Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by an excessive inflammatory response within the lungs and severely impaired gas exchange resulting from alveolar-capillary barrier disruption and pulmonary edema. The costimulatory protein B7H3 functions as both a costimulator and coinhibitor to regulate the adaptive and innate immune response, thus participating in the development of microbial sepsis and pneumococcal meningitis. However, it is unclear whether B7H3 exerts a beneficial or detrimental role during ALI. In the present study we examined the impact of B7H3 on pulmonary inflammatory response, polymorphonuclear neutrophil (PMN) influx and lung tissue damage in a murine model of lipopolysaccharide (LPS)-induced direct ALI. Treatment with B7H3 protected mice against LPS-induced ALI, with significantly attenuated pulmonary PMN infiltration, decreased lung myeloperoxidase (MPO) activity, reduced bronchoalveolar lavage fluid (BALF) protein content and ameliorated lung pathological changes. In addition, B7H3 significantly diminished LPS-stimulated PMN chemoattractant CXCL2 production by inhibiting NF-κB p65 phosphorylation and substantially attenuated LPS-induced PMN chemotaxis and transendothelial migration by down-regulating CXCR2 and Mac-1 expression. These results demonstrate that B7H3 substantially ameliorates LPS-induced ALI and this protection afforded by B7H3 is predominantly associated with its inhibitory effect on pulmonary PMN migration and infiltration.

Background: Three-dimensional (3D) culture has been reported to increase the therapeutic potential of mesenchymal stem cells (MSCs). The present study assessed the therapeutic efficacy of extracellular vesicles (EVs) from 3D cultures of human placental MSCs (hPMSCs) for acute kidney injury (AKI). Methods: The supernatants from monolayer culture (2D) and 3D culture of hPMSCs were ultra-centrifuged for EVs isolation. C57BL/6 male mice were submitted to 45 min bilateral ischemia of kidney, followed by renal intra-capsular administration of EVs within a 72 h reperfusion period. Histological, immunohistochemical, and ELISA analyses of kidney samples were performed to evaluate cell death and inflammation. Kidney function was evaluated by measuring serum creatinine and urea nitrogen. The miRNA expression profiles of EVs from 2D and 3D culture of hPMSCs were evaluated using miRNA microarray analysis. Results: The 3D culture of hPMSCs formed spheroids with different diameters depending on the cell density seeded. The hPMSCs produced significantly more EVs in 3D culture than in 2D culture. More importantly, injection of EVs from 3D culture of hPMSCs into mouse kidney with ischemia-reperfusion (I/R)-AKI was more beneficial in protecting from progression of I/R than those from 2D culture. The EVs from 3D culture of hPMSCs were more efficient against apoptosis and inflammation than those from 2D culture, which resulted in a reduction in tissue damage and amelioration of renal function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in EVs from 3D culture of hPMSCs, especially miR-93-5p. Conclusion: The EVs from 3D culture of hPMSCs have therapeutic potential for I/R-AKI.

Background: Infectious mononucleosis (IM) is a common disease in children; however, liver injury is its most common complication. However, the pathogenesis of IM complicated with liver injury is ambiguous. Thus, this study aimed to explore the potential mechanism of IM-associated liver injury. Methods: This study was conducted at the Children’s Hospital of Soochow University by collecting peripheral blood of 70 hospitalized children with IM. These patients were categorized into the liver injury (LIG, n = 35) and the non-liver injury groups (NLIG, n = 35), respectively. Subsequently, PBMCs and plasma were separated and obtained. PBMCs transcriptome sequencing was performed in two groups (5 cases in each group), and significantly differentially expressed genes (DEGs) were screened. Additionally, GO function enrichment, KEGG enrichment and GSEA analyses were performed. RT-PCR helped to detect the relative GBP5, NLRP3 and caspase-1 expressions in two groups (30 cases in each group) while the two groups’ caspase-1, IL-1β and IL-18 in plasma levels were measured by ELISA. Thus, clinical and laboratory datas of 60 hospitalized children with IM were evaluated. Results: Transcriptome sequencing results showed that 171 DEGs were screened in the NLIG group, compared with the LIG. Among them, 154 DEGs were up-regulated, and 17 were down-regulated, respectively. KEGG and GSEA analyses showed that IM-associated liver injury is correlated with a NOD-like receptor signaling pathway. Statistically significant differences were observed in the white blood cell and lymphocyte counts, CD3⁺CD4⁺ T cells, CD3⁺CD8⁺T cells, alanine aminotransferase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) of the two groups (p < 0.05). Compared with NLIG, GBP5, NLRP3 and caspase-1 expressions in PBMCs, as well as the caspase-1, IL-1β and IL-18 in plasma levels, were significantly higher in LIG (p < 0.001). A correlation analysis revealed a positive correlation of GBP5 with LDH, ALT, AST, CD3⁺CD8⁺T cells and NLRP3 (p < 0.05). Conclusions: Our findings demonstrate that GBP5 contributes to liver injury in IM children through the NLRP3-dependent pathway.