Cucurbitacin B protects against myocardial ischemia-reperfusion injury through activating JAK2/STAT3 signaling pathway.

Cucurbitacin B, a tetracyclic triterpenoid compound extracted from various plants, has been proven to exert a vital role in various diseases. However, the effect of cucurbitacin B on myocardial infarction (MI) and ischemia-reperfusion (I/R) injury is still relatively unclear. The main purpose of the present study was to investigate the effect of cucurbitacin B on cell apoptosis and oxidative damage after myocardial I/R injury in vitro and in vivo and elucidate the molecular mechanisms underlying its role. The 56-day-old adult mice and 1-day-old neonatal mice cardiomyocytes were used to construct I/R or oxygen-glucose deprivation/reoxygenation (OGD/R) injury models. The oxidative injury, western blot and TUNEL assay were performed to evaluate cardiomyocyte damage in the present study. In vitro， we confirmed that cucurbitacin B could attenuate LDH release, oxidative stress and cell apoptosis in cardiomyocytes exposed to OGD/R. Besides, we confirmed in an adult I/R mouse model that cucurbitacin B can improve cardiac repair and block cell apoptosis in the acute phase (24 h) post-myocardial I/R injury, as well as promote long-term cardiac function and fiber scar area after 28 days of I/R. Mechanically, we clarify that cucurbitacin B exerts cardiomyocyte protective effects through activating the JAK2/STAT3 signaling pathway. In conclusion, our study elucidates for the first time the protective role of cucurbitacin B in cardiac I/R injury, which provides a novel perspective for better prevention of I/R injury through the JAK2/STAT3 signaling pathway.

Glycoprotein Ia C807T: Polymorphisms and Their Association with Platelet Function in Patients with the Acute Coronary Syndrome.

OBJECTIVES: In the current study, we explored the relationship between glycoprotein Ia (GPIa) C807T polymorphisms and platelet function, and the sensitivity to dual antiplatelet treatment after percutaneous coronary intervention. MATERIALS AND METHODS: We conducted a case-control study in 220 patients diagnosed with acute coronary syndrome (ACS) and 220 healthy controls. The platelet GPIa C807T genotypes of patients and controls were determined, and platelet aggregation and plasma concentrations of α-granule membrane protein (GMP-140) were assessed following stimulation with arachidonic acid and adenosine diphosphate. RESULTS: The frequency of the GPIa T allele was higher in the ACS group than in controls. In the ACS group, platelet aggregation was significantly higher in individuals with the T allele than in those with the C allele. Dual antiplatelet treatment reduced platelet aggregation in all three genotypes, and patients carrying the CC genotype were more sensitive to antiplatelet treatment than those with the T allele, particularly the ones with the TT genotype. There were no differences in plasma GMP-140 levels. CONCLUSIONS: The GPIa C807T polymorphism might be a risk factor for the development and relapse of ACS. The GP Ia T allele may help to identify a group of patients who need more aggressive antithrombotic treatment.

Valsartan inhibits angiotensin II-induced proliferation of vascular smooth muscle cells via regulating the expression of mitofusin 2.

Angiotensin II (ANGII) plays an important role in the pathogenesis of atherosclerosis by inducing proliferation of vascular smooth muscle cells (VSMCs). In our study, we observed the effects of valsartan on proliferation of cultured VSMCs treated with or without ANGII by cell counting and methyl thiazolyl tetrazolium (MTT) assay, and detected the expression of mitofusin 2 (Mfn2), a newly discovered cell proliferation inhibitor and a related cell proliferation signaling pathway protein by Western blotting. ANGII at a concentration of 10(-6) mol/L significantly stimulated VSMCs proliferation, down-regulated the expression of Mfn2 and up-regulated the expression of Raf and ERK1/2. Valsartan inhibited such effects of ANGII at concentrations of 10(-5) and 10(-6) mol/L, but not at 10(-7) mol/L. Valsartan had no significant effect on the proliferation of untreated VSMCs. These results suggest that valsartan inhibits ANGII-induced proliferation of VSMCs in vitro via Mfn2-Ras-Raf-ERK/MAPK signaling pathway.

[Clinical analysis of cervical internal carotid artery malformation].

Objective:To introduce the clinical features and clinical imaging grading methods of cervical internal carotid artery（ICA） malformation. Methods:The clinical data of 6 cases with cervical ICA malformation admitted to the department of Otolaryngology, Head and Neck Surgery, the First Affiliated Hospital of Chengdu Medical College from April 2018 to February 2021 were retrospectively analyzed and graded according to the clinical imaging grading method. Results:All 6 patients were confirmed by enhanced CT or CT angiography. The minimum distance from deformity ICA to pharyngeal mucosa was 0 - 2.0 mm, while the median distance was 1.3 mm. According to the clinical imaging grading standards, the four cases with oropharyngeal ICA were grade Ⅳ, which is considered extremely high risk of ICA injury. The two cases with hypopharyngeal ICA were grade Ⅲ, which is considered high risk of ICA injury. Conclusion:ICA malformation is not a rare condition, and can be definitively diagnosed by enhanced CT and CT angiography. The clinical imaging grading can be used to assess the risk of damaged ICA malformation, which has great clinical significance. Otolaryngologists and anesthesiologists should pay attention to this malformation to prevent ICA damage in the operation which could lead to fatal hemorrhage.

Valsartan Inhibits Angiotensin Ⅱ-induced Proliferation of Vascular Smooth Muscle Cells via Regulating the Expression of Mitofusin 2 / 华中科技大学学报（医学）（英德文版）

Angiotensin Ⅱ (ANG Ⅱ) plays an important role in the pathogenesis of atherosclerosis by inducing proliferation of vascular smooth muscle cells (VSMCs).In our study,we observed the effects of valsartan on proliferation of cultured VSMCs treated with or without ANG Ⅱ by cell count ing and methyl thiazolyl tetrazolium (MTT) assay,and detected the expression of mitofusin 2 (Mfn2),a newly discovered cell proliferation inhibitor and a related cell proliferation signaling pathway protein by Western blotting.ANGⅡ at a concentration of 10-6 mol/L significantly stimulated VSMCs proliferation,down-regulated the expression of Mfn2 and up-regulated the expression of Raf and ERK1/2.Valsartan inhibited such effects of ANG Ⅱ at concentrations of 10-5 and 10-6 mol/L,but not at 10-7 mol/L.Valsartan had no significant effect on the proliferation of untreated VSMCs.These results suggest that valsartan inhibits ANGⅡ-induced proliferation of VSMCs in vitro via Mfn2-Ras-Raf-ERK/MAPK signaling pathway.