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Background: This study aimed to assess the histological and radiographic effects of sodium hexametaphosphate (SHMP) as a direct pulp capping (DPC) agent in immature permanent dog premolars., Methods: A split-mouth design was employed with three healthy 4-month-old Mongrel dogs, each having 36 premolars. The premolars were randomly assigned to either SHMP or MTA. The specimens were stained with hematoxylin and eosin (H&E) and Masson's trichrome, and histologically examined three months after the animals were sacrificed. To assess root maturity, radiographic changes in root length (RL), root surface area (RSA), and apical foramen width (AFW) were measured at baseline and after 3 months. Quantitative data were analyzed using the paired-sample t-test, while the qualitative data based on Stanley's histological scoring system were tested using the Monte Carlo exact test. The level of significance was set at 5%., Results: Histological findings showed no significant differences between the two groups, except for the average thickness of the predentin and odontoblastic layers, which was significantly higher in the SHMP specimens (P < 0.0001). The frequencies of fully calcified dentin bridges and regularly arranged dentinal tubules were significantly higher in the SHMP specimens (P < 0.05). Both materials showed comparable radiographic measurements (P > 0.05), except for the change in RL, which was significantly longer in the SHMP group (P < 0.05)., Conclusions: There were no significant differences between SHMP and MTA in some respects. Histological evaluation showed that SHMP provided better bioinductive and biocompatible properties compared to MTA. Radiographically, both materials showed comparable root maturogenesis outcomes, except for the significant increase in RL in the SHMP group. SHMP may be a suitable alternative material for DPC in the treatment of immature permanent teeth., Competing Interests: Declarations. Ethics approval and consent to participate: The project title was "Histopathologic and radiographic evaluation of pulpal response to sodium hexametaphosphate (SHMP) compared to mineral trioxide aggregate in direct pulp capping of young permanent dog teeth" was reviewed by the Research Ethics Committee, Faculty of Dentistry Minia University (Approval no. 708). The date of registration was Feb 28, 2023. All experimental procedures were performed in accordance with the guidelines of the European Union Council (86/609/EU). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Diabetic nephropathy (DN) is a significant global health concern with a high morbidity rate. Accumulating evidence reveals that Galectin-3 (Gal-3), a β-galactoside-binding lectin, is a biomarker in kidney diseases. Our study aimed to assess the advantageous impacts of modified citrus pectin (MCP) as an alternative therapeutic strategy for the initial and ongoing progression of DN in mice with type 2 diabetes mellitus (T2DM). The animal model has been split into four groups: control group, T2DM group (mice received intraperitoneal injections of nicotinamide (NA) and streptozotocin (STZ), T2DM+MCP group (mice received 100 mg/kg/day MCP following T2DM induction), and MCP group (mice received 100 mg/kg/day). After 4 weeks, kidney weight, blood glucose level, serum kidney function tests, histopathological structure alterations, oxidative stress, inflammation, apoptosis, and fibrosis parameters were determined in renal tissues. Our findings demonstrated that MCP treatment reduced blood glucose levels, renal histological damage, and restored kidney weight and kidney function tests. Additionally, MCP reduced malondialdehyde level and restored glutathione level, and catalase activity. MCP demonstrated a notable reduction in inflammatory and apoptosis mediators TNF-α, iNOS, TGF-βRII and caspase-3. Overall, MCP could alleviate renal injury in an experimental model of DN by suppressing renal oxidative stress, inflammation, fibrosis, and apoptosis mediators., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The male reproductive system is negatively influenced by Al exposure. Al represented a considerable hazard to men's reproduction capabilities. Amygdalin (AMG) and spirulina platensis (SP) have been considered to have a strong antioxidant and repro-protective activity; also, targeted drug delivery systems called niosomes improve the distribution of water-soluble medications like amygdalin and spirulina. Current study targeted to determine the effectiveness of AMG and SP against negative reproductive impact resulted by aluminum chloride (AlCl 3 ) toxicity. Sixty adult male albino rats were separated into 6 groups, including the control group, which received distilled water; AlCl 3 group, which received AlCl 3 ; AMG+AlCl 3 group, which received AlCl 3 +AMG; AMGLN+AlCl 3 group, which received AlCl 3 +amygdalin-loaded niosomes; SP+AlCl 3 group, which received AlCl 3 +SP; and SPLN+AlCl 3 group, which received AlCl 3 +spirulina-loaded niosomes. All treatments were orally gavaged daily for 5 weeks, and rats were weighed weekly. At the termination of the experiment, some males (three from each group) were used for fertility traits via mating thirty virgin rat females (in a ratio of 1:2 and 2:3 male:female, respectively) followed by recording of birth weights and litter size (number of pups per each female) at birth to assess males' reproductive capability. Other males were euthanized for collection of serum, epididymal semen samples, and tissue samples for biochemical, sperm evaluation, gene expression, and histopathological measurements. There are a considerable number of negative impacts of AlCl 3 on male fertility clarified by declined serum testosterone levels; an increased oxidative stress (MDA, TAC); deteriorated semen quality; down-regulation of CYP11A1, StAR, and HSD-3b gene expressions; and testicular tissue degenerative changes. In addition, litter size (number of pups per each female) and birth weights of pups obtained from mated females were affected. AMG and SP treatments, either in niosomal or conventional form, alleviated the AlCl 3 negative effects by reducing oxidative stress; increasing testosterone levels; improving semen quality; upregulating of CYP11A1, StAR, and HSD-3b gene expressions; and reducing degenerative changes of testicular tissue. Besides, negative reproductive effect was diminished as observed by changes in the litter size (number of pups per each female) and birth weights of pups obtained from mated females. AMG and SP treatments (either in niosomal or conventional form), ameliorated the AlCl 3 negative effects as they possess powerful antioxidant activity, as well as they have the ability to improve the reproductive activity of affected males., (© 2023. The Author(s).)

Background: Red ginseng and propolis are well-known antioxidants that have been related to a reduction in oxidative stress., Objective: This study evaluated the efficiency of red ginseng and propolis, either in powder or as nano-forms against dexamethasone-induced testicular oxidative challenges in adult male albino rats., Methods: Forty rats were divided into 8 equal groups including control negative group that was given vehicle (DMSO), control positive group that was administered dexamethasone in addition to the nano-propolis, nano-ginseng, nano-propolis + dexamethasone, nano ginseng+dexamethasone, propolis+dexamethasone and ginseng + dexamethasone groups. Serum, semen and tissue samples were obtained., Results: Lower testosterone levels, higher levels of MDA, and lower levels of total antioxidant capacity in serum, as well as impaired semen quality and a disturbed histopathological picture of both the testis and seminal glands, were all observed as significant negative effects of dexamethasone. These findings were confirmed by lower gene expression profiles of CYP11A1, StAR, HSD-3b, Nrf-2 and ACTB-3b in testicular and seminal gland tissues. The most powerful anti-dexamethasone effects were obtained with either propolis in nanoform or conventional ginseng., Conclusion: Propolis nano-formulation and ginseng in conventional form could be considered excellent candidates to ameliorate the oxidative stress provoked by dexamethasone, however, neither nano-ginseng nor conventional propolis showed such effects., (© 2023. The Author(s).)

This study aimed to evaluate impacts of dietary probiotics (Bacillus subtilis PB6) and humate substances (HS) supplementation on histomorphometry of small intestine and immune organs, blood parameters of growing quail. A total of 216 unsexed quails (seven days old) were randomly distributed to six groups. The 1 st group did not receive any supplements (control), 2 nd group received B. subtilis (CloSTAT: 0.5 g/kg diet), 3 rd and 4 th groups received HS (4 and 8 g/kg diet, respectively), 5 th and 6 th groups received CloSTAT + 4g HS and CloSTAT + 8g HS, respectively. Results showed that the inclusion of B. subtilis alone in quail diets significantly improved histomorphometry indices of intestine and immune organs compared to the control. Dietary supplementation of HS alone led to deteriorating histomorphometry indices of intestinal segments and immune organs compared to the control. CloSTAT, HS or both improved lipid profile and antioxidant parameters. Serum mineral levels did not differ significantly among groups except for Ca levels. In conclusion, dietary probiotics supplementation enhanced histomorphometry of intestine and immune organs and improved serum Ca, lipid profile and antioxidant indices. Moreover, the addition of HS (4 or 8 g/kg diet) improved lipid profile and antioxidant indices, but led to undesirable results in intestinal development and immune organs.

Atrazine, as an herbicide, is used widely worldwide. Because of its prolonged persistence in the environment and accumulation in the body, atrazine exposure is a potential threat to human health. The present study evaluated the possible protective effects of zinc oxide nanoparticles and vitamin C against atrazine-induced hepatotoxicity in rats. Atrazine administered to rats orally at a dose of 300 mg/kg for 21 days caused liver oxidative stress as it increased malondialdehyde (MDA) formation and decreased reduced glutathione (GSH) contents. Atrazine induced inflammation accompanied by apoptosis via upregulation of hepatic gene expression levels of NF-κB, TNF-α, BAX, and caspase-3 and downregulation of Bcl-2 gene expression levels. Additionally, it disturbed the metabolic activities of cytochrome P450 as it downregulated hepatic gene expression levels of CYP1A1, CYP1B1, CYP2E1. The liver function biomarkers were greatly affected upon atrazine administration, and the serum levels of AST and ALT were significantly increased, while BWG%, albumin, globulins, and total proteins levels were markedly decreased. As a result of the above-mentioned influences of atrazine, histopathological changes in liver tissue were recorded in our findings. The administration of zinc oxide nanoparticles or vitamin C orally at a dose of 10 mg/kg and 200 mg/kg, respectively, for 30 days prior and along with atrazine, could significantly ameliorate the oxidative stress, inflammation, and apoptosis induced by atrazine and regulated the hepatic cytochrome P450 activities. Furthermore, they improved liver function biomarkers and histopathology. In conclusion, our results revealed that zinc oxide nanoparticles and vitamin C supplementations could effectively protect against atrazine-induced hepatotoxicity., (© 2023. The Author(s).)

This study was conducted to evaluate the effects of Spirulina platensis in Nile tilapia diets on growth performance, blood hematological and biochemical parameters, immunological status, and intestinal histomorphometry. A total of 228 fish were randomly allocated into four groups with triplicates (19 fish per replicate). The first group was fed the control diet, which contained no Spirulina supplementation. The other three groups were fed diets containing graded levels of powdered Spirulina: 2.5%, 5.0%, and 10.0% in the second, third, and fourth group, respectively. S. platensis was added to the diets partially substituting the fish meal content. The experiment lasted for 8 weeks. The results showed that dietary Spirulina supplementation improved (P < 0.05) the body weight and length, weight gain, specific growth rate, condition factor, and feed conversion efficiency. Moreover, Spirulina increased significantly (P < 0.05) the hemoglobin, PCV, RBCs, and WBCs count. Also, it increased the lymphocytes, eosinophils, IgM level, lysozyme activity, and phagocytic activity in the blood. Additionally, the Spirulina raised (P < 0.05) the serum albumin level but reduced (P < 0.05) the creatinine and urea levels. The addition of Spirulina increased (P < 0.05) the height and width of intestinal villi and the lymphocytes and goblet cells count in the intestine. The obtained results were increased by increasing the inclusion level of Spirulina, especially for body weight and length, weight gain, FCR, phagocytic activity, and intestinal parameters. In conclusion, supplementing S. platensis can improve the growth performance of fish. Moreover, it can stimulate the immunity of fish through increasing the level of immunological blood indicators (IgM, lysozyme, phagocytic activity, lymphocytes, and eosinophils) as well as the local intestinal immunity (lymphocytes and goblet cells). So, it can be recommended to use S. platensis in fish diets not only to improve the growth performance but also to enhance the immune status., (© 2023. The Author(s).)

Chronic kidney disease is a crucial health problem associated with high morbidity and mortality. Eugenol is a natural phenolic plant compound with various pharmacological activities including antioxidant and anti-inflammatory properties. This study was designed to evaluate the possible protective effect of different eugenol doses in an experimental model of chronic CCl 4 -induced renal damage and investigate various mechanisms that underlie this postulated effect. Eugenol treatment (100 mg/kg) ameliorated kidney damage induced by CCl 4 and rectified the distorted kidney function parameters and renal histological structure. Additionally, eugenol at a dose of 100 mg/kg suppressed the upregulated oxidative stress, inflammation and apoptosis in CCl 4 -treated rats as evident by down regulations of NADPH oxidase (NOX2 and NOX4), proinflammatory markers (IL-6 and TNF-α) and proapoptotic markers (cyt c and caspase-3), respectively. Importantly, eugenol co-administration in rats challenged with CCl 4 downregulated the renal protein expressions of both TGF-β as well as pAkt compared with CCl 4 group. In conclusion, eugenol showed a potent nephroprotective effect against CCl 4 -induced renal damage through its antioxidant, anti-inflammatory and anti-fibrotic activities., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The physiological effects of dietary boron (B) supplementation for farm animals specifically goat on male fertility are still scarce and need deep investigation. Thus, the current study was designed to investigate how adding B to the diet of male goats affected their testicular and thyroid activity. For that purpose, twelve male goats were divided randomly into two groups (six animals each); control group that was fed the basal diet and B group that was fed the basal diet containing 70 mg B/kg diet for 6 months. Serum samples were collected at different intervals, while testicular biopsies were obtained at the end of the experiment. The results showed that 6 months of dietary B supplementation resulted in a significant increment in serum B concentration. The results of repeated measure analysis showed that there were significant GROUP and TIME × GROUP interactions effects on blood testosterone levels (F = 119.408, p = .000 and F = 6.794, p = .013, respectively), demonstrating that compared with control, B supplementation caused a significant rise in serum testosterone levels over time. However, the mean animal body weights and the serum levels of triiodothyronine (T3) and thyroxine (T4) were kept comparable with the control ones at the different time points. The most striking finding is that B supplementation increased significantly the mRNA expression of the CYP17A1 which is essential for steroidogenesis (p < .001). In addition, a histological examination of testicular tissue corroborated our findings and demonstrated that B supplementation had a positive effect. As a result, B might be considered an excellent food supplement that could be safely added to the male goats' diet at the current dose to improve their reproductive capacity., (© 2022 Wiley-VCH GmbH.)

This study was conducted to evaluate the effect of using protease in diets of Nile tilapia on growth performance, water quality, blood parameters and intestinal morphology. The cost of these diets and their return on fish performance was calculated. A total of 360 fish were randomly allocated into four groups with triplicates (30 fish per replicate). Four diets were formulated; two controls (without protease supplementation) and two experimental diets (supplemented with protease). The first control diet contained the normal protein requirement (30% CP; control +ve), while the second control had a low protein content (29% CP; control -ve). The third diet was supplemented with protease at a dose of 500 g/ton, and its CP content was reduced to 29.0%, by reducing the fish meal content. The fourth diet contained the same CP level as the first control (30%) and supplemented with 250 g protease per ton feed. The experiment lasted for 14 weeks. The results showed that body weight and length, weight gain, specific growth rate, feed intake and feed conversion efficiency in the control -ve group (low CP) supplemented with protease were similar (p > 0.05) to that of the control +ve with normal CP content. However, these performance parameters were lower (p < 0.05) in fish fed low CP diet without protease supplementation. Providing protease to the control +ve diet improved all measured performance indices. The ammonia and nitrite concentrations of the water were reduced (p < 0.05) in control -ve and protease-supplemented groups. The height and width of intestinal villi were increased (p < 0.05) in fish fed diets containing protease. The inclusion of protease reduced the diet cost and also the feed cost of fish weight gain. In conclusion, supplementation of protease can improve the productive performance of fish, spare dietary protein and produce economical diets. Moreover, it can help in improving the water quality of fish via lowering the ammonia and nitrite contents, or through increasing the degradation of dietary protein., (© 2021 Wiley-VCH GmbH.)

The purpose of this study was to assess the effects of dietary humate substances (HS) and CloSTAT (Bacillus subtilis PB6) on the thyroid activity and histology, iron profile, blood haematology and performance of growing Japanese quail. A total of 216 unsexed 7-day-old quail chicks were randomly assigned to six groups. The first group was fed a basal diet (BD) without any additives (control); the 2nd group received BD plus 0.05% CloSTAT, the 3rd and 4th groups were given BD plus 0.4% and 0.8% HS, respectively; and the 5th and 6th groups were administered BD plus CloSTAT + 0.4% HS and BD plus CloSTAT + 0.8% HS, respectively. The results showed that the growth performance was improved with the addition of CloSTAT alone or in combination with 0.4% HS compared with the control. Haematological parameters, iron level and transferrin saturation % were significantly (p < 0.001) increased by feeding HS compared with the control group. Serum thyroxin and triiodothyronine levels were significantly (p = 0.001) increased by adding CloSTAT relative to the control. Supplementation of 0.8% HS caused deterioration in histomorphometry parameters of the thyroid gland, but these parameters were improved in response to CloSTAT compared with the control. In conclusion, dietary B. subtilis PB6 as CloSTAT or CloSTAT + 0.4% HS supplementation may be efficacious in enhancing the growth performance and boosting the thyroid activity of growing Japanese quail. Moreover, the addition of 0.4% or 0.8% HS to quail diets boosted their iron profile and haematological parameters., (© 2021 Wiley-VCH GmbH.)

Pulmonary fibrosis is a serious ailment that may progress to lung remodeling and demolition, where the key participants in its incidence are fibroblasts responding to growth factors and cellular calcium swinging. Calcium channel blockers, like nifedipine (NFD), may represent auspicious agents in pulmonary fibrosis treatment. Unfortunately, NFD bears complicated pharmacodynamics and a diminished systemic bioavailability. Thus, the current study aimed to develop a novel, non-invasive nanoplatform for NFD for direct/effective pulmonary targeting via intratracheal instillation. A modified solvent emulsification-evaporation method was adopted for the fabrication of NFD-nanocomposites, integrating poly(D,L-lactide-co-glycolide) (PLGA), chitosan (CTS), and polyvinyl alcohol, and optimized for different physiochemical properties according to the 3 2 full factorial design. Additionally, the aerodynamic behavior of the nanocomposites was scrutinized through cascade impaction. Moreover, the pharmacokinetic investigations were conducted in rats. Furthermore, the optimum formulation was tested in bleomycin-induced pulmonary fibrosis in rats, wherein fibrotic and oxidative stress parameters were measured. The optimum nanocomposites disclosed a nanosized spherical morphology (226.46 nm), a high entrapment efficiency (61.81%) and a sustained release profile over 24 h (50.4%). As well, it displayed a boosted in vitro lung deposition performance with a mass median aerodynamic diameter of 1.12 µm. Pharmacokinetic studies manifested snowballed bioavailability of the optimal nanocomposites by 3.68- and 2.36-fold compared to both the oral and intratracheal suspensions, respectively. The intratracheal nanocomposites revealed a significant reduction in lung fibrotic and oxidative stress markers notably analogous to normal control besides repairing abnormality in TGF-β/β-catenin pathway. Our results conferred a compelling proof-of-principle that NFD-CTS-PLGA nanocomposites can function as a promising nanoparadigm for pulmonary fibrosis management.

The precise analysis of the contents of the red carrot is still ambiguous and its role in the maintenance of male fertility needs to be further reconnoitered. Hence, this study targets the physiological impacts of either red carrot methanolic extract (RCME) or vitamin E (Vit. E), co-administrated with cadmium chloride (CdCl 2 ) on rat testes, specifically those concerned with apoptosis and oxidative challenge. Four groups of adult male rats ( n = 12) are used; control, CdCl 2 , CdCl 2 + Vit. E and CdCl 2 + RCME. LC-MS analysis of RCME reveals the presence of 20 different phytochemical compounds. Our data clarify the deleterious effects of CdCl 2 on testicular weights, semen quality, serum hormonal profile, oxidative markers and Bax/Bcl-2 ratio. Histopathological changes in testicular, prostatic and semen vesicle glandular tissues are also observed. Interestingly, our data clearly demonstrate that co-administration of either RCME or Vit. E with CdCl 2 significantly succeeded in the modulation ( p < 0.05) of all of these negative effects. The most striking is that they were potent enough to modulate the Bax/Bcl-2 ratio as well as having the ability to correct the impaired semen picture, oxidant status and hormonal profile. Thus, RCME and Vit. E could be used as effective prophylactic treatments to protect the male reproductive physiology against CdCl 2 insult.

Nicotine is the major alkaloid present in cigarettes that induces various biochemical and behavioral changes. Nanonaringenin (NNG) and vitamin E are antioxidants that are reported to mitigate serious impairments caused by some toxins and oxidants. Thus, we aimed to investigate the efficacy of NNG, vitamin E, and their combinations to ameliorate behavioral, biochemical, and histological alterations induced by nicotine in rats. Adult male albino rats were randomly grouped into six equal groups (10 rats/group): control, N (nicotine 1 mg/kg b.w./day S/C from 15 th to 45 th day, 5 days a week), NNG (25 mg/kg b.w./day orally for 45 days), N + NNG, N + E (nicotine + vitamin E 200 mg/kg b.w./day orally), and N + NNG + E (nicotine + NNG + vitamin E at the aforementioned doses). Behavioral tests were conducted on day 15 and 30 postnicotine injection, while memory tests, brain neurotransmitters, antioxidants, and histopathological examination were examined at day 30 only. As a result, nicotine impaired rats' activity (hypoactivity and hyperactivity) and memory, induced anxiolytic and anxiogenic effects on rats, and altered neurotransmitters (acetylcholinesterase, serotonin, and dopamine), and redox markers (MDA, H 2 O 2 , GSH, and catalase) levels in brain homogenates. Thickening and congestion of the meninges and degeneration of the cerebral neurons and glia cells were observed. Cosupplementation with NNG, vitamin E, and their combination with nicotine was beneficial in the alleviation of activity impairments and improved short memory and cognition defects and exploratory behaviors. Our results indicate the antioxidant potential of NNG and vitamin E by modulating redox markers and neurotransmitters in the brain. Thus, data suggest that the prophylactic use of NNG, vitamin E, and/or their combination for (45 days) may have a successful amelioration of the disrupted behavior and cognition and biochemical and histopathological alterations induced by nicotine., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Mohamed A. Kandeil et al.)

Gestational bisphenol A (BPA) exposure induced multiple programmed diseases in the adult offsprings. Thus, this study targeted exploring the physiological impacts of melatonin (MEL) as a reprogramming strategy against in utero BPA exposure on reproductive capacity of adult F1 female rat offspring. Forty adult pregnant albino female rats were divided equally into 5 groups (n = 8): group I (control), group II (low-dose BPA; 25 μg BPA/kg B.w.t.), group III (low-dose BPA + 10 mg MEL/kg B.w.t.), group IV (high-dose BPA; 250 μg/kg B.w.t.), and group V (high-dose BPA + MEL). Treatments were given daily by subcutaneous (s/c) injection from the fourth day of pregnancy until full term. After delivery, female offspring were selected, and on postnatal day 60, adult offspring were examined for estrus regularity and then were sacrificed at estrus to collect blood and tissue samples. Findings clarified that in utero BPA exposure (both doses) increased significantly (P < 0.05) the ovarian weights and the serum levels of estrogen but decreased that of triiodothyronine (T3) compared to control groups. Significant increasing of serum malondialdehyde (MDA) and decreasing of total antioxidant capacity (TAC) were also detected. Both doses of BPA disturbed remarkably the estrus cycles and caused marked aberrations in ovarian and uterine tissues. Interestingly, prenatal MEL co-treatment with BPA mitigated significantly all of these degenerative changes. Thus, this study first demonstrated that prenatal MEL therapy could be used as a potent reprogramming intervention against BPA-induced reproductive disorders in the adult F1 female rat offspring.

Plant hormones are small regulatory molecules that exert pharmacological actions in mammalian cells such as anti-oxidative and pro-metabolic effects. Kinetin belongs to the group of plant hormones cytokinin and has been associated with modulatory functions in mammalian cells. The mammalian adenosine receptor (A2a-R) is known to modulate multiple physiological responses in animal cells. Here, we describe that kinetin binds to the adenosine receptor (A2a-R) through the Asn253 residue in an adenosine dependent manner. To harness the beneficial effects of kinetin for future human use, we assess its acute toxicity by analyzing different biochemical and histological markers in rats. Kinetin at a dose below 1 mg/kg had no adverse effects on the serum level of glucose or on the activity of serum alanine transaminase (ALT) or aspartate aminotransferase (AST) enzymes in the kinetin treated rats. Whereas, creatinine levels increased after a kinetin treatment at a dose of 0.5 mg/kg. Furthermore, 5 mg/kg treated kinetin rats showed normal renal corpuscles, but a mild degeneration was observed in the renal glomeruli and renal tubules, as well as few degenerated hepatocytes were also observed in the liver. Kinetin doses below 5 mg/kg did not show any localized toxicity in the liver and kidney tissues. In addition to unraveling the binding interaction between kinetin and A2a-R, our findings suggest safe dose limits for the future use of kinetin as a therapeutic and modulatory agent against various pathophysiological conditions.

Prevention of coccidiosis is one of the best ways of controlling disease. Therefore, the present study was carried out to evaluate the protective effect of ultraviolet (UV)-irradiated sporulated oocysts of Eimeria species against coccidiosis in layer chickens. One hundred forty-four one-day-old layer chicks were randomly divided into 4 groups (n = 36), including non-immunized/non-challenged negative control group (NC group), non-immunized/challenged control group (NIC group), non-irradiated sporulated oocyst/challenged group (CA group), and UV-irradiated sporulated oocyst/challenged (UV group). At the age of 4 days, chickens in groups UV and CA were both orally inoculated with 1.0 × 10 4 UV-irradiated and non-irradiated sporulated oocysts of Eimeria species, respectively. Chickens in groups NIC and NC were served as positive and negative controls, respectively. Chickens in all groups were orally challenged with 7.5 × 10 4 sporulated oocysts of Eimeria species except the NC group at the age of 21 days. The results revealed that chicks receiving UV-irradiated sporulated oocysts had no signs of illness with minimal or no changes in the cecal integrity and a significantly lower oocyst shedding (OPG) than in the NIC group. Additionally, the cytokine gene expression profiles were evaluated. Expression levels of IL-2, IL-12, and IFN-γ were significantly higher in the spleen of chicks in the UV and CA groups than in the NC group post-challenge. As expected, treatment with irradiated oocysts resulted in a significant reduction in oocyst shedding and maintenance of cecal mucosal integrity. Furthermore, the body weight was higher in chickens inoculated with UV-irradiated oocysts than their non-irradiated counterparts. In conclusion, our results demonstrate that inoculation with UV-irradiated sporulated oocysts of Eimeria species can produce a substantial reduction in infection symptoms.

Diclazuril, which is widely used for the prevention of coccidiosis in chickens, has a lethal effect on asexual and sexual stages of Eimeria spp. However, little is known about its effect on the exogenous stages of Eimeria spp. In this study, we evaluated the effect of in vitro treatment with 0.2% diclazuril on unsporulated and sporulated oocysts of Eimeria spp. For this purpose, a total of 180 male layer chicks aged one day were randomly divided into 5 experimental groups. Each group was divided into 3 replicates of 12 chicks each. Group 1 (G1) and Group 2 (G2) were negative (non-immunized and non-challenged) and positive (non-immunized and challenged) controls, respectively. Group 3 (G3) was immunized per os with 1.0 × 10 4 non-diclazuril treated-sporulated oocysts. Groups 4 (G4) was immunized per os with 0.2% diclazuril treated-unsporulated oocysts (1.0 × 10 4 ) in which diclazzuril didn't affect sporulation. Group 5 (G5) was immunized per os with 0.2% diclazuril treated-sporulated oocysts (1.0 × 10 4 ). Chicks of G2, G3, G4, and G5 were challenged with 7.5 × 10 4 untreated sporulated oocysts at the age of 21 days, while the group 1 chicks remained unchallenged. G4 and G5 animals immunized with 0.2% diclazuril-treated oocysts showed a significant decrease in bloody diarrhea severity, lesion scores, and oocyst counts in comparison to those immunized with untreated oocysts. Furthermore, histopathologic findings showed a low number of parasitic stages in cecal tissues in G4 and G5. A significant increased body weight gain was observed in Gs 4 and 5 in comparison to G2. In addition, expression levels of IL-2, IL-12, and IFN-γ were significantly increased in G4 and G5. In conclusion, diclazuril is effective in attenuating Eimeria oocysts and thus provides an alternative approach for using diclazuril-treated oocysts to protect chicks against Eimeria challenge., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: Cisplatin (CP) is a widely used broad-spectrum antineoplastic agent used to treat a variety of human malignancies. Neurotoxicity is clinically evident in patients who have undergone a full course of chemotherapy. The aim of this study was to investigate the possible protective effects of thymoquinone (TQ) and geraniol (Ger) against CP-induced neurotoxicity in rats., Main Methods: Forty male Wistar albino rats were allocated into four groups as follows: normal control, CP-induced neurotoxicity, CP + TQ and CP + Ger., Key Findings: Our results demonstrated that simultaneous treatment with either TQ or Ger and CP significantly abrogated oxidative stress and downregulated the apoptotic markers p38 mitogen-activated protein kinase (MAPK), STAT-1, p53, p21 and MMP9; FMO3, however, was insignificantly decreased. In addition to the biochemical results, we assessed the histopathological findings, which confirmed the protective effect of TQ and Ger against the brain damage induced by CP., Significance: The results of the present study indicate that simultaneous treatment with either TQ or Ger as natural antioxidants can provide protection against cisplatin-induced neurotoxicity in rats by attenuating oxidative stress and cell apoptosis., (Copyright © 2019. Published by Elsevier Inc.)

New strategies must be developed to improve poultry performance and health. One of these strategies is the use of supplementations as sodium butyrate (SB) to improve the physiological status and then increasing the growth performance, but the best period of age in which the addition of SB is more effective on birds is not well understood. Therefore, the aim of this study was to investigate the effect of dietary inclusion of SB supplementation through the first, second or whole growth period on some physiological indices and growth performance of growing Japanese quail. In total, 240 unsexed 1-day-old quail chicks were divided into four groups (three replicates per group of 20 chicks in each). The first group was fed basal diet without SB from 1 to 42 days (control, T1), while SB at a rate of 1 g/kg basal diet was mixed with the feed of the 2nd, 3rd and 4th groups of chicks from 1 to 21 days (SB 1 to 21, T2), 1 to 42 days (SB 1 to 42, T3) and 22 to 42 days (SB 22 to 42, T4) of age, respectively. The results stated that addition of SB significantly improved live BW at 21 days, feed conversion ratio (FCR) and BW gain (BWG) during 1 to 21 days in T2 and T3 groups compared to T1 and T4 groups. During the whole period, group T3 had higher BWG and better FCR than the other groups (T1, T2 and T4). At 21 days, no significant differences among all treatments were detected on haematology and serum biochemistry except total protein and cholesterol. At 42 days, SB supplementation significantly improved most serum constituents, haematological parameters, villus height and width of intestine and morphometry of immune organs. The group fed SB throughout the experiment (T3) showed the best results. In conclusion, it is recommended feeding quail on diets containing SB through the whole growth period to show its affirmative impact on the growth and physiological indices.

Schistosomiasis is one of the major health problems in many tropical and developing countries. Infection takes place once cerceriae penetrate human skin, then it changed into schistosomules. The schistosomules takes iron in the form of heme from host's haemoglobin, ferritin and transferrin. Iron is a vital element not only for growth and sexual maturity of schistosomules to adults but also for oogenesis. Since the trapped eggs are the pathological causative agent for most of pathogenesis and complications, the current work was designed to study the effects of early deprivation of schistosomules from iron in the host (in vivo) by chelating it with deferoxamine (DFO). The iron chelation has effects on growth, maturity and egg deposition, as well as it has ameliorative effects on liver pathology such as hepatic fibrosis. Mice were classified into four groups, normal control, DFO treated only, Schistosoma mansoni (S. mansoni) infected DFO untreated and S. mansoni infected DFO treated. The infected DFO treated mice showed significant reduction in fecal egg excretion with increased percentage of dead eggs and this was accompanied with a significant reduction of both total worm burden and hepatic egg load and increased dead egg percentage compared to the infected DFO untreated group. There was also a significant reduction in both serum and hepatic tissue ferritin concentrations in the infected DFO treated mice in comparison to the infected DFO untreated group. Additionally, a significant decrease in number and size of granulomas with subsequent improvement of liver fibrosis was recorded in the infected DFO treated group. This immunopathology was also associated with significant up regulation of Interlukine12 (IL12), Interferon gamma (IFN γ) and significant down regulation in interleukin4 (IL4), interleukin10 (IL10) in both serum and hepatic tissue in the infected DFO treated compared to other groups. Entirely, DFO succeeded in diminishing the growth, maturity and fecundity of S. mansoni with a subsequent improvement of hepatic pathology. As a result of the above findings, it can be concluded that DFO could be considered as a useful treatment against schistosomal infection., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Sildenafil citrate (SIL), a type 5-specific phosphodiesterase inhibitor, demonstrates valuable results in the management of infertility in women; however, the absence of vaginal dosage form in addition to the associated oral adverse effects minimize its clinical performance. The present study is concerned with SIL uterine targeting following intravaginal administration via optimization of cubosomal in situ gelling sponges (CIS). An emulsification method was employed for preparation of cubosomal dispersions incorporating glyceryl monooleate as a lipid phase and poloxamer 407 as a surfactant with or without polyvinyl alcohol as a stabilizer. Cubosomes were estimated regarding entrapment efficiency (EE%), particle size, and in vitro drug release. Chitosan (2% w/w) was incorporated into the optimum formulation and then lyophilized into small sponges. For the CIS, in vivo histopathological and pharmacokinetic studies were conducted on female Wistar rats and compared with intravaginal free SIL sponges (FIS) and oral SIL solution. SIL-loaded cubosomes showed EE% ranging between 32.15 and 72.01%, particle size in the range of 150.81-446.02 nm and sustained drug release over 8 h. Histopathological study revealed a significant enlargement in endometrial thickness with congestion and dilatation of endometrial blood vessels in intravaginal CIS compared to intravaginal FIS and oral-treated groups. The pharmacokinetic study demonstrated higher AUC 0-∞ and C max with oral administration compared to intravaginal CIS or intravaginal FIS indicating potential involvement of first uterine pass effect after intravaginal administration. Finally, intravaginal CIS could be considered as a promising platform for SIL uterine targeting with minimized systemic exposure and side effects.

SAPK-JNK pathway performs a significant role in the pathogenesis of type 2 diabetes. Balanites aegyptiaca (BA) is used as an anti-diabetic agent in folk medicine however its hypoglycemic mechanism is not fully elucidated. The current study aimed to evaluate the effect of crude extract, butanol, and dichloromethane fractions from BA on the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK-JNK) pathway in experimental diabetic rats. Six groups of male Wistar rats were included: normal control, diabetic, diabetic rats treated with crude, butanol or dichloromethane fraction from BA (50 mg/kg BW) and diabetic rats treated with gliclazide as a reference drug for one month. Our results suggested a protective role of treatment of diabetic rats with BA against oxidative stress-induced SAPK-JNK pathway. Moreover, BA treatment produced a reduction in plasma glucose, HbA 1c , lactic acid, lipid profile, malondialdehyde levels and produced an increase in insulin, reduced glutathione levels, catalase and superoxide dismutase activities compared with untreated diabetic rats. Moreover, it decreased apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase 1, protein 53 and increased insulin receptor substrate 1 in rat pancreas while it increased glucose transporter 4 in rat muscle. Analysis of BA extracts by LC-HRMS revealed the presence of different saponins with reported hypoglycemic effect. In conclusion, BA exerted hypoglycemic, hypolipidemic, insulinotropic and antioxidant effects. Additionally, it reduced apoptosis in pancreatic β-cells and increased glucose uptake in muscle. These results suggest that the hypoglycemic effect of BA is due to the inhibition of the SAPK-JNK pathway., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)