Life sciences最新文献

Aims

Materials and methods

Key findings

Significance

Cognitive dysfunction is a commonly reported feature of Long COVID (LC). With the overlap of assessment and treatment for cognitive concerns across multiple disciplines, coupled with current guidelines supporting interdisciplinary care, the aim of this clinically focused article is to provide a review of current guidelines and research related to assessment and interventions to address LC-related cognitive concerns within clinical practice from a multidisciplinary perspective, incorporating best practices for collaboration among Clinical Neuropsychologists, Rehabilitation Psychologists, and Speech-Language Pathologists. Current guidelines for assessment and interventions for cognitive functioning are provided, with clinical suggestions for best practices offered. Additional considerations related to diversity and variable patient presentations are identified. This article provides guidance based on current research and practice standards regarding the utilization of a multidisciplinary, collaborative approach to provide comprehensive assessment and treatment for individuals with LC-related cognitive concerns.

Gynecological cancers are currently a major public health concern due to increase in incidence and mortality globally. PIWI-interacting RNA (piRNA) are small non-coding RNA consisting of 24–32 nucleotides that plays regulatory role by interacting with piwi family of protein. Recent studies have revealed that piRNAs are expressed in various kinds of human tissues and influences key signalling pathways at transcriptional and post transcriptional levels. Studies have also that suggested piRNA and PIWI proteins display frequently altered expression in several cancers. Recent research has indicated that abnormal expression of piRNA may play a significant role in development and progression of gynecological cancers. Clinical studies suggested that, abnormally expressed piRNAs may serve as diagnostic and prognostic marker, and as potential therapeutic targets in these cancers. In the present review article, we discussed the emerging role of piRNA and their utility as diagnostic and prognostic marker in gynecological cancers.

Exosomes, a subset of small extracellular vesicles that play a crucial role in intercellular communication, have garnered significant attention for their potential applications in the diagnosis and treatment of cardiomyopathies. Cardiomyopathies, which encompass a spectrum of heart muscle disorders, present complex challenges in diagnosis and management. Understanding the role of exosomes in the etiology of cardiomyopathies such as dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM), arrhythmogenic cardiomyopathy (AC), and hypertrophic cardiomyopathy (HCM) may open new possibilities for therapeutic intervention and diagnosis. Exosomes have indeed demonstrated promise as diagnostic biomarkers, particularly in identifying cardiac conditions such as atrial fibrillation (AF) and in the timely classification of high-risk patients with different forms of cardiomyopathy. In DCM, exosomes have been implicated in mediating pathological responses in cardiomyocytes, potentially exacerbating disease progression. Moreover, in RCM, AC, and HCM, exosomes present significant potential as diagnostic biomarkers and therapeutic targets, offering insights into disease pathogenesis and potential avenues for intervention. Understanding the influence of exosomes on disease progression and identifying the specific molecular pathways involved in cardiomyopathy pathogenesis may significantly advance diagnostic and treatment strategies. While key findings highlight the multifaceted role of exosomes in cardiomyopathy, they also emphasize the need for further research to elucidate molecular mechanisms and translate findings into clinical practice. This review highlights the evolving landscape of exosome research in cardiomyopathies and underscores the importance of ongoing investigations to harness the full potential of exosomes in improving patient outcomes.

Aims

The production of reactive oxygen species (ROS) by NADPH oxidase (NOX) is able to induce platelet activation, making NOX a promising target for antiplatelet therapy. In this study, we examined the effects of setanaxib, a dual NOX1/4 inhibitor, on human platelet function and ROS-related signaling pathways.

Materials and methods

In collagen-stimulated human platelets, aggregometry, assessment of ROS and Ca²⁺, immunoblotting, ELISA, flow cytometry, platelet adhesion assay, and assessment of mouse arterial thrombosis were performed in this study.

Key findings

Setanaxib inhibited both intracellular and extracellular ROS production in collagen-activated platelets. Additionally, setanaxib significantly inhibited collagen-induced platelet aggregation, P-selectin exposure from α-granule release, and ATP release from dense granules. Setanaxib blocked the specific tyrosine phosphorylation-mediated activation of Syk, LAT, Vav1, and Btk within collagen receptor signaling pathways, leading to reduced activation of PLCγ2, PKC, and Ca²⁺ mobilization. Setanaxib also inhibited collagen-induced activation of integrin αIIbβ3, which is linked to increased cGMP levels and VASP phosphorylation. Furthermore, setanaxib suppressed collagen-induced p38 MAPK activation, resulting in decreased phosphorylation of cytosolic PLA₂ and reduced TXA₂ generation. Setanaxib also inhibited ERK5 activation, affecting the exposure of procoagulant phosphatidylserine. Setanaxib reduced thrombus formation under shear conditions by preventing platelet adhesion to collagen. Finally, in vivo administration of setanaxib in animal models led to the inhibition of arterial thrombosis.

Significance

This study is the first to show that setanaxib suppresses ROS generation, platelet activation, and collagen-induced thrombus formation, suggesting its potential use in treating thrombotic or cardiovascular diseases.

SETD3 is a member of SET domain-containing proteins. It has been discovered as the first metazoan protein (actin) histidine methyltransferase. In addition to this well-characterized molecular function of SETD3, it has been clearly shown to be involved in multiple biological processes, such as cell differentiation, tumorigenesis and viral infection. Here, we summarize the current knowledge on the roles of SETD3 beyond its histidine methyltransferase activity, and outline its cellular and molecular modes of action, as well as the upstream regulation on SETD3, therefore providing insights for the molecular basis of how SETD3 fine regulates multiple physiological and pathological processes.