Design, Synthesis, and Biological Evaluation of Newly Synthesized Cinnamide-Fluorinated Containing Compounds as Bioactive Anticancer Agents.

A new series of cinnamide-fluorinated derivatives has been synthesized and characterized by using different spectroscopic and elemental microanalyses methods. All of the prepared p-fluorocinnamide derivatives were evaluated for their cytotoxic activity against the HepG2 liver cancerous cell line. The imidazolone derivative 6, which bears N-(N-pyrimidin-2-ylbenzenesulphamoyl) moiety, displayed antiproliferative activity against HepG2 liver cancerous cells with an IC50 value of 4.23 µM as compared to staurosporin (STU) (IC50 = 5.59 µM). In addition, compound 6 experienced epidermal growth factor receptor (EGFR) inhibitory activity comparable to palatinib. The cell cycle analysis by flow cytometry indicated that compound 6 arrested the cellular cycle of HepG2 cells at the G1 phase. Additionally, as demonstrated by the fluorescence-activated cell sorting (FACS) technique, compound 6 increased both early and late apoptotic ratios compared to control untreated HepG2 cells. Moreover, imidazolone compound 6 induced apoptosis via the intrinsic apoptotic pathway by decreasing the level of mitochondrial membrane polarization (MMP) compared to untreated HepG2 cells. Therefore, the new N-(N-pyrimidin-2-ylbenzenesulphamoyl)imidazolone derivative 6 could be considered a potential platform for further optimizing an antitumor agent against hepatocellular carcinoma.

Design, synthesis and cytotoxic activity of molecular hybrids based on quinolin-8-yloxy and cinnamide hybrids and their apoptosis inducing property.

The present work aims at design and synthesis of a congeneric series of small hybrids 5 and 6a-i featuring the privileged quinoline scaffold tethered with 2-(arylamido)cinnamide moiety as potential anticancer tubulin polymerization inhibitors. Most of the synthesized hybrids 5 and 6a-i significantly inhibited the growth of the HepG2 cell line, with IC50 ranged from 2.46 to 41.31 µM. In particular, 2-(3,4,5-trimethoxybenzamido)-4-methoxycinnamide-quinoline hybrid 6e displayed potent IC50 value toward the examined cell line, and hence chosen for further mechanistic investigations. It is noteworthy that the antiproliferative action of compound 6e highly correlated well with its ability to inhibit tubulin polymerization. In addition, the most potent hybrid 6e demonstrated a significant modification in the cellular cycle distribution, in addition to provoke of apoptotic death within the tested HepG2 cell line. Furthermore, the mechanistic approach was confirmed by a substantial upregulation in the quantity of active caspase 9 by 5.81-fold relative to untreated control cells.

Therapeutic effect of N, N-Diphenyl-1,4-phenylenediamine and adipose-derived stem cells coadministration on diabetic cardiomyopathy in type 1 diabetes mellitus-rat model.

Type 1 diabetes stem-cell-based treatment approach is among the leading therapeutic strategies for treating cardiac damage owing to the stem cells' regeneration capabilities. Mesenchymal stem cells derived from adipose tissue (AD-MSCs) have shown great potential in treating diabetic cardiomyopathy (DCM). Herein, we explored the antioxidant-supporting role of N, N'-diphenyl-1,4-phenylenediamine (DPPD) in enhancing the MSCs' therapeutic role in alleviating DCM complications in heart tissues of type 1 diabetic rats. Six male albinos Wistar rat groups have been designed into the control group, DPPD (250 mg/kg, i.p.) group, diabetic-untreated group, and three diabetic rat groups treated with either AD-MSCs (1 × 106 cell/rat, i.v.) or DPPD or both. Interestingly, all three treated diabetic groups exhibited a significant decrease in serum glucose, HbA1c, heart dysfunction markers (lactate dehydrogenase and CK-MP) levels, and lipid profile fractions (except for HDL-C), as well as some cardiac oxidative stress (OS) levels (MDA, AGEs, XO, and ROS). On the contrary, serum insulin, C-peptide, and various cardiac antioxidant levels (GSH, GST, CAT, SOD, TAC, and HO-1), beside viable cardiac cells (G0/G1%), were markedly elevated compared with the diabetic untreated group. In support of these findings, the histological assay reflected a marked enhancement in the cardiac tissues of all diabetic-treated groups, with obvious excellency of the AD-MSCs + DPPD diabetic-treated group. Such results strongly suggested the great therapeutic potentiality of either DPPD or AD-MSCs single injection in enhancing the cardiac function of diabetic rats, with a great noted enhancement superiority of DPPD and AD-MSCs coadministration.

Synthesis and spectroscopic study of novel mixed ligand formula "Artemisinin/Zn" and assessment of its inhibitory effect against "SARS-CoV-2″.

Background: Herein, a newly synthesised mixed ligand artemisinin/zinc (Art/Zn) is chemically characterised and examined against SARS-CoV-2. Methods: The synthesised complex was thoroughly characterised using various spectroscopic methods (FT-IR, UV and XRD). Its surface morphology and chemical purity were investigated using transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) analysis. The synthesised Art/Zn complex was tested for its inhibitory effects against SARS-CoV-2 using inhibitory concentration 50 (IC50) and cytotoxicity concentration 50 (CC50). Results: The results reveal that the Art/Zn complex exhibits a moderate in vitro inhibitory effects against SARS-CoV-2, with a CC50 index of 213.6 µg/ml and an IC50 index of 66.79 µg/ml. Notably, it exhibits the inhibitory effect (IC50 = 66.79 µg/ml) at a very low concentration without any observable cytotoxic effects on host cells (CC50 = 213.6 µg/ml). Its mode of action against SARS-CoV-2 involves inhibiting the viral replication. The predicted target classes that Art/Zn may affect include kinases, which can regulate and inhibit the viral replication and binding to the angiotensin-converting enzyme-2 (ACE2) receptor and the main protease inhibitor (MPro), thereby inhibiting the activity of SARS-CoV-2 and proved by the molecular dynamics simulation. Conclusion: We recommend using the Art/Zn complex owing to its moderate inhibitory and antiviral effects against the SARS-CoV-2 with a low cytotoxic effect on host (Vero E6) cells. We suggest conducting further prospective studies to investigate the biological effects of Art/Zn in animal models at different concentrations for testing its clinical efficacy and safety in inhibiting SARS-CoV-2 activities.

Therapeutic potential and protection enhancement of mesenchymal stem cell against cisplatin-induced nephrotoxicity using hyaluronic acid-chitosan nanoparticles as an adjuvant.

A newly synthesized nanoplatform of hyaluronic acid and chitosan nanoparticles (HA/CNPs) was applied to improve the therapeutic efficacy and protection of bone marrow mesenchymal stem cells (BM-MSCs) against cisplatin (CDDP)-induced nephrotoxicity in rats. CDDP administration causes significant increases in levels of serum creatinine (SCr), urea, and KIM-1 coupled with significant albumin level falls, as indicative of acute renal dysfunction. Moreover, the level of the antioxidant enzyme (GSH) was significantly decreased, while the levels of lipid peroxidation (MDA) and inflammatory (IL-6) and apoptotic (caspase-3) markers were significantly increased, indicating a decline in the kidney's antioxidant defense and increased inflammation. In contrast, when rats were pre-treated with either MSCs or MSCs-HA/CNPs before receiving CDDP, the levels of SCr, urea, KIM-1, MDA, IL-6, and caspase-3 were significantly decreased with simultaneous significant rises in GSH and albumin, impelling a great improvement in the antioxidant and anti-inflammatory defenses of the kidney as well as its functions. Intriguingly, MSCs-HA/CNPs were more effective against caspase-3 than MSCs alone, revealing the high anti-apoptotic capability of HA/CNPs. This finding suggests that HA/CNPs could effectively protect MSCs from oxidative stress and apoptosis and thus increase their stability and longevity.

Integration of Chemoinformatics and Multi-Omics Analysis Defines ECT2 as a Potential Target for Cancer Drug Therapy.

Epithelial cell transforming 2 (ECT2) is a potential oncogene and a number of recent studies have correlated it with the progression of several human cancers. Despite this elevated attention for ECT2 in oncology-related reports, there is no collective study to combine and integrate the expression and oncogenic behavior of ECT2 in a panel of human cancers. The current study started with a differential expression analysis of ECT2 in cancerous versus normal tissue. Following that, the study asked for the correlation between ECT2 upregulation and tumor stage, grade, and metastasis, along with its effect on patient survival. Moreover, the methylation and phosphorylation status of ECT2 in tumor versus normal tissue was assessed, in addition to the investigation of the ECT2 effect on the immune cell infiltration in the tumor microenvironment. The current study revealed that ECT2 was upregulated as mRNA and protein levels in a list of human tumors, a feature that allowed for the increased filtration of myeloid-derived suppressor cells (MDSC) and decreased the level of natural killer T (NKT) cells, which ultimately led to a poor prognosis survival. Lastly, we screened for several drugs that could inhibit ECT2 and act as antitumor agents. Collectively, this study nominated ECT2 as a prognostic and immunological biomarker, with reported inhibitors that represent potential antitumor drugs.

Inhibition Mechanism of Methicillin-Resistant Staphylococcus aureus by Zinc Oxide Nanorods via Suppresses Penicillin-Binding Protein 2a.

Methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening infections. Zinc oxide is well known as an effective antibacterial drug against many bacterial strains. We investigated the performance of zinc oxide nanorods synthesized by Albmiun as a biotemplate as an antibacterial drug in this study; the fabrication of zinc oxide nanorods was synthesized by sol-gel methods. We performed physicochemical characterization of zinc oxide nanorods by physiochemical techniques such as FTIR spectroscopy, X-ray diffraction, and TEM and investigation of their antimicrobial toxicity efficiency by MIC, ATPase activity assay, anti-biofilm activity, and kill time assays, as well as the mecA, mecR1, blaR1, blaZ, and biofilm genes (ica A, ica D, and fnb A) by using a quantitative RT-PCR assay and the penicillin-binding protein 2a (PBP2a) level of MRSA by using a Western blot. The data confirmed the fabrication of rod-shaped zinc oxide nanorods with a diameter in the range of 50 nm, which emphasized the formation of zinc oxide nanoparticles with regular shapes. The results show that zinc oxide nanorods inhibited methicillin-resistant S. aureus effectively. The MIC value was 23 µg/mL. The time kill of ZnO-NRs against MRSA was achieved after 2 h of incubation at 4MIC (92 µg/mL) and after 3 h of incubation at 2MIC (46 µg/mL), respectively. The lowest concentration of zinc oxide nanorods with over 75% biofilm killing in all strains tested was 32 µg/mL. Also, we examined the influence of the zinc oxide nanorods on MRSA by analyzing mecA, mecR1, blaR1, and blaZ by using a quantitative RT-PCR assay. The data obtained revealed that the presence of 2× MIC (46 µg/mL) of ZnO-NRs reduced the transcriptional levels of blaZ, blaR1, mecA, and mecR1 by 3.4-fold, 3.6-fold, 4-fold, and 3.8-fold, respectively. Furthermore, the gene expression of biofilm encoding genes (ica A, ica B, ica D, and fnb A) was tested using quantitative real-time reverse transcriptase-polymerase chain reaction (rt-PCR). The results showed that the presence of 2× MIC (46 µg/mL) of ZnO-NRs reduced the transcriptional levels of ica A, ica B, ica D, and fnb A. Also, the PBP2a level was markedly reduced after treatment with ZnO-NRs.

Amelioration effect of 18ß-Glycyrrhetinic acid on methylation inhibitors in hepatocarcinogenesis -induced by diethylnitrosamine.

Aim: suppression of methylation inhibitors (epigenetic genes) in hepatocarcinogenesis induced by diethylnitrosamine using glycyrrhetinic acid. Method: In the current work, we investigated the effect of sole GA combined with different agents such as doxorubicin (DOX) or probiotic bacteria (Lactobacillus rhamanosus) against hepatocarcinogenesis induced by diethylnitrosamine to improve efficiency. The genomic DNA was isolated from rats' liver tissues to evaluate either methylation-sensitive or methylation-dependent resection enzymes. The methylation activity of the targeting genes DLC-1, TET-1, NF-kB, and STAT-3 was examined using specific primers and cleaved DNA products. Furthermore, flow cytometry was used to determine the protein expression profiles of DLC-1 and TET-1 in treated rats' liver tissue. Results: Our results demonstrated the activity of GA to reduce the methylation activity in TET-1 and DLC-1 by 33.6% and 78%, respectively. As compared with the positive control. Furthermore, the association of GA with DOX avoided the methylation activity by 88% and 91% for TET-1 and DLC-1, respectively, as compared with the positive control. Similarly, the combined use of GA with probiotics suppressed the methylation activity in the TET-1 and DLC-1 genes by 75% and 81% for TET-1 and DLC-1, respectively. Also, GA and its combination with bacteria attenuated the adverse effect in hepatocarcinogenesis rats by altering potential methylomic genes such as NF-kb and STAT3 genes by 76% and 83%, respectively. Conclusion: GA has an ameliorative effect against methylation inhibitors in hepatocellular carcinoma (HCC) by decreasing the methylation activity genes.

Ultrastructural analysis of zinc oxide nanospheres enhances anti-tumor efficacy against Hepatoma.

Zinc oxide nanomaterial is a potential material in the field of cancer therapy. In this study, zinc oxide nanospheres (ZnO-NS) were synthesized by Sol-gel method using yeast extract as a non-toxic bio-template and investigated their physicochemical properties through various techniques such as FTIR, XR, DLS, and TEM. Furthermore, free zinc ions released from the zinc oxide nanosphere suspended medium were evaluated by using the ICP-AS technique. Therefore, the cytotoxicity of ZnO nanospheres and released Zn ions on both HuH7 and Vero cells was studied using the MTT assay. The data demonstrated that the effectiveness of ZnO nanospheres on HuH7 was better than free Zn ions. Similarly, ZnO-Ns were significantly more toxic to HuH7 cell lines than Vero cells in a concentration-dependent manner. The cell cycle of ZnO-Ns against Huh7 and Vero cell lines was arrested at G2/M. Also, the apoptosis assay using Annexin-V/PI showed that apoptosis of HuH7 and Vero cell lines by ZnO nanospheres was concentration and time-dependent. Caspase 3 assay results showed that the apoptosis mechanism may be intrinsic and extrinsic pathways. The mechanism of apoptosis was determined by applying the RT-PCR technique. The results revealed significantly up-regulated Bax, P53, and Cytochrome C, while the Bcl2 results displayed significant down-regulation and the western blot data confirmed the RT-PCR data. There is oxidative stress of the ZnO nanospheres and free Zn+2 ions. Results indicated that the ZnO nanospheres and free Zn+2 ions induced oxidative stress through increasing reactive oxygen species (ROS) and lipid peroxidation. The morphology of the HuH7 cell line after exposure to ZnO nanospheres at different time intervals revealed the presence of the chromatin condensation of the nuclear periphery fragmentation. Interestingly, the appearance of canonical ultrastructure features of apoptotic morphology of Huh7, Furthermore, many vacuoles existed in the cytoplasm, the majority of which were lipid droplets, which were like foamy cells. Also, there are vesicles intact with membranes that are recognized as swollen mitochondria.

Ameliorative Effect of Pomegranate Peel Extract (PPE) on Hepatotoxicity Prompted by Iron Oxide Nanoparticles (Fe2O3-NPs) in Mice.

An evaluation of the ameliorative effect of pomegranate peel extract (PPE) in counteracting the toxicity of iron oxide nanoparticles (Fe2O3-NPs) that cause hepatic tissue damage is focused on herein. Forty male albino mice were haphazardly grouped into four groups as follows: the first control group was orally gavage daily with physiological saline; the second group received 100 mg/kg of PPE by the oral route day after day; the third group received 30 mg/kg Fe2O3-NPs orally; and the fourth group received both PPE and Fe2O3-NPs by the oral route, the same as the second and third sets. Later, after the completion of the experiment, we collected the liver, blood, and bone marrow of bone specimens that were obtained for further laboratory tests. For instance, exposure to Fe2O3-NPs significantly altered serum antioxidant biomarkers by decreasing the levels of total antioxidant capacity (TAC), catalase (CAT), and glutathione s-transferase (GST). Additionally, it caused changes in the morphology of hepatocytes, hepatic sinusoids, and inflammatory Kupffer cells. Furthermore, they significantly elevated the number of chromosomal aberrations including gaps, breaks, deletions, fragments, polyploidies, and ring chromosomes. Moreover, they caused a significant overexpression of TIMP-1, TNF-α, and BAX mRNA levels. Finally, the use of PPE alleviates the toxicity of Fe2O3-NPs that were induced in the hepatic tissues of mice. It is concluded that PPE extract has mitigative roles against the damage induced by Fe2O3-NPs, as it serves as an antioxidant and hepatoprotective agent. The use of PPE as a modulator of Fe2O3-NPs' hepatotoxicity could be considered as a pioneering method in the use of phytochemicals against the toxicity of nanoparticles.

Synergistic antibacterial activity of compact silver/magnetite core-shell nanoparticles core shell against Gram-negative foodborne pathogens.

The development of innovative antibacterial drugs against foodborne pathogens has led to an interest in novel materials such as nanomaterials. The unique features of nanomaterial qualify it for use as an antibacterial treatment. Noble metals and metal oxide nanoparticles, such as silver and magnetite nanoparticles, have been shown to be effective antibacterial medications against a range of microorganisms. In this work, Ag@Fe3O4 -NPs were fabricated by using a wet chemical reduction and modified co-precipitation techniques. The antibacterial efficiency of the Ag/Fe3O4 core shell nanoparticles was investigated by applying various techniques, such as the Kirby-Bauer Disk Diffusion test, minimum inhibitory concentration (MIC) and bactericidal concentration (MBC), Colony Forming Unit (CFU), and kill time assay. The toxicity mechanism of Ag@Fe3O4 -NPs against Salmonella typhimurium and Escherichia coli was studied by apoptosis and reactive oxygen species (ROS) assays. The data revealed that a cubic core was surrounded by a silver shell, which indicated the regular morphology of silver magnetite core shell nanoparticles without any aggregation. Furthermore, Ag@Fe3O4 -NPs is more toxic against S. typhimurium and E. coli than Ag-NPs and Fe3O4 NPs. The MIC values for Ag/Fe3O4 NPs against S. typhimurium and E. coli were 3.1 and 5.4 µg/ml, respectively, whereas the MIC values for Ag-NPs and MNPs against S. typhimurium and E. coli were 4.1 and 8.2 µg/ml for Ag-NPs and 6.9 and 10.3 µg/ml for MNPs. The results showed the ability of Ag@Fe3O4 -NPs to induce apoptosis by generating ROS. Also, the ability of Ag@Fe3O4 -NPs to liberate free Ag+ and generate ROS via the Haber-Weiss cycle may be a plausible mechanism to explain the toxicity of Ag@Fe3O4 -NPs - NPs.

Correlation between Apelin and Some Angiogenic Factors in the Pathogenesis of Preeclampsia: Apelin-13 as Novel Drug for Treating Preeclampsia and Its Physiological Effects on Placenta.

Preeclampsia (PE) is one of the commonest causes for maternal and fetal morbidity and mortality. Imbalances of angiogenic factors, oxidative stress, and inflammatory response have a role in the pathogenesis of PE. Data regarding the circulating apelin level and its role in PE remains controversial. This study was formulated to assess the serum apelin level in PE, investigate its correlation with some inflammatory, oxidative stress, and angiogenic proteins in a nitric oxide synthase inhibitor; the N (gamma)-nitro-L-arginine methyl ester (L-NAME)-induced rat model of PE and determine whether apelin administration could protect against development of PE. 40 healthy adult female albino rats and 10 adult male albino rats were used in this study. The pregnant female rats were randomly divided into three groups: group 1 (normal pregnant group), group 2 (PE-induced group), injected subcutaneously with 75 mg L-NAME/kg bodyweight/day starting from day 9 to 20 of gestation, and group 3 (PE-induced group supplemented with apelin (PE + apelin)); PE induced as before and simultaneously subcutaneously injected with apelin-13 (6 × 10-8 mol/kg bodyweight/twice daily) beginning from day 6 to 20 of gestation. In all groups, blood pressure and urine protein were determined at gestation days (GD) 0, 10, and 18. Moreover, serum apelin, placental growth factor (PLGF), vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), interferon-gamma (IFN-γ), and interleukin-10 (IL-10) levels and serum superoxide dismutase enzyme (SOD) and catalase (CAT) activities of all groups were estimated at the end of experiment. Placental histopathological examination was also performed. PE-induced rats showed significantly decreased serum apelin levels. Moreover, they showed significantly increased blood pressures, urine proteins, sFlt-1, sEng, and IFN-γ (mean arterial blood pressure, urine proteins, sFlt-1, sEng, and IFN-γ showed significant negative correlations with serum apelin level), but it showed significantly decreased VEGF, PLGF, IL-10, SOD, and CAT (VEGF, PLGF, IL-10, and SOD showed significant positive correlations with serum apelin level). In contrast, exogenous apelin administration significantly ameliorated these parameters together with improvement in the placental histoarchitecture in the apelin-supplemented PE group. This study demonstrated the protective effects of apelin administration on the pathogenesis of PE.

In Situ Neutral System Synthesis, Spectroscopic, and Biological Interpretations of Magnesium(II), Calcium(II), Chromium(III), Zinc(II), Copper(II) and Selenium(IV) Sitagliptin Complexes.

Magnesium(II), calcium(II), chromium(III), zinc(II), copper(II), and selenium(IV) sitagliptin (STG) complexes-with the general formulas [Mg(STG)2(Cl)2]·6H2O, [Ca(STG)2(Cl)2], [Cr(STG)2(Cl)2]Cl.6H2O, [Zn(STG)2(Cl)2], [Cu(STG)2(Cl)2]·2H2O, and [Se(STG)2(Cl)2]Cl2, respectively-were designed and synthesized by the chemical reactions between metal(II, III, and IV) chloride salts with an STG ligand in situ methanol solvent in a 1:2 stoichiometric ratio (metal:ligand). Tentative structures of the complexes were proposed based on elemental analysis, molar conductance, magnetic moments, thermogravimetric analysis, and spectral (infrared, electronic, and 1H NMR) data. The particle size and morphological investigation were checked on the bases of scanning electron microscopy, transmission electron microscopy, and X-ray powder diffraction analyses. All the Mg2+, Ca2+, Cr3+, Zn2+, Cu2+, and Se4+ complexes were found to be six-coordinated, wherein the STG ligands act as bidentate chelating agents. This study demonstrates that pancreatic tissues are affected by the induction of experimental diabetes mellitus and clarifies the potential of the synthesized STG complexes, which was found to more significantly improve insulin secretion and the pancreatic and glycometabolic complications of diabetic rats than STG alone.

Quercetin/Zinc complex and stem cells: A new drug therapy to ameliorate glycometabolic control and pulmonary dysfunction in diabetes mellitus: Structural characterization and genetic studies.

Medicinal uses and applications of metals and their complexes are of increasing clinical and commercial importance. The ligation behavior of quercetin (Q), which is a flavonoid, and its Zn (II) (Q/Zn) complex were studied and characterized based on elemental analysis, molar conductance, Fourier-transform infrared (FTIR) spectra, electronic spectra, proton nuclear magnetic resonance (1H-NMR), thermogravimetric analysis, and transmission electron microscopy (TEM). FTIR spectral data revealed that Q acts as a bidentate ligand (chelating ligand) through carbonyl C(4) = O oxygen and phenolic C(3)-OH oxygen in conjugation with Zn. Electronic, FTIR, and 1H-NMR spectral data revealed that the Q/Zn complex has a distorted octahedral geometry, with the following chemical formula: [Zn(Q)(NO3)(H2O)2].5H2O. Diabetes was induced by streptozotocin (STZ) injection. A total of 70 male albino rats were divided into seven groups: control, diabetic untreated group and diabetic groups treated with either MSCs and/or Q and/or Q/Zn or their combination. Serum insulin, glucose, C-peptide, glycosylated hemoglobin, lipid profile, and enzymatic and non-enzymatic antioxidant levels were determined. Pancreatic and lung histology and TEM for pancreatic tissues in addition to gene expression of both SOD and CAT in pulmonary tissues were evaluated. MSCs in combination with Q/Zn therapy exhibited potent protective effects against STZ induced hyperglycemia and suppressed oxidative stress, genotoxicity, glycometabolic disturbances, and structural alterations. Engrafted MSCs were found inside pancreatic tissue at the end of the experiment. In conclusion, Q/Zn with MSC therapy produced a synergistic effect against oxidative stress and genotoxicity and can be considered potential ameliorative therapy against diabetes with pulmonary dysfunction, which may benefit against COVID-19.

Efficacy of Vanadyl Sulfate and Selenium Tetrachloride as Anti-Diabetic Agents against Hyperglycemia and Oxidative Stress Induced by Diabetes Mellitus in Male Rats.

The use of metals in medicine has grown in popularity in clinical and commercial settings. In this study, the immune-protecting effects and the hypoglycemic and antioxidant activity of vanadyl sulfate (VOSO4) and/or selenium tetrachloride (Se) on oxidative injury, DNA damage, insulin resistance, and hyperglycemia were assessed. Fifty male albino rats were divided into five groups, and all treatments were administrated at 9:00 a.m. daily for 60 successive days: control, STZ (Streptozotocin; 50 mg/kg of STZ was given to 6 h fasted animals in a single dose, followed by confirmation of diabetic state occurrence after 72 h by blood glucose estimation at >280 mg/dl), STZ (Diabetic) plus administration of VOSO4 (15 mg/kg) for 60 days, STZ (Diabetic) plus administration of selenium tetrachloride (0.87 mg/Kg), and STZ plus VOSO4 and, after 1/2 h, administration of selenium tetrachloride at the above doses. The test subjects' blood glucose, insulin hormone, HbA1C, C-peptide, antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, myeloperoxidase, and xanthine oxidase), markers of lipid peroxidation (MDA), and histological sections of pancreatic tissues were evaluated, and a comet assay was performed. Histological sections in pancreas tissues were treated as indicators of both VOSO4 and selenium tetrachloride efficacy, either alone or combined, for the alleviation of STZ toxicity. The genotoxicity of diabetes mellitus was assessed, and the possible therapeutic roles of VOSO4 or selenium tetrachloride, or both, on antioxidant enzymes were studied. The findings show that the administration of VOSO4 with selenium tetrachloride reduced oxidative stress to normal levels, lowered blood glucose levels, and elevated insulin hormone. Additionally, VOSO4 with selenium tetrachloride had a synergistic effect and significantly decreased pancreatic genotoxicity. The data clearly show that both VOSO4 and selenium tetrachloride inhibit pancreatic and DNA injury and improve the oxidative state in male rats, suggesting that the use of VOSO4 with selenium tetrachloride is a promising synergistic potential ameliorative agent in the diabetic animal model.

Chitosan and Lecithin Ameliorate Osteoarthritis Symptoms Induced by Monoiodoacetate in a Rat Model.

The present work aimed to assess the chondroprotective influence of chitosan and lecithin in a monoiodoacetate (MIA)-induced experimental osteoarthritis (OA) model. Forty male rats weighing 180-200 g were randomly distributed among the following five experimental groups (eight per group): control, MIA-induced OA, MIA-induced OA + chitosan, MIA-induced OA + lecithin, and MIA-induced OA + chitosan + lecithin. The levels of TNF-α, IL6, RF, ROS, and CRP, as well as mitochondrial markers such as mitochondrial swelling, cytochrome C oxidase (complex IV), MMP, and serum oxidative/antioxidant status (MDA level) (MPO and XO activities) were elevated in MIA-induced OA. Also, SDH (complex II) activity in addition to the levels of ATP, glutathione (GSH), and thiol was markedly diminished in the MIA-induced OA group compared to in control rats. These findings show that mitochondrial function is associated with OA pathophysiology and suggest that chitosan and lecithin could be promising potential ameliorative agents in OA animal models. Lecithin was more effective than chitosan in ameliorating all of the abovementioned parameters.

Zinc oxide nanoparticles with green tea extract complex in the pancreas of rats against monosodium glutamate toxicity.

OBJECTIVES: Nanotechnology is an exciting field for investigators. Green zinc oxide nanoparticles (ZnO NPs) with Camellia sinensis extract complex are proved to be used in the treatment of the toxicity of monosodium glutamate (MSG) in the liver, kidney, and testis of rats. Therefore, the synthesized complex of green nanoparticles using green tea extract (GTE) was tested against the toxicity of MSG on the pancreas. METHODS: The glucose and insulin levels were estimated as well as some biochemical parameters for evaluating the antioxidant status of the pancreas tissue. The histopathological change of the pancreas also has been determined. RESULTS: It indicates the biomedical capability of ZnO NPs/GTE to act as potent antidiabetic through decreasing blood glucose and increasing serum insulin also, inhibition of lipid peroxidation and enhancement of the antioxidant parameters. CONCLUSIONS: The ZnO NPs/GTE enhanced the pancreatic cell and Langerhans islets as well lowered the sugar levels and stimulated insulin.

Ameliorative Role of Green Tea and Zinc Oxide Nanoparticles Complex Against Monosodium Glutamate-Induced Testicular Toxicity in Male Rats.

BACKGROUND AND OBJECTIVE: This study was designed to estimate the long-term effects of zinc oxide nanoparticles/green tea (ZnONPs/GTE) complex against monosodium glutamate (MSG). The antioxidant/oxidative status, testosterone levels, DNA damage, and histopathological changes of testis were evaluated. METHODS: The rats were divided into eight groups that were treated as follows: saline, the lower dosage of MSG (6.0 mg/kg), the higher dosage of MSG (17.5 mg/Kg), GTE, ZnONPs, ZnONPs/GTE and the last two groups were treated with the lower dosage of MSG or the higher dosage of MSG with ZnONPs/GTE complex. The data showed minimal toxicity in testicular tissue after the administration of ZnONPs. RESULTS: The MSG treatment in the adult male rats reduced testosterone levels and disrupted testicular histology, which revealed dose-dependence of MSG. Also, ZnONPs induced testicular dysfunction through the interference of antioxidant/oxidant balance and suppression of testosterone levels as well as induction of cellular damage of testis. The combination of ZnONPs with GTE complex significantly protects against MSG or ZnONPs toxicity by decreasing the DNA damage, oxidative stress, and enhancement of antioxidant as well as histological structure of testis. CONCLUSION: We could recommend using ZnONPs/GTE complex to reduce the toxicity of ZnONPs and MSG on the testis at the cellular and oxidative stress levels.

Evaluation of the effects of the green nanoparticles zinc oxide on monosodium glutamate-induced toxicity in the brain of rats.

BACKGROUND: Monosodium glutamate (MSG) is used extensively as a food additive in the diets of many countries around the world. AIM OF THE STUDY: Our aim was to determine the effects of green zinc oxide nanoparticles on MSG-induced oxidative damage, neurotransmitter changes, and histopathological alternation in the cerebral cortexes of rats. METHODS: MSG was administered orally at two doses of 6 and 17.5 mg/kg body weight. The higher dose was associated with a significant decline in the activities of superoxide dismutase, catalase, and glutathione peroxidase, as well as the levels of brain-derived neurotrophic factor (BDNF) and glutathione (GSH) in the cerebral cortex of rats. RESULTS: The administration of zinc oxide nanoparticles/green tea extract (ZnO NPs/GTE) to 17.5 mg/kg MSG-treated rats was associated with significant improvements in all parameters previously shown to be altered by MSG. The higher dose of MSG induced significant histopathological variation in brain tissue. Co-treatment of rats with ZnO NPs/GTE and MSG-HD inhibited the reduction of neurotransmitters and acetylcholinesterase by MSG. CONCLUSIONS: ZnO NPs/GTE have the potential to protect against oxidative stress and neuronal necrosis induced by MSG-HD. ZnO NPs/GTE conferred a greater benefit than the control treatment or ZnO NPs or GTE administered separately.

Evaluation of the Effect of Nanoparticles Zinc Oxide/Camellia sinensis Complex on the Kidney of Rats Treated with Monosodium Glutamate: Antioxidant and Histological Approaches.

BACKGROUND: Zinc oxide nanoparticles (ZnO NPs) are robustly used biomedicine. Moreover, no study has been conducted to explore the consequence of green synthesis of ZnO NPs with Camellia sinensis (green tea extract, GTE) on kidneys of rats treated with monosodium glutamate (MSG). METHODS: Therefore, the objective of the research was designed to explore the possible defensive effect of GTE/ZnO NPs against MSG-induced renal stress investigated at redox and histopathological points. RESULTS: The levels of urea and creatinine increased as the effect of a high dose of MSG, in addition, the myeloperoxidase and xanthine oxidase activates were elevated significantly with the high dose of MSG. The levels of non-enzymatic antioxidants (uric acid, glutathione, and thiol) were decreased sharply in MSG-treated rats as compared to the normal group. CONCLUSION: The data displayed that GTE/ZnO NPs reduced the effects of MSG significantly by reduction of the level peroxidation and enhancement intracellular antioxidant. These biochemical findings were supported by histopathology evaluation, which showed minor morphological changes in the kidneys of rats.