The association between spinal cord injury (SCI) and bladder symptoms has been intensively described. Human umbilical cord mesenchymal stem cell (hUC-MSC) treatment is beneficial to the recovery of bladder function after SCI, but its mechanism is unclear. We established an SCI model, and prepared hUC-MSCs in advance, followed by verification using flow cytometry. The Basso, Beattie and Bresnahan (BBB) score and urodynamic index were employed to evaluate motor function and bladder functions, respectively. Hematoxylin-eosin staining, luxol fast blue staining, and Masson's trichrome staining were utilized to assess pathological changes. Real-time quantitative PCR and Western blot were used to determine the mRNA and protein expressions in bladder tissues. The immunophenotypes of the HUC-MSCs were CD90+ and CD105+, but CD34-, CD45- and HLA-DR-. Rats appeared severe motor dysfunction after SCI, but the BBB score was increased in hUC-MSCs after the second week. Pathologically, the improvement of the lesion area on the dorsal spinal cord, augmented anterior gray horn neuron cells of the spinal cord and lessened bladder tissue remodeling (fibrosis, collagen deposition) as well as modulated inflammation could be observed. Besides, SCI increased bladder weight, bladder capacity, urine volume and residual urine volume, and decreased urination efficiency. HUC-MSCs ameliorated SCI-induced pathological changes and bladder functions, the expressions of Collagen I, Collagen III, fibroblast growth factor 2 (FGF2), phospho-p38, transient receptor potential vanilloid 1, Toll-like receptor 4 and phospho-nuclear factor-kappa B (p-NF-κB). To sum up, HUC-MSCs contribute to the reconstruction of bladder function after SCI by repressing p38 MAPK/NF-κB pathway.

Macrophages play a critical role in the regulation of the inflammatory responses in sepsis. Methyltransferase like 7B (METTL7B) has been implicated in several pathophysiological conditions. Nevertheless, the potential engagement of METTL7B in sepsis remains to be elucidated. In this study, we retrieved transcriptomic profile data of septic patients and healthy donors and compared the expression level of METTL7B between septic patients and healthy controls. We also collected septic patient samples to analyze METTL7B expression via RT-qPCR. Murine bone marrow-derived macrophages (BMDMs) were isolated and treated with incremental doses of LPS as an in vitro cell model. METTL7B was overexpressed or knocked down in BMDMs, and lipopolysaccharide (LPS)-mediated inflammatory cytokines production and macrophage polarization were evaluated. We found that METTL7B was upregulated in the blood and peripheral blood mononuclear cells (PBMC) of septic patients, which also showed a significant diagnostic potential for sepsis. In BMDMs, METTL7B was induced in a time and dose-dependent manner by LPS. Modulating the expression level of METTL7B could regulate LPS-mediated inflammatory cytokines production and macrophage polarization. The functional role of METTL7B was also validated in a septic mouse model. Our findings indicate that METTL7B is implicated in the immunopathogenesis of sepsis through modulating macrophage-mediated inflammatory responses. METTL7B may serve as a potential diagnostic and therapeutic target for sepsis.

Danhong injection (DHI) restrains diabetic retinopathy and nephropathy (DR and DN) advancement in diabetic mice. However, the downstream mechanism of its modulation is not fully studied. Diabetic model mice (db/db mice) were intravenously injected with DHI and corresponding virus particles. MiR-30d-5p and JAK1 were detected. The body weight and fasting blood glucose mice were measured every 4 weeks. The renal tissues and serum of mice were collected, and the contents of creatinine and blood urea nitrogen were biochemically analyzed. IL-6, IFN-γ and TNF-α were detected by ELISA, with the pathological conditions of renal tissues in mice by He staining, and the adjustment conditions by TUNEL. Human retinal pigment epithelium (ARPE-19) cells were selected to induce DR model in vitro by high glucose, and exposed to DHI for treatment. The corresponding plasmids were transfected, and miR-30d-5p and JAK1 were detected, with the proliferation ability by plate cloning, apoptosis by flow cytometry, and cell migration ability by Transwell. The angiogenesis ability of cells was assessed by tube formation assay. The targeting relationship between miR-30d-5p and JAK1 was detected. The results manifested that miR-30d-5p was declined in DR and DN, while JAK1 expression was elevated. DHI was able to improve DR and renal injury. DHI could regulate the miR-30d-5p-JAK1 axis in vivo, and miR-30d-5p targeted and regulated JAK1. Upregulation of miR-30d-5p or inhibition of JAK1 could improve DR and renal injury. The results implies that DHI can repress the development of DR and DN by elevating miR-30d-5p and targeting JAK1.