Non-coding RNAs (ncRNAs) and multidrug resistance in glioblastoma: Therapeutic challenges and opportunities.

Non-coding RNAs (ncRNAs) have been recognized as pivotal regulators of transcriptional and post-transcriptional gene modulation, exerting a profound influence on a diverse array of biological and pathological cascades, including the intricate mechanisms underlying tumorigenesis and the acquisition of drug resistance in neoplastic cells. Glioblastoma (GBM), recognized as the foremost and most aggressive neoplasm originating in the brain, is distinguished by its formidable resistance to the cytotoxic effects of chemotherapeutic agents and ionizing radiation. Recent years have witnessed an escalating interest in comprehending the involvement of ncRNAs, particularly lncRNAs, in GBM chemoresistance. LncRNAs, a subclass of ncRNAs, have been demonstrated as dynamic modulators of gene expression at the epigenetic, transcriptional, and post-transcriptional levels. Disruption in the regulation of lncRNAs has been observed across various human malignancies, including GBM, and has been linked with developing multidrug resistance (MDR) against standard chemotherapeutic agents. The potential of targeting specific ncRNAs or their downstream effectors to surmount chemoresistance is also critically evaluated, specifically focusing on ongoing preclinical and clinical investigations exploring ncRNA-based therapeutic strategies for glioblastoma. Nonetheless, targeting lncRNAs for therapeutic objectives presents hurdles, including overcoming the blood-brain barrier and the brief lifespan of oligonucleotide RNA molecules. Understanding the complex relationship between ncRNAs and the chemoresistance characteristic in glioblastoma provides valuable insights into the fundamental molecular mechanisms. It opens the path for the progression of innovative and effective therapeutic approaches to counter the therapeutic challenges posed by this aggressive brain tumor. This comprehensive review highlights the complex functions of diverse ncRNAs, including miRNAs, circRNAs, and lncRNAs, in mediating glioblastoma's chemoresistance.

Protocol for systematic review and meta-analysis on randomized clinical trials for direct oral anticoagulant in subjects with acute coronary syndrome

Background: Recently, direct oral anticoagulant (DOAC) has been projected for secondary prevention of recurrent ischemic events post-acute coronary syndrome (ACS). The addition of a DOAC to the antiplatelet regimen of subjects with the ACS is clinically practiced in candidates where compelling anticoagulation is indicated by high thromboembolic risk. The current evidence provides approved compelling indication for the DOAC, particularly for rivaroxaban which bears the strongest existing evidence. Objective: We intend to assess the role of DOAC in addition to single or dual antiplatelet therapy in subjects with ACS. We will compare the clinical characteristics and explore the efficacy and safety of the DOAC class members (apixaban, betrixaban, dabigatran, edoxaban and rivaroxaban) in terms of reduction in ischemic events in subjects with ACS (ST-segment elevation myocardial infarction [STEMI] or non–ST-segment elevation [NSTEMI]) or subjects who underwent percutaneous coronary intervention (PCI) and or ACS and coexisting atrial fibrillation (AF). Methods: Relevant data will be searched on known data-bases such as Embase, Google Scholar, the Cochrane Central, and PubMed. The trials included will be randomized controlled trials from 2009 to 2022. Subjects will be receiving DOAC for ACS were evaluated for inclusion. The extraction, synthesis, quality, and validity of data will follow the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The risk of bias tool, version 2.0 (Cochrane) will be used for risk of bias assessment. Data will be pooled using random-effects models. The primary outcome measure will be efficacy end point (composite of cardiovascular death, myocardial infarction, and stroke), while the safety outcome will be minor/major bleeding. (AU)