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Doaa Abdelrahaman,1 Ola A Habotta,2 Ahmed Ateya,3 Ahmed A Aldarmahi,4,5 Reham A El-Shafei,6 Mohamed M Badawy,7,8 Ahmed A El-Mansy,9,10 Thoraya M A-Elgadir,11 Aml M Nada,12 Mona G Elhadidy,13,14 Eman Hamza,15,16 Khairiah M Alwutayed,17 Mohamed El-Sherbiny,18 Liana Fericean,19 Florin Imbrea,20 Ahmed Abdeen21 1Department of Internal Medicine, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia; 2Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt; 3Department of Animal Husbandry and Wealth Development, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt; 4Department of Basic Science, College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia; 5National Guard- Health Affairs, King Abdullah International Medical Research Centre, Jeddah, 21582, Saudi Arabia; 6Department of Pharmacology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt; 7Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 8Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Delta University for Science and Technology, Gamasa, Egypt; 9Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa, Jordan; 10Department of Medical Histology and Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 11Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia; 12Department of Internal Medicine and Endocrinology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 13Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 14Department of Medical Physiology, Faculty of Medicine, Al-Baha University, Al Aqiq, Saudi Arabia; 15Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 16Department of Medical Biochemistry and Molecular Biology, Horus University, Damietta, Egypt; 17Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia; 18Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, 11597, Saudi Arabia; 19Department of Biology and Plant Protection, Faculty of Agriculture, University of Life Sciences “king Michael I” from Timișoara, Calea Aradului, Romania; 20Department of Crop Science, Faculty of Agriculture, University of Life Sciences “King Mihai I” from Timisoara, Calea Aradului, Romania; 21Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Toukh, EgyptCorrespondence: Florin Imbrea, University of Life Sciences “King Mihai I” from Timisoara, 119, Calea Aradului, Timisoara, 300645, Romania, Email florin_imbrea@usab-tm.ro Ahmed Abdeen, Benha University, Toukh, 13736, Egypt, Email ahmed.abdeen@fvtm.bu.edu.egBackground: Nootkatone (NK), a bioactive sesquiterpene ketone, is a major ingredient in grapefruit that has distinguished biological activities. Melamine (MM), a food adulterant, was reported to induce toxic effects including renal disorders. Hence, this protocol was devoted to evaluate the renoprotective impact of NK toward MM-evoked renal damage.Methods: Rats were either exposed to MM (700 mg/kg) or a combination of MM and two doses of NK (5 and 10 mg/kg).Results: The results showed that NK therapy notably decreased the kidney functional parameters, along with KIM-1 and NGAL expressions of MM group. Furthermore, a decrease in MDA and NO levels as well as an elevation in SOD, CAT, GSH, and SOD and NRF2 mRNA expression in the NK group demonstrated NK’s ability to enhance the renal antioxidant defense of the MM group. Significant suppression in renal inflammatory markers was achieved by NK via lessening of IL-1β and TNF-α, besides downregulation of NF-κB and IL-1β expressions. NK also downregulated vimentin, nestin, and desmin in the MM group. Additionally, in response to the MM exposure, NK hindered renal apoptosis by decreasing caspase-3 expression and restoring renal histopathological features.Conclusion: These outcomes suggest that NK can be considered as a prospective candidate to guard against MM exposure-mediated renal toxic effects.Keywords: apoptosis, inflammation, intermediate proteins, melamine nephrotoxicity, nootkatone, oxidative stress

Ahmed Mowafy Tafish,1,2 Mohamed El-Sherbiny,3,4 Ahmed A Al‐Karmalawy,5,6 Osama Abd El-Azeem Soliman,1 Noha Mohamed Saleh1 1Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Horus University, New Damietta, 34518, Egypt; 3Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia; 4Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt; 5Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University, New Damietta, 34518, Egypt; 6Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza, 12566, EgyptCorrespondence: Noha Mohamed Saleh, Associate Professor of Pharmaceutics, Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt, Tel +2 01064536677, Fax +2 050 2247496, Email nunu_ramy@mans.edu.egBackground: Despite recent advances in wound healing products, phytochemicals have been considered promising and attractive alternatives. Carvacrol (CAR), a natural phenolic compound, has been reported to be effective in wound healing.Purpose: This work endeavored to develop novel CAR-loaded phytosomes for the enhancement of the wound healing process.Methods: Molecular docking was performed to compare the affinities of the different types of phospholipids to CAR. Phytosomes were prepared by three methods (thin-film hydration, cosolvency, and salting out) using Lipoid S100 and Phospholipon 90H with three levels of saturation percent (0%, 50%, and 100%), and three levels of phospholipid molar percent (66.67%, 75%, and 80%). The optimization was performed using Design Expert where particle size, polydispersity index, and zeta potential were chosen as dependent variables. The optimized formula (F1) was further investigated regarding entrapment efficiency, TEM, 1H-NMR, FT-IR, DSC, X-RD, in vitro release, ex vivo permeation, and stability. Furthermore, it was incorporated into a hydrogel formulation, and an in vivo study was conducted to investigate the wound-healing properties of F1.Results: F1 was chosen as the optimized formula prepared via the thin-film hydration method with a saturation percent and a phospholipid molar percent of zero and 66.67, respectively. TEM revealed the spherical shape of phytosomal vesicles with uniform size, while the results of 1H-NMR, FT-IR, DSC, and X-RD confirmed the formation of the phytosomal complex. F1 demonstrated a higher in vitro release and a slower permeation than free CAR. The wound area of F1-treated animals showed a marked reduction associated with a high degree of collagen fiber deposition and enhanced cellular proliferation.Conclusion: F1 can be considered as a promising remedy for the enhancement of wound healing and hence it would be hoped to undergo further investigation.Graphical Abstract: Keywords: carvacrol, phospholipids, docking, phytosome, release, topical, wound healing

Mohamed Ahmed Eladl,1,2 Wael M Elsaed,2,3 Hoda Atef,4 Mohamed El-Sherbiny2 1Department of Basic Medical Sciences, University of Sharjah, Sharjah, United Arab Emirates; 2Anatomy and Embryology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 3Anatomy and Embryology Department, Faculty of Medicine, Taibah University, Madinah, Saudi Arabia; 4Department of Histology, University of Mansoura, Mansoura, Egypt Background: Several renal disorders affect the glomerular podocytes. Compensatory structural and functional changes have been observed in animals that have undergone unilateral renal ablation. These changes occur as a pliant response to quench the increased functional demand to maintain homeostasis of fluid and solutes. Nestin is an intermediate filament protein present in the glomerular podocytes of the adult kidney and is linked with the maintenance of its foot process structure. Structural changes in the podocytes ultimately restructure the filtration barrier. Very few studies related to the ultrastructural and histopathologic changes of the podocytes are documented. The present study aimed to assess the histopathologic changes at the ultrastructural level in the adapted kidney at different time intervals following unilateral renal ablation in adult rats and its relation with nestin.Methods: Forty-eight rats were divided into four groups (n=12 in each group). The animals of Group A were control naïve rats, while the group B, group C and group D animals underwent left unilateral nephrectomy and the remaining right kidney was removed on days 10, 20 and 30, respectively. Each group included four sham-operated rats, which were sacrificed at the same time as the naïve rats. Each nephrectomized sample was weighed and its sections were subjected to hematoxylin and eosin examination, transmission electron microscopic study as well as immunostaining using the intermediate filament protein nestin.Results: No difference was found between the kidney sections from the control group and the sham-operated groups. A significant increase in the weight of the right kidneys was noted in groups B, C and D (P

This paper reports work carried out to determine the influence of the Pyramidal indenter geometrical errors and tolerances on the accuracy of Vickers hardness measurements. The angle between the opposite faces and line of conjunction of nine indenters were measured by the optical comparator. The influence of the indenter geometry on the hardness accuracy is investigated. Three calibrated reference hardness test blocks were used to check the Vickers hardness test using the nine selected indenters. The results show that the geometrical error of the indenters (specially the angles) considerably affects the accuracy of the hardness measurement. Finite element analysis of the indentation process into metallic test pieces was conducted. Comparison of the experimental results with the numerical findings was discussed. Errors in the experimental values are correlated with measured tolerances in the angles between faces.

This research investigates the biocompatibility, mechanical strength, and tribological properties of a hybrid composite material composed of high-density polyethylene (HDPE), hydroxyapatite (HAp), and titanium dioxide nanoparticles (Ti O 2 ). The study explores the microstructural characteristics of the composite material using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD). Samples of HDPE-30%HAp with varying concentrations of Ti O 2 (5, 10, 15, and 20%) were prepared and extruded using a twin-screw machine. The hybrid composite materials underwent mechanical tests (tensile, flexural, and hardness), tribological tests (friction and wear rate), and antibacterial tests (resistance to Escherichia coli and Staphylococcus aureus bacteria). The results indicate that the optimal hybrid composite sample was HDPE-30%HAP-10% Ti O 2 , which demonstrated excellent mechanical properties (maximum tensile strength of 25.93 MPa and young modulus of 480 MPa) and a low coefficient of friction (COF∼ 0.07) while achieving high wear resistance (wear rate in the order of 1 0 − 4 m m 3 N − 1 m − 1 ). The study shows that the improvement in mechanical properties results in a corresponding improvement in tribological properties. The antibacterial tests revealed that the hybrid composite material exhibited resistance to E. coli and S. aureus bacteria. The findings of this study suggest that the HDPE-30%HAP-10% Ti O 2 composite is a promising material for use in biomedical applications due to its excellent biocompatibility and desirable mechanical and tribological properties. The study demonstrates the potential of reinforced hybrid composite materials in overcoming the disadvantages of monolithic and hybrid micro-composites and highlights the importance of investigating the microstructural, tribological, and mechanical strength characteristics of composite materials for biomedical applications. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Diabetes mellitus (DM) has been considered a major problem because of its related complications and growing incidence worldwide. Testicular dysfunction has become a predominant diabetic complication characterized by impaired reproductive function and testicular damage. Stevia rebaudiana Bertoni has been known for its antioxidant effect on diabetes, inflammation, and obesity. The current study investigates the protective effect of Stevia on diabetic-induced testicular injury. MATERIALS AND METHODS: Sprague Dawley adult male rats were divided into three groups: the control group, the diabetic group, and the diabetic + Stevia group, type 2 diabetes is induced by a high-fat diet (HFD) and a single dose of 35 mg/kg streptozotocin injection. The effects of Stevia were evaluated regarding biochemical, oxidative stress, histopathological and ultrastructural changes, and immunohistochemical expression of vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), receptor-interacting serine/threonine-protein kinase 1 (RIPK 1), and caspase 3. RESULTS: Stevia extract attenuated the diabetic-induced oxidative stress, restored the testicular architecture, and decreased testicular damage, inflammation, necroptosis, and apoptosis by upregulating VEGF and downregulating VCAM 1, RIPK 1, and caspase 3. CONCLUSIONS: The current study highlights the importance of Stevia as an antioxidant anti-inflammatory that ameliorates diabetic-induced testicular injury by modulating oxidative stress, inflammation, necroptosis, and apoptosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aims to explore underlying molecular variations in the expression of miRNAs in kidney tissues of ginger-treated and non-treated cyclophosphamide (CP)-intoxicated rats. MATERIALS AND METHODS: A total of 40 adult male Wistar rats were randomly divided into four groups of 10 each: Group I (control: received normal food and water), Group II (received ginger at a dose of 300 mg/kg), Group III (received CP 75 mg/kg, i.p.), and Group IV (received the same dose of CP and ginger extract). Rats received a single injection of 75 mg/kg CP on days 3, 4, 5, 19, 20, and 21. In CP-intoxicated rats, the treatment with ginger extract at a dose of 300 mg/kg was received by oral gavage starting seven days before CP and continuing throughout the duration of the experiment for four weeks. Molecular variations in the expression of miRNAs, apoptotic genes, histological kidney damage, and abnormal kidney function in control, ginger, and CP-intoxicated rats were identified by using real-time RT-PCR Analysis, immunohistochemical, and colorimetric assays. In addition, HPLC analysis and liquid chromatography spectrophotometry analysis using Diphenyl-1-picrylhydrazyl (DPPH) radical, and -Carotene-linoleic acid reagents were applied respectively for in-vitro screening of phytoconstituents and antioxidant activity for ginger extract. RESULTS: The kidney tissues of CP-intoxicated rats displayed an increase in lipid peroxidation marker malonaldehyde (MDA), DNA damage, and fibrosis markers like hyaluronic acid (HA) and hydroxyproline Hypx) with a decrease in the superoxide dismutase (SOD) and total antioxidant capacity (TAC). In addition, molecular expressions of mRNA fibrotic genes such as collagen, type 1, alpha 1 (COL1A1), and a-smooth muscle actin (aSMA). Molecular expressions of levels of B-cell lymphoma 2 (BCl-2) mRNA gene were down-regulated, and the expression of mRNA apoptotic; BCL2 associated X gene (Bax), caspase-3, Bax/BCl-2 ratio genes were significantly up-regulated respectively. Moreover, cellular oxidative genes, erythroid 2-related factor (Nrf2), and heme oxygenase-1 (HO-1) were down-regulated, respectively. The miR-155-5p, miR-34a-5p, miR-21-5p significantly increased while the miR-193b-3p, miR-455-3p, and miR-342-3p significantly decreased. Ginger also increased the expression of Nrf2, HO-1, and BCl-2 genes in the kidneys of rats induced with CP. In addition, active phytoconstituents, particularly 6]]-shogaol and 6]]-gingerol, were significantly identified in ginger extract using HPLC analysis. Antioxidant activity of these active metabolites were shown to be higher against in vitro free radicals (DPPH and 1-Carotene-linoleic acid), suggesting the potential antioxidant and antiapoptotic properties of ginger against CP-toxicity. CONCLUSIONS: Treatment with ginger in rats induced with CP resulted in significant improvement in the expression of certain molecular miRNAs. The kidney tissues of these rats showed a marked decrease in the expression of miR-155-5p, miR-34a-5p, and miR-21-5p, while the levels of miR-193b-3p, miR-455-3p, and miR-342-3p were observed to increase significantly. In conclusion, ginger can protect rats from CP-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The current study considered assessing the role of miRNA-155 and miRNA-24 in collagen-induced rheumatoid arthritis (RA) in rats' temporomandibular joint (TMJ). Their role in histological aggressiveness of the disease and therapy response to glycogen synthase kinase (GSK) inhibitor 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) will be studied. MATERIALS AND METHODS: Rats were randomly distributed to four groups (8 rats/group): group I negative control, group II collagen-induced rheumatoid arthritis (CIA), group III Control+ TDZD-8 treated group, and group IV CIA+TDZD-8 treated group. Then were euthanized 42 days after the start of the experiment. H&E staining, Masson trichrome staining, and immunohistochemical antibodies against S100 were performed. qRT-PCR of miRNA-155 and miRNA-24 were done for frozen synovial tissues. RESULTS: Histological analysis showed that the most affected structure in induced rheumatoid arthritis of TMJ is the articular disc, condylar head, and subchondral bone. Combined treatment with TDZD-8 improved histological status in the joint. Masson's trichrome (MTC) histochemical staining revealed disarrangement of collagen fibers and adherence between the articular disc and condylar cartilage. Meanwhile, the morphology and collagen composition of the disc and condyle in CIA+ TDZD-8 were similar to those of healthy tissues. Immunohistochemical analysis for S100A4 revealed increased immunoreactivity staining in the CIA group. The immunoreactivity was significantly decreased in CIA+ TDZD-8 treated group. TDZD-8 significantly decreased the levels of miRNA-155 and miRNA-24 in synovial tissue. CONCLUSIONS: Our results reveal for the first-time correlation of miRNA-155 and miRNA-24 that might be implicated in the onset of TMJ RA. Consequently, the treatment of CIA with GSK inhibitor (TDZD-8) yields encouraging results. We predicted the TDZD-8 might protect against CIA by suppressing miRNA-155, miRNA-24, and S100A4 protein levels. [ABSTRACT FROM AUTHOR]

Melt-quenching technique was used to prepare borosilicate glasses of composition xSiO2- (75-x) B2O3–24.7Li2O-0.3Cr2O3 (x = 0, 10, 20, 30, 40 and 50 mol%). With increasing the former content, both Cr6+ and Cr3+ optical transitions undergo strong intensity variations. The crystal field strength (10Dq) is increased, while Racah parameters (C,B) are decreased with increasing SiO2 content. The ratio estimated Dq/B values confirmed a weak crystal field environment for Cr3+ions, and further suggest a more covalent bond character. The ESR results revealed that Si-contained samples exhibit a strong microwave absorption signal, and justified the presence of both Cr3+ and Cr6+(charge transfer into 3d0 2p6+ = 3d1Cr5+) oxidation states. The fingerprints of borate and silicate relevant structural groups were clearly identified from FTIR spectroscopy. [ABSTRACT FROM AUTHOR]