Antimicrobial Activity of Chitosan Scaffold Loaded with Soluble Factors of Different Probiotic Strains Against Multidrug Resistant Pseudomonas aeruginosa.

Background: Bacterial infection remains the most frequent complication of burn injury, which can lead to sepsis, even if antibiotics are used topically and systemically. Pseudomonas aeruginosa (P. aeruginosa) is the main causative agent in many cases. The emergence of antibiotic-resistant strains in recent years has increased the need to find novel alternative therapies, such as probiotics. Therefore, this study aimed to examine the antimicrobial properties of probiotic cell-free supernatant (CFS), along with the potential use of a chitosan scaffold both as an antimicrobial agent and as a carrier for the delivery of these complexes. Objective: Evaluation of the antimicrobial properties of cell-free soluble factors of probiotic bacteria both alone and in combination with chitosan scaffolds. Materials and Methods: Nine isolates of P. aeruginosa previously identified by standard diagnostic tests were investigated. The antimicrobial effects of probiotics in the form of Pedilact® oral drop which contained three probiotic strains, Kidilact® sachet, which contained seven probiotic strains, and strains of Lactobacillus casei (L. casei) and Lactobacillus acidophilus (L. acidophilus) isolated from yogurt were studied by an agar well diffusion assay and by using CFS harvested at various growth stages, without pH neutralization. Chitosan with different concentrations of glutaraldehyde (GA) as a crosslinking agent was fabricated to produce a suitable scaffold for loading cell-free supernatants of probiotic strains. The scaffolds were then characterized using scanning electron microscopy. The antimicrobial properties of the CFS, chitosan, and chitosan scaffolds loaded with CFS were analyzed against MDR P. aeruginosa. Results: In the agar well diffusion assay, CFS obtained from probiotic strains effectively inhibited the growth of a clinical strain of P. aeruginosa. This effect was observed when CFS was assessed without pH neutralization. Kidilact® was the most promising synbiotic formulation based on its inhibitory activity. The chitosan scaffold was successfully fabricated, as shown by SEM, and its structure was not affected by acidic CFS. The fabricated scaffolds were able to deliver CFS and, interestingly, antibacterial activity against P. aeruginosa when CFS was loaded on the chitosan scaffold was enhanced significantly. Conclusion: The results of this study showed chitosan scaffold loaded with cell-free probiotics metabolites can be considered to be a promising antimicrobial dressing in wound healing applications.

Non-coding RNAs in leukemia drug resistance: new perspectives on molecular mechanisms and signaling pathways.

Like almost all cancer types, timely diagnosis is needed for leukemias to be effectively cured. Drug efflux, attenuated drug uptake, altered drug metabolism, and epigenetic alterations are just several of the key mechanisms by which drug resistance develops. All of these mechanisms are orchestrated by up- and downregulators, in which non-coding RNAs (ncRNAs) do not encode specific proteins in most cases; albeit, some of them have been found to exhibit the potential for protein-coding. Notwithstanding, ncRNAs are chiefly known for their contribution to the regulation of physiological processes, as well as the pathological ones, such as cell proliferation, apoptosis, and immune responses. Specifically, in the case of leukemia chemo-resistance, ncRNAs have been recognized to be responsible for modulating the initiation and progression of drug resistance. Herein, we comprehensively reviewed the role of ncRNAs, specifically its effect on molecular mechanisms and signaling pathways, in the development of leukemia drug resistance.

Circular RNAs: pivotal role in the leukemogenesis and novel indicators for the diagnosis and prognosis of acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy and affected patients have poor overall survival (OS) rates. Circular RNAs (circRNAs) are a novel class of non-coding RNAs (ncRNAs) with a unique loop structure. In recent years, with the development of high-throughput RNA sequencing, many circRNAs have been identified exhibiting either up-regulation or down-regulation in AML patients compared with healthy controls. Recent studies have reported that circRNAs regulate leukemia cell proliferation, stemness, and apoptosis, both positively and negatively. Additionally, circRNAs could be promising biomarkers and therapeutic targets in AML. In this study, we present a comprehensive review of the regulatory roles and potentials of a number of dysregulated circRNAs in AML.

Antisense technology as a potential strategy for the treatment of coronaviruses infection: With focus on COVID-19.

After the outbreak of coronavirus disease 2019 (COVID-19) in December 2019 and the increasing number of SARS-CoV-2 infections all over the world, researchers are struggling to investigate effective therapeutic strategies for the treatment of this infection. Targeting viral small molecules that are involved in the process of infection is a promising strategy. Since many host factors are also used by SARS-CoV-2 during various stages of infection, down-regulating or silencing these factors can serve as an effective therapeutic tool. Several nucleic acid-based technologies including short interfering RNAs, antisense oligonucleotides, aptamers, DNAzymes, and ribozymes have been suggested for the control of SARS-CoV-2 as well as other respiratory viruses. The antisense technology also plays an indispensable role in the treatment of many other diseases including cancer, influenza, and acquired immunodeficiency syndrome. In this review, we summarised the potential applications of antisense technology for the treatment of coronaviruses and specifically COVID-19 infection.

Retrospective analysis of direct antiglobulin test positivity at tertiary academic hospital over 10 years.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a clinically significant problem that may potentially affect any pregnancy. Direct antiglobulin test (DAT) is considered to be an important test in identifying newborns who are suspected to have HDN. This study aims in reviewing data regarding a positive DAT result concerning etiology and the development of HDN over a period of 10 years. STUDY DESIGN AND METHODS: A retrospective study of all neonates with a positive DAT result between January 2011 and December 2020 was performed. Data were obtained from patients' electronic hospital files, transfusion medicine databases, and medical birth records. Laboratory parameters along with clinical interventions in neonates with a DAT-positive result and a comparison group of DAT-negative neonates were performed. RESULTS: 36,000 deliveries were registered in this period. 176 (2.65 %) neonates had a positive DAT result. ABO-incompatibility was the most common cause with 59.1 %; Rh incompatibility 13.8 %, minor blood group incompatibility, and other RBC-related antibodies 10.1 %, and unspecified etiology in 17 % of cases. Among DAT-positive cases, 32.7 % of neonates were diagnosed with HDN. ABO-incompatibility was the major reason as well. Initial mean total bilirubin levels were higher in the DAT-positive group than the control group (p < 0.001), and these neonates also had a lower initial hemoglobin level (p < 0.001). The need for therapeutic interventions was significantly higher in DAT-positive neonates (p < 0.001) as 86.8 % underwent phototherapy, with 32.7 %, and 17.6 % receiving exchange transfusion (ET) and intravenous immunoglobulin (IVIG), respectively. CONCLUSION: In conclusion, ABO incompatibility was the most common cause for neonatal DAT positivity. Besides the common causes of DAT positivity, there would be rare but important conditions that may lead to a positive result, such as antibodies passively acquired from mothers in the context of alloimmunizations or using drugs. In addition, as a high rate of therapeutic intervention was identified among neonates with a DAT-positive result, there is a crucial need for increasing awareness regarding early diagnosis of the condition, careful monitoring, and the employment of prenatal alloimmunization screening tests.