UNASSIGNED: Lipopolysaccharides (LPS) stimulate production of inflammatory cytokines. Chrysin is flavonoid beneficial for treatment of inflammatory conditions. Bone marrow mesenchymal stem cell (BM-MSC) exosomes have regenerative ability in different tissues.
UNASSIGNED: To assess potential role of chrysin and BM-MSC exosomes on ultra-structure, viability and function of human dermal fibroblasts-adult (HDFa) stimulated by LPS.
UNASSIGNED: HDFa cells were divided into: Group I: Cells received no treatment. Group II: Cells were stimulated with LPS. Group III: LPS stimulated cells were treated with chrysin. Group IV: LPS stimulated cells were treated with exosomes.
UNASSIGNED: After 48 h, ultrastructural examination of HDFa cells in Group I revealed intact plasma membrane and numerous cytoplasmic organelles. Group II displayed destructed plasma membrane and apoptotic bodies. Group III showed intact plasma membrane with loss of its integrity at some areas. Group IV demonstrated intact plasma membrane that showed fusion with exosomes at some areas. Statistical analysis of MTT represented highest mean value of cell viability% in Group IV followed by Groups III, I and II respectively. Statistical analysis of enzyme-linked immunosorbent assay (ELISA) showed the highest mean value of interleukin-1β (IL-1β) was in Group II followed by Groups III, IV and I, while highest mean values of interleukin-10 (IL-10), nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins were in Group I, followed by Groups IV, III and II respectively.
UNASSIGNED: LPS have harmful consequences on ultra-structure, viability and function of HDFa cells. BM-MSC exosomes have better regenerative action on inflamed fibroblasts in comparison to chrysin.

Pancreatic cancer (PC) is one of the most lethal malignant tumors and has the lowest survival rate due to early metastasis and drug resistance. Exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs) have emerged as crucial regulators of the progression of various tumors. These vesicles contain abundant circRNAs that have important biological functions. This study aimed to elucidate the role of exosomal circRNAs in PC progression. In this study, we successfully isolated BM-MSCs from human bone marrow based on their surface marker expression and osteogenic and adipogenic differentiation potential. We found that BM-MSC-derived exosomes significantly reduced the invasion, migration, and proliferation of PC cells, as well as tumor stemness. According to whole-transcriptome resequencing and clustering heat map analysis, we identified the key molecule circ_0030167 and miR-338-5p, its downstream target. We revealed that circ_0030167 mainly regulates miR-338-5p, enhances Wif1 expression, and inhibits the Wnt8/β-catenin pathway, thereby inhibiting the stemness of PC cells and tumor progression. Overall, BM-MSC exosomal circ_0030167 contributes to the progression and stemness of PC cells via the miR-338-5p/wif1/Wnt 8/β-catenin axis. Our study provides a new perspective for the treatment of PC.

Immunotherapy has gained increasing focus in treating pancreatic ductal adenocarcinoma (PDAC), since conventional therapies like chemotherapy could not provide satisfactory improvement in overall survival outcome of PDAC patients. However, it is still not the game changing solution due to the unique tumor microenvironment and low cancer immunogenicity of PDAC. Thus, inducing more intratumoral effector immune cells as well as reversing immunosuppression is the core of PDAC treatment. Herein, we demonstrate an exosome-based dual delivery biosystem for enhancing PDAC immunotherapy as well as reversing tumor immunosuppression of M2-like tumor associated macrophages (M2-TAMs) upon disruption of galectin-9/dectin 1 axis. The deliver system is constructed from bone marrow mesenchymal stem cell (BM-MSC) exosomes, electroporation-loaded galectin-9 siRNA, and surficially modified with oxaliplatin (OXA) prodrug as an immunogenic cell death (ICD)-trigger. The use of biomaterials, BM-MSC exosomes, can significantly improve tumor targeting efficacy, thus increasing drug accumulation in the tumor site. The combined therapy (iEXO-OXA) elicits anti-tumor immunity through tumor-suppressive macrophage polarization, cytotoxic T lymphocytes recruitment and Tregs downregulation, and achieves significant therapeutic efficacy in cancer treatment.