Nile University

Glioblastoma (GBM) is one of the most aggressive types of brain cancer, characterized by its poor prognosis and low survival rate despite current treatment modalities. Because GBM is lethal, clarifying the pathogenesis’s underlying mechanisms is important, which are still poorly understood. Recent discoveries in the fields of molecular genetics and cancer biology have demonstrated the critical role that non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), play in the molecular pathophysiology of GBM growth. LncRNAs are transcripts longer than 200 nucleotides that do not encode proteins. They are significant epigenetic modulators that control gene e expression at several levels. Their dysregulation and interactions with important signaling pathways play a major role in the malignancy and development of GBM. The increasing role of lncRNAs in GBM pathogenesis is thoroughly examined in this review, with particular attention given to their regulation mechanisms in key signaling pathways such as PI3K/AKT, Wnt/β-catenin, and p53. It also looks into lncRNAs’ potential as new biomarkers and treatment targets for GBM. In addition, the study discusses the difficulties in delivering lncRNA-based medicines across the blood-brain barrier and identifies areas that need more research to advance lncRNA-oriented treatments for this deadly cancer. Graphical abstract

Background Patients with betathalassemia have higher risk of various metabolic disturbances. The literature presents conflicting results about the patterns of abnormal lipid profile among patients with betathalassemia. This systematic review aimed to assess dyslipidemia patterns among patients with betathalassemia when compared with healthy individuals. Methods The methods used were adherent to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Systematic searches of the literature were done across Medline/PubMed, Web of Science, Science Direct, and Regional Portal of the World Health Organization Virtual Health Library. Calculation of standardized mean difference (SMD) estimates and their associated 95% confidence intervals (CIs) were done through Jamovi software. Results The systematic review included 21 studies meeting the criteria for the analyses. Patients with beta-thalassemia major displayed significantly elevated triglyceride levels (SMD: 0.448, 95% CI, 0.214 to 0.682; P < .001) and reduced total serum cholesterol (SMD: -2.26 (95% CI-2.834 to -1.678; P < .001), as well as decreased levels of both low-density lipoprotein cholesterol (SMD: -1.88, 95% CI, -2.614 to -1.147; P < .001) and high-density lipoprotein cholesterol (SMD: -1.32, 95% CI, -1.786 to -0.860; P < .001). Similarly, beta-thalassemia intermedia patients exhibited comparable lipid profile abnormalities to those with beta-thalassemia major. Conversely, beta-thalassemia minor patients only showed significantly lower total serum cholesterol levels (SMD: -0.66, 95% CI, -0.860 to -0.472; P < .001). Conclusion Evidence indicates alterations in lipid profile markers among beta-thalassemia patients. The findings indicate the importance of assessing hypertriglyceridemia and hypocholesterolemia in these patients, especially those with major and intermedia forms, as these lipid profile abnormalities increase the risk of cardiovascular disease.

The evolution of the Fifth Generation (5G) networks and the rise of Open Radio Access Network (O-RAN) architecture introduced a new era of wireless connectivity, offering exceptional speeds, low latency, and increased capacity. However, the open and disaggregated nature of O-RAN itself leads to serious security challenges. This paper gives an in-depth analysis of the current security posture of the 5G O-RAN, assessing the security protocol stack in use to harden the 5G O-RAN framework. We show the strengths and weaknesses inherited in each protocol of the current stack and propose enhancements to fortify the security of the 5G O-RAN deployments.

Hypoxia is one of the main hallmarks of hepatocellular carcinoma (HCC) resulting from improper oxygenation and insufficient nourishment of the HCC microenvironment. The effect of hypoxia is mediated by hypoxia-inducible factor-1A (HIF-1A) via targeting various downstream pathways, including glycolysis, angiogenesis, and survival signaling. However, HCC cell lines in a 2-dimensional (2D) setting do not resemble the metabolic signature of HCC. Here we aim to overcome these limitations by developing an HCC organoid that recapitulates the HIF-1A metabolic shift. The enrichment analysis of the RNA-Seq data revealed that HIF-1A-driven glycolytic shift is of the significant pathways. The established organoid model, using xeno-free plasma-derived extracellular matrix (ECM) as a scaffold and nutritive biomatrix, maintained its structural integrity and viability for up to 14 days; the comparative analysis of the cobalt (II) chloride (CoCl2)-treated organoids to the untreated ones unveiled reduced size and proliferative capacity. Interestingly, our organoid model showed an elevated expression of HIF-1A and glycolysis enzymes compared to their counterparts in the CoCl2-treated organoids. HIF-1A molecular expression-translated biochemical signature is further assessed in our spontaneously growing organoids showing an increase in glucose uptake, intracellular pyruvate, extracellular lactate dehydrogenase expression, and extracellular lactate production, while hydrogen peroxide (H2O2), a marker for oxidative metabolism, is reduced. Our data confirmed the potency of the established organoid model to mimic the molecular and biochemical HIF-1A-driven metabolism, which validates its potential use as an in vitro HCC model. Our model naturally simulates hypoxic conditions and simultaneous HIF-1A-dependent glycolysis within HCC rather than using of CoCl2-induced hypoxic conditions.

Background/Objectives: Raloxifene (RLF) is a therapeutic option for invasive breast cancer because it blocks estrogen receptors selectively. Low solubility, limited targeting, first-pass action, and poor absorption are some of the challenges that make RLF in oral form less effective. This study aimed to create an intra-tumoral in situ pH-responsive formulation of RLF-invasome (IPHRLI) for breast cancer treatment, with the goals of sustaining RLF release, minimizing adverse effects, and enhancing solubility, bioavailability, targeting, and effectiveness. Methods: Numerous RLF-invasome formulations were optimized using design expert software (version 12.0.6.0, StatEase Inc., Minneapolis, MN, USA). Integrating an optimal formulation with an amalgam of chitosan and glyceryl monooleate resulted in the IPHRLI formulation. In vivo testing of the IPHRLI formulation was conducted utilizing the Ehrlich cancer model. Results: Requirements for an optimum RLF-invasome formulation were met by a mixture of phospholipids (2.46%), ethanol (2.84%), and cineole (0.5%). The IPHRLI formulation substantially sustained its release by 75.41% after 8 h relative to free RLF. The bioavailability of intra-tumoral IPHRLI was substantially raised by 4.07-fold compared to oral free RLF. Histopathological and tumor volume analyses of intra-tumoral IPHRLI confirmed its efficacy and targeting effect. Conclusions: the intra-tumoral administration of the IPHRLI formulation may provide a potential strategy for breast cancer management.

Citation: Aati, S.; Farouk, H.O.; Elkarmalawy, M.H.; Aati, H.Y.; Tolba, N.S.; Hassan, H.M.; Rateb, M.E.; Hamad, D.S. Intratracheal Abstract: Background: Itraconazole (ITZ) is an antiangiogenic agent recognized as a potent suppressor of endothelial cell growth that suppresses angiogenesis. Nevertheless, its exploitation is significantly restricted by its low bioavailability and systematic side effects. The objective of this study was to utilize glycerosomes (GLY), glycerol-developed vesicles, as innovative nanovesicles for successful ITZ pulmonary drug delivery. Methods: The glycerosomes were functionalized with hyaluronic acid (HA-GLY) to potentiate the anticancer efficacy of ITZ and extend its local bio-fate. ITZ-HA-GLY were fabricated using soybean phosphatidylcholine, tween 80, HA, and sonication time via a thin-film hydration approach according to a 24 full factorial design. The impact of formulation parameters on ITZ-HA-GLY physicochemical properties, as well as the optimal formulation option, was evaluated using Design-Expert ®. Sulphorhodamine-B (SRB) colorimetric cytotoxicity assay of the optimized ITZ-HA-GLY versus ITZ suspension was explored in the human A549 cell line. The in vivo pharmacokinetics and bio-distribution examined subsequent to intratracheal administrations of ITZ suspension, and ITZ-HA-GLY were scrutinized in rats. Results: The optimized ITZ-HA-GLY unveiled vesicles of size 210.23 ± 6.43 nm, zeta potential of 41.06 ± 2.62 mV, and entrapment efficiency of 73.65 ± 1.76%. Additionally, ITZ-HA-GLY manifested a far lower IC50 of 13.03 ± 0.2 µg/mL on the A549 cell line than that of ITZ suspension (28.14 ± 1.6 µg/mL). Additionally, the biodistribution analysis revealed a higher concentration of ITZ-HA-GLY within the lung tissues by 3.64-fold as compared to ITZ suspension. Furthermore, the mean resistance time of ITZ-HA-GLY declined more slowly with 14 h as compared to ITZ suspension, confirming the accumulation of ITZ inside the lungs and their promising usage as a target for the treatment of lung disease. Conclusions: These data indicate that the improved ITZ-HA-GLY demonstrates significant promise and represents an exciting prospect in intratracheal delivery systems for lung cancer treatment, meriting further investigation.

Plane, nonlinear Rayleigh wave propagation is investigated in a three-layer sandwich structure of a thermoelastic medium, within the frame of dual-phase-lag theory. The thermal conductivity is taken as a linear function of temperature. This induces nonlinearity in the evolution equations for the heat flux components. A particular solution is found in the form of Poincaré expansion in a small parameter that reflects the fluctuations of temperature about a steady value. This solution is discussed and plots are provided for a special case when both external faces of the structure are traction-free and under prescribed temperature regime. It is noted, in particular, that some quantities of practical interest suffer jumps at the interfaces. Some of the jumps appear only starting from the second order of approximation. The existence of jumps may be favourably used to carry out some measurements of material parameters.

Introduction Mitochondria are essential organelles in eukaryotic cells, producing ATP through the electron transport chain to supply energy for cellular activities. Beyond energy production, mitochondria play crucial roles in cellular signaling, stress responses, and the regulation of reactive oxygen species. In plants, mitochondria are one of the keys to responding to environmental stresses which can significantly affect crop productivity, particularly in crops like wheat. RNA editing, a post-transcriptional RNA modification process in mitochondria, is linked to regulating these stress responses. Methods This study explores RNA editing patterns in the nad9 gene of wheat drought-tolerant (Giza168) and drought-sensitive (Gemmiza10) wheat cultivars under drought stress to understand plant adaptation mechanisms. RNA-seq data for these cultivars were analyzed using CLC Genomic Workbench to identify RNA editing sites in the nad9 gene, examining subsequent amino acid changes and predicting secondary structure modifications. These RNA editing sites were validated using qRT-PCR on drought-treated seedlings at 0, 2, and 12 hours post-treatment. Protein models were generated using AlphaFold, with functional predictions and structure verification conducted using various bioinformatics tools to investigate the effect of RNA editing on protein level. Results The results showed significant RNA editing events, especially C-to-T conversions, in the nad9 gene across different drought exposure times. Giza168 had 22 editing sites, while Gemmiza10 had 19, with several showing significant differences between control and stress conditions. RNA editing influenced the NAD9 protein's secondary structure, particularly beta sheets, and 3D modeling highlighted the structural impacts of these edits. The N-terminal region of NAD9 contained important regulatory motifs, suggesting a complex regulatory environment. Discussion This study reveals key editing sites that differ between drought-tolerant and sensitive wheat cultivars, impacting NAD9 protein structures and highlighting the role of RNA editing in enhancing drought resilience. Additionally, the study suggests potential regulatory mechanisms, including phosphorylation and ubiquitination that influence mitochondrial stability and function.

Hepatocellular carcinoma (HCC) is a leading liver cancer that significantly impacts global life expectancy and remains challenging to treat due to often late diagnoses. Despite advances in treatment, the prognosis is still poor, especially in advanced stages. Studies have pointed out that investigations into the molecular mechanisms underlying HCC, including mitochondrial dysfunction and epigenetic regulators, are potentially important targets for diagnosis and therapy. Mitoepigenetics, or the epigenetic modifications of mitochondrial DNA, have drawn wide attention for their role in HCC progression. Besides, molecular biomarkers such as mitochondrial DNA alterations and non-coding RNAs showed early diagnosis and prognosis potential. Additionally, natural compounds like alkaloids, resveratrol, curcumin, and flavonoids show promise in HCC show promise in modulating mitochondrial and epigenetic pathways involved in cancer-related processes. This review discusses how mitochondrial dysfunction and epigenetic modifications, especially mitoepigenetics, influence HCC and delves into the potential of natural products as new adjuvant treatments against HCC.

Objective This research examined how the IL-13-1055C/T promoter polymorphism affects the likelihood of Sudanese children developing severe malaria. Method The research was carried out in 2020 and included 115 children with malaria and 49 healthy youngsters from Al Gadaref, Sudan. To analyze the IL-13 1055C/T SNP, the DNA product was digested by the restriction enzyme BstFNI. The ELISA Sandwich method was used to investigate serum IL-13 and IgE. Results The IL-13 gene1055C/T SNP differed significantly between malaria patients and healthy individuals. The results revealed a highly significant difference between various alleles of the IL-13 gene 1055C/T position and malaria severity groups (P-value < 0.001). The IL-13 SNP was found to be closely associated with the allele frequency in the healthy control group. (C: T% = 70.4:29.6), with a p-value < 0.001. The findings show a significant positive relationship between IL-13 and IgE levels in individuals with malaria. (r = 811; P value < 0.001). IL-13 levels differ significantly between malaria patients and healthy individuals, with a P value = 0.000. Malaria patients exhibited considerably greater IgE levels than healthy children, P value < 0.001. Conclusion Our findings revealed substantial relationships between the IL-13 gene polymorphism at the − 1055 locus and severe malaria anemia, uncomplicated malaria, and cerebral malaria cases, implying that the IL-13 gene could have a significant impact on the development of severe malaria.

Metamaterials for refractive index sensing applications have garnered significant attention in recent years. However, achieving an optimal balance between high sensitivity and quality factor, which together determine the Figure of Merit of sensors, necessitates extensive optimization efforts. In this paper, we present the metaheuristic optimization of a refractive index-based plasmonic sensor operating at a wavelength of 1500 nm, which has the potential to open new avenues for applications in biomedical sensing and beyond. Particle Swarm Optimization is utilized to maximize the performance of the proposed infrared metamaterial sensor. The proposed design features two overlapping E-shaped silver patches placed on top of a grounded $\mathrm {Al_{2}O_{3}}$ substrate. This configuration results in a narrow-band absorption spectrum with peak resonances caused by the confinement of the electric field within the gaps of the E-shaped metallic arms. The metaheuristic optimization process yielded sensor dimensions that achieve a high sensitivity of 834.7 nm/RIU,Q = 865 and a Figure of Merit of 481.34 $\textrm{RIU}^{-1}$, demonstrating outstanding performance in cancer cell detection.

Autonomous Vehicles (AV) is one of the most evolving industries in the last decade. However, one of the bottlenecks of this evolution is providing data that contains different scenarios and scenes to improve the models without exposing the privacy and security of the edge vehicles. The authors of this research propose a secure and efficient novel solution for lane segmentation in AVs through the use of Federated Learning (FL). FedLane involves initial training of U-Net, ResUNet, and ResUNet++ models, followed by real-time inference in edge devices and the application of FL to update the server model using clients’ data. The study found that FL has enhanced the performance of lane segmentation significantly over baseline, enabling decentralized privacy-preserving collaborative optimization with increased dice coef from 0.9429 to 0.9794 for U-Net, from 0.9291 to 0.9854 for ResUNet and from 0.9079 to 0.9675 for ResUNet++. Additionally, the models show increased stability over the training iterations, highlighting the potential of FL to play a significant role in the future of automation in the AV industry.

Network Intrusion Detection Systems (NIDS) are critical for protecting computer networks from unauthorized activities. Traditional NIDS rely on rule-based signatures, which can be limiting in detecting emerging threats. This study investigates the effectiveness of the random forest classifier in advancing NIDS capabilities through machine learning. Using the CICIDS-2017 dataset, the data are preprocessed to enhance their quality by removing redundancies. feature selection and permutation importance were employed to identify the most relevant features. The methodology involves rigorous testing and analysis of the random forest classifier’s performance, focusing on f1-score rates compared to other machine learning models. Results demonstrate that by optimizing class weights, applying a custom prediction function and leveraging 26 key features, the random forest classifier achieves an outstanding 99.8% in the weighted f1-score and 93.31% in the macro f1-score in various attack types. This research highlights the potential of machine learning to significantly enhance NIDS effectiveness, offering a robust defense mechanism against evolving cybersecurity threats in modern networks.

Aim An ineffective immune response resulting from dysregulation of cytokine production might encourage viral persistence and cause chronic viral hepatitis to worsen. This study examined the relationship between alterations in interleukin-6 (IL-6) levels and the IL-6 − 174 G > C (rs1800795) polymorphism, as well as how this polymorphism affects the development and progression of chronic hepatitis brought on by hepatitis B (HBV) and hepatitis C (HCV) into hepatocellular carcinoma (HCC). Patients and methods Whole blood samples from 126 Egyptian patients with HCC (111 with HCV and 15 with HBV), as well as 126 age- and sex-matched healthy individuals, were used to extract DNA. Using PCR-based allele-specific amplification (ASA), the existence of the IL-6 G-174C polymorphism was investigated. Additionally, each participant's serum IL-6 levels were determined using an enzyme-linked immunosorbent assay (ELISA). Results The primary observations revealed that HCC patients had greater serum levels of IL-6 compared to the control groups ( p < 0.001). Patients with the variant (CG and GG) genotype in the HCC group were found to have more disease severity indicated by higher levels of alpha-fetoprotein (AFP) and a higher ascites grade, as well as increased inflammatory activity as defined by higher levels of IL-6 and C-reactive protein (CRP) ( p < 0.001 for both) in comparison to patients with the wild-type (CC) genotype ( p < 0.001 and p = 0.002, respectively). Conclusion The rs1800795 SNP in the IL-6 gene was associated with increased inflammatory activity and high levels of IL-6, indicating that this SNP may play a role in the development of HCC in Egyptian patients with chronic viral hepatitis.