Background: Because of the complexity of the blood-brain barrier (BBB), brain tumors, especially the most common and aggressive primary malignant tumor type arising from the central nervous system (CNS), glioblastoma, remain an essential challenge regarding diagnostic and treatment. There are no approved circulating diagnostic or prognostic biomarkers, nor novel therapies like immune checkpoint inhibitors for glioblastoma, and chemotherapy brings only minimal survival benefits. The development of molecular biology led to the discovery of new potential diagnostic tools and therapeutic targets, offering the premise to detect patients at earlier stages and overcome the current poor prognosis. Main body: One potential diagnostic and therapeutic breakthrough might come from microRNAs (miRNAs). It is wellknown that miRNAs play a role in the initiation and development of various types of cancer, including glioblastoma. The review aims to answer the following questions concerning the role of RNA theranostics for brain tumors: (1) which miRNAs are the best candidates to become early diagnostic and prognostic circulating biomarkers?; (2) how to deliver the therapeutic agents in the CNS to overcome the BBB?; (3) which are the best methods to restore/inhibit miRNAs? Conclusions: Because of the proven roles played by miRNAs in gliomagenesis and of their capacity to pass from the CNS tissue into the blood or cerebrospinal fluid (CSF), we propose miRNAs as ideal diagnostic and prognostic biomarkers. Moreover, recent advances in direct miRNA restoration (miRNA mimics) and miRNA inhibition therapy (antisense oligonucleotides, antagomirs, locked nucleic acid anti-miRNA, small molecule miRNA inhibitors) make miRNAs perfect candidates for entering clinical trials for glioblastoma treatment.
Currently, for seemingly every type of cancer, dysregulated levels of non-coding RNAs (ncRNAs) are reported and non-coding transcripts are expected to be the next class of diagnostic and therapeutic tools in oncology. Recently, alterations to the ncRNAs transcriptome have emerged as a novel hallmark of cancer. Historically, ncRNAs were characterized mainly as regulators and little attention was paid to the mechanisms that regulate them. The role of modifications, which can control the function of ncRNAs post-transcriptionally, only recently began to emerge. Typically, these modifications can be divided into reversible (i.e., chemical modifications: m5C, hm5C, m6A, m1A, and pseudouridine) and non-reversible (i.e., editing: ADAR dependent, APOBEC dependent and ADAR/APOBEC independent). The first research papers showed that levels of these modifications are altered in cancer and can be part of the tumorigenic process. Hence, the aim of this review paper is to describe the most common regulatory modifications (editing and chemical modifications) of the traditionally considered “non-functional” ncRNAs (i.e., microRNAs, long non-coding RNAs and circular RNAs) in the context of malignant disease. We consider that only by understanding this extra regulatory layer it is possible to translate the knowledge about ncRNAs and their modifications into clinical practice.
Acute respiratory distress syndrome (ARDS) has no specific treatment, the only effective therapy currently being limited to minimizing potentially harmful ventilation and avoiding a positive fluid balance. These treatments could not be completely effective in severe disease and several measures must be undertaken simultaneously, including pharmacological therapies aimed at correcting the etiology or targeting the pathogenesis. In this review article we provide update on pharmacological therapies in ARDS, showing their effect on outcome in recent trials.
"Surgical site infections (SSI) greatly concern clinicians, as they are associated with significant morbidity and mortality, prolonged hospitalization, and costs. Antibiotic prophylaxis plays a pivotal role among the procedures that are usually employed for the prevention of surgical-related infections. This narrative review aims to cover some of the particular situations when the clinician might consider individualizing antibiotic prophylaxis for a patient. With the rising incidence of multi-drug resistant bacteria carriage among not only hospitalized or institutionalized patients but also patients from the community, there might be a tendency to use extended-spectrum antibiotics for longer periods for surgical infection prevention. However, the inappropriate use of antibiotics increases the selection pressure, thus favoring the spreading of resistant bacteria. Moreover, specific patient characteristics or pathologies might need to be considered to customize the type, dose, or length of administration of an antibiotic as surgical prophylaxis. Using prosthetic material or prolonged surgeries with large fluid shifts are other situations when individualized antibiotic prophylaxis might be thought of. Keeping in mind that it is of utmost importance that everyone adheres to the current guidelines for surgical antibiotic prophylaxis, customization of local protocols according to well-thought-out strategies might prove beneficial in SSI prevention."
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