Modulatory mechanisms of copperII-albumin complex toward N-nitrosodiethylamine-induced neurotoxicity in mice via regulating oxidative damage, inflammatory, and apoptotic signaling pathways.

N-nitrosodiethylamine (ND) is an extremely toxic unavoidable environmental contaminant. CopperII-albumin (CuAB) complex, a newly developed Cu complex, showed antioxidant and anti-inflammatory potential. Hereby, we explored the plausible neuroprotective role of CuAB complex toward ND-evoked neurotoxicity in mice. Twenty-four male mice were sorted into 4 groups (6 mice each). Control group, mice were administered oral distilled water; and CuAB group, mice received CuAB complex at a dose of 817 µg/kg orally, three times weekly. In ND group, ND was given intraperitoneally (50 mg/kg body weight, once weekly for 6 w). CuAB+ND group, mice were administered a combination of CuAB and ND. The brain was quickly extracted upon completion of the experimental protocol for the evaluation of the oxidative/antioxidative markers, inflammatory cytokines, and histopathological examination. Oxidative stress was induced after ND exposure indicated by a reduction in GSH and SOD1 level, with increased MDA level. In addition, decreased expression of SOD1 proteins, Nrf2, and 5-HT mRNA expression levels were noticed. An apoptotic cascade has also been elicited, evidenced by overexpression of Cyt c, Cl. Casp 3. In addition, increased regulation of proinflammatory genes (TNF-α, IL-6, iNOS, Casp1, and NF-κB (p65/p50); besides, increment of protein expression of P-IKBα and reduced expression of IKBα. Pretreatment with CuAB complex significantly ameliorated ND neuronal damage. Our results recommend CuAB complex supplementation because it exerts neuroprotective effects against ND-induced toxicity.

Nephroprotective effects of Acacia senegal against aflatoxicosis via targeting inflammatory and apoptotic signaling pathways.

Aflatoxin B1 (AFB1) is a common environmental pollutant that poses a major hazard to both humans and animals. Acacia senegal (Gum) is well-known for having antioxidant and anti-inflammatory bioactive compounds. Our study aimed to scout the nephroprotective effects of Acacia gum (Gum) against AFB1-induced renal damage. Four groups of rats were designed: Control, Gum (7.5 mg/kg), AFB1 (200 µg/kg b.w) and AFB1-Gum, rats were co-treated with both Gum and AFB1. Gas chromatography-mass spectrometry (GC/MS) analysis was done to determine the phytochemical constituents in Gum. AFB1 triggered profound alterations in kidney function parameters (urea, creatinine, uric acid, and alkaline phosphatase) and renal histological architecture. Additionally, AFB1 exposure evoked up-regulation of mRNA expression levels of inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor α (TNFα), inducible nitric oxide synthase (iNOS), and nuclear factor kB p65 (NF-κB/P65) in renal tissue. The oxidative distress and apoptotic cascade are also instigated by AFB1 intoxication as depicted in down-regulated protein expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) and superoxide dismutase type 1 (SOD1) along with upregulation of cytochrome c (Cyto c), and cleaved Caspase3 (Casp3-17 and 19) in renal tissue. In conclusion, current study obviously confirms the alleviating effects of Gum supplementation against AFB1-induced renal dysfunction, oxidative harm, inflammation, and cell death. These mitigating effects are suggested to be attributed to Gum's antioxidant and anti-inflammatory activities. Our results recommend Gum supplementation as add-on agents to food that might aid in protection from AFB1-induced nephrotoxicity.

Treatment of Inactive Ovaries of Holstein Dairy Cows by Epidural Injection of GnRH Analogue (Receptal) and Its Impact on the Reproductive Hormones, Oxidant/Antioxidant Profile and Micro and Macro-Elements Profile.

This study was designed to evaluate a new therapeutic approach for inactive ovaries based on the epidural administration of a GnRH agonist (Receptal) and an investigation of the impact of this treatment on the hormonal, oxidant/antioxidant and micro- and macro-element profiles. Sixty cows with postpartum anestrus were divided into two groups: the first group (group Repid, n = 30) was administered an epidural injection of Receptal, while the second group (group Cepid, n = 30) received saline and was considered the control group. Evaluation of hormonal (progesterone, FSH, LH, testosterone, and cortisol), oxidant/antioxidant (MDA, SOD, GPx and TAC) as well as micro- and macroelement (calcium, phosphorus, manganese and magnesium) profiles was done in serum. The results showed that the epidural injection of Receptal has the potential to induce estrus response and conception incidence in treated cows. Compared to the control group, progesterone, FSH, and LH concentrations were significantly increased in the treated group, whereas testosterone and cortisol decreased (p < 0.05) following treatment. In addition, the treated group had greater TAC and GPx concentrations than the control group. Serum concentrations of magnesium increased (p < 0.05) following receptal treatment, but differences in other minerals were not detected. This research suggests a novel, effective method of treating inactive ovaries with epidural infusion of a GnRH agonist.

High relatedness of bioinformatic data and realistic experimental works on the potentials of Fasciola hepatica and F. gigantica cathepsin L1 as a diagnostic and vaccine antigen.

Introduction: Fascioliasis is a parasitic foodborne disease caused by the liver flukes, Fasciola hepatica and F. gigantica. Such parasites cause serious illness in numerous domestic animals and also in humans. Following infection, the parasite secretes a variety of molecules that immediately interact with the host immunity to establish successful infection. These molecules include cathepsin L peptidase 1 (CatL1); the highly investigated diagnostic and vaccine antigens using various animal models. However, a few studies have analyzed the potentials of FhCatL1 as a diagnostic or vaccine antigen using bioinformatic tools and much less for FgCatL1. The present study provides inclusive and exclusive information on the physico-chemical, antigenic and immunogenic properties of F. hepatica cathepsin L1 (FhCatL1) protein using multiple bioinformatic analysis tools and several online web servers. Also, the validation of our employed available online servers was conducted against a huge collection of previously published studies focusing on the properties of FhCatL1as a diagnostic and vaccine antigen. Methods: For this purpose, the secondary, tertiary, and quaternary structure of FhCatL1 protein were also predicted and analyzed using the SWISS-MODEL server. Validation of the modeled structures was performed by Ramachandran plots. The antigenic epitopes of the protein were predicted by IEDB server. Results and discussion: Our findings revealed the low similarity of FhCatL1 with mammalian CatL1, lacking signal peptides or transmembrane domain, and the presence of 33 phosphorylation sites. Also, the containment of FhCatL1 for many topological, physico-chemical, immunological properties that favored its function of solubility and interaction with the immune components were reported. In addition, the earlier worldwide reports documented the high efficacy of FhCatL1 as a diagnostic and vaccine antigen in different animals. Altogether, FhCatL1 is considered an excellent candidate for using in commercialized diagnostic assays or vaccine products against fascioliasis in different animal species. Our assessment also included FgCatL1 and reported very similar findings and outputs to those of FhCatL1.

Arabic Gum Could Alleviate the Aflatoxin B1-provoked Hepatic Injury in Rat: The Involvement of Oxidative Stress, Inflammatory, and Apoptotic Pathways.

Aflatoxin B1 (AF) is an unavoidable environmental pollutant that contaminates food, feed, and grains, which seriously threatens human and animal health. Arabic gum (AG) has recently evoked much attention owing to its promising therapeutic potential. Thus, the current study was conducted to look into the possible mechanisms beyond the ameliorative activity of AG against AF-inflicted hepatic injury. Male Wistar rats were assigned into four groups: Control, AG (7.5 g/kg b.w/day, orally), AF (200 µg/kg b.w), and AG plus AF group. AF induced marked liver damage expounded by considerable changes in biochemical profile and histological architecture. The oxidative stress stimulated by AF boosted the production of plasma malondialdehyde (MDA) level along with decreases in the total antioxidant capacity (TAC) level and glutathione peroxidase (GPx) activity. Additionally, AF exposure was associated with down-regulation of the nuclear factor erythroid2-related factor2 (Nrf2) and superoxide dismutase1 (SOD1) protein expression in liver tissue. Apoptotic cascade has also been evoked following AF-exposure, as depicted in overexpression of cytochrome c (Cyto c), cleaved Caspase3 (Cl. Casp3), along with enhanced up-regulation of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, inducible nitric oxide synthase (iNOS), and nuclear factor kappa-B transcription factor/p65 (NF-κB/p65) mRNA expression levels. Interestingly, the antioxidant and anti-inflammatory contents of AG may reverse the induced oxidative damage, inflammation, and apoptosis in AF-exposed animals.

Ameliorative Effect of Oxytocin on FBN1 and PEPCK Gene Expression, and Behavioral Patterns in Rats' Obesity-Induced Diabetes.

Amelioration of hyperinsulinemia and insulin resistance associated with obesity is a cardinal target for therapeutics. Therefore, we investigated the relation of Fibrilln-1 (FBN1) mRNA expression and hepatic phosphoenolpyruvate caboxykinase (PEPCK) enzyme to the ameliorative impact of oxytocin on obesity-induced diabetes, suggesting glycogenolysis markers in diabetic models. Four groups of forty male Wistar rats were formed (n = 10): a control group fed basal diet and intraperitoneal injections of saline; an oxytocin-injected group; a diet-induced obese group fed a high-fat/high-sugar diet and injected with saline; a diet-induced obese group injected with oxytocin. Depending on blood glucose levels, obese groups were further sub-grouped into prediabetic, and diabetic rats, with 5 rats each, at the ninth and the 16th week of the feeding period, respectively. FBN1 expression and PEPCK activity were determined using the qPCR technique and some biochemical parameters (glycemic, lipid profile, kidney, and liver functions) were determined using kits. Obese groups showed an elevation of brain FBN1 expression, high serum lipid profile, high glucose level, and a deleterious impact on liver and kidney functions. Obese groups showed the stimulator effect of the PEPCK enzyme and time-dependent pathological changes in renal and hepatic tissues. The motor activities were negatively correlated with FBN1 gene expression in prediabetic and diabetic rats. In addition to our previous review of the crucial role of asprosin, here we showed that oxytocin could ameliorate obesity-induced diabetes and decrease FBN1 gene expression centrally to block appetite. Oxytocin caused decreases in PEPCK enzyme activity as well as glycogenolysis in the liver. Therefore, oxytocin has a potential effect on FBN1 expression and PEPCK enzyme activity in the obesity-induced diabetic-rat model.

Impact of polyherbal formulation oral administration on the estrus response, luteal activity, and oxidative stress in postpartum dairy cows with ovarian subfunction.

Background and Aim: The reproductive performance of dairy cows is of a high economic value to maintain efficient and sustainable productivity. Postpartum anestrus is one of the major infertility problems that cause limitation of dairy cow reproductive performance and productivity. The previous studies have reported using a polyherbal formulation for different purposes, including reproductive performance. This study was conducted to examine the efficacy of polyherbal formulation administration on the reproductive performance of cows and to establish the oral administration of polyherbal formulations as a safe, effective, and economic treatment for dairy cows with postpartum anestrus due to nutritional disorders, negative energy balance, high milk production, and/or heat stress. Materials and Methods: A total of 14 dairy cows with postpartum anestrus were randomly divided into two groups, which were subjected to oral administration of distilled water that served as the control (Ctrl; n=5) or polyherbal treatment (polyherbal treated; n=9) for two shots of treatment (each for 3 successive days) with a 10-day interval. Blood sampling and ultrasonography were performed before treatment and after the first and second shots of treatment. Progesterone (P4) assay was also performed. Results: The estrus induction rate was 66.7% after the first shot of treatment in the polyherbal-treated group, which increased significantly to 88.9% after the second shot of treatment, compared with the Ctrl group (20%). The estrus response was confirmed by ultrasonography and P4 hormone assay, wherein the polyherbal treatment significantly increased the P4 concentration in the polyherbal-treated group after the second shot of treatment compared to that before treatment and in the Ctrl group at all time points. On pregnancy diagnosis, the treated dairy cows showed conception rates of 66.7% and 20.0% in the polyherbal-treated and Ctrl groups, respectively. In contrast, the concentration of malondialdehyde, an oxidative stress marker, and the total antioxidant capacity remained unchanged between both groups before and after treatment. Conclusion: The polyherbal formulation containing tubers of C. rotundus, M. pterygosperma, rhizome of Z. officinale, and A. cepa has the potential to induce estrus response and luteal activity in dairy cows and is a possible treatment for ovarian inactivity in dairy farms.

Plasmalogens ensure the stability of non-neuronal (microglial) cells during long-term cytotoxicity.

Microglia (MG) are resident phagocytes in the brain responsible for neuronal maintenance. The regulation of MG necroptosis is required for protecting neurons during neurodegenerative diseases. Therefore, this study proposed to elucidate the molecular mechanisms underlying microglia necroptosis during long-time apoptotic stimuli (lipopolysaccharide, LPS). The protective role of plasmalogens (PLS) was also investigated against LPS insult in MG cells (including BV2 and MG6 cell lines). LPS produced time-dependent decreases in the survival of BV2 and MG6 cells mediated by the caspase signaling pathway. Interestingly, MG death was mediated by caspase-8 and 9 signaling pathways suggesting that MG necroptosis was actively attributed to long-time LPS treatment through intrinsic and extrinsic pathways. Notably, caspase signaling was markedly inhibited in the PLS-pretreated cells; thereby, PLS were capable of maintaining the MG cell population and inhibit the MG necroptosis against the longtime of LPS administration via its antioxidant and anti-inflammatory properties.

Cefepime and diclofenac sodium combined treatment-potentiated multiple organ injury: Role of oxidative damage and disrupted lipid metabolism.

Concurrent exposure to antimicrobial and nonsteroidal anti-inflammatory drugs (NSAIDs) is usually inevitable in most infections and postsurgery. Consequently, the present study was designed to assess the intertwining impact of coadministration of cefepime (CP, a wide spectrum antibiotic) and diclofenac sodium (DF, an NSAID) on rat's liver, kidney, and testes. Rats received saline, CP (180 mg/kg/day, IM), DF (10 mg/kg/day, IM), or a combination of CP and DF. After 14 days, CP or DF induced tissue damage expressed by marked biochemical alterations in hepatic and renal function tests. Besides this, disrupted lipid metabolism and testosterone levels along with significant histological changes in hepatic, renal, and testicular tissues were noticed. A significant increase in malondialdehyde and decreases in superoxide dismutase and catalase activities alongside significant upregulated caspase 3 expression in tissues following CP or DF treatment suggested a bearable influence of oxidative stress, lipid peroxidation, and cell death. Accordingly, the simultaneous therapy of CP and DF evoked more obvious tissue damage than their individual treatment. Overall, data concluded that concurrent use of CP and DF in medical practice is a worrisome matter, so it should be done cautiously to avoid synergistic deleterious outcomes.

Egg Yolk IgY: A Novel Trend of Feed Additives to Limit Drugs and to Improve Poultry Meat Quality.

Drugs that are commonly used in poultry farms can potentially cause a detrimental effect on meat consumers as a result of chemical residues. Therefore, seeking a natural alternative is crucial for the health of the consumers. The egg yolk immunoglobulin Y (IgY) is a promising natural replacement for antibiotics in the broilers' diet. There is a scarce focus on the influence of probiotics and IgY on the quality and the nutritive values of broiler meat and whether it can efficiently displace the anti-microbial power of antibiotics. Herein we used 40 Ross chicks (1.2 ± 0.43 days old) and separated them into four groups with variant feed additives (basal diet "control," probiotic, IgY, and probiotic + IgY). Our findings showed that the combination of probiotic and IgY supplementation enhanced the carcass quality traits and decreased the pH values that could retard spoilage due to bacteria and improve shelf life and meat quality. The same group also achieved a significant reduction in thiobarbituric acid value, indicating an improvement of meat quality. Moreover, color, shear force, water holding capacity, and cooking loss were most acceptable in broiler meat supplemented with IgY, which confirmed the highest carcass quality. Notably, the weight gain in the combination group has been greatly increased. Also, the protein percentage was the highest (22.26 ± 0.29, P < 0.001) in this combined supplementation group, which revealed the highest nutritive values. Staphylococcus aureus and Escherichia coli could not be detected in the meat of the probiotics group and/or in the combined treatment group. Interestingly, the IgY group showed an evidence of the killing power (log colony-forming units per milliliter) of S. aureus and Listeria monocytogenes at 1,500 µg/ml. Our findings, in vitro as well as in vivo, revealed that the combination group had antimicrobial bioactivity and enhanced the chickens' immunity. Therefore, IgY, a novel trend of feed additives, can be used to limit drugs. Additionally, the mortality percentage recorded was zero in all groups that received feed supplementation, while the combination group reached the best financial advantages. We concluded that feeding IgY powder with probiotic is a frontier to improve the productivity, immunity, and meat quality of broilers.

Nutritional characterization of various classes of Egyptian beef luncheon.

OBJECTIVES: The present work was conducted to investigate the nutritional profile of the highly consumed beef luncheon in Egypt. Besides, the potential health hazards associated with the consumption of luncheon were highlighted. MATERIAL AND METHODS: A total of 60 beef luncheon samples were collected from Egyptian markets. They were classified into three classes: A, B, and C based on their prices. The collected samples were examined for their chemical composition by determining moisture, protein, fat, ash, carbohydrate, and energy percentage. The contents of trace elements were also investigated. RESULTS: The obtained findings showed a comprehensive dissimilarity in the chemical composition. According to the fresh weight base, moisture, protein, fat, ash, and carbohydrate fluctuated from 56.97 to 64.52, 3.50 to 16.10, 4.73 to 13.39, 3.30 to 3.51, and 11.32 to 27.44% w/w, respectively. The highest price class A Egyptian beef luncheon had more accepted nutritive value and dietary energy content. All the examined classes were low in calcium, potassium, zinc, and magnesium. The target hazard quotient indicated that the trace elements did not present any risks for consumers except for sodium. High phosphorous content and high phosphorus-protein ratio were observed in all categories which had a harmful health effect, hence named "new cholesterol." CONCLUSION: Based on the information, this study is the leading work that deeply investigated the chemical composition of the Egyptian luncheon classes, and the obtained data could be beneficial to update the nutritional knowledge used by dietitians and the responsible for nutrition assessment and surveillance by the government.

The Impact of Probiotics and Egg Yolk IgY on Behavior and Blood Parameters in a Broiler Immune Stress Model.

Feed additives are used frequently in variable combinations to maximize broiler productivity and consumer safety. Therefore, we evaluated the efficiency of feed additives used in four different diets: a basal diet, a probiotic (PRO-PAC®) supplement diet, an egg yolk purified immunoglobulin Y (IgY) supplemented diet, and a combination of IgY and PRO-PAC® supplement (n = 15 for each group). We assessed the improvement of behavioral and hematological parameters of Ross broilers before and after an immune stress challenge using lipopolysaccharide (LPS). Behavioral as well as physiological parameters were analyzed. The standing frequency was the highest (P < 0.05) in broilers supplemented with a combination of probiotics and IgY. Likewise, latency approach score to a novel object improved (P < 0.01) in the combination group at week-3. After intraperitoneal injection of LPS, this combination group achieved the best gait score at week-3, followed by week-5, compared to birds fed the basal diet. The heterophil/lymphocyte (H/L) ratio, heterophil differential count, and eosinophil differential count in the basal diet group that was challenged with LPS were significantly increased (P < 0.01, P < 0.001, P < 0.05, respectively) compared to the combination groups. Therefore, we concluded that the combination of IgY and probiotics can significantly improve the behavior and the underlying physiological parameters of Ross broilers. Consequently, this combination can improve the broilers' health, welfare and produce a safe meat free from harmful chemical residues.

Novel PRMT5-mediated arginine methylations of HSP90A are essential for maintenance of HSP90A function in NDRG2low ATL and various cancer cells.

N-myc downstream-regulated gene 2 (NDRG2) as a tumor suppressor is frequently downregulated in human T-lymphotropic retrovirus (HTLV-1)-infected adult T-cell leukemia (ATL) and variety of cancers, and negatively regulates PI3K signaling pathways through dephosphorylation of PTEN with protein phosphatase 2A (PP2A). We recently identified that protein arginine methyltransferase 5 (PRMT5) is one of novel NDRG2 binding proteins and the knockdown of PRMT5 induces cell apoptosis with degradation of several signaling molecules. To investigate how the apoptosis is induced by the knockdown PRMT5 expression, heat shock protein 90 alpha (HSP90A) was identified as a binding protein for NDRG2 or PRMT5 by immunoprecipitation-mass analysis. NDRG2/PP2A complex inhibited arginine methyltransferase activity of PRMT5 through dephosphorylation at Serine 335 (S335); however, in NDRG2low ATL-related cells, highly phosphorylated PRMT5 at S335 was mainly localized in cytoplasm with binding to HSP90A, resulting in enhancing arginine-methylation at the middle domain (R345 and R386). Since knockdown of PRMT5 expression or forced expression of HSP90A with alanine replacement of R345 or R386 induced apoptosis with the degradation of client proteins in NDRG2low ATL-related and other cancer cells, we here identified that the novel arginine methylations of HSP90A are essential for maintenance of its function in NDRG2low ATL and other cancer cells.

Identification of serum N-glycoproteins as a biological correlate underlying chronic stress response in mice.

Glycosylation is a post-translational protein modification in eukaryotes and plays an important role in controlling several diseases. N-glycan structure is emerging as a new paradigm for biomarker discovery of neuropsychiatric disorders. However, the relationship between N-glycosylation pattern and depression is not well elucidated to date. This study aimed to explore whether serum N-glycan structures are altered in depressive-like behavior using a stress based mouse model. We used two groups of BALB/c mice; (i) treated group exposed to chronic unpredictable mild stress (CUMS) as a model of depression, and (ii) control group. Behavioral tests in mice (e.g., sucrose preference test, forced swimming test, and fear conditioning test) were used to evaluate the threshold level to which mice displayed a depressive-like phenotype. Serum N-glycans were analyzed carefully using glycoblotting followed by Matrix-assisted laser desorption ionization-time of flight/mass spectrometry (MALDI-TOF/MS) to exhibit N-glycan expression levels and to illustrate the changes in the N-glycome profile. N-glycan expression levels were commonly altered in the depressive-like model and correlated well with the behavioral data. Our results indicated that sialylated N-glycan was identified as a biomarker associated with depressive symptoms, which may have utility as a candidate biomarker for the clinical diagnosis and monitoring of depression.