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BACKGROUND: Heterakis gallinarum (H. gallinarum) is a common poultry parasite that can be found in the ceca of many gallinaceous bird species, causing minor pathology and reduced weight gain. Most infections go unnoticed in commercial flocks due to the dependence on fecal egg counts, which are prone to false-negative diagnoses. Furthermore, there is a lack of research on gastrointestinal nematodes that use molecular identification methods, which could be essential for rapid diagnosis and developing efficient control approaches. As a result, the study aimed to look at the cause of mortality in layer chickens induced by H. gallinarum in Egyptian poultry farms using morphological, ultrastructural, and molecular characterization. Histopathological, immunohistochemical, and cell-mediated immune responses from damaged cecal tissues were also examined. RESULTS: Seventy bird samples from ten-layer flocks of different breeds (Native, white, and brown layers) suffering from diarrhea, decreased egg output, and emaciation were collected. Cecal samples were collected from affected and non-affected birds and were examined for parasitic diseases using light and a scanning electron microscope. The mitochondrial cytochrome oxidase 1 (COX1) gene was used to characterize H. gallinarum. Our results showed that the collected nematodal worms were identified as H. gallinarum (male and female), further confirmed by COX1 gene amplification and sequence alignment. Gene expression analysis of the inflammatory markers in infected tissues showed a significant up-regulation of IL-2, IFN-γ, TLR-4, and IL-1ß and a significant down-regulation of the anti-inflammatory IL-10. The mRNA level of the apoptotic cas-3 revealed apoptotic activity among the H. gallinarum samples compared to the control group. CONCLUSIONS: Our results implemented the use of molecular methods for the diagnosis of Heterakis, and this is the first report showing the tissue immune response following infection in layers: upregulation of IL-1ß, IFN-γ, Il-2, and TLR-4, while down-regulation of anti-inflammatory IL-10 in cecal tissue, Cas-3 apoptotic activity and Nuclear factor-κB (NF-κB)activity with immunophenotyping of T-cells in Heterakis infected tissue.
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Ciego , Pollos , Enfermedades de las Aves de Corral , Tiflitis , Animales , Enfermedades de las Aves de Corral/parasitología , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/patología , Tiflitis/veterinaria , Tiflitis/parasitología , Tiflitis/patología , Ciego/parasitología , Ciego/patología , Femenino , Inmunidad Celular , Infecciones por Ascaridida/veterinaria , Infecciones por Ascaridida/parasitología , Ascaridoidea , EgiptoRESUMEN
Novel goose parvovirus (NGPV) is continuously threatening the global duck industry, as it causes short beak and dwarfism syndrome among different duck breeds. In this study, we investigated the viral pathogenesis in the tongue of affected ducks, as a new approach for deeper understanding of the syndrome. Seventy-three, 14- to 60-day-old commercial Pekin ducks were clinically examined. Thirty tissue pools of intestine and tongue (15 per tissue) were submitted for molecular identification. Clinical signs in the examined ducks were suggestive of parvovirus infection. All examined ducks had short beaks. Necrotic, swollen, and congested protruding tongues were recorded in adult ducks (37/73, 51%). Tongue protrusion without any marked congestion or swelling was observed in 20-day-old ducklings (13/73, 18%), and no tongue protrusion was observed in 15-day-old ducklings (23/73, 32%). Microscopically, the protruding tongues of adult ducks showed necrosis of the superficial epithelial layer with vacuolar degeneration. Glossitis was present in the nonprotruding tongues of young ducks, which was characterized by multifocal lymphoplasmacytic aggregates and edema in the propria submucosa. Immunohistochemical examination displayed parvovirus immunolabeling, mainly in the tongue propria submucosa. Based on polymerase chain reaction, goose parvovirus was detected in 9 out of 15 tongue sample pools (60%). Next-generation sequencing confirmed the presence of a variant goose parvovirus that is globally named NGPV and closely related to Chinese NGPV isolates. Novel insights are being gained from the study of NGPV pathogenesis in the tongue based on molecular and immunohistochemical identification.
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[This corrects the article DOI: 10.1007/s12639-023-01637-z.].
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Complications of parasite infections, especially kidney disease, have been linked to poorer outcomes. Acute kidney damage, glomerulonephritis, and tubular dysfunction are the most prevalent renal consequences of Parascaris equorum infection. The purpose of this study was to determine the pharmacological effects of green-produced zinc oxide nanoparticles (ZnO NPs) on P. equorum infection in male Wistar rats. Thirty-six male rats were divided into two groups of 18 each: infected and non-infected. Both groups were separated into three subgroups, each of which received distilled water, 30 mg/kg ZnO NPs, and 60 mg/kg ZnO NPs. After 10 days of ZnO NPs administration, four larvae per gram of kidney tissue were present in the untreated infected group. While, no larvae were present in ZnO NPs (30 mg/kg) treated group, and one larva/g.tissue was present in ZnO NPs (60 mg/kg) treated group compared to untreated infected animals. P. equorum infected rats had increased kidney biomarkers (creatinine, urea, uric acid), malondialdehyde, and nitric oxide, with a significant decrease in their antioxidant systems. On the other hand, infected treated rats with green-produced zinc oxide nanoparticles had a substantial drop in creatinine, urea, uric acid, malondialdehyde, and nitric oxide, as well as a significant rise in their antioxidant systems. P. equorum infection in rats caused severe degenerative and necrotic renal tissues. On the other hand, there were no detectable histopathological alterations in rats treated with ZnO NPs (30, 60 mg/kg) as compared to the infected untreated animals. When compared to infected untreated mice, immunohistochemical examination of nuclear factor-kappa B showed a significant decrease during treatment with ZnO NPs (30, 60 mg/kg). Green-produced zinc oxide nanoparticles are a viable therapeutic strategy for Parascaris equorum infection due to their potent anthelmintic activity, including a significant decrease in larval burden in infected treated rats.
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Rheumatoid arthritis (RA) is a joint-destructive autoimmune disease that severely affects joint function. Despite the variability of treatment protocols, all of them are associated with severe side effects that compromise patient compliance. The main aim of the current study is to prepare localized effective RA treatment with reduced side effects by combining nanoencapsulation, photodynamic therapy (PDT) and hollow microneedles (Ho-MNs) to maximize the pharmacological effects of hypericin (HYP). To attain this, HYP-loaded emulsomes (EMLs) were prepared, characterized and administered through intradermal injection using AdminPen™ Ho-MNs combined with PDT in rats with an adjuvant-induced RA model. The prepared EMLs had a spherical shape and particle size was about 93.46 nm with an absolute entrapment efficiency. Moreover, confocal imaging indicated the interesting capability of Ho-MNs to deposit the HYP EMLs to a depth reaching 1560 µm into the subcutaneous tissue. In vivo, study results demonstrated that the group treated with HYP EMLs through Ho-MNs combined with PDT had no significant differences in joint diameter, TNF-α, IL1, HO-1, NRF2 and SD levels compared with the negative control group. Similarly, rats treated with the combination of HYP EMLs, Ho-MNs and PDT showed superior joint healing efficacy compared with the groups treated with HYP EMLs in dark, HYP ointment or HYP in microneedles in histopathological examination. These findings highlight the promising potential of photoactivated HYP EMLs when combined with Ho-MNs technology for RA management. The presented therapeutic EMLs-MNs platform could serve as a powerful game-changer in the development of future localized RA treatments.
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Artritis Reumatoide , Perileno/análogos & derivados , Fotoquimioterapia , Humanos , Ratas , Animales , Fotoquimioterapia/métodos , Antracenos , Artritis Reumatoide/tratamiento farmacológico , Fármacos FotosensibilizantesRESUMEN
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-1ß, 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.
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Coccidiosis , Coinfección , Eimeria , Parásitos , Enfermedades de las Aves de Corral , Animales , Coccidiosis/epidemiología , Coccidiosis/veterinaria , Coccidiosis/parasitología , Pollos/parasitología , Coinfección/epidemiología , Coinfección/veterinaria , Enfermedades de las Aves de Corral/parasitología , Óvulo , Eimeria/genéticaRESUMEN
Background: Hemolytic anemia (HA) is a serious health condition resulting from reduced erythrocytes' average life span. Echinochrome (Ech) is a dark-red pigment found in shells and spines of sea urchins. Aim: Studying the potential therapeutic effect of Ech on phenylhydrazine (PHZ)-induced HA in rats. Methods: Eighteen rats were divided into three groups (n = 6): the control group, the phenylhydrazine-induced HA group and the Ech group, injected intraperitoneally with PHZ and supplemented with oral Ech daily for 6 days. Results: Ech resulted in a considerable increase in RBCs, WBCs, and platelets counts, hemoglobin, reduced glutathione, catalase, and glutathione-S-transferase levels, and a significant decrease in aspartate & alanine aminotransferases, alkaline phosphatase, gamma-glutamyl transferase, bilirubin, creatinine, urea, urate, malondialdehyde & nitric oxide levels in anemic rats. Histopathological examination of liver and kidney tissue samples showed marked improvement. Conclusion: Ech ameliorated phenylhydrazine-induced HA with a hepatorenal protective effect owing to its anti-inflammatory and antioxidant properties.
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Anemia Hemolítica , Estrés Oxidativo , Ratas , Animales , Antioxidantes/farmacología , Anemia Hemolítica/inducido químicamente , gamma-Glutamiltransferasa/farmacología , Glutatión Transferasa/efectos adversos , Fenilhidrazinas/efectos adversosRESUMEN
MAIN CONCLUSIONS: Green-synthesized zinc oxide nanoparticle is a promising treatment modality against parasitic infection through its powerful anthelmintic, antioxidant, healing promotion, and anti-inflammation effects. BACKGROUND: Nanoparticles have many properties, depending on their size, shape, and morphology, allowing them to interact with microorganisms, plants, and animals. OBJECTIVES: Investigation of the therapeutic effects of green-synthesized zinc oxide nanoparticles (ZnO NPs) on Parascaris equorum infection in rats. METHODS: Thirty-six rats were divided into two divisions: the first division is noninfected groups were allocated into three groups. Group 1: Control, group 2: ZnO NPs (30 mg/kg), and group 3: ZnO NPs (60 mg/kg). The second division is infected groups were allocated into three groups. Group 1: vehicle, group 2: ZnO NPs (30 mg/kg), and group 3: ZnO NPs (60 mg/kg). FINDINGS: Ten days post-infection, two larvae per gram of liver tissue were present in the vehicle group compared to the control group. No larvae were recovered from ZnO NPs (30 mg/kg), and one larva/g.tissue from ZnO NPs (60 mg/kg)-treated groups compared to untreated infected animals. Green-synthesized ZnO NPs caused a significant decrease in liver functions, low-density lipoprotein (LDL), cholesterol, triglycerides, malondialdehyde (MDA), and nitric oxide (NO). While it caused a significant increase in hemoglobin (HB), high-density lipoprotein (HDL), butyrylcholinesterase (BCHE), glutathione (GSH), catalase (CAT), and glutathione S-transferase (GST) in infected treated rats. The histological inflammation and fibroplasia scores showed a significant enhancement during the treatment with ZnO NPs (30, 60 mg/kg) compared to the infected untreated animals that scored the highest pathological destruction score. Immunohistochemical markers of NF-κB showed a significant decrease during the treatment with ZnO NPs (30, 60 mg/kg) compared to the infected untreated animals.
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This study investigated the effect of oral dosing of titanium dioxide nanoparticles (TNPs) and cadmium (Cd2+) on rat liver and the potential protective role of coenzyme Q10 (CQ10) against TNPs and Cd2+-induced hepatic injury. Seventy male Sprague Dawley rats were divided into seven groups and orally given distilled water, corn oil, CQ10 (10 mg/kg b.wt), TNPs (50 mg/kg b.wt), Cd2+ (5 mg/kg b.wt), TNPs + Cd2+, or TNPs + Cd2++CQ10 by gastric gavage for 60 successive days. The results showed that individual or mutual exposure to TNPs and Cd2+ significantly increased the serum levels of various hepatic enzymes and lipids, depleted the hepatic content of antioxidant enzymes, and increased malondialdehyde. Moreover, the hepatic titanium and Cd2+ content were increased considerably in TNPs and/or Cd2+-exposed rats. Furthermore, marked histopathological perturbations with increased immunoexpression of tumor necrosis factor-alpha and nuclear factor kappa B were evident in TNPs and/or Cd2+-exposed rats. However, CQ10 significantly counteracted the damaging effect of combined exposure of TNPs and Cd2+ on the liver. The study concluded that TNPs and Cd2+ exposure harm hepatic function and its architecture, particularly at their mutual exposure, but CQ10 could be a candidate protective agent against TNPs and Cd2+ hepatotoxic impacts.
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Nanopartículas , Factor de Necrosis Tumoral alfa , Ratas , Masculino , Animales , Factor de Necrosis Tumoral alfa/metabolismo , FN-kappa B/metabolismo , Titanio/toxicidad , Cadmio/toxicidad , Cadmio/metabolismo , Estrés Oxidativo , Ratas Sprague-Dawley , Antioxidantes/farmacología , Antioxidantes/metabolismo , Hígado , Nanopartículas/toxicidadRESUMEN
BACKGROUND: Lead exposure results in a terrible rise in heat shock protein levels. OBJECTIVE: This research was conducted to look at the effects of lead poisoning on heat shock response, oxidative stress, and inflammatory markers in albino rats, as well as the power of selenium and vitamin E to resist lead toxic effects. METHODS: Eight groups of albino rats are used. Each group contained six rats where the first group represented the negative control, and the other groups were treated with olive oil, vitamin E, selenium, lead, (vitamin E + lead), (selenium + lead), and (vitamin E + selenium + lead). All the treatments lasted for 28 days. Then, the mRNA expression of interested heat shock proteins (HSP90, HSP70, and HSP60) was assessed. For oxidative stress disruption, we investigated nitric oxide (NO) and malondialdehyde (MDA) content, and enzymatic and non-enzymatic antioxidants activity respectively in rat livers. RESULTS: our results revealed the synergetic protective effect of the combination of two antioxidants (vitamin E and selenium) against lead poising. This was clear in regulating HSPs expression, inflammatory markers, glucose, lipid profile, liver functions, and antioxidant enzymes more than the treatment with one antioxidant. CONCLUSION: Pb is a toxic material that can induce HSPs and inflammatory markers expression. Selenium and vitamin E can give excellent effects in ameliorating Pb toxicity when used together.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Selenio , Ratas , Animales , Selenio/farmacología , Antioxidantes/farmacología , Antioxidantes/metabolismo , Vitamina E/farmacología , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/farmacología , FN-kappa B/metabolismo , Plomo/toxicidad , ARN Mensajero/genética , Estrés Oxidativo , Acetatos/farmacologíaRESUMEN
Many chemotherapeutic drugs cause adverse pulmonary reactions leading to severe pulmonary disease. Though methotrexate (MTX) is used for the treatment of cancer and other diseases, it is highly toxic with multiple adverse effects including pulmonary toxicity. Essential oils represent an open frontier for pharmaceutical sciences due to their wide range of pharmacological properties. Pumpkin seeds oil (PSO) was used to investigate its ability to alleviate methotrexate-induced lung toxicity in rats. Lung tissue from MTX-treated group revealed a decrease in malondialdehyde, glutathione, and nitric oxide accompanied by a marked inhibition in cholinesterase activity, and enhanced catalase activity, tumor necrosis factor-α, interleukin-6 and vascular endothelial growth factor levels. Analysis of PSO revealed that the oil was rich in hexadecanoic acid, decane methyl esters, squalene, polydecane, docosane, and other derivatives. Administration of PSO ameliorated the oxidant/antioxidant and proinflammatory changes induced by MTX in the lung tissue. Histological examinations confirmed the potency of PSO in reducing the histopathological alterations induced by MTX. Immunohistochemical analysis showed decreased nuclear factor-kappa B and caspase 3 expression after PSO. The present data indicated the protective efficiency of PSO against MTX-induced lung injury by decreasing oxidative damage, inflammation and apoptosis and could thus be recommended as an adjuvant therapy.
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Cucurbita , Metotrexato , Ratas , Animales , Metotrexato/toxicidad , Ratas Wistar , Factor A de Crecimiento Endotelial Vascular/farmacología , Antioxidantes/farmacología , Aceites de Plantas/farmacología , Aceites de Plantas/uso terapéutico , Estrés Oxidativo , PulmónRESUMEN
BACKGROUND: Multiple sclerosis (MS) is a progressive autoimmune demyelinating disease of the central nervous system. To date, there is no effective therapy for it. Our study aimed to determine the potential role of platelet-rich plasma (PRP) in the treatment of MS in cats. METHODS: The current study was conducted on 15 adult Persian cats that were divided into three groups: control negative, control positive (ethidium bromide (EB)-treated group), and PRP co-treated group (EB-treated group intrathecally injected with PRP on day 14 post-spinal cord injury). PRP was obtained by centrifuging blood on anticoagulant citrate dextrose and activating it with red and green laser diodes. The Basso-Beattie-Bresnahan (BBB) scores were used to assess the motor function recovery on days 1, 3, 7, 14, 20, and 28 following 14 days from EB injection. Moreover, magnetic resonance imaging (MRI) analysis, histopathological investigations, transmission electron microscopy (TEM) studies, and immunohistochemical analysis were conducted, and the gene expressions of nerve growth factors (NGFs), brain-derived neurotrophic factors (BDNF), and stromal cell-derived factors (SDF) were evaluated. RESULTS: Our results indicated that PRP had a significant ameliorative effect on the motor function of the hindlimbs as early as day 20 and so on. MRI revealed that the size and intensity of the lesion were significantly reduced in the PRP co-treated group. The histopathological and TEM investigations demonstrated that the PRP co-treated group had a significant improvement in the structure and organization of the white matter, as well as a high remyelination capacity. Furthermore, a significant increase in myelin basic protein and Olig2 immunoreactivity as well as a reduction in Bax and glial fibrillar acidic protein immune markers was observed. NGFs were found to be upregulated by gene expression. CONCLUSION: As a result, we concluded that the intrathecal injection of PRP was an effective, safe, and promising method for the treatment of MS.
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Inclusion body hepatitis (IBH) is an economically significant viral disease that primarily affects broiler chickens. At least 12 different aviadenovirus serotypes are responsible for causing IBH. This study aimed to use polymerase chain reaction (PCR) and phylogenetic analysis to characterize fowl adenovirus isolates that were in circulation from 2019 to 2021 and investigate the pathogenicity of the isolated strains in commercial broiler chickens. Suspected liver samples were molecularly identified using hexon gene targeting by PCR, and viruses were isolated using chick embryo liver cell culture. For serotype identification, the fowl adenovirus-positive samples were subjected to hexon gene sequencing and phylogenetic analysis. The pathogenicity of two isolates was tested in commercial chickens via the oral route. The phylogenetic analysis of the hexon gene showed that the isolated viruses clustered with serotype 8a species E. On testing the pathogenicity of the isolates based on necropsy and histopathological examination, no mortality was observed; however, lesions were observed in the liver, kidney, heart, pancreas, bursa, and lung specimens with intermittent virus shedding at different time points throughout the experimental period. Further research on the likelihood of vaccine production is warranted to limit disease-related losses.
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Infecciones por Adenoviridae , Aviadenovirus , Enfermedades de las Aves de Corral , Animales , Embrión de Pollo , Pollos , Serogrupo , Adenoviridae , Virulencia , Filogenia , Infecciones por Adenoviridae/veterinariaRESUMEN
Systemic rheumatoid arthritis treatment has been associated with numerous side effects. We attempted to formulate hyaluronic acid (HA)-coated teriflunomide (TER)-loaded nanostructured lipid carriers (NLCs) that can target inflamed rheumatic joints following oral administration. In vitro evaluation including colloidal characteristics, drug release and stability studies were conducted. Also, cytotoxicity studies on THP1 and peripheral blood mononuclear cells besides testing the binding of HA coated TER-NLCs to CD44 receptors were carried out. Furthermore, pharmacokinetics following oral administration, anti-arthritic effects, hepato and nephrotoxicity of NLCs were assessed. Selected NLCs formulation was approximately 284.9 ± 3.8 nm in size with 96.89 ± 0.45% entrapment efficiency and provided a sustained release for 30 days. NLCs showed good stability that was confirmed by TEM examination. Cell culture studies revealed that HA-coated TER- NLCs showed superior cytotoxicity and binding affinity to CD44 receptors compared with TER suspension. In vivo studies demonstrated the superiority of NLCs in increasing TER bioavailability, reducing TNF-α serum levels and improving joint healing that was evidenced in both histopathological and X-ray radiographic examination. This may be attributed to the ability of HA-coated TER-NLCs to target rheumatic joints passively and actively by targeting CD44 receptors that are overexpressed in rheumatic joints.
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Artritis Reumatoide , Nanoestructuras , Administración Oral , Artritis Reumatoide/tratamiento farmacológico , Crotonatos , Portadores de Fármacos , Humanos , Ácido Hialurónico/uso terapéutico , Hidroxibutiratos , Leucocitos Mononucleares , Lípidos , Nitrilos , Tamaño de la Partícula , ToluidinasRESUMEN
Age-related diseases, including dementia, are a major health concern affecting daily human life. Strawberry (Fragaria ananassa Duch.) is the most eaten fruit worldwide due to its exceptional aroma and flavor. However, it's rapid softening and decay limit its shelf-life. Freezing and boiling represent the well-known conservation methods to extend its shelf-life. Therefore, we aimed to discover the phytochemical content differences of fresh and processed strawberries associated with investigating and comparing their neuroprotective effects in a rat model of aging. Female Wistar rats were orally pretreated with fresh, boiled, and frozen F. ananassa methanolic extracts (250 mg kg-1) for 2 weeks, and then these extracts were concomitantly exposed to D-galactose [65 mg kg-1, subcutaneously (S/C)] and AlCl3 (200 mg kg-1, orally) for 6 weeks to develop aging-like symptoms. The results of UPLC/ESI-MS phytochemical profiling revealed 36 secondary metabolites, including phenolics, flavonoids, and their glycoside derivatives. Compared with boiled and frozen extracts, the fresh extract ameliorated the behavioral deficits including anxiety and cognitive dysfunction, upregulated brain HO-1 and Nrf2 levels, and markedly reduced caspase-3 and PPAR-γ levels. Moreover, LDH and miRNA-9, 124 and 132 protein expressions were reduced. The histological architecture of the brain hippocampus was restored and glial fibrillary acidic protein (GFAP) immunoexpression was downregulated. In conclusion, the fresh extract has neuroprotective activity that could have a promising role in ameliorating age-related neurodegeneration.
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Fragaria , Envejecimiento , Cloruro de Aluminio , Animales , Femenino , Fragaria/química , Frutas/química , Galactosa/efectos adversos , Galactosa/metabolismo , Humanos , Fenoles/análisis , Fitoquímicos/análisis , Extractos Vegetales/metabolismo , Ratas , Ratas WistarRESUMEN
Preparation and evaluation of a non-invasive intranasal luteolin delivery for the management of cognitive dysfunction in Alzheimer's disease (AD) using novel chitosan decorated nanoparticles. Development of luteolin-loaded chitosomes was followed by full in vitro characterization. In vivo efficacy was evaluated using a sporadic Alzheimer's disease (SAD) animal model via intracerebroventricular injection of 3 mg/kg streptozotocin (ICV-STZ). Treatment groups of luteolin suspension and chitosomes (50 mg/kg) were then intranasally administered after 5 h of ICV-STZ followed by everyday administration for 21 consecutive days. Behavioral, histological, immunohistochemical, and biochemical studies were conducted. Chitosomes yielded promising quality attributes in terms of particle size (PS) (412.8 ± 3.28 nm), polydispersity index (PDI) (0.378 ± 0.07), Zeta potential (ZP) (37.4 ± 2.13 mv), and percentage entrapment efficiency (EE%) (86.6 ± 2.05%). Behavioral findings showed obvious improvement in the acquisition of short-term and long-term spatial memory. Furthermore, histological evaluation revealed an increased neuronal survival rate with a reduction in the number of amyloid plaques. Biochemical results showed improved antioxidant effects and reduced pro-inflammatory mediators' levels. In addition, a suppression by half was observed in the levels of both Aß aggregation and hyperphosphorylated-tau protein in comparison to the model control group which in turn confirmed the capability of luteolin-loaded chitosomes (LUT-CHS) in attenuating the pathological changes of AD. The prepared nanoparticles are considered a promising safe, effective, and non-invasive nanodelivery system that improves cognitive function in SAD albino mice as opposed to luteolin suspension.
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OBJECTIVE: Berberine (BBR) is a known alkaloid that has verified its protective effects against ischemia/reperfusion (I/RN) lesion in multiple organs but its poor oral bioavailability limited its use. Despite the previous works, its possible impact on the warm hepatic I/RN-induced lesion is not clear. Accordingly, a nanostructured lipid carrier of BBR (NLC BBR) was developed for enhancing its efficiency and to inspect its protective mechanistic against warm hepatic I/RN. METHODS: NLC BBR formula was evaluated pharmaceutically. Wistar rats were orally pre-treated with either BBR or NLC BBR (100 mg/kg) for 2 weeks followed by hepatic I/RN (30 min/24 h). Biochemical, ELISA, qPCR, western blot, histopathological, and immunohistochemical studies were performed. KEY FINDINGS: Optimized NLC BBR was prepared with a particle size of 130 ± 8.3 nm. NLC BBR divulged its aptitude to safeguard the hepatic tissues partly due to anti-inflammatory capacity through downsizing the HMGB1/TLR4/NF-κB trajectory with concomitant rebating of TNF-α, iNOS, COX-2, and MPO content. Furthermore, NLC BBR antiapoptotic trait was confirmed by boosting the prosurvival protein (Bcl-2) and cutting down the pro-apoptotic marker (Bax). Moreover, its antioxidant nature was confirmed by TAC uplifting besides MDA subsiding. On the other hand, NLC BBR action embroiled autophagy flux spiking merit exemplified in Beclin-1 and LC3-II enhancement. Finally, NLC BBR administration ascertained its hepatocyte guarding action by recovering the histopathological ailment and diminishing serum transaminases. CONCLUSION: NLC BBR purveyed reasonable shielding mechanisms and subsided incidents contemporaneous to warm hepatic I/RN lesion in part, by moderating HMGB1/TLR4/NF-κB inï¬ammatory signaling, autophagy, and apoptosis.
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Berberina/farmacología , Hepatopatías/tratamiento farmacológico , Nanoestructuras , Daño por Reperfusión/tratamiento farmacológico , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Berberina/administración & dosificación , Portadores de Fármacos/química , Proteína HMGB1/metabolismo , Lípidos/química , Hepatopatías/patología , Masculino , FN-kappa B/metabolismo , Tamaño de la Partícula , Ratas , Ratas Wistar , Daño por Reperfusión/patología , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismoRESUMEN
This study aimed to develop propolis and tea tree oil nanoemulsion loaded with clindamycin hydrochloride to heal wound effectively. Nanoemulsion formulae were prepared and characterized by droplet size analysis, zeta potential, viscosity, ex-vivo permeation, and skin deposition. The optimal formula was evaluated in terms of morphology, cytotoxicity, and in-vitro wound healing assay. Also, the efficacy of the optimal formula was evaluated by in-vivo wound healing and histopathological studies. The optimal formula (F3) was composed of 9% tea tree oil and 0.4% propolis extracts with mean droplet size 19.42 ± 1.7 nm, zeta potential value -24.5 ± 0.2 mV, and viscosity 69.4 ± 1.8 mP. Furthermore, the optimal formula showed the highest skin deposition value 550.00 ± 4.9 µg/cm2 compared to other formulae. The TEM micrograph of the optimal formula showed that the nanoemulsion droplet has an almost spherical shape. Also, the optimal formula did not show noticeable toxicity to the human skin fibroblast cells. The in-vitro and in-vivo wound healing assay showed unexpected results that the un-loaded drug nanoemulsion formula had a comparable wound healing efficacy to the drug-loaded nanoemulsion formula. These results were confirmed with histopathological studies. Our results showed that the propolis and tea tree oil nanoemulsion, whether loaded or unloaded with an antibiotic, is an efficient local therapy for wound healing.
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The objective of this study was to improve effectiveness of resveratrol (RES) through brain targeting by the intranasal olfactory mucosa for the treatment Alzheimer's disease (AD). To attain this, chitosan coated bilosomes (non ionic surfactant vesicles stabilized by bile salts, loaded with RES and superparamagnetic iron oxide nanoparticles (SPIONs) were prepared and incorporated into sodium alginate/PVP wafers. In vitro characterization of bilosomes including colloidal characteristics, entrapment efficiency and in vitro release was carried out. Hydration capacity, porosity percentage, morphology and in vitro release for selected wafer formulation were also investigated. Particle size of selected bilosomes, CS coated bilosome and SPION bilosomes was 208, 238 and 243 nm, respectively and they provided sustained RES release for 24 h. Both formulations were loaded in wafers and intra-nasally administered in mice with lipopolysaccharide induced AD model. Neurobehavioral tests, AD markers analysis, RT-PCR, western blotting and histopathological evaluation of the dissected brains were carried out. Results revealed the superiority of SPION bilosomes over conventional bilosomes and RES suspension in improving cognitive and memory functions, reduction of pro-inflammatory markers levels and down regulation of expression of NF-κB and P38. This may be attributed to enhanced RES therapeutic effects upon nanoencapsulation, loading into wafers, nasal administration and enhanced targeting the application of an external magnetic field.
Asunto(s)
Quitosano , Animales , Encéfalo , Compuestos Férricos , Liposomas , Nanopartículas Magnéticas de Óxido de Hierro , Fenómenos Magnéticos , Ratones , ResveratrolRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Jasminum grandiflorum L. is a medicinal plant widely used in the traditional system of Medicine as an anthelmintic in ringworm infections, for treating ulcers, stomatitis, skin diseases, and wounds. AIM OF THE STUDY: The emergence of resistance by different parasites to currently used chemicals has been reported. There are increasing needs for more effective and safer parasiticides. Therefore, the current study was designed to investigate the methanolic extract of the aerial parts of J. grandiflorum subsp. Floribundum (JGTE) to confirm its traditional uses as anthelmintic through a bioassay-guided fractionation and isolation of the active components with anthelmintic activity. MATERIALS AND METHODS: The JGTE was partitioned into dichloromethane (DCM-F) and n-butanol (BuOH-F) fractions. The JGTE, fractions, and the isolated compounds were tested in vitro for their anthelmintic activity using two nematodes; one larval stage of cestode and one arthropod. Four major compounds were isolated from the most active fraction (BuOH-F) including two flavonoids and two secoirridoid glycosides, identified as kaempferol-3-O-neohesperoside (1), rutin (2), oleuropein (3), and ligstroside (4). RESULTS: Among the isolated compounds from most active fraction (BuOH-F), rutin (2) displayed the highest anthelmintic activity in a dose-dependent activity with IC50 of 41.04 µg/mL against H. muscae adult worm, followed by ligstroside (4) with IC50 of 50.56 µg/mL. CONCLUSIONS: These findings could advocate the traditional use of J. grandiflorum L. and provide further insight into the anthelmintic activity of flavonoids.