Cardiovascular & hematological disorders drug targets最新文献

Introduction: 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.

Methods: 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 in silico tools.

Results: Molecular docking of MAL2-11B with all Plasmodium falciparum 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.

Conclusion: After in vitro validation, these data may be used as the groundwork for the design and development of new inhibitors and drugs against malaria.

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.

Introduction: 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.

Case report: 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.

Conclusion: Thrombocytosis, a rare consequence of dengue infection, is usually asymptomatic. Nevertheless, ongoing monitoring of dengue patients is required to avoid complications.

Background: Gallstone disease (GD) is increasing in the world and has various complications.

Objective: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

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.

Introduction: Subacute Bacterial Endocarditis (SBE) is a slowly developing type of infective endocarditis. Aneurysm is more common in this type of endocarditis. Currently, SBE is an uncommon cause of unexplained fever (FUO) because rapid diagnostic capabilities, such as echocardiography, have improved. Despite echocardiography, endocarditis and valvular aneurysm were missed in our patient due to the location and special shape of the aneurysm near the annulus.

Case representation: We present a case of SBE resulting in an isolated ruptured mycotic mitral valve aneurysm in a patient on dialysis. Mycotic mitral valve aneurysm is an uncommon and serious complication of infective endocarditis, particularly subacute endocarditis.

Conclusion: In order to diagnose this complication, there should be clinical suspicion in the presence of severe regurgitation without any cause, and a detailed echocardiography should be performed.

Arterial Hypertension (HTN) is the leading cause of cardiovascular diseases, which, in turn, are the primary cause of mortality worldwide. The success rates in Blood Pressure (BP) control among the general population remain unacceptably low. HTN etiology is multifactorial, but ample evidence has shown an essential role of the Autonomic Nervous System (ANS) dysfunction in its physiopathology. Concurrently, studies have pointed to the promising effect of non-invasive cortical stimulation techniques, such as transcranial Direct Current Stimulation (tDCS), on modulating blood pressure and the ANS. tDCS involves the application of a direct low-intensity electric current between two electrodes (cathode and anode) placed on the scalp and skull over areas of interest in the cerebral cortex. The impacts of this technique on regulating BP levels and cardiovascular autonomic modulation have excellent potential to be explored in hypertension. This study aimed to review and discuss the existing evidence concerning the efficacy of tDCS in modulating BP and ANS, focusing on its potential as a therapeutic intervention for HTN. This narrative mini-review presents and discusses critical findings regarding using tDCS to modulate BP and the ANS. Data obtained from clinical and preclinical studies have been addressed in this work. The evidence gathered and discussed in this mini-review suggests the promising role of tDCS as a non-invasive intervention for HTN; however, the underlying mechanisms through which it exerts its effects remain poorly understood. More mechanistic studies must be carried out to draw definitive conclusions regarding the effectiveness and safety of tDCS as a treatment for HTN.

Background: About 15% of coronary artery interventions are performed on coronary artery bifurcation. Managing these lesions presents a significant therapeutic obstacle in the context of coronary artery issues. Addressing both immediate and lasting side effects of these lesions demands ongoing monitoring and action. The introduction of drug-eluting stents has raised hopes for better outcomes in patients experiencing cardiovascular events.

Methods: In this study, we selected 51 patients (out of 850) who had received ≥1 cobalt-chromium, biodegradable polymer, Biolimus A9-eluting stent (CoCr-BP-BES) Biomatrix Alpha stent. Immediately after stenting, thrombolysis in myocardial infarction (TIMI) flow score in the coronary artery and its bypass branch, plaque shift, and lateral dissection immediately after angioplasty were evaluated.

Results: The mean age for patients was 65 (±10.35) years, where 49.02% of them were male and 45.1% had diabetes. No lateral dissection and death were reported in any of the patients. Also, the TIMI flow grade was 3 for the main branch in all patients. Plaque shifts were compared at different degrees of the TIMI flow coronary artery bypass graft. A statistical study revealed a noteworthy distinction between the groups. There was no discernible change when gender, diabetes, systolic and diastolic blood pressure with plaque changes were all controlled for.

Conclusion: We discovered that the Biomatrix Alpha stents' instant clinical results are admissible. Our findings confirm the clinical utility of the recently developed biolimus-eluting (BES) stent technology, which combines the BA-9 medication, a thin-strut CoCr stent platform, and a biodegradable polymer. This aligns with the existing body of research on the most recent generation of drug-eluting stents (DES).

Cardiovascular diseases (CVDs), which stand as the primary contributors to illness and death on a global scale, include vital risk factors like hyperlipidemia, hypertension, diabetes, and smoking, to name a few. However, conventional cardiovascular risk factors offer only partial insight into the complexity of CVDs. Lately, a growing body of research has illuminated that the gut microbiome and its by-products are also of paramount importance in the initiation and progression of CVDs. The gastrointestinal tract houses trillions of microorganisms, commonly known as gut microbiota, that metabolize nutrients, yielding substances like trimethylamine-N-oxide (TMAO), bile acids (BAs), short-chain fatty acids (SCFAs), indoxyl sulfate (IS), and so on. Strategies aimed at addressing these microbes and their correlated biological pathways have shown promise in the management and diagnosis of CVDs. This review offers a comprehensive examination of how the gut microbiota contributes to the pathogenesis of CVDs, particularly atherosclerosis, hypertension, heart failure (HF), and atrial fibrillation (AF), explores potential underlying mechanisms, and highlights emerging therapeutic prospects in this dynamic domain.

Objective: This review aims to comprehensively analyse the fear of eating behaviour in individuals with diabetes, known as diabulimia or ED-DMT1. The emotional and psychological factors contributing to disordered eating behaviours, their impact on diabetes management, and potential consequences on physical health are explored. Various therapeutic interventions, including cognitive-behavioural therapy and psychological support, the role of nutrition education, individualized treatment plans support groups in managing fear of eating behaviour in diabetes are examined and discussed.

Methods: A comprehensive literature search was conducted to identify relevant studies, articles, and guidelines related to fear of eating behaviour in diabetes. The search included databases such as PubMed and Google Scholar using appropriate keywords.

Results: The review highlights the emotional and psychological factors that contribute to the fear of eating behaviour in diabetes, including body image concerns, fear of weight gain, and disordered eating patterns. These behaviours can significantly impact diabetes management, leading to poor glycaemic control, increased risk of complications, and reduced overall well-being. Various therapeutic interventions, such as cognitive-behavioural therapy and mindfulness-based interventions, have shown promise in addressing the fear of eating behaviour.

Conclusion: A multidisciplinary strategy combining healthcare specialists specializing in diabetes management, mental health, and nutrition is required for effective therapy of fear of eating behaviour in diabetes. Cognitive-behavioral therapy and mindfulness-based therapies, as well as psychological support, have shown potential in reducing the fear of eating habits. This analysis gives significant information for healthcare providers to help patients with diabetes who are afraid of eating and urges additional research on the topic.