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.

The Effect of Curcumin Nanoparticles on Paracetamol-induced Liver Injury in Male Wistar Rats.

INTRODUCTION: Curcumin is a naturally occurring compound that has antioxidant properties, acts as a hepatoprotective, and lowers lipid peroxidation. However, curcumin's low solubility and bioavailability are its primary drawbacks and prevent its use as a therapeutic agent. In this study, curcumin nanoparticles will be created using the ultrasonic-assisted extraction method, and their effectiveness against paracetamol-induced changes in ALT, AST, SOD, MDA, and TNF-α will be compared to that of pure curcumin. PURPOSE: This study aimed to determine the hepatoprotective effect of curcumin nanoparticles in paracetamol- induced rats as a model for liver injury. METHODS: Thirty-six male Wistar rats, aged 6 to 8 weeks, with a minimum weight of 120 grams, were used in an experimental laboratory investigation with a post-test-only group design. Rats in each group received 100 mg/kgBW pure curcumin, 100 mg/kgBW curcumin nanoparticles, and 50 mg/kgBW curcumin nanoparticles for 7 days before paracetamol induction. On day 8, 300 mg/kgBW of paracetamol was intraperitoneally injected to cause liver damage. One of the groups received NAC as an antidote 10 hours after paracetamol induction. Detection of ALT and AST using a Chemistry Analyzer. ELISA approach for the detection of SOD, MDA, and TNF-α. The Roenigk score was calculated by two examiners after the liver histopathology preparations were stained using the Hematoxylin-Eosin method. Post hoc analyses were performed after the One Way Annova and Kruskal Wallis tests to examine the data. RESULTS: According to PSA results, the smallest formula that formed curcumin nanoparticles (10.2 nm) was 8 g of curcumin formula mixed with a mixture of Tween 20 4.5 ml, Kolliphor EL 1.5 ml, Propylene Glycol 1.5 ml, and Capryol 90 1 ml for 21 minutes using an ultrasonic process. MDA and TNF-α levels, as well as the liver's histological Roenigk score, were significantly lower in the 100 mg/kgBB pure curcumin group (C100) when compared to the model group (model). The levels of AST, MDA, TNF-α, and the liver histopathology score were significantly lower in the 100 mg/kgBB (NC100) and 50 mg/kgBB (NC50) curcumin nanoparticle groups compared to the model group (model) and pure curcumin group (C100) (p< 0.05). CONCLUSION: Curcumin nanoparticles showed better hepatoprotective ability than pure curcumin.

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.

Takayasu arteritis with congestive heart failure in 26-year-old male: a case report.

BACKGROUND: Takayasu arteritis (TA) is included in large vessel vasculitis with unknown aetiopathogenesis. TA is one of the rare diseases with a predilection for young women. The diagnosis of TA is difficult due to variation in clinical presentations and non-specific initial symptoms. This case demonstrates rare TA in a young male with congestive heart failure as the predominant manifestation. CASE PRESENTATION: We report a 26-year-old male presented with severe dyspnea, palpitation, orthopnea, paroxysmal nocturnal dyspnea, and claudication in the left arm. Four limbs blood pressure discrepancy was present. Chest X-ray showed cardiomegaly with calcification aortic arch and pulmonary edema. Echocardiography revealed that left ventricular ejection fraction decreased with severe aortic and mitral valve regurgitation. Computed tomography angiography showed stenosis of the left common carotid artery and total occlusion of the left subclavian artery with collateral artery. There was vascular thickness and calcification from the peri-aortic valve, ascending aorta, aortic arch, and thoracic descending aorta until abdominal aorta with high-grade stenosis on the inferior side of the renal artery branching accompanied by a post-stenotic dilatation. CONCLUSIONS: This patient's heart failure was precipitated by secondary hypertension and aortic regurgitation caused by vasculitis of TA. In general, there is no difference in the management of congestive heart failure in patients with TA. Optimized pharmacology therapy with combination steroid and methotrexate successfully inducing remission of TA after 3-months follow-up.

Effect of Garcinia mangostana pericarp extract on glial NF-κB levels and expression of serum inflammation markers in an obese-type 2 diabetes mellitus animal model.

Type 2 diabetes mellitus (T2DM) is an age-related disease associated with cerebral inflammation and Alzheimer's disease. Garcinia mangostana pericarp (GMP) possesses antihyperglycemic, antidiabetic and anti-inflammatory effects. The aim of the present study was to evaluate the effect of GMP extract on cerebral inflammation in Wistar rats with T2DM by examining the expression levels of glial nuclear factor-κB (NF-κB), interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and superoxide dismutase (SOD). A total of 36 8-10-week-old male Wistar rats were randomly divided into six groups and provided a standard diet (normal control; C1), high-fat diet (HFD) with 200 g/kg GMP extract BW/day (GMP control; C2), HFD with streptozotocin-nicotinamide (diabetic control; C3), and HFD with 100 (M1), 200 (M2) or 400 g/kg body weight (BW)/day (M3) GMP extract for Wistar rats with diabetes. GMP extract was administered for 8 weeks after induction of T2DM was confirmed. Glial NF-κB activity was assessed by immunohistochemical staining, and by measuring IL-6 levels, TNF-α levels and SOD activity in the serum using ELISA. BW significantly increased following HFD treatment. After 7 weeks, the BW remained significantly higher compared with the normal control and GMP extract-treated groups, but decreased continuously in the T2DM groups. Glial NF-κB immunoreaction in the hippocampal region was significantly higher in the diabetic Wistar rats compared with the normal control Wistar rats, and 200 g/kg BW/day GMP significantly reduced its activity. The T2DM Wistar rats showed significantly higher expression levels of serum IL-6 and TNF-α and lower activity of SOD compared with the normal control Wistar rats. Meanwhile, rats in GMP groups M1, M2 and M3 exhibited significant reductions in the levels of IL-6 and TNF-α expression, and increases in SOD activity. GMP extract treatment effectively reduced hippocampal NF-κB, IL-6 and TNF-α levels and increased antioxidant SOD activity. These results suggest that GMP extract prevents cerebral inflammation in T2DM Wistar rats.