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Thoracic aortic dissection (TAD) is a severe and extremely dangerous cardiovascular disease. Proliferation, migration and phenotypic switching of vascular smooth muscle cells (SMCs) are major pathogenetic mechanisms involved in the development of TAD. The present study was designed to investigate the expression and potential function of serine peptidase inhibitor Kunitz type 2 (SPINT2) in TAD. The gene expression profile data for ascending aorta from patients with TAD were downloaded from the GEO database with the accession number GSE52093. Bioinformatics analysis using GEO2R indicated that the differentially expressed SPINT2 was prominently decreased in TAD. The expression levels of SPINT2 mRNA and protein in aortic dissection specimens and normal aorta tissues were measured using reverse transcription-quantitative PCR and western blotting. SPINT2 expression was downregulated in clinical samples from aortic dissection specimens of patients with TAD compared with the corresponding expression noted in tissues derived from patients without TAD. In vitro, platelet-derived growth factor BB (PDGF-BB) was applied to induce the isolated primary mouse aortic SMC phenotypic modulation (a significant upregulation in the expression levels of synthetic markers), and the SMCs were infected with the adenoviral vector, Ad-SPINT2, to construct SPINT2-overexpressed cell lines. SMC viability was detected by an MTT assay and SMC proliferation was detected via the presence of Ki-67-positive cells (immunofluorescence staining). To explore the effects of SPINT2 on SMC migration, a wound healing assay was conducted. ELISA and western blotting assays were used to measure the content and expression levels of MMP-2 and MMP-9. The expression levels of vimentin, collagen I, α-SMA and SM22α were measured using western blotting. The PDGF-BB-induced proliferation and migration of SMCs were recovered by SPINT2 overexpression. The increase in the expression levels of SPINT2 reduced the expression levels of active matrix metalloproteinases (MMPs), MMP-2 and MMP-9. Overexpression of SPINT2 suppressed SMC switching from a contractile to a synthetic type, as evidenced by decreased vimentin and collagen I expression levels along with increased α-smooth muscle actin and smooth muscle protein 22-α expression levels. Furthermore, activation of ERK was inhibited in SPINT2-overexpressing SMCs. A specific ERK agonist, 12-O-tetradecanoylphorbol-13-acetate, reversed the SPINT2-mediated inhibition of SMC migration and the phenotypic switching. Collectively, the data indicated that SPINT2 was implicated in the proliferation, migration and phenotypic switching of aortic SMCs, suggesting that it may be involved in TAD progression.
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OBJECTIVE: To investigate the effects of silver foam combined with Dermlin wound healing dressing on concentrations of inflammatory factors of wound surface and quality of life of the patients with diabetic lower limb ulcers. METHODS: A total of 60 patients with diabetic lower limb ulcers admitted to the First Affiliated Hospital of Anhui Medical University during January 2020 and December 2020 were retrospectively enrolled in this study. According to the different treatments, they were divided into a control group (30 cases treated with Dermlin wound healing dressing only), and a research group (30 cases treated with silver foam combined with Dermlin dressing). The clinical efficacy, wound healing status, pain intensity (visual analog scale (VAS) scores), concentrations of inflammatory factor (high-sensitivity C-reactive protein (hsCRP), leukocyte interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), procalcitonin (PCT)), angiogenesis factors levels (basic fibroblast growth factor (BFGF), vascular endothelial growth factor (VEGF)), oxidative stress reaction indexes (advanced protein oxidation products (AOPP), malondialdehyde (MDA) and superoxide dismutase (SOD)) and quality of life (SF-36 scale) were compared between two groups. The bacterial removal rate was calculated based on the results of bacterial culture before and after treatment. The central granulated tissue was collected after the granulation tissue coverage rate was calculated. RESULTS: The research group had significantly higher overall response rate (96.67% vs 73.33%), shorter wound healing time and higher wound healing rate than the control group (all P<0.05). The VAS scores were decreased in both Groups 1, 3 and 7 d after treatment as compared with those before treatment, and the VAS scores were significantly lower in the research group than in the control group during the same period (all P<0.05). After treatment, the concentrations of hsCRP, IL-6, TNF-α, PCT, AOPP and MDA were decreased in both groups, while the levels of bFGF, VEGF, l TGF-ß1, SOD and SF-36 scores were increased significantly (all P<0.05). The above-mentioned indicators of the research group improved significantly compared with those of the control group (all P<0.05). The bacterial removal rate and granulation tissue coverage rate of the research group were significantly higher than those of the control group (both P<0.05). CONCLUSION: The treatment of diabetic lower limb ulcers with silver foam combined with Dermlin dressing can effectively promote wound healing, reduce pain intensity, and improve quality of life in patients with diabetic lower limb ulcers. Such effects may be attributed to lower levels of inflammatory factor levels, regulation of oxidative stress, and improvement of angiogenesis.
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INTRODUCTION: More and more evidence show that periodontal anaerobes contribute to pathogenesis of peripheral artery diseases. As a typical oral anaerobe that results in periodontitis, P.gingivalis aggregates platelets in PRP in vitro and participated in artery thrombosis. However, in vivo effect on platelet activation and aggregation remains unclear. This study aimed to clarify its role on platelets activation on more physiological environment, that is, on whole blood and systemic circulation. MATERIALS AND METHODS: To fully estimate platelet activation, CD62P(P-selectin) expression on platelet surface and fibrinogen binding of platelet via conjugated glycoprotein GPIIb/IIIa in whole blood were assayed by flow cytometry, and platelet aggregation was measured on an impedance aggregometor. As primary study, platelet reactivity was assessed after in vitro rat whole blood incubation with P.gingivalis strain 381 in tubes, followed or not followed by ADP and arachidonic acid stimulation. In addition, PBS solution of P.gingivalis was infused into rat to produce transient bacteremia model for 5 minutes and blood samples were subjected to analysis for platelet activation in vivo. RESULTS: P.gingivalis could not induce rat platelet aggregation in whole blood in vitro, but increased aggregation when irritated by collagen stimulation. Flow cytometric study showed that incubation with P.gingivalis increased CD62P expression and fibrinogen binding of platelet. Moreover, further stress by 10 µmol/L ADP and 260 mmlol/L arachidonic acid yielded additional expression. As in vivo study, after P.gingivalis solution challenged, rat platelet aggregability was enhanced, and CD62P positive percentage of platelets and further reactivity to ADP stimulation improved. CONCLUSION: In whole blood and in systemic circulation, P.gingivalis could induce rat platelet activation and increase aggregability transiently. The results helped to understand the mechanism underlining which P.gingivalis promoted arteriosclerosis and thrombo-embolic disorders. Further study about chronic infection with P.gingivalis on platelet activity is expected.
