Impaired wound healing is commonly encountered in patients with diabetes mellitus, which may lead to severe outcomes such as amputation, if untreated timely. Macrophage plays a critical role in the healing process including the resolution phase. Although magnetic therapy is known to improve microcirculation, its effect on wound healing remains uncertain. In the present study, we found that 0.6 T static magnetic field (SMF) significantly accelerated wound closure and elevated reepithelialization and revascularization in diabetic mice. Notably, SMF promoted the wound healing by skewing the macrophage polarization towards M2 phenotype, thus facilitating the resolution of inflammation. In addition, SMF upregulated anti-inflammatory gene expression via activating STAT6 and suppressing STAT1 in macrophage. Taken together, our results indicate that SMF may be a promising adjuvant therapeutic tool for treating diabetic wounds.

Background Osteoporosis is a common metabolic bone disease without effective treatment. Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to differentiate into multiple cell types. Increased adipogenic differentiation or reduced osteogenic differentiation of BMSCs might lead to osteoporosis. Whether static magnetic fields (SMFs) might influence the adipo-osteogenic differentiation balance of BMSCs remains unknown. Methods The effects of SMFs on lineage differentiation of BMSCs and development of osteoporosis were determined by various biochemical (RT-PCR and Western blot), morphological (staining and optical microscopy), and micro-CT assays. Bioinformatics analysis was also used to explore the signaling pathways. Results In this study, we found that SMFs (0.2–0.6 T) inhibited the adipogenic differentiation of BMSCs but promoted their osteoblastic differentiation in an intensity-dependent manner. Whole genomic RNA-seq and bioinformatics analysis revealed that SMF (0.6 T) decreased the PPARγ-mediated gene expression but increased the RUNX2-mediated gene transcription in BMSCs. Moreover, SMFs markedly alleviated bone mass loss induced by either dexamethasone or all-trans retinoic acid in mice. Conclusions Taken together, our results suggested that SMF-based magnetotherapy might serve as an adjunctive therapeutic option for patients with osteoporosis.

Renal fibrosis is a common pathological hallmark of chronic kidney disease (CKD). Renal sympathetic nerve activity is elevated in patients and experimental animals with CKD and contributes to renal interstitial fibrosis in obstructive nephropathy. However, the mechanisms underlying sympathetic overactivation in renal fibrosis remain unknown. Norepinephrine (NE), the main sympathetic neurotransmitter, was found to promote TGF-β1-induced epithelial-mesenchymal transition (EMT) and fibrotic gene expression in the human renal proximal epithelial cell line HK-2. Using both genetic and pharmacological approaches, we identified that NE binds Gαqcoupled α1-adrenoceptor (α1-AR) to enhance EMT of HK-2 cells by activating p38/ Smad3 signaling. Inhibition of p38 diminished the NE-exaggerated EMT process and increased the fibrotic gene expression in TGF-β1-treated HK-2 cells. Moreover, the pharmacological blockade of α1-AR reduced the kidney injury and renal fibrosis in a unilateral ureteral obstruction mouse model by suppressing EMT in the kidneys. Thus, sympathetic overactivation facilitates EMT of renal epithelial cells and fibrosis via the α1-AR/p38/Smad3 signaling pathway, and α1-AR inhibition may be a promising approach toward treating renal fibrosis.

Impaired wound healing is commonly encountered in patients with diabetes mellitus, which may lead to severe outcomes such as amputation, if untreated timely. Macrophage plays a critical role in the healing process including the resolution phase. Although magnetic therapy is known to improve microcirculation, its effect on wound healing remains uncertain. In the present study, the model of diabetic mice was used to prove the effect of static magnetic field (SMF) in wound healing process. The positive role of SMF in macrophage polarization was observed in wound areas of db/db mice by the immunofluorescence staining and flow cytometric analysis. In order to examine the molecular mechanism of SMF in the wound healing, peritoneal macrophages were isolated from db/db mice and treated by LPS or IL‐4. We found 0.6 T SMF significantly accelerated wound closure rate by 50%. Histological analyses revealed significantly shorter distances by 26.7% between the epithelial tips of punched wound and distances by 33.3% between the edges of the panniculus carnosus in SMF group at day 7 postoperatively. SMF promoted M2 macrophage recruitment by 87.5% and reduced M1 macrophages accumulation by 24.3%, which was observed by immunofluorescence staining in wound areas of db/db mice. Flow cytometry analysis also revealed that M2 macrophages (F4/80+CD206+) were increased and M1 macrophages (F4/80+CD206−) were significantly decreased, indicating SMF facilitates M2 polarization in inflamed tissues. The expression levels of pro‐inflammatory markers (iNOS, IL‐6, IL‐1β, CCR7) in injured tissues were paradoxically downregulated in the SMF group. Meanwhile, SMF significantly raised the expression levels of reparative genes (CD206, Fizz1, Arg‐1, IL‐10). The pro‐inflammatory iNOS expression was decreased and anti‐inflammatory Arg‐1 was increased in SMF/LPS/IL‐4‐treated macrophages. Furthermore, SMF inhibited LPS‐induced STAT1 phosphorylation and augmented IL‐4‐induced STAT6 phosphorylation in the macrophages. In summary, our study showed for the first time the effect of 0.6 T SMF on wound healing in diabetic mice. These results indicate that SMF accelerates diabetic wound healing by promoting macrophage polarization and resolution of inflammation through modulation of the JAK‐STAT pathway. Therefore, focusing on SMF in therapeutic interventions might be useful for treating diabetic wound by re‐normalizing the healing process. Support or Funding Information This work was supported by the National Natural Science Foundation of China (grants 81703591).