No abstract

Radiation proctopathy (RP) is characterized by inflammation of colorectal tissue and is a common complication of radiation therapy for pelvic malignancies with high incidence but lacking effective treatment. Here, we found that platelet-derived growth factor C (PDGF-C) and fibrosis markers were up-regulated in tissue samples from patients with RP and in rectal tissues after irradiation in a mouse model of RP. Genetic deletion of Pdgf-c in mice ameliorated RP-induced injuries. Genome-wide gene expression profiling and in vitro assays revealed that the promotive effect of PDGF-C in RP development was mediated by activation of PDGF receptors (PDGFRs) and C-X-C motif chemokine receptor 4, a proinflammatory chemokine regulated by transcription factor ETS variant transcription factor 1. Treatment with crenolanib, a selective inhibitor of PDGFRs, prevented or reduced RP in mice after irradiation. These results reveal that inhibition of PDGF-C signaling may have therapeutic value for the treatment of RP.

Mesenchymal stem cells (MSCs) have become a recent focus of experimental and clinical research regarding myocardial regeneration. However, the therapeutic potential of these cells is limited by poor survival. Prostaglandin E1 (PGE1) is known to have anti-inflammatory and anti-apoptotic effects on the myocardium. The aim of the present study was to determine whether PGE1 could protect MSCs against serum deprivation (SD)-induced apoptosis. An SD model was used to induce apoptosis in MSCs in vitro. Apoptotic morphological changes were detected by Hoechst 33258 fluorescent nuclear staining; and Annexin V-fluorescein isothiocyanate/propidium iodide (PI) double staining and flow cytometry was used to quantify the rate of apoptosis. Western blot analysis was used to detect the expression levels of the apoptosis-associated proteins Bcl-2, Bax and caspase-3. The results of the present study demonstrated that SD induced apoptosis of MSCs, and that treatment with PGE1 attenuated the morphological changes characteristic of apoptosis. Annexin V/PI staining showed that the rate of apoptosis gradually increased with the duration of ischemia. Furthermore, treatment with PGE1 significantly reduced SD-induced apoptosis, decreased the protein expression levels of Bax and caspase-3, and increased the expression levels of Bcl-2. These data suggest that PGE1 is able to influence the survival of MSCs under certain conditions. These results may aid in improving the therapeutic efficacy of MSC transplantation used to treat chronic ischemic heart disease.

Water kefir, a natural and stable functional microbiota system consisting of a symbiotic mixture of probiotics, showed multiple bioactivities, but it was little known about the effect of water kefir...