Phenotypic switching of vascular smooth muscle cells (VSMCs) plays an initial role in neointimal hyperplasia, the main cause of many occlusive vascular diseases. The aim of this study was to measure the effects of resveratrol (RSV) on the phenotypic transformation of VSMCs and to investigate its mechanism of action.Cultured VSMCs isolated from rat thoracic aorta were prepared with serum starvation for 72 hours followed by RSV treatment (50-200 μmol/L) and 10% serum stimulation. Male Sprague-Dawley rats, subjected to carotid arteries injury from a balloon catheter, were exposed to intraperitoneal injection of RSV (1 mg/kg) or saline and were killed after 7 or 28 days.Compared with cells in the serum-induced group, VSMCs in the RSV or N-[N-(3, 5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) treatment group exhibited significant decreases of proliferation and migration. The total and cytoplasmic Notch-1 levels were declined by RSV, accompanied by a significant increase in smooth muscle α-actin and smooth muscle myosin heavy chain protein. The expression of Notch-1, Jagged-1, Hey-1, and Hey-2 mRNA in balloon-injured arteries at 7 days was decreased by RSV treatment. Arteries from RSV-treated rats showed less neointimal hyperplasia, lower collagen content, and a lower rate of cells positive for proliferating cell nuclear antigen 28 days after injury, compared with saline controls.The results indicate that RSV can attenuate phenotypic switching of VSMCs after arterial injury through inhibition of the Notch pathway.
Objective To investigate the effects on the patients of acute cerebral vascular ischemia diseases (ACVID) treated early by the High - energy Bio - ion instrument. Methods 101 cases of ACYTD were divided randomly into two groups:①ControIIed group: the patients in this group were treated by the usual therapeutic methods; ②Therapy group: the patients in this group were treated not only by the usula therapeutic methods but also by the treatment with the High - energy Bio- ion instrument. Observing data;①Scores of neurologic deficit:②The mean velocities (Mvs) of the cerebral arteries. Results Both the numbers of the obvious improvement and the Mvs in the therapy groups were significanly great (P 0.05) compared with the controlled goups. Conclusions The treatment with the High - energy Bio - ion instrument was one of the effective therapy ways of ACVID.
Abstract Background Optical coherence tomography (OCT) guided percutaneous coronary intervention (PCI) has been demonstrated to improve short and long-term outcomes compared with standard angiography-guided PCI. However, little is known about the impact of cholesterol crystals on the prognosis of patients with acute coronary syndrome (ACS) in the setting of receiving OCT-guided PCI. Purpose This study aims to investigate the association between cholesterol crystals and 6-month outcomes in ACS patients who underwent OCT-guided PCI. Methods Patients with ACS who underwent OCT-guided PCI in a high-volume PCI center between July 2020 and June 2022 were retrospectively enrolled and were further divided into two groups according to the presence or absence of cholesterol crystals. OCT imaging characteristics including plaque morphology before the PCI procedure in target lesions were assessed. The primary outcome was a composite of all-cause death, ischemia-driven revascularization, or readmission for heart failure in a 6-month follow-up period. The association between cholesterol crystals and 6-month outcomes was evaluated using Kaplan-Meier curves. Independent predictors for cholesterol crystals and 6-month outcomes were evaluated by the logistic regression and Cox proportional hazards regression analyses, respectively. Results 403 patients were enrolled in this study. The mean age was 61 years old and 79.4% were men. Cholesterol crystals were presented in 224 (55.6%) target lesions in patients with ACS. Baseline characteristics were not statistically different between the two groups in age, sex, smoke, previous hyperlipidemia, and other clinical features, except for diabetes, multivessel disease, and ACS classification (p <0.05). In the multivariable logistic regression analysis, cholesterol crystals were associated with diabetes, plaque rupture, lipid length, calcification, macrophage infiltration, and thin-capped fibroatheroma (all p <0.05). Patients with cholesterol crystals had higher risks of poor 6-month composite outcomes when compared to those without cholesterol crystals (13.4% vs. 6.7%, HR 2.09, 95%CI 1.07-4.09, p = 0.031), even after confounders adjustment for age, sex, diabetes, multivessel disease and ACS classification using inverse probability of treatment weighting (p = 0.027). Subgroup analysis showed significant interactions between cholesterol crystals and 6-month outcomes with respect to the male (HR 2.82, 95%CI 1.22-6.51, p = 0.015), target lesions in LAD (HR 4.47, 95%CI 1.29-15.44, p = 0.018), and incomplete revascularization (HR 3.08, 95%CI 1.04-8.98, p = 0.042). The Cox regression analysis identified cholesterol crystal as an independent predictor for 6-month composite outcomes (HR 2.12, 95%CI 1.08-4.19, p = 0.030). Conclusions The presence of cholesterol crystals was associated with a poor 6-month prognosis in patients with ACS, even in the setting of receiving OCT-guided PCI.
OBJECTIVE To investigate the effects of heme oxygenase-1 (HO-1) gene on human islets in vitro, and to explore the potential value of gene therapy in clinical islet transplantation. METHODS Adenovirus vector carrying human HO-1 gene (Ad-HO-1) or EGPF (Ad-EGFP) were established respectively. Human cadaveric pancreases were isolated, purified, cultured, and divided into 3 groups to be transfected with Ad-HO-1, Ad-EGFP or blank vector. Human tumor necrosis factor and cyclohexamide (CHX) were added into the culture fluid of the pancreatic islets. 48 hours later the pancreatic islets were digested into single cells. Flow cytometry was used to detect the apoptosis. Glucose of the concentration of 16.7 mmol/L was added into the culture fluid of the 3 groups of islet cells. After 1-hour co-incubation radioimmunochemistry was used to detect the level of insulin in the supernatant. RESULTS After stimulation of glucose the insulin concentration in the supernatant of the Ad-HO-1 group was 270 mIU/L +/- 89 mIU/L, significantly higher than those of the Ad-EGFP group (189 mIU/L +/- 88 mIU/L) and control group (182 mIU/L +/- 59 mIU/L, both P < 0.05). The apoptotic ratio of the Ad-HO-1 group was 63.1% +/- 10.9%, significantly lower than that of the control group (90.9% +/- 11.3%, P < 0.01) after treatment with TNFalpha and CHX. CONCLUSION Transfection of Ad-HO-1 into human islets improves anti-apoptotic function in cultured human islets and promotes insulin release of human pancreatic islets.
After fertilization, the zygote undergoes cell division. Up to the 8-cell stage, the blastomeres of mouse preimplantation embryos are morphologically identical. The first cell differentiation starts in the morula leading to the formation of trophectoderm cells and inner cell mass cells of the blastocyst. The regulation of the differentiation event and the formation of blastocysts are not fully known. Lethal-7 (let-7) is a family of evolutionarily conserved microRNAs. Here, we showed that the expression of let-7a and let-7g decreased drastically from the 1-cell stage to the 2-cell stage, remained low up to the 8-cell stage and slightly increased after the morula stage of mouse embryos. The expression of let-7 in the inner cell mass was higher than that in the trophectoderm. Forced expression of let-7a in embryos at the 1-cell and 4-cell stage inhibited blastocyst formation and downregulated the expression of CDX2 but maintained that of OCT4 in the trophectoderm. Forced expression of other let-7 isoforms exhibited similar inhibitory action on blastulation. On the other hand, inhibition of let-7a at the 4-cell stage and the 8-cell stage enhanced blastocyst formation. Co-injection of green fluorescent protein (GFP) mRNA (lineage tracer) with either precursor of let-7a (pre-let-7a) or scramble control into one blastomere of 2-cell embryos showed that ~75% of the resulting blastocysts possessed GFP+ cells in their inner cell mass only. The biased development towards the inner cell mass with forced expression of let-7 was reproduced in 2-cell chimeric embryos consisting of one wildtype blastomere and one GFP mRNA-injected blastomere from another 2-cell embryo carrying a doxycycline-inducible let-7g gene. Bioinformatics analysis indicated that Tead4 was a potential target of let-7. Let-7 bound to the 3'UTR of Tead4 and let-7 forced expression downregulated the expression of Tead4 in mouse blastocysts. Co-injection of Tead4 mRNA partially nullified the modulatory roles of let-7a in the inner cell mass cell fate. In conclusion, a high level of let-7 at the 2-cell stage favored the formation of the inner cell mass, whereas a low level of let-7 at the 4-cell to 8-cell stage enhanced blastocyst formation. Tead4 mediated the action of let-7 on the inner cell mass cell-fate determination.
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