MicroRNA-Transcription factor regulatory networks in the early strobilar development of Echinococcus granulosus protoscoleces.

BACKGROUND: Echinococcus granulosus sensu lato has a complex developmental biology with a variety of factors relating to both intermediate and final hosts. To achieve maximum parasite adaptability, the development of the cestode is dependent on essential changes in transcript regulation. Transcription factors (TFs) and miRNAs are known as master regulators that affect the expression of downstream genes through a wide range of metabolic and signaling pathways. In this study, we aimed to develop a regulatory miRNA-Transcription factor (miRNA-TF) network across early developmental stages of E. granulosus protoscoleces by performing in silico analysis, and to experimentally validate TFs expression in protoscoleces obtained from in vitro culture, and from in vivo experiments. RESULTS: We obtained list of 394 unique E. granulosus TFs and matched them with 818 differentially expressed genes which identified 41 predicted TFs with differential expression. These TFs were used to predict the potential targets of 31 differentially expressed miRNAs. As a result, eight miRNAs and eight TFs were found, and the predicted network was constructed using Cytoscape. At least four miRNAs (egr-miR-124a, egr-miR-124b-3p, egr-miR-745-3p, and egr-miR-87-3p) and their corresponding differentially expressed TFs (Zinc finger protein 45, Early growth response protein 3, Ecdysone induced protein 78c and ETS transcription factor elf 2) were highlighted in this investigation. The expression of predicted differentially expressed TFs obtained from in vitro and in vivo experiments, were experimentally validated by quantitative polymerase chain reaction. This confirmed findings of RNA-seq data. CONCLUSION: miRNA-TF networks presented in this study control some of the most important metabolic and signaling pathways in the development and life cycle of E. granulosus, providing a potential approach for disrupting the early hours of dog infection and preventing the development of the helminth in the final host.

Gallocin-derived Engineered Peptides Targeting EGFR and VEGFR in Colorectal Cancer: A Bioinformatic Approach.

BACKGROUND: Colorectal cancer (CRC) treatment using time-saving and cost-effective targeted therapies with high selectivity and low toxicity drugs, is a great challenge. In primary investigations on Gallocin, as the most proposed factor in CRC pathogenesis caused by Streptococcus gallolyticus, it was surprisingly found that this bacteriocin has four α-helix structures and some anti-cancer sequences. OBJECTIVE: The aim of this study was to determine the ability of Gallocin-based anticancer peptides (ACPs) against epidermal growth factor receptor (EGFR) and vascular epidermal growth factor receptor (VEGFR) and the evaluation of their pharmacokinetic properties using bioinformatic approaches. METHODS: Support vector machine algorithm web-based tools were used for predicting ACPs. The physicochemical characteristics and the potential of anti-cancer activity of Gallocin-derived ACPs were determined by in silico tools. The 3D structure of predicted ACPs was modeled using modeling tools. The interactions between predicted ACPs and targets were investigated by molecular docking exercises. Then, the stability of ligand-receptor interactions was determined by molecular dynamic simulation. Finally, ADMET analysis was carried out to check the pharmacokinetic properties and toxicity of ACPs. RESULTS: Four amino acid sequences with anti-cancer potential were selected. Through molecular docking, Pep2, and Pep3 gained the best scores, more binding affinity, and strong attachments by the formation of reasonable H-bonds with both EGFR and VEGFR. Molecular simulation confirmed the stability of Pep3- EGFR. According to pharmacokinetic analysis, the ACPs were safe and truthful. CONCLUSION: Designed peptides can be nominated as drugs for CRC treatment. However, different in-vitro and in-vivo assessments are required to approve this claim.

Rapid eye movement sleep behavior disorder and its relation to Parkinson's disease: The potential of graph measures as brain biomarkers to identify the underlying physiopathology of the disorder.

Rapid eye movement behavior disorder (RBD) is a parasomnia characterized by the loss of skeletal muscle atonia during the rapid eye movement (REM) sleep phase. On the other hand, idiopathic RDB (iRBD) is considered the prelude of the various α-synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy. Consequently, over 40% of patients eventually develop PD. Recent neuroimaging studies utilizing structural magnetic resonance imaging (s-MRI), diffusion-weighted imaging (DWI), and functional magnetic resonance imaging (fMRI) with graph theoretical analysis have demonstrated that patients with iRBD and Parkinson's disease have extensive brain abnormalities. Thus, it is crucial to identify new biomarkers that aid in determining the underlying physiopathology of iRBD group. This review was conducted systematically on the included full-text articles of s-MRI, DWI, and fMRI studies using graph theoretical analysis on patients with iRBD, per the procedures recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The literature search was conducted through the PubMed and Google scholar databases concentrating on studies from September to January 2022. Based on the three perspectives of integration, segregation, and centrality, the reviewed articles demonstrated that iRBD is associated with segregation disorders in frontal and limbic brain regions. Moreover, this study highlighted the need for additional longitudinal and multicenter studies to better understand the potential of graph metrics as brain biomarkers for identifying the underlying physiopathology of iRBD group.

Effects of pyridoxine supplementation on severity, frequency and duration of migraine attacks in migraine patients with aura: A double-blind randomized clinical trial study in Iran.

BACKGROUND: Migraine is a chronic disease that affects nearly 6% of men and 18% of women worldwide. There are various drugs, which can successfully decrease migraine symptoms and frequency of migraine attacks, but these drugs usually are expensive. Hence, this study aimed to assess the effects of pyridoxine supplementation on severity, frequency and duration of migraine attacks as well as headache diary results (HDR). METHODS: This double-blind randomized clinical trial study was conducted on 66 patients with migraine with aura (MA) in Khorshid and Emam Mosa Sadr clinics of Isfahan University of Medical Sciences, Iran, in 2013. Patients were randomly allocated to receive either pyridoxine supplements (80 mg pyridoxine per day) or placebo. Severity, frequency and duration of migraine attacks and HDR were measured at baseline and at the end of the study. RESULTS: Mean age of patients was 34.24 ± 9.44 years old. Pyridoxine supplementation led to a significant decrease in headache severity (-2.20 ± 1.70 compared with -1 ± 1.50; P = 0.007), attacks duration (-8.30 ± 12.60 compared with -1.70 ± 9.60; P = 0.030) and HDR (-89.70 ± 134.60 compared with -6.10 ± 155.50; P = 0.040) compared with placebo, but was not effective on the frequency of migraine attacks (-2.30 ± 4 compared with -1.20 ± 7.80; P = 0.510). CONCLUSION: Pyridoxine supplementation in patients with MA was effective on headache severity, attacks duration and HDR, but did not affect the frequency of migraine attacks.