Silver and gold nanoparticles as a novel approach to fight Sarcoptic mange in rabbits.

Various kinds of pets have been known to contract the ectoparasite Sarcoptes scabiei. Current acaricides are becoming less effective because of the resistance developed by the mite besides their adverse effects on the general activity and reproductive performance of domestic pets. For this reason, the present study aims to discover a novel and safe approach using silver and gold nanoparticles to fight Sarcoptic mange in rabbits as well as to explain their mechanism of action. 15 pet rabbits with clinical signs of Sarcoptic mange that were confirmed by the microscopic examination were used in our study. All rabbits used in this study were assessed positive for the presence of different developing stages of S. scabiei. Three groups of rabbits (n = 5) were used as follows: group (1) didn't receive any treatment, and group (2 and 3) was treated with either AgNPs or GNPs, respectively. Both nanoparticles were applied daily on the affected skin areas via a dressing and injected subcutaneously once a week for 2 weeks at a dose of 0.5 mg/kg bwt. Our results revealed that all rabbits were severely infested and took a mean score = 3. The skin lesions in rabbits that didn't receive any treatments progressed extensively and took a mean score = of 4. On the other hand, all nanoparticle-treated groups displayed marked improvement in the skin lesion and took an average score of 0-1. All NPs treated groups showed remarkable improvement in the microscopic pictures along with mild iNOS, TNF-α, and Cox-2 expression. Both nanoparticles could downregulate the m-RNA levels of IL-6 and IFγ and upregulate IL-10 and TGF-1ß genes to promote skin healing. Dressing rabbits with both NPs didn't affect either liver and kidney biomarkers or serum Ig levels indicating their safety. Our residual analysis detected AgNPs in the liver of rabbits but did not detect any residues of GNPs in such organs. We recommend using GNPs as an alternative acaricide to fight rabbit mange.

The effects of TiO2, ZnO, IONs and Al2O3 metallic nanoparticles on the CYP1A1 and NBN transcripts in rat liver.

Introduction: Metal oxide nanoparticles are currently used widely in many aspects of human and animal life with broad prospects for biomedical purposes. The present work was carried out to investigate the effects of orally administrated TiO2NPs, ZnONPs, IONs and Al2O3NPs on the mRNA expression level of CYP 1A1 and NBN in the rat liver. Materials and Methods: Four groups of male Albino rats were given their respective treatment orally for 60 days in a dose of 1/20 of the LD50 TiO2NPs (600 mg/Kg b.wt/day), ZnONPs (340 mg/Kg b.wt/day), IONs (200 mg/kg b.wt/day) and Al2O3NPs (100 mg/Kg b.wt/day) and a fifth group served as a control group. Rresults: The mRNA level of CYP 1A1 and NBN showed up-regulation in all the NPs-treated groups relative to the control group. ZnONPs group recorded the highest expression level while the TiO2NPs group showed the lowest expression level transcript. Conclusion:The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide, iron oxide nanoparticles and titanium dioxide, respectively.

Novel insights on the probable mechanism associated with histamine oral model-inducing neuropathological and behavioral toxicity in rats.

Histamine (HIS) is an important chemical mediator that causes vasodilation and contributes to anaphylactic reactions. Recently, HIS is an understudied neurotransmitter in the central nervous system, and its potential role in neuroinflammation and neurodegeneration is a critical area of research. So, the study's goal is to investigate the consequences of repeated oral intake of HIS on the rat's brain and explore the mechanistic way of its neurotoxicity. Thirty male rats were divided into three groups (n = 10). The following treatments were administered orally to all rats every day for 14 days. Group (1) was given distilled water, whereas groups (2 & 3) were given HIS at dosage levels 250 and 500 mg/kg body weight (BWT), respectively. Brain tissue samples were collected at 7- and 14-days from the beginning of the experiment. Our results revealed that continuous oral administration of HIS at both doses for 14 days significantly reduced the BWT and induced severe neurobehavioral changes, including depression, dullness, lethargy, tremors, abnormal walking, and loss of spatial learning and memory in rats. In all HIS receiving groups, HPLC data showed a considerable raise in the HIS contents of the brain. Additionally, the daily consumption of HIS causes oxidative stress that is dose- and time-dependent which is characterized by elevation of malondialdehyde levels along with reduction of catalase activity and reduced glutathione levels. The neuropathological lesions were commonly observed in the cerebrum, striatum, and cerebellum and confirmed by the immunohistochemistry staining that demonstrating moderate to strong caspase-3 and inducible nitric oxide synthase expressions in all HIS receiving groups, mainly those receiving 500 mg/kg HIS. NF-κB, TNF-α, and IL-1ß gene levels were also upregulated at 7- and 14-days in all HIS groups, particularly in those getting 500 mg/kg. We concluded that ROS-induced apoptosis and inflammation was the essential mechanism involved in HIS-mediated neurobehavioral toxicity and histopathology.

Combined laser-activated SVF and PRP remodeled spinal sclerosis via activation of Olig-2, MBP, and neurotrophic factors and inhibition of BAX and GFAP.

A single injection of platelet-rich plasma (PRP) or stromal vascular fraction (SVF) in treating neurological ailments suggests promise; however, there is limited evidence of the efficacy of combination therapy. This trial aimed to determine whether combining SVF and PRP could provide further therapeutic effects in treating multiple sclerosis (MS). Fifteen Persian cats were separated into three groups (n = 5): group I (control negative), and group II (control positive); EB was injected intrathecally into the spinal cord and then treated 14 days later with intrathecal phosphate buffered saline injection, and group III (SVF + PRP), cats were injected intrathecally with EB through the spinal cord, followed by a combination of SVF and PRP 14 days after induction. Therapeutic effects were evaluated using the Basso-Beattie-Bresnahan scale throughout the treatment timeline and at the end. Together with morphological, MRI scan, immunohistochemical, transmission electron microscopy, and gene expression investigations. The results demonstrated that combining SVF and PRP successfully reduced lesion intensity on gross inspection and MRI. In addition to increased immunoreactivity to Olig2 and MBP and decreased immunoreactivity to Bax and GFAP, there was a significant improvement in BBB scores and an increase in neurotrophic factor (BDNF, NGF, and SDF) expression when compared to the positive control group. Finally, intrathecal SVF + PRP is the most promising and safe therapy for multiple sclerosis, resulting in clinical advantages such as functional recovery, MRI enhancement, and axonal remyelination.

Receptor-based pharmacophore modeling, molecular docking, synthesis and biological evaluation of novel VEGFR-2, FGFR-1, and BRAF multi-kinase inhibitors.

A receptor-based pharmacophore model describing the binding features required for the multi-kinase inhibition of the target kinases (VEGFR-2, FGFR-1, and BRAF) were constructed and validated. It showed a good overall quality in discriminating between the active and the inactive in a compiled test set compounds with F1 score of 0.502 and Mathew's correlation coefficient of 0.513. It described the ligand binding to the hinge region Cys or Ala, the glutamate residue of the Glu-Lys αC helix conserved pair, the DFG motif Asp at the activation loop, and the allosteric back pocket next to the ATP binding site. Moreover, excluded volumes were used to define the steric extent of the binding sites. The application of the developed pharmacophore model in virtual screening of an in-house scaffold dataset resulted in the identification of a benzimidazole-based scaffold as a promising hit within the dataset. Compounds 8a-u were designed through structural optimization of the hit benzimidazole-based scaffold through (un)substituted aryl substitution on 2 and 5 positions of the benzimidazole ring. Molecular docking simulations and ADME properties predictions confirmed the promising characteristics of the designed compounds in terms of binding affinity and pharmacokinetic properties, respectively. The designed compounds 8a-u were synthesized, and they demonstrated moderate to potent VEGFR-2 inhibitory activity at 10 µM. Compound 8u exhibited a potent inhibitory activity against the target kinases (VEGFR-2, FGFR-1, and BRAF) with IC50 values of 0.93, 3.74, 0.25 µM, respectively. The benzimidazole derivatives 8a-u were all selected by the NCI (USA) to conduct their anti-proliferation screening. Compounds 8a and 8d resulted in a potent mean growth inhibition % (GI%) of 97.73% and 92.51%, respectively. Whereas compounds 8h, 8j, 8k, 8o, 8q, 8r, and 8u showed a mean GI% > 100% (lethal effect). The most potent compounds on the NCI panel of 60 different cancer cell lines were progressed further to NCI five-dose testing. The benzimidazole derivatives 8a, 8d, 8h, 8j, 8k, 8o, 8q, 8r and 8u exhibited potent anticancer activity on the tested cell lines reaching sub-micromolar range. Moreover, 8u was found to induce cell cycle arrest of MCF-7 cell line at the G2/M phase and accumulating cells at the sub-G1 phase as a result of cell apoptosis.

Ameliorative effects of rutin and rutin-loaded chitosan nanoparticles on testicular oxidative stress and histological damage induced by cyclophosphamide in male rats.

Cyclophosphamide (CP) is broadly used to kill various tumor cells; however, its repeated uses have been reported to cause reproductive dysfunction and infertility. Natural flavonoid, rutin (RUT), possesses strong antioxidant and antiapoptotic activity that is attributed to ameliorate the reproductive dysfunction induced by CP. Many previous studies proved that the formulation of flavonoids in nanoemulsion has a promising perspective in mitigating the side effects of chemotherapy. Therefore, the main objective of this study was to investigate the ameliorative effects of RUT and RUT-loaded chitosan nanoparticles (RUT-CH NPs) against CP-induced reproductive dysfunction in male rats. For this aim, thirty-six male albino rats were randomly allocated into six groups as follows: control, RUT, RUT-CH NPs, CP, CP + RUT, and CP + RUT-CH NPs. In the CP groups, a single intraperitoneal injection of CP (150 mg/kg bwt) was administered on the first day of the experiment. RUT and RUT-CH NPs were orally administered either alone or with CP injection at a dose of 10 mg/kg bwt per day for 60 days. The results revealed that CP administration caused significant testicular oxidative stress damage through increasing the nitric oxide and malondialdehyde levels as well as decreasing the total antioxidant capacity and reduced glutathione contents. It also impaired spermatogenesis and steroidogenesis via altering the transcription levels of CYP11A1, HSD-3b, StAR, Bax, bcl-2, and Nrf-2 genes. Otherwise, the oral intake of either RUT or RUT-CH NPs with CP injection effectively attenuated these alterations and significantly improved the microscopic appearance of testicular tissue. In conclusion, this study highlights the potential of RUT either free or NPs in mitigating CP-induced testicular dysfunction via its antioxidant and anti-apoptotic properties.

Introducing the f0% method: a reliable and accurate approach for qPCR analysis.

BACKGROUND: qPCR is a widely used technique in scientific research as a basic tool in gene expression analysis. Classically, the quantitative endpoint of qPCR is the threshold cycle (CT) that ignores differences in amplification efficiency among many other drawbacks. While other methods have been developed to analyze qPCR results, none has statistically proven to perform better than the CT method. Therefore, we aimed to develop a new qPCR analysis method that overcomes the limitations of the CT method. Our f0% [eff naught percent] method depends on a modified flexible sigmoid function to fit the amplification curve with a linear part to subtract the background noise. Then, the initial fluorescence is estimated and reported as a percentage of the predicted maximum fluorescence (f0%). RESULTS: The performance of the new f0% method was compared against the CT method along with another two outstanding methods-LinRegPCR and Cy0. The comparison regarded absolute and relative quantifications and used 20 dilution curves obtained from 7 different datasets that utilize different DNA-binding dyes. In the case of absolute quantification, f0% reduced CV%, variance, and absolute relative error by 1.66, 2.78, and 1.8 folds relative to CT; and by 1.65, 2.61, and 1.71 folds relative to LinRegPCR, respectively. While, regarding relative quantification, f0% reduced CV% by 1.76, 1.55, and 1.25 folds and variance by 3.13, 2.31, and 1.57 folds regarding CT, LinRegPCR, and Cy0, respectively. Finally, f0% reduced the absolute relative error caused by LinRegPCR by 1.83 folds. CONCLUSIONS: We recommend using the f0% method to analyze and report qPCR results based on its reported advantages. Finally, to simplify the usage of the f0% method, it was implemented in a macro-enabled Excel file with a user manual located on https://github.com/Mahmoud0Gamal/F0-perc/releases .

Physiological roles of propolis and red ginseng nanoplatforms in alleviating dexamethasone-induced male reproductive challenges in a rat model.

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.

Mechanistic Approach on the Pulmonary Oxido-Inflammatory Stress Induced by Cobalt Ferrite Nanoparticles in Rats.

Cobalt ferrite nanoparticles (CFN) are employed in data storage, imaging, medication administration, and catalysis due to their superparamagnetic characteristics. The widespread use of CFN led to significantly increased exposure to people and the environment to these nanoparticles. Until now, there is not any published paper describing the adverse effect of repeated oral intake of this nanoformulation on rats' lungs. So, the current research aims to elucidate the pulmonary toxicity prompted by different concentrations of CFN in rats as well as to explore the mechanistic way of such toxicity. We used 28 rats that were divided equally into 4 groups. The control group received normal saline, and the experimental groups received CFN at dosage levels 0.05, 0.5, and 5 mg/kg bwt. Our findings revealed that CFN enhanced dose-dependent oxidative stress manifested by raising in the MDA levels and declining in the GSH content. The histopathological examination revealed interstitial pulmonary inflammation along with bronchial and alveolar damage in both 0.5 and 5 mg CFN given groups. All these lesions were confirmed by the immunohistochemical staining that demonstrated strong iNOS and Cox-2 protein expression. There was also a significant upregulation of TNFα, Cox-2, and IL-1ß genes with downregulation of IL-10 and TGF-ß genes. Additionally, the group receiving 0.05 mg CFN did not exhibit any considerable toxicity in all measurable parameters. We concluded that the daily oral intake of either 0.5 or 5 mg CFN, but not 0.05 mg, could induce pulmonary toxicity via NPs and/or its leached components (cobalt and iron)-mediated oxido-inflammatory stress. Our findings may help to clarify the mechanisms of pulmonary toxicity generated by these nanoparticles through outlining the standards for risk assessment in rats as a human model.

Coinfection of the gut with protozoal and metazoal parasites in broiler and laying chickens.

The chicken business faces substantial economic losses due to the risk of parasitic coinfection. Because the current study aimed to investigate enteric parasitic coinfections problems among the suspected examined chicken farms, samples were collected during the field investigation from suspected freshly dead birds, clinically diseased, apparently healthy, and litter samples for further laboratory parasitological, histopathological, and immunological examinations. Variable mortalities with various clinical indicators, such as ruffled feathers, weight loss, diarrhea of various colors, and a decline in egg production, occurred on the farms under investigation. In addition, the treatment protocols of each of the farms that were evaluated were documented and the m-RNA levels of some cytokines and apoptotic genes among the infected poultry have been assessed. The prevalence rate of parasitic coinfection in the current study was found to be 8/120 (6.66%). Parasitological analysis of the samples revealed that they belonged to distinct species of Eimeria, cestodes, and Ascaridia galli. When deposited, A. galli eggs were nonembryonated and ellipsoidal, but cestodes eggs possessed a thin, translucent membrane that was subspherical. Eimeria spp. oocysts in layer chickens were identified as Eimeria acervulina and Eimeria maxima in broiler chickens. Our findings proved that coinfection significantly upregulated the IL-1ß, BAX, and Cas-3 genes. Conversely, the IL-10, BCL-2, and AKT mRNA levels were downregulated, indicating that nematode triggered apoptosis. The existence of parasite coinfection was verified by histological investigation of the various intestinal segments obtained from affected flocks. A. galli and cestodes obstructed the intestinal lumen, causing different histological alternations in the intestinal mucosa. Additionally, the lamina propria revealed different developmental stages of Eimeria spp. It was determined that parasite coinfection poses a significant risk to the poultry industry. It was recommended that stringent sanitary measures management methods, together with appropriate treatment and preventative procedures, be employed in order to resolve such issues.

Estimating the in vitro cytotoxicity of the newly emerged zinc oxide (ZnO) doped chromium nanoparticles using the human fetal lung fibroblast cells (WI38 cells).

Advances in nanotechnology have been increased for more smart applications and getting the highest level of benefits, recently modification of the surface characters of nanoparticles is a new trend to get the optimal benefits, one of these modification is doping of zinc oxide with chromium nanoparticles (ZnO doped Cr NPs), the present study aimed to identify the surface characters of doped ZnO and their possible cytotoxic effects. The doped NPs were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR), Field emission scanning electron microscope (FESEM), and Electromagnetic Data Exchange (EDX). Human fetal lung fibroblast cells (WI38 Cells) was treated with variable concentrations of pure ZnO and ZnO doped Cr (0.01 %, 0.02 %, 0.03 % and 0.04 %) for 24 hr at 37 °C followed by the MTT assay. The cells treated with the obtained half-maximal inhibitory concentration (IC50). The supernatant and cells were collected for oxidant/anti-oxidant and molecular analysis.The observed FESEM features are in line with the reported XRD analysis confirming the hexagonal crystal symmetry of all samples. The findings revealed that pure ZnO exhibited potent cytotoxic effects followed by (0.03 % and 0.04 %). All tested NPs produce lipid peroxidation significantly (0.03 % and 0.04 %). The significant up regulation of Bcl-2-associated X protein (BAX) and apoptotic Caspase (Cas-3) transcription level were reported in ZnO and 0.03 % and 0.04 % in contrast the anti apoptitic B-cell lymphoma 2 (Bcl-2) is elevated in 0.01 % and 0.02 %. Doping of ZnO with Cr causing significant morphological changes which effect on their toxicity especially with 0.03 % and 0.04 %.

Repro-protective activity of amygdalin and spirulina platensis in niosomes and conventional forms against aluminum chloride-induced testicular challenge in adult rats: role of CYP11A1, StAR, and HSD-3B expressions.

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 (AlCl3) toxicity. Sixty adult male albino rats were separated into 6 groups, including the control group, which received distilled water; AlCl3 group, which received AlCl3; AMG+AlCl3 group, which received AlCl3+AMG; AMGLN+AlCl3 group, which received AlCl3+amygdalin-loaded niosomes; SP+AlCl3 group, which received AlCl3+SP; and SPLN+AlCl3 group, which received AlCl3+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 AlCl3 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 AlCl3 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 AlCl3 negative effects as they possess powerful antioxidant activity, as well as they have the ability to improve the reproductive activity of affected males.

Protective effects of N-acetyl-l-cysteine against penconazole-triggered hepatorenal toxicity in adult rats.

Introduction: Penconazole (PEN) is a widely applied triazole fungicide. This study sought to define the efficacy of N-acetyl-l-cysteine (NAC) in mitigating PEN-triggered hepatorenal toxicity in rats. Material and Methods: Twenty-eight adult male albino Wistar rats were assigned to four groups: a normal control (NC), a PEN group, a NAC group and a PEN+NAC group. Administration of PEN (50 mg/kg body weight (b.w.) every 2 days) and NAC (150 mg/kg b.w., daily) took place via oral gavage for 10 days. Results: Effective amelioration by NAC of PEN-induced liver and kidney dysfunction was indicated by a significant reduction in the circulating liver and kidney markers (aspartate aminotransferase, alanine aminotransferase, urea and creatinine). Attenuation of PEN-induced oxidative stress and lipid peroxidation in liver and kidney tissues was evident in a significant reduction in malondialdehyde and enhanced total antioxidant capacity. Moreover, NAC significantly reduced the histopathological alterations and the expression of tumour necrosis factor α in liver and kidney tissue. Furthermore, NAC maintained the messenger RNA levels of nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase 1, and Kelch-like erythroid cell-derived protein 1 and prevented nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein upregulation caused by PEN. Conclusion: N-acetyl-1-cysteine protected against PEN-induced hepatorenal oxidative damage and inflammatory response via activation of Nrf2 and inhibition of NF-κB pathways.

Effectiveness of natural biomaterials in the protection and healing of experimentally induced gastric mucosa Ulcer in rats.

BACKGROUND: A gastric ulcer is a painful lesion of the gastric mucosa that can be debilitating or even fatal. The effectiveness of several plant extracts in the therapy of this illness has been demonstrated in traditional pharmacopoeias. AIM: this study was aimed to see if propolis, ginseng in normal or nano form, and amygdalin might help in preventing the ulcerative effects of absolute ethanol. METHODS: Gastroprotective properties of pretreatments before ethanol gavage in rats were compared to omeprazole. The ulcer and stomach parameters (ulcerated regions) were measured (mm2), ulcer inhibition percentage, the stomachs were assessed macroscopically with gastric biopsy histological examinations. RESULTS: Amygdalin, normal and nano ginseng, nano propolis followed by propolis all showed great efficacy in protecting the cyto-architecture and function of the gastric mucosa. The number of ulcerated sites was greatly reduced, and the percentage of stomach protection was increased. Histopathological examination had confirmed great protective effects of the nanoformulations followed by amygdalin. The protection and healing rate was completed to about 100% in all tested materials while ulcer areas were still partially unhealed in normal propolis and omeprazole. Quantitative assay of the m-RNA levels Enothelin 1(ET-1), leukotriene4 (LT-4), and caspase 3(Cas-3) genes and Histamine were done and revealed significant up-regulations in ethanol group and the maximum protective effect was reported with ginseng nano, moreover the histamine content was significantly decreased with nano- formulated extracts. CONCLUSION: Amygdalin and the nanoformulated ginseng and propolis had exhibited a marked protective effect against the ulcerative toxic effects of ethanol.

Anti-cancer effect of nano-encapsulated boswellic acids, curcumin and naringenin against HepG-2 cell line.

BACKGROUND: liver cancer is one of the most common cancers in the world. So far, there is no gold standard treatment for hepatocellular carcinoma. We conducted this in vitro study to assess the effect of three natural products: Boswellic acids, curcumin and naringin versus corresponding nanoparticles (NPs) on Hep G2 cells proliferation. METHODS: Boswellic acid, curcumin, naringin-loaded NPs were prepared using nanoprecipitation method. Human liver (HepG2) cell line was cultured in Dulbecco's modified Eagle's medium (DMEM). The cell growth inhibition and cytotoxicity were evaluated by MTT assay. RESULTS: Boswellic acid, curcumin, naringin were able to inhibit HepG2 cells proliferation. IC50 at 24 h, 48 h showed significant lower values in NPs versus Free herbs. IC50 values of free Boswellic acids and NPs at 24 h were (24.60 ± 1.89 and 7.78 ± 0.54, P < 0.001), at 48 h were (22.45 ± 1.13 and 5.58 ± 0.27, P < 0.001) respectively. IC50 values of free curcumin and NPs at 24 h were (5.89 ± 0.8 and 3.46 ± 0.23, P < 0.05), at 48 h were (5.57 ± 0.94 and 2.51 ± 0.11, P < 0.05), respectively. For free and naringenin NPs, IC50 values at 24 h were (14.57 ± 1.78 and 7.25 ± 0.17, P < 0.01), at 48 h were (11.37 ± 1.45 and 5.21 ± 0.18, P < 0.01) respectively. CONCLUSION: Boswellic acid, curcumin, naringin and their nanoprecipitation prepared nanoparticles suppressed Hep G2 cells proliferation.

Selenium and vitamin E ameliorate lead acetate-induced hepatotoxicity in rats via suppression of oxidative stress, mRNA of heat shock proteins, and NF-kB production.

BACKGROUND: Lead exposure results in a terrible rise in heat shock protein levels. OBJECTIVE: This research was conducted to look at the effects of lead poisoning on heat shock response, oxidative stress, and inflammatory markers in albino rats, as well as the power of selenium and vitamin E to resist lead toxic effects. METHODS: Eight groups of albino rats are used. Each group contained six rats where the first group represented the negative control, and the other groups were treated with olive oil, vitamin E, selenium, lead, (vitamin E + lead), (selenium + lead), and (vitamin E + selenium + lead). All the treatments lasted for 28 days. Then, the mRNA expression of interested heat shock proteins (HSP90, HSP70, and HSP60) was assessed. For oxidative stress disruption, we investigated nitric oxide (NO) and malondialdehyde (MDA) content, and enzymatic and non-enzymatic antioxidants activity respectively in rat livers. RESULTS: our results revealed the synergetic protective effect of the combination of two antioxidants (vitamin E and selenium) against lead poising. This was clear in regulating HSPs expression, inflammatory markers, glucose, lipid profile, liver functions, and antioxidant enzymes more than the treatment with one antioxidant. CONCLUSION: Pb is a toxic material that can induce HSPs and inflammatory markers expression. Selenium and vitamin E can give excellent effects in ameliorating Pb toxicity when used together.

Neuroprotective effect of quercetin and nano-quercetin against cyclophosphamide-induced oxidative stress in the rat brain: Role of Nrf2/ HO-1/Keap-1 signaling pathway.

Quercetin (Qu) is a powerful flavanol antioxidant that is naturally found in plants and is part of the flavonoid family. Qu has a wide range of biological properties, such as neuroprotective, anti-cancer, anti-diabetic, anti-inflammatory, and radical scavenging capabilities. However, the in vivo application of Qu is limited by its poor water solubility and low bioavailability. These issues could be addressed by utilizing Qu nanoformulations. Cyclophosphamide (CP) is a potent chemotherapeutic agent that causes severe neuronal damage and cognitive impairment due to reactive oxygen species (ROS) overproduction. The present study aimed to explore the proposed neuroprotective mechanism of quercetin (Qu) and quercetin-loaded Chitosan nanoparticles (Qu-Ch NPs) against the brain oxidative damage induced by CP in male albino rats. For this aim, thirty-six adult male rats were randomly divided into six groups (n = 6). Rats were pretreated with Qu and Qu-Ch NPs orally in doses of 10 mg/kg bwt/day for 2 weeks, and CP (75 mg/kg bwt) was administered intraperitoneally 24 h before the termination of the experiment. After 2 weeks, some neurobehavioral parameters were evaluated, and then euthanization was done to collect the brain and blood samples. Results showed that CP induces neurobehavioral deteriorations and impaired brain neurochemical status demonstrated by a significant decrease in brain glutathione (GSH), serum total antioxidant capacity (TAC), and serotonin (5-HT) levels while malondialdehyde (MDA), nitric oxide (NO), Tumor necrosis factor α (TNFα), and choline esterase (ChE) concentrations increased significantly compared to the control group. Pretreatment with Qu and Qu-Ch NPs showed a significant anti-oxidative, anti-depressive, and neuroprotective effect through modification of the above-mentioned parameters. The results were further validated by assessing the expression levels of selected genes in brain homogenates and histopathological investigations were done to pinpoint the exact brain-altered regions. It could be concluded that Qu and Qu-Ch NPs can be useful neuroprotective adjunct therapy to overcome neurochemical damage induced by CP.

Potential Mechanisms of Imidacloprid-Induced Neurotoxicity in Adult Rats with Attempts on Protection Using Origanum majorana L. Oil/Extract: In Vivo and In Silico Studies.

Imidacloprid (IMI) insecticide is rapidly metabolized in mammals and contributes to neurotoxicity via the blocking of nicotinic acetylcholine receptors, as in insects. Origanum majorana retains its great antioxidant potential in both fresh and dry forms. No data is available on the neuroprotective effect of this plant in laboratory animals. In this context, aerial parts of O. majorana were used to prepare the essential oil (OMO) and methanol extract (OME). The potential neuroprotective impact of both OMO and OME against IMI-induced neurotoxicity in rats was explored. Forty-two rats were divided into 6 groups, with 7 rats in each one. Rats were daily administered the oral treatments: normal saline, OMO, OME, IMI, IMI + OMO, and IMI + OME. Our results revealed the identification of 55 components in O. majorana essential oil, most belonging to the oxygenated and hydrocarbon monoterpenoid group. Moreover, 37 constituents were identified in the methanol extract, mostly phenolics. The potent neurotoxic effect of IMI on rats was confirmed by neurobehavioral and neuropathological alterations and a reduction of both acetylcholine esterase (AchE) activity and dopamine (DA), serotonin (5HT), and γ-aminobutyric acid (GABA) levels in the brain. Exposure of rats to IMI elevates the malondialdehyde (MDA) levels and reduces the antioxidant capacity. IMI could upregulate the transcription levels of nuclear factor-κB (NF-κB), interleukin-1 ß (IL-1ß), and tumor necrosis factor (TNF-α) genes and express strong caspase-3 and inducible nitric oxide synthase (iNOS) immunostaining in most examined brain areas. On the other hand, rats coadministered OMO or OME with IMI showed a marked improvement in all of the studied toxicological parameters. In conclusion, cotreatment of O. majorana extracts with IMI can protect against IMI neurotoxicity via their potent antioxidant, anti-inflammatory, and anti-apoptotic effects. Thus, we recommend a daily intake of O. majorana to protect against insecticide's oxidative stress-mediated neuroinflammatory stress and apoptosis. The molecular docking study of linalool, rosmarinic acid, γ-terpene, and terpene-4-ol justify the observed normalization of the elevated iNOS and TNF-α levels induced after exposure to IMI.

Monitoring of health status, performance and transcript abundance of some genes in dairy heifers produced by embryo transfer or artificial insemination.

The use of multiple ovulation and embryo transfer (MOET) technology in the dairy cattle industry has increased dramatically in recent decades for the production of offspring from genetically superior cows. Yet, its long-term ramifications on adult performance have not been adequately clarified. Therefore, this study targeted comparing dairy heifers born after the transfer of in vivo-produced embryos (MOET-heifers, n = 400) and those born after artificial insemination (AI-heifers, n = 340). The performance of MOET-heifers and AI-heifers was compared from birth till completion of the first lactation regarding health, fertility and some lactational performance parameters. The transcript abundance of several genes was also assessed in peripheral blood leukocytes (PBWC). Results showed greater pre-weaning mortalities, greater likelihood of being culled as a nulliparous heifer and younger age at first insemination in AI-heifers (p < .001). At their first calving, primiparous MOET-heifers experienced a greater (p < .01) incidence of stillbirth compared to primiparous AI-heifers. In spite of that, primiparous AI-heifers were more likely to be culled due to infertility (p < .001), took a greater number of inseminations to achieve pregnancy (p < .01) and displayed a longer first calving interval. There was a similar lactational performance between the two groups. Upregulation of the transcript levels of TAC3, LOC522763, TFF2, SAXO2, CNKSR3 and ALAS2 was interestingly observed in primiparous MOET-heifers, compared to primiparous AI-heifers. In conclusion, MOET-heifers were less likely to be culled during the first year of life, had superior reproductive performance versus AI-heifers during their first lactation and expressed upregulation of genes associated with fertility.