Cardiovascular & hematological agents in medicinal chemistry最新文献

Background: Coronary collaterals are the feeding bridges between the main epicardial arteries, and research has shown that this collateral development plays a crucial role in myocardial performance, especially in patients with coronary artery disease. However, the evolution of these collaterals has not been fully explained.

Objective: In this study, we aimed to reveal the effect of CD31 on coronary collateral development.

Methods: As a result of coronary angiography performed in our clinic, 89 patients with coronary artery disease and 90 patients with normal coronary arteries were included in the study. Collateral development degrees were recorded from the angiographic images of the subjects. CD31 values were compared between the group with coronary artery disease and the control group. In addition, the coronary artery disease group was divided into subgroups according to the collateral development in terms of good collateral development and poor collateral development, and the factors that may affect the collateral development were tried to be determined.

Results: CD31 levels were significantly higher in the group with coronary artery disease compared to the control group (p <0.001). In addition, CD31 levels in the subgroup with good collateral were significantly higher than in the group with weak collateral (p <0.001). In the correlation analysis, a significant positive correlation was found between serum CD31 level and SYNTAX score, age, glucose, and rentrop grade. Multivariate logistic regression analysis showed CD31 to be an independent predictor of good coronary collateral development.

Conclusion: CD31, a marker of angiogenesis, may be involved in coronary collateral development.

Type 2 diabetes is characterized by elevated blood glucose levels, leading to an increased risk of cardiovascular diseases. Sodium butyrate, the sodium salt of the short-chain fatty acid butyric acid produced by gut microbiota fermentation, has shown promising effects on metabolic diseases, including type 2 diabetes and cardiovascular diseases. Sodium butyrate demonstrates anti-inflammatory, anti-oxidative, and lipid-lowering properties and can improve insulin sensitivity and reduce hepatic steatosis. In this review, we investigate how sodium butyrate influences cardiovascular complications of type 2 diabetes, including atherosclerosis (AS), heart failure (HF), hypertension, and angiogenesis. Moreover, we explore the pathophysiology of cardiovascular disease in type 2 diabetes, focusing on hyperglycemia, oxidative stress, inflammation, and genetic factors playing crucial roles. The review suggests that sodium butyrate can be a potential preventive and therapeutic agent for cardiovascular complications in individuals with type 2 diabetes.

Introduction: The drug discovery and development domain has witnessed remarkable advancements due to the integration of computational methods, particularly Computer-Aided Drug Design (CADD). Discovering and creating new drugs involves structural modifications to enhance their effectiveness and physical attributes. This frequently includes employing semisynthetic techniques to investigate structure-activity relationships thoroughly. Noticeable progress in molecular biology, computational chemistry, combinatorial chemistry, and highthroughput screening is steering transformative changes in the pharmaceutical industry.

Background: High blood pressure or hypertension, a significant health issue, elevates the chances of heart, kidney, and brain complications, among other health concerns. It's a leading cause of untimely mortality globally. Therefore, it is important to search for new antihypertensive compounds that have fewer side effects and higher therapeutic activity.

Methods: Following molecular docking of the pyridazine derivatives, compounds were subjected to In-silico ADMET analysis. Subsequently, a low molecular weight compound was synthesized. Among the synthesized compounds characterization procedures include TLC, FT-IR, 1HNMR, and LC-MS techniques.

Result: Compound 8 exhibited the most favorable molecular docking results with alpha A1 and beta 1 adrenergic receptors. Compounds 3, 5, and 6 fulfilled the essential ADMET criteria. Subsequently, Compounds 3, 4, and 5 underwent additional synthesis and characterization procedures, including TLC, FT-IR, 1H-NMR, and LC-MS techniques.

Conclusion: Similar behavior was observed in compounds 6, 8, 10, and 11, all violating Pfizer's 3/75 rules in terms of TPAS. Hydrazinolysis of these b-benzoyl propionic acids produced pyridazine, which was utilized in synthesizing pyridazine derivatives. TLC, FT-IR, 1HNMR, and LCMS have characterized the compounds.

Background: Warfarin is an effective anticoagulant but requires close International Normalized Ratio (INR) monitoring and may occasionally require correction of excessive anticoagulation. Current guidelines provide limited practical guidance on the administration of vitamin K for the management of supratherapeutic INR levels ≥ 5.0 in non-bleeding outpatients.

Objective: Based on expert consensus and guidelines, the Atrius Health Anticoagulation Management Services (AMS) has developed internal guidance for oral vitamin K use in highly selected populations. This study will describe the internal guidance for oral vitamin K use and present associated results and clinical outcomes.

Methods: Episodes with INR > 5.0 were included, with vitamin K considered for episodes with INR ≥ 6. Moreover, compelling indications and exclusions to select ideal patients for vitamin K intervention were also defined.

Results: Overall, episodes were managed conservatively; of the 246 collected episodes of excessive anticoagulation, in 18 episodes (7%), patients received vitamin K, and in 228 (93%) episodes, patients did not receive vitamin K. The mean index INR was 6.0 (range 5.0 - 10.5, SD 1.07), with nearly 57% of episodes achieving INR correction and 15% of episodes developing INR overcorrection. High thrombotic risk patients, regardless of hemorrhagic risk, were less likely to receive vitamin K. Three episodes (1.2%) resulted in bleeding complications. No thrombotic complications occurred during the 30-day follow-up of the index INR value ≥ 5.0.

Conclusion: Our internal guidance is a novel, standardized approach that serves as a decision support tool for the management of warfarin-associated coagulopathy and vitamin K intervention using patient-specific characteristics and index INR values. This guidance may assist other anticoagulation management services with practical applications and require validation in a prospective clinical trial.

Background: Pulmonary Hypertension (PH) leads to changes in pulmonary vascular architecture, hypertrophy of the right ventricle, and heart failure. Sildenafil is a drug that can modulate PH by inducing smooth muscle relaxation and vasodilation.

Aims: To investigate the ability of sildenafil to alleviate the monocritaline (MCT)-induced PH in rats and to estimate the role and its effect on the atrial natriuretic peptide (ANP) levels.

Methods: 28 adult male rats were divided randomly into four groups: Group A (control group; n=7). Group B (MCT-treated group; n=7) was given a single dose of MCT 60 mg/kg subcutaneously. Group C (The reversal group; n=7) received a single dose of MCT 60 mg/kg subcutaneously for three weeks and then sildenafil at 50 mg/kg/day, given daily for another three weeks. Group D (The prevention group; n=7) simultaneously received a single dose of MCT 60 mg/kg subcutaneously and sildenafil daily at 50 mg/kg for three weeks.

Results: The animals in the prevention group showed a significant decrease in ANP levels compared to the reversal and MCT-treated groups. This decrease was associated with a significant reduction in the Fulton index ratio in the prevention group compared to the reversal group. The nitric oxide levels were also significantly higher in the reversal group than in the control group.

Conclusion: Preventive sildenafil treatment was associated with a significant decrease in ANP levels and reduced MCT-induced cardiac hypertrophy in rats.

Overproduction of reactive nitrogen and oxygen species (RNS and ROS) has been linked to the pathogenesis of diabetes, hypertension, hyperlipidemia, stroke, angina, and other cardiovascular diseases. These species are produced in part by the mitochondrial respiratory chain, NADPH oxidase, and xanthine oxidase. RNS and ROS both contribute to oxidative stress, which is necessary for the development of cardiovascular disorders. In addition to ROS species like hydroxyl ion, hydrogen peroxide, and superoxide anion, RNS species like nitric oxide, peroxynitrous acid, peroxynitrite, and nitrogen dioxide radicals have also been linked to a number of cardiovascular conditions. They promote endothelial dysfunction, vascular inflammation, lipid peroxidation, and oxidative damage, all of which contribute to the development of cardiovascular pathologies. It's crucial to understand the mechanisms that result in the production of RNS and ROS in order to identify potential therapeutic targets. Redox biomarkers serve as indicators of oxidative stress, making them crucial tools for diagnosing and predicting cardiovascular states. The advancements in proteomics, metabolomics, genomics, and transcriptomics have made the identification and detection of these small molecules possible. The following redox biomarkers are notable examples: 3-nitrotyrosine, 4-hydroxy-2-nonenal, 8- iso-prostaglandin F2, 8-hydroxy-2-deoxyguanosine, malondialdehyde, Diacron reactive oxygen metabolites, total thiol, and specific microRNAs (e.g. miRNA199, miRNA21, miRNA1254, miRNA1306-5p, miRNA26b-5p, and miRNA660-5p) are examples. Although redox biomarkers have great potential, their clinical applicability faces challenges. Redox biomarkers frequently have a short half-life and exist in small quantities in the blood, making them challenging to identify and measure. The interpretation of biomarker data may also be influenced by confounding factors and the complex interplay of various oxidative stress pathways. Therefore, in-depth validation studies and the development of sensitive and precise detection methods are needed to address these problems. In the search for redox biomarkers, cutting-edge techniques like mass spectrometry, immunoassays, and molecular diagnostics are applied. New platforms and technologies have made it possible to accurately detect and monitor redox biomarkers, which facilitates their use in clinical settings. Our expanding knowledge of RNS and ROS involvement in cardiovascular disorders has made it possible to develop redox biomarkers as diagnostic and prognostic tools. Overcoming the challenges associated with their utility and utilizing advanced detection techniques, which will improve their clinical applicability, will ultimately benefit the management and treatment of cardiovascular conditions.

Introduction: Doxorubicin (Dox), an antineoplastic agent is used as a primary anticancerous drug against various types of cancers. However, its associated toxicity to the cardiovascular system is major. Literature has recorded the cases of mortality due to poor validation and lack of prediagnosis of Dox-induced cardiotoxicity. Therapeutic interventions using natural products having cardioprotective properties with low toxic outcomes hold therapeutic potential for future cardio-oncological therapies. Syzygium cumini (Black berry), a traditional Indian herbal plant, has been researched and found to exert cardioprotective, anti-inflammatory, and antioxidant activities, which have been credited due to the presence of polyphenols, flavonoids, and tannins.

Methods: In the current research, we investigated the cardioprotective potential of Syzygium cumini against Doxorubicin-induced cardiotoxicity (DIC) in H9C2 cardiomyocytes. Methanolic seed extract preparation of Syzygium cumini was performed using the Soxhlet apparatus. Cell viability and cell death assays were performed to determine the cardiotoxic doses of Doxorubicin. Furthermore, the cardioprotective potential of Syzygium cumini extract against DIC was studied. Morphological and nuclear alterations in H9C2 cells were studied by microscopic assays using Giemsa, Haematoxylin-Eosin stain, and PI. The intracellular stress level and ROS production were studied using DCFH-DA followed by mitochondrial integrity analysis using fluorescent microscopic methods.

Results: In the results, we investigated that Dox exerted a dose and time-dependent cardiotoxicity on H9C2 cardiomyocytes. Moreover, we observed that morphological and nuclear alterations caused by doxorubicin in dose-dependent manner were prevented by supplementing with Syzygium cumini polyphenols and it attenuated the oxidative stress in H9C2 cardiomyocytes effectively.

Conclusion: Conclusively, Syzygium cumini possesses cardioprotective potential in H9C2 cardiomyocytes in dox-induced cardiotoxicity.

Background: Post-myocardial infarction (MI) changes have been frequently reported in the literature and are associated with determining the prognosis.

Aims: The aim of this study is to find a prognosis marker for the favorability of determination of the medium-term outcomes in patients with acute MI.

Objectives: MI patients' prognosis is poorly understood and requires further elaboration.

Materials and methods: A single center, cross-sectional cohort study involved 211 patients' medical history with acute MI, for the period 2014-2019, had been evaluated retrospectively for 76 parameters. The data was collected from the Republic Rehabilitation Mordovian Hospital. The described measurement units were used in the local laboratories to describe the values. The descriptive values were expressed in the mean average and standard deviation. For statistical analysis, descriptive statistics, t-test independent by groups and dependent by numerical variables for repeated analysis for the same patients, multinomial logistic regression, Pearson's correlation coefficient, ROC analysis, and for clarification purposes, diagrams and bar figures were used. For performing the statistical analysis, the SPSS program, version 28 was used.

Results: Descriptive statistics showed a proportion of men to females 7:3. The mean age of the MI patients was 61.50 years (Std. Dev. ± 10.68), and the mean height of the sample was 171.00 cm (Std. Dev. ± 7.20). The mean body weight of the sample is 83.62 kg (Std. Dev. ± 12.35), and the body mass index (BMI) is 29.02 kg/m2 (Std. Dev. ± 5.07). The total hospitalization days are 14.79 (Std. Dev. ± 3.41). The mean heart rate (HR) beat per minute (bpm) was 79.03 (Std. Dev. ± 15.63), and the mean blood pressure was 138.53/84.09 mmHg (Std. Dev. ± 28.66/12.79). On the complete blood count (CBC), the mean level of the hemoglobin (Hb) 136.33 g/l (Std. Dev. ± 15.29), the mean level of the leukocytes (WBC) 8.76 /μl (Std. Dev. ± 2.77), the mean level of the red blood cells (RBC) 4.55 /μl (Std. Dev. ± 0.52), the mean level of the relative value of the lymphocytes 24.46 % (Std. Dev. ± 9.015), and the mean level of the thrombocytes 207.87 /μl (Std. Dev. ± 64.035). The mean erythrocytes segmentation rate (ESR) is 18.99 mm/hr (Std. Dev. ± 12.16). The regression analysis demonstrated that the dependent variable, complication, in particular, pericarditis, and the independent factor, concomitant disease, in particular, chronic heart failure, has a significant regression coefficient of 29.101 at p <0.05. Furthermore, the dependent variable, complication, in particular, pneumonitis, and the independent factor, concomitant disease, particularly, arrhythmia, have a significant regression coefficient of 21.937 at p <0.05.

Conclusion: An elevated level of CPK-MB/LDH/Troponin I is linked to the development of arrhythmia. Patient

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disorder, in which genetic and environmental factors are involved in disease onset. Although, by definition, the disease is considered idiopathic in nature, evidence-based studies have indicated familial cases of pulmonary fibrosis, in which genetic factors contribute to IPF pathogenesis.

Methods: Both common as well as rare genetic variants are associated with sporadic as well as familial forms of IPF. Although clinical inferences of the genetic association have still not been explored properly, observation-based studies have found a genotypic influence on disease development and outcome.

Results: Based on genetic studies, individuals with a risk of IPF can be easily identified and can be classified more precisely. Identification of genetic variants also helps to develop more effective therapeutic approaches.

Conclusion: Further comprehensive research is needed to get a blueprint of IPF pathogenesis. The rapidly evolving field of genetic engineering and molecular biology, along with the bioinformatics approach, will possibly explore a new horizon very soon to achieve this goal.