B cell activation, and extracellular space, were associated with the activity of Hypo-EV INH against asthma mice. In addition, Hypo-EVs could load exogenous miR-146a-5p (miR-146a-5p-EVs). Furthermore, INH administration of miR-146a-5p-EVs resulted in a significantly increased expression of miR-146a-5p mostly in lungs, and offered greater protection against the OVA-induced increase in airway inflammation, subepithelial collagen accumulation and myofibroblast compared with nebulized Hypo-EVs. Overall, nebulized Hypo-EVs effectively attenuated allergic airway inflammation and remodeling, potentially creating a non-invasive route for the use of MSC-EVs in asthma treatment.

MiR-30c-5p loss-induced PELI1 accumulation regulates cell proliferation and migration via activating PI3K/AKT pathway in papillary thyroid carcinoma.

BACKGROUND: The aberrant expression of E3 ubiquitin ligase Pellino-1 (PELI1) contributes to several human cancer development and progression. However, its expression patterns and functional importance in papillary thyroid cancer (PTC) remains unknown. METHODS: PELI1 expression profiles in PTC tissues were obtained and analyzed through the starBase v3.0 analysis. Real-time PCR, Immunohistochemical assays (IHC) and Western blot were used to investigate the mRNA and protein levels of PELI1 in PTC. The effects of PELI1 on PTC cell progression were evaluated through CCK-8, colony formation, Transwell, and Wound healing assay in vitro, and a PTC xenograft mouse model in vivo. The downstream target signal of PELI1 in PTC was analyzed by using Kyoto encyclopedia of genes and genomes (KEGG), and bioinformatics tools were used to identify potential miRNAs targeting PELI1. Human umbilical cord mesenchymal stem cells were modified by miR-30c-5p and the miR-30c-5p containing extracellular vesicles were collected (miR-30c-5p-EVs) by ultra-high-speed centrifugation method. Then, the effects of miR-30c-5p-EVs on PELI1 expression and PTC progression were evaluated both in vitro and in vivo. RESULTS: Both mRNA and protein expression of PELI1 were widely increased in PTC tissues, and overexpression of PELI1 was positively correlated with bigger tumor size and lymph node metastases. PELI1 promoted PTC cell proliferation and migration in vitro. While, PELI1 silencing significantly suppressed PTC growth in vivo accompanied with reduced expression of Ki-67 and matrix metallopeptidase 2 (MMP-2). Mechanistically, PI3K-AKT pathway was identified as the downstream target of PELI1, and mediated the functional influence of PELI1 in PTC cells. Moreover, we found that the expression of miR-30c-5p was inversely correlated with PELI1 in PTC samples and further confirmed that miR-30c-5p was a tumor-suppressive miRNA that directly targeted PELI1 to inhibit PTC cell proliferation and migration. Furthermore, we showed that miR-30c-5p-EVs could effectively downregulate PELI1 expression and suppress the PTC cell growth in vitro and in vivo. CONCLUSION: This study not only supported the first evidence that miR-30c-5p loss-induced PELI1 accumulation facilitated cell proliferation and migration by activating the PI3K-AKT pathway in PTC but also provided novel insights into PTC therapy based on miR-carrying-hUCMSC-EVs.

Magnetic field effects on the open circuit potential of ferromagnetic electrodes in corroding solutions.

Magnetic fields shift the open circuit potential (OCP) of ferromagnetic electrodes (Fe, Co, and Ni) in corroding solutions. The OCP changes we observe (a) follow the series Fe>Co>Ni; (b) increase with the magnetic flux density; (c) reach a maximum with disk electrodes approximately 1 mm in diameter; and (d) depend on the orientation of the electrode. We report that when the surface of the electrode is oriented parallel (theta = 90 degrees) or perpendicular (theta = 0 degrees) to the magnetic field, the open circuit potential moves in opposite directions (positive and negative, respectively) with the largest changes occurring when the electrode surface is parallel to the magnetic field. Nonconvective sleeve electrodes produce the same behavior. The overall experimental evidence suggests that the magnetic field changes the OCP by modifying the surface concentrations of the paramagnetic participants in the corrosion process of the ferromagnetic electrode by species in solution; this in turn is accomplished by imposing a field-gradient driven mode of mass transfer upon paramagnetic species in solution (magnetophoresis). Simulations of the magnetic field around the ferromagnetic electrode at the two extreme orientations considered here show that in one case (theta = 90 degrees) field gradients actually repel, while in the other case (theta = 0 degrees) they attract paramagnetic species in the vicinity of the electrode.

Nd-Fe-B permanent magnet electrodes. Theoretical evaluation and experimental demonstration of the paramagnetic body forces.

Cyclic voltammetry with Nd-Fe-B disk magnet electrodes (3.2 mm diameter) at slow sweep rates (< or = 0.01 V s(-1)) in relatively concentrated solutions (e.g., 80 mM) of diamagnetic redox-active species (e.g., TMPD) is controlled by diffusion. Under similar conditions, cyclic voltammetry with conventional noble metal disk millielectrodes is characterized by the absence of diffusion waves and the presence of density gradient driven natural convection. Although the magnetic field in the vicinity of Nd-Fe-B electrodes is relatively strong (approximately 0.5 T at the surface of the magnet electrode), the absence of magnetohydrodynamic stirring effects is attributed to the fact that the i and B vectors are almost parallel, and therefore the magnetohydrodynamic force F(B) (=i x B) is very small. On the other hand, the absence of natural convection is attributed to the two possible paramagnetic body forces, F(inverted Delta B) and F(inverted Delta C), exerted by the magnet electrode on the diffusion layer. Of those two forces, the former depends on field gradients (F(inverted Delta B) approximately B x inverted Delta B), while the latter depends on concentration gradients (F(inverted Delta C) approximately inverted Delta C(j)) and is directed toward areas with higher concentration of paramagnetic j. Through thorough analysis of the magnetic field and its gradients, it is found that the average F(inverted Delta C) force acting upon the entire diffusion layer is approximately 1.75 times stronger than F(inverted Delta B). Nevertheless, it is calculated that either force independently is strong enough and would have been able to hold the diffusion layer by itself. Further evidence suggests that, integrated over the entire solution, F(inverted Delta B) is the dominant paramagnetic force when the redox-active species is paramagnetic, e.g., [Co(bipy)(3)](ClO(4))(2) (bipy = 2,2'-bipyridine). Finally, convective behavior with diamagnetic redox-active species and magnet millielectrodes can be observed by holding closely (2-3 mm away) a repelling second magnet that bends the induction B to the point that the i x B product is not equal to 0. with Nd-Fe-B disk ma