Non-coding RNAs as key players in the neurodegenerative diseases: Multi-platform strategies and approaches for exploring the Genome's dark matter.

A growing amount of evidence in the last few years has begun to unravel that non-coding RNAs have a myriad of functions in gene regulation. Intensive investigation on non-coding RNAs (ncRNAs) has led to exploring their broad role in neurodegenerative diseases (NDs) owing to their regulatory role in gene expression. RNA sequencing technologies and transcriptome analysis has unveiled significant dysregulation of ncRNAs attributed to their biogenesis, upregulation, downregulation, aberrant epigenetic regulation, and abnormal transcription. Despite these advances, the understanding of their potential as therapeutic targets and biomarkers underpinning detailed mechanisms is still unknown. Advancements in bioinformatics and molecular technologies have improved our knowledge of the dark matter of the genome in terms of recognition and functional validation. This review aims to shed light on ncRNAs biogenesis, function, and potential role in NDs. Further deepening of their role is provided through a focus on the most recent platforms, experimental approaches, and computational analysis to investigate ncRNAs. Furthermore, this review summarizes and evaluates well-studied miRNAs, lncRNAs and circRNAs concerning their potential role in pathogenesis and use as biomarkers in NDs. Finally, a perspective on the main challenges and novel methods for the future and broad therapeutic use of ncRNAs is offered.

Structural and compositional segregation of the gut microbiota in HCV and liver cirrhotic patients: A clinical pilot study.

Gut microbial dysbiosis during the development of Hepatitis C virus and liver-related diseases is not well studied. Nowadays, HCV and liver cirrhosis are the major concerns that cause gut bacterial alteration, which leads to dysbiosis. For this purpose, the present study was aimed at correlating the gut bacterial community of the control group in comparison to HCV and liver cirrhotic patients. A total of 23 stool samples were collected, including control (9), liver cirrhotic (8), and HCV (6). The collected samples were subjected to 16 S rRNA Illumina gene sequencing. In comparison with control, a significant gut bacterial alteration was observed in the progression of HCV and liver cirrhosis. Overall, Firmicutes were significantly abundant in the whole study. No significant difference was observed in the alpha diversity of the control and patient studies. Additionally, the beta diversity based on non-metric multidimensional scaling (NMDS) has a significant difference (p = 0.005) (ANOSIM R2 = 0.14) in all groups. The discriminative results based on the LEfSe tool revealed that the HCV-infected patients had higher Enterobacteriaceae and Enterobacterial, as well as Lactobacillus and Bacilli in comparison than the liver-cirrhotic patients. These taxa were significantly different from the control group (p < 0.05). Regarding prospects, a detailed analysis of the function through metagenomics and transcriptomics is needed.

The potential role of adjunctive ascorbic acid in the prevention of colistin-induced nephrotoxicity in critically ill patients: A retrospective study.

Background: Colistin is considered a valuable and last-resort therapeutic option for MDR gram-negative bacteria. Nephrotoxicity is the most clinically pertinent adverse effect of colistin. Vivo studies suggest that administering oxidative stress-reducing agents, such as ascorbic acid, is a promising strategy to overcome colistin-induced nephrotoxicity (CIN). However, limited clinical data explores the potential benefit of adjunctive ascorbic acid therapy for preventing CIN. Therefore, this study aims to assess the potential nephroprotective role of ascorbic acid as adjunctive therapy against CIN in critically ill patients. Method: This was a retrospective cohort study at King Abdulaziz Medical City (KAMC) for all critically ill adult patients who received IV colistin. Eligible patients were classified into two groups based on the ascorbic acid use as concomitant therapy within three days of colistin initiation. The primary outcome was CIN odds after colistin initiation, while the secondary outcomes were 30-day mortality, in-hospital mortality, ICU, and hospital LOS. Propensity score (PS) matching was used (1:1 ratio) based on the patient's age, SOFA score, and serum creatinine. Results: A total of 451 patients were screened for eligibility; 90 patients were included after propensity score matching based on the selected criteria. The odds of developing CIN after colistin initiation were similar between patients who received ascorbic acid (AA) as adjunctive therapy compared to patients who did not (OR (95 %CI): 0.83 (0.33, 2.10), p-value = 0.68). In addition, the 30-day mortality, in-hospital mortality, ICU, and hospital LOS were similar between the two groups. Conclusion: Adjunctive use of Ascorbic acid during colistin therapy was not associated with lower odds of CIN. Further studies with a larger sample size are required to confirm these findings.

Prospective multicentre study in intensive care units in five cities from the Kingdom of Saudi Arabia: Impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional approach on rates of central line-associated bloodstream infection.

OBJECTIVE: To analyse the impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Approach (IMA) and INICC Surveillance Online System (ISOS) on central line-associated bloodstream infection (CLABSI) rates in five intensive care units (ICUs) from October 2013 to September 2015. DESIGN: Prospective, before-after surveillance study of 3769 patients hospitalised in four adult ICUs and one paediatric ICU in five hospitals in five cities. During baseline, we performed outcome and process surveillance of CLABSI applying CDC/NHSN definitions. During intervention, we implemented IMA and ISOS, which included: (1) a bundle of infection prevention practice interventions; (2) education; (3) outcome surveillance; (4) process surveillance; (5) feedback on CLABSI rates and consequences; and (6) performance feedback of process surveillance. Bivariate and multivariate regression analyses were performed. RESULTS: During baseline, 4468 central line (CL) days and 31 CLABSIs were recorded, accounting for 6.9 CLABSIs per 1000 CL-days. During intervention, 12,027 CL-days and 37 CLABSIs were recorded, accounting for 3.1 CLABSIs per 1000 CL-days. The CLABSI rate was reduced by 56% (incidence-density rate, 0.44; 95% confidence interval, 0.28-0.72; P = 0.001). CONCLUSIONS: Implementing IMA through ISOS was associated with a significant reduction in the CLABSI rate in the ICUs of Saudi Arabia.