Nagar, E. E. M. S., H. M. Salem, M. A. N. Gamal, and M. A. El-Saied, Patho-molecular identification of circulating H9N2 avian influenza virus in Egypt, , 2024.
Mosallam, F. M., M. A. Shafik, S. A. Abd Elmawgoud, M. A. El-Saied, and R. M. Elshimy, "In vitro and in vivo attenuation of Salmonella resistance using a novel synthesized chloramphenicol magnesium Nano-complex.", Microbial pathogenesis, vol. 203, pp. 107511, 2025. Abstract

In this study, Chloramphenicol-Mg-Nano-complex (CHL-Mg-NC) was synthesized as a novel antimicrobial agent to attenuate chloramphenicol resistant Salmonella clinical isolates in vitro and in vivo. The CHL-Mg-NC was prepared in presence of gamma radiation and validated by SEM, DLS, Zeta potential, and FTIR, that revealed typical CHL-Mg-NC characteristics. The Phenotypes, biochemical investigations and molecular identification assays defined Salmonella isolates and further detection of invA gene in S. Paratyphi A NCRR-CHR1, S. Enteritidis NCRR-CHR2 and S. Typhimurium NCRR-CHR3 were appraised. In vitro anti-Salmonella efficacy of CHL-Mg-NC was assessed against Salmonella isolates in addition to Typhimurium ATCC 700720. Gamma radiation improved CHL-Mg-NC synthesis in dose-depend manner up to 5 kGy. CHL-Mg-NC showed MIC at a range from 0.156 to 0.625 μg/mL and MBC from 0.3125 to 2.5 μg/mL with MBC/MIC ratio less than or equal to 4. CHL-Mg-NC inhibited biofilm formation in the range of 45.31 %-100 %. It also had bactericidal activity at 2MIC within the low time ranged from 2h to 4h. The in vivo efficacy of CHL-Mg-NC was observed by the reduction in the number of viable Salmonella recovered from feces in infected mice and showed evident improvement in CHL-Mg-NC treated groups.CHL-Mg-NC has no significant cytotoxic effects on normal cells and CC is 13.5 μg/mL against CACO2 cells. Acute toxicity of CHL-Mg-NC indicates that the CHL-Mg-NC is safe at high concentrations.

Ahmed, R. F., A. M. Elgamal, H. A. S. El-Nashar, N. A. Mowaad, R. Elgohary, M. A. El-Saied, M. A. Farag, H. Imagawa, A. I. Elshamy, and A. M. Abd-ElGawad, "Phenolic-rich extracts of Teucrium oliverianum confer protection against thioacetamide-induced liver fibrosis in rats: Insights from metabolomics, biochemical and histopathological analysis.", PloS one, vol. 20, issue 9, pp. e0330595, 2025. Abstract

BACKGROUND: Hepatic fibrosis unfolds as a pathological buildup of extracellular matrix triggered by liver injury. Thioacetamide (TAA) plays a versatile role across various fields-from industrial processes and laboratory research to chemical stabilization. Teucrium plants, widely traditional plants, owing to its myriads of pharmacological activities.

METHODS AND FINDINGS: T. oliverianum ethanolic (TO-EtOH) and ethyl acetate (TO-EtOAc) extracts were explored for their bioactive metabolites via UHPLC-ESI-qTOF-MS/MS that yielded 48 compounds, mainly flavonoids and phenylethanoid glycosides, alongside phenolic acids, iridoid glycosides, and limonoids. Both extracts showed notable hepatoprotective effects in a thioacetamide (TAA)-induced liver injury model, supporting their therapeutic potential. The TAA group showed a significant increase in AST, ALT, ALP, MDA and TNF-α levels concurrent with a significant decrease of GSH level versus normal control group. In contrast, TO-EtOAC and TO-EtOH administered rats showed a decrease in liver enzymes, including ALT, AST, ALP, total bilirubin, and MDA, and an increase in GSH as compared to the TAA model group. Furthermore, both extracts considerably decreased the overall liver TNF-α content inferring anti-inflammatory action. The histo- and immunohistochemical assays of liver tissue of rats in TAA revealed prominent pathological alterations with bridging fibroplasia in multiple hepatic lobules. A restorative effect that improved hepatic morphology with apparent normal hepatic cells and nominal fibroplasia was evident in the administration of both extracts. Among both extracts, TO-EtOH appeared more effective than TO-EtOAC as manifested by a significant improvement in liver's biochemical parameters and structural organization.

CONCLUSION: This study provides robust evidence supporting the antifibrotic effects of T. oliverianum in a TAA-induced liver injury model. The anti-proliferative activity and hepatoprotective effects are likely to be mediated by its richness in phenolic acids, flavonoids and phenylethanoids.

Abdelhameed, M. F., M. A. El-Baset, A. R. Khattab, R. F. Taher, M. A. El-Saied, A. S. Abd Elkarim, A. F. Essa, A. A. El-Rashedy, M. A. Farag, H. Imagawa, et al., "Hepatoprotective action of Sonchus oleraceus against paracetamol-induced toxicity via Nrf2/KEAP-1/HO-1 pathway in relation to its metabolite fingerprint and in silico studies.", PloS one, vol. 20, issue 6, pp. e0325782, 2025. Abstract

BACKGROUND: Paracetamol overdose causes severe hepatotoxicity. Sonchus oleraceus is traditionally used to treat liver disorders, but its potential against paracetamol-induced liver injury is unexplored. This work aimed to investigate the protective mechanisms of an S. oleraceus extract (SOEtOH) using in vivo, histological and biochemical assessments along with metabolomics profiling and in silico studies, including molecular docking and dynamic simulations (MD).

METHODS AND FINDINGS: SOEtOH was administered to rats with paracetamol-induced hepatotoxicity at 50, 100, and 200 mg/kg doses. Serum enzymes, hepatic antioxidants, and histopathology were evaluated. UPLC-MS characterized bioactive metabolites and molecular docking and assessed their anti-inflammatory potential. SOEtOH significantly restored serum ALT and AST toward normal levels in a dose-dependent manner. It also replenished depleted hepatic glutathione (up to 3.9-fold) and superoxide dismutase (up to 4.7-fold). Immunohistochemistry revealed SOEtOH progressively attenuated caspase-3 expression related to apoptosis. It also ameliorated characteristic histopathological alterations like necrosis, inflammation, and sinusoidal congestion. Thirty-two bioactive metabolites, including flavonoids, phenolic acids, and terpenes, were identified. Molecular docking revealed potent anti-inflammatory effects via JNK inhibition, with luteolin-O-dihexoside, isorhamnetin-O-hexoside, di-O-caffeoylquinic, and kaempferol-O-hexoside having the strongest binding affinities. MD simulations demonstrated that these compounds' complexes significantly contribute to JNK1 and JNK2's catalytic binding site.

CONCLUSION: This integrated study demonstrates that SOEtOH protects against paracetamol hepatotoxicity by mitigating oxidative stress and inhibiting pro-inflammatory/apoptotic signaling. Our results reveal therapeutic lead compounds that may be further explored for clinical applications.

Hassan, N. F., M. R. El-Ansary, A. R. El-Ansary, M. A. El-Saied, and O. S. Zaki, "Unveiling the protective potential of mirabegron against thioacetamide-induced hepatic encephalopathy in rats: Insights into cAMP/PPAR-γ/p-ERK1/2/p S536 NF-κB p 65 and p-CREB/BDNF/TrkB in parallel with oxidative and apoptotic trajectories.", Biochemical pharmacology, vol. 229, pp. 116504, 2024. Abstract

Hepatic encephalopathy (HE) is one of the most prevalent and severe hepatic and brain disorders in which escalation of the oxidative, inflammatory and apoptotic trajectories pathologically connects acute liver injury with neurological impairment. Mirabegron (Mira) is a beta3 adrenergic receptor agonist with proven antioxidant and anti-inflammatory activities. The current research pointed to exploring Mira's hepato-and neuroprotective impacts against thioacetamide (TAA)-induced HE in rats. Rats were distributed into three experimental groups: the normal control group, the TAA group, received TAA (200 mg/kg/day for three consecutive days) and the Mira-treated group received Mira (10 mg/kg/day; oral gavage) for 15 consecutive days and intoxicated with TAA from the 13th to the 15th day of the experimental period. Mira counteracted hyperammonemia, enhanced rats' locomotor capability and motor coordination. It attenuated hepatic/neurological injuries by its antioxidant, anti-apoptotic as well as anti-inflammatory potentials. Mira predominantly targeted cyclic adenosine monophosphate (cAMP)/phosphorylated extracellular signal-regulated kinase (p-Erk1/2)/peroxisome proliferator-activated receptor gamma (PPARγ) dependent pathways via downregulation of p S536-nuclear factor kappa B p65 (p S536 NF-κB p 65)/tumor necrosis alpha (TNF-α) axis. Meanwhile, it attenuated nuclear factor erythroid 2-related factor (Nrf2) depletion in parallel with restoring of the neuroprotective defensive pathway by upregulation of cerebral cAMP/PPAR-γ/p-ERK1/2 and p-CREB/BDNF/TrkB besides reduction of GFAP immunoreactivity. Mira showed anti-apoptotic activity through inhibition of Bax immunoreactivity and elevation of Bcl2. To summarize, Mira exhibited a hepato-and neuroprotective effect against TAA-induced HE in rats via shielding antioxidant defense and mitigation of the pathological inflammatory and apoptotic axis besides upregulation of neuroprotective signaling pathways.

NAGY, A. H. M. E. D. M., M. F. Abdelhameed, S. Rihan, K. A. Diab, M. El-Saied, S. S. Mohamed, W. S. El-Nattat, and A. M. M. Hammam, "extract mitigates potassium dichromate-induced testicular degeneration in male rats: Insights from the Nrf2 and its target genes signaling pathway.", Toxicology reports, vol. 13, pp. 101700, 2024. Abstract

This study aimed to investigate the protective effects of Rosemary ethanol extract (ROEE) on testicular damage induced by potassium Dichromate (PDC) in male rats regarding the signaling pathway of Nrf2 and its target genes and proteins. A total of 28 male rats were divided into four groups: control, PDC only (15 mg/kg b.w. orally), PDC + low dose ROEE (220 mg/kg b.w.), and PDC + high dose ROEE (440 mg/kg b.w.). After 28 days of consecutive treatment, the rats were sacrificed for histological, immunohistochemistry, and biochemical analyses. The results revealed that the ROEE treatment up-regulated the Nrf2 and its target genes (NQO1, HO-1) mRNA expressions compared to the PDC group. correspondingly, the protein levels of GCLM, GSH, SOD, and catalase were significantly increased in the ROEE-treated animals compared to the PDC-treated animals. Furthermore, ROEE administration led to increased serum levels of testosterone (T4) and decreased levels of estrogen (E2) compared to the PDC group. Semen analysis and histopathology demonstrated that ROEE administration significantly improved spermatological impairment caused by PDC. The immunoexpression of cytoplasmic HSP-90 was reduced in the ROEE-treated groups, while the expression of androgen receptor (AR) was markedly improved. ROEE exhibited protective effects against PDC-induced testicular damage, likely due to its antioxidant properties. However, further investigation is required to elucidate the underlying mechanisms of action.

Elghonemy, M. M., M. G. Sharaf El-Din, D. Aboelsoued, M. F. Abdelhameed, M. A. El-Saied, N. I. Toaleb, M. A. Farag, A. I. Elshamy, and A. M. Elgamal, "Anticryptosporidial action mechanisms of Launaea spinosa extracts in Cryptosporidium parvum experimentally infected mice in relation to its UHPLC-MS metabolite profile and biochemometric tools.", PloS one, vol. 20, issue 3, pp. e0317497, 2025. Abstract

BACKGROUND: Cryptosporidium parvum, a leading cause of diarrhea, is responsible for millions of food and waterborne illnesses in humans and animals worldwide. Launaea spinosa (Asteraceae family) is a common herb found in the desert of the Mediterranean region, encompassing the peninsula of Sinai. Traditionally, it has been utilized for managing gastrointestinal issues and inflammation.

METHODS AND FINDINGS: The present study aimed to assess Launaea spinosa (LS) extracts viz. ethyl acetate (LS-EtOAc), ethanol (LS-EtOH), and n-butanol (LS-BuOH), of different polarities against C. parvum in experimentally infected mice based on immunological, biochemical, histo- and immunohistochemical assays. Extracts were characterized via UHPLC-ESI-LIT-Orbitrap-MS and metabolite profiles were subjected to correlation modeling with bioactivities via supervised Partial Least Square (PLS) to identify active agents. Most L. spinosa extracts reduced fecal C. parvum oocyst count and mucosal burden (P < 0.05) than untreated infected mice, with LS-BuOH (200 mg/kg) exerting the highest reduction percentage (97%). These extracts increased immunoglobulin G (IgG) levels in infected and treated mice at all examined days post treatment. Also, the highest Interferon-Gamma (IFN-γ) and Interleukin-15 (IL-15) levels were obtained after 10 days of post inoculation (dPI), which were restored to a healthy state after 21 days, concurrent with a decrease in Tumor Necrosis Factor-Alpha (TNF-α) (P < 0.001). The increased liver enzyme (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) levels with infection were likewise reduced with extract administration. The LS extracts caused a significant increase in antioxidant glutathione peroxidase (GSH-Px) and catalase (P < 0.001). Examination of colon tissue revealed that infected-treated mice with LS extracts exhibited a reduction in the expression of cleaved caspase-3, damage score, and degenerative changes. Metabolite profiling of different L. spinosa extracts led to the identification of 86 components, primarily phenolic acids, flavonoids, triterpenoid saponins, and fatty acids, with the first report of sulfated triterpenoid saponins in Launaea genus. PLS regression analysis revealed that bioeffects were significantly positioned close to LS-BuOH extract (R2: 0.9) mostly attributed to triterpenoid saponins and flavonoid glycosides.

CONCLUSIONS: This study demonstrated potential anti-cryptosporidial effects of LS extracts, especially LS-BuOH, suggesting its potential for inclusion in future nutraceuticals aimed at C. parvum treatment.

Khalil, R. M., M. F. Abdelhameed, S. A. Taleb, M. A. El-Saied, and E. S. Shalaby, "Preparation and characterisation of esculetin-loaded nanostructured lipid carriers gels for topical treatment of UV-induced psoriasis.", Pharmaceutical development and technology, vol. 29, issue 8, pp. 886-898, 2024. Abstract

SIGNIFICANCE: As an inflammatory and autoimmune skin condition, psoriasis affects 2-3% of people worldwide. Psoriasis requires prolonged treatments with immunosuppressive medications which have severe adverse effects. Esculetin (Esc) is a natural medication that has been utilised to treat psoriasis.

OBJECTIVE: The goal of this work is to improve Esc's solubility by developing novel Esc nanostructured lipid carriers (NLCs) for treating psoriasis and increasing the residence time on the skin which infers better skin absorption.

METHODS: The particle size, zeta potential and entrapment efficiency (EE) of Esc NLCs were assessed. Incorporating NLCs into gum Arabic gel preparation enhances their industrial applicability, absorption and residence time on the skin. Esc NLC gels were evaluated by release and effectiveness on a rat model of UV-induced psoriasis.

RESULTS: Esc NLCs showed high EE reaching more than 95% and reasonable particle size ranging between (53.86 ± 0.38 to 236.3 ± 0.11 nm) and were spherical. The release study of Esc NLCs gel demonstrated a fast release of Esc denoting enhanced bioavailability. Compared to free Esc, Esc NLCs gel (F2) could considerably lower the level of CD34 and TNF-α in the skin. The results were validated through histopathological analysis.

CONCLUSION: As Esc NLCs gel (F2) has strong anti-inflammatory properties, our results showed that it presented a significant potential for healing psoriasis.

Mousa, M. R., M. M. Attia, H. M. Salem, N. Al-Hoshani, H. Thabit, Marwa A Ibrahim, H. H. Albohiri, S. A. Khan, M. T. El-Saadony, K. A. El-Tarabily, et al., "Coinfection of the gut with protozoal and metazoal parasites in broiler and laying chickens.", Poultry science, vol. 103, issue 1, pp. 103227, 2024. Abstract

The chicken business faces substantial economic losses due to the risk of parasitic coinfection. Because the current study aimed to investigate enteric parasitic coinfections problems among the suspected examined chicken farms, samples were collected during the field investigation from suspected freshly dead birds, clinically diseased, apparently healthy, and litter samples for further laboratory parasitological, histopathological, and immunological examinations. Variable mortalities with various clinical indicators, such as ruffled feathers, weight loss, diarrhea of various colors, and a decline in egg production, occurred on the farms under investigation. In addition, the treatment protocols of each of the farms that were evaluated were documented and the m-RNA levels of some cytokines and apoptotic genes among the infected poultry have been assessed. The prevalence rate of parasitic coinfection in the current study was found to be 8/120 (6.66%). Parasitological analysis of the samples revealed that they belonged to distinct species of Eimeria, cestodes, and Ascaridia galli. When deposited, A. galli eggs were nonembryonated and ellipsoidal, but cestodes eggs possessed a thin, translucent membrane that was subspherical. Eimeria spp. oocysts in layer chickens were identified as Eimeria acervulina and Eimeria maxima in broiler chickens. Our findings proved that coinfection significantly upregulated the IL-1β, BAX, and Cas-3 genes. Conversely, the IL-10, BCL-2, and AKT mRNA levels were downregulated, indicating that nematode triggered apoptosis. The existence of parasite coinfection was verified by histological investigation of the various intestinal segments obtained from affected flocks. A. galli and cestodes obstructed the intestinal lumen, causing different histological alternations in the intestinal mucosa. Additionally, the lamina propria revealed different developmental stages of Eimeria spp. It was determined that parasite coinfection poses a significant risk to the poultry industry. It was recommended that stringent sanitary measures management methods, together with appropriate treatment and preventative procedures, be employed in order to resolve such issues.

Khaled, M. M., A. M. Ibrahium, A. I. Abdelgalil, M. A. El-Saied, and S. H. El-Bably, "Regenerative Strategies in Treatment of Peripheral Nerve Injuries in Different Animal Models.", Tissue engineering and regenerative medicine, vol. 20, issue 6, pp. 839-877, 2023. Abstract

BACKGROUND: Peripheral nerve damage mainly resulted from traumatic or infectious causes; the main signs of a damaged nerve are the loss of sensory and/or motor functions. The injured nerve has limited regenerative capacity and is recovered by the body itself, the recovery process depends on the severity of damage to the nerve, nowadays the use of stem cells is one of the new and advanced methods for treatment of these problems.

METHOD: Following our review, data are collected from different databases "Google scholar, Springer, Elsevier, Egyptian Knowledge Bank, and PubMed" using different keywords such as Peripheral nerve damage, Radial Nerve, Sciatic Nerve, Animals, Nerve regeneration, and Stem cell to investigate the different methods taken in consideration for regeneration of PNI.

RESULT: This review contains tables illustrating all forms and types of regenerative medicine used in treatment of peripheral nerve injuries (PNI) including different types of stem cells " adipose-derived stem cells, bone marrow stem cells, Human umbilical cord stem cells, embryonic stem cells" and their effect on re-constitution and functional recovery of the damaged nerve which evaluated by physical, histological, Immuno-histochemical, biochemical evaluation, and the review illuminated the best regenerative strategies help in rapid peripheral nerve regeneration in different animal models included horse, dog, cat, sheep, monkey, pig, mice and rat.

CONCLUSION: Old surgical attempts such as neurorrhaphy, autogenic nerve transplantation, and Schwann cell implantation have a limited power of recovery in cases of large nerve defects. Stem cell therapy including mesenchymal stromal cells has a high potential differentiation capacity to renew and form a new nerve and also restore its function.

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