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Abstract Alzheimer disease (AD) is among the most prevalent neurodegenerative diseases globally, marked by cognitive and behavioral disruptions. Ferroptosis is a form of controlled cell death characterized by intracellular iron accumulation associated with lipid peroxide formation, which subsequently promotes AD initiation and progression. We hypothesized that targeting the ferroptosis pathway may help in AD management. Therefore, our study aimed to evaluate the potential neuroprotective effect of the antifungal Ciclopirox olamine (CPX-O) that acts through iron chelation. We employed CPX-O separately or in combination with the JNK inhibitor (SP600125) in a mice model of AlCl3-induced AD. Animals underwent examination for behavioral, biochemical, histological, and immunohistochemical findings. Our results revealed that AlCl3 was associated with disruptions in learning and memory parameters, neuronal degeneration in the hippocampus, increased immunoreactivity of amyloid-β and tau proteins, a significant rise in iron, nitric oxide (NO), malondialdehyde (MDA), JNK, and P53 levels, along with the significant decrease in glutathione peroxidase activity. Interestingly, the administration of CPX-O alone or in combination with SP600125 in the AlCl3-induced AD model caused an improvement in the previously described examination findings. Therefore, CPX-O may be a promising candidate for AD treatment, and future clinical trials will be required to confirm these preclinical findings.

AbstractBreast cancer stands as the leading cause of cancer-related fatalities among women globally, presenting a diverse landscape of histological and molecular c characteristics, treatment response, and prognosis. This investigation examined the impact of soyasaponin IV, a natural product, on mice carrying Ehrlich’s ascites carcinoma (EAC), exploring its potential in blostering the hosts’ defense against cancer. The isolated compounds underwent scrutiny for their cytotoxic effects on breast cancer cell line, with Doxorubicin as the reference standard. Notably, Soyasaponin IV exhibited the highest cytotoxicity. Evaluation of its in vivo antitumor efficacy against EAC revealed a substantial reduction in tumor weight and volume, accompanied by improved histological features of tumor cells. EAC-induced abnormalities, including elevated levels of Malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and nuclear factor-kappa B (NF-κB) were all shown to be upregulated by EAC, while glutathione (GSH), were mitigated in a dose-dependent manner by soyasaponin IV treatment. Soyasaponin IV emerged as a promising strategy for suppressing EAC by impeding the NF-κB and VEGF pathways.

Abstract A simple technique was utilized to fabricate pure hexagonal La2O3 nanorods by utilizing lanthanum(III) nitrate hexahydrate (La(NO3)3·6H2O) and ammonia (NH4OH). The La2O3 nanoparticles were analyzed using XRD, TGA, Raman, SEM, FTIR, TEM, PL spectroscopy, and Mott–Schottky techniques. The XRD analysis confirmed the production of La(OH)3 nanorods under appropriate conditions, which were then successfully converted into La2O2CO3 and finally into La2O3 nanorods through annealing. The TGA analysis showed that the total weight loss was due to water evaporation and the dissolution of minimal moisture present in the environment. The FTIR analysis confirmed the presence of functional groups. The SEM analysis revealed changes in morphology. The TEM analysis to determine the particle size. The PL findings showed three emission peaks at 390, 520, and 698 nm due to interband transitions and defects in the samples. The Mott–Schottky analysis demonstrated that the flatband potential and acceptor density varied with annealing temperature, ranging from 1 to 1.2 V and 2 × 1018 to 1.4 × 1019 cm−3, respectively. Annealing at 1000 °C resulted in the lowest resistance to charge transfer (Rct).

Background: Paracetamol is one of the most popular drugs; it is used daily by many people especially the elderly, without a limitation on the length of the period allowed for continuous use. Harms from long-term use are less clear, particularly in extrahepatic regions. Aim: This study aimed to investigate whether using paracetamol at a NOAEL (non-observable adverse effect level) dose, known not to cause toxic effect, for long period can induce toxicity in aged male albino rats. Methods: A daily dose of 500 milligrams per kg body weight of paracetamol was given to adult male albino rats for 12 weeks. During this period, rats were sacrificed at 4, 6, 8, 10, and 12 weeks to evaluate the toxic changes at several time intervals. Results: Chemical analysis revealed elevated serum ALT, AST, ALP, urea, creatinine, and declined level of total protein in N-acetyl-p-aminophenol (APAP)-treated group; it also caused oxidative stress, as shown by decreased GSH, SOD, and elevated MDA in the liver, kidney, and brain. Histopathological examination demonstrated cytoplasmic vacuolation and sinusoidal congestion with the development of single-cell necrosis in the liver. Renal tubular necrosis and glomerular atrophy, and ischemic neuronal injury, especially in the hippocampus were observed. the deleterious effects of APAP were increased in severity with increasing the period of treatment. Conclusion: Our results suggest that acetaminophen in a subtoxic dose for a long period could result in mild toxic effects on the liver but more serious lesions in kidney, and brain. [Open Vet J 2024; 14(1.000): 316-323]

Background: Sodium nitrite (NaNO2) is a chemical substance used to enhance taste, add color, and keep food products fit for consumption for a longer time. NaNO2 gives rise to a negative adverse effect on male reproductive function. Odontonema cuspidatum (OC) is a natural plant that possesses antioxidant capacity. Aim: Our research evaluates the potential beneficial effect of Odontonema cuspidatum extract on the harmful effects caused by NaNO2 on the testicular tissue and sperm characteristics of male rats. Methods: Four groups with a total of forty rats: the control, the NaNO2-received group, the OC-administered group, and the fourth group received both NaNO2 and OC. All groups were administered daily for two months. Sperm characteristics, testicular antioxidant status and histopathological changes were evaluated. Results: Coadministration of NaNO2 and OC, in comparison with NaNO2 alone, contributed to a notable enhancement in acrosomal integrity, decreasing sperm abnormalities and restoring serum testosterone levels. Moreover, such coadministration reduced the oxidative stress marker, MDA, and increased SOD in testicular tissue, lowering TNF-α gene expression, and increasing the expression of P450scc and StAR genes. Additionally, the NaNO2 and OC combination decreased the testicular histopathological changes and the Caspase-3 and PCNA immunoexpression in seminiferous tubules compared with the NaNO2 group. Conclusion: The extract of Odontonema cuspidatum exhibited the ability to decrease oxidative stress and ameliorate the detrimental effects caused by NaNO2. [Open Vet J 2024; 14(1.000): 304-315]

An immune system response known as inflammation can be carried on by a variety of things, such as infections, damaged cells, and noxious substances. These factors may cause acute or chronic inflammatory responses in the heart, pancreas, liver, kidney, lungs, brain, colon, and reproductive system, which may cause disease or tissue damage. Inflammatory cells and signaling pathways are activated by both pathogenic and non-pathogenic agents, cell injury, and infectious agents. The most ubiquitous types of these include tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), High mobility group box 1 protein (HMGB1), mitogen-activated protein kinase (MAPK), monocyte chemoattractant protein (MCP1), interleukin 1 beta (IL1β), and Janus kinase-signal transducer and activator of transcription (JAK-STAT). Severe inflammation has the potential to cause systemic inflammatory response syndrome. The most severe forms of this condition are characterized by hyperinflammation and can cause organ damage, shock, and even death. We concentrate on the origin of inflammation, all conceivable inflammatory mechanisms, and organ-specific inflammatory responses in this study on inflammatory reactions inside organs.

Abstract This comparative study was conducted to assess the intramedullary bone tissue reaction of an ion-releasing resin modified glass-ionomer cement with claimed bioactivity (ACTIVA bioactive resin) restorative material versus Mineral Trioxide Aggregate High Plasticity (MTA HP) and bioceramic putty iRoot BP Plus. Fifty-six adult male Wistar rats were assigned into 4 equal groups (14 rats each). A surgical intramedullary bi-lateral tibial bone defects were performed in rats of the control group I (GI) and left without any treatment to be considered as controls (n = 28). The rats of groups II, III and IV were handled as group I except that the tibial bone defects were filled with ACTIVA, MTA HP and iRoot BP, respectively. In all groups, rats were euthanized after one month and specimens were processed to histological investigation, SEM examination and EDX elemental analysis. In addition, semi-quantitative histomorphometric scoring system was conducted for the following parameters; new bone formation, inflammatory response, angiogenesis, granulation tissue, osteoblasts and osteoclasts. The clinical follow-up outcome of this study revealed the recovery of rats after 4 days post-surgical procedure. It was observed that the animal subjects returned to their routine activities, e.g., walking, grooming and eating. The rats showed normal chewing efficiency without any weight loss or postoperative complications. Histologically, the control group sections showed scanty, very thin, new bone trabeculae of immature woven type located mostly at the peripheral part of the tibial bone defects. These defects exhibited greater amount of thick bands of typically organized granulation tissue with central and peripheral orientation. Meanwhile, bone defects of ACTIVA group showed an empty space surrounded by thick, newly formed, immature woven bone trabeculae. Moreover, bone defects of MTA HP group were partially filled with thick newly formed woven bone trabeculae with wide marrow spaces presented centrally and at the periphery with little amount of mature granulation tissue at the central part. The iRoot BP Plus group section exhibited an observable woven bone formation of normal trabecular structures with narrow marrow spaces presented centrally and at the periphery showed lesser amount of well-organized/mature granulation tissue formation. Kruskal Wallis test revealed total significant differences between the control, ACTIVA, MTAHP and iRoot BP Plus groups (p 0.05). The elemental analysis outcome showed that the lesions of the control group specimens were filled with recently created trabecular bone with limited marrow spaces. EDX tests (Ca and P analysis) indicated a lower degree of mineralization. Lower amounts of Ca and P was expressed in the mapping analysis compared with other test groups. Calcium silicate-based cements induce more bone formation when compared to an ion-releasing resin modified glass-ionomer restoration with claimed bioactivity. Moreover, the bio-inductive properties of the three tested materials are likely the same. Clinical significance: bioactive resin composite can be used as a retrograde filling.

Introduction: Ionizing radiation (IR) is effectively used in the treatment of oral malignancies; however, it might also significantly harm the surrounding tissues. Whey protein isolate (WP) is a protein derived from milk that exhibits a wide range of bioactivities. Therefore, the present research aimed to delineate the mitigating impact of WP against gamma irradiation-induced lingual damage.Methods: Rats were randomized into 5 groups: Control (saline, orally, 14 days), WP (WP; 0.5 g/kg b. w., orally, 14 days), IR (saline, orally, 14 days, exposed to 6 and 3 Gy on days 4 and 6, respectively), WP+IR (WP was given orally for 14 days before and after IR exposure; exposed to 6 and 3 Gy on days 4 and 6, respectively), and IR+WP (WP, orally, started 24 h after 1st IR exposure till the end of the experiment) groups. Samples were collected at two-time intervals (on the 7th and 14th days).Results and Discussion: Oxidative stress was stimulated upon IR exposure in tongue, indicated by boosted malondialdehyde (MDA) level, along with a decrease in the total antioxidant capacity (TAC) level, superoxide dismutase (SOD), and catalase (CAT) activities. Additionally, IR exposure depicted an increase of serum IgE, inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, along with overexpression mRNA levels of nuclear factor kappa-B transcription factor/p65 (NF-κB/p65), and down-regulation of nuclear factor erythroid 2–related factor 2 (NRF2) and heme oxygenase (HO-1) mRNA levels in tongue tissue. Moreover, IR triggered alterations in lingual histological architecture. The antioxidant and anti-inflammatory properties of WP mitigated oxidative damage, inflammation, and desquamation that were brought on following IR exposure. The protective administration of WP markedly decreases IR-induced lingual harm compared to the mitigation protocol. Our findings recommend WP supplements to the diets of cancer patients undergoing IR that might aid radioprotective effects.

Background and Aim: In late 2017, an H5N8 highly pathogenic avian influenza (HPAI) virus, clade 2.3.4.4, was isolated from domestic ducks in Egypt, which was associated with high morbidity and low mortality. The pathogenicity increased due to the continuous circulation of virus in ducks. Thus, this study aimed to monitor the pathogenesis and pathogenicity of new H5N8 Avian influenza (AI) virus in mule ducklings. Materials and Methods: The lethal dose 50 (LD50) for this new local HPAI H5N8 isolate was calculated. Twenty ducklings were inoculated with 0.1 mL of dilution containing 10 LD50 HPAI per duck. The clinical signs and mortalities were recorded until 30 days post-infection (DPI) to confirm viral pathogenesis. Reverse transcription polymerase chain reaction was used to detect viral shedding from collected cloacal swabs after 3rd, 5th, 7th, 10th, 14th, 21st, and 30th DPI. The main histopathological lesions associated with the presence of HPAI virus were also recorded on the 3rd and 14th DPI. Results: The result showed that the LD50 of the new HPAI H5N8 was 104 log10. Clinical signs were observed after 2nd DPI, but it was clinically severe on 3rd, 4th, and 5th DPI in the form of respiratory and gastric disorders, forming 90% of all diseased ducklings, whereas 30% of the infected ducks only showed nervous signs. The mortality rate peaked on 4th and 5th DPI with a cumulative mortality rate of 60% for the inoculated ducks, whereas no mortality was recorded after 6th DPI. Dead ducks showed typical postmortem lesions of AI disease. Necrosis and ecchymotic or petechial hemorrhages on the heart, pancreas, liver, and spleen were observed, whereas the lung showed pneumonia. With regard to viral shedding, infected ducklings shed the virus from its gut until 7th DPI, but the number of duck shedders gradually decreased until 14th DPI after viral shedding. The histopathological findings indicated that the spleen and thymus showed necrosis and hemorrhages, whereas the brain showed multifocal malacic foci and spread meningitis. Moreover, the lung had intrabronchial hyaline degeneration and fibrinous pneumonia on 3rd DPI. Furthermore, the liver showed multifocal necrotic foci and subcapsular hemorrhage, whereas the kidney showed remarkable tubular degeneration, mostly within the collecting tubules. Furthermore, the heart showed marked myocardiolysis of the cardiac muscle fibers. On 14th DPI, all histopathological lesions of the examined organs were restored to normal. Conclusion: The currently circulating HPAI H5N8 virus strain has high virulence, particularly for imported mule ducks that originated from non-vaccinated breeder ducks. Therefore, vaccination and quarantine measures must be applied on imported 1-day-old mule ducklings. Moreover, the pathogenesis must be reviewed and monitored for updating circulating AI strains caused by the continuous and rapid evolution of AI viruses.

Objective: To assess the bacterial colonisation of mice organs and faeces infected with 3 strains of Klebsiella pneumoniae, to measure levels of tumour necrosis factor-alpha, tumour necrosis factor-beta and interleukin-6 in mice serum, and to evaluate immune response of mice infected with Klebsiella pneumoniae. Method: The animal study was conducted at Kafreslsheikh University, Egypt, in 2021, and comprised mice 5-7 weeks old who were infected with 3 strains of Klebsiella pneumoniae; K80uge+ (uri, kfu+, mrkD+; K68 gyrA+(gyrase A), mrkD+; and K84 uge+, kfu+, mrkD+”. They were monitored for 14 days. The bacterial colonisation of mice livers, lungs, spleens and faeces were determined using culture on MacConkey agar. The percentage of neutrophils detected as cluster of differentiation 11b+ and cluster of differentiation 45+ in the mice serum was determined by flow cytometry. Levels of tumour necrosis factor-alpha and tumour necrosis factor-beta were measured using enzyme-linked immunosorbent assay. Results: There were 4 sets of female mice [1 control and 3 infected groups for which 3 K. pneumoniae strains (K80 uge+, kfu+, mrkD+; K68 gyrA+, mrkD+; and K84 “uge+, kfu+, mrkD+)] weighing 13-24gm was used. Colonisation of mice organs and faeces was high after 24 hours then declined rapidly after 3 days, 10 days and 14 days in case of infection with capsulated and non-capsulated strains of bacteria. Livers, lungs and spleens showed maximum inflammation after 24 hours, then declined rapidly. Both cytokine production and organ inflammation increased after one day of infection. There was a significant correlation between the produced cytokines and histopathological changes in liver, lung and spleen. The neutrophils increase in case of infection with K84 and K80 was more than non-capsulated K68. Conclusion: Neutrophils were found to play an important role in the clearance and treatment of Klebsiella pneumoniae. Keywords: Mice, Interleukin, Neutrophils, Spleen, Cytometry, Lung, Inflammation, Liver, Faeces, Enzyme, Immunity.

Abstract Background The adverse effect of aflatoxin in broilers is well known. However, dietary supplementation of Saccharomyces cell wall and/or Nanocurcumin may decrease the negative effect of aflatoxin B1 because of the bio-adsorbing feature of the functional ingredients in Yeast Cell Wall and the detoxification effect of curcumin nanoparticles. The goal of this study was to see how Saccharomyces cell wall/Nanocurcumin alone or in combination with the aflatoxin-contaminated diet ameliorated the toxic effects of aflatoxin B1 on broiler development, blood and serum parameters, carcass traits, histology, immune histochemistry, liver gene expression, and aflatoxin residue in the liver and muscle tissue of broilers for 35 days. Moreover, the withdrawal time of aflatoxin was measured after feeding the aflatoxicated group an aflatoxin-free diet. Broiler chicks one day old were distributed into five groups according to Saccharomyces cell wall and/or nanocurcumin with aflatoxin supplementation. The G1 group was given a formulated diet without any supplements. The G2 group was supplemented with aflatoxin (0.25 mg/kg diet) in the formulated diet. The G3 group was supplemented with aflatoxin (0.25 mg/kg diet) and Saccharomyces cell wall (1 kg/ton diet) in the formulated diet. The G4 group was supplemented with aflatoxin (0.25 mg/kg diet) and nanocurcumin (400 mg/kg) in the formulated diet. The G5 group was supplemented with aflatoxin (0.25 mg/kg diet) and Saccharomyces cell wall (1 kg/ton diet) in combination with nanocurcumin (200 mg/kg) in the formulated diet. Results According to the results of this study, aflatoxin supplementation had a detrimental impact on the growth performance, blood and serum parameters, carcass traits, and aflatoxin residue in the liver and muscle tissue of broilers. In addition, aflatoxin supplementation led to a liver injury that was indicated by serum biochemistry and pathological lesions in the liver tissue. Moreover, the shortening of villi length in aflatoxicated birds resulted in a decrease in both the crypt depth ratio and the villi length ratio. The expression of CYP1A1 and Nrf2 genes in the liver tissue increased and decreased, respectively, in the aflatoxicated group. In addition, the aflatoxin residue was significantly (P ≤ 0.05) decreased in the liver tissue of the aflatoxicated group after 2 weeks from the end of the experiment. Conclusion Saccharomyces cell wall alone or with nanocurcumin attenuated these negative effects and anomalies and improved all of the above-mentioned metrics.

Avian orthoreovirus (ARV) is among the important viruses that cause drastic economic losses in the Egyptian poultry industry. Despite regular vaccination of breeder birds, a high prevalence of ARV infection in broilers has been noted in recent years. However, no reports have revealed the genetic and antigenic characteristics of Egyptian field ARV and vaccines used against it. Thus, this study was conducted to detect the molecular nature of emerging ARV strains in broiler chickens suffering from arthritis and tenosynovitis in comparison to vaccine strains. Synovial fluid samples (n = 400) were collected from 40 commercial broiler flocks in the Gharbia governorate, Egypt, and then pooled to obtain 40 samples, which were then used to screen ARV using reverse transcriptase polymerase chain reaction (RT-PCR) with the partial amplification of ARV sigma C gene. The obtained RT-PCR products were then sequenced, and their nucleotide and deduced amino acid sequences were analyzed together with other ARV field and vaccine strains from GenBank. RT-PCR successfully amplified the predicted 940 bp PCR products from all tested samples. The phylogenetic tree revealed that the analyzed ARV strains were clustered into six genotypic clusters and six protein clusters, with high antigenic diversity between the genotypic clusters. Surprisingly, our isolates were genetically different from vaccine strains, which aligned in genotypic cluster I/protein cluster I, while our strains were aligned in genotypic cluster V/protein cluster V. More importantly, our strains were highly divergent from vaccine strains used in Egypt, with 55.09–56.23% diversity. Sequence analysis using BioEdit software revealed high genetic and protein diversity between our isolates and vaccine strains (397/797 nucleotide substitutions and 148-149/265 amino acid substitutions). This high genetic diversity explains the vaccination failure and recurrent circulation of ARV in Egypt. The present data highlight the need to formulate a new effective vaccine from locally isolated ARV strains after a thorough screening of the molecular nature of circulating ARV in Egypt.

Malus domestica Borkh, the apple tree, exhibited numerous pharmacological properties including antioxidant, neuroprotective, anti-inflammatory, anticancer and antimicrobial activities. The present work aimed to annotate the secondary metabolites from a butanol fraction of apple leaves (BLE), evaluate the gastro-protective and healing effects of this fraction against indomethacin-induced gastric ulcers in rats and to identify its mechanism of action. BLE (100, and 200 mg/kg) was orally administered in rats as an acute treatment against indomethacin-induced gastric ulcer in comparison with famotidine as reference anti-ulcer drug. The stomachs of rats were collected to determine the ulcer index, the preventive ratio, measure the activity of glutathione peroxidase (GPx), and estimate the expression of cyclooxygenase-2 (COX-2), and heat shock protein 70 (HSP70). Furthermore, we evaluated both inflammatory and oxidative stress markers in the gastric tissues. We also performed histopathological study of gastric mucosa using H&E stain and periodic Schiff base stain to evaluate both gastric injury scores and gastric mucus content respectively. Pretreatment with BLE markedly lowered the severity of gastric injury induced by indomethacin, decreased oxidative stress, inflammatory cytokines, and COX-2 expression in the examined gastric tissues. The gastric healing effect of BLE was associated with increased mucoglycoproteins, and HSP70 expression. Additionally, gastric healing effect of high dose of BLE was superior to that of famotidine in decreasing gastric injury scores, COX-2, inflammatory cytokines, lipid peroxidation and in increasing gastric mucin content, HSP70, and reduced glutathione. These findings indicate that BLE is effective in accelerating ulcer healing by boosting HSP70 expression, and decreasing COX-2 expression, oxidative stress, and gastric inflammation which might be related to the presence of 21 phytoconstituents.

Avian pathogenic Escherichia coli is one of the principal causes of heavy economic losses to the poultry industry. Little is known about the underlying mechanisms, particularly the potential role of immunoglobulin A and the DNA damage, involving the beneficial effects of dietary supplementation of probiotics and prebiotics in avian colibacillosis. The current study investigated the potential effects of probiotic and prebiotic dietary supplementation on E. coli-infected broiler chicks. A total of 120 1-day-old unsexed Hubbard chicks were divided into six groups: Group 1 was considered as a negative control; Group 2 was supplemented with 1 g/kg feed of Lactobacillus plantarum; Group 3 was supplemented with amylase enzyme; Group 4 served as a positive control infected orally by E. coli O78; Group 5 was supplemented with L. plantarum from 1-day-old chicken and then infected orally with E. coli O78; and Group 6 was supplemented with amylase enzyme from 1-day old chicken and then infected orally with E. coli O78. For all examined groups, the experimental period lasted for 42 days. The E. coli-infected group revealed a decrease in body performance parameters with a significant increase in the liver enzymes and renal function tests. The same group recorded a significant decrease in serum total proteins, albumins, and globulins, and the alteration of immunological parameters, antioxidant enzymes, oxidative stress parameters, and comet assay revealed highly damaged DNA in the liver and the intestine. By histopathological examination, a series of histopathological changes in the liver, the kidney, and the intestine were observed. The infected chick pretreated with probiotics or prebiotics demonstrated an improvement in body performance parameters besides a significant decrease in the hepatic enzymes and renal function tests. We noticed that, in treated groups, there was a significant increase in serum total proteins in the serum albumin and globulin levels, immunological parameters, and antioxidant enzymes. Furthermore, DNA damage and histopathological changes within hepatic, renal, and intestinal tissues were markedly diminished in the treated groups compared with the infected group. We concluded that the adverse effects of E. coli could be modulated through the chemopreventive administration of probiotics and prebiotics.

The ameliorative effects of Spirulina and Saccharomyces cerevisiae (S. cerevisiae) against fipronil toxicity in Nile tilapia fish were investigated. Fipronil is a kind of pesticide that is widely used in agriculture, thus this trial was conducted to evaluate the effect of fipronil on growth related parameters (final body weight, feed intake, weight gain, feed conversion ratio, specific growth rate, and protein efficiency ratio), hematology related parameters (RBCs, WBCs, hemoglobin, packed cell volume, and deferential leukocytic count), biochemistry related parameters (alanine aminotransferase, aspartate aminotransferase, total protein, albumin, urea, and creatinine), histopathology of liver, intestine, gills, and spleen, and gene expression of antioxidants, stress, inflammatory, apoptotic, and related to junction proteins genes as SOD and GPx, COX II, TNF-α, Casp-3, and Claudin-3, respectively, in Nile tilapia (Oreochromis niloticus). Four hundred and five Nile tilapia fish were distributed in a glass aquarium into nine groups according to the Spirulina and S. cerevisiae supplemented diets, with or without fipronil contaminated water. The classified groups are control, Sc: S. cerevisiae (4 g/Kg diet), Sp: Spirulina (1 g/100 g diet), Fb1: 0.0021 mg fipronil/L, ScFb1: S. cerevisiae (4 g/Kg diet) with 0.0021 mg fipronil/L, SpFb1: Spirulina (1 g/100 g diet) with 0.0021 mg fipronil/L, Fb2: 0.0042 mg fipronil/L, ScFb2: S. cerevisiae (4 g/Kg diet) with 0.0042 mg fipronil/L, and SpFb2: Spirulina (1 g/100 g diet) with 0.0042 mg fipronil/L. The results of the present investigation indicated the negative effect of fipronil on the growth performance parameters of Nile tilapia, which was confirmed by the results of hematology, biochemistry, and histopathology. In addition, the results of gene expression of antioxidants, stress, inflammatory, and apoptotic genes indicate the genotoxicity of fipronil. However, these negative effects were ameliorated by Spirulina and Saccharomyces dietary supplementation.

Abstract Cisplatin (CP) is one of the most frequently used chemotherapy agents. The objective of this design was to determine the ameliorative effect of lycopene (LP) and/or N-acetylcysteine (NAC) in rats with hepatic and renal toxicity induced by CP. Rats were divided randomly into 7 groups (7 rats/group): control vehicle group (saline only), the LP group (10 mg/kg, orally), the NAC group (150 mg/kg, orally), the CP group (7.5 mg/kg, IP on day 27), the LP-CP group, the NAC-CP group, and the LP-NAC-CP group. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (APK), and levels of urea, creatinine, and lipids (cholesterol, triglycerides, and low-density lipoprotein-cholesterol) increased after CP injection in the serum. Moreover, CP decreased levels of protein, albumin, and HDL cholesterol. Meanwhile, malondialdehyde significantly increased with a decrease in reduced glutathione, superoxide dismutase, and catalase in the liver and kidney tissues. CP also induced some pathological lesions and increased the expression of caspase-3 in the liver and kidney tissues. Administration of LP and NAC alone or in combinations ameliorated hepatorenal toxicity and apoptosis induced by CP.

Doxorubicin (DOX) is a frequent chemotherapeutic drug used to treat various malignant tumors. One of the key factors that diminish its therapeutic importance is DOX-induced nephrotoxicity. The first-line oral antidiabetic drug is metformin (Met), which also has antioxidant properties. The purpose of our study was to investigate the underlying molecular mechanisms for the potential protective effects of Met on DOX-triggered nephrotoxicity. Four animal groups were assigned as follows; animals received vehicle (control group), 200 mg/kg Met (Met group), DOX 15 mg/kg DOX (DOX group), and a combination of DOX and Met (DOX/Met group). Our results demonstrated that DOX administration caused marked histological alterations of widespread inflammation and tubular degeneration. Notably, the DOX-induced dramatic up-regulation of the nuclear factor-kappa B/P65 (NF-κB/P65), microtubule-associated protein light chain 3B (LC3B), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-1beta (IL-1β), 8-hydroxy-2′ -deoxyguanosine (8-OHdG), and Beclin-1 in renal tissue. A marked increase in the malondialdehyde (MDA) tissue level and a decrease in the total antioxidant capacity (TAC) were also recorded in DOX-exposed animals. Interestingly, Met could minimize all histopathological changes as well as the disruptions caused by DOX in the aforementioned measures. Thus, Met provided a workable method for suppressing the nephrotoxicity that occurred during the DOX regimen via the deactivation of the Beclin-1/LC3B pathway.

Abstract Malathion is considered one of the vastest pesticides use all over the world. Malathion-inhalation toxicity commonly occurred in many occupational farmers. Therefore, this study aimed to ameliorate the possible malathion-induced pulmonary toxicity through thymoquinone administration. Forty animals were used to conduct our study, divided into five groups; G1 control group, G2 thymoquinone (50 mg/kg) group, G3 malathion group (animals inhaled 100 mg/ml/m3 for 15 min for 5 days/week for three weeks), G4 and G5 were subjected to the same malathion inhalation protocol beside oral thymoquinone administration at doses of 25 and 50 (mg/kg), respectively. Malathion-inhalation induced marked systemic toxicity as hepatotoxicity and nephrotoxicity associated with increased serum hepatic and renal enzymes, and hypersensitivity accompanied with increased total IgE serum level. The lung showed severe interstitial pneumonia associated with severe vascular damage and marked eosinophil infiltration. Moreover, the lung showed a marked decrease in the pulmonary surfactant protein, especially SP-D gene expression. While, thymoquinone treatment to malathion-inhaled animals decremented the following; hepatic enzymes and renal function tests, total IgE as well as pneumonia and hypersensitivity pathological features, and augmented the expression of SP-D. In conclusion, thymoquinone could be potentially used in pest control workers to ameliorate the systemic and pulmonary intoxication caused by one of the most field-used pesticides.

Avian coccidiosis is one of the major parasitic diseases in the poultry industry. The infection is caused by Eimeria species, and its treatment relies mainly on the administration of anticoccidial drugs, which can result in drug resistance and side effects. The recent trends in avian coccidiosis treatment is directed to the development of a new therapy using herbal compounds. S-Methylcysteine (SMC) is considered one of the organosulfur compounds in garlic that showed promising activity in the treatment of different pathological conditions via a wide range of anti-inflammatory and antioxidant mechanisms. In this study, the anticoccidial activity of SMC was investigated in Eimeria tenella-infected chickens compared to diclazuril as a widely used anticoccidial drug. In this regard, 14-day-old broilers were divided into six groups (n = 18). The first group (G1) was the healthy control group, while the second group (G2) was the non-infected SMC group treated at a dose of 50 mg/kg b.w. (high dose). Moreover, the third group (G3) was the positive control group (infected and non-treated). The fourth group (G4) was the infected group treated with SMC of 25 mg/kg b.w. (low dose), while the fifth group (G5) was the infected group treated with SMC of 50 mg/kg b.w. (high dose). Conversely, the sixth group (G6) was the diclazuril-treated group. The anticoccidial effects of SMC and diclazuril were evaluated by counting oocysts and recording the body weight gain, feed conversion ratio, clinical signs, lesions, and mortality rate. Interestingly, SMC showed potent anticoccidial activity, which was exemplified by reduction of oocyst count. Furthermore, the biochemical, antioxidant, and anti-inflammatory parameters in the cecal tissues were restored toward their control levels in G4, G5, and G6. Histopathological observation of cecal tissues was consistent with the aforementioned results revealing the ameliorative effect of SMC against E. tenella infection. This study concluded novel findings in relation to the anticoccidial role of SMC as a plant-based compound against the E. tenella-induced coccidiosis in broiler chickens combined with its antioxidative and anti-inflammatory properties. Further studies for exploring the mechanistic pathways involved in this activity and the potential benefits from its use in association with conventional anticoccidial drugs are warranted.

Newcastle disease virus (NDV) is a highly contagious virus infects a wide range of avian species including chicken and ducks. The disease can be fatal for many types of them. It was believed that ducks and geese act as natural reservoirs of NDV because of their natural resistance. Recently, NDV isolates were pathogenic for ducks. Therefore, our study aimed to investigate the pathogenicity of highly pathogenic NDV genotype VII in white Ross commercial broiler chickens and Mallard ducks on the basis of clinical, histological observation and immunohistochemistry findings of virus antigen through studying the sequential pathological lesions of both species at 2nd, 5th and 10th dpi. Both species were inoculated via intranasal route by NDV genotype VII (accession number MT887290). Clinical lesions and mortalities were evident mostly in chickens rather than in ducks. Respiratory, digestive and nervous signs were clearly manifested in chickens. Ducks showed low level of mortalities and the nervous signs were the most obvious symptoms. Microscopic findings of chickens showed severe pancreatitis, pneumonia, enteritis as well as pericarditis and brain malacia. Similar findings were noticed in ducks but with lower degree of severity. Brain lesions in ducks included encephalitis and perivascular reaction mostly within the cerebellar tissue. Immunohistochemistry reaction against NDV antigen showed marked immunostaining within epithelial cells, purkinje cells and inflammatory cells mostly the macrophages. The immunohistochemistry reaction was correlated with the pathological findings in both species. In conclusion, the mortality and lesions of NDV in both species were correlated with systemic alterations associated with pancreatitis, pneumonia and encephalopathy. Moreover, the obtained data revealed possible susceptibility of ducks to NDV genotype VII, which might be need forthcoming viral vaccination strategy for ducks against NDV.

This study aimed to investigate a sheeppox outbreak in a highly susceptible naive sheep population in Kharsit village, Gharbia Governorate, Egypt. Moreover, to compare commercial sheeppox vaccines, the Romanian strain and RM-65 vaccines, as emergency vaccination against sheeppox under field conditions. In December 2018, a sheeppox outbreak occurred in a flock of 65 sheep upon the purchase of an apparently healthy ewe from outside the village. This ewe showed a systemic disease with cutaneous lesions after a few days, thereafter more cases began to appear. Cutaneous lesions in other sheep in the flock in the form of macules, papules, and scabs were common in wool-less areas of the body, in addition to fever and respiratory disorders. Postmortem findings revealed the congestion of visceral organs with apparent gross pathology of the lung. Biopsies of cutaneous lesions and visceral organs were collected, and sheeppox was identified by histopathology and transmission electron microscopy, which showed the existence of sheeppox cells and intracytoplasmic brick-shape sheeppox virions. The Romanian strain and RM-65 vaccines were used for the emergency vaccination for two different groups of animals and the third group was left as a control group. Serum samples were collected before vaccination as well as 21 days post-vaccination, and serum protein fractionation analysis was performed for all groups. The outbreak ended after 2.5 months, the cumulative incidence was 66.2%, and the overall case fatality was 51.1%. There was significantly higher protection against sheeppox infection and mortalities among RM-65 vaccine immunized group compared to Romanian strain vaccine-immunized animals at p < 0.05. RM-65-vaccinated animals did not show sheeppox cases or mortalities, compared to Romanian strain-vaccinated animals, which had mild pox signs in 78% of animals and case fatality of 35.7%. The serum protein analysis also indicated the superior performance of the RM-65 vaccine; it increased the level of α1-globulin and β-globulin compared to the Romanian strain, which increased the level of β-globulin only. The current study shows a better performance of the tested RM-65 than the Romanian strain vaccine for emergency vaccination against sheeppox under field conditions. These findings point to the validity of emergency vaccination against sheeppox and the importance of the comparative field evaluation of vaccines; however, wide-scale studies are required for further evaluation. Future investigation of whether the Romanian strain itself or vaccine-production-related issues are responsible for these findings is required.

We previously profiled the chemical composition of wax apple, Syzygium samarangense, leaf extract using HR-LC-MS/MS and reported its antioxidant, hepatoprotective and antitrypanosomal activities. The plant is widely used in traditional medicine to cure several ailments like bronchitis, asthma, diabetes, fever, pathogenic infections, gut spasms, as well as renal diseases. However, neither the gastroprotective effects nor the underlying mechanisms were explored. Here, we investigated the gastroprotective potential of the leaf extract on indomethacin-induced gastric ulcer in rats and explored the involved mechanism(s) of action. Administration of indomethacin significantly increased the ulcer index, mucosal injury, the gastric levels of the inflammatory markers nuclear factor kabba B-p65(NF-κB p65), myeloperoxidase (MPO), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), lipid peroxidation product, malondialdehyde (MDA) and Caspase-3 expression. It reduced the gastric levels of the endogenous antioxidants glutathione as well peroxidase (GPx), reduced glutathione (GSH) and the gastric mucosal protective factors, mucus secretion and goblet cells. Pretreatment with the leaf extract displayed a prominent decrease in the ulcer index, inflammatory cell infiltration, inflammatory markers, MDA, protein expression of Caspase-3 and a significant increase in the gastric levels of the endogenous antioxidants, mucus content and goblet cell proliferation when compared to the indomethacin group. The individual secondary metabolites of the extract exhibited low binding energy when docked into the prostaglandin receptors EP3 and EP4. This study revealed the gastroprotective effect of S. samarangense on indomethacin-induced gastric ulcer in rats. The gastroprotective effects might be attributed to cytoprotective, antioxidant, anti-inflammatory and antiapoptotic activities with a possible potential of activating EP3 and EP4 receptors. In conclusion, S. samarangense has a promising potential in the prevention of NSAIDs-induced ulcers.

This research was conducted to evaluate the impact of dietary or drinking water Ruminococcus sp. supplementation and/or heat stress (HS) on the growth, serum biochemistry, tissue antioxidant, phagocytic assay, histopathology, and bursa gene expression of broilers. Day-old broiler chicks were allotted into six groups according to HS and/or Ruminococcus with or without enzyme supplementation. The first group was the control one, with a formulated diet and normal environmental temperature but without any supplement. The second group fed on Ruminococcus-supplemented diet (1 kg/kg diet). The third group fed on a formulated diet without supplement, and Ruminococcus and digestive enzymes were given in drinking water (0.1 ml/L). The fourth one was the heat stress group, with a normal formulated diet. The fifth and the sixth groups served as second and third groups, respectively, but with heat stress. The results of this experiment indicated that thermal temperature negatively affected the parameters of growth performance, serum biochemical, tissue antioxidants, and phagocytic assay. Moreover, heat stress led to pathological lesions in the internal organs and affected the expression of some genes related to heat stress, including proapoptotic genes such as caspase8 and bax, inflammatory genes such as NF-κβ1, and heat shock protein such as HSP 70 in the bursal tissue. These bad effects and abnormalities were mitigated by Ruminococcus alone or with enzyme supplementation, which improved all the above-mentioned parameters.

Abstract Background The purpose of this study was to compare the biocompatibility of three bioactive materials, namely ACTIVA bioactive restorative resin composite, iRoot BP plus and Mineral Trioxide Aggregate (MTA) Angelus-HP. Methods Seventy-five Wistar male rats were subjected to subcutaneous implantation of four polyethylene tubes; one empty tube was used as control (Group 1), and the other tubes were filled with ACTIVA (Group 2), iRoot BP (Group 3) and MTA-HP (Group 4). Then, the rats were subdivided into 3 groups according to the sacrification time into one, two and 4 weeks (n = 25 rats). Tissue specimens were submitted to histopathological and immunohistochemical analysis of α-SMA and caspase 3. Results The one-way Anova test revealed that ACTIVA group exhibited minimal inflammation in comparison to calcium silicate cements (iRoot BP and MTA-HP groups). iRoot BP group significantly revealed a more severe degree of chronic inflammation in comparison to other groups (P

Schistosomiasis, a major parasitic illness, has high morbidity and negative financial effects in subtropical and tropical countries, including Egypt. The present study investigated the therapeutic effects of Spirulina platensis (SP) and matcha green tea (MGT) in Schistosoma mansoni-infected mice combined with tracing their possible antioxidant and anti-inflammatory impacts and their protective potency. A total of 60 Swiss albino mice were randomly allocated into six groups (n = 10): control group (CNT, received normal saline); SP–MGT group [received oral SP (3 g/kg bodyweight/day) plus MGT (3 g/kg bodyweight/day)]; S. mansoni group (infected with S. mansoni cercariae, 100 ± 10/mouse, using the tail immersion method); SP-infected group (infected with S. mansoni and received oral SP); MGT-infected group (received oral MGT after S. mansoni infection); and SP–MGT-infected group (received combined treatment of SP and MGT after S. mansoni infection). Treatment with SP and MGT started 4 weeks after S. mansoni infection and ended 10 weeks after. SP and MGT treatment (SP-infected and MGT-infected groups) and the combined treatment (SP–MGT-infected group) minimized the hepatic damage induced by S. mansoni; circulating alanine aminotransferase and aspartate transaminase decreased, and total protein, albumin, and globulin serum levels increased. The serum level of malondialdehyde significantly declined, and catalase, glutathione peroxidase, superoxide dismutase, and total antioxidant capacity increased in SP-infected, MGT-infected, and SP–MGT-infected groups compared with the infected group. Co-administration of SP and MGT reduced serum cytokine levels (tumor necrosis factor-alpha, interferon-gamma, and interleukin-13) and increased interleukin-10 levels after S. mansoni infection compared with the infected group. Moreover, treatment with SP and/or MGT decreased the number of granulomas in hepatic and splenic tissues compared with the infected group. Collectively, our results suggest that combined SP and MGT treatment is effective for S. mansoni infection. Liver and spleen tissue alterations were improved, the antioxidant systems were stimulated, and the inflammatory response was suppressed. Further research is recommended to investigate the mechanisms of the combined SP and MGT treatment effects to facilitate the development of novel therapies against this disease.

The recent emergence of COVID‐19 represents one of the biggest challenges facing the world today. Despite the recent attempts to understand the epidemiological pattern and pathogenesis of the disease, detailed data about the physiology and pathology of the disease is still out of reach. Moreover, the lack of a widespread vaccine prompts an urgent call for developing a proper intervention strategy against the virus. Importantly, identification of novel molecules that target replication of the virus represents one of the promising strategies for the control this pandemic crisis. Among others, honey bee products contain numerous bioactive compounds such as propolis and several phenolic compounds that possess a wide range of therapeutic properties for combating various pathological disorders and infectious agents. The intention of the present review is to highlight the stages of SARS-CoV-2 lifecycle, the molecular mechanisms explaining the health benefits of honey bee products on COVID‐19 physiology and pathology and the possible limitations. Further future research is suggested to explore more about bee natural bioactive compounds as potential candidates against SARS-CoV-2.

Camel milk has become more popular among customers in recent years as a result of its therapeutic effects. In many parts of the world, it is considered one of the primary components of human nutrition. The present study aimed to develop a novel synbiotic ice cream from camel milk formulated with black rice powder (BRP) and investigate the viability of probiotic bacteria (Lactobacillus acidophilus LA-5) during the storage period (60 days). Skim milk powder was replaced by BRP at levels of 0, 25, 50, and 75%. The produced ice cream was examined for some physicochemical, rheological, microbiological, and sensorial properties. The obtained results indicated that the incorporation of BRP into ice cream blends resulted in significant increases in the overrun, viscosity, and melting resistance of ice cream samples (p < 0.05). However, the freezing point decreased with increasing the proportion of BRP in the blend. The sensory evaluation results showed that the most acceptable treatments were those formulated with 25% and could be increased to 50% of BRP with no significant differences. The incorporation of BRP improved the viability of Lactobacillus acidophilus LA-5 in ice cream samples over 60 days of storage. Collectively, a synbiotic camel milk ice cream formulated with black rice powder was produced that, in turn, enhanced the physicochemical and rheological properties of ice cream samples and produced a significant protective effect on the viability of probiotic bacteria.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Newcastle disease virus (NDV) remains a constant threat to the poultry industry. There is scarce information concerning the pathogenicity and genetic characteristics of the circulating velogenic Newcastle disease virus (NDV) in Egypt. In the present work, NDV was screened from tracheal swabs collected from several broiler chicken farms (N = 12) in Dakahlia Governorate, Egypt. Real-time reverse transcriptase polymerase chain reaction (RRT-PCR) was used for screening of velogenic and mesogenic NDV strains through targeting F gene fragment amplification, followed by sequencing of the resulting PCR products. The identified strain, namely, NDV-CH-EGYPT-F42-DAKAHLIA-2019, was isolated and titrated in the allantoic cavity of 10 day old specific pathogen-free (SPF) embryonated chicken eggs (ECEs), and then their virulence was determined by mean death time (MDT) and intracerebral pathogenicity index (ICPI). The pathogenicity of the identified velogenic NDV strain was also assessed in 28 day old chickens using different inoculation routes as follows: intraocular, choanal slit, intranasal routes, and a combination of both intranasal and intraocular routes. In addition, sera were collected 5 and 10 days post inoculation (pi) for the detection of NDV antibodies by hemagglutination inhibition test (HI), and tissue samples from different organs were collected for histopathological and immunohistochemical examination. A series of different clinical signs and postmortem lesions were recorded with the various routes. Interestingly, histopathology and immunohistochemistry for NDV nucleoprotein displayed widespread systemic distribution. The intensity of viral nucleoprotein immunolabeling was detected within different cells including the epithelial and endothelium lining, as well as macrophages. The onset, distribution, and severity of the observed lesions were remarkably different between various inoculation routes. Collectively, a time-course comparative pathogenesis study of NDV infection demonstrated the role of different routes in the pathogenicity of NDV. The intranasal challenge was associated with a prominent increase in NDV lesions, whereas the choanal slit route was the route least accompanied by severe NDV pathological findings. Clearly, the present findings might be helpful for implementation of proper vaccination strategies against NDV.

Colon illnesses, particularly ulcerative colitis, are considered a major cause of death in both men and women around the world. The present study investigated the underlying molecular mechanisms for the potential anti-inflammatory effect of Dapagliflozin (DAPA) against ulcerative colitis (UC) induced by intracolonic instillation of 3% v/v acetic acid (AA). DAPA was administered to rats (1 mg/kg, orally) for two weeks during the treatment regimen. Interestingly, compared to the normal group, a marked increase in the index of colon/body weight, colon weight/colon length ratio, serum lactate dehydrogenase (LDH), and C-reactive protein (CRP), besides decrease in the serum total antioxidant capacity (TAC), were reported in the AA control group (p ˂ 0.05). Elevation in colon monocyte chemoattractant protein (MCP1), Interleukin 18 (IL-18), and inflammasome contents were also reported in the AA control group in comparison with the normal group. In addition, colon-specimen immunohistochemical staining revealed increased expression of nuclear factor-kappa B (NF-κB) and Caspase-3 with histopathological changes. Moreover, DAPA significantly (p ˂ 0.05) reduced the colon/body weight index, colon weight/colon length ratio, clinical evaluation, and macroscopic scoring of UC, and preserved the histopathological architecture of tissues. The inflammatory biomarkers, including colon MCP1, IL-18, inflammasome, Caspase-3, and NF-κB, were suppressed following DAPA treatment and oxidants/antioxidants hemostasis was also restored. Collectively, the present data demonstrate that DAPA represents an attractive approach to ameliorating ulcerative colitis through inhibiting MCP1/NF-κB/IL-18 pathways, thus preserving colon function. Antioxidant, anti-inflammatory, and anti-apoptotic properties of DAPA are implicated in its observed therapeutic benefits.

Well-differentiated thyroid cancer (WDTC) is a malignant head and neck tumor with a very high incidence. Thyroidectomized WDTC patients have been referred to nuclear medicine for radioactive iodine (RAI) ablation therapy and/or annual follow-up with diagnostic whole-body imaging. Serum thyroglobulin (TG) and thyroglobulin antibodies (TGAb) are biochemical tumor markers used to monitor WDTC. A global rise in the prevalence of WDTC is increasing the number of thyroidectomized patients requiring lifelong monitoring for persistent or recurrent diseases. The present study aimed to identify the most successful prognostic factors in well-defined thyroid carcinoma patients following total thyroidectomy and RAI therapy, followed by an estimation of the cutoff value of TG and TGAb. In this context, a total of 100 subjects were recruited and classified as follows: 60 thyroid carcinoma patients underwent total thyroidectomy and successful RAI therapy, while 40 normal healthy individuals matched for age, sex, and socioeconomic status constituted the control group. Interestingly, the levels of TG did not differ significantly between the relapsed and non-relapsed cases, but the levels of TGAb differed significantly between the relapsed and non-relapsed cases. Collectively, TG and TGAb are considered the most successful prognostic factors in well-defined thyroid carcinoma patients after total thyroidectomy and RAI therapy. The present study also concluded that the TGAb determination was better than that of the TG level, with a cutoff value of 10 ng/mL. These findings provide baseline information for follow-up and lifelong monitoring of thyroidectomized WDTC patients. Further research is warranted to explore more about serum TG and TGAb in thyroid carcinoma patients on a larger scale.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used postoperative analgesics, antipyretics, and anti-inflammatories, and they help prevent blood clotting. However, most NSAIDs delay bone healing. This study was aimed to investigate bone healing in a rabbit animal model by assessing the ability of flunixin meglumine (FM) and ketoprofen to induce fracture healing by examining histology, radiological changes, and vascular endothelial growth factor (VEGF) immunostaining during bone healing. For this purpose, 24 New Zealand rabbits were assigned to three groups: the control group, the FM group, and the ketoprofen group. Our results revealed that there were no intraoperative complications, and all surviving rabbits achieved full-weight bearing. Significant periosteal reaction and callus formation were confirmed at 2 postoperative weeks. Interestingly, FM enhanced callus formation, bone union, and remodeling in the FM group compared to the control and ketoprofen groups. FM enhanced bone healing through early collagen deposition and marked angiogenesis process activation by increasing the expression of VEGF. Our findings demonstrated, for the first time, the potential imperative action of FM in the bone healing process rather than other NSAIDs in animals.

Doxorubicin (DOX; Adricin) is an anthracycline antibiotic, which is an efficient anticancer chemotherapeutic agent that targets many types of adult and pediatric tumors, such as breast cancer, leukemia, and lymphomas. However, use of DOX is limited due to its cardiotoxic effects. This study sequentially investigated the mechanistic pathways of the cardiotoxic process of DOX in rats at different post-treatment periods using cumulative dose, which is used in therapeutic regimes. In this regard, 56 male albino rats were used for the experiment. The experimental animals were divided into seven groups (n = 8/group) based on dose and sacrifice schedule as follows: G1 (2 mg/kg body weight [BW] and sacrificed at day 4), G2 (4 mg/kg BW and sacrificed at day 8), G3 (6 mg/kg BW and sacrificed at day 15), G4 (8 mg/kg BW and sacrificed at day 30), G5 (10 mg/kg BW and sacrificed at day 60), G6 (10 mg/kg BW and sacrificed at day 90), and G7 (10 mg/kg BW and sacrificed at day 120). As expected, G1, G2, and G3-treated groups revealed features of acute toxic myocarditis associated with degenerative and necrotic changes in myocytes, mitochondrial damage, elevation of cardiac biomarkers, and depletion of cellular antioxidant enzymes. However, these changes increased in severity with subsequent treatment with the same dose until reaching a cumulative dose of 10 mg/kg BW for 30 d. Furthermore, after a cumulative dose of 10 mg/kg BW with a withdrawal period of 2–3 months, various predominant changes in chronicity were reported, such as disorganization and atrophy of myocytes, condensation and atrophy of mitochondria, degranulation of mast cells, and fibrosis with occasional focal necrosis, indicating incomplete elimination of DOX and/or its metabolites. Altogether, these data provide interesting observations associated with the cardiotoxic process of DOX in rats that would help understand the accompanying changes underlying the major toxic effects of the drug. Future research is suggested to explore more about the dose-dependent mechanisms of such induced toxicity of DOX that would help determine the proper doses and understand the resulting cardiomyopathy.

Hepatocellular carcinoma (HCC) is the most common cancer in humans. Despite advances in its treatment, liver cancer remains one of the most difficult cancers to treat. This study aimed to investigate the ameliorative action and potential mechanism of Aspergillus awamori (ASP) administration against the initiation process of liver carcinogenesis induced by diethylnitrosamine (DEN) in male Wistar rats. Seventy-two male rats were divided equally into eight groups as follows, Group 1: untreated control; Group 2: DEN (200 mg/kg bw) intra-peritoneally for the initiation of HCC; Groups 3–5: DEN + ASP at a dose of 1, 0.5, and 0.25 mg/kg bw and groups 6–8: ASP at a dose of 1, 0.5, and 0.25 mg/kg bw. Supplementation of A. awamori significantly lightened the adverse impacts induced by DEN via restoring the leukogram to normal, lowering the elevated serum aspartate aminotransferase (AST), alanine transaminase (ALT), and γ-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Furthermore, it enhanced the hepatic antioxidant capacity through increasing the reduced glutathione (GSH) level and catalase (CAT) activity with a marked reduction in malondialdehyde (MDA) level. In addition, it decreased the positive GST-P foci. Likewise, a significant alteration of DEN-associated hepatocarcinogenesis occurred through inhibiting cytochrome P450 (Cyp19) and activating p53 gene expression. In conclusion, supplementation of A. awamori counteracts the negative effects of DEN, inhibits the early development of GST-P-positive foci and could be used as a new alternative strategy for its chemo-preventive effect in liver cancer. To the best of our knowledge, the present study is the first to report the hepato-protective effect of A. awamori in induced hepatocarcinogenesis.

The current experiment was randomly designed in a 2×2 factorial design. Two dietary protein sources were utilized; fish meal and soybean meal; with betaine incorporation to both of them. This study aimed to determine the impact of incorporation of betaine into soybean meal-based (SBM) diets through its effects on growth performance, intestinal healthiness and expression of some lipid metabolism- and growth-related genes. Fish (19.84±0.20 g) were stocked in 12 aquaria and allotted into triplicate four groups (10 fish per aquarium). Four test diets were formulated to contain fish meal (FM) as a positive control, FM with betaine (FM + Betaine), SBM diet and SBM with betaine (SBM + Betaine), respectively. After 60 days, dietary betaine improved the growth performance of fish fed FM or SBM as revealed by higher final body weight, body weight gain and average daily gain and lower feed conversion ratio. Monitoring the whole-body composition revealed that addition of betaine to diet relatively augmented flesh protein content and reduced its fat content. In addition, betaine incorporation in diets significantly (P

Newcastle disease (ND) is considered to be one of the most economically significant avian viral diseases. It has a worldwide distribution and a continuous diversity of genotypes. Despite its limited zoonotic potential, Newcastle disease virus (NDV) outbreaks in Egypt occur frequently and result in serious economic losses in the poultry industry. In this study, we investigated and characterized NDV in wild cattle egrets and house sparrows. Fifty cattle egrets and fifty house sparrows were collected from the vicinity of chicken farms in Kafrelsheikh Governorate, Egypt, which has a history of NDV infection. Lung, spleen, and brain tissue samples were pooled from each bird and screened for NDV by real-time reverse transcriptase polymerase chain reaction (RRT-PCR) and reverse transcriptase polymerase chain reaction (RT-PCR) to amplify the 370 bp NDV F gene fragment. NDV was detected by RRT-PCR in 22 of 50 (44%) cattle egrets and 13 of 50 (26%) house sparrows, while the conventional RT-PCR detected NDV in 18 of 50 (36%) cattle egrets and 10 of 50 (20%) of house sparrows. Phylogenic analysis revealed that the NDV strains identified in the present study are closely related to other Egyptian class II, sub-genotype VII.1.1 NDV strains from GenBank, having 99.7–98.5% identity. The pathogenicity of the wild-bird-origin NDV sub-genotype VII.1.1 NDV strains were assessed by experimental inoculation of identified strains (KFS-Motobas-2, KFS-Elhamoul-1, and KFS-Elhamoul-3) in 28-day-old specific-pathogen-free (SPF) Cobb chickens. The clinical signs and post-mortem changes of velogenic NDV genotype VII (GVII) were observed in inoculated chickens 3 to 7 days post-inoculation, with 67.5–70% mortality rates. NDV was detected in all NDV-inoculated chickens by RRT-PCR and RT-PCR at 3, 7, and 10 days post-inoculation. The histopathological findings of the experimentally infected chickens showed marked pulmonary congestion and pneumonia associated with complete bronchial stenosis. The spleen showed histocytic cell proliferation with marked lymphoid depletion, while the brain had malacia and diffuse gliosis. These findings provide interesting data about the characterization of NDV in wild birds from Egypt and add to our understanding of their possible role in the transmission dynamics of the disease in Egypt. Further research is needed to explore the role of other species of wild birds in the epidemiology of this disease and to compare the strains circulating in wild birds with those found in poultry.

We have previously reported that the leaf extract of Albizia anthelmintica exhibited substantial antioxidant, anti-inflammatory, analgesic, and antipyretic properties in vivo. We also comprehensively characterized the active phytoconstituents and found several flavonoids and galloyl glucosides derivatives. In the current work, we explored the gastroprotective effects of the leaf extract in an indomethacin-induced ulcer model and the mechanisms involved. The rats being pretreated with the tested extract (100 and 200 mg kg−1) significantly prevented gastric lesions by 87.4% and 92.3%, respectively, and they had no structural derangements in the gastric mucosa. The extract significantly reduced the elevated levels of IKκB, NF-κB, TNF-α, IL-6, iNOS, and lipid peroxidation; increased the reduced level of glutathione peroxidase (GPx) activity; and reduced glutathione (GSH) in the indomethacin-induced ulcer model. The protective activities of the extract were similar in most aspects to those exerted by the known anti-ulcer drug famotidine. These activities might be attributed to the anti-inflammatory and antioxidant activities, and the reduction of iNOS levels. In conclusion, Albizia anthelmintica is a potential candidate for management of gastric ulcers with antioxidant properties.

Cryptosporidiosis has been proposed to be one of the major causes of diarrhoeal disease in humans worldwide that possesses zoonotic concern. Thereby, this study investigated the potential effects of s-Methylcysteine (SMC) on the parasite in vivo followed by the measurement of cytokines, oxidative stress parameters, and an investigation of the major histopathological changes. Sixty male Swiss albino mice weighing 20–25 g were allocated equally into five groups and orally administered saline only (control), SMC only (SMC50) (50 mg/kg b.w.), and 104Cryptosporidium parvum oocysts per mouse via an esophageal tube (C + ve untreated). The fourth and fifth groups (C + SMC25, C + SMC50) administrated 104C. parvum oocysts combined with SMC25 (low dose) and 50 (high dose) mg/kg b.w., respectively. At days 7 and 14 post-infection (PI), the feces was collected from each group in order to count C. parvum oocysts. After two weeks of treatment, the animals were euthanized and the serum was collected for biochemical analysis. Next, the intestinal, spleen, and liver sections were dissected for histopathological examination. The results revealed lower oocyst numbers in the C + SMC25 and C + SMC50 groups compared to the infected untreated group. Moreover, higher doses of SMC treatment significantly reduced the enteritis induced by C. parvum in a dose-dependent manner. The hepatic lesions were also mitigated as demonstrated in C + SMC25 and C + SMC50 groups unlike the infected group via lowering the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) enzymes and increasing albumin and globulin serum levels. SMC administration also reduced cytokines production (SAP, TNF-α, IL-6, and IFN-γ) mediated by Cryptosporidium infection in contrast to the infected untreated group. There were marked lymphoid depletion and amyloidosis observed in the infected untreated group, while the treated groups showed obvious increase in the lymphoid elements. Moreover, the scoring of intestinal parasites, hepatic, and splenic lesions in the SMC-treated groups exhibited significantly lower pathological lesions in different organs in a dose-dependent manner, compared to the infected untreated group. Our results also revealed a significant change in the malondialdehyde content with an elevation of glutathione and superoxide dismutase in the intestines collected from C + SMC25 and C + SMC50 mice relative to the untreated group. Taken together, our results indicated that SMC could be a promising effective compound for treating and declining C. parvum infestation via restoring structural alterations in different tissues, enhancing antioxidant enzymes, and suppressing the cytokines liberation.

This study aimed to follow the time-course pathogenesis of EHV-9 abortion in early and late trimesters. Twenty-seven pregnant hamster dams were divided into three groups: (G1) control, (G2) EHV-9-inoculated on the 5th day (early trimester), and (G3) EHV-9-inoculated on the 10th day of gestation (late trimester). Dams were sacrificed at different time points during gestation and examined for viremia and viral DNA in different fetal and maternal tissues and pathological changes in fetal tissue, placenta, and cytokines. Animals in G3 showed a marked increase in the number of dead fetuses than those in G2. Histopathological findings of G2 showed early band coagulative necrosis of maternal spaces and stromal decidual cells. Necrotic changes were observed within the decidua basalis, spongiotrophoblast layer, and labyrinth. First, the virus was localized within mononuclear leukocytes in the decidua capsularis and basalis, and within the necrotic chorionic villi and cervical epithelium. G3 demonstrated degenerative changes within the chorionic villi and trophospongium. The virus antigen was observed within the chorionic villi, trophoblasts, mononuclear cells, and fetal tissues. In conclusion, EHV-9 induced abortion mostly occurs through necrosis of the chorionic villi and cannot cross through the capsular placenta in the early trimester but can through the developed decidual placentation.

Hepatocellular carcinoma (HCC) is the most common hepatobiliary malignancy with limited therapeutic options. On the other hand, melatonin is an indoleamine that modulates a variety of potential therapeutic effects. In addition to its important role in the regulation of sleep–wake rhythms, several previous studies linked the biologic effects of melatonin to various substantial endocrine, neural, immune and antioxidant functions, among others. Furthermore, the effects of melatonin could be influenced through receptor dependent and receptor independent manner. Among the other numerous physiological and therapeutic effects of melatonin, controlling the survival and differentiation of mesenchymal stem cells (MSCs) has been recently discussed. Given its controversial interaction, several previous reports revealed the therapeutic potential of MSCs in controlling the hepatocellular carcinoma (HCC). Taken together, the intention of the present review is to highlight the effects of melatonin and mesenchymal stem cells as a key for functional integrity for liver cancer treatment. We hope to provide solid piece of information that may be helpful in designing novel drug targets to control HCC.

Testes of seasonally breeding species experience a severe functional regression before the non-breeding period, which implies a substantial mass reduction due to massive germ-cell depletion. Two alternative mechanisms of seasonal germ-cell depletion have been described in mammals, apoptosis and desquamation (sloughing), but their prevalence has not been determined yet due to reduced number of species studied. We performed a morphological, hormonal, and molecular study of the mechanism of seasonal testicular regression in males of the Egyptian long eared-hedgehog (Hemiechinus auritus). Our results show that live, non-apoptotic, germ cells are massively depleted by desquamation during the testis regression process. This is concomitant with both decreased levels of serum testosterone and irregular distribution of the cell-adhesion molecules in the seminiferous epithelium. The inactive testes maintain some meiotic activity as meiosis onset is not halted and spermatocytes die by apoptosis at the pachytene stage. Our data support the notion that apoptosis is not the major testis regression effector in mammals. Instead, desquamation appears to be a common mechanism in this class.

Objective: To investigate the in vitro anticancer effect of Aloe vera (A. vera) and Calligonum comosum (C. comosum) extracts against hepatocellular carcinoma (HepG2) cells. Methods: HepG2 cells were tested against different doses of A. vera and C. comosum. Viability of the cells was assessed by MTT assay. Evaluation of apoptosis and DNA damage in HepG2 cells were performed using annexin V apoptosis detection kit. The expression of p53 and anti-apoptotic (Bcl-2) were tested by real time-PCR and flow cytometer analyser. Hematoxylin and eosin stained sections from untreated and treated HepG2 cells were observed using light microscopy. Results: The IC50 values of A. vera and C. comosum extracts were (10.45 ± 0.31) and (9.60 ± 0.01) µg/mL respectively. The extracts separately increased cytotoxicity against HepG2 cells in a time and dose dependent manners. Also, it apparently induced apoptosis through increase P53 and decrease Bcl-2 genes expressions. Conclusions: The results indicated that the extracts could have anti-hepatocarcinogenic effect, at least in part, through modulation of apoptosis.

Paratanaisia spp. was recorded from the right kidney of a cattle egret (Bubulcus ibis) in Kafr Elsheikh governorate, Nile Delta, Egypt. The bird showed marked emaciation and dissipation. Necropsy findings revealed marked enlargement and brownish discoloration of the kidney. Microscopic examination demonstrated marked dilatation of renal tubules with hyperplasia of lining epithelium due to presence of a trematode consistent withParatanaisia spp. Eggs of this parasite were also noticed deeply within the interstitial tissue, surrounded with mononuclear cell infiltration, thus indicating their pathogenic potential. This result is the first report of trematodes of this genus parasitizing the kidneys of cattle egrets.