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Atherosclerosis is still considered a disease burden with long-term damaging processes towards the cardiovascular system. Evaluation of atherosclerotic stages requires the use of independent markers such as those already considered traditional, that remain the main therapeutic target for patients with atherosclerosis, together with emerging biomarkers. The challenge is finding models of predictive markers that are particularly tailored to detect and evaluate the evolution of incipient vascular lesions. Important advances have been made in this field, resulting in a more comprehensible and stronger linkage between the lipidic profile and the continuous inflammatory process. In this paper, we analysed the most recent data from the literature studying the molecular mechanisms of biomarkers and their involvement in the cascade of events that occur in the pathophysiology of atherosclerosis. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is the second most common hematological malignancy. Despite the huge therapeutic progress thanks to the introduction of novel therapies, MM remains an incurable disease. Extensive research is currently ongoing to find new options. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression at a post-transcriptional level. Aberrant expression of miRNAs in MM is common. Depending on their role in MM development, miRNAs have been reported as oncogenes and tumor suppressors. It was demonstrated that specific miRNA alterations using miRNA mimics or antagomirs can normalize the gene regulatory network and signaling pathways in the microenvironment and MM cells. These properties make miRNAs attractive targets in anti-myeloma therapy. However, only a few miRNA-based drugs have been entered into clinical trials. In this review, we discuss the role of the miRNAs in the pathogenesis of MM, their current status in preclinical/clinical trials, and the mechanisms by which miRNAs can theoretically achieve therapeutic benefit in MM treatment. [ABSTRACT FROM AUTHOR]

The atherosclerotic vascular disease is a cardiovascular continuum in which the main role is attributed to atherosclerosis, from its appearance to its associated complications. The increasing prevalence of cardiovascular risk factors, population ageing, and burden on both the economy and the healthcare system have led to the development of new diagnostic and therapeutic strategies in the field. The better understanding or discovery of new pathophysiological mechanisms and molecules modulating various signaling pathways involved in atherosclerosis have led to the development of potential new biomarkers, with key role in early, subclinical diagnosis. The evolution of technological processes in medicine has shifted the attention of researchers from the profiling of classical risk factors to the identification of new biomarkers such as midregional pro-adrenomedullin, midkine, stromelysin-2, pentraxin 3, inflammasomes, or endothelial cell-derived extracellular vesicles. These molecules are seen as future therapeutic targets associated with decreased morbidity and mortality through early diagnosis of atherosclerotic lesions and future research directions. [ABSTRACT FROM AUTHOR]

Waldenström Macroglobulinemia (WM) is an indolent lymphoplasmacytic lymphoma, characterized by the production of excess immunoglobulin M monoclonal protein. WM belongs to the spectrum of IgM gammopathies, ranging from asymptomatic IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), through IgM-related disorders and asymptomatic WM to symptomatic WM. In recent years, its complex genomic and transcriptomic landscape has been extensively explored, hereby elucidating the biological mechanisms underlying disease onset, progression and therapy response. An increasing number of mutations, cytogenetic abnormalities, and molecular signatures have been described that have diagnostic, phenotype defining or prognostic implications. Moreover, cell-free nucleic acid biomarkers are increasingly being investigated, benefiting the patient in a minimally invasive way. This review aims to provide an extensive overview of molecular biomarkers in WM and IgM-MGUS, considering current shortcomings, as well as potential future applications in a precision medicine approach. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates that extracellular vesicles (EVs) released from both tumor cells and the cells of the bone marrow microenvironment contribute to the pathobiology of multiple myeloma (MM). Recent studies on the mechanisms by which EVs exert their biological activity have indicated that the non-coding RNA(ncRNA) cargo is key in mediating their effect on MM development and progression. In this review, we will first discuss the role of EV-associated ncRNAs in different aspects of MM pathobiology, including proliferation, angiogenesis, bone disease development, and drug resistance. Finally, since ncRNAs carried by MM vesicles have also emerged as a promising tool for early diagnosis and therapy response prediction, we will report evidence of their potential use as clinical biomarkers. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a malignancy of terminally differentiated plasma cells and is the second most common hematological cancer. MM frequently occurs in the elderly population with the median age as the middle sixties. Over the last 10 years, the prognosis of MM has been dramatically improved by new therapeutic drugs; however, MM is still incurable. The pathogenesis of MM is still unclear, thus greater understanding of the molecular mechanisms of MM malignancy is desirable. Recently, microRNAs (miRNAs) were shown to modulate the expression of genes critical for MM pathogenesis. In addition, miRNAs are secreted via extracellular vesicles (EVs), which are released from various cell types including MM cells, and these miRNAs are involved in multiple types of cell-cell interactions, which lead to the malignancy of MM. In this review, we summarize the current knowledge regarding the role of miRNA secretion via EVs and of EVs themselves in MM development. We also discuss the potential clinical applications of EVs as promising biomarkers and new therapeutic targets for improving the outcome of MM, resulting in a brighter future for aging societies. [ABSTRACT FROM AUTHOR]

MiRNA-8074 is a molecule with the potential to regulate the expression of key genes related to the pathogenesis of multiple myeloma (MM), i.e., TP53, MYC, MAPK1, and KIAA. We analyzed the predictive and prognostic value of miRNA-8074 expression in MM patients. In total, 105 newly diagnosed MM patients treated with thalidomide (n = 27), bortezomib (n = 41) and bortezomib with thalidomide (n = 37) were studied. For miRNA analysis, the column method and the Real-Time PCR technique with specific TaqMan Fast Advanced Master Mix and TaqMan probes were used. Factors that were associated with a significant reduction in progression-free survival (PFS) included: ECOG > 1, ISS stage III, low hemoglobin, thrombocytopenia, hypoalbuminemia, abnormal renal function, elevated creatinine, GFR < 60 mL/min/1.73 m2, elevated LDH, del(17p), t(11;14), the use of a single drug regimen (thalidomide or bortezomib) and high miRNA-8074 expression (HR = 2.01, 95% CI: 1.16–3.49; p = 0.0233). In addition to the known prognostic factors, such as ECOG > 1, Durie–Salmon stage III, diagnosis of light chain disease or non-secreting MM, renal failure, hypoalbuminemia, hypercalcemia, high β2-microglobulin, elevated LDH, and t(14;16), a high expression of miRNA-8074 was significantly associated with a higher risk of death (HR = 4.12, 95% CI: 2.20–7.70; p = 0.0009). In summary, miRNA-8074 may be a useful diagnostic tool to assess the prognosis in MM patients. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is a fast-progressing bone tumor with high incidence in children and adolescents. The main diagnostic methods for OS are imaging exams and biopsies. In spite of the several resources available for detecting the disease, establishing an early diagnosis is still difficult, resulting in worse prognosis and lower survival rates for patients with OS. The identification of novel biomarkers would be helpful, and recently, circulating microRNAs (miRNAs) have been pointed to as possible non-invasive biomarkers. In order to assess the effectiveness of miRNA research, we performed a systematic review to assess the potential role of circulating miRNAs as biomarkers for OS diagnosis. We performed a search in various databases—PubMed, LILACS (Literatura Latino-americana e do Caribe em Ciências da Saúde), VHL (Virtual Health Library), Elsevier, Web of Science, Gale Academic One File—using the terms: "Circulating microRNAs" OR "plasma microRNAs" OR "serum microRNAs" OR "blood microRNAs" OR "cell-free microRNAs" OR "exosome microRNAs" OR "extracellular vesicles microRNAs" OR "liquid biopsy" AND "osteosarcoma" AND "diagnostic". We found 35 eligible studies that were independently identified and had had their quality assessed according to Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Despite the useful number of publications on this subject and the fact that several microRNAs showed excellent diagnostic performance for OS, the lack of consistency in results suggests that additional prospective studies are needed to confirm the role of circulating miRNAs as non-invasive biomarkers in OS. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer onset and progression are promoted by high deregulation of the immune system. Recently, major advances in molecular and clinical cancer immunology have been achieved, offering new agents for the treatment of common tumors, often with astonishing benefits in terms of prolonged survival and even cure. Unfortunately, most tumors are still resistant to current immune therapy approaches, and basic knowledge of the resistance mechanisms is eagerly awaited. We focused our attention on noncoding RNAs, a class of RNA that regulates many biological processes by targeting selectively crucial molecular pathways and that, recently, had their role in cancer cell immune escape and modulation of the tumor microenvironment identified, suggesting their function as promising immunotherapeutic targets. In this scenario, we point out that noncoding RNAs are progressively emerging as immunoregulators, and we depict the current information on the complex network involving the immune system and noncoding RNAs and the promising therapeutic options under investigation. Novel opportunities are emerging from noncoding-RNAs for the treatment of immune-refractory tumors. Immunotherapy is presently one of the most promising areas of investigation and development for the treatment of cancer. While immune checkpoint-blocking monoclonal antibodies and chimeric antigen receptor (CAR) T-cell-based therapy have recently provided in some cases valuable therapeutic options, the goal of cure has not yet been achieved for most malignancies and more efforts are urgently needed. Noncoding RNAs (ncRNA), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), regulate several biological processes via selective targeting of crucial molecular signaling pathways. Recently, the key roles of miRNA and lncRNAs as regulators of the immune-response in cancer have progressively emerged, since they may act (i) by shaping the intrinsic tumor cell and microenvironment (TME) properties; (ii) by regulating angiogenesis, immune-escape, epithelial-to-mesenchymal transition, invasion, and drug resistance; and (iii) by acting as potential biomarkers for prognostic assessment and prediction of response to immunotherapy. In this review, we provide an overview on the role of ncRNAs in modulating the immune response and the TME. We discuss the potential use of ncRNAs as potential biomarkers or as targets for development or clinical translation of new therapeutics. Finally, we discuss the potential combinatory approaches based on ncRNA targeting agents and tumor immune-checkpoint inhibitor antibodies or CAR-T for the experimental treatment of human cancer. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder that currently affects 1% of the population over the age of 60 years, for which no disease-modifying treatments exist. This lack of effective treatments is related to the advanced stage of neurodegeneration existing at the time of diagnosis. Thus, the identification of early stage biomarkers is crucial. Biomarker discovery is often guided by the underlying molecular mechanisms leading to the pathology. One of the central pathways deregulated during PD, supported both by genetic and functional studies, is the autophagy-lysosomal pathway. Hence, this review presents different studies on the expression and activity of autophagic and lysosomal proteins, and their functional consequences, performed in peripheral human biospecimens. Although most biomarkers are inconsistent between studies, some of them, namely HSC70 levels in sporadic PD patients, and cathepsin D levels and glucocerebrosidase activity in PD patients carrying GBA mutations, seem to be consistent. Hence, evidence exists that the impairment of the autophagy-lysosomal pathway underlying PD pathophysiology can be detected in peripheral biosamples and further tested as potential biomarkers. However, longitudinal, stratified, and standardized analyses are needed to confirm their clinical validity and utility. [ABSTRACT FROM AUTHOR]