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Abstract Chicken astroviruses (CAstV) were associated with retarded growth, enteritis, kidney diseases, and white chick syndrome. In the current study, we aimed to evaluate the effect of CAstV infection on growth, performance, and gross and histopathological picture of commercial chicken flocks suffering increased culling rate and decreased performance. Samples were collected for virus isolation, identification, and sequencing on day one, 15 days, and 30 days of age. Body weight, feed conversion rate, and mortality rates were determined. A gross examination was performed, and tissue samples from the liver, intestine, kidneys, heart, and lungs were kept in formalin for histopathological evaluation. Embryos inoculated with CAstV revealed dwarfism, and edema. The cytopathic effect on CAstV inoculated cells included aggregation,, and sloughing. The isolated Egyptian isolates shared the highest nucleotide homology (93%) with the Korean isolate Kr/ADL102655-1/2010 and showed the most distant relation to the Indian isolate Indovax/APF/1319 with 82–83% homology. Body weight exhibited significant reduction with a decrease in feed conversion rate in CAstV infected flocks. Gross examination of CAstV-infected chickens revealed white feathered chicks on day one, and poor body condition in older chickens as well as swollen kidneys. Histopathological examination of CAstV-infected birds showed mild proventriculitis, shortening of intestinal villi, enteritis, focal hepatocellular necrosis, pericarditis, myocarditis, and proliferative response in lung tissue. Kidneys showed interstitial nephritis, urate deposition, and glomerular hypercellularity. CAstV is a chicken pathogen that could be related to decreased performance, and screening of flocks for CAstV might be an essential step for breeders.

Industrial toxicants such as Carbon tetrachloride (CCl4) are known to disrupt the oxidative–antioxidative balance, which generates excessive amounts of free radicals leading to chronic or acute liver damage. Natural antioxidants, including Ajwa, play an important role in protecting against hepatotoxicity. This study investigated the prophylactic impacts of ajwa seeds aqueous extract (ASE) against hepatic oxidative injury in rats induced by CCl4. Eighty male Wistar albino rats were equally assigned to eight groups: one group receive no treatment, four groups were received CCl4-olive oil mixture [1:1(v/v)] (0.2 ml/100 g body weight (bw), intraperitoneally) two times/week for 4 weeks/rat alone or with 200 mg Vit. C/kg bw or 5 ml ASE/rat or both, and three groups received olive oil, Vit. C, or ASE. Vitamin C and ASE were orally administrated two weeks before CCl4 injection and 4 weeks concomitant with CCl4. Lipid peroxidation, lipogenesis-related genes, hepatic histopathology, Bax immunostaining and DNA fragmentation were assessed. ASE protected hepatic damage by suppressing oxidative stress and elevating activities of antioxidant enzymes, including superoxide dismutase and catalase. ASE also regulated hepatic dyslipidemia, hepatic lipid accumulation and expression of SREBP-1 and FAS genes in CCl4-treated rats. ASE decreased apoptosis through inhibition of CCl4 induced Bax activation in hepatocytes. These observations provide evidence for the hepatoprotective potential of ASE via inhibiting hepatic lipogenesis and oxidative stress, suggesting being used as a natural product in attenuating CCl4 induced oxidative damage, hepatotoxicity and associated dysfunction.

Introduction: Polysaccharides have numerous therapeutic values including immunity stimulation, angiotensin converting enzyme inhibition, wound healing, anti-diabetic and cytotoxic activities, in addition to their potent anti-oxidant properties. This work examined the gastroprotective and ulcer healing potential of mucilage fraction isolated from Solenostemma argel (Delile) Hayne (MFA) against ethanol-induced gastric ulcer in rats. Methods: Forty Sprague-Dawley rats were divided into five groups (n=8); normal control (I), ethanol control (II), 20 mg/kg Antodine pretreated rats (III), 100 mg/kg, and 200 mg/kg MFA pretreated rats, respectively (IV & V). All rats in groups II-V received single intragastric dose of ethanol (5 mL/kg) to induce gastric ulcer. Gastric mucosal injuries were assessed by stomach gross examination as well as histopathology, and immunohistochemistry of apoptotic markers. Also, several biochemical parameters including oxidative stress, proinflammatory cytokines, cytoprotective and cell proliferative biomarkers were measured. Results: High-performance liquid chromatography (HPLC) analysis of MFA revealed its composition of glucose, D-fucose and N-acetyl glucosamine as monosaccharaides, in addition to glucuronic and galacturonic acids. The data showed that MFA, 200 mg/kg had potent antioxidant, anti-inflammatory, cytoprotective, cell proliferative, and antiapoptotic activities which were better than Antodine. Conclusion: This study revealed that MFA had significant gastroprotective effects against ethanol-induced gastric injuries and could be a promising adjuvant therapy for ulcer treatment.

Autism spectrum disorder (ASD) is an extreme neuropsychotic disturbance with both environmental and genetic origins. Sodium propionate (PPA) a metabolic bioproduct of gut microbiota is well-thought-out as a successful autism animal model. Nevertheless, Liposomal drug delivery system possess the advantagous of biocompatibility, targeting organs, ability to carry large drug payloads and skipping macrophages for this purpose the current study was carried out to investigate the hypothesis that Calcium Voltage-Gated channel subunit alpha 1 C (CACNA1C) and glial fibrillary acidic protein (GFAP) signaling pathways crosstalk with the efficacy of Co-enzyme Q10 (Co-Q10) and liposomal loaded Co-enzyme Q10 (L Co-Q10) in PPA mediated autistic rat model. Autism was conducted by buffered PPA (500 mg/Kg b.wt) daily for 5 consecutive days subsequently treatment via Co-Q10 in a dose of (10 mg/kg b.wt) and L Co-Q10 (2 mg/kg b.wt) for four weeks then the autistic model was followed for signs of autism at different time intervals of (one, two and four weeks). The control, PPA intoxicated, and treated groups were subjected to behavioral tests (Y-Maze and open field), antioxidant analysis, gene expression analysis, and histological examination at different time intervals of the study. The results revealed that Co-Q10 and L Co-Q10 significantly elevated antioxidative stress biomarkers, comprising superoxide dismutase (SOD), glutathione (GSH), and total antioxidant capacity (TAC). In addition, they significantly ameliorated the oxidative stress biomarker malondialdehyde (MDA). Meanwhile, they significantly downregulated GFAP and CACNA1C mRNA gene expressions, Co-Q10 and LCo-Q10 showed improvement in almost brain regions post PPA histopathological alterations, even better results were manifested via LCo-Q10 groups. These results showed the superiority of LCo-Q10 over Co-Q10 in competing autism. In conclusion

The aim of this study is to assess the toxicity of some heavy metals and parasitic infection in fishes as well as the immunological status of these fishes infected with different parasites. Between January 2018 and January 2019, 360 Nile tilapia (Oreochromis niloticus) near four farms and in the Nile River in Giza were examined for external and internal parasites. In addition, samples were expressed for two genes using quantitative real-time polymerase chain reaction. Samples were also taken from muscles and water for toxicological analysis of different heavy metals. In the skin, the mean TNF-α levels in the monogenea and mixed protozoan parasites (Trichodina and Myxobolus spp.) were 18.00 ± 0.67 and 13.65 ± 0.54, respectively. In the gills, the mean TNF-α of monogenea, Centrocestus formosanus, and encysted metacercaria (EMC) with monogenea group means was 20.45 ± 0.74, 23.00 ± 0.74, and 25.78 ± 0.74, respectively. In muscles with EMC, the mean TNF-α level was 14.67 ± 0.70. In livers with EMC, the mean TNF-α level was 26.78 ± 0.70. In the skin, the mean IL-1β level in monogenea and protozoan parasites (Trichodina and Myxobolus spp.) was significantly different (25.00 ± 0.69 and 15.00 ± 0.43, respectively). In the gills, the mean IL-1β level of the monogenean group was 21.00 ± 0.79, whereas C. formosanus showed the significantly highest value (27.00 ± 0.74). The mean IL-1β level of EMC with the monogenea group was 24.00 ± 1.54. Results showed that the level of Zn, Pb, Cu, and Cd was the highest in tissues of fish than permissible limits (PLs). Histopathological examination of different examined tissues exhibited serious pathological alterations. Monogenetic trematodes were detected in the examined fish, and their presence was accompanied by hyperplasia and fusion of the secondary gill lamellae. EMC of digenetic trematodes was frequently observed in the gills and in the cartilage rod. In conclusion, the parasite infection can upregulate the immunological cytokines with different levels with different infections.

Purpose The aim of this study is to develop efficient localized therapy of sertaconazole nitrate for the treatment of vaginal candidiasis. Methods Sertaconazole nitrate-loaded cationic liposomes were prepared by thin-film hydration method and coated with different concentrations of pectin (0.05%, 0.1% and 0.2%) to develop mucoadhesive liposomes. The formulated mucoadhesive vesicles were characterized in terms of morphology, entrapment efficiency, particle size, zeta value, mucoadhesive properties and drug release. The selected formula was incorporated into a gel base and further characterized by an ex vivo permeation study in comparison with conventional sertaconazole gel. Also, the in vivo study was performed to assess the efficacy of sertaconazole mucoadhesive liposomal gel in treating rats with vaginal candidiasis. Results The mucoadhesive liposomes were spherical. Coating liposomes with pectin results in increased entrapment efficiency and particle size compared with uncoated vesicles. On the contrary, zeta values were reduced upon coating liposomes with pectin indicating efficient coating of liposomes with pectin. Mucoadhesive liposomes showed a more prolonged and sustained drug release compared with uncoated liposomes. Ex vivo study results showed that mucoadhesive liposomal gel increased sertaconazole tissue retention and reduced drug tissue penetration. In the invivo study, the mucoadhesive liposomal gel showed a significant reduction in the microbial count with a subsequent reduction in inflammatory responses with the lowest histopathological change compared with conventional gel. Conclusion The study confirmed the potentiality of employing mucoadhesive liposomes as a successful carrier for the vaginal delivery of antifungal drugs.

Ashwagandha (ASH), a vital herb in Ayurvedic medicine, demonstrated potent preclinical hepato- and neuroprotective effects. However, its efficacy is limited due to low oral bioavailability. Accordingly, we encapsulated ASH extract in chitosan–alginate bipolymeric nanocapsules (ASH-BPNCs) to enhance its physical stability and therapeutic effectiveness in the gastrointestinal tract. ASH-BPNC was prepared by emulsification followed by sonication. The NCs showed small particle size (< 220 nm), zeta-potential of 25.2 mV, relatively high entrapment efficiency (79%), physical stability at acidic and neutral pH, and in vitro release profile that extended over 48 h. ASH-BPNC was then investigated in a thioacetamide-induced hepatic encephalopathy (HE) rat model. Compared with free ASH, ASH-BPNC improved survival, neurological score, general motor activity, and cognitive task-performance. ASH-BPNC restored ALT, AST and ammonia serum levels, and maintained hepatic and brain architecture. ASH-BPNC also restored GSH, MDA, and glutathione synthetase levels, and Nrf2 and MAPK signaling pathways in liver and brain tissues. Moreover, ASH-BPNC downregulated hepatic NF-κB immunohistochemical expression. Moreover, the in vivo biodistribution studies demonstrated that most of the administered ASH-BPNC is accumulated in the brain and hepatic tissues. In conclusion, chitosan–alginate BPNCs enhanced the hepatoprotective and neuroprotective effects of ASH, thus providing a promising therapeutic approach for HE. Graphical abstract

Equine gastrointestinal tract is infected with

With growing concern about including unconventional dietary protein sources in poultry diets to substitute the protein sources that are essential for human consumption such as soybean meal, Azolla leaf meal (ALM) has grown in popularity. In our prior experiment, ALM was used at inclusion rates of 5 and 10%. Five per cent inclusion of ALM increased broiler chicken growth performance, the concentration of cecal propionic acid, and activation of skeletal muscle p70S6 Kinase1 (p70S6K1) without having detrimental effects on the meat quality. Those results prompted us to further evaluate the effect of the same inclusion rates of ALM on phase feeding and intestine and liver health of the broiler chicks. The current study hypothesis is that dietary ALM positively affects phase feeding, intestinal morphology and p70S6K1 activation, cecal microbial gene expression, and improves the liver energy status. For this, we enrolled 135 one-day-old broiler chicks and collected growth performance data (starter, grower, and finisher stages) and samples of the gastrointestinal tract to analyse the morphology of the villi, immune-related organs, mucin, and abundance of intestinal p70S6K1. Cecal bacterial species were analysed using qPCR and liver samples were collected to analyse adenosine monophosphate (AMP) and ATP content and selected oxidative stress biomarkers. ALM increased BW and feed intake during the starter and grower phases but did not affect the feed conversion ratio. Liver oxidative stress and AMP: ATP ratio increased in chickens fed on a diet containing 10% ALM (AZ10; P

The interest in biodiesel production from oil-bearing seeds rather than soybean necessitates the scientific validation of other good quality protein sources that could substitute soybean meal in animal diets, particularly, broiler chickens where soybean meal constitutes a large portion of their diet. Therefore, the present study was conducted to investigate the effect of sun-dried Azolla leaf meal (ALM) as an unconventional dietary protein source in broiler chicken diet on growth performance, meat quality, skeletal muscle cell growth and protein synthesis through regulation of ribosomal protein S6 kinase (p70S6 kinase α). A total of 120 male Ross 308 broiler chicks were randomly allocated to three dietary treatments. Each treatment had four cages (i.e. replicates) with 10 birds/cage. The control group was fed with a corn–soy-based diet, the AZ5 group was supplemented with 5% ALM and the AZ10 group was supplemented with 10% ALM for 37 days. A 5-day trial was also conducted to measure the apparent nutrient digestibility. Growth performance parameters were measured weekly. At the end of the experiment, 12 birds from each group (3/cage) were euthanized and used for samplings. Inclusion of ALM tended to improve BW gain (P = 0.06) and increased feed intake (P < 0.01). Additionally, ALM decreased the percentage of breast meat cooking loss linearly (P < 0.01). In addition, ALM at a dose of 5% increased the production of propionate in the cecum (P = 0.01). Activation of breast muscle p70S6 kinase was higher when ALM was included in a dose-dependent manner (P < 0.01). The inclusion of ALM increased breast meat redness (P < 0.01); however, the lightness was within the normal range in all groups. Findings from our study suggest that ALM could be included in a broiler chicken diet up to 5% without any major negative effect on meat quality or performance, and it regulates muscle protein synthesis through activation of mammalian target of rapamycin/6S kinase signaling.

Several signaling events have been identified for mediating cisplatin-induced chronic inflammation and progressive renal fibrosis, but the majority of them have not yet been established as therapeutic targets. This study investigated the modulatory effects of berberine on purinergic 2X7 receptors (P2X7R) and some potential intracellular profibrogenic signaling as molecular mechanisms that could hinder renal fibrosis associated with cisplatin administration in rats.For induction of kidney injury, rats were injected with cisplatin (1 mg/kg, i.p.) daily for two weeks. Concurrently, the rats were treated with berberine (100 or 200 mg/kg, p.o). The gene expressions of P2X7R, dual-specificity phosphatase 6 (DUSP6), and murine double-minute 2 (MDM2) were determined. The expressions of alpha smooth-muscle actin and tumor necrosis factor alpha (TNF-α) were assessed by immunohistochemical staining. Phosphorylated extracellular signal-regulated kinase 1/2, (p-ERK1/2) was evaluated by western blotting. Sirtuin 2 (SIRT2), kidney injury molecule-1, and galectin-3 were measured by enzyme-linked immunosorbent assay. The degree of renal fibrosis was assessed by microscopic examination and picrosirius red staining.Berberine effectively inhibited cisplatin-induced renal histopathological changes, enhanced renal function, and markedly mitigated inflammatory and fibrotic alterations as well as TNF-α protein expression. Additionally, P2X7R, p-ERK1/2, MDM2, and SIRT2 were suppressed and DUSP6 was upregulated by berberine.The nephroprotective effects of berberine were mediated in part by downregulating P2X7R and modulating DUSP6-mediated inactivation of ERK1/2 as well as by suppressing SIRT2/MDM2-triggered renal fibrosis.

This work was carried out to compare the modifying roles of ascorbic and metformin during Ehrlich (ESC) tumor-bearing mice irradiation.Fifty Swiss albino male mice were segmented into seven groups, including one control group and six Ehrlich induced tumors treated with ascorbic, ascorbic plus radiation, metformin, metformin plus radiation, and radiation only. Many tests, including behavioral, biochemical, immunohistochemistry, gene expression, DNA fragmentation, oxidative stress markers, and EPR, were performed to interrogate the modifying effects on tumor and liver tissues.Remarkable apoptosis was found in metformin irradiated animals compared to irradiated ascorbic counterparts. The irradiated metformin mice showed the greatest reduction in PCNA. There was a significant reduction of DNA fragmentation in the liver tissues of the irradiated metformin group. Irradiated metformin and irradiated ascorbic acid animals showed a reduced signal of ERK as well as c-Fos genes. There was a tendency of metformin and metformin irradiated animals to reduce MDA levels in liver tissues. ESC-bearing mice treated with ascorbic or metformin showed an improvement in the spontaneous alternation percentage (SAP%) and improved short-term memory. There was also an improvement in long memory tests.The study added more preclinical evidence on the utility of metformin in cancer treatment during radiotherapy. Metformin was shown to reduce lipid peroxidation in irradiated healthy tissues, increase tumor cytotoxicity, downregulate critical pathways involved in tumor progression and proliferation, and enhance tumor apoptosis. Controlled clinical trials using metformin are highly warranted.

Objective Morin (MRN), a known natural flavonol, has demonstrated its shielding aptitude against ischemia/reperfusion (I/Re) lesion in various organs. Nonetheless, its potential influence on hepatic I/Re-induced injury modulation has not been fully elucidated. Consequently, the current study strived to investigate the mechanistic maneuvering of MRN against hepatic I/Re. Furthermore, the effects of MRN on Nrf2, TLR4, and NLRP3 proteins were evaluated via molecular docking studies. Methods For fulfilling this aim, Sprague-Dawley rats were allotted into 4 groups; Sham-operated (ShG), hepatic I/Re (30 min/24 h), and 10 days orally pre-treated MRN (50 and 100 mg/kg). Key findings MRN mechanistic maneuver disclosed its ability to safeguard the hepatocytes partially due to antioxidant aptitude through intensifying the expression/content of Nrf2/HO-1 trajectory accompanied by total antioxidant capacity boosting besides MDA lessening. In addition, MRN anti-inflammatory attribute was affirmed by downsizing the expression/content of TLR4/NF-κB trajectory accompanied by a sequent lessening of TNF-α, IL-1β, IL-6, and ICAM-1 content. Moreover, MRN action entangled NLRP3 inhibitory character with subsequent MPO rebating. Furthermore, MRN anti-apoptotic trait verified by diminishing the pro-apoptotic and the executioner markers; Bax and caspase-3 levels, respectively. On the other hand, MRN administration proved its shielding action by improving the histopathological deterioration and lessening the serum ALT and AST levels. Finally, in silico studies exhibited moderate to promising binding affinities of MRN with the selected proteins ranging from −4.23 to −6.09 kcal mol−1. Conclusion Higher and lower doses of MRN purveyed plausible defensive mechanisms and abated episodes concomitant with hepatic I/Re mischief in part, by modifying oxidative status and inflammation by the impact on Nrf2/HO-1, TLR4/ NF-κB, and NLRP3 pathway.

Industrial toxicants such as Carbon tetrachloride (CClThis study investigated the prophylactic impacts of ajwa seeds aqueous extract (ASE) against hepatic oxidative injury in rats induced by CClThese observations provide evidence for the hepatoprotective potential of ASE via inhibiting hepatic lipogenesis and oxidative stress, suggesting being used as a natural product in attenuating CCl

Many researches have been undergone to hasten the natural wound healing process. In this study, several Hibiscus species (leaves) were extracted with petroleum ether, methanol, and their mucilage was separated. All the tested species extracts were assessed for their viability percentage using the water-soluble tetrazolium. H.syriacus was the plant of choice to be incorporated in a new drug delivery system and evaluated for its wound healing activity. H.syriacus petroleum ether extract (PEE) showed a high percentage of palmitic and oleic acids while its mucilage demonstrated high glucosamine and galacturonic acid. It was selected to be formulated and pharmaceutically evaluated into three different composite sponges using chitosan in various ratios. Fourier-transformed infrared spectroscopy investigated the chemical interaction between the utilized sponges' ingredients. Morphological characteristics were evaluated using scanning electron microscopy. H.syriacus composite sponge of mucilage: chitosan (1:5) was loaded with three different concentrations of PEE. Medicated formulations were assessed in rat model of excision wound model. The wound healing ability was clearly proved by the clinical acceleration, histopathological examination, and modulation of correlated inflammatory parameters as tumor necrosis factor in addition to vascular endothelial growth factor suggesting a promising valuable candidate that supports the management of excision wounds using single-dose preparation.

Di-(2-ethylhexyl) phthalate (DEHP) is an endocrine disruptor that causes reproductive defects in male animal models. This study was conducted to explore the plausible modulatory effects of mangiferin (MF) against DEHP-induced testicular injury in rats. Thirty-two adult male albino rats were allocated into four groups. Two groups were given DEHP (2 g/kg/day, p.o) for 14 days. One of these groups was treated with MF (20 mg/kg/day, i.p) for 7 days before and 14 days after DEHP administration. A vehicle-treated control was included, and another group of rats was given MF only. Results revealed that MF treatment suppressed oxidative testicular injury by amplifying the mRNA expression of nuclear factor-erythroid 2 related factor-2 (Nrf2) and increasing hemoxygenase-1 (HO-1), glutathione, and total antioxidant capacity (TAC) levels. This treatment also enhanced superoxide dismutase activity, but it decreased malondialdehyde and nitric oxide levels. MF had an anti-inflammatory characteristic, as demonstrated by the downregulation of the mRNA of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The content of tumor necrosis factor-alpha also decreased. MF modulated the apoptotic pathway by suppressing the mRNA of cytochrome c (Cyt c), Fas ligand content, Bax IHC expression, caspase-3 activity and cleaved caspase-3 IHC expression. It also upregulated the expression levels of heat-shock protein 70 (HSP70) and B-cell lymphoma 2. Moreover, MF upregulated the mRNA expression levels of HSP70 and c-kit and enriched the content of steroidogenic acute regulatory (StAR) protein, which were reflected in serum testosterone levels. This result indicated that MF played crucial roles in steroidogenesis and spermatogenesis. Besides, the activities of testicular marker enzymes, namely, acid and alkaline phosphatases, and lactate dehydrogenase, significantly increased. Histopathological observations provided evidence supporting the biochemical and molecular measurements. In conclusion, MF provided protective mechanisms against the DEHP-mediated deterioration of testicular functions partially through its antioxidant, anti-inflammatory, and anti-apoptotic properties. It also involved the restoration of steroidogenesis and spermatogenesis through the modulation of Nrf2/HO-1, NF-κB/Cyt c/HSP70, and c-Kit signaling cascades.

The endocannabinoid system plays a pivotal role, whether it is promoting or dampening hepatic fibrosis. This study investigated the role of Cannabinoid receptor 2 (CB

Aims Cilostazol (Cilo), a phosphodiesterase-III inhibitor, has signified its efficacy against different ischemia/reperfusion (IS/RE) models. Nevertheless, it has not fully illuminated its potential effect against intestinal IS/RE-induced lung injury. Consequently, the study was fashioned to evaluate the feasible mechanism of action of Cilo against intestinal IS/RE-induced lung injury. Main methods Wistar rats were treated with Cilo (0.1 g/kg, p.o.) or with a vehicle for 14 days prior to IS/RE, induced by clamping of the superior mesenteric artery for 30 min with subsequent clamp removal for 2 h. Key findings The mechanistic study disclosed that Cilo protected the two studied organs, viz., lung, and intestine partially by intensifying the expression/content of PPAR-γ accompanied by reducing the expression/content of NF-қB-p65 and STAT3. In addition to normalizing MDA, iNOS, and NOx, the Cilo antioxidant power was confirmed by intensifying tissues content of the total antioxidant capacity. With regard to the anti-inflammatory effect, Cilo reduced the effects of TNF-α, IL-6, and ICAM-1, which were reflected in MPO activity. Furthermore, Cilo had an anti-apoptotic attribute demonstrated by enhancing Bcl-2 content and lessening caspase-3 level. Significance Cilo provided conceivable protective mechanisms to modulate events concomitant with mesenteric IS/RE partly by modulating oxidative stress, inflammation, and apoptosis feasibly via the participation of PPAR-γ, STAT3, and NF-κB p65 signaling pathways.

Geraniol (GOH) is a natural essential oil that possesses antioxidant, anti-inflammatory, and antiapoptotic properties by various signaling pathways. Liver ischemia-reperfusion injury (IRI) is a serious event that triggers liver dysfunction or even failure. Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcriptional factor, maintains cellular defense mechanism through antioxidant and anti-inflammatory properties. To detect GOH effect against liver IRI through the activation of the Nrf2/HO-1 antioxidant pathway, five groups of rats were randomized to normal, sham, IR, GOH, and GOH/IR. Blood samples and liver tissues were collected to measure various biochemical parameters related to liver function, and oxidative stress as well as inflammatory and apoptotic indicators besides liver tissue histopathology was evaluated by light microscopy. GOH induces activation of Nrf2 along with the upregulation of HO-1 expression. Also, the antioxidant activity of GOH was shown by the elevation of total antioxidant capacity and GSH levels, together with normalizing malondialdehyde. Regarding the anti-inflammatory effect of GOH, it suppresses the levels of TNF-α, iNOS, and COX-2. Additionally, the antiapoptotic effect of GOH, Bax, and caspase-3, 9 were reduced in liver tissue. GOH is a promising hepatoprotective agent in liver IRI through the activation of Nrf2/HO-1 antioxidant pathway.

Ethnopharmacological relevance Ashwagandha (ASH) is one of the medicinal plants used in traditional Indian, Ayurvedic, and Unani medicines for their broad range of pharmacological activities including, tonic, aphrodisiac, energy stimulant, and counteracting chronic fatigue. Besides, it is used in the treatment of nervous exhaustion, memory-related conditions, insomnia, as well as improving learning ability and memory capacity. ASH is preclinically proven to be efficient in hepatoprotection and improving cognitive impairment, however, its beneficial effects against hepatic encephalopathy (HE) is still unclear. Therefore, this study aimed at investigating the protective effects of ASH root extract against thioacetamide (TAA)-induced HE and delineate the underlying behavioral and pharmacological mechanisms. Materials and methods ASH metabolites were identified using UPLC-HRMS. Rats were pretreated with ASH (200 and 400 mg/kg) for 29 days and administrated TAA (i.p, 350 mg/kg) in a single dose. Then, behavioral (open field test, Y-maze, modified elevated plus maze and novel object recognition test), and biochemical (ammonia and hepatic toxicity indices) assessments, as well as oxidative stress markers (MDA and GSH) were evaluated. The hepatic and brain levels of glutamine synthetase (GS), nuclear factor erythroid 2-related factor 2 (Nrf2), heme-oxygenase (HO)-1, inducible nitric oxide synthase (iNOS) were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of p38/ERK½ were determined using real-time polymerase chain reaction (PCR). Moreover, histopathological investigations and immunohistochemical (NF-κB and TNF-α immunohistochemical expressions) examinations were performed. Results Metabolite profiling of ASH revealed more than 45 identified metabolites including phenolic acids, flavonoids and steroidal lactone triterpenoids. Compared to the TAA-intoxicated group, ASH improved the locomotor and cognitive deficits, serum hepatotoxicity indices and ammonia levels, as well as brain and hepatic histopathological alterations. ASH reduced hepatic and brain levels of MDA, GS, and iNOS, and increased their GSH, Nrf2, and HO-1 levels. Also, ASH downregulated p38 and ERK½ mRNA expressions, and NF-κB and TNF-α immunohistochemical expressions in brain and hepatic tissues. Conclusions Our results provided insights into the promising hepato- and neuroprotective effects of ASH, with superiority to 400 mg/kg ASH, to ameliorate HE with its sequential hyperammonemia and liver/brain injuries. This could be attributed to the recorded increase in the spontaneous alternation % and recognition index, antioxidant and anti-inflammatory activities, as well as upregulation of Nrf2 and downregualtion of MAPK signaling pathways.

Objective Dimethyl fumarate (DMFU), a known Nrf2 activator, has proven its positive effect in different organs against ischemia/reperfusion (Is/Re) injury. Nevertheless, its possible impact to modulate intestinal Is/Re-induced injury has not been previously demonstrated before. Hence, this study aimed to investigate DMFU mechanistic maneuver against intestinal Is/Re. Methods To accomplish this goal, Wistar rats were allocated into four groups; Sham-operated (SOP), intestinal Is/Re (1 h/6 h), and 14 days pre-treated DMFU (15 and 25 mg/kg/day, p.o). Results The mechanistic maneuver divulged that DMFU safeguarded the intestine partly via amplifying the expression/content of Nrf2 along with enhancing its downstream, HO-1 expression/content. In addition, DMFU lessened GSK-3β expression/content accompanied by enriching β-catenin expression/content. The antioxidant action was affirmed by enhancing total antioxidant capacity, besides reducing MDA, iNOS, and its by-product, NOx. The DMFU action entailed anti-inflammatory character manifested by down-regulation of expression/content NF-κB with subsequent rebating the contents of TNF-α, IL-1β, and P-selectin, as well as MPO activity. Moreover, DMFU had anti-apoptotic nature demonstrated through enriching Bcl-2 level and diminishing that of caspase-3. Conclusion DMFU purveyed tenable novel protective mechanisms and mitigated events associated with intestinal Is/Re mischief either in the lower or the high dose partly by amending of oxidative stress and inflammation through the modulation of Nrf2/HO-1, GSK-3β, and Wnt/β-catenin pathways.

The endocannabinoid system plays a pivotal role, whether it is promoting or dampening hepatic fibrosis. This study investigated the role of Cannabinoid receptor 2 (CB2) activation by the synthetic analog (AM1241) on revoking the progress of liver fibrosis. Thioacetamide (TAA) was used to induce liver fibrosis in rats for three weeks followed by its concurrent administration with AM1241 at two different doses for another three weeks. Markers for liver function and oxidative stress, hepatic TNF-α, IL-1β and IL-6, qRT-PCR expression of Toll like receptor 4 (TLR4), TGF-β1, α-SMA and microRNA-155 (miR-155) genes, Western blot for protein levels of Vimentin and E-cadherin, immunohistochemical expression of NFκB p65 and histopathology of liver tissue were all investigated. AM1241 administration significantly maintained liver function markers and decreased; malondialdehyde, Vimentin, TLR4, TGF-β1, α-SMA and miR-155 genes expression, NFκB p65 immune-expression and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6). Additionally, AM1241 significantly increased E-Cadherin level, GSH and SOD content. Histologically, AM1241 limited fibroplasia extension, and broke the itinerary of bridging fibrosis. In conclusion, activation of the CB2 receptors by AM1241 promoted liver regeneration and overrun the progression of liver fibrosis through; inhibition of TLR4/miR-155/NFκB p65 pathway, suppression of pro-inflammatory IL-6, IL-1β and TNF-α, reducing TGF-β1, α-SMA, Vimentin and up-regulating E-Cadherin.

Gastric ulcers are a very common public health problem affecting up to 10% worldwide. Russelioside B is a steroidal glycoside isolated from several Caralluma species. No study tested the ulcer healing potential of the compound. The current study aimed to assess the protective effect of russelioside B against ethanol-induced gastric mucosal injury in rats. Ulcer was induced on rats by a single intragastric dose of absolute ethanol (5 mL/kg). Rats were randomly assorted into four groups (n = 8) and given treatments (Antodine, 20 mg/kg or russelioside B, 50 mg/kg) by oral gavage 1 h before ulcer induction. Pretreatment with russelioside B (50 mg/kg) attenuated the gastric mucosal injury as proved by a decrease of ulcer index, and histological scores. It suppressed the gastric inflammation by a significant lowering the tumor necrosis factor-α and interleukin-6 levels with myeloperoxidase activity (which are also aggravating factors in the case of Covid-19 infection). In addition, administration of russelioside B halted the gastric oxidative stress via inhibition of lipid peroxides by maintaining reduced glutathione and by decreasing malondialdehyde. It was able also to restore the sharp drop in the levels of heat shock protein-70, vascular endothelial growth factor and prostaglandin E2 induced by ethanol. Additionally, it showed carbonic anhydrase inhibition activity. The gastroprotective action of russelioside B was umpired through multi mechanistic actions; suppression of gastric oxidative stress, inflammation, anti-apoptotic activities and enhanced gastric mucosal protection by up-regulation of endothelial growth factor, normalization of heat shock protein-70 and prostaglandin E2. These actions were comparable in part to some classical antiulcer drugs such as Antodine.

Greater understanding of the efficiency of nanoparticles will assist future research related to male reproductive performance. The current study was performed to assess the potency of selenium nanoparticles (SeNPs) in alleviating deltamethrin (DLM)-induced detrimental effects on sperm characteristics, oxidative status, sexual behavior, and the histological structure of the testes and epididymis in male rats. Thirty-two male Wister rats were divided into four groups according to treatment received orally by gavage 3 times/week for 60 days; control, DLM (0.6 mg/kg bwt), SeNPs (0.5 mg/kg bwt), and DLM-SeNPs groups. DLM caused a significant reduction in sperm count, motility, and viability percent, as well as in body weight and serum testosterone level, blood total antioxidant capacity (TAC), and glutathione peroxidase (GPx) activity. The DLM-treated group showed a significant increase in blood malondialdehyde (MDA) concentration and sperm abnormalities (%), as well as a significant reduction in sexual activity, manifested as an increase in mount, intromission, or ejaculation latency and a reduction in mount or intromission frequency. These toxic effects were confirmed by histological alterations, represented by a significant reduction in the diameter of the seminiferous tubules and spermatogenesis. Conversely, treatment with SeNPs improved DLM-induced negative effects on sperm characteristics, testosterone, and antioxidant biomarkers, as well as behavioral and histopathological alterations. The SeNPs treated group showed improved semen parameters, antioxidant status, and sexual performance. In conclusion, SeNPs may represent an effective treatment for reducing the detrimental effects of DLM on male fertility, and lead to enhanced male reproductive performance.

Conjugated linoleic acid was detected in rabbit caecotrophs, due to the presence of microbial lipid activity in rabbit cecum. However, the effect of CLA as a functional food in growing rabbit is not well established. Therefore, this study was conducted to determine the effect of CLA on production, meat quality, and its nutrigenomic effect on edible parts of rabbit carcass including skeletal muscle, liver, and adipose tissue. Therefore, seventy five weaned V-Line male rabbits, 30 days old, were randomly allocated into three dietary treatments receiving either basal control diet, diet supplemented with 0.5% (CLAL), or 1% CLA (CLAH). Total experimental period (63 d) was segmented into 7 days adaptation and 56 days experimental period. Dietary supplementation of CLA did not alter growth performance, however, the fat percentage of longissimus lumborum muscle was decreased, with an increase in protein and polyunsaturated fatty acids (PUFA) percentage. Saturated fatty acids (SFA) and mono unsaturated fatty acids (MUFA) were not increased in CLA treated groups. There was tissue specific sensing of CLA, since subcutaneous adipose tissue gene expression of PPARA was downregulated, however, CPT1A tended to be upregulated in liver of CLAL group only (P = 0.09). In skeletal muscle, FASN and PPARG were upregulated in CLAH group only (P ≤0.01). Marked cytoplasmic vacuolation was noticed in liver of CLAH group without altering hepatocyte structure. Adipocyte size was decreased in CLA fed groups, in a dose dependent manner (P

Summary Reasons for performing study: Donkeys (Equus africanus asinus) are important working animals, particularly in countries where the majority of the population lives below the poverty line. Gastric ulceration has been shown to be common in British donkeys but donkeys from other parts of the world have not been as extensively researched. Objectives: This study was performed as a preliminary overview of the severity and distribution of gastric lesions in mature donkeys and to document which parasites were present. Study design: Descriptive study of pathological findings. Methods: Stomachs of 35 mature draught donkeys were examined grossly and histopathology samples taken from 5 regions of the gastric mucosa. Results: Gross examination revealed hyperaemia, oedema, erosions and ulcers in addition to parasitic lesions. Histopathological examination revealed hyperkeratosis, acanthosis, vacuolar degeneration of stratified squamous cells, gastritis, erosions, ulcerations, scarring, hyperactivity of mucus glands, periglandular fibroplasia and parasitic granulomes with infestation by Gasterophilus spp. larvae, Habronema spp. and Draschia megastoma. Conclusions: In donkeys, ulceration of the nonglandular regions of the stomach is more prominent than the glandular regions and parasitic infestations were frequent.

Pathology digital lab is the modern, flexible and time effec- tive research assistant. The process of creating pathology slides contains five creation steps from the tissue samples collection till clearing and staining stage. The reservation and sharing of such slides using classical models limit the ability of pathologists to benefit from important and rare slides. The virtual lab with its digital slides conquers those limita- tions and adds more intelligence to research and diagnosis fields. Having the digital slides, it is easy to save, share, search, apply automatic di- agnosis through pattern recognition techniques, getting alerts for new slides and much more. The target of this work is to present the virtual lab design with its functionalities by explaining the glass slides creation process and then digitalize through scanners and the digital lab platform.