1,721,120 research outputs found
Non-coding RNAs as biomarkers of myocardial infarction
Full text linkNon-coding RNAs (ncRNAs) encompass a family of ubiquitous RNA molecules that lack protein-coding potential and have tissue-specific expression. A significant body of evidence indicates that ncRNA's aberrant expression plays a critical role in disease onset and development. NcRNAs' biochemical characteristics such as disease-associated concentration changes, structural stability, and high abundance in body fluids make them promising prognostic and diagnostic biomarkers. Myocardial infarction (MI) is a leading cause of mortality worldwide. Acute myocardial infarction (AMI), the term in use to describe MI's early phase, is generally diagnosed by physical examination, electrocardiogram (ECG), and the presence of specific biomarkers. In this regard, compared to standard MI biomarkers, such as the cardiac troponin isoforms (cTnT & cTnI) and the Creatinine Kinase (CK), ncRNAs appears to provide better sensitivity and specificity, ensuring a rapid and correct diagnosis, an earlier treatment, and consequently a good prognosis for the patients. This review aims to summarize and discuss the most promising and recent data on the potential clinical use of circulating ncRNAs as MI biomarkers. Specifically, we focused primarily on miRNAs and lncRNAs, highlighting their significant specificity and sensitivity, discussing their limitations, and suggesting possible overcoming approaches
Pathogenic mechanisms, diagnostic, and therapeutic potential of microvesicles in diabetes and its complications
No full textExtracellular vesicles (EVs), particularly microvesicles (MVs), have gained significant attention for their role as mediators of intercellular communication in both physiological and pathological contexts, including diabetes mellitus (DM) and its complications. This review provides a comprehensive analysis of the emerging roles of MVs in the pathogenesis of diabetes and associated complications such as nephropathy, retinopathy, cardiomyopathy, and neuropathy. MVs, through their cargo of proteins, lipids, mRNAs, and miRNAs, regulate critical processes like inflammation, oxidative stress, immune responses, and tissue remodeling, all of which contribute to the progression of diabetes and its complications. We examine the molecular mechanisms underlying MVs' involvement in these pathological processes and discuss their potential as biomarkers and therapeutic tools, particularly for drug delivery. Despite promising evidence, challenges remain in isolating and characterizing MVs, understanding their molecular mechanisms, and validating them for clinical use. Advanced techniques such as single-cell RNA sequencing and proteomics are required to gain deeper insights. Improved isolation and purification methods are essential for translating MVs into clinical applications, with potential to develop novel diagnostic and therapeutic strategies to improve patient outcomes in diabetes.This work has been developed within the framework of the project eINS-Ecosystem of Innovation for Next Generation Sardinia (cod. ECS 00000038), funded by the Italian Ministry for Research and Education (MUR) under the National Recovery and Resilience Plan (PNRR). This work was also made possible thanks to \u201CProgetto Fondazione di Sardegna -Bando 2022\u20132023\u201D and \u201CDM 737/2021 resources 2021\u20132022, funded by the European Union\u2014NextGenerationEU\u201D.Scopu
Potential Therapeutic Targets of Resveratrol in the Prevention and Treatment of Pulmonary Fibrosis
Full text linkPulmonary fibrosis (PF) is a feared component in over 200 interstitial pulmonary diseases, which are characterized by increased alveolar wall thickness, excessive scarring, and aberrant extracellular matrix restructuring that, ultimately, affect lung compliance and capacity. As a result of its broad range of biological activities, including antioxidant, anti-inflammatory, antiapoptotic, and many others, resveratrol has been shown to be an effective treatment for respiratory system diseases, including interstitial lung disease, infectious diseases, and lung cancer. This work reviews the known molecular therapeutic targets of resveratrol and its potential mechanisms of action in attenuating PF in respiratory diseases, including cancer, COVID-19, interstitial lung diseases (ILDs) of known etiologies, idiopathic interstitial pneumonia, and ILDs associated with systemic disorders, such as rheumatoid arthritis, systemic sclerosis, Schrödinger’s syndrome, systemic lupus erythematosus, and pulmonary hypertension. The current issues and controversies related to the possible use of resveratrol as a pharmaceutical drug or supplement are also discussed.This work has been made possible thanks to grants from “Progetto Fondazione di Sardegna-Bando 2022–2023”, “FAR2020-Pintus”, and “DM 737/2021 resources 2021–2022, funded by the European Union - NextGenerationEU”
NASAL EXPRESSION OF ANIOTENSIN-CONVERTING ENZYME 2 (ACE2) IN CHILDREN AND ADULTS WITH COVID-19
Full text link"Emerging evidence suggests that the lower expression of SARS-CoV-2 entry factor angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in the nasal epithelium of children may contribute to lower incidence of COVID-19 in this age group compared to adults, yet no direct evidence is available for this hypothesis. In this study, we compared the transcript levels of ACE2 and TMPRSS2 in nasopharyngeal swabs (NPS) of children and their companion adults within COVID-19 exposed-families (n=207), to assess their association with infection status. Additionally, NPS specimens from COVID-19 positive and symptomatic children (n=24) and adults (n=10) were assessed for associations of ACE2 and TMPRSS2 expression with patients' clinical and laboratory outcomes. In the paired dataset, the expression of both genes was higher among adults (n=115) compared to children (n=92), but the expression was not significantly different between COVID-19 positive and negative patients of all ages or within the same age group. Within the same families, the expression of ACE2 and TMPRSS2 was higher in COVID-19 positive adults when compared to COVID-19 negative children (p=0.0002 and 0.0061, for ACE2 and TMPRSS2, respectively, by Wilcoxon Signed-Rank test, n=94), but the expression of these genes was not significantly different between COVID-19 positive adults and children or between COVID-19 negative adults and positive children. Consistently, the expression of both genes was positively associated with SARS-CoV-2 positivity in this subgroup only (OR: 1.146, 95%CI: 1.038-1.284, p=0.0114 for ACE2 and OR: 1.123, 95%CI: 1.012-1.254, p=0.0334 for TMPRSS2). These findings suggest that children with lower expression of nasal ACE2 and TMPRSS2 are likely to remain COVID-19 negative despite being exposed to a COVID-19 positive family member. Using data from all specimens collected in this study and by grouping them as negative, asymptomatic and symptomatic for COVID-19, no significant association was found between the expression of ACE2 and TMPRSS2 genes and clinical symptoms or laboratory findings.
Molecular insights and emerging therapeutic perspectives of the lncRNA GAS5/miR-21 axis in cancer, fibrosis, cardiovascular, and immune disorders
No full textNon-coding RNAs (ncRNAs) have redefined the complexity of gene regulation, with the long non-coding (lncRNA) GAS5/miR-21 axis emerging as a critical determinant of cell fate across diverse pathological contexts. This review examines the molecular mechanisms by which GAS5 regulates miR-21 activity, thereby restoring tumor suppressor networks and controlling key pathways, including the PI3K/AKT, MAPK/ERK, and Wnt/β-catenin pathways. We detail how dysregulation of this axis fuels cancer progression, metastasis, therapy resistance, fibrosis, cardiovascular diseases, osteoporosis, osteoarthritis, and autoimmune conditions like systemic lupus erythematosus. Beyond its role as a master regulator of apoptosis, proliferation, and EMT, the GAS5/miR-21 interaction holds immense promise as a therapeutic target and a liquid biopsy biomarker. However, clinical translation demands solutions to major challenges, including RNA delivery barriers, context-dependent effects, and adaptive resistance. Leveraging multi-omics integration, gene-editing technologies, and personalized RNA therapeutics will be pivotal to overcoming these obstacles. By critically integrating current knowledge and outlining future directions, this review positions the GAS5/miR-21 axis at the forefront of next-generation ncRNA therapeutics. Harnessing its full potential could not only revolutionize treatment paradigms but also transform our understanding of RNA-driven disease networks
Anticancer Activity of Guggulsterone in Human Leukemic Cells
Full text linkLeukemia is a group of blood cancers that is characterized by the uncontrolled
proliferation of hematopoietic cells and their progressive accumulation within the bone
marrow (BM) and secondary lymphoid tissues. The main cause of leukemia remains
unclear, with a combination of genetic and environmental factors involved. Current
treatment options have several limitations with major side effects, mainly related to
high toxicity. In that respect, alternative forms of treatment are required to effectively
manage and treat leukemia patients. Natural products have been shown to effectively
treat several types of human cancers. These natural products include plants and other
natural substances. Once natural product that has shown promising anti-cancer
properties and has been found to possess cancer chemopreventive and therapeutic
potential in a number of cancer cell lines is the plant polyphenol Guggulsterone (GS),
which is extracted from the gum resin of the commiphora mukul tree. Nevertheless, to
date, few studies have investigated the effects of GS in the treatment of leukemia. In
this respect, this study focuses on the efficiency of GS in the treatment of leukemia. In
this study, we demonstrated that guggulsterone inhibited the viability of human
leukemia cells by inducing apoptosis through activation of the intrinsic mitochondrial
pathway. Anti-tumour activity of guggusterone has been found to be associated with
activation of caspase cascade, upregulation of the proapoptotic proteins (Bax and Bid)
and downregulation of the antiapoptotic proteins (Bcl-2, Bcl-xL, xIAP, cIAP-1, cIAP-
2 and survivin). Furthermore, guggulsterone was found to regulate STAT3 signalingpathway. Another specific objective of this study was to exploit the anticancer potential
of guggulsterone in combination with the existing chemotherapeutic approved platinum
drug cisplatin. Our results revealed that guggulsterone acts synergistically with
cisplatin to inhibit the viability of leukemia cells and improved the chemosensitivity of
cisplatin. Our results demonstrate that guggulsterone could serve as a potent natural
anti-cancer agent that may serve as a promising effective treatment option for leukemia
alone or in combination therapies. Our findings serve as a basis for investigating novel
regimens to prevent or delay the development of platinum resistance and overall
improve the treatment of leukemia
Exploring the role of exosomes in the pathogenesis and treatment of cardiomyopathies: A comprehensive literature review
Full text linkExosomes, 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
Substitution impact of highly conserved arginine residue at position 75 in GJB1 gene in association with X-linked Charcot–Marie-tooth disease: A computational study
No full textX-linked Charcot-Marie-Tooth type 1 X (CMTX1) disease is a subtype of Charcot-Marie-Tooth (CMT), which is mainly caused by mutations in the GJB1 gene. It is also known as connexin 32 (Cx32) that leads to Schwann cell abnormalities and peripheral neuropathy. CMTX1 is considered as the second most common form of CMT disease. The aim of this study is to computationally predict the potential impact of different single amino acid substitutions at position 75 of Cx32, from arginine (R) to proline (P), glutamine (Q) and tryptophan (W). This position is known to be highly conserved among the family of connexin. To understand the structural and functional changes due to these single amino acid substitutions, we employed a homology-modeling technique to build the three-dimensional structure models for the native and mutant proteins. The protein structures were further embedded into a POPC lipid bilayer, inserted into a water box, and subjected to molecular dynamics simulation for 50 ns. Our results show that the mutants R75P, R75Q and R75W display variable structural conformation and dynamic behavior compared to the native protein. Our data proves useful in predicting the potential pathogenicity of the mutant proteins and is expected to serve as a platform for drug discovery for patients with CMT
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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