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Background and Objectives@#Galectin-3 promotes fibroblast-to-myofibroblast differentiation and facilitates injury repair. Previous studies have shown that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) promote the differentiation of myocardial fibroblasts into myofibroblasts under inflammatory environment. Whether hucMSC-ex derived Galectin-3 (hucMSC-ex-Galectin-3) plays an important role in fibroblast-to-myofibroblast differentiation is the focus of this study. @*Methods@#and Results: Galectin-3 was knocked-down by siRNA in hucMSCs, and then exosomes were extracted. Fibroblasts were treated with LPS, LPS＋hucMSC-ex, LPS＋negative control-siRNA-ex (NC-ex), or LPS＋ Galectin-3-siRNA-ex (si-ex) in vitro. The coronary artery of the left anterior descending (LAD) branch was permanently ligated, followed by intramyocardial injection with phosphate buffered saline(PBS), hucMSC-ex, hucMSC-NC-ex, or hucMSC-si-ex in vivo. Western blot, RT-PCR, and immunohistochemistry were used to detect the expression of markers related to fibroblast-to-myofibroblast differentiation and inflammatory factors. Migration and contraction functions of fibroblasts were evaluated using Transwell migration and collagen contraction assays, respectively. β-catenin expression was detected by western blot and immunofluorescence. The results showed that hucMSC-ex increased the protein expression of myofibroblast markers, anti-inflammatory factors, and β-catenin. HucMSC-ex also reduced the migration and promoted the contractility of fibroblasts. However, hucMSC-si-ex did not show these activities. @*Conclusions@#HucMSC-ex-Galectin-3 promoted the differentiation of cardiac fibroblasts into myofibroblasts in an inflammatory environment, which was associated with increased β-catenin levels.
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Background and Objectives@#Galectin-3 promotes fibroblast-to-myofibroblast differentiation and facilitates injury repair. Previous studies have shown that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) promote the differentiation of myocardial fibroblasts into myofibroblasts under inflammatory environment. Whether hucMSC-ex derived Galectin-3 (hucMSC-ex-Galectin-3) plays an important role in fibroblast-to-myofibroblast differentiation is the focus of this study. @*Methods@#and Results: Galectin-3 was knocked-down by siRNA in hucMSCs, and then exosomes were extracted. Fibroblasts were treated with LPS, LPS＋hucMSC-ex, LPS＋negative control-siRNA-ex (NC-ex), or LPS＋ Galectin-3-siRNA-ex (si-ex) in vitro. The coronary artery of the left anterior descending (LAD) branch was permanently ligated, followed by intramyocardial injection with phosphate buffered saline(PBS), hucMSC-ex, hucMSC-NC-ex, or hucMSC-si-ex in vivo. Western blot, RT-PCR, and immunohistochemistry were used to detect the expression of markers related to fibroblast-to-myofibroblast differentiation and inflammatory factors. Migration and contraction functions of fibroblasts were evaluated using Transwell migration and collagen contraction assays, respectively. β-catenin expression was detected by western blot and immunofluorescence. The results showed that hucMSC-ex increased the protein expression of myofibroblast markers, anti-inflammatory factors, and β-catenin. HucMSC-ex also reduced the migration and promoted the contractility of fibroblasts. However, hucMSC-si-ex did not show these activities. @*Conclusions@#HucMSC-ex-Galectin-3 promoted the differentiation of cardiac fibroblasts into myofibroblasts in an inflammatory environment, which was associated with increased β-catenin levels.
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Background@#and Purpose Despite administration of evidence-based therapies, residual risk of stroke recurrence persists. This study aimed to evaluate the residual risk of recurrent stroke in acute ischemic stroke or transient ischemic attack (TIA) with adherence to guideline-based secondary stroke prevention and identify the risk factors of the residual risk. @*Methods@#Patients with acute ischemic stroke or TIA within 7 hours were enrolled from 169 hospitals in Third China National Stroke Registry (CNSR-III) in China. Adherence to guideline-based secondary stroke prevention was defined as persistently receiving all of the five secondary prevention medications (antithrombotic, antidiabetic and antihypertensive agents, statin and anticoagulants) during hospitalization, at discharge, at 3, 6, and 12 months if eligible. The primary outcome was a new stroke at 12 months. @*Results@#Among 9,022 included patients (median age 63.0 years and 31.7% female), 3,146 (34.9%) were identified as adherence to guideline-based secondary prevention. Of all, 864 (9.6%) patients had recurrent stroke at 12 months, and the residual risk in patients with adherence to guidelinebased secondary prevention was 8.3%. Compared with those without adherence, patients with adherence to guideline-based secondary prevention had lower rate of recurrent stroke (hazard ratio, 0.85; 95% confidence interval, 0.74 to 0.99; P=0.04) at 12 months. Female, history of stroke, interleukin-6 ≥5.63 ng/L, and relevant intracranial artery stenosis were independent risk factors of the residual risk. @*Conclusions@#There was still a substantial residual risk of 12-month recurrent stroke even in patients with persistent adherence to guideline-based secondary stroke prevention. Future research should focus on efforts to reduce the residual risk.
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Objective Abnormalities of lipid profile were considered as risk factors of hemorrhage after ischemic stroke. We aimed to determine the relationship between lipid levels and bleeding in minor stroke or transient ischemic attack (TIA) patients receiving antiplatelet therapy. Methods Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride were tested in a subgroup of 3044 consecutive patients from Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. Patients were randomized to clopidogrel plus aspirin group or single aspirin group. The primary endpoint was any bleeding within 90 days. The secondary endpoint was severe bleeding according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) definition. Cox proportional hazards models were used to assess the associations of lipid levels and outcomes. Results A total of 59 (1.9％) bleeding events occurred at 90 days. High-density lipoprotein cholesterol (adjusted HR=2.16; 95％CI 1.17-4.00, P=0.014) and age (adjusted HR=1.04;95％CI 1.01-1.06, P=0.006) were significantly associated with any bleeding. High-density lipoprotein cholesterol was also associated with severe bleeding (adjusted HR=3.05;95％CI 1.39-6.68, per 1 mmol/L increase). No correlations between outcomes and levels of total cholesterol, low-density lipoprotein cholesterol and triglyceride were found. There was no interaction of any lipid component level with randomized antiplatelet therapy. Conclusions Elevated high-density lipoprotein cholesterol is independently associated with any bleeding and severe bleeding in the patients with acute minor stroke or high-risk TIA on antiplatelet therapy.
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Objective To study the antagonistic effects of magnesium-selenium-fluorine preparation on dental fluorosis of mice and its mechanism,and to provide a foundational basis for prevention and control of dental fluorosis.Methods Eighty male SPF ICR mice,were divided into 8 groups according to body weight by random number table method:control group,magnesium group,selenium group,magnesium-selenium group,fluoride group,magnesium-fluorine group,selenium-fluorine group and magnesium-selenium-fluorine group.The control group,magnesium group,selenium group and magnesium-selenium group drank double steamed water,and the other four groups drank 50 mg/L F-double steamed water.The control group and fluoride group fed conventionally.Magnesium group and magnesium-fluorine group fed conventionally by adding MgSO4·7H2O 162.5 mg/kg.Selenium group andselenium-fluorine group fed conventionally by adding Na2SeO3 ·5H2O 2.0 mg/kg.Magnesium-selenium group and magnesium-selenium-fluorine group fed conventionally by adding MgSO4·7H2O 162.5 mg/kg and Na2SeO3·5H2O 2.0mg/kg.Then incisor specimens were obtained after the mice were put into death after treatment for 42 days.The expression of amelogenin was observed with immunohistochemical staining.And gray value is expressed as a result,the greater the gray value,the less protein expression.Results The results of light microscope showed that ameloblasts in the fluoride group showed disarrangement and even had vacuolar.The change of ameloblasts in the magnesium-selenium-fluorine group had no significant difference with control group.The expressions of amelogenin in enamel matrix of fluoride group (131.03 ± 11.14) was significantly higher than those of others (control group:143.44 ± 2.52,magnesium group:143.73 ± 12.43,selenium group:148.89 ± 2.85,magnesium-selenium group:148.38 ± 7.58,magnesium-fluorine group:145.90 ± 7.00,selenium-fluorine group:148.70 ± 4.90,and magnesiumselenium-fluorine group:151.89 4± 4.59,all P ＜ 0.05).The expression of amelogenin in ameloblast of fluoride group (165.49 ± 5.66) was significantly lower than those of control group,magnesium group,magnesium-fluorine group and selenium group (151.35 ± 2.52,149.27 ± 11.13,146.21 ± 4.84 and 150.39 ± 6.65,all P ＜ 0.05).The expression of amelogenin in ameloblast of selenium-fluorine group (165.46 ± 5.81) was significantly lower than those of magnesium group,magnesium-fluorine group and selenium group (all P ＜ 0.05).The results of factorial analysis showed that magnesium and selenium affected the expression of amelogenin in enamel matrix (F =4.195,15.009,all P ＜ 0.05),the interaction between fluoride and magnesium had an effect on the expression of amelogenin in enamel matrix (F =4.402,P ＜ 0.05).Interaction of fluoride,magnesium and selenium had no effect on the expression of amelogenin in enamel matrix (F =1.561,P ＞ 0.05).The fluoride,magnesium and selenium affected the expression of amelogenin in ameloblast (F =18.463,9.372,4.741,all P ＜ 0.05),the interactions between fluoride and magnesium,magnesium and selenium had effects on the expression of amelogenin in ameloblast (F =10.351,5.919,all P ＜ 0.05).Interaction of fluoride,magnesium and selenium had no effect on the expression of amelogenin in ameloblast (F =1.460,P ＞ 0.05).Conclusions There is an antagonistic effect of magnesium on the expression of enamel protein in fluorosis mice.However,it can not be considered that there is an effect of selenium on the expression of enamel protein in fluorosis mice.