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STING-induced blood-brain barrier opening combined with radiotherapy potentiates antitumor response in a high-grade glioma model

Research Abstract

Radiation therapy (RT) is the standard of care for glioblastoma but is not curative. Triggering the cGAS/stimulator of interferon genes (STING) pathway with potent agonists, such as 8803, exerts activity across high-grade glioma preclinical models. To determine if the combination of 8803 with RT warrants consideration in the up-front treatment setting and to clarify the underlying mechanisms of therapeutic activity, C57BL/6J mice harboring intracerebral CT-2A or QPP8v gliomas were treated with RT, intratumoral 8803, or both. The treatment with the combination resulted in 80% long-term survival in the CT-2A model but not in the radiation-resistant QPP8v model. This therapeutic effect was maintained in Sting–/– CT-2A cells, highlighting the direct role of the immune system in mediating the survival benefit. Single-cell RNA-Seq identified increased nitric oxide synthase 2 (Nos2) in inflammatory tumor-associated macrophages; however, the therapeutic effect was maintained in Nos2–/– mice. Additionally, 8803 reprogrammed the blood-brain barrier (BBB) by altering the Pecam and Cd147 pathways in endothelial cells; intracranial injection of 8803 induced bihemispheric BBB opening for up to 24 hours. Sting activation was visualized longitudinally using 3’-deoxy-3’-[18F]-fluorothymidine ([18F]-FLT) PET, which peaked 72–96 hours after 8803 administration. In summary, 8803 combined with RT triggers distinctive antiglioma immune reactivity, facilitates BBB opening, and warrants consideration for up-front clinical trials in glioblastoma, where treatment effects can be monitored using [18F]-FLT PET imaging.

Research Authors
Shashwat Tripathi,....,,,,,,,...Heba Ali.....
Research Date
Research Department
Research Journal
The Journal of Clinical Investigation
Research Member
Research Website
https://dm5migu4zj3pb.cloudfront.net/manuscripts/198000/198843/cache/198843highres.1-20260123155655-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf
Research Year
2026

YBX1&YBX3 as novel targets to potentiate immune checkpoint blockade response in gliomas

Research Abstract

Abstract

Background: Glioblastoma (GBM) exhibits profound resistance to CD8⁺ T cell-mediated killing, yet the tumor-intrinsic mechanisms driving this immune evasion remain poorly defined. Our earlier study revealed Checkpoint Kinase 2 (Chek2) as the driver of CD8+ T cell resistance. This study investigates the immunomodulatory program exerted by the CHK2-YBX1&YBX3 regulatory hub.

Methods: Protein-protein interactions were investigated through immunoprecipitation (IP) followed by mass spectrometry (MS) and phosphoproteomics. Single gene knockout of CHEK2, Y-box-binding protein 1 (YBX1), and Y-box-binding protein 3 (YBX3) were generated in human and mouse glioma cells. Transcriptomic and epigenetic alterations were characterized by bulk RNA sequencing and chromatin immunoprecipitation sequencing (ChIP-seq). Single-cell RNA sequencing and spatial transcriptomics analysis were performed to evaluate CHK2-YBX1&YBX3 related phenotype in human GBM tumors. In vivo survival studies were conducted to assess the therapeutic potential of CHK2-YBX1&YBX3 degradation and immune checkpoint blockade (ICB).

Results: CHK2, YBX1, and YBX3 exhibited reciprocal positive regulation and depletion of any of these genes resulted in derepression of pro-inflammatory gene expression. Pharmacological inhibition with the drug targeting YBX1 led to degradation of the CHK2-YBX1&YBX3 hub accompanied by enhanced antigen presentation and antigen-specific CD8⁺ T cell proliferation. Combination therapy targeting CHK2-YBX1&YBX3 hub and ICB significantly improved survival in preclinical glioma models.

Conclusions: These findings define a novel glioma-intrinsic immunosuppressive program and proposes targeting the CHK2-YBX1&YBX3 hub to potentiate response to ICB in glioma.

Research Authors
Heba Ali
Research Date
Research Department
Research Journal
Neuro-Oncology
Research Member
Research Publisher
OXFORD
Research Website
https://academic.oup.com/neuro-oncology/article-abstract/28/1/159/8268576?redirectedFrom=fulltext&login=false
Research Year
2025

Nanoparticle-driven defense in wheat (Triticum aestivum L.): Enhancing antioxidant and rhizosphere responses under arsenic and microplastic stress

Research Authors
Arwa Abdulkreem AL-Huqail, Doaa Bahaa Eldin Darwish, Dalia Mohammad Melebari, Hanan El Sayed Osman, Shiah M. Alasimi, Suliman Mohammed Suliman Alghanem, Haifa Abdul Aziz Sakit Alhaithloul, Khalid Ali Khan, H.A. Abeed Amany, Willie Peijnenburg
Research Date
Research Journal
Ecotoxicology and Environmental Safety
Research Year
2025

Spectral light quality regulates salinity stress tolerance in maize (Zea mays L.) by enhancing photosynthetic efficiency and antioxidant mechanisms

Research Authors
A. A. Al-Huqail, D. B. E. Darwish, Al-Robai Alghanem, S. M. S., H. A. A. S. S. A., Alhaithloul, A. H. A. Abeed
Research Date
Research Journal
Journal of Plant Growth Regulation
Research Year
2025

Flash flood hazard, vulnerability, and risk assessment in Wadi Feiran Basin, Southwestern Sinai, Egypt, using the analytic hierarchy process and geospatial techniques

Research Abstract

Flash floods are among the most dangerous natural hazards, especially in arid and semi-arid regions, where their sudden onset can lead to devastating impacts. This study presents an integrated assessment of flash flood hazards and risks in the Wadi Feiran Basin, a hyper-arid region in Egypt’s Sinai Peninsula that experiences recurring flood events. Surface runoff was estimated using the Soil Conservation Service Curve Number (SCS-CN) method, incorporating spatial datasets on hydrology, topography, and land use. A comprehensive risk assessment was then carried out by integrating the Analytic Hierarchy Process (AHP) within a Geographic Information System (GIS) framework to generate three key models: a Flood Hazard Index (FHI), a Vulnerability Index (VI), and a combined Flood Risk Index (FRI). Results show that approximately 14.5% of the basin falls in the high flood hazard zone, and nearly 30% is classified as very highly vulnerable. The FRI model highlights that 14.5% of the area is at very high risk, while 23.5% is at high risk. Critically exposed zones include urban settlements in Feiran city, northeastern Saint Catherine, and main roads connecting to Dahab and Abu Zenima. The region's cultural and touristic significance further amplifies the consequences of such hazards. This study offers essential spatial tools and decision-support data for policymakers, urban planners, and disaster risk managers to prioritize mitigation, strengthen infrastructure resilience, and guide sustainable development in Wadi Feiran and similar arid, flood-prone regions.

Research Authors
Eltaher M. Shams, Ahmed A. Asmoay, Abrar Abdel-Salam, Sahar N. E. Tawfik & Rashad Sawires
Research Date
Research Department
Research Journal
Natural Hazards
Research Member
Research Pages
382
Research Rank
Q1 Web of Science
Research Vol
122
Research Website
https://doi.org/10.1007/s11069-026-08090-0
Research Year
2026

A new formulation of traditional charge simulation method for field calculations in high-voltage arrangements involving dielectrics and semiconductors

Research Abstract

High-voltage (HV) terminations are commonly used in HV connections, such as cable-to-transformer connections, to limit local electric field intensifications that may result in electrical breakdown. The termination contains a conductor and multiple dielectric layers with an embedded semiconductive (SC) layer, which is essential for reliable insulation design and breakdown prevention. The traditional charge simulation method (CSM) for electric field calculation is limited to two pure dielectric media. The present paper is aimed at proposing a new formulation of the traditional CSM for calculation of the electric field in HV terminations with more than two dielectric layers, including an SC layer. The conductor, dielectric interfaces, and surrounding air are modeled using sets of fictitious ring charges. By considering the governing pertinent boundary conditions, namely the Dirichlet condition on the conductor surface, and the continuity of both the electric potential and the normal electric flux density at the dielectric interfaces, the simulation charges are evaluated, and hence the electric field. To account for the presence of SC layers with relatively high conductivity, a hybrid numerical approach combining the CSM and the finite difference method (FDM) is developed, where the SC region is solved using FDM and coupled to the CSM domain through the continuity conditions of potential and normal flux density. The proposed formulation is validated through comparison with COMSOL Multiphysics simulations. The results demonstrate excellent agreement in the potential and electric field distributions across all dielectric layers, including in regions near to the interfaces and sheds. The newly-formulated CSM with hybrid CSM–FDM provides an efficient and accurate tool for electric field calculation in complex plasma reactors and HV cable terminations, accommodating multi-dielectric layers, including SC ones 
 

Research Authors
Ahmed Khamis, Mazen Abdel-Salam, Abdel-Haleem Turky, Azza Hashem and Hadeer H El-Hawary
Research Date
Research Department
Research Journal
Journal of Physics D: Applied Physics
Research Member
Research Pages
145502
Research Publisher
IOP
Research Vol
49
Research Website
DOI 10.1088/1361-6463/ae5668
Research Year
2026

Impact of trypanosomiasis on male camel infertility

Research Abstract

Introduction:

Blood parasitism is a significant clinical disease that silently undermines the livestock industry, particularly affecting camels. This study aimed to assess the prevalence of Trypanosoma evansi in Arabian camels (Camelus dromedarius) and its impact on infertility by examining serum protein fractions, lipids, reproductive indices, and the expression of heat shock protein (HSP70) during breeding season.

Methods:

A total of 107 male post-pubertal camels, aged between 5 and 10 years, were collected randomly from slaughtering house in Assiut Governorate, Egypt.

Results:

Microscopic and serological examinations revealed that 23.4% (25/107) of the camels were infected with T. evansi. Infected camels exhibited a highly significant increase in total serum protein. The assessment of dyslipidemia, measure as binary variables for lipid profiles (cholesterol, triglycerides, HDL, and LDL), indicated a nonsignificant increase in risk of dyslipidemia in infected camels compared to healthy camels. Proteomic analysis identified four major protein fractions in the infected camels compared to healthy camels with molecular weights of 181.72, 87.59, 30.5, and 19.5 kDa using SDS electrophoresis. Testicular tissue of the infected camels showed degeneration and necrotic changes in seminiferous tubules and interstitial tissue, along with edema and congestion. There was a significant reduction in the diameter of seminiferous tubules and germinal epithelium height. A marked reduction in testosterone levels and a high expression of HSP70 in spermatogonia, spermatocytes, Sertoli cells, and Leydig cells were observed.

Research Authors
Sara Salah Abdel-Hakeem 1*, Gaber Megahed2, Ahmed M. Al-Hakami3, Mohammed E. M. Tolba3 and Yasser F. M. Karar4
Research Date
Research Department
Research Journal
Frontiers in veterinary science
Research Year
2025

Integrative supporting techniques for the taxonomy of Schistorchis carneus Lühe, 1906 (Digenea: Megaperidae) with perspective for the existence of species complexes

Research Abstract

The morphology and host-parasite data of Schistorchis carneus Lühe, 1906 indicate low host specificity and geographical range variation, accompanied by a large scale of intraspecific variability and ambiguous molecular phylogeny, confusing in determining biodiversity extent and specificity to a particular host and/or locality. To address the challenging circumstances of records of S. carneus, a detailed morphological description, molecular characterization and species delimitation analyses were conducted using a combination of comparative morphology, molecular phylogeny, multivariate analyses, and hostparasite data. Several morphological features exhibited an extensive intra-variation, as well as a wide morphometric range in many measurements within and across records. Phylogenetic analyses showed that the classification of schistorchiines is highly correlated with the morphology/nature of the oral sucker and highlighted the limitations of ribosomal 28S rDNA and ITS2 rDNA in distinguishing morphologically close/related taxa. Species delimitation analyses reflected the critical importance of host distinction in schistorchiines recognition/differentiation, even those that are indistinct morphologically. The clustering of schistorchiines into certain groups was driven by host differences. Additionally, host variation typically corresponds to a distinct schistorchiine species, even if it is morphologically identical to another. Cluster analysis associated with host-parasite data revealed high morphometric convergence and significant diversity among Egyptian and Sri-Lankan records of S. carneus. It also confirmed the distinction between Indian records from the Bay of Bengal and those from the Gulf of Mannar (previously mentioned as Manaar), each in their own distant group. In conclusion, the records of S. carneus represent a repository for a group of closely related cryptic species. The restricted concept of S. carneus should include only records from the white-spotted puffer, Arothron hispidus (Linnaeus) and the stellate puffer, Arothron stellatus (Anonymous). The Australian specimens from the narrow-lined puffer, Arothron manilensis (Marion de Procé) and the Indian record from the lunartail puffer, Lagocephalus lunaris (Bloch & Schneider) likely represent a free-standing cryptic species with limited distribution, requiring further characterization. 

Research Authors
ALI MANSOUR1, YASSER F. M. KARAR2, HEMELY ABDEL-SHAFY HASSAN1, HODA S. MOHAMADAIN1 & SARA SALAH ABDEL-HAKEEM3
Research Date
Research Department
Research Journal
Zootaxa
Research Year
2025

Environmental bovine subclinical mastitis gram-negative pathogens: Prevalence, antimicrobial resistance with special reference to extended-spectrum β-lactamases and carbapenemase production

Research Abstract

This study investigates mastitis in the dairy industry, with a focus on the issue of antibiotic resistance. This study was designed to evaluate mastitis prevalence and investigate the bacteriological profiles of subclinical mastitis (SCM) milk, mastitis-free milk, and market milk. Out of 374 quarter milk samples, 26.2 % were from animals with SCM. Bacteriological examination identified 87 Gram-negative bacterial strains from subclinical mastitis milk (SCMM) (42.9 %), subclinical mastitis-free milk (SCMFM) (17.97 %), and market milk (MM) (58 %). MALDI-TOF MS identified species including E. coli, K. pneumoniae, Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Acinetobacter baumannii, with E. coli being the most frequent. Multi-drug resistant (MDR) phenotype was found in 43.7 % of isolates, with 57.1 % from SCMM, 43.8 % from SCMFM, and 24.1 % from MM. Biofilm production was observed in 44.8 % of isolates, with a significant correlation between MDR and biofilm formation. Eight strains (9.2 %) were extended-spectrum β-lactamases (ESBLs) producers, with blaCTX-M, blaTEM, and blaSHV genes detected. A. baumannii harbored multiple resistance genes, including blaTEM, blaCTX-M, blaOXA51, blaOXA23, and blaNDM, showing both phenotypic and genotypic ESBLs and carbapenemase activity. The presence of MDR, ESBLs, and carbapenemase producing Gram-negative bacteria in SCMM, SCMFM, and MM indicates a concerning exchange of bacteria and antimicrobial resistance genes between human and animal hosts, posing risks of milk contamination and environmental hazards. A one-health approach is essential for controlling antimicrobial-resistant bacteria, emphasizing prudent antimicrobial use in human and animal healthcare, and improving farm hygiene practices. 

Research Authors
Reda Abdel-Hameed a,*, Hanan H. Abd-Elhafeez b,*, Sara Salah Abdel-Hakeem c, Mahmoud AlElaimi a, Nagah M. Abourashed a, Ashraf M. Ashmawy a, Eshraqa Ali a, Bader Huwaimel d, Freah Alshammary e, Alaa Sayed Abou-Elhamd f, Mona Ahmed El-Zamkan g
Research Date
Research Department
Research Journal
Research in Veterinary Science
Research Year
2025

An overview of fasciolosis in human and cattle populations in New Valley, Egypt

Research Abstract

Introduction: Fascioliasis, a significant global zoonotic disease caused by trematode parasites of the genus Fasciola, affects various livestock species. Aim: This study aimed to identify demographic, epidemiological, clinical manifestations, pathological, and genetic characteristics in New Valley, Egypt’s human, and cattle populations.

Methods: This study is made of two parts, the first part is a cohort study of 1000 cattle slaughtered at three abattoirs in El Kharja, El Dakhilah, and El Farafra from February 2023 to January 2024. A retrospective analysis of patients visiting El Kharja hospital with clinical symptoms and confirmed with coprological and radiological examinations.

Results: The study revealed a high prevalence in cattle (23%) and humans (3.6%). Enrolled human fascioliasis was diagnosed in 58.3% and 41.7% by coprological and radiological analysis, respectively. A 66.7% of enrolled cases were females, with a median age range of 37 ± 13 years old. Treatment outcomes demonstrated a response of 25%, 50%, and 25% to single, two, and three doses of the treatment, respectively. In cattle, infection rate was 20.0% in females compared to 24.9% in males with low prevalence in animals <1 year (12.7%) and high in animals >3 years (30.4%). Autumn had the highest prevalence (28.7%), whereas summer had the lowest prevalence (18.0%). A significant difference in the prevalence of fasciolasis was observed between human and animals. Morphological and histopathological analysis elucidated acute and chronic manifestations of hepatic fascioliasis with ectopic migration to cattle lung tissue. Genetic characterization of ectopic worm confirmed Fasciola hepatica infection, with genetic similarity to human isolates from Iran.

Discussion: The study highlights the importance of one health approach in understanding and managing fascioliasis. 

Research Date
Research Department
Research Journal
Frontiers in veterinary science
Research Year
2025
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