Pathological and phylogenetic characterization of a rare fowl adenovirus (FAdV-8b) associated with inclusion body hepatitis in naturally infected Meleagris gallopavo.

Adenoviruses are a diverse group of viruses that can cause a variety of diseases in poultry, including respiratory and gastrointestinal infections. In turkeys (Meleagris gallopavo), adenoviruses commonly cause hemorrhagic enteritis and, rarely, inclusion body hepatitis. In this study, we investigated fowl adenoviruses (FAdVs) circulating in turkeys in Egypt. Following clinical examination of 500 birds, a portion of the hexon gene was amplified from four out of 50 samples from diseased birds (8%), and one amplicon that produced a strong band was selected for sequencing. Molecular and phylogenetic analysis revealed that the virus in that sample belonged to serotype FAdV-8b. Histopathological and immunohistochemical examinations of prepared tissue sections were performed to confirm the pathological findings. Diseased birds exhibited ruffled feathers, low body weight, a crouching posture, and diarrhea. Gross examination revealed petechial hemorrhage on the spleen, swollen pale liver, and congested intestine. Microscopic examination revealed the presence of eosinophilic and basophilic intranuclear inclusion bodies, nuclear pyknosis, and apoptotic bodies in the liver, congestion, hemorrhage, and fibrosis in the lungs, and desquamation of enterocytes. The presence of viral antigens in the liver, lungs, and intestine was confirmed by immunohistochemistry. To our knowledge, this is the first report of the characterization of an outbreak of inclusion body hepatitis in turkeys (hybrid converter breeds) due to FAdV-8b in Egypt. This finding raises an epidemiological alarm, necessitating further studies, including full-genome sequencing, to trace the virus's origin and genetic diversity.

Pathological and phylogenetic characteristics of fowl AOAV-1 and H5 isolated from naturally infected Meleagris Gallopavo.

BACKGROUND: In this study, we investigated the prevalence of respiratory viruses in four Hybrid Converter Turkey (Meleagris gallopavo) farms in Egypt. The infected birds displayed severe respiratory signs, accompanied by high mortality rates, suggesting viral infections. Five representative samples from each farm were pooled and tested for H5 & H9 subtypes of avian influenza viruses (AIVs), Avian Orthoavulavirus-1 (AOAV-1), and turkey rhinotracheitis (TRT) using real-time RT-PCR and conventional RT-PCR. Representative tissue samples from positive cases were subjected to histopathology and immunohistochemistry (IHC). RESULTS: The PCR techniques confirmed the presence of AOAV-1 and H5 AIV genes, while none of the tested samples were positive for H9 or TRT. Microscopic examination of tissue samples revealed congestion and hemorrhage in the lungs, liver, and intestines with leukocytic infiltration. IHC revealed viral antigens in the lungs, liver, and intestines. Phylogenetic analysis revealed that H5 HA belonged to 2.3.4.4b H5 sublineage and AOAV-1 belonged to VII 1.1 genotype. CONCLUSIONS: The study highlights the need for proper monitoring of hybrid converter breeds for viral diseases, and the importance of vaccination programs to prevent unnecessary losses. To our knowledge, this is the first study that reports the isolation of AOAV-1 and H5Nx viruses from Hybrid Converter Turkeys in Egypt.

Synergistic therapeutic strategies and engineered nanoparticles for anti-vascular endothelial growth factor therapy in cancer.

Angiogenesis is one of the defining characteristics of cancer. Vascular endothelial growth factor (VEGF) is crucial for the development of angiogenesis. A growing interest in cancer therapy is being caused by the widespread use of antiangiogenic drugs in treating several types of human cancer. However, this therapeutic approach can worsen resistance, invasion, and overall survival. As we proceed, refining combination strategies and addressing the constraint of targeted treatments are paramount. Therefore, major challenges in using novel combinations of antiangiogenic agents with cytotoxic treatments are currently focused on illustrating the potential of synergistic therapeutic strategies, alongside advancements in nanomedicine and gene therapy, present opportunities for more precise interference with angiogenesis pathways and tumor environments. Nanoparticles have the potential to regulate several crucial activities and improve several drug limitations such as lack of selectivity, non-targeted cytotoxicity, insufficient drug delivery at tumor sites, and multi-drug resistance based on their unique features. The goal of this updated review is to illustrate the enormous potential of novel synergistic therapeutic strategies and the targeted nanoparticles as an alternate strategy for t treating a variety of tumors employing antiangiogenic therapy.

Design, synthesis, and biological evaluation of pseudo-bicyclic pyrimidine-based compounds as potential EGFR inhibitors.

Cancer is one of the most dangerous diseases harvesting millions of lives every year globally, which mandates the development of new therapies. In this report, we designed and synthesized a novel series of compounds based on the structure of lapatinib and AF8c, a compound we developed and reported previously, to target EGFR kinase. The series was assayed against a panel of 60 cancer cell lines at the National Cancer Institute (NCI). Compounds 4a, 4f, 4 g, and 4 l showed high efficacy against melanoma, colon, and blood cancers, with 4a being the most effective. The evaluation of the potency of 4a against the 60 cell lines in a five-dose assay revealed a significant potency compared to lapatinib against melanoma, colon, and blood cancers. In vitro enzyme assay over 30 kinases showed significant potency against EGFR and high selectivity to EGFR among the tested kinases. A molecular modeling study of 4a and lapatinib inside the pockets of EGFR revealed that both compounds bind strongly inside the ATP-binding pocket of the EGFR kinase domain. Therefore, we present 4a as a novel EGFR kinase inhibitor with potent in vitro cellular activity against diverse types of cancer cells.

Sequence Analysis of Egyptian Foot-and-Mouth Disease Virus Field and Vaccine Strains: Intertypic Recombination and Evidence for Accidental Release of Virulent Virus.

In spite of annual mass vaccination programs with polyvalent inactivated vaccines, the incidence and economic impact of foot-and-mouth disease (FMD) in Egypt is high. Viruses of the A, O and SAT 2 serotypes are endemic and repeated incursions of new lineages from other countries lead to an unstable situation that makes the selection of appropriate vaccine antigens very difficult. In this study, whole genome sequencing of a 2016 serotype A isolate from Egypt revealed a recombination event with an African serotype O virus. Based on available vaccine matching data, none of the vaccines currently used in Egypt are expected to sufficiently protect against this virus or other viruses of this lineage (A/AFRICA/G-IV) circulating there since 2012. In addition to the risk of vaccine failure caused by strain mismatch, the production of inactivated FMD vaccines is dangerous if adequate biosafety cannot be maintained. Using a high-throughput sequencing protocol optimized for short nucleic acid fragments, the composition of a local inactivated vaccine was analyzed in depth. The serotype O strain identified in the vaccine was genetically identical to viruses found in recent FMD outbreaks in Egypt.