Effect of Colchicine in reducing MMP-9, NOX2, and TGF- ß1 after myocardial infarction.

BACKGROUND: According to WHO 2020, CAD is the second leading cause of death in Indonesia with death cases reaching 259,297 or 15.33% of total deaths. Unfortunately, most of the patients of CAD in Indonesia did not match the golden period or decline to be treated with Percutaneous Coronary Intervention (PCI). Based on the recent study, there were increases in MMP-9, NOX2, and TGF-ß1 in STEMI patients which contribute to cardiac remodeling. Moreover, there is controversy regarding the benefit of late PCI (12-48 hours after onset of STEMI) in stable patients. Lately, colchicine is widely used in cardiovascular disease. This study was conducted to explore the effect of colchicine to reduce MMP- 9, NOX2, and TGF-ß1 levels after myocardial infarction in stable patients. METHOD: In this clinical trial study, we assessed 129 STEMI patients, about 102 patients who met inclusion criteria were randomized into four groups. Around 25 patients received late PCI (12-48 h after the onset of chest pain), optimal medical treatment (OMT) for STEMI, and colchicine; 24 patients received late PCI and OMT; 22 patients didn't get the revascularization (No Revas), OMT, and colchicine; and 31 patients received No Revas and OMT only. The laboratory test for MMP-9, NOX2, and TGF-ß1 were tested in Day-1 and Day-5. The data were analyzed using Mann-Whitney. RESULTS: A total of 102 patients with mean age of 56 ± 9.9, were assigned into four groups. The data analysis showed significant results within No Revas + OMT + Colchicine group versus No Revas + OMT + Placebo in MMP-9 (Day-1: p = 0.001; Day-5: p = 0.022), NOX2 (Day-1: p = 0.02; Day-5: p = 0.026), and TGF-ß1 (Day-1: p = 0.00; Day-5: p = 0.00) with the less three markers in OMT + Colchicine group than OMT + Placebo group. There were no significant differences within the late PCI + OMT + colchicine group and PCI + OMT + Placebo group. CONCLUSIONS: Colchicine could significantly reduce MMP-9, NOX2, and TGF-ß1 levels in stable STEMI patients. So that, colchicine could be a potential agent in STEMI patients and prevent cardiac remodeling events.

Blood-based circulating microRNAs as diagnostic biomarkers for subclinical carotid atherosclerosis: A systematic review and meta-analysis with bioinformatics analysis.

BACKGROUND: Atherosclerosis in carotid arteries can remain clinically undetected in its early development until an acute cerebrovascular event such as stroke emerges. Recently, microRNAs (miRNAs) circulating in blood have emerged as potential diagnostic biomarkers, but their performance in detecting subclinical carotid atherosclerosis has yet to be systematically researched. AIM: To investigate the diagnostic performance of circulating miRNAs in detecting subclinical carotid atherosclerosis. METHODS: We systematically searched five electronic databases from inception to July 23, 2022. Subclinical carotid atherosclerosis was defined using carotid intima-media thickness (CIMT). Diagnostic accuracy parameters and correlation coefficients were pooled. A gene network visualisation and enrichment bioinformatics analysis were additionally conducted to search for potential target genes and pathway regulations of the miRNAs. RESULTS: Fifteen studies (15 unique miRNAs) comprising 2542 subjects were identified. Circulating miRNAs had a pooled sensitivity of 85% (95% CI 80%-89%), specificity of 84% (95% CI 78%-88%), positive likelihood ratio of 5.19 (95% CI 3.97-6.80), negative likelihood ratio of 0.18 (95% CI 0.13-0.23), diagnostic odds ratio of 29.48 (95% CI 21.15-41.11), and area under the summary receiver operating characteristic curve of 0.91 (95% CI 0.88-0.93), with a strong correlation to CIMT (pooled coefficient 0.701; 95% CI 0.664-0.731). Bioinformatics analysis revealed a major role of the miRNAs, as shown by their relation with CCND1, KCTD15, SPARC, WWTR1, VEGFA genes, and multiple pathways involved in the pathogenesis of carotid atherosclerosis. CONCLUSION: Circulating miRNAs had excellent accuracy in detecting subclinical carotid atherosclerosis, suggesting their utilisation as novel diagnostic tools.

Pulsed Radiofrequency Decreases pERK and Affects Intracellular Ca2+ Influx, Cytosolic ATP Level, and Mitochondrial Membrane Potential in the Sensitized Dorsal Root Ganglion Neuron Induced by N-Methyl D-Aspartate.

Background: The molecular mechanism of pulsed radiofrequency (PRF) in chronic pain management is not fully understood. Chronic pain involves the activation of specific N-Methyl D-Aspartate receptors (NMDAR) to induce central sensitization. This study aims to determine the effect of PRF on central sensitization biomarker phosphorylated extracellular signal-regulated kinase (pERK), Ca2+ influx, cytosolic ATP level, and mitochondrial membrane potential (Δψm) of the sensitized dorsal root ganglion (DRG) neuron following NMDAR activation. Methods: This study is a true experimental in-vitro study on a sensitized DRG neuron induced with 80 µM NMDA. There are six treatment groups including control, NMDA 80 µM, Ketamine 100 µM, PRF 2Hz, NMDA 80 µM + PRF 2 Hz, and NMDA 80 µM + PRF 2 Hz + ketamine 100 µM. We use PRF 2 Hz 20 ms for 360 seconds. Statistical analysis was performed using the One-Way ANOVA and the Pearson correlation test with α=5%. Results: In the sensitized DRG neuron, there is a significant elevation of pERK. There is a strong correlation between Ca2+, cytosolic ATP level, and Δψm with pERK intensity (p<0.05). PRF treatment decreases pERK intensity from 108.48 ± 16.95 AU to 38.57 ± 5.20 AU (p<0.05). PRF exposure to sensitized neurons also exhibits a Ca2+ influx, but still lower than in the unexposed neuron. PRF exposure in sensitized neurons has a higher cytosolic ATP level (0.0458 ± 0.0010 mM) than in the unexposed sensitized neuron (0.0198 ± 0.0004 mM) (p<0.05). PRF also decreases Δψm in the sensitized neuron from 109.24 ± 6.43 AU to 33.21 ± 1.769 AU (p<0.05). Conclusion: PRF mechanisms related to DRG neuron sensitization are by decreasing pERK, altering Ca2+ influx, increasing cytosolic ATP level, and decreasing Δψm which is associated with neuron sensitization following NMDAR activation.

Focused Chest Pain Assessment for Early Detection of Acute Coronary Syndrome: Development of a Cardiovascular Digital Health Intervention.

Background: Chest pain misinterpretation is the leading cause of pre-hospital delay in acute coronary syndrome (ACS). This study aims to identify and differentiate the chest pain characteristics associated with ACS. Methods: A total of 164 patients with a primary complaint of chest pain in the ER were included in the study. ACS diagnosis was made by a cardiologist based on the WHO criteria, and the patients were interviewed 48 hours after their admission. Furthermore, every question was analysed using the crosstabs method to obtain the odds ratio, and logistic regression analysis was applied to identify the model of focused questions on chest pain assessment. Results: Among the samples, 50% of them had an ACS. Four questions fitted the final model of ACS chest pain focused questions: 1) Did the chest pain occur at the left/middle chest? 2) Did the chest pain radiate to the back? 3) Was the chest pain provoked by activity and relieved by rest? 4) Was the chest pain provoked by food ingestion, positional changes, or breathing? This model has 92.7% sensitivity, 84.1% specificity, 85% positive predictive value (PPV), 86% negative predictive value (NPV), and 86% accuracy. After adjusting for gender and diabetes mellitus (DM), the final model has a significant increase in Nagelkerke R-square to 0.737 and Hosmer and Lemeshow test statistic of 0.639. Conclusion: Focused questions on 1) left/middle chest pain, 2) retrosternal chest pain, 3) exertional chest pain that is relieved by rest, and 4) chest pain from food ingestion, positional changes, or breathing triggering can be used to rule out ACS with high predictive value. The findings from this study can be used in health promotion materials and campaigns to improve public awareness regarding ACS symptoms. Additionally, digital health interventions to triage patients' suffering with chest pain can also be developed.

The Effects of Percutaneous Coronary Intervention on Biomarkers and Quality of Life in Patients With Chronic Total Coronary Artery Obstruction.

Background: Chronic total occlusion (CTO) is an angiographic picture of total occlusion without blood flow which is estimated to have lasted at least 3 months. This study attempted to provide an overview of the levels of matrix metalloproteinase-9 (MMP-9), soluble suppression tumorigenicity 2 (sST2), and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) as remodeling, inflammatory, and atherosclerotic markers, as well as changes in the angina severity in patients with CTO who underwent percutaneous coronary intervention (PCI) compared to those without PCI. Methods: This study is a preliminary report with quasi-experimental design study with a pre-test and post-test approach to compare PCI's effect in CTO patients towards changes in MMP-9, sST2, NT-pro-BNP levels, and changes in the angina severity. Twenty subjects underwent PCI and 20 subjects with optimal medical therapy, who were then assessed at baseline and 8 weeks after intervention. Results: The results of this preliminary report showed that decreased MMP-9 (pre-test: 12.07 ± 1.27 ng/mL vs. post-test: 9.91 ± 5.19 ng/mL, P = 0.049), sST2 (pre-test: 37.65 ± 20.00 ng/mL vs. post-test: 29.74 ± 15.17 ng/mL, P = 0.026) and NT-pro-BNP (pre-test: 0.63 ± 0.23 ng/mL vs. post-test: 0.24 ± 0.10 ng/mL, P < 0.001) levels were found after 8 weeks of PCI compared to those without such intervention. The levels of NT-pro-BNP were lower in the PCI group (0.24 ± 0.10 ng/mL) than in the non-PCI group (0.56 ± 0.23 ng/mL; P < 0.001). Moreover, there was an improvement of angina severity in PCI group than without PCI (P < 0.039). Conclusions: Although this preliminary report found a significant decrease in MMP-9, NT-pro-BNP, and sST2 levels in CTO patients who had undergone PCI compared to those without PCI, as well as improved angina severity in these patients, this study still has limitations. The number of samples was so small that similar studies with larger sample sizes or multicenter investigations are required to deliver more trustworthy and useful results. Nevertheless, we encourage this study as a preliminary baseline for further studies in the future.

Colchicine as potential inhibitor targeting MMP-9, NOX2 and TGF-ß1 in myocardial infarction: a combination of docking and molecular dynamic simulation study.

The global data revealed that myocardial infarction (MI) in coronary heart disease has been the leading cause of mortality worldwide in both developing and developed countries. The remodeling process after MI is essential to be the leading cause of heart failure due to cardiac remodeling. The evidence showed the increment of MMP-9, NOX2 and TGF-ß1 expressions are biomarkers that influence cardiac remodeling. Lately, colchicine is widely used in the treatment of cardiovascular diseases. The effects of colchicine on NOX2, MMP-9 and TGF-ß1 in the molecular models are still not yet discussed. We proposed a molecular docking and molecular dynamics simulation study to show the interaction between colchicine, NOX2, MMP-9 and TGF-ß1. Colchicine has a good binding affinity with MMP-9, NOX2 and TGF-ß1 based on the value, which are -8.3 Kcal/mol, -6.7 Kcal/mol and -6.5 Kcal/mol, respectively. Colchicine also binds to some catalytic residues in MMP-9, NOX2 and TGF-ß1 that are responsible for inhibitor effects. The RMSD values between colchicine and MMP-9, NOX2 and TGF-ß1 are 2.4 Å, 2 Å and 2.1 Å, respectively. The RMSF values of ligand and receptors complex showed relatively similar fluctuations. The SASA analysis showed that colchicine could create a more stable interaction with MMP-9. PCA analysis revealed that colchicine is capable of creating a solid and stable interaction with MMP-9 mainly, also NOX2 and TGF-ß1. In conclusion, docking and molecular dynamics analysis showed evidence of colchicine roles in the inhibition of MMP-9, NOX2 and TGF-ß1 in order to inhibit the remodeling process after MI.Communicated by Ramaswamy H. Sarma.

Pentraxin 3 regulates tyrosine kinase inhibitor-associated cardiomyocyte contraction and mitochondrial dysfunction via ERK/JNK signalling pathways.

BACKGROUND: Hepatocellular carcinoma (HCC) patients suffer varying degrees of heart dysfunction after tyrosine kinase inhibitor (TKI) treatment. Interestingly, HCC patients often have higher levels of pentraxin 3 (PTX3), and PTX3 inhibition was found to improve left ventricular dysfunction in animal models. OBJECTIVES: We sought to assess the therapeutic potential of PTX3 inhibition on TKI-associated cardiotoxicity. METHODS: We used a human embryonic stem cell line, RUES2, to generate cardiomyocyte cultures (RUES2-CM) for functional testing. We also assessed heart function and PTX3 expression levels in 16 HCC patients who received TKI treatment, 3 HCC patients who did not receive TKIs, and 7 healthy volunteers. RESULTS: Significantly higher PTX3 expression was noted in HCC patients with TKI treatment versus those without, and 38% of male and 33% of female patients had QTc prolongation after TKI treatment. Treatment of cardiomyocyte cultures with sorafenib also increased PTX3 expression and induced cytoskeletal remodelling, contraction reduction, sodium current inhibition, and mitochondrial respiratory dysfunction. PTX3 colocalised with CD44 in cardiomyocytes, and cardiomyocyte contraction, mitochondrial respiratory function, and regular cytoskeletal and apoptotic protein expression were restored with PTX3 inhibition. CD44 knockdown confirmed PTX3/CD44 signalling. These results suggest a possible mechanism in which sorafenib treatment increases PTX3 expression, thereby resulting in reduced extracellular signal-regulated kinase (ERK) 1/2 expression that affects cardiomyocyte contraction, while also activating c-Jun N-terminal kinase (JNK) downstream pathways to disrupt mitochondrial respiration and trigger apoptosis. CONCLUSIONS: TKI-induced cardiotoxicity may be partly mediated by the upregulation of PTX3, and thus PTX3 inhibition has potential as a therapeutic strategy.

The two facets of receptor tyrosine kinase in cardiovascular calcification-can tyrosine kinase inhibitors benefit cardiovascular system?

Tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment due to their effectiveness in cancer cell killing. However, an off-target of this agent limits its success. Cardiotoxicity-associated TKIs have been widely reported. Tyrosine kinase is involved in many regulatory processes in a cell, and it is involved in cancer formation. Recent evidence suggests the role of tyrosine kinase in cardiovascular calcification, specifically, the calcification of heart vessels and valves. Herein, we summarized the accumulating evidence of the crucial role of receptor tyrosine kinase (RTK) in cardiovascular calcification and provided the potential clinical implication of TKIs-related ectopic calcification. We found that RTKs, depending on the ligand and tissue, can induce or suppress cardiovascular calcification. Therefore, RTKs may have varying effects on ectopic calcification. Additionally, in the context of cardiovascular calcification, TKIs do not always relate to an unfavored outcome-they might offer benefits in some cases.

Serine racemase interaction with N-methyl-D-aspartate receptors antagonist reveals potential alternative target of chronic pain treatment: Molecular docking study.

Serine racemase (SR) catalyzes L-serine racemization to activate the N-methyl-D-aspartate receptor (NMDAR). NMDAR activation is associated with the progression of acute-to-chronic neuropathic pain. This study aimed to investigate NMDAR antagonist interactions with SR to obtain potential chronic pain target therapy. Several NMDAR antagonist drugs were obtained from the drug bank, and malonate was used as a control inhibitor. Ligands were prepared using the open babel feature on PyRx. The SR structure was obtained from Protein data bank (PDB) (3l6B) and then docked with ligands using the AutoDock Vina. Haloperidol had a lower binding affinity than malonate and other ligands. Ethanol had the highest binding affinity than other drugs but could bind to the Adenosine triphosphate (ATP)-binding domain. Haloperidol is bound to reface that function for reprotonation in racemization reaction to produce D-serine. Halothane bond with Arg135 residues aligned negatively charged substrates to be reprotonated properly by reface. Tramadol is bound to amino acid residues in the triple serine loop, which determines the direction of the SR reaction. Several NMDAR antagonists such as haloperidol, halothane, ethanol, and tramadol bind to SR in the specific binding site. It reveals that SR potentially becomes an alternative target for chronic pain treatment.

Prophylactic Cavotricuspid Isthmus Ablation in Atrial Fibrillation without Documented Typical Atrial Flutter: A Systematic Review and Meta-analysis.

Background: The advantage of prophylactic cavotricuspid isthmus (CTI) ablation for AF patients without documented atrial flutter is still unclear. The present study aimed to evaluate the role of prophylactic CTI ablation in this population. Methods: A systematic review and meta-analysis study was conducted. The overall effects estimation was conducted using random effects models. The pooled effects were presented as the risk difference and standardised mean difference for dichotomous and continuous outcomes, respectively. Results: A total of 1,476 patients from four studies were included. The risk of atrial tachyarrhythmias following a successful catheter ablation procedure was greater in the pulmonary vein isolation + CTI ablation group than pulmonary vein isolation alone group (34.8% versus 28.2%; risk difference 0.08; 95% CI [0.00-0.17]; p=0.04). Prophylactic CTI ablation was associated with a higher recurrent AF rate (33.8% versus 27.1%; risk difference 0.07; 95% CI [0.01-0.13]; p=0.02). Additional prophylactic CTI ablation to pulmonary vein isolation significantly increased the radio frequency application time (standardised mean difference 0.52; 95% CI [0.04-1.01]; p=0.03). Conclusion: This study suggested that prophylactic CTI ablation was an ineffective and inefficient approach in AF without documented typical atrial flutter patients.

Doxorubicin induced immune abnormalities and inflammatory responses via HMGB1, HIF1-α and VEGF pathway in progressive of cardiovascular damage.

Background: Doxorubicin (DOX) is a commonly used treatment for cancer and the mechanism of DOX-induced cardiomyocyte damage in cardiovascular disease is not fully understood. High-mobility group box 1 (HMGB1), strong induce proinflammatory cytokines via damage associated molecular pattern (DAMP) which its interaction with the receptor of advanced glycation end products (RAGE), that affect cytokine release, and angiogenesis via the role of HMBG1, HIF-1α and VEGF as an important regulator in these cardiac failure processes. Hypoxia-inducible factor-1α (HIF-1α) is plays an important role in the cellular response to systemic oxygen levels of cells and VEGF is an angiogenic factor and can stimulate cellular responses on the surface of endothelial cells will be described. Objective: The aim of this article is to comprehensively review the role of HMGB1, HIF-1α, and VEGF in DOX-induced Cardiovascular Disease and its molecular mechanisms. Methods: The data in this study were collect by search the keyword combinations of medical subject headings (MeSH) of "HMGB1", "HIF-1 α", "VEGF", "DOX" and "Cardiovascular disease" and relevant reference lists were manually searched in PubMed, EMBASE and Scopus database. All relevant articles in data base above were included and narratively discussed in this review article. Results: Several articles were revealed that molecular mechanisms of the DOX in cardiomyocyte damage and related to HMGB1, HIF-1α and VEGF and may potential treatment and prevention to cardiovascular disease in DOX intervention. Conclusion: HMGB1, HIF-1α and VEGF has a pivotal regulator in DOX-induce cardiomyocyte damage and predominantly acts through different pathways. The role of HMGB1 in DOX-induced myocardial damage suggests that HMGB1 is a mediator of DOX-induced damage. In addition, DOX can inhibit HIF-1α activity where DOX can decrease HIF-1α expression and HIF-1α is also responsible for upregulation of several angiogenic factors, including VEGF. VEGF plays an important role in angiogenesis and anti-angiogenesis both in vitro and in vivo and reduces the side effects of DOX markedly. In addition, the administration of anti-angiogenesis will show an inhibitory effect on angiogenesis mediated by the VEGF signaling pathway and triggered by DOX in cells.

Role of Glycosylation in Vascular Calcification.

Glycosylation is an important step in post-translational protein modification. Altered glycosylation results in an abnormality that causes diseases such as malignancy and cardiovascular diseases. Recent emerging evidence highlights the importance of glycosylation in vascular calcification. Two major types of glycosylation, N-glycosylation and O-glycosylation, are involved in vascular calcification. Other glycosylation mechanisms, which polymerize the glycosaminoglycan (GAG) chain onto protein, resulting in proteoglycan (PG), also have an impact on vascular calcification. This paper discusses the role of glycosylation in vascular calcification.

Chest pain symptoms differences between diabetes mellitus and non-diabetes mellitus patients with acute coronary syndrome: A pilot study.

BACKGROUND: Chest pain is considered one of the crucial indicators in detecting acute coronary syndrome (ACS), and one of the most common complaints frequently found in hospitals. Atypical characteristics of chest pain have prevented patients from being aware of ACS. Chest pain symptoms have become ambiguous, particularly for specific parameters, such as gender, diabetes mellitus (DM), or other clinical conditions. Therefore, it is critical for high-risk patients to have adequate knowledge of specific symptoms of ACS, which is frequently associated with late treatment or prehospital delay. Therefore, this study aims to identify the particular characteristics of chest pain symptoms in DM and non-DM patients with ACS. DESIGN AND METHODS: This is a quantitative and non-experimental research, with the cross-sectional approach used to carry out the analytical observation at a general hospital from January-April 2019. Data were obtained from a total sample of 61 patients, comprising 33 ACS with DM and 28 ACS non-DM patients. RESULTS: The result showed that the characteristic of patients with chest pain symptoms has a significant relation to DM and ACS. Therefore, non-DM patients with ACS are more likely to feel chest pain at moderate to a severe level, while ACS-DM patients are more likely to have low to moderate chest pain levels. CONCLUSION: The significant differences in the characteristics of chest pain in DM and non-DM patients suffering from acute coronary syndrome are the points of location of chest pain radiating to the neck and quality of pain.

Characteristic differences of chest pain in male and female patients with acute coronary syndrome: A pilot study.

BACKGROUND: The typical sign or main symptom in acute coronary syndrome (ACS) patients is chest pain, which is an initial benchmark or early sign for diagnosis. Certain factors, such as gender differences, the presence of diabetes mellitus or other clinical conditions, may make the patient not realize they have ACS. Therefore, this study aims to identify the characteristics of chest pain symptoms in male and female patients with ACS. DESIGN AND METHODS: This is a non-experimental quantitative study, namely analytical observation using a cross-sectional approach within 4 months (January-April 2019). Furthermore, the samples were 53 ACS patients (28 male and 25 female). RESULTS: The chest pain characteristics that have a significant relationship with gender differences in ACS patients are shown based on the aspects of location, pain duration and quality. Male patients are more likely to feel pain at the left or middle chest, the duration is between <20 to >20 min with moderate pain quality, which tends to become severe, while females are more likely to feel pain at the chest which radiates to the neck and chin, the duration is usually >20 min, with mild to moderate pain quality. CONCLUSIONS: The result showed a significant difference in chest pain characteristics in male and female patients with ACS. Regarding location, duration and quality of chest pain, male ACS patients mostly have more typical symptoms, while females' symptoms are atypical.

An Intervention Study for Impact Assessment of Health Education by Empowered Community Health Workers in Improving Treatment and Diet Adherence in Hypertension.

CONTEXT: Medication and low salt diet adherence play as an essential factor in blood pressure target achievement. Community health worker empowerment was reported to be a highly effective social intervention to medication and low salt diet adherence. AIMS: This study aimed to investigate the effect of structured health education regarding hypertension on community health workers on medication and low salt diet adherence among hypertensive patients in Malang. SUBJECTS AND METHODS: A quasi-experimental study was conducted in health workers and their hypertensive patients who join in the Integrated Health Service Post for the Elderly (IHSP-Elderly) program in Malang. Medication adherence was measured by the medication adherence questionnaire and low salt diet adherence was measured by dietary salt restriction questionnaire. The data were analyzed by Chi-square analysis for categorical data and independent t-test for numerical data. RESULTS: This study showed that hypertensive patients in the intervention group had better knowledge regarding hypertension compared to those of the control group (P < 0.05). The patients' satisfaction in intervention group improved significantly after health education (P < 0.01). The proportion of patients with good medication adherence improved significantly (P < 0.01) from 20% to 70% after health education in intervention group. Moreover, the proportion of patients with good low salt diet compliance improved significantly (P < 0.01) from 39% to 85%. Conversely, the proportion of good medication and low salt diet adherence in control group relatively similar between pre- and post-test. CONCLUSIONS: This study showed that health education on community health workers improved hypertensive patients' medication and low salt diet adherence.

Beneficial effects of green coffee and green tea extract combination on metabolic syndrome improvement by affecting AMPK and PPAR-α gene expression.

Effect of green coffee and green tea extract on metabolic syndrome. To explore green coffee and green tea extract combination effect on metabolic profile and blood pressure improvement through adenosine monophosphate-activated protein kinase (AMPK) and Peroxisome Proliferator-Activated Receptor α (PPARα) gene expression modulation. Experimental laboratory research with pre- and post-control group design. Twenty-five metabolic syndrome rats model were grouped into five groups (n = 5): standard control (normal), metabolic syndrome (SM), green coffee extract (GC), green tea extract (GT), and combination green coffee and green tea extract (CM). The extract was given during 9 weeks. Serum glucose, triglyceride, high-density lipoprotein, and systolic blood pressure level were analyzed before and after the extract administration. At the end of the study, PPAR-α and AMPK-α2 gene were analyzed. Independent t-test. CM group had significantly higher PPAR-α, and AMPK-α2 gene expression compared to those of SM, GC, and GT group. Green coffee and green tea extract combination administration improved metabolic profile and blood pressure on metabolic syndrome through affecting PPAR-α and AMPK-α2 gene expression.

Comparison of major bleeding in patients with acute coronary syndrome that underwent coronary artery bypass grafting treated with clopidogrel or ticagrelor: a systematic review and meta-analysis.

Background: There is controversy among physicians regarding the use of dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients treated with coronary artery bypass grafting (CABG). Moreover, the evidence of previous studies about this topic remained inconclusive. This study aimed to perform a meta-analysis concerning the relation between the risk of major bleeding and the use of different DAPT (clopidogrel or ticagrelor) in ACS patients treated with CABG. Methods: A meta-analysis was conducted during March to October 2019. Searches were carried out in Pubmed, Embase, Cochrane, and Web of Science. The predictor covariate in our present study was DAPT (clopidogrel or ticagrelor), and the outcome measure was the risk of major bleeding. Sub-group analysis was also performed, where data were classified into pre- and post-CABG. Furthermore, to determine the correlation and effect estimation, data were analyzed using fixed or random effect model. Results: A total of 13 studies consisting 34,015 patients treated with clopidogrel and 32,661 patients treated with ticagrelor was included in our study. Our pooled calculation revealed that the incidence of major bleeding was not different significantly between clopidogrel and ticagrelor. In pre- and post-CABG sub-groups, our results also found no significant difference in major bleeding incidence between clopidogrel and ticagrelor groups. Conclusions: Our meta-analysis clarifies that clopidogrel, compared to ticagrelor, or vice versa, is not associated with the risk of major bleeding in ACS patients treated with CABG.

The predictors of no reflow phenomenon after percutaneous coronary intervention in patients with ST elevation myocardial infarction: A meta-analysis.

OBJECTIVE: To investigate the no reflow risk factors after percutaneous coronary intervention in ST elevation myocardial infarction patients. METHOD: Sample size, mean±standard deviation (SD) or frequencies (percent) of normal and no reflow groups were extracted from each study. RESULTS: Of 27 retrospective and prospective studies, we found that increasing risks of no reflow were associated with advanced age, male, family history of coronary artery disease, smoking, diabetes mellitus, hypertension, delayed reperfusion, killip class ≥2, elevated blood glucose, increased creatinine, elevated creatine kinase (CK), higher heart rate, decreased left ventricular ejection fraction (LVEF), collateral flow ≤1, longer lesion length, multivessel disease, reference luminal diameter, initial thrombolysis in myocardial infarction (TIMI) flow, and high thrombus burden. Moreover, initial TIMI flow ≤1 and high thrombus burden had the greater impact on no reflow (OR95%CI=3.83 [2.77-5.29], p<0.0001 and 3.69 [2.39-5.68], p<0.0001, respectively). CONCLUSION: Our meta-analysis reveals that initial TIMI flow ≤1 and high thrombus burden are the most impacted no reflow risk factors.

ABO Gene Polymorphism and Thrombomodulin -33G>A Polymorphism Were Not Risk Factors for Myocardial Infarction in Javanese Men.

Genetic factors contribute to about a half of coronary artery diseases. During the last several decades, some studies suggested that non-O blood group and thrombomodulin polymorphism -33G>A are the risk factors of coronary artery disease especially in Asia. There was no prior study in Indonesia regarding this issue. Hence, this study was designed to investigate the correlation of ABO polymorphism and thrombomodulin polymorphism -33G>A with the incidence of acute myocardial infarction (AMI). A total of 192 subjects were enrolled in this case control study. AMI patients were diagnosed based on World Health Organization criteria. Healthy patients were subjects with AMI risk factor without any sign and symptoms of AMI. Patients with diabetes mellitus, cancer, and arrhythmia were excluded from this study. Genotyping for both polymorphisms was performed by PCR RFLP methods. The result of this study suggested that ABO polymorphism and thrombomodulin polymorphism -33G>A were not risk factors of AMI, p = 0.727 and p = 0.699, respectively. Furthermore, the analysis to identify the synergy of these polymorphisms failed to prove their correlation with AMI (p = 0.118). Conclusively, this study showed that ABO polymorphism and thrombomodulin polymorphism -33G>A were not risk factors of AMI.

Methanolic Extract of Ceplukan Leaf (Physalis minima L.) Attenuates Ventricular Fibrosis through Inhibition of TNF-α in Ovariectomized Rats.

The increase of heart failure prevalence on menopausal women was correlated with the decrease of estrogen level. The aim of this study is to investigate the effects of ceplukan leaf (Physalis minima L.), which contains phytoestrogen physalin and withanolides, on ventricular TNF-α level and fibrosis in ovariectomized rats. Wistar rats were divided into six groups (control (-); OVX 5: 5-week ovariectomy (OVX); OVX 9: 9-week ovariectomy; treatments I, II, and III: 9-weeks OVX + 4-week ceplukan leaf's methanolic extract doses 500, 1500, and 2500 mg/kgBW, resp.). TNF-α levels were measured with ELISA. Fibrosis was counted as blue colored tissues percentage using Masson's Trichrome staining. This study showed that prolonged hypoestrogen increases ventricular fibrosis (p < 0.05). Ceplukan leaf treatment also resulted in a decrease of ventricular fibrosis and TNF-α level in dose dependent manner compared to without treatment group (p < 0.05). Furthermore, the TNF-α level was normalized in 2500 mg/kgBW Physalis minima L. (p < 0.05) treatment. The reduction of fibrosis positively correlated with TNF-α level (p < 0.05, r = 0.873). Methanolic extract of ceplukan leaf decreases ventricular fibrosis through the inhibition of ventricular TNF-α level in ovariectomized rats.