Cardiovascular & hematological disorders drug targets最新文献

{"title":"Circumventing Cardiovascular Calamities: The Dawn of ANGPTL3 Blockade in Severe Dyslipidemia Management.","authors":"Alim Namitokov, Karina Karabakhtsieva","doi":"10.2174/011871529X305291240715112812","DOIUrl":"10.2174/011871529X305291240715112812","url":null,"abstract":"<p><p>The landscape of severe dyslipidemia treatment is undergoing a remarkable transformation with the advent of angiopoietin-like 3 (ANGPTL3) inhibitors. ANGPTL3, a pivotal regulator of lipoprotein lipase and endothelial lipase, orchestrates the catabolism of triglyceride-rich and high-density lipoproteins, thus playing a critical role in lipid homeostasis. This review article examines the therapeutic potential of ANGPTL3 blockade and its implications for patients with severe dyslipidemias, particularly those unresponsive to traditional lipid-lowering regimens. We delve into the molecular mechanisms by which ANGPTL3 influences lipid metabolism and appraise the clinical utility of emerging therapeutics, such as monoclonal antibodies and antisense oligonucleotides. Moreover, we discuss the impact of ANGPTL3 inhibition on cardiovascular risk factors and project its promising role in reducing cardiovascular morbidity and mortality. The narrative synthesizes data from recent clinical trials, including the efficacy and safety profiles of ANGPTL3 inhibitors, and forecasts the potential of these agents to revolutionize the management of dyslipidemic conditions. The advent of ANGPTL3-targeted therapies signifies a potential breakthrough in the therapeutic armamentarium against complex lipid disorders, heralding a new era of precision medicine in cardiovascular risk mitigation.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":" ","pages":"59-64"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atrial Septal Abnormalities and Cryptogenic Stroke: A Cross-Sectional Study.","authors":"Marzieh Aliramezany, Mansoor Moazenzadeh, Amin Sayyadi, Khadijeh Mohammadi, Hamidreza Barzegar, Maryam Aliramezany","doi":"10.2174/011871529X294809240415070950","DOIUrl":"10.2174/011871529X294809240415070950","url":null,"abstract":"<p><strong>Background: </strong>Cryptogenic stroke, whose underlying pathology is unknown, accounts for 30-40% of all ischemic strokes. Studies have mentioned the association between atrial septal abnormalities and cryptogenic stroke, but there are still disparities in the results among different studies.</p><p><strong>Objective: </strong>We aimed to clarify the prevalence of atrial septal abnormalities in patients with cryptogenic stroke.</p><p><strong>Methods: </strong>We conducted a cross-sectional study on 91 patients with cryptogenic stroke/transient ischemic attack from March 2021 to March 2022. We evaluated the demographic data of the patients and also the existence of neurologic attacks. Furthermore, echocardiography was performed to determine the type of atrial septal abnormality.</p><p><strong>Results: </strong>Out of 91 patients with cryptogenic stroke/transient ischemic attack, 16 patients (17.5%) had patent foramen ovale, 1 man (1.1%) had atrial septal aneurysm, and 1 woman (1.1%) had an atrial septal defect. Patients with patent foramen ovale were significantly younger than those without. The size of patent foramen ovale in patients with cryptogenic stroke was larger than those with transient ischemic attack, but this difference was not significant. Also, the size of the patent foramen ovale (length and width) was not significantly related to any of the demographic variables (p-value = 0.544, 0.604).</p><p><strong>Conclusion: </strong>Based on our results, the prevalence of atrial septal abnormalities was relatively high. Considering these issues and the importance of preventing neurological accidents in patients, especially young people, it is recommended to always consider atrial septal disorders and, if diagnosed, to carry out the necessary treatment in this field.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":" ","pages":"40-46"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Antihypertensive Potential of Aqueous extract of <i>Peristrophe Bivalvis</i> (L.) Merr. is <i>via</i> Up-regulation of Cyclic Guanosine Monophosphate and Down-regulation of the Renin-angiotensin System.","authors":"Esther Oluwasola Aluko, Ubong Edem David, Abodunrin Adebayo Ojetola, Adesoji Adedipe Fasanmade","doi":"10.2174/011871529X301799240715091918","DOIUrl":"10.2174/011871529X301799240715091918","url":null,"abstract":"<p><strong>Background: </strong>Hypertension is a major risk factor for cardiovascular diseases. <i>Peristrophe bivalvis</i> (PB) is used for the treatment of hypertension, painful sprains, skin diseases, tuberculosis, acute bronchitis, anti-inflammatory conditions, hepatitis, and diabetes. Its antihypertensive potential has been investigated and documented. This study investigated the antihypertensive mechanism of aqueous extract of PB leaf (APB) on L-NAME-induced hypertension.</p><p><strong>Methods: </strong>Thirty male wistar rats (150-170 g) were grouped into five (n=5). Group 1 received 10 mL/kg of distilled water (control), while groups 2-5 were administered 60 mg/kg of L-NAME (L-NAME60) orally for eight weeks to induce hypertension. After eight weeks, groups 2-5 received L-NAME60+distilled water (HNT), distilled water (HRE), L-NAME60+APB (200 mg/kg, [HAPB]), and L-NAME60+ramipril (10 mg/kg, [HRA]), respectively, for five weeks. The BP was measured by the tail-cuff method. The blood sample was obtained under anesthesia, and tissue samples were obtained after euthanasia. Serum renin, ACE, angiotensin-II, endothelin-1, and cyclic guanosine monophosphate (cGMP) levels were measured using ELISA techniques. Malondialdehyde, superoxide dismutase (SOD), and reduced glutathione (GSH) levels were measured by spectrophotometry. Data were analyzed using ANOVA at α0.05.</p><p><strong>Results: </strong>The BP significantly decreased in HAPB compared to HNT. Renin, ACE, and angiotensin- II levels significantly decreased while cGMP levels increased in the HAPB group compared to HNT. Malondialdehyde levels significantly decreased, and SOD and GSH levels increased compared to HNT.</p><p><strong>Conclusion: </strong><i>Peristrophe bivalvis</i> aqueous leaf extract reduced blood pressure in hypertensive rats by modulating the cGMP signalling pathway and the renin-angiotensin system.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":" ","pages":"172-183"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diltiazem Hydrochloride Floating Matrix Tablet: Formulation and <i>in vitro-in vivo</i> Evaluation.","authors":"Krishna D Koradia, Bhavin K Jotaniya, Hiral D Koradia","doi":"10.2174/011871529X304157240712072316","DOIUrl":"10.2174/011871529X304157240712072316","url":null,"abstract":"<p><strong>Background: </strong>Diltiazem hydrochloride is a calcium channel-blocker with a plasma elimination half-life of 4.4 ± 1.3 h and has a narrow absorption window. So, this work aimed to prepare a gastro-retentive floating matrix tablet.</p><p><strong>Methods: </strong>The direct compression method was used to manufacture tablets. 3² factorial design was applied for optimization, taking Hydroxypropyl Methylcellulose K100M (HPMC K 100M) and the amount of sodium bicarbonate as independent factors and cumulative percentage release at 1 h, at 6 h, and at 12 h and floating lag time as dependent variables.</p><p><strong>Results: </strong>The high amount of HPMC K100M and sodium bicarbonate shows good results. The optimized preparation was evaluated for differential scanning calorimetry, <i>in-vivo</i> gastric retention in male albino rabbits, kinetic modeling, and stability study. An <i>in vivo</i> study revealed gastric retention of tablets up to 6 h in healthy male Albino rabbits. The stability study indicated no significant change in the buoyancy and release profiles of the drug.</p><p><strong>Conclusion: </strong>From this study, it can be concluded that the gastro-retentive diltiazem hydrochloride floating matrix tablet was successfully prepared and retained inside the rabbit stomach for up to 6 h and was stable under accelerated stability study.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":" ","pages":"110-124"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining the Difficulties in Identifying and Handling Cardiac Amyloidosis; Acquiring Important Knowledge and Robust Treatment Methods.","authors":"Ghadir Mohammed Saleh Ali, William Ale Emmanuel Seme, Kiran Dudhat","doi":"10.2174/011871529X301954240715041558","DOIUrl":"10.2174/011871529X301954240715041558","url":null,"abstract":"<p><p>Systemic amyloidosis is a rare protein misfolding and deposition condition that causes slow organ failure. Each of the more than 15 exclusive sorts of systemic amyloidosis, which encourage amyloid production and tissue deposition, is introduced by a unique precursor protein. Amyloidosis can affect various organs, including the heart, kidneys, liver, nerves, gastrointestinal tract, lungs, muscles, skin, and soft tissues. It can either be acquired or hereditary. Insidious and doubtful signs often cause a put-off in diagnosis. In the closing decade, noteworthy progressions have been made in the identity, prediction, and handling of amyloidosis. Shotgun proteomics based on mass spectrometry has revolutionized amyloid typing and enabled the identification of novel amyloid forms. It is critical to correctly identify the precursor protein implicated in amyloidosis because the kind of protein influences the proper treatment strategy. Cardiac amyloidosis is a disorder characterized by the systemic accumulation of amyloid protein in the myocardium's extracellular space, which causes a variety of symptoms. The buildup of amyloid aggregates precipitates myocardial thickening and stiffening, culminating in diastolic dysfunction and, in due course, heart failure. We examine every kind of systemic amyloidosis in this text to offer practitioners beneficial equipment for diagnosing and treating those unusual diseases. This review presents a comprehensive analysis of cardiac amyloidosis and consolidates current methods for screening, diagnosis, evaluation, and treatment alternatives.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":" ","pages":"65-82"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding Interactions between a Potential Antimalarial 'MAL2-11B' and its Targets using <i>In Silico</i> Methods.","authors":"Komalpreet Kaur Sandhu, Satinder Kaur, Rachna Hora, Prakash Chandra Mishra","doi":"10.2174/011871529X309936240821072630","DOIUrl":"10.2174/011871529X309936240821072630","url":null,"abstract":"<p><strong>Introduction: </strong>The 70 kDa heat shock proteins (Hsp70) are ubiquitous molecules that play central roles in protein homeostasis. Their nucleotide-binding domains (NBD) are associated with the J domains of 40 kDa co-chaperone 'HSP40' in performing their functions. Interruption of this interaction significantly impacts the critical ATPase activity of Hsp70s, making them dysfunctional.</p><p><strong>Methods: </strong>MAL2-11B is a dihydropyrimidine derivative that blocks Hsp70-Hsp40 interaction and hence holds the potential to be used as a drug. This Hsp70 inhibitor is a structural analogue of MAL3-101 that has proven anti-cancer and antiparasitic activity. MAL2-11B is predicted to have better drug-likeness, solubility, and absorption properties than MAL3-101. In the present study, we have therefore explored the potential of MAL2-11B as an antimalarial by using <i>in silico</i> tools.</p><p><strong>Results: </strong>Molecular docking of MAL2-11B with all <i>Plasmodium falciparum</i> Hsp70 (PfHsp70) proteins revealed its preferential affinity for two out of four homologs at the nucleotide-binding site. Detailed analysis of the docked complexes helped us to predict the kind of protein-inhibitor interactions and specific amino acid residues involved in binding.</p><p><strong>Conclusion: </strong>After <i>in vitro</i> validation, these data may be used as the groundwork for the design and development of new inhibitors and drugs against malaria.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":" ","pages":"151-162"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dengue Fever Related Reactive Thrombocytosis in Young Male: A Case Report and Review Literature.","authors":"Jitendra Singh, Anju Dinkar, Nilesh Kumar, Kailash Kumar, Vikrant","doi":"10.2174/011871529X325967240916075554","DOIUrl":"10.2174/011871529X325967240916075554","url":null,"abstract":"<p><strong>Introduction: </strong>Dengue fever is prevalent in tropical nations, especially India. Leucopenia and thrombocytopenia are distinctive features of acute dengue fever that revert to normal levels after the patient's recovery. Dengue fever is associated with numerous unusual clinical manifestations of different body systems. Additionally, the emergence of severe thrombocytosis following thrombocytopenia is extremely rare. Based on our extensive knowledge, only three cases similar to this have been documented in the literature.</p><p><strong>Case report: </strong>Here, we present a case of a 36-year-old healthy man who had acute dengue and subsequently developed severe reactive thrombocytosis. The patient was treated conservatively and discharged. Subsequently, he developed thrombocytosis. Aspirin was given for a short period to alleviate any potential repercussions.</p><p><strong>Conclusion: </strong>Thrombocytosis, a rare consequence of dengue infection, is usually asymptomatic. Nevertheless, ongoing monitoring of dengue patients is required to avoid complications.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":" ","pages":"196-199"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Therapies for Nonalcoholic Steatohepatitis (NASH) and Cardiovascular Risk Reduction.","authors":"Tarun Biswas, Angelica Lehker, Debabrata Mukherjee","doi":"10.2174/011871529X345190241113103911","DOIUrl":"10.2174/011871529X345190241113103911","url":null,"abstract":"<p><p>Nonalcoholic steatohepatitis (NASH) is a type of nonalcoholic fatty liver disease (NAFLD) characterized by hepatocyte injury and inflammation, in addition to only the presence of steatosis NAFLD. We review the existing data on available novel therapies for NASH and NAFLD and also discuss several therapies in development. We assessed therapies for NASH by searching the databases of PubMed, EMBASE, and Web of Science (SCI) from their inception dates until September 15, 2024. Search terms used were: nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, liver inflammation and hepatocyte injury.Until very recently, therapeutic lifestyle change was the primary modality of treatment for NASH, including modification of diet and physical activity. The FDA recently approved resmetirom using its expedited approval mechanism for NASH. There are also several pharmacotherapies in development for NASH which aim at weight loss, insulin sensitization and improvement in lipid levels, although some drugs may have multiple effects which are discussed. The availability of resmetirom offers patients with NASH an effective adjunctive therapy in addition to lifestyle changes. Several other novel therapies are also currently being tested and will add to our therapeutic armamentarium.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":" ","pages":"211-217"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombosis in Myeloid Malignancies: From CHIP to AML.","authors":"Beatrice Borsellino, Carlos Bravo-Perez, Valeria Visconte, Luca Guarnera","doi":"10.2174/011871529X307253240530060107","DOIUrl":"10.2174/011871529X307253240530060107","url":null,"abstract":"<p><p>The development of myeloid malignancies is a multi-step process starting from pre-malignant stages. Large-scale studies on clonal hematopoiesis of indeterminate potential (CHIP) identified this condition as a risk factor for developing hematologic malignancies, in particular myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). In parallel, CHIP was found to confer an enhanced thrombotic risk, in particular for cardiovascular diseases. In a similar fashion, in recent years, alongside their life-threatening features, increasing attention has been drawn toward thrombotic complications in myeloid malignancies. Thus, the purpose of this review is to gather a growing body of evidence on incidence, pathogenesis and clinical impact of thrombosis in myeloid malignancies at every step of malignant progression, from CHIP to AML.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":" ","pages":"2-12"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141328140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Gallstone Disease and Risk of Mortality of Cardiovascular Disease and Cancer: A Systematic Review and Meta-Analysis.","authors":"Rasoul Rahimi, Shahab Masoumi, Ahmadreza Badali, Negar Jafari, Saeid Heidari-Soureshjani, Catherine M T Sherwin","doi":"10.2174/011871529X298791240607041246","DOIUrl":"10.2174/011871529X298791240607041246","url":null,"abstract":"<p><strong>Background: </strong>Gallstone disease (GD) is increasing in the world and has various complications.</p><p><strong>Objective: </strong>This study aims to examine the relationship between GD and the risk of mortality from cardiovascular disease (CVD) and cancer using a systematic review and meta-analysis approach.</p><p><strong>Methods: </strong>A comprehensive and systematic search was done in various databases, such as Web of Science (WOS), Scopus, MEDLINE/PubMed, Cochrane, and Embase. The search included studies published from 1980 to December 2023. Heterogeneity was assessed using Chi-square, I2, and forest plots, while publication bias was evaluated through Begg's and Egger's tests. All analyses were performed using Stata 15, with statistical significance set at p <0.05.</p><p><strong>Results: </strong>A pooled analysis of five studies involving 161,671 participants demonstrated that individuals with GD had a significantly higher risk of mortality from CVD (RR 1.29, 95% CI: 1.11-1.50, p <0.001). Importantly, no evidence of publication bias was found based on the results of Begg's test (p =0.806) and Egger's test (p =0.138). Furthermore, the pooled analysis of seven studies, encompassing a total of 562,625 participants, indicated an increased risk of cancer mortality among individuals with GD (RR 1.45, 95% CI: 1.16-1.82, p <0.001). Similarly, no publication bias was detected through Begg's test (p =0.133) and Egger's test (p =0.089).</p><p><strong>Conclusion: </strong>In this study, the evidence of a significant association between GD and an elevated risk of mortality from CVD and canceris provided. These findings suggest that implementing targeted interventions for individuals with gallstone disease could reduce mortality rates among these patients.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":" ","pages":"47-58"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}