A high matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 (MMP9/TIMP1) ratio is associated with poor ulcer healing, yet how the ratio of MMP9/TIMP1 changes in diabetic foot ulcers (DFUs) with infection and how these changes may affect wound healing remain unclear. Therefore, the objective of this investigation was to explore relationships among the MMP9/TIMP1 ratio, infection, and DFUs. After being informed of the details of this study, 32 patients signed consent forms. Skin biopsies were performed for all patients. Wound tissues were obtained from all patients with wounds, and healthy skin samples were collected from patients without wounds during orthopedic surgery. Microbial cultures were obtained using the samples from diabetic patients with wounds. All patients were divided into 4 groups according to colony-forming units (CFUs) per gram of tissue (>1 × 10 or <1 × 10): group A (diabetic wounds with high quantities of bacteria), group B (diabetic wounds with low quantities of bacteria), group C (diabetic patients without wounds), and group D (nondiabetic patients with wounds). In addition, the biopsies were evaluated by both reverse transcription-quantitative polymerase chain reaction and Western blotting to assess the levels of MMP9, TIMP1, and vascular endothelial growth factor (VEGF). The results show that for both mRNA and protein, expression of MMP9 (fold change 1.14 ± 0.12 vs 0.60 ± 0.08 vs 0.39±0.09 vs 0.13 ± 0.06, P < .01) decreased, whereas that of TIMP1 (1.01 ± 0.09 vs 2.86 ± 0.85 vs 4.88 ± 0.83 vs 7.29 ± 1.55, P < .01) and VEGF (1.01 ± 0.22 vs 3.55 ± 0.97 vs 5.72 ± 0.55 vs 6.92 ± 1.55, P < .01) increased from group A to group D. These results suggest that an increase in the MMP9/TIMP1 ratio in infected DFUs may induce a decrease in VEGF expression.

Background: The dysfunction of vascular smooth muscle cells (VSMCs) contributes to the development of atherosclerosis. This study aimed to investigate the role of circular RNA-0010283 (circ_0010283) in oxidized low-density lipoprotein (ox-LDL)-treated VSMCs and the associated action mechanism. Methods and Results: The expression of circ_0010283 was investigated using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was monitored by using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was detected by using flow cytometry assay. A transwell assay was performed to observe migration and invasion, and a scratch assay was implemented to test migration. The expression of proliferation, apoptosis and migration/invasion-related proteins was measured by using a western blot. The targeted relationship was predicted by using a bioinformatics tool (Starbase) and verified by using a dual-luciferase reporter assay, a RNA immunoprecipitation (RIP) assay and a RNA pull-down assay. circ_0010283 was highly expressed in serum samples from atherosclerosis patients and ox-LDL-treated human VSMCs (HVSMCs). circ_0010283 knockdown suppressed ox-LDL-induced proliferation, migration and invasion in HVSMCs. MicroRNA-133a-3p (miR-133a-3p) was confirmed as a target of circ_0010283, and miR-133a-3p deficiency reversed the effects of circ_0010283 knockdown. Moreover, pregnancy-associated plasma protein A (PAPPA) was targeted by miR-133a-3p, and PAPPA overexpression reversed the effects of miR-133a-3p restoration. Interestingly, circ_0010283 could regulate PAPPA expression by mediating miR-133a-3p. Conclusions: circ_0010283 participated in ox-LDL-induced dysfunctions of HVSMCs by modulating the miR-133a-3p/PAPPA pathway, suggesting that circ_0010283 might be associated with atherosclerosis pathogenesis.

Numerous studies have proposed the transplantation of mesenchymal stem cells (MSCs) in the treatment of typical type 2 diabetes mellitus (T2DM). We aimed to find a new strategy with MSC therapy at an early stage of T2DM to efficiently prevent the progressive deterioration of organic dysfunction. Using the high-fat-fed hyperinsulinemia rat model, we found that before the onset of typical T2DM, bone marrow-derived MSCs (BM-MSCs) significantly attenuated rising insulin with decline in glucose as well as restored lipometabolic disorder and liver dysfunction. BM-MSCs also favored the histological structure recovery and proliferative capacity of pancreatic islet cells. More importantly, BM-MSC administration successfully reversed the abnormal expression of insulin resistance-related proteins including GLUT4, phosphorylated insulin receptor substrate 1, and protein kinase Akt and proinflammatory cytokines IL-6 and TNFα in liver. These findings suggested that MSCs transplantation during hyperinsulinemia could prevent most potential risks of T2DM for patients.