RNA-RNA competitive interactions: a molecular civil war ruling cell physiology and diseases

The idea that proteins are the main determining factors in the functioning of cells and organisms, and their dysfunctions are the first cause of pathologies, has been predominant in biology and biomedicine until recently. This protein-centered view was too simplistic and failed to explain the physiological and pathological complexity of the cell. About 80% of the human genome is dynamically and pervasively transcribed, mostly as non-protein-coding RNAs (ncRNAs), which competitively interact with each other and with coding RNAs generating a complex RNA network regulating RNA processing, stability, and translation and, accordingly, fine-tuning the gene expression of the cells. Qualitative and quantitative dysregulations of RNA-RNA interaction networks are strongly involved in the onset and progression of many pathologies, including cancers and degenerative diseases. This review will summarize the RNA species involved in the competitive endogenous RNA network, their mechanisms of action, and involvement in pathological phenotypes. Moreover, it will give an overview of the most advanced experimental and computational methods to dissect and rebuild RNA networks

Metabolomic Approaches for Detection and Identification of Biomarkers and Altered Pathways in Bladder Cancer

Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a “signature pathway” associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice

Metabolomic Approaches for Detection and Identification of Biomarkers and Altered Pathways in Bladder Cancer

Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a “signature pathway” associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice

Renal Cell Carcinoma as a Metabolic Disease: An Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets

: Clear cell renal cell carcinoma (ccRCC) is the most frequent histological kidney cancer subtype. Over the last decade, significant progress has been made in identifying the genetic and metabolic alterations driving ccRCC development. In particular, an integrated approach using transcriptomics, metabolomics, and lipidomics has led to a better understanding of ccRCC as a metabolic disease. The metabolic profiling of this cancer could help define and predict its behavior in terms of aggressiveness, prognosis, and therapeutic responsiveness, and would be an innovative strategy for choosing the optimal therapy for a specific patient. This review article describes the current state-of-the-art in research on ccRCC metabolic pathways and potential therapeutic applications. In addition, the clinical implication of pharmacometabolomic intervention is analyzed, which represents a new field for novel stage-related and patient-tailored strategies according to the specific susceptibility to new classes of drugs

Diagnostic and Prognostic Value of Conventional Brain MRI in the Clinical Work-Up of Patients with Amyotrophic Lateral Sclerosis

open14noClinical signs of upper motor neuron (UMN) involvement are important in the diagnosis of amyotrophic lateral sclerosis (ALS) though are often difficult to analyze. Many studies using both qualitative and quantitative evaluations have reported abnormal Magnetic Resonance Imaging (MRI) findings at the level of the pyramidal pathway in patients with ALS. Although the most interesting results were obtained by quantitative studies using advanced MR techniques, the qualitative evaluation of MRI images remains the most-used in clinical practice. We evaluated the diagnostic and prognostic contribution of conventional 3T-MRI in the clinical work-up of ALS patients. Two neuroradiologists retrospectively assessed 3T-MRI data of 93 ALS patients and 89 controls. The features of interest were corticospinal tract (CST) T2/FLAIR hyperintensity, motor cortex (MC) T2*/SWI hypointensity, and selective MC atrophy. All MRI features were significantly more prevalent in ALS patients than in controls. The simultaneous presence of CST FLAIR hyperintensity and MC SWI hypointensity was associated with the highest diagnostic accuracy (sensitivity: 70%; specificity: 81%; positive predictive value, PPV: 90%; negative predictive value, NPV: 51%; accuracy: 73%) and a shorter survival (HR: 6.56,p= 0.002). Conventional 3T-MRI can be a feasible tool to detect specific qualitative changes based on UMN involvement and to support clinical diagnosis of ALS. Importantly, CST FLAIR hyperintensity and MC SWI hypointensity are predictors of shorter survival in ALS patients.openRizzo, Giovanni; Marliani, Anna Federica; Battaglia, Stella; Albini Riccioli, Luca; De Pasqua, Silvia; Vacchiano, Veria; Infante, Rossella; Avoni, Patrizia; Donadio, Vincenzo; Passaretti, Massimiliano; Bartolomei, Ilaria; Salvi, Fabrizio; Liguori, Rocco; On Behalf Of The BoReALS Group, nullRizzo, Giovanni; Marliani, Anna Federica; Battaglia, Stella; Albini Riccioli, Luca; De Pasqua, Silvia; Vacchiano, Veria; Infante, Rossella; Avoni, Patrizia; Donadio, Vincenzo; Passaretti, Massimiliano; Bartolomei, Ilaria; Salvi, Fabrizio; Liguori, Rocco; On Behalf Of The BoReALS Group, nul

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

Insight from an Italian Delphi Consensus on EVAR feasibility outside the instruction for use: the SAFE EVAR Study

BACKGROUND: The SAfety and FEasibility of standard EVAR outside the instruction for use (SAFE-EVAR) Study was designed to define the attitude of Italian vascular surgeons towards the use of standard endovascular repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA) outside the instruction for use (IFU) through a Delphi consensus endorsed by the Italian Society of Vascular and Endovascular Surgery (Societa Italiana di Chirurgia Vascolare ed Endovascolare - SICVE). METHODS: A questionnaire consisting of 26 statements was developed, validated by an 18 -member Advisory Board, and then sent to 600 Italian vascular surgeons. The Delphi process was structured in three subsequent rounds which took place between April and June 2023. In the first two rounds, respondents could indicate one of the following five degrees of agreement: 1) strongly agree; 2) partially agree; 3) neither agree nor disagree; 4) partially disagree; 5) strongly disagree; while in the third round only three different choices were proposed: 1) agree; 2) neither agree nor disagree; 3) disagree. We considered the consensus reached when >70% of respondents agreed on one of the options. After the conclusion of each round, a report describing the percentage distribution of the answers was sent to all the participants. RESULTS: Two -hundred -forty-four (40.6%) Italian Vascular Surgeons agreed to participate the first round of the Delphi Consensus; the second and the third rounds of the Delphi collected 230 responders (94.3% of the first -round responders). Four statements (15.4%) reached a consensus in the first rounds. Among the 22 remaining statements, one more consensus (3.8%) was achieved in the second round. Finally, seven more statements (26.9%) reached a consensus in the simplified last round. Globally, a consensus was reached for almost half of the proposed statements (46.1%). CONCLUSIONS: The relatively low consensus rate obtained in this Delphi seems to confirm the discrepancy between Guideline recommendations and daily clinical practice. The data collected could represent the source for a possible guidelines' revision and the proposal of specific Good Practice Points in all those aspects with only little evidence available