Degradation of Bisphonel AF (BPAF) by zero-valent iron activated persulfate: Kinetics, mechanisms, theoretical calculations, and effect of co-existing chloride.

The removal of Bisphonel AF (BPAF) by zero-valent iron activated persulfate (Fe0/PS) system was systematically evaluated in this work. 30.0 µM BPAF was removed by 94.4% in 60 min of treatment under optimal conditions of pH = 3.0 and [PS] = [Fe0] = 3.0 mM. Cl- significantly accelerated the removal of BPAF, resulting from accelerated Fe2+ release and reactive chlorine species (RCS) formation. Liquid chromatography-time-of-flight-mass spectrometry identified thirteen degradation products, and bond breaking, coupling reactions, hydroxylation and sulfate addition were considered as the major transformation pathways. When Cl- was present, six new chlorinated byproducts were also generated. Based on density functional theory (DFT) calculations, the occurrence of radical addition reactions was verified and the preferential reaction channels were determined. Significantly BPAF degradation products were less toxic, according to toxicity assessment by the ECOSAR program. Moreover, a high removal efficiency of BPAF (>90%) was also obtained in the three actual water matrixes. The present work demonstrates the feasibility of Fe0/PS system for treating BPAF, which could also provide new insights into the influence of coexisting Cl- on the environmental fate of organic pollutants in sulfate radicals based advanced oxidation processes.

Insight into the photodegradation and universal interactive products of 2,2',4,4'-tetrabromodiphenyl ether on three microplastics.

The transformation process of contaminants on microplastics (MPs) exposed to sunlight has attracted increasing attention. However, the interactions between them are typically disregarded; therefore, this work investigated the photodegradation of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on three MPs (polystyrene (PS), polypropylene (PP) and polyethylene (PE)) and the interactions between these two. The inhibition of aged PS on the elimination of BDE-47 was due to light shielding, while aged PP and PE increased the degradation rate. More hydroxyl radicals (HO•) was detected in the PS system, which resulted in the higher degradation rate of BDE-47 on PS. A total of 33 different products were identified and four reaction pathways were presented, and the reaction mechanisms mainly included debromination, hydroxylation, carbon-oxygen-bond breaking and interactive reactions. The Ecological Structure Activity Relationship (ECOSAR) and Toxicity Estimation Software Tool (TEST) programs were used to evaluate the toxicity of reaction products, and the results indicated that even though BDE-47 was the most toxic, the interaction products were still toxic or harmful to aquatic organisms. This study provides significant information on the photodegradation of contaminants on common microplastics and their interaction, which cannot be ignored.

Insight into the Loading Properties of Na+ Green-Functionalized Clinoptilolite as a Potential Carrier for the 5-Fluorouracil Drug, its Release Kinetics, and Cytotoxicity.

Herein, natural zeolite (clinoptilolite) was functionalized by Na+ ions (G.Na+/Clino) utilizing a green tea extract prepared by a green production method as a potential carrier for the 5-fluorouracil (5-Fu) drug with enhanced physicochemical behaviors. The G.Na+/Clino-modified product showed enhanced surface area (312 m2/g) and ion-exchange capacity (387 mequiv/100 g). The loading studies reflect high and controlled loading properties of G.Na+/Clino with an actual loading capacity of 291 and 462 mg/g, respectively. The loading reactions of 5-Fu into G.Na+/Clino were of pseudo-second-order kinetics and exhibited Langmuir isotherm properties. This suggested a monolayer and homogeneous loading process by chemical complexation and ion-exchange mechanisms with a Gaussian energy value of 10.47 kJ/mol. Additionally, these reactions were of endothermic and spontaneous nature based on the determined thermodynamic parameters. The release studies demonstrated the 5-Fu release profile for about 150 h at pH 1.2 and for 80 h at pH 7.4. The release reactions had non-Fickian transport properties and were controlled by both erosion and diffusion mechanisms, considering the release kinetic findings and the values of the diffusion exponent (0.42 at pH 1.2 and 0.37 at pH 7.4). The composite showed remarkable biocompatibility based on the measured cell viability and a cytotoxic effect on normal colorectal cells (CCD-18Co). Additionally, the application of G.Na+/Clino as an inorganic carrier for the 5-Fu drug prompted the cytotoxic effect of the drug on colon cancer cell treatment (HCT-116).

Isoliquiritigenin prevents Doxorubicin-induced hepatic damage in rats by upregulating and activating SIRT1.

This study evaluated if the hepatic protective effect of Isoliquiritigenin (ISL) against doxorubicin (DOX)-treated rats involves upregulating sirtuin-1 (SIRT1) signaling. Adult male was divides into 5 groups (n = 6 rats/each) as control (vehicle), ISL (25 mg/kg), DOX (15 mg/kg), DOX + ISL, and DOX + ISL + EX-527 (a SIRT1 inhibitor, 5 mg/kg). ISL and EX-527 were administered 10 days before and after the single treatment of DOX. Also, cultured AML-12 hepatocytes (5 ×104) were treated with 10 µM of ISL for 24 h with or without DOX-treatments (10 µM) and in the presence or absence of EX-527 (5 µM). ISL prevented hepatocyte damage and decreased serum levels of hepatic transaminases, hepatic levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and hepatic mRNA levels of Bax and caspases-3,8, and 9. In the liver of the control and DOX-treated rats, ISL reduced levels of malondialdehyde (MDA) but increased hepatic levels of glutathione (GSH), superoxide dismutase (SOD), and catalase, as well as mRNA levels of Bcl2. In vitro, ISL stimulated cell survival and lowered levels of ROS but increased GSH levels. In vivo and in vitro, in the livers of control and DOX-treated animals, ISL significantly increased the nuclear activity and mRNA levels of SIRT1, enhanced the nuclear levels of Nrf2, and reduced nuclear levels of NF-κB p65. In conclusion, ISL alleviates DOX-induced hepatocyte toxicity by stimulating the Nrf2/antioxidants axis and concomitant suppression of NF-κB, mainly by upregulating/activating SIRT1.

Insight into the Technical Qualification of the Sonocogreen CaO/Clinoptilolite Nanocomposite (CaO(NP)/Clino) as an Advanced Delivery System for 5-Fluorouracil: Equilibrium and Cytotoxicity.

Clinoptilolite as a natural zeolite was integrated with green CaO nanoparticles forming the green nanocomposite CaO(NP)/Clino. The CaO(NP)/Clino composite was assessed as a potential carrier for 5-fluorouracil (5-FL) drug. The CaO(NP)/Clino carrier achieved an enhanced 5-FL loading capacity of 305.3 mg/g as compared to 163 mg/g for pure clinoptilolite. The kinetics of the 5-FL loading follow the properties of the pseudo-first-order model, while the equilibrium results are related to the Langmuir isotherm. Therefore, the 5-FL loading processes occurred in the monolayer formed by homogeneous active loading receptors on the surface of the CaO(NP)/Clino carrier. The Gaussian energy of the 5-FL loading reaction (9.2 KJ/mol) reflected the dominant effect for the chemical mechanisms, especially the zeolitic ion-exchange mechanisms. Additionally, the thermodynamic parameters suggested endothermic, feasible, and spontaneous properties for the occurred 5-FL loading reactions. The release profile of 5-FL from CaO(NP)/Clino has continuous and long properties (150 h) at pH 1.2 (gastric fluid) and pH 7.4 (intestinal fluid). The kinetic studies of the release reactions show considerable agreement with Higuchi, Hixson-Crowell, and Korsmeyer-Peppas models. Such high fitting results and the diffusion exponent values (0.49 at pH 1.2 and 0.48 at pH 7.4) reflected the release properties of the Fickian transport behavior involving complex erosion and diffusion mechanisms. The cytotoxicity study of CaO(NP)/Clino on colorectal normal cells (CCD-18Co) declare the safe and biocompatible effect as a carrier for the 5-FL drug. Additionally, CaO(NP)/Clino as a carrier causes considerable enhancement for the cytotoxic effect of the loaded 5-FL drug on colon cancer cells (HCT-116).

Wound dressing of chitosan-based-crosslinked gelatin/ polyvinyl pyrrolidone embedded silver nanoparticles, for targeting multidrug resistance microbes.

Wound dressing composed of chitosan, based crosslinked gelatin/ polyvinyl pyrrolidone, embedded silver nanoparticles were fabricated using solution casting method. The membrane was characterized by FTIR, SEM and TGA. Glutaraldehyde (0.5 %) was used for the crosslinking of membrane components and associated with 7-folds boosted mechanical performance, 28 % more hydrolytic stability, 3-folds thickness reduction and morphological roughness. Silver nanoparticles were characterized by UV-vis, XRD and TEM for an average size of 9.9 nm. The membrane with higher concentration of silver nanoparticles showed maximum antibacterial activity against human pathogenic bacteria; and the measured inhibition zones ranged from 1.5 to 3 cm. The activity of the particles ranged from severe to complete reduction in Penicillin, Erythromycin and Macrolide family's resistance genes expression such as ß-Lactamase, mecA and erm. This developed membrane can serve as promising and cost-effective system against severe diabetic and burn wound infections.

Edaravone and Acetovanillone Upregulate Nrf2 and PI3K/Akt/mTOR Signaling and Prevent Cyclophosphamide Cardiotoxicity in Rats.

INTRODUCTION: Cyclophosphamide (CP) causes redox imbalance and its use is associated with marked cardiotoxicity that limits its clinical applications. The present study investigated the protective effects of acetovanillone (AV) and edaravone (ED) against CP-induced oxidative stress and cardiac damage, emphasizing the role of PI3K/Akt/mTOR and Nrf2 signaling. MATERIALS AND METHODS: Rats received either AV (100 mg/kg) or ED (20 mg/kg) orally for 10 days and CP (200 mg/kg) on day 7. At day 11, the rats were sacrificed, and samples were collected for analysis. RESULTS: AV and ED ameliorated serum troponin I, CK-MB, LDH, AST and ALP, and prevented cardiac histological alterations in CP-intoxicated rats. Both treatments decreased cardiac lipid peroxidation and enhanced GSH, SOD and cytoglobin in CP-induced rats. AV and ED downregulated Keap1, whereas increased the expression of PI3K, Akt, mTOR and Nrf2 in the heart of rats received CP. Additionally, the binding modes of AV and ED to Keap1 were pinpointed in silico using molecular docking simulations. CONCLUSION: AV and ED prevent CP cardiotoxicity by attenuating oxidative stress and tissue injury, and modulating cytoglobin, and PI3K/Akt/mTOR and Keap1/Nrf2 signaling. Therefore, AV and ED may represent promising agents that can prevent cardiac injury in patients receiving CP.

Consequences of various housing systems and dietary supplementation of thymol, carvacrol, and euganol on performance, egg quality, blood chemistry, and antioxidant parameters.

The present work was carried out to investigate the influences of housing system and dietary essential oils (EOs) supplementation to laying hens on the productive performance, egg quality, immunity, antioxidant parameters, and hematology. A factorial arrangement (2 × 4) was performed, including 2 housing systems and 4 different types of EOs (without EOs, thymol, carvacrol, and euganol) during the production stages (from 28-78 wk of age). Birds were randomly divided into 2 groups with each of 2,000 birds. The first group was moved to laying cages while the second group was a floor reared. Each group was randomly divided into 4 groups (5 replicates of 100 birds each): The first were considered as a control group, and the second, third, and fourth groups were treated with thymol, carvacrol, and euganol EO, respectively. The results showed that hens reared in cage system had higher egg weight (P < 0.05), egg production, egg mass, and feed intake and better feed conversion ratio (P < 0.001) than those reared in the floor system. Blood picture values (except white blood cells), phagocytic index, phagocytic activity, and blood chemistry parameters (except calcium, phosphorus, and urea values) of laying hens were not affected (P > 0.05) by housing system. The groups fed EOs showed a rapid improvement (P < 0.001) in the egg production%, egg weight, egg mass, and egg quality. Thymol group had the highest egg production (P < 0.001). Thymol and eugenol groups had the highest egg weight, egg mass, and egg quality (P < 0.001). The groups fed diets containing thymol or eugenol consumed lower feed and had better feed conversion ratio (P < 0.001) than the control group. Immunity indices (phagocytic activity [P < 0.05], avian influenza [AIH5 and AIH9], P < 0.001) were improved with the presence of EOs in the laying hen diet. These results strongly suggest that dietary EO supplementation could be a successful attempt to improve the productive performance, egg quality, and immunity of laying hens.

Evaluation of different forms of Egyptian diatomite for the removal of ammonium ions from Lake Qarun: A realistic study to avoid eutrophication.

Three types of diatomite-based adsorbents-diatomaceous earth (DE), purified diatomite (PD), and diatomite@MgO/CaO (D@MgO) were used for adsorption decontamination of ammonium from Lake Qarun water (28.7 mg/L). The adsorption properties of the three diatomite-based adsorbents were evaluated by both batch and fixed-bed column adsorption studies. The kinetic results demonstrated removal percentages of 97.2%, 69.5%, and 100% using DE, PD, and D@MgO, respectively, at a 1 g/L adsorbent dosage. The adsorption results using DE and D@MgO showed the best fitness with pseudo-first-order kinetic and Langmuir isotherm models, while the obtained results using PD demonstrate better fitness with the Freunlidich model. The recognised fitting results with the pseudo-first-order model and estimated adsorption energies demonstrated physical uptake of ammonium by DE (5.93 kJ/mol), PD (4.05 kJ/mol), and D@MgO (7.81 kJ/mol). The theoretical maximum ammonium uptake capacity of DE, PD, and D@MgO were 63.16 mg/g, 59.5 mg/g, and 78.3 mg/g, respectively. Using synthetic adsorbents in a fixed-bed column system for treating ammonium ions in Lake Qarun water resulted in removal percentages of 57.4%, 53.3%, and 62.6% using a DE bed, PD bed, and D@MgO bed, respectively, after treating approximately 7.2 L of Lake Qarun water using a bed thickness of 3 cm, a flow rate of 5 mL/min, pH 8, and the determined ammonium concentration in Lake Qarun water (28.7 mg/L). The curves demonstrated breakthrough times of 900 min, 900 min, and 960 min for the DE bed, PD bed, and D@MgO bed, respectively, with 1440 min as the saturation time. The columns' performances also were studied based on the Thomas model, the Adams-Bohart model, and the Yoon-Nelson model.

Effect of a Diet Supplemented with the Moringa oleifera Seed Powder on the Performance, Egg Quality, and Gene Expression in Japanese Laying Quail under Heat-Stress.

This study was conducted to evaluate the effect of three concentrations of the Moringa oleifera seed powder as a feed supplement on the productive performance and egg quality traits of laying Japanese quail (Coturnix japonica) exposed to heat stress. The expression patterns of the genes estrogen receptors (ESR2), follicle-stimulating hormone receptor (FSHR), prolactin receptor (PRLR), and steroidogenic acute regulatory protein (STAR) were estimated in ovaries, using a quantitative real-time polymerase chain reaction. A total of 200 laying quail aged seven weeks were randomly allocated to the following four experimental groups-the control (CNT), T1, T2, and T3 groups; each group comprised 50 quail females with 5 replicates (10 per group). The CNT group was fed a basal diet, whereas the T1, T2, and T3 groups were fed the basal diet supplemented with 0.1%, 0.2%, and 0.3% M. oleifera seed powder, respectively. The results revealed that the T3 group showed the highest hen-day egg production (%) as well as the highest egg yolk index. Feed intake and feed conversion ratio improved significantly (p < 0.05) with increased concentrations of the M. oleifera seed powder supplementation. Furthermore, the mRNA expressions of ESR2, FSHR, and STAR increased significantly in the T3 group, compared to those in the CNT group. Alterations in ovarian gene expressions corresponded to the reproductive patterns of the treated Japanese quail. Thus, it was concluded that the supplementation of the Japanese quail feed with 0.3% M. oleifera seed powder during the laying period might enhance resistance to heat stress and consequently improve egg productivity.

The efficiency of blackberry loaded AgNPs, AuNPs and Ag@AuNPs mediated pectin in the treatment of cisplatin-induced cardiotoxicity in experimental rats.

Cisplatin (cis-Diaminedichloroplatinum) is one of the most effective chemotherapeutic because of its anti-neoplastic properties against various types of tumor. However, it has a wide variety of side effects such as hepato, gastrointestinal, neuro, nephro, and cardiotoxicity (acute and/or chronic) that highly restricted its usage. Thus, research work was planned to detect the role of gold (AuNPs), silver nanoparticles (AgNPs) and their corepshell (Ag@AuNPs) as a carrier for blackberry extract and to enhance its benifit in treatment of cisplatin-induced cardiotoxicity. In our work, solid-state process was used in order to prepare these nanoparticles using pectin as an ecologically friendly-polymer acting as reductant for ions and at the same time as stabilizing agent for the produced nanoparticles. This nominated method for large-scale preparation of nanoparticles is simple, efficient, and convenient. The presence of individual metallic Ag, Au and both has been proven by UV-vis spectroscopy. Transmission electron microscopy (TEM) and particle size analyzer confirmed the preparation of spherical small size with a main diameter <40 nm. The data obtained from zeta potential evaluation displayed the well stabilization for the produced nanoparticles. Transmission electron microscopy (TEM), scanning electron microscopy (SEM) and particle size analyzer have verified that the spherical small size is <40 nm in diameter. Data from zeta potential assessment revealed the good stability of the produced nanoparticles. To this end, fifty sex rats were used in this study and divided into control, cisplatin (cispt), and five treated groups. After the experimental period, lipid profile was estimated and atherogenic coefficient (AC), atherogenic index (AI), and cardiac risk ratio (CRR) were calculated. Oxidant and antioxidant parameters were also estimated. Cardiovascular disease markers were estimated by ELISA. The mean levels of cholesterol, triglycerides, malondialdehyde (MDA), advanced oxidative protein products (AOPP), and cardiovascular markers were significantly increased in cispt group compared to control; whereas these parameters were attenuated in all treated groups in particular that received blackberry (bb) loaded Ag@AuNPs. Based on these results, it can be concluded that bb has antioxidant and antilipidemic effect that help in protecting against cardiovascular disease specially when loaded with Ag@AuNPs.

Protective Effect of Genistein against Compound 48/80 Induced Anaphylactoid Shock via Inhibiting MAS Related G Protein-Coupled Receptor X2 (MRGPRX2).

Anaphylactoid shock is a fatal hypersensitivity response caused by non-IgE mediated mast cell activation. These reactions are mediated by a family of G protein-coupled receptors (GPCRs) known as Mas related GPCRX2 (MRGPRX2). Several US FDA approved drugs which are used in day to day life have been reported to cause anaphylactoid shock. Surprisingly, no therapeutic drugs are available which can directly target MRGPRX2 for treatment of anaphylactoid shock. Genistein is a non-steroidal polyphenol known for its diverse physiological and pharmacological activities. In recent studies, Genistein has been reported for its anti-inflammatory activity on mast cells. However, the effects and mechanistic pathways of Genistein on anaphylactoid reaction remain unknown. In the present study, we designed a battery of in-vitro, in-silico and in-vivo experiments to evaluate the anti-anaphylactoid activity of Genistein in order to understand the possible molecular mechanisms of its action. The in-vitro results demonstrated the inhibitory activity of Genistein on MRGPRX2 activation. Further, a mouse model of anaphylactoid shock was used to evaluate the inhibitory activity of Genistein on blood vessel leakage and hind paw edema. Taken together, our findings have demonstrated a therapeutic potential of Genistein as a lead compound in the treatment of anaphylactoid shock via MRGPRX2.

Detoxification Impacts of Ascorbic Acid and Clay on Laying Japanese Quail Fed Diets Polluted by Various Levels of Cadmium.

A total number of 360 laying Japanese quail (8 weeks of age) were randomly divided into 12 groups. Birds in all groups had nearly the same average initial body weight. A factorial arrangement (4 × 3) was performed including four levels of dietary cadmium (Cd) as cadmium chloride (0, 50, 100, and 150 mg/kg diet) and three levels of feed additives (without, 300 mg/kg ascorbic acid and 1.50% natural clay). Results revealed that Cd contaminated feed caused significant (p < 0.01) retardation in body weight, lower egg number and egg mass and worse feed conversion. On the other hand, the addition of ascorbic acid or natural clay to quail diets caused a significant (p < 0.01) improvement in all studied traits. With respect to the interaction among Cd and the experimental additives, results showed that within each Cd level, ascorbic acid or clay supplementation recorded the highest body weight, egg number, egg weight and mass in addition to improved feed conversion. Cadmium levels decreased (p < 0.05) blood total protein, albumen and A/G ratio. Both 300 mg ascorbic acid and 1.50% clay increased (p < 0.05) blood total protein and albumen compared to non-supplemented groups. It could be concluded that the consumption of polluted diets Cd causes deleterious effects on the productive performance of laying Japanese quail. The addition of ascorbic acid or natural clay to the diets causes beneficial effects on productive performance traits, improves egg quality criteria and diminishes the toxic effects of Cd.

The pH-dependent toxicity of triclosan to five aquatic organisms (Daphnia magna, Photobacterium phosphoreum, Danio rerio, Limnodrilus hoffmeisteri, and Carassius auratus).

Triclosan (TCS) is an antibacterial and antifungal agent widely used in personal care products, and it has been frequently detected in the aquatic environment. In the present study, the acute toxicity of TCS to Daphnia magna, Photobacterium phosphoreum, Danio rerio, and Limnodrilus hoffmeisteri was assessed under different pH conditions. Generally, TCS was more toxic to the four aquatic organisms in acidic medium. The LC50 values for D. magna and D. rerio were smaller among the selected species, suggesting that D. magna and D. rerio were more sensitive to TCS. In addition, the oxidative stress-inducing potential of TCS was evaluated in Carassius auratus at three pH values. Changes of superoxide dismutase (SOD) and catalase (CAT) activity, glutathione (GSH) level, and malondialdehyde (MDA) content were commonly observed in all TCS exposure groups, indicating the occurrence of oxidative stress in the liver of C. auratus. The integrated biomarker response (IBR) index revealed that a high concentration of TCS induced great oxidative stress in goldfish under acidic condition. This work supplements the presently available data on the toxicity data of TCS, which would provide some useful information for the environmental risk assessment of this compound.

Camellia sinensis Prevents Perinatal Nicotine-Induced Neurobehavioral Alterations, Tissue Injury, and Oxidative Stress in Male and Female Mice Newborns.

Nicotine exposure during pregnancy induces oxidative stress and leads to behavioral alterations in early childhood and young adulthood. The current study aimed to investigate the possible protective effects of green tea (Camellia sinensis) against perinatal nicotine-induced behavioral alterations and oxidative stress in mice newborns. Pregnant mice received 50 mg/kg C. sinensis on gestational day 1 (PD1) to postnatal day 15 (D15) and were subcutaneously injected with 0.25 mg/kg nicotine from PD12 to D15. Nicotine-exposed newborns showed significant delay in eye opening and hair appearance and declined body weight at birth and at D21. Nicotine induced neuromotor alterations in both male and female newborns evidenced by the suppressed righting, rotating, and cliff avoidance reflexes. Nicotine-exposed newborns exhibited declined memory, learning, and equilibrium capabilities, as well as marked anxiety behavior. C. sinensis significantly improved the physical development, neuromotor maturation, and behavioral performance in nicotine-exposed male and female newborns. In addition, C. sinensis prevented nicotine-induced tissue injury and lipid peroxidation and enhanced antioxidant defenses in the cerebellum and medulla oblongata of male and female newborns. In conclusion, this study shows that C. sinensis confers protective effects against perinatal nicotine-induced neurobehavioral alterations, tissue injury, and oxidative stress in mice newborns.

GENO PROTECTIVE AND ANTI-APOPTOTIC EFFECT OF GREEN TEA AGAINST PERINATAL LIPOPOLYSACCHARIDE-EXPOSURE INDUCED LIVER TOXICITY IN RAT NEWBORNS.

BACKGROUND: This study aims to examine the protective effect of green tea on the disturbances in oxidative stress and apoptosis related factors, mostly produced due to perinatal lipopolysaccharide (LPS) exposure, that subsequently induces liver cell damage. MATERIALS AND METHODS: Anti-free radical, Antioxidant, scavenging, geno-protective, and antiapoptotic activity of aqueous green tea extract (AGTE) were assessed against LPS-induced hepatic dysfunction in newborn-rats. AGTE at doses of 100 & 200 mg/kg was orally administered daily to rat dams, during gestation and lactation. RESULTS: AGTE was observed to exhibit protective effects by significantly attenuating LPS-induced alterations in serum AST, ALT, bilirubin, and albumin levels. Significant increase in the total antioxidant capacity (TAC), DNA contents, and reduction in nitric oxide (NO) levels were observed in AGTE treated rats comparing LPS-toxicated ones. Additionally, AGTE treatment significantly down-regulated apoptotic markers and this effect was directly correlated to the degree of hepatic fibrosis. The possible mechanisms of the potential therapeutic-liver protective effect of AGTE could be due to free radical scavenging potential and antiapoptotic properties caused by the presence of antioxidant polyphenolic components in AGTE. CONCLUSION: We thereby propose, based on our findings, that the anti-free radical and anti-apoptotic inducing properties of AGTE active constituents attribute to its functional efficacy as anti-fibrotic agent.

Novel Nano-Therapeutic Approach Actively Targets Human Ovarian Cancer Stem Cells after Xenograft into Nude Mice.

The power of tumorigenesis, chemo-resistance and metastasis in malignant ovarian tumors resides in a tiny population of cancer cells known as ovarian cancer stem cells (OCSCs). Developing nano-therapeutic targeting of OCSCs is considered a great challenge. The potential use of poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) was investigated as a drug delivery system for paclitaxel (PTX) against OCSCs in vitro and in vivo. PTX-loaded PLGA NPs were prepared by an emulsion solvent evaporation method, supported by incorporation of folic acid (FA) as the ligand. NPs were characterized for size, surface morphology, drug loading, and encapsulation efficiency. In vitro cytotoxicity of PTX-loaded FA/PLGA NPs was tested against OCSCs with MTT assay. In vivo anti-tumoral efficiency and active targeting potential of prepared NPs against tumors in nude mice were investigated. In vitro results revealed that IC50 of PTX was significantly reduced after loading on PLGA NPs. On the other hand, in vivo results showed that PLGA NPs enhanced the tumor suppression efficiency of PTX. Investigation with real time quantitative PCR analysis revealed the limiting expression of chemo-resistant genes (ABCG2 and MDR1) after applying PLGA NPs as a drug delivery system for PTX. Histopathological examination of tumors showed the effective biological influence of PTX-loaded FA/PLGA NPs through the appearance of reactive lymphoid follicles. Targeting potential of PTX was activated by FA/PLGA NPs through significant preservation of body weight (p < 0.0001) and minimizing the systemic toxicity in healthy tissues. Immunohistochemical investigation revealed a high expression of apoptotic markers in tumor tissue, supporting the targeting effect of FA/PLGA NPs. A drug delivery system based on FA/PLGA NPs can enhance PTX's in vitro cytotoxicity and in vivo targeting potential against OCSCs.

Anti-Inflammatory and Antioxidative Stress Effects of Oryzanol in Glaucomatous Rabbits.

Purpose. γ-Oryzanol works by anti-inflammatory and radical scavenging activity as a neuroprotective, anticancer, antiulcer, and immunosuppressive agent. The present study was conducted to investigate effect of oryzanol in acute and chronic experimental glaucoma in rabbits. Methods. Effect of oryzanol was evaluated in 5% dextrose induced acute model of ocular hypertension in rabbit eye. Chronic model of glaucoma was induced with subconjunctival injection of 5% of 0.3 ml phenol. Treatment with oryzanol was given for next two weeks after induction of glaucoma. From anterior chamber of rabbit eye aqueous humor was collected to assess various oxidative stress parameters like malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, nitric oxide, and inflammatory parameters like TNF-α and IL-6. Structural damage in eye was examined by histopathological studies. Results. In acute model of ocular hypertension oryzanol did not alter raised intraocular pressure. In chronic model of glaucoma oryzanol exhibited significant reduction in oxidative stress followed by reduction in intraocular pressure. Oryzanol treatment reduced level of TNF-α and IL-6. Histopathological studies revealed decreased structural damage of trabecular meshwork, lamina cribrosa, and retina with oryzanol treatment. Conclusions. Oryzanol showed protective effect against glaucoma by its antioxidative stress and anti-inflammatory property. Treatment with oryzanol can reduce optic nerve damage.

Correlation between vitamin D levels and apoptosis in geriatric patients infected with hepatitis C virus genotype 4.

BACKGROUND: Vitamin D levels play a pivotal role in most biological processes and differ according to age. A deficiency of vitamin D in chronic hepatitis C (CHC) patients has been shown to be linked with the severity of liver fibrosis, but little is known about the mechanism of this association. OBJECTIVE: In this study, we evaluate the potential interrelation between vitamin D levels, oxidative stress, and apoptosis, based on liver fibrosis in geriatric patients infected with hepatitis C virus (HCV) genotype 4. SUBJECTS AND METHODS: A total of 120 adult individuals aged 30-68 years were recruited in this study. Of these, 20 healthy subjects (15 men and five women) with a mean age of 48.3±6.1 years were selected as controls, and 100 patients with a mean age of 47.8±4.9 years with chronic HCV (CHC) who had undergone liver biopsy (80 men and 20 women) were included in this study. Based on liver radiographic (computed tomography, magnetic resonance imaging) and histological Metavir system analyses, the CHC patients were classified into three groups: asymptomatic CHC carriers (n=30), fibrosis (n=25), and cirrhosis (n=45). HCV RNA, HCV genotypes, inflammatory cytokines AFP and TNFα, 25-hydroxyvitamin D (25[OH]D) levels, apoptotic markers single-stranded DNA (ssDNA) and soluble Fas (sFas), and oxidative stress markers nitric oxide (NO) and total antioxidant capacity (TAC) were estimated by using molecular, immunoassay, and colorimetric techniques. RESULTS: Approximately 30% of the study population (n=30) were diagnosed as asymptomatic CHC carriers, and 70% of the study population (n=70) had severe fibrosis; these were classified into fibrosis and cirrhosis. There was a significant reduction in 25(OH)D levels and TAC activity, along with an increase in levels of NO, AFP, TNFα, ssDNA, and sFas in fibrosis and cirrhosis subjects compared with those of asymptomatic CHC carriers and health controls. The deficiency in 25(OH)D levels correlated positively with sFas, ssDNA, AFP, TNFα, NO, and TAC, and negatively with age, sex, liver function, body mass index, homeostatic model assessment - insulin resistance, HCV RNA, and viral load. Significant intercorrelation was reported between serum 25(OH)D concentrations and apoptotic and oxidative markers, which suggested progression of liver pathogenesis and fibrogenesis via oxidative and apoptotic mechanisms. CONCLUSION: The data showed that vitamin D status was significantly correlated with pathogenesis and fibrogenesis of the liver in geriatric patients infected with HCV genotype 4. The deficiency in 25(OH)D levels was shown to have a pivotal role in the pathogenesis of liver via apoptotic, oxidative stress, and inflammatory mechanistic pathways. The data point to adequate vitamin D levels being recommended for a good response to treatment strategies, especially in older CHC patients.

Oral administration of potassium bromate induces neurobehavioral changes, alters cerebral neurotransmitters level and impairs brain tissue of swiss mice.

BACKGROUND: Potassium bromate (KBrO3) is widely used as a food additive and is a major water disinfection by-product. The present study reports the side effects of KBrO3 administration on the brain functions and behaviour of albino mice. METHODS: Animals were divided into three groups: control, low dose KBrO3 (100 mg/kg/day) and high dose KBrO3 (200 mg/kg/day) groups. RESULTS: Administration of KBrO3 led to a significant change in the body weight in the animals of the high dose group in the first, second and the last weeks while water consumption was not significantly changed. Neurobehavioral changes and a reduced Neurotransmitters levels were observed in both KBrO3 groups of mice. Also, the brain level of reduced glutathione (GSH) in KBrO3 receiving animals was decreased. Histological studies favoured these biochemical results showing extensive damage in the histological sections of brain of KBrO3-treated animals. CONCLUSIONS: These results show that KBrO3 has serious damaging effects on the central nervous system and therefore, its use should be avoided.