BACKGROUND: Thromboembolic disorders including Myocardial infarction[ MI] and stroke represent the leading causes of death worldwide. Fibrinolytic enzymes extracted from microbial sources showed high efficacy in the dissolution of different blood clots. AIM OF THE STUDY: Screening and the bacterial recombinant DNA manufacture of bacterial fibrinolytic enzymes from different soil environments in Egypt. METHODOLOGY: A total of 50 soil samples were screened for their fibrinolytic enzyme production. The potent fibrinolytic enzyme-producing bacterial isolates were evaluated for their thrombolytic activities using the plasma plate method. The characterization of the enzyme activity and thermostability were carried out; also, the determination of molecular mass using a mass spectrometer and western blot technique was performed. The purification of the fibrinolytic enzymes was done through the affinity chromatography technique. On the other hand, the production of the purified bacterial fibrinolytic enzyme was achieved via bacterial recombinant DNA technology. Formulation of fibrinolytic enzymes in different dosage forms was tried. RESULTS: In the present study, the purified bacterial fibrinolytic enzyme was approximately 83% pure through affinity chromatography and SDS-PAGE assay. The predominating bacterial isolate secreting fibrinolytic enzymes was found to be Bacillus cereus. The fibrinolytic enzyme activities of 50 soil samples were found to be in the range of 0.167-1.853 U/ ml. The fibrinolytic activity of the extracellular enzyme refined from the culture supernatant of Bacillus cereus was relatively stable over the PH range from 7.4-10 for 18 hours and also it showed stability with the highest productivity at a temperature of 43 0C for nearly 60 minutes. The enzyme was called fibrin-proteinase[ FP] in the present study. The FP degraded the fibrin clots via direct thrombolysis. The specific activity and the molecular mass of the FP were estimated to be nearly 40.71 Units/ mg protein and nearly 30 KDa respectively. Protease activity was noticed to be slightly increased in the presence of Fe+3; While it was inhibited in the presence of EDTA. On the other hand, the FP fibrinolytic activity was enhanced greatly after the addition of monovalent cations such as K+1 and Na +1. The enzyme was also active over the temperature range of 20- 65 0C with the highest activity at 55 0C. The optimum temperature and PH of protease production was at 35-43 0C and PH 8.0-10. Conclusion: During the present study, the thermostable fibrinolytic enzyme FP purified from Bacillus cereus in different soil environments in Egypt was a promising fibrinolytic enzyme because it showed a broader efficacious fibrinolytic activity as well as less adverse effects than the current fibrinolytic enzymes globally. It is recommended in the future advanced exploration of the optimization of suitable formulation of bacterial fibrinolytic enzymes to aid in the dissolution of various blood clots and as a consequence overcoming the high rate of mortality globally.

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment ele-vation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued. Out-of-hospital car-diac arrest and cardiogenic shock remain a major cause of high in-hospital mortality, whilst the growing burden of heart failure in long-term STEMI survivors presents a growing problem. Many elements aiming to optimize STEMI treatment are still subject to debate or lack sufficient evidence. This review provides an overview of the most contentious current issues in pPCI in STEMI patients, with an emphasis on unresolved questions and persistent challenges.

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. In particular, the modRNA-based COVID-19 vaccines have proven that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options. MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and improves cardiac dysfunction. However, it remains elusive whether the early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. To obtain acute CCN5 expression, we used modRNA-mediated gene transfer in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: 1) preventive intervention and 2) therapeutic intervention. Cardiac function and structural changes were measured by echocardiography and magnetic resonance imaging. Finally, fibrosis and the underlying molecular pathway were analyzed by western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. The modRNA-CCN5 gene transfer successfully ameliorated CF and enhanced cardiac function in both preventive and therapeutic interventions without LV rupture or any adverse cardiac remodeling. Conclusively, early intervention in CF by modRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure without adverse structural remodeling.

Background: Stress hyperglycemia (SH) is common is patients with ST-elevation myocardial infraction (STEMI). The aims of the study were to analyze the impact of SH on the incidence of all-cause mortality and major adverse cardiovascular events (MACE-cardiovascular death, non-fatal reinfarction, target vessel revascularization and stroke) in STEMI patients without diabetes mellitus (DM) who have been treated successfully with primary PCI (pPCI) Method: we analyzed 2,362 STEMI patients treated with successful pPCI (post-procedural flow TIMI=3) and without DM and cardiogenic shock at admission. SH was defined as plasma glucose level above 7.8mmol/L at admission. The follow-up period was 8 years. Results: Incidence of SH was 26.9%. Eight-year all-cause mortality and MACE rates were significantly higher in patients with SH, as compared to patients without SH (9.7% vs 4.2%, p

Myocardial fibrosis is a pivotal pathophysiological step of various cardiovascular diseases, which eventually leads to heart failure and death. Cardiac fibroblasts activation and subsequently differentiate into myofibroblasts are pivotal pathophysiological step in myocardial fibrosis. Phosphoglycerate mutase 1 (PGAM1) directly interacts with α-smooth muscle actin (ACTA2) and participate in fibrosis regulation. Allosteric inhibitor of PGAM1 could attenuates fibrosis through break the interaction of PGAM1 and ACTA2. In this study, we aimed to screen and identify novel ligand of PGAM1 in natural product library. Firstly, various natural products were screened via DARTS assay and Carthamus tinctorius L. was identified as a target pool for molecular docking. Then, in silico screening assay identified baicalein as a novel ligand. In addition, baicalein could directly bind to the PGAM1 protein with a KD value of 34.6 μM. Molecular dynamics simulation revealed that baicalin and PGAM1 interactions were stable. These findings indicate that PGAM1 is a direct pharmacological target of baicalein. Immunoblot analysis further demonstrated that baicalin inhibits the activation of fibroblasts in vitro. Finally, the anti-myocardial fibrosis effect of baicalein was verified in vivo. Taken together, our findings suggest that baicalein is a novel PGAM1 templates for developing new therapeutics against myocardial fibrosis.

Background. Transcatheter edge-to-edge repair (TEER) is a safe and effective treatment in symptomatic patients with mitral regurgitation (MR). We aimed to investigate the short-term impact of mitral TEER on left ventricular (LV) performance and identify echocardiographic prognostic indicators. Methods. Seventy-eight patients with severe MR (organic and functional etiologies) were included retrospectively. All patients had a baseline and short-term echocardi-ography after TEER and were followed up for the primary composite endpoint (heart failure hos-pitalization and cardiovascular death) over a median period of 13 months. Results. A significant decrease in left ventricular ejection fraction (LVEF), all myocardial work indices (except global wasted work), and left atrial reservoir were observed after TEER. Additionally, there was an im-provement in the pulmonary artery systolic pressure and tricuspid annular plane systolic excur-sion/pulmonary artery systolic pressure (TAPSE/PASP) ratio. 34% of all patients presented the primary composite endpoint. A TAPSE/PASP ratio post-TEER < 0.47 (HR: 4.76, p-value = 0.039), and left atrial reservoir post-TEER < 9.0% (HR: 2.77, p-value = 0.047) were independently associ-ated with the primary endpoint. Conclusions. Echocardiography post-TEER reflects impairment in ventricular performance due to preload reduction and right ventricular to pulmonary artery coupling improvement. Short-term echocardiography after TEER identifies high-risk patients who could benefit from a close clinical follow-up.