Allicin treats myocardial infarction in I/R through the promotion of the SHP2 axis to inhibit p-PERK-mediated oxidative stress.

OBJECTIVE: The study attempted to explore how allicin reduces oxidative stress levels by promoting SHP2 expression to inhibit p-PERK in I/R mice. METHODS: The GEO database and RNA sequencing were used to predict downstream gene. TTC staining was used to visualize the myocardial infarction area. Masson staining was used to assess the level of fibrosis. IF was used to examine the expression of SHP2, CTGF, ROS. RT-PCR analysis was used to quantify the expression of SHP2 mRNA. Western blot was used to detect the protein expression levels of SHP2, p-PERK, MFN1, NLRP3, NOX2, and NOX3. RESULTS: GEO and transcriptomic data revealed low expression of SHP2 in the heart tissues I/R mice. In the I/R mouse model, TTC staining result showed that allicin can reduce the area of myocardial infarction; Masson staining results indicated that allicin can reduce fibrosis; Macrophage transcriptome sequencing found SHP2 is a target gene of allicin; Immunofluorescence showed allicin can increase SHP2; qPCR results showed allicin can raise SHP2 mRNA level; Immunofluorescence indicated that allicin can inhibit ROS in myocardial infarction tissue, but the specific SHP2-KD eliminates changes in ROS. Western blot analysis demonstrated allicin can increase SHP2 protein and reduce the expression of p-PERK, MFN1, NLRP3, NOX2, and NOX3; SHP2-KD eliminates the expression differences in p-PERK, MFN1, NLRP3, NOX2, and NOX3. CONCLUSIONS: Allicin can modulate p-PERK activation by enhancing the expression of SHP2, thereby inhibiting myocardial ischemia-reperfusion-induced oxidative stress in mice.

The low expression of miR-155 promotes the expression of SHP2 by inhibiting the activation of the ERK1/2 pathway and improves cell pyroptosis induced by I/R in mice.

This study aims to explore the specific mechanism by which miR-155 regulates SHP2 expression in mouse ischemia-reperfusion (I/R) induced necroptosis. Various methods including cardiac ultrasound, TTC staining, Masson staining, TUNEL staining, and Western blotting were used to examine changes in the morphology and function of the rat left ventricle, myocardial fibrosis, as well as the expression of proteins related to tissue and cardiomyocyte necroptosis pathways. In vivo results showed that knockdown (KD) of miR-155 significantly improved cardiac ultrasound parameters (EF, FS, LVAW;d, and LVAW;s), reduced the myocardial infarction area, myocardial fibrosis, and cell apoptosis in I/R mice, upregulated cardiac SHP2 protein expression, and other proteins including p-ERK1/2, NLRP3, GSDMD, caspase-3, caspase-4, and caspase-11 were also significantly decreased. In vitro experiments showed that compared with the SHP2 WT miR-155 KD group, SHP2 protein expression was significantly increased in the SHP2 WT miR-155 KD group, while the expression of other proteins was significantly reduced, consistent with in vivo results. MiR-155 can regulate ERK1/2 and NLRP3 through SHP2. After adding the ERK1/2 inhibitor U0126 to cardiomyocytes from SHP2 KO mice, it was found that the expression of proteins other than SHP2 significantly decreased compared to SHP2 KO cells without the inhibitor. In summary, low expression of miR-155 promoted the expression of SHP2 and improved mouse I/R-induced necroptosis by inhibiting the activation of the ERK1/2 pathway.

Monitoring of the regulatory ability and regulatory state of the autonomic nervous system and its application to the management of hypertensive patients: a study protocol for randomised controlled trials.

INTRODUCTION: Many causes lead to sympathetic-vagus imbalance, which promotes the development of hypertension and accelerates the process of target organ damage. Many studies have shown that exercise training and heart rate variability (HRV) biofeedback can improve diseases caused by autonomic nerve dysfunction, such as hypertension. Based on these theories and the Yin-Yang balance theory of traditional Chinese medicine and Cannon's homeostasis theory, we have developed an assessment system of autonomic nerve regulation system and a harmony instrument. In this study, we aimed to find a new way to control blood pressure of hypertensive patients via cardiopulmonary resonance indices-based respiratory feedback training. METHODS AND ANALYSIS: This is a prospective, randomised, parallel-controlled clinical trial, which aims to evaluate the effectiveness and safety of biofeedback therapy and exercise rehabilitation combined intervention in hypertension management. 176 healthy individuals will be recruited to get their autonomic nerve function parameters as normal control, while 352 hypertensive patients will be enrolled and randomly divided into a conventional treatment group and an experiment group in a ratio of 1:1. All patients will continue to receive standard hypertension blood pressure treatment, except that patients in the experiment group will have to complete additional daily respiratory training for 6 months. The primary outcome is the difference of clinical systolic blood pressure (SBP) between the two groups after 6 months of intervention. The secondary outcomes include the changes in the mean SBP and diastolic blood pressure (DBP) by 24-hour blood pressure monitoring, home SBP, clinical and home DBP, clinical and home heart rate, the standard-reaching rate of clinic and home SBP and the incidence of composite endpoint events at 6 months. ETHICS AND DISSEMINATION: This study has been approved by the clinical research ethics committee of China-Japan Friendship Hospital (No. 2018-132 K98-2), the results of this study will be disseminated via peer-reviewed publications or conference presentations. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR1800019457, registered on 12 August 2018.

Xuesaitong promotes myocardial angiogenesis in myocardial infarction mice by inhibiting MiR-3158-3p targeting Nur77.

This study aims to investigate the regulatory effect of Xuesaitong (XST) and miR-3158-3p on angiogenesis. All mice were randomly assigned into Sham group, Model group, XST group, XST + miR-3158-3P-overexpression (miRNA-OE) group. XST was found to increase the left ventricular anterior wall thickness at end diastole and end systole (LVAWd and LVAWs), left ventricular internal dimension at end diastole and end systole (LVIDd and LVIDs), fractional shortening (FS), and ejection fraction (EF) and decrease the proportion of fibrotic areas in mice. In contrast to those in Sham group, the protein expressions of Nur77, p-PI3K, HIF-1α, VEGFs, COX-2 in the heart tissues of mice in Model group were elevated and further increased after XST treatment in comparison with those in Model group. Nur77-/- mice were utilized. It was found that XST enhanced cell viability through a methyl thiazolyl tetrazolium assay and facilitated angiogenesis in each group, as assessed by a catheter formation assay. Specifically, XST was shown to promote the formation of blood vessels. Moreover, the protein expression levels of Associated proteins in the heart tissues of Nur77-/- mice were dramatically reduced in mice in Model and XST group compared with those in WT mice. Additionally, the above-mentioned protein expressions in the heart tissues of Nur77-/- mice did not change significantly in mice in Model + miRNA-OE + XST group compared with those in WT mice, suggesting that miR-3158-3p can specifically inhibit the expression of Nur77. In conclusion, XST inhibits miR-3158-3p targeting Nur77 to facilitate myocardial angiogenesis in mice with myocardial infarction.

Functional Evaluation of Percutaneous Coronary Intervention Based on CT Images of Three-Dimensional Reconstructed Coronary Artery Model.

In order to explore the computerized tomography (CT) based on three-dimensional reconstruction of coronary artery model, the functional evaluation was made after percutaneous coronary intervention (PCI). In this study, 90 patients with coronary heart disease who received elective PCI were selected. The blood flow reserve fraction (FFR) and SYNTAX score were calculated by three-dimensional reconstruction of CT images, followed up for 2-4 years. According to the SYNTAX score, 0-22 points were defined as the low group (28 cases), 23-32 points as the medium group (33 cases), and 33 points as the high group (29 cases). In this paper, the accuracy, sensitivity, and specificity of CT images of three-dimensional reconstructed coronary artery model are 91%, 73%, and 62%, respectively. The follow-up results showed that the incidence of major adverse cerebrovascular events in the high group was significantly higher than that in the low group and the middle group, and the difference was statistically significant (P < 0.05). Pearson correlation analysis showed that SYNTAX score was related to serum total cholesterol (r = 0.234, P=0.003), triglyceride (r = 0.237, P=0.014), low-density lipoprotein cholesterol (r = 0.285, P=0.004), and ApoB/ApoA1 (R = 0.004). In this study, FFR is calculated by CT images based on three-dimensional reconstruction of coronary artery model, which can provide support for the diagnosis and treatment of coronary heart disease. SYNTAX score can be used as a risk predictor for PCI patients with coronary heart disease.

An unusual contrast-induced encephalopathy following percutaneous coronary intervention in patients with cerebrovascular abnormalities: A case report.

Introduction: Contrast-induced encephalopathy (CIE) is a complication associated with the administration of iodinated contrast, which usually happens minutes to hours after contact with contrast, and fully recovers within 72 h. The clinical manifestations of CIE are diverse, and the pathological mechanism is not explicit. Methods: We report the case of a 66-year-old female who suffered from a delayed CIE following the administration of iodinated contrast agent. Symptoms were severe. Imaging examination, biochemical and etiological detection were performed timely. The course of neurological symptoms was atypical. Her complex complications of hypothyroidism and cerebrovascular abnormalities contributed to more challenges, which were also clues to the diagnosis. With prompt and active treatment, the patient recovered fully over 10 days. Discussion: The diagnosis standard of CIE highly depends on the association with the contact of contrast and the exclusion of other nervous system diseases. Complicated clinical circumstances and individual specificity can lead to different clinical manifestations of CIE, making it even more difficult to diagnose and treat. Prompt and dynamic imaging examination would provide great value in the diagnosis and evaluation of CIE. Timely diagnosis and intervention may be the key to its satisfying prognosis.

Atypical Takotsubo cardiomyopathy presenting as acute coronary syndrome: A case report.

BACKGROUND: Takotsubo cardiomyopathy (TS) is a rare acute cardiac disease with clinical features, symptoms, and electrocardiographic manifestations similar to those of acute myocardial infarction. We present the case of a patient with TS caused by a pheochromocytoma, which was confirmed by the postoperative pathology. Furthermore, we present the patient's subsequent management, treatment, and outcome. CASE SUMMARY: A 64-year-old woman was admitted to the hospital with episodic chest pain and palpitations, electrocardiogram (ECG) findings suggestive of high lateral wall myocardial infarction, echocardiogram showing left ventricular wall segmental motion abnormalities, and elevated levels of the myocardial marker troponin. The patient underwent coronary angiography, which revealed unobstructed blood flow without obvious stenosis. During their hospitalization, the patient had paroxysmal elevation of blood pressure accompanied by palpitations and profuse sweating, with elevated blood catecholamine levels during seizures. Subsequent computerized tomography of the adrenal glands revealed the presence of a nodule in the right adrenal, which was resected and determined to be an adrenal pheochromocytoma. Therefore, the diagnosis of pheochromocytoma-induced atypical TS was made. The patient had an uneventful postoperative recovery. CONCLUSION: Cardiologists should consider pheochromocytoma in patients with TS. Early detection allows timely intervention, benefiting patients.

LncRNA H19 inhibits ER stress induced apoptosis and improves diabetic cardiomyopathy by regulating PI3K/AKT/mTOR axis.

OBJECTIVE: Extensive studies have shown that ERS may be implicated in the pathogenesis of DCM. We explored the therapeutic effects of lncRNAH19 on DCM and its effect on ERS-associated cardiomyocyte apoptosis. METHODS: C57/BL-6j mice were randomly divided into 3 groups: non-DM group (controls), DM group (DCM), and lncRNAH19 overexpression group (DCM+H19 group). The effect of H19 on cardiac function was detected. The effect of H19 on cardiomyocyte apoptosis and cardiac fibrosis in DM was examined. Differentially expressed genes (DEGs) and activated pathways were examined by bioinformatics analysis. STRING database was applied to construct a PPI network using Cytoscape software. The expression of p-PERK, p-IRE1, ATF6, CHOP, cleaved caspase-3, -9, -12 and BAX proteins in cardiac tissue was used to determine the ERS-associated apoptotic indicators. We established the HG-stimulated inflammatory cell model. The expression of p-PERK and CHOP in HL-1 cells following HG was determined by immunofluorescence labeling. The effects of H19 on ERS and PI3K/AKT/mTOR pathway were also detected. RESULTS: H19 improved left ventricular dysfunction in DM. H19 could reduce cardiomyocytes apoptosis and improve fibrosis in vivo. H19 could reduce the expression of p-PERK, p-IRE1α, ATF6, CHOP, cleaved caspase-3, cleaved caspase-9, cleaved caspase-12, and BAX proteins in cardiac tissues. Furthermore, H19 repressed oxidative stress, ERS and apoptosis in vitro. Moreover, the effect of H19 on ERS-associated apoptosis might be rescued by LY294002 (the specific inhibitor for PI3K and AKT). CONCLUSION: H19 attenuates DCM in DM and ROS, ERS-induced cardiomyocyte apoptosis, which is associated with the activation of PI3K/AKT/mTOR signaling pathway.

Effect of Calcification Based on Computer-Aided System on CT-Fractional Flow Reserve in Diagnosis of Coronary Artery Lesion.

This study was to analyze the diagnostic value of coronary computed tomography angiography (CCTA) and fractional flow reserve (FFR) based on computer-aided diagnosis (CAD) system for coronary lesions and the possible impact of calcification. 80 patients who underwent CCTA and FFR examination in hospital were selected as the subjects. The FFR value of 0.8 was used as the dividing line and divided into the ischemic group (FFR ≤ 0.8) and nonischemic group (FFR > 0.8). The basic data and imaging characteristics of patients were analyzed. The maximum diameter stenosis rate (MDS %), maximum area stenosis rate (MAS %), and napkin ring sign (NRS) in the ischemic group were significantly lower than those in the nonischemic group (P < 0.05). Remodeling index (RI) and eccentric index (EI) compared with the nonischemic group had no significant difference (P > 0.05). The total plaque volume (TPV), total plaque burden (TPB), calcified plaque volume (CPV), lipid plaque volume (LPV), and lipid plaque burden (LPB) in the ischemic group were significantly different from those in the non-ischemic group (P < 0.05). MAS % had the largest area under curve (AUC) for the diagnosis of coronary myocardial ischemia (0.74), followed by MDS % (0.69) and LPV (0.68). CT-FFR had high diagnostic sensitivity, specificity, accuracy, truncation value, and AUC area data for patients in the ischemic group and nonischemic group. The diagnostic sensitivity, specificity, accuracy, cutoff value, and AUC area data of CT-FFR were higher in the ischemic group (89.93%, 92.07%, 95.84%, 60.51%, 0.932) and nonischemic group (93.75%, 90.88%, 96.24%, 58.22%, 0.944), but there were no significant differences between the two groups (P > 0.05). In summary, CT-FFR based on CAD system has high accuracy in evaluating myocardial ischemia caused by coronary artery stenosis, and within a certain range of calcification scores, calcification does not affect the diagnostic accuracy of CT-FFR.

Comparison of long-term clinical outcomes of percutaneous coronary intervention for chronic total occlusion between patients with and without diabetes mellitus: a single-center retrospective observational study.

BACKGROUND: The prognosis of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) between patients with diabetes mellitus (DM) and those without DM is unknown. This study aimed to investigate whether DM has adverse effects on CTO PCI patients. METHODS: This single-center retrospective study included consecutive patients who underwent PCI for CTO at the China-Japan Friendship Hospital (Beijing, China) between January 2016 and April 2019. The clinical outcomes during follow-up were compared between patients with DM and those without DM. RESULTS: The analysis included 187 patients (152 males) aged 62.6±11.5 years. A total of 99 participants (52.9%) had DM, which involved a higher body mass index (BMI) and triglyceride level than those without DM (P<0.05). Participants with DM and those without DM had similar PCI success rates (89.9% vs. 95.4%, respectively) and complete revascularization rates (82.8% vs. 84.1%, respectively). There were no significant differences between groups in the rates of all-cause mortality, cardiac death, major adverse cardiovascular events (MACEs), readmission, recurrence of angina, target vessel revascularization (TVR), or myocardial infarction (MI) during a median follow-up of 20.5 months. Multivariable logistic regression revealed that CTO in a coronary branch vessel was associated with higher odds of all-cause death (odds ratio (OR): 53.56; 95% confidence interval (CI): 2.48 to 1,155.41; P<0.05) and failure of PCI for CTO (OR: 5.40; 95% CI: 1.263 to 23.098; P<0.05). Additionally, PCI for single CTO was associated with lower odds of MACEs (OR: 0.300; 95% CI: 0.118 to 0.765; P<0.05). CONCLUSIONS: The performance of PCI for CTO has a high success rate in both patients with DM and those without DM, and clinical outcomes are comparable between groups.

Evaluation of Bivalirudin-Associated Major Adverse Cardiac and Hemorrhagic Events in Acute Coronary Syndrome Patients on Chronic Dialysis Following Percutaneous Coronary Intervention.

BACKGROUND AND AIM: Patients with chronic dialysis dependency undergoing percutaneous coronary intervention (PCI) are at a greater risk of hemorrhagic and ischemic events. Due to their exclusion from randomized clinical trials, the optimal antithrombotic regimen for this population remains unknown. Bivalirudin has been associated with fewer hemorrhagic complications than unfractionated heparin (UFH) in patients undergoing PCI. We evaluated major adverse cardiac event (MACE) and hemorrhagic event rates for an antithrombotic regimen using bivalirudin or UFH during PCI in acute coronary syndrome (ACS) patients with chronic dialysis dependency. METHODS: A retrospective study was performed, including 211 patients on dialysis undergoing PCI due to ACS from January 2014 to April 2019 at the China-Japan Friendship Hospital. Patients were divided into 2 groups based on anticoagulation regimen: the bivalirudin group (86 cases) or the UFH group (125 cases) during and after PCI. Statistical analyses were used to compare MACE and hemorrhagic events between groups at 30 days after PCI. RESULTS: No patients experienced stent thrombosis within 30 days after PCI regardless of anticoagulant. There was no difference in the incidence of MACE in the bivalirudin group compared with the UFH group (6.98% vs 8.80%, respectively; P>.05). The rate of hemorrhagic events in the bivalirudin group was significantly lower than in the UHP group (5.81% vs 18.4%, respectively; P<.05), particularly for rates of mild bleeding (4.65% vs 15.2%, respectively; P<.05). There were no significant differences in rates of severe bleeding between the bivalirudin and UFH groups (1.16% vs 4.00%, respectively; P>.05), although fewer severe hemorrhagic events occurred in the bivalirudin group. CONCLUSION: Bivalirudin was associated with fewer bleeding events following PCI in individuals with end-stage renal disease on dialysis.

Allicin protects against myocardial I/R by accelerating angiogenesis via the miR-19a-3p/PI3K/AKT axis.

OBJECTIVES: Allicin is an allyl 2-propenethiosulfinate or diallyl thiosulfinate acid with cardioprotective effects in myocardial ischemia/reperfusion (MI/R) injury. This study aims to examine the underlying mechanism by which Allicin protects against MI/R. METHODS: C57BL6 mice were subjected to either sham or MI/R surgery, and mice in the Allicin group were injected with Allicin (5 mg/ml) before the induction of ischemia. The cardiac function and histopathology of experimental mice were evaluated by ultrasound quantification and Masson staining. We next measured the capillary angiogenesis of the peri-infarct area by Masson staining and immunohistochemical staining. The miRNA microarray was carried out to examine the expressed miRNAs in MI/R tissues and corresponding normal tissues. Real-time quantitative polymerase chain reaction (q-PCR) was performed to validate the selected miRNA-19α-3p gene expression. Besides, we evaluated the myocardial lactate dehydrogenase and COX-2 by immunofluorescence staining. The western blot analysis was used to evaluate the protein levels of p-AKT, p-PI3K, p-mTOR, COX-2, and VEGF protein in the Allicin and Model group. In vitro study, LPS stimulated Tie2 expressing macrophages were cultured in an ischemic buffer. We evaluated the accumulation of VEGF by fura-2/AM fluorescence. Besides, Western blotting was performed to examine the protein levels of p-PI3K, p-AKT, p-mTOR, VEGF, COX2, and MMP2. The PI3K inhibitor was applied to investigate whether Allicin-induced myocardial ischemia-reperfusion injury protection is mediated via the PI3K/AKT pathway. And the miR-19α-3p mimic/inhibitor were transfected to promote/inhibit the expression of miR-19a-3p for verifying the regulation of miR-19a-3p on PI3K pathway. RESULTS: Allicin pretreatment significantly improved I/R-induced cardiac function damage. Furthermore, Allicin could repress cardiac fibrosis, as evidenced by reduced areas of cardiac fibrosis. Allicin's effect on the MI/R was associated with increased capillary angiogenesis. Microarray analysis exposed that miR-19a-3p down-regulated PIK3CA (PI3K) expression by directly targeting the PIK3CA gene. The regulation of the angiogenesis pathway and gene miRNA-19a-3p might affect the Allicin-induced MI/R protection. Immunofluorescence staining revealed that COX-2 and myocardial lactate dehydrogenase were significantly increased after Allicin treatment. Furthermore, western blot analysis demonstrated that p-AKT, p-PI3K, p-mTOR, COX-2, and VEGF protein levels were also increased in the Allicin group. In vitro study, the protein levels of p-PI3K, p-AKT, p-mTOR, VEGF, COX2, and MMP2 were significantly increased in the Allicin-treated Tie2 expressing macrophages. These effects were partially reversed by PI3K inhibitor (Wortmannin) treatment. MiR-19α-3p plays an important role in myocardial I/R injury. It could regulate the activity of the PI3K-AKT pathway. And inhibition of miR-19a-3p promoted angiogenesis by regulating PI3K/AKT pathway. CONCLUSIONS: Allicin pretreatment protects against myocardial I/R and activating the miR-19a-3p/PI3K/AKT pathway.

A Study Protocol for a Randomized, Double-Blind, Placebo-Controlled Clinical Study on the Effect of Qishen Yiqi Dripping Pills on Exercise Endurance and Quality of Life in Patients with Coronary Heart Disease after Percutaneous Coronary Intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) is widely used in China, but it does not fundamentally improve exercise endurance or reduce mortality associated with cardiovascular disease. Standardized cardiac rehabilitation (CR) can reduce the mortality associated with coronary heart disease and reduce the need for repeated PCI procedures. Currently, research on CR after PCI is mainly based on traditional exercise prescription, while research on TCM is limited. Often, the combination of traditional Chinese medicine (TCM) and exercise rehabilitation is adopted, from which it is difficult to determine the unique advantages of TCM. Qishen Yiqi dripping pills (QSYQ) can improve myocardial energy metabolism and alleviate myocardial reperfusion injury after PCI. This paper describes the protocol for the clinical assessment of QSYQ on CR. METHODS: A randomized, double-blind, placebo-controlled trial will be used to evaluate the efficacy and safety of QSYQ on improving exercise endurance and quality of life. We plan to recruit 66 patients with stable angina pectoris with Qi deficiency and blood stasis syndrome differentiation after PCI from the China-Japan Friendship Hospital. On the basis of conventional drug treatment, QSYQ or placebo will be used for 12 weeks. PeakVO2 will be the main efficacy evaluation index, while Seattle scale and quality of life scale will be the secondary efficacy evaluation indexes. Discussion. CR therapy with integrated traditional Chinese and Western medicine has been developed as a treatment modality in China and has been included in the expert consensus of TCM diagnosis and treatment. A rigorous trial design will ensure objective and scientific evaluation of the efficacy and safety of QSYQ in improving exercise endurance and quality of life in patients with PCI. Trial Registration. This trial is registered with Clinical trial registration in China: ChiCTR2000040838 (registration date: December 11, 2020).

Traditional Chinese medicine for acute coronary syndrome: A meta-analysis of clinical manifestations and objective indicators.

BACKGROUND: Modern clinical trials and experimental researches of traditional Chinese medicine (TCM) have been conducted for decades and provided support for the prevention and treatment of acute coronary syndrome (ACS). However the level of evidence and the proper application of TCM were still barely satisfactory. METHODS: In this study, we divided ACS into 3 different stages, including unstable angina, acute myocardial infarction, and post myocardial infarction. Then we systematically reviewed and meta-analyzed the existing randomized controlled trials on both clinical manifestations and objective indicators, in these 3 aspects. RESULTS: The results indicate that TCM can both improve the clinical manifestations and ameliorate the objective parameters in different courses of ACS, including C-reactive protein in unstable angina, left ventricular ejection fraction in acute myocardial infarction and post myocardial infarction. And the incidence of short-term cardiovascular events are lower in TCM intervention group. Some of the improvements lead to potential long-term benefits. CONCLUSION: TCM treatment is beneficial to different courses of ACS. To acquire more solid and comprehensive evidence of TCM in treating ACS, more rigorously designed randomized controlled trials with longer follow-up duration are warranted.

The protective effect of allicin on myocardial ischemia-reperfusion by inhibition of Ca2+ overload-induced cardiomyocyte apoptosis via the PI3K/GRK2/PLC-γ/IP3R signaling pathway.

PURPOSE: To investigate the protective effect and mechanism of allicin on myocardial ischemia-reperfusion (MI/R) injury. METHODS: We investigated the mechanisms by which allicin attenuated the MI/R injury by focusing on phosphoinositide 3-kinase, G protein coupled receptor kinases 2, phospholipase Cγ and cardiomyocyte apoptosis. Sixty male mice were randomly assigned into three groups: repeated MI/R (model), sham-operated (control), and MI/R+ allicin group (allicin). Ultrasound examination was used to examine the cardiac function. Masson staining was used to evaluate the myocardial infarct area. TUNEL assay was performed to examine the anti-apoptotic effect of allicin. Differentially expressed genes (DEGs) and pathways were analyzed by mRNA microarray analysis. Immunofluorescence staining and western blot were carried out to detect the effect of allicin on the PI3K. A pan-PLC activator, m-3M3FBS, was applied to investigate whether allicin induced cardiomyocyte apoptosis was via the GRK2/PLC/IP3R signaling pathway. RESULTS: Masson staining and the TUNEL assay revealed that allicin reduced infarct size and played an anti-apoptotic role in M/IR. Ultrasound examination revealed that allicin improved cardiac function after M/IR injury. Gene ontology analysis indicated that the calcium signaling pathway and PI3KCA(PI3K) were selected. Immunofluorescence staining and western blot exposed that PI3K was activated by allicin during MI/R injury. Fura-2AM staining revealed that the PI3K -mediated GRK2/PLC-γ/IP3R pathway may be involved in the protective effect of allicin on MI/R injury. CONCLUSIONS: Allicin has a protective effect on MI/R injury. This effect might be associated with the inhibition of Ca2+ overload-induced apoptosis and the inhibition of the PI3K -mediated GRK2/PLC-γ/IP3R signaling pathway.

Allicin attenuates myocardial apoptosis, inflammation and mitochondrial injury during hypoxia-reoxygenation: an in vitro study.

BACKGROUND: Myocardial ischemia-reperfusion (IR) injury is a damage due to an initial reduction in blood flow to the heart, preventing it from receiving enough oxygen, and subsequent restoration of blood flow through the opening of an occluded coronary artery producing paradoxical harmful effects. The finding of new therapies to prevent IR is of utmost importance. Allicin is a compound isolated from garlic having the ability to prevent and cure different diseases, and a protective effect on the myocardium was also demonstrated. Therefore, the aim of this study was to evaluate the in vitro protective effect of Allicin against myocardial IR injury on cardiomyocytes. METHODS: We established an in vitro hypoxia-reoxygenation (HR) model of primary porcine cardiomyocytes to simulate myocardial IR injury. Primary porcine cardiomyocytes were extracted from Mini-musk swines (1 day old). After a period of adaptation of at least 2-3 days, cardiomyocytes in good condition were selected and randomly divided into control group (normal oxygen for 5 h), HR group (2 h of hypoxia/3 h of reoxygenation), and HR + Allicin group (hypoxia/reoxygenation + Allicin treatment). RESULTS: After the induction of hypoxia/reoxygenation, Allicin treatment enhanced the cell viability. Moreover, Allicin treatment resulted in a reduction of apoptosis from 13.5 ± 1.2% to 6.11 ± 0.15% compared with the HR group (p < 0.05), and the apoptosis related proteins were regulated as well, with a decreased expression of Bax, cleaved caspase-3 and cytosolic cytochrome C and an increase in Bcl-2 expression in the HR + Allicin group (all p < 0.01). Pro-inflammatory cytokines, such as interleukin-6 and tumor necrosis factor alpha were down-regulated by the treatment with Allicin (both p < 0.01). In addition, it significantly decreased intracellular reactive oxygen species generation (p < 0.01) and reduced the loss of mitochondrial membrane potential (p < 0.01). Furthermore, the expression of PPARγ coactivator-1α and endothelial nitric oxide synthase was up-regulated (both p < 0.01), while the expression of Endothelin-1, hypoxia inducing factor-1α and transforming growth factor beta was down-regulated (all p < 0.01) by Allicin treatment. CONCLUSIONS: These results suggested that Allicin protected the cardiomyocytes against HR damage by reducing apoptosis, inflammation and mitochondrial injury, thus providing a basis for its potential use in the treatment of myocardial IR.

Synthesis and in vitro anticancer activities of biotinylated derivatives of glaucocalyxin A and oridonin.

Fourteen glaucocalyxin A biotinylated derivatives, one glaucocalyxin C biotinylated derivative, and two oridonin biotinylated derivatives were designed and synthesized. Their structures were confirmed from 1H NMR, 13C NMR and HRMS data. The derivatives were evaluated for cytotoxic activities against lung (A549), cervical cancer cell line HeLa derivative (KB), multidrug-resistant KB subline (KB-VIN), triple-negative breast (MDA-MB-231), and estrogen receptor-positive breast (MCF-7) cancer cell lines.[Formula: see text].

Case Report and Literature Review on Low-Osmolar, Non-Ionic Iodine-Based Contrast-Induced Encephalopathy.

Contrast-induced encephalopathy (CIE) is a rare complication following percutaneous carotid and coronary interventions, and important diagnostic radiological signs include brain edema and cortical enhancement. In this report, we detail a case of probable CIE in an 84-year-old woman following a normal diagnostic coronary angiography (CAG) that involved 20 mL of the low-osmolar, non-ionic monomeric, iodine-based contrast agent iopromide (Ultravist 370). The patient was unconscious and presented with hemiparesis, hemianopia, recurrent seizures, and cardiac and respiratory arrest within minutes to hours following the procedure. Non-contrast computed tomography (CT) of the head showed increased subarachnoid density, cortical enhancement, and brain edema in the right hemisphere. Three days of rehydration, reduction in cranial pressure, and treatment with an anticonvulsant and dexamethasone resulted in a gradual recovery with no neurological deficits. This case highlights that severe neurotoxic symptoms may occur in response to low doses of low-osmolar, non-ionic, monomeric contrast agents. This finding is of importance to interventional cardiologists for diagnostic considerations and development of treatment plans.

B-lines by lung ultrasound predict heart failure in hospitalized patients with acute anterior wall STEMI.

OBJECTIVE: B-line imaging by lung ultrasound (LUS) is a new tool for evaluating subclinical pulmonary congestion. The aim of this study was to explore the prognostic value of B-line number at admission in predicting symptomatic heart failure (HF) during hospitalization in acute anterior wall STEMI patients. METHODS: This was a prospective cohort study which consecutively enrolled 96 anterior wall STEMI patients without dyspnea at admission. Pulmonary auscultation, NT-proBNP test, LUS, and echocardiography were performed within 5 hours after primary PCI. Rale occurrence, plasma NT-proBNP levels, B-line number, LVEF, E/e' were recorded, and their predictive value for HF in-hospital was analyzed. RESULTS: A total of 19 patients developed symptomatic HF. Median B-line number, NT-proBNP levels, and E/e' in the HF group were higher than those of the nonheart-failure (NHF) group (P < 0.001) while LVEF was lower (P = 0.002). There was no statistical difference in rale occurrence between the two groups. Multivariate logistic regression demonstrated that B-lines, E/e', and NT-proBNP independently predicted HF during hospitalization. According to the area under the ROC curve, the strongest predictor is B-lines (0.972), followed by NT-proBNP (0.936) and E/e' (0.928), and combining the three indicators was better than any single parameter (P = 0.048). B-line cutoff ≥18 could well predict HF event with specificity and sensitivity of 94.7% and 94.8%, respectively. CONCLUSION: Subclinical pulmonary congestion reflected by B-lines can independently predict symptomatic HF during hospitalization in patients with anterior wall STEMI, LUS will act as a complementary tool for evaluating cardiac function.