二乙酰基莲心碱对猪冠状动脉条的影响

目的:观察二乙酰基莲心碱拮抗氯化钾、乙酰胆碱(Ach)和组胺(His)所致猪冠状动脉条收缩的作用.方法:离体平滑肌实验方法,观察二乙酰基莲心碱对氯化钾,Ach,His所致猪冠状动脉条收缩曲线的影响以及在无钙克氏液中,对His引起猪冠状动脉条第一相收缩和钙引起第二相收缩的影响.结果:不同剂量二乙酰基莲心碱可使氯化钾,Ach,His所致冠脉条收缩量效曲线呈非竞争性拮抗作用,对冠脉条第一相和第二相收缩都有明显的抑制作用结论:二乙酰基莲心碱具有扩张冠脉的作用,此作用与拮抗细胞内钙的释放和抑制外钙内流有关.     

Role of metabolism by intestinal microbiota in pharmacokinetics of oral baicalin

Baicalin (baicalein-7-glucuronide) is a flavonoid purified from Scutellaria baicalensis Georgi that has traditionally been used for treatment of hypertension, cardiovascular diseases, and viral hepatitis. In this study, the effects of intestinal microbiota on the pharmacokinetics of baicalin were investigated in normal and antibiotic-pretreated rats following p.o. administration of 100 mg/kg baicalin by using liquid chromatography/ion trap mass spectrometry. When rats were pretreated orally with cefadroxil, oxytetracycline and erythromycin for 3 days to control the number of intestinal bacteria, the pharmacokinetic parameters of oral baicalin were significantly affected by antibiotics: C_max, T_1/2(β), K_el and AUC values were significantly changed compared to those in normal rats. These results indicate that intestinal microbiota might play a key role in the oral pharmacokinetics of baicalin.     

Vulvar epithelioid sarcoma: A case report with literature review

ObjectiveTo report a case of vulvar epithelioid sarcoma, a rare type of tumor that has been reported in 37 cases in the English literature to date.Case reportWe report three cases of vulvar epithelioid sarcoma, proximal type. Wide excisions of the mass were performed with margins free of tumor in all three cases.ConclusionDue to its low incidence, there are no evidence-based diagnostic algorithms or published recommendations for treatment. Locoregional lymph node involvement, vascular invasion, tumor size larger than 2 cm, deep localization, presence of necrosis, and a high mitotic index are known as poor prognostic factors. Adjuvant radiotherapy is advisable in the presence of a high-grade tumor or positive margins. The beneficial effect of adjuvant chemotherapy is not well established. Treatment decisions should be made based on the individual case presentation and pathology evaluation.     

Inflammatory features of melasma lesions in Asian skin

Melasma is triggered by various factors including ultraviolet radiation and estrogen; however, its pathogenesis is unclear. To investigate the inflammatory features of melasma lesions as triggers for this disorder, 197 women with melasma who attended Asan Medical Center and Kangskin Clinic, Seoul, from June 2011 to October 2011 completed a questionnaire concerning triggering or aggravating factors. These cases were divided into “non‐inflammatory” and “inflammatory” groups. Skin biopsies and immunostaining for CD68, CD117, and leukocyte common antigen (LCA) were performed in the lesional and peri‐lesional skin of ten cases in the non‐inflammatory group and nine cases in the inflammatory group. Among the 197 subjects (mean age, 41.5 years; mean age of melasma onset, 33.8 years), 50 patients (25.4%) were categorized into the inflammatory group. This group comprised cases that had inflammatory symptoms and events that triggered the melasma lesions. The lesional dermis contained more CD68⁺ melanophages, CD117⁺ mast cells, and LCA⁺ leukocytes in the inflammatory group than in the non‐inflammatory group. Inflammatory clinical features and an increased number of inflammatory cells in the lesion may be involved in the development of melasma in Asian skin.     

p53抑制剂pifithrin-α对肝原代细胞增殖的影响

目的:观察p53抑制剂pifithrin-α对肝原代细胞增殖及增殖相关蛋白表达的影响。方法:肝原代细胞分别经0、10、20和30μmol/L的pifithrin-α处理1h后,再用10nmol/LEGF诱导30、36和48h,用放射性计数法测定细胞增殖水平。另取肝原代细胞,分3组,对照组常规培养,EGF组用10nmol/L的EGF诱导,EGF+pifithrin-α组用30μmol/Lpifithrin-α和10nmol/LEGF诱导,EGF诱导24、30h后,Westernblot法检测细胞中P53、P21、CyclinD、CyclinE、pErk蛋白的表达水平。结果:pifithrin-α作用后,EGF诱导的细胞增殖水平均降低,且pifithrin-α浓度越大,增殖水平越低(F剂量=54.690,F时间=214.370,F交互=50.450,P<0.001)。与对照组比较,EGF组细胞P53、Cyc-linE蛋白表达水平未发生变化,但P21、CyclinD及pErk表达水平升高(P<0.05),EGF+pifithrin-α组细胞P21、CyclinD及pErk蛋白表达水平较EGF组降低(P<0.05)。结论:P53蛋白可能通过激活MAPK信号通路、上调Cy-clinD表达,从而发挥促进肝原代细胞增殖的作用。     

Melatonin-stimulated exosomes enhance the regenerative potential of chronic kidney disease-derived mesenchymal stem/stromal cells via cellular prion proteins

Chronic kidney disease (CKD) is caused by dysfunctional kidneys, which result in complications like cardiovascular diseases. Chronic kidney disease-induced pathophysiological conditions decrease efficacy of autologous mesenchymal stem/stromal cell (MSC)-based therapy by reducing MSC functionality. To enhance therapeutic potential in patients with CKD, we isolated exosomes derived from melatonin-treated healthy MSCs (MT exosomes) and assessed the biological functions of MT exosome–treated MSCs isolated from patients with CKD (CKD-MSCs). Treatment with melatonin increased the expression of cellular prion protein (PrP^C) in exosomes isolated from MSCs through the upregulation of miR-4516. Treatment with MT exosomes protected mitochondrial function, cellular senescence, and proliferative potential of CKD-MSCs. MT exosomes significantly increased the level of angiogenesis-associated proteins in CKD-MSCs. In a murine hindlimb ischemia model with CKD, MT exosome–treated CKD-MSCs improved functional recovery and vessel repair. These findings elucidate the regenerative potential of MT exosome–treated CKD-MSCs via the miR-4516-PrP^C signaling axis. This study suggests that the treatment of CKD-MSCs with MT exosomes might be a powerful strategy for developing autologous MSC-based therapeutics for patients with CKD. Furthermore, miR-4516 and PrP^C could be key molecules for enhancing the regenerative potential of MSCs in ischemic diseases.