The organic zinc with moderate chelation strength enhances the expression of related transporters in the jejunum and ileum of broilers.

Our previous study demonstrated that the zinc (Zn) proteinate with moderate chelation strength (Zn-Prot M) enhanced the Zn absorption in the small intestine partially via increasing the expression of some Zn and amino acid transporters in the duodenum of broilers. However, it remains unknown whether the Zn-Prot M could also regulate the expression of related transporters in the jejunum and ileum of broilers in the above enhancement of Zn absorption. The present study was conducted to investigate the effect of the Zn-Prot M on the expression of related transporters in the jejunum and ileum of broilers compared to the Zn sulfate (ZnS). Zinc-deficient broilers (13-d-old) were fed with the Zn-unsupplemented basal diets (control) or the basal diets supplemented with 60 mg Zn/kg as ZnS or Zn-Prot M for 26 d. The results showed that in the jejunum, compared to the control, supplementation of the organic or inorganic Zn increased (P < 0.05) mRNA and protein expression of b0,+-type amino acid transporter (rBAT), Zn transporter 10 (ZnT10), and peptide-transporter 1 (PepT1) mRNA expression and Zn transporter 7 (ZnT7) protein expression on d 28, while y+L-type amino transporter 2 (y+LAT2) mRNA and protein expression, and protein expression of ZnT7 and ZnT10 on 28 d and zrt-irt-like protein 3 (ZIP3) and zrt-irt-like protein 5 (ZIP5) on d 39 were higher (P < 0.05) for Zn-Prot M than for ZnS. In the ileum, Zn addition regardless of Zn source up-regulated (P < 0.05) mRNA expression of Zn transporter 9 (ZnT9) and ZIP3, ZIP5, and y+LAT2 protein expression on d 28, and PepT1 mRNA and protein expression, ZIP3 and y+LAT2 mRNA expression and ZnT10 protein expression on d 39. Furthermore, Zn transporter 4 (ZnT4) and ZnT9 mRNA expression and Zn transporter 1 (ZnT1) protein expression on d 28, and y+LAT2 mRNA expression and ZnT10 and PepT1 protein expression on d 39 were higher (P < 0.05) for Zn-Prot M than for ZnS. It was concluded that the Zn-Prot M enhanced the expression of the ZnT1, ZnT4, ZnT9, ZnT10, ZIP3, ZIP5, y+LAT2, and PepT1 in the jejunum or ileum of broilers compared to the ZnS.

Systematically evaluating DOTATATE and FDG as PET immuno-imaging tracers of cardiovascular inflammation.

In recent years, cardiovascular immuno-imaging by positron emission tomography (PET) has undergone tremendous progress in preclinical settings. Clinically, two approved PET tracers hold great potential for inflammation imaging in cardiovascular patients, namely FDG and DOTATATE. While the former is a widely applied metabolic tracer, DOTATATE is a relatively new PET tracer targeting the somatostatin receptor 2 (SST2). In the current study, we performed a detailed, head-to-head comparison of DOTATATE-based radiotracers and [18F]F-FDG in mouse and rabbit models of cardiovascular inflammation. For mouse experiments, we labeled DOTATATE with the long-lived isotope [64Cu]Cu to enable studying the tracer's mode of action by complementing in vivo PET/CT experiments with thorough ex vivo immunological analyses. For translational PET/MRI rabbit studies, we employed the more widely clinically used [68Ga]Ga-labeled DOTATATE, which was approved by the FDA in 2016. DOTATATE's pharmacokinetics and timed biodistribution were determined in control and atherosclerotic mice and rabbits by ex vivo gamma counting of blood and organs. Additionally, we performed in vivo PET/CT experiments in mice with atherosclerosis, mice subjected to myocardial infarction and control animals, using both [64Cu]Cu-DOTATATE and [18F]F-FDG. To evaluate differences in the tracers' cellular specificity, we performed ensuing ex vivo flow cytometry and gamma counting. In mice subjected to myocardial infarction, in vivo [64Cu]Cu-DOTATATE PET showed higher differential uptake between infarcted (SUVmax 1.3, IQR, 1.2-1.4, N = 4) and remote myocardium (SUVmax 0.7, IQR, 0.5-0.8, N = 4, p = 0.0286), and with respect to controls (SUVmax 0.6, IQR, 0.5-0.7, N = 4, p = 0.0286), than [18F]F-FDG PET. In atherosclerotic mice, [64Cu]Cu-DOTATATE PET aortic signal, but not [18F]F-FDG PET, was higher compared to controls (SUVmax 1.1, IQR, 0.9-1.3 and 0.5, IQR, 0.5-0.6, respectively, N = 4, p = 0.0286). In both models, [64Cu]Cu-DOTATATE demonstrated preferential accumulation in macrophages with respect to other myeloid cells, while [18F]F-FDG was taken up by macrophages and other leukocytes. In a translational PET/MRI study in atherosclerotic rabbits, we then compared [68Ga]Ga-DOTATATE and [18F]F-FDG for the assessment of aortic inflammation, combined with ex vivo radiometric assays and near-infrared imaging of macrophage burden. Rabbit experiments showed significantly higher aortic accumulation of both [68Ga]Ga-DOTATATE and [18F]F-FDG in atherosclerotic (SUVmax 0.415, IQR, 0.338-0.499, N = 32 and 0.446, IQR, 0.387-0.536, N = 27, respectively) compared to control animals (SUVmax 0.253, IQR, 0.197-0.285, p = 0.0002, N = 10 and 0.349, IQR, 0.299-0.423, p = 0.0159, N = 11, respectively). In conclusion, we present a detailed, head-to-head comparison of the novel SST2-specific tracer DOTATATE and the validated metabolic tracer [18F]F-FDG for the evaluation of inflammation in small animal models of cardiovascular disease. Our results support further investigations on the use of DOTATATE to assess cardiovascular inflammation as a complementary readout to the widely used [18F]F-FDG.

THE PECULIARITIES OF MORPOLOGICAL CHANGES OF RATS' OVARY AND BIOCHEMICAL STATE UNDER THE DAMAGE WITH DIFFERENT DOSES OF LEAD ACETATE.

OBJECTIVE: The aim of the study was to study the effect of low and high doses of lead acetate on biochemical parameters and morphological status of rat ovaries in the experiment. PATIENTS AND METHODS: Materials and methods: The study was performed on 36 nonlinear female rats weighing 180-210 g, aged 4 months, divided into 3 experimental groups: I - control (C), II - rats, which were given 30 days to drink a solution of lead acetate with at the rate of 0,05 mg / kg of animal weight, group III - rats, which were given for 30 days to drink a solution of lead acetate at the rate of 60 mg/kg of animal weight. Biochemical research methods were included determination of diene conjugate concentration in animals' blood, concentration of TBA-active products, study of oxidative modification of proteins in blood plasma, determination of superoxide dismutase and catalase activities. Endogenous intoxication was assessed by the definition of medium-mass molecules, the content was expressed in units of extinction. The material for light microscopy investigation from the ovary was performed according to the generally accepted method. RESULTS: Results: Lead acetate causes activation of peroxidation of lipids and proteins in the body of female rats, which is directly dependent on the dose of lead. In response to the activation of free radical oxidation there are changes in the antioxidant system, which depend on the dose of lead acetate: at a dose of 0.05 mg / kg superoxide dismutase and catalase activity increase, at a dose of 60 mg / kg superoxide dismutase and catalase activity. Small doses of lead do not cause endogenous intoxication. Lead acetate causes the development of endogenous intoxication in animals only in large doses: increases the formation of toxic compounds, cell apoptosis, decreased excretory function of the kidneys, which is associated with multiorgan disorders. As a result of the action of lead acetate, morphological changes of the ovaries were observed, which increased with increasing dose of lead acetate. There was a dose-dependent decrease in massometric parameters, the number of follicles and changes in the thickness of the surface structures of the ovary, which is more pronounced at 60 mg/kg. CONCLUSION: Conclusions: Under the influence of small and large doses of lead acetate on biochemical changes in blood and morphological changes in the ovaries in male rats the oxidative stress is developed. Under the influence of small doses, the changes are adaptive, and under the influence of large doses - damaging.

Evaluation of the compounds commonly known as superoxide dismutase and catalase mimics in cellular models.

Oxidative stress that results from an imbalance between the concentrations of reactive species (RS) and antioxidant defenses is associated with many pathologies. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase are among the key enzymes that maintain the low nanomolar physiological concentrations of superoxide and hydrogen peroxide. The increase in the levels of these species and their progeny could have deleterious effects. In this context, chemists have developed SOD and CAT mimics to supplement them when cells are overwhelmed with oxidative stress. However, the beneficial activity of such molecules in cells depends not only on their intrinsic catalytic activities but also on their stability in biological context, their cell penetration and their cellular localization. We have employed cellular assays to characterize several compounds that possess SOD and CAT activities and have been frequently used in cellular and animal models. We used cellular assays that address SOD and CAT activities of the compounds. Finally, we determined the effect of compounds on the suppression of the inflammation in HT29-MD2 cells challenged by lipopolysaccharide. When the assay requires penetration inside cells, the SOD mimics Mn(III) meso-tetrakis(N-(2'-n-butoxyethyl)pyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP5+) and Mn(II) dichloro[(4aR,13aR,17aR,21aR)-1,2,3,4,4a,5,6,12,13,13a,14,15,16,17,17a,18,19,20,21,21a-eicosahydro-11,7-nitrilo-7Hdibenzo[b,h] [1,4, 7,10] tetraazacycloheptadecine-κN5,κN13,κN18,κN21,κN22] (Imisopasem manganese, M40403, CG4419) were found efficacious at 10 µM, while Mn(II) chloro N-(phenolato)-N,N'-bis[2-(N-methyl-imidazolyl)methyl]-ethane-1,2-diamine (Mn1) requires an incubation at 100 µM. This study thus demonstrates that MnTnBuOE-2-PyP5+, M40403 and Mn1 were efficacious in suppressing inflammatory response in HT29-MD2 cells and such action appears to be related to their ability to enter the cells and modulate reactive oxygen species (ROS) levels.

Cytoplasmic aggregation of uranium in human dopaminergic cells after continuous exposure to soluble uranyl at non-cytotoxic concentrations.

Uranium exposure can lead to neurobehavioral alterations in particular of the monoaminergic system, even at non-cytotoxic concentrations. However, the mechanisms of uranium neurotoxicity after non-cytotoxic exposure are still poorly understood. In particular, imaging uranium in neurons at low intracellular concentration is still very challenging. We investigated uranium intracellular localization by means of synchrotron X-ray fluorescence imaging with high spatial resolution (< 300 nm) and high analytical sensitivity (< 1 µg.g-1 per 300 nm pixel). Neuron-like SH-SY5Y human cells differentiated into a dopaminergic phenotype were continuously exposed, for seven days, to a non-cytotoxic concentration (10 µM) of soluble natural uranyl. Cytoplasmic submicron uranium aggregates were observed accounting on average for 62 % of the intracellular uranium content. In some aggregates, uranium and iron were co-localized suggesting common metabolic pathways between uranium and iron storage. Uranium aggregates contained no calcium or phosphorous indicating that detoxification mechanisms in neuron-like cells are different from those described in bone or kidney cells. Uranium intracellular distribution was compared to fluorescently labeled organelles (lysosomes, early and late endosomes) and to fetuin-A, a high affinity uranium-binding protein. A strict correlation could not be evidenced between uranium and the labeled organelles, or with vesicles containing fetuin-A. Our results indicate a new mechanism of uranium cytoplasmic aggregation after non-cytotoxic uranyl exposure that could be involved in neuronal defense through uranium sequestration into less reactive species. The remaining soluble fraction of uranium would be responsible for protein binding and for the resulting neurotoxic effects.

Sorafenib-Conjugated Zinc Phthalocyanine Based Nanocapsule for Trimodal Therapy in an Orthotopic Hepatocellular Carcinoma Xenograft Mouse Model.

Sorafenib, a multitargeted kinase inhibitor, has been reported to elicit a limited therapeutic effect in hepatocellular carcinoma (HCC). Currently, phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is emerging as a powerful modality for cancer therapy. However, few studies have been reported the effectiveness of the combination of sorafenib with PDT and PTT in HCC. Herein, we designed and synthesized bovine serum albumin (BSA)-coated zinc phthalocyanine (ZnPc) and sorafenib (SFB) nanoparticle (ZnPc/SFB@BSA). The obtained ZnPc/SFB@BSA was able to trigger PDT, PTT, and chemotherapy. After irradiation by a 730 nm light, ZnPc/SFB@BSA significantly suppressed HCC cell proliferation and metastasis while promoted cell apoptosis in vitro. Furthermore, intravenous injection of ZnPc/SFB@BSA led to dramatically reduced tumor growth in an orthotopic xenograft HCC model. More importantly, ZnPc/SFB@BSA presented low toxicity and adequate blood compatibility. Therefore, a combination of ZnPc with sorafenib via BSA-assembled nanoparticle can markedly suppress HCC growth, representing a promising strategy for HCC patients.

Ameliorative effect of curcumin on lead-induced hematological and hepatorenal toxicity in a rat model.

INTRODUCTION: Lead (Pb) is a ubiquitous toxic heavy metal that inflicts numerous clinical consequences on humans. Curcumin is the principal component of turmeric, which is reported to have antioxidative properties. This study aimed at evaluating the ameliorative effects of curcumin on Pb-induced hepatorenal toxicity in a rat model. METHODS: Thirty-six male Sprague-Dawley rats were randomly assigned into five groups with 12 rats in the control (normal saline) and six rats each for the lead-treated group (LTG) (50 mg/kg lead acetate [Pb acetate] for 4 weeks), recovery group (50 mg/kg Pb acetate for 4 weeks and left with no treatment for another 4 weeks), treatment group 1 (Cur100) (50 mg/kg Pb acetate for 4 weeks, followed by 100 mg/kg curcumin for 4 weeks), and treatment group 2 (Cur200) (50 mg/kg Pb acetate for 4 weeks, followed by 200 mg/kg curcumin for 4 weeks). All the experimental groups received oral treatments via orogastric-tube on alternate days. Pb concentration in the liver and kidney of the rats were evaluated using inductive-coupled plasma mass spectrometry techniques. RESULTS: Pb-administered rats revealed significant alteration in oxidative status and increased Pb concentration in their liver and kidney with obvious reduction of hemogram and increased in leukogram as well as aberration in histological architecture of the liver and kidney. However, treatment with curcumin reduces the tissue Pb concentrations and ameliorates the above mention alterations. CONCLUSIONS: The results in this study suggested that curcumin attenuates Pb-induced hepatorenal toxicity via chelating activity and inhibition of oxidative stress.

Multi-spectroscopic and computational evaluation on the binding of sinapic acid and its Cu(II) complex with bovine serum albumin.

Researches based on metal complexes of plant-derived phenolic acids have attracted much attention due to their beneficial applications in the development of functional food products, dietary supplements and pharmacology. Binding of phenolic acids with serum proteins greatly influences their pharmacological properties. In this context, interactions of a naturally occurring phenolic acid, sinapic acid (SA) and its Cu2+ complex with a model transport protein, bovine serum albumin (BSA), have been explored by means of different spectroscopic and theoretical tools. Spectroscopic studies revealed that the interaction of SA and its Cu2+ complex with BSA occurred through quenching of intrinsic fluorescence of BSA. Site-specific experimental and docking studies were performed to predict the binding site. The geometies of bound Cu2+ and interacting residues of protein were predicted from a solution dynamics study. Interestingly, the complexation of SA with Cu2+ enhanced the antioxidant activity of SA.

Effects of zinc methionine supplementation on laying performance, zinc status, intestinal morphology, and expressions of zinc transporters' mRNA in laying hens.

BACKGROUND: This study was conducted to investigate effects of dietary zinc methionine (Zn-Met) supplementation on laying performance, zinc (Zn) status, intestinal morphology, and Zn transporters in laying hens compared with zinc sulfate (ZnSO4 ). A total of 384 Hyline Grey laying hens (38 weeks old) with similar performance (1.42 ± 0.07 kg) were randomly allotted to four dietary treatments and fed with a basal diet (control) or the basal diet supplemented with Zn, either as Zn-Met at 40 and 80 mg Zn/kilogram diet or as ZnSO4 at 80 mg Zn/kilogram diet, for 10 weeks. RESULTS: There was no difference in egg weight, egg production, feed intake, and feed conversation ratio among all groups (P > 0.05). Compared with the control, Zn contents were increased (P < 0.05) in the liver, duodenum, and jejunum of laying hens fed diets supplemented with different Zn sources. There was no difference (P > 0.05) in Zn contents in liver, duodenum, and jejunum between diets supplemented with Zn-Met or ZnSO4 at 80 mg Zn/kilogram diet. Compared with the control and the ZnSO4 group (80 mg Zn/kilogram diet), supplementation with Zn-Met of 80 mg Zn/kilogram diet increased (P < 0.05) villus height, villus area, and villus height/crypt depth ratio but reduced (P < 0.05) crypt depth in jejunum. Expression of metallothionein messenger RNA of jejunum in the group fed a diet containing Zn-Met (80 mg Zn/kilogram diet) was higher (P < 0.05) than that in the control. CONCLUSION: These results indicated that Zn-Met has positive effects on the Zn status of liver, duodenum, and jejunum, intestinal morphology, and metallothionein messenger RNA expression in jejunum of laying hens compared with ZnSO4 . © 2019 Society of Chemical Industry.

Chirality-Selected Chemical Modulation of Amyloid Aggregation.

Due to the composed α-helical/ß-strand structures, ß-amyloid peptide (Aß) is sensitive to chiral environments. The orientation and chirality of the Aß strand strongly influence its aggregation. Aß-formed fibrils have a cascade of chirality. Therefore, for selectively targeting amyloid aggregates, chirality preference can be one key issue. Inspired by the natural stereoselectivity and the ß-sheet structure, herein, we synthesized a series of d- and l-amino acid-modified polyoxometalate (POM) derivatives, including positively charged amino acids (d-His and l-His) and negatively charged (d-Glu and l-Glu) and hydrophobic amino acids (d-Leu, l-Leu, d-Phe, and l-Phe), to modulate Aß aggregation. Intriguingly, Phe-modified POMs showed a stronger inhibition effect than other amino acid-modified POMs, as evidenced by multiple biophysical and spectral assays, including fluorescence, circular dichroism, NMR, molecular dynamic simulations, and isothermal titration calorimetry. More importantly, d-Phe-modified POM had an 8-fold stronger inhibition effect than l-Phe-modified POM, indicating high enantioselectivity. Furthermore, in vivo studies demonstrated that the chiral POM derivatives crossed the blood-brain barrier, extended the life span of AD transgenic Caenorhabditis elegans CL2006 strain, and had low cytotoxicity, even at a high dosage.

Zn-DTSM, A Zinc Ionophore with Therapeutic Potential for Acrodermatitis Enteropathica?

Acrodermatitis enteropathica (AE) is a rare disease characterised by a failure in intestinal zinc absorption, which results in a host of symptoms that can ultimately lead to death if left untreated. Current clinical treatment involves life-long high-dose zinc supplements, which can introduce complications for overall nutrient balance in the body. Previous studies have therefore explored the pharmacological treatment of AE utilising metal ionophore/transport compounds in an animal model of the disease (conditional knockout (KO) of the zinc transporter, Zip4), with the perspective of finding an alternative to zinc supplementation. In this study we have assessed the utility of a different class of zinc ionophore compound (zinc diethyl bis(N4-methylthiosemicarbazone), Zn-DTSM; Collaborative Medicinal Development, Sausalito, CA, USA) to the one we have previously described (clioquinol), to determine whether it is effective at preventing the stereotypical weight loss present in the animal model of disease. We first utilised an in vitro assay to assess the ionophore capacity of the compound, and then assessed the effect of the compound in three in vivo animal studies (in 1.5-month-old mice at 30 mg/kg/day, and in 5-month old mice at 3 mg/kg/day and 30 mg/kg/day). Our data demonstrate that Zn-DTSM has a pronounced effect on preventing weight loss when administered daily at 30 mg/kg/day; this was apparent in the absence of any added exogenous zinc. This compound had little overall effect on zinc content in various tissues that were assessed, although further characterisation is required to more fully explore the cellular changes underlying the physiological benefit of this compound. These data suggest that Zn-DTSM, or similar compounds, should be further explored as potential therapeutic options for the long-term treatment of AE.

Effects of organic zinc on tibia quality, mineral deposit, and metallothionein expression level of aged hens.

The study aimed to determine the effects of methionine hydroxy analog chelate zinc on the tibia quality, mineral deposit, apparent retention of nutrients, and liver metallothionein (MT) expression level of aged laying hens. A total of 960 layers (Hy-Line Grey, 57 wk old) were randomly assigned into 4 groups, and each group had 8 replicates of 30 hens. During the first 2 wk, groups were fed a basal diet without extra zinc (Zn: 35.08 mg/kg). During the ensuing 14 wk, 4 levels of Zn (inorganic Zn: 80 mg/kg; organic Zn: 20, 40, 80 mg/kg) were added to the diet. The results indicated that both the Zn source and level did influence tibia strength and calcium (Ca) and Zn concentrations of tibia (P < 0.05), whereas there were no differences in the copper (Cu) and phosphorus (P) concentrations of the tibia and the tibia length (P > 0.05). Moreover, dietary supplementation with 40 or 80 mg/kg of organic Zn showed higher Zn and Ca concentrations in the tibia and higher tibia strength. The Cu concentration in the liver showed no difference among the 4 treatments, whereas the Zn concentration in the liver increased with the increasing Zn level. The apparent retention of P, iron (Fe), and manganese (Mn) was not affected by the Zn level or source (P > 0.05). However, the organic Zn group increased the apparent retention of Cu, Zn, Ca, crude protein (CP), and energy, and the group supplemented with 40 or 80 mg/kg of organic Zn obtained significant effects (P < 0.05). Moreover, dietary supplementation with 40 or 80 mg/kg organic Zn increased the MT mRNA expression of the liver at week 72, whereas 20 mg/kg of organic Zn decreased it (P < 0.05). In conclusion, this study suggested that an optimum dietary (40 mg/kg) organic Zn level plays a key role in promoting the apparent retention of minerals and nutrients, trace element deposit, and MT mRNA expression.

Effects of dietary Zn-methionine supplementation on the laying performance, egg quality, antioxidant capacity, and serum parameters of laying hens.

This study was to determine the effects of dietary Zn-methionine (Zn-Met) supplementation on the laying performance, egg quality, antioxidant capacity, and serum parameters of laying hens. Jingh ong-1 strain laying hens (n = 720, 49 wk of age) were randomly assigned to 6 treatments with 6 replications of 20 birds. The control was fed a basal diet supplemented with 80 mg of Zn/kg as Zn sulphate of diet and the 5 groups were fed a basal diet supplemented with 20, 40, 60, 80, and 100 mg of Zn/kg as Zn-Met of diet for 10 wk, respectively. At the terminal experiment, there were significant differences between control and 80 mg/kg Zn-Met group in feed intake (P < 0.05) and feed conversion ratio (FCR) (P < 0.01). Egg weight (P < 0.05) and albumen height (P < 0.01) reduced and were not significantly influenced by supplemental 80 mg/kg Zn-Met group until being stored 15 d as compared to the control. Zn-Met group in 100 mg/kg significantly increased haugh unit (P < 0.05) as compared to the control. The activity of MDA in serum had a linear decrease in 20 to 100 mg/kg Zn-Met. The activity of CAT in liver and GSH-Px in serum had quadratic effects in response to the Zn-Met treatments. Compared to the control, 60 mg/kg Zn-Met group increased the T-AOC, GSH-Px activity in serum (P < 0.01), and the T-AOC (P < 0.05), CuZnSOD (P < 0.01), GSH-Px (P < 0.01) activity in liver. Compared with the control, the concentration of serum ionic Ca in 80, 100 mg/kg Zn-Met treatments reduced (P < 0.01) significantly while the activity of serum alkaline phosphatase (AKP) increased in the Zn-Met groups of 40, 60, and 80 mg/kg (P < 0.01), and 100 mg/kg (P < 0.05). In conclusion, dietary Zn-Met supplementation at 60 to 80 mg/kg had more positive effects on performance, egg quality, and antioxidant capacity in laying hens as compared to 80 mg/kg ZnSO4.

Effects of Dietary Organic, Inorganic, and Nanoparticulate Zinc on Rainbow Trout, Oncorhynchus mykiss Larvae.

The present study was conducted to investigate the effects of different dietary zinc sources on growth performance, survival, and body composition of larval rainbow trout, Oncorhynchus mykiss. A total of 3240 larvae with an average weight of 82.3 ± 11.6 mg were randomly divided into four groups by three replicates and were fed for 70 days. Organic zinc (Zn-proteinate, Bioplex Zn®), mineral zinc (ZnSO4), and nanoparticulate zinc (ZnO-NPs) were each added to the basal diet at 50-mg/kg diet. In all of the zinc-supplemented groups, final body weight (FBW) and weight gain (WG) increased significantly (P < 0.05) compared to the control at the termination of the feeding trial. There was no significant difference in specific growth rate (SGR) in experimental groups. Fish fed with mineral and nanoparticulate zinc, respectively, demonstrated the highest and lowest survival rates (P < 0.05) as compared to other experimental diets. Feed conversion ratio (FCR) significantly decreased (P < 0.05) in groups fed with organic and mineral zinc. There were no significant differences in protein, lipid, moisture, and ash content among fish fed the experimental diets. Fish fed mineral zinc showed the highest (P < 0.05) zinc content in the whole body than the other groups. The data of the present study confirm positive effects of the use of 50 mg kg-1 of zinc sources in early diet to enhance growth performance of rainbow trout larvae.

DNA binding, prominent photonuclease activity and antibacterial PDT of cobalt(II) complexes of phenanthroline based photosensitizers.

The chemistry of Co(II) complexes showing efficient light induced DNA cleavage activity, binding propensity to calf thymus DNA and antibacterial PDT is summarized in this article. Complexes of formulation [Co(mqt)(B)2]ClO4 1-3 where mqt is 4-methylquinoline-2-thiol and B is N,N-donor heterocyclic base, viz. 1,10-phenanthroline (phen 1), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq 2) and dipyrido[3,2-a:2',3'-c]phenazine (dppz 3) have been prepared and characterized. The DNA-binding behaviors of these three complexes were explored by absorption spectra, viscosity measurements and thermal denaturation studies. The DNA binding constants for complexes 1, 2 and 3 were determined to be 1.6 × 103 M-1, 1.1 × 104 M-1 and 6.4 × 104 M-1 respectively. The experimental results suggest that these complexes interact with DNA through groove binding mode. The complexes show significant photocleavage of supercoiled (SC) DNA proceeds via a type-II process forming singlet oxygen as the reactive species. Antimicrobial photodynamic therapy was studied using photodynamic antimicrobial chemotherapy (PACT) assay against E. coli and all complexes exhibited significant reduction in bacterial growth on photoirradiation.

Characterization of Thermally Activated Metalloenediyne Cytotoxicity in Human Melanoma Cells.

Enediynes are a highly cytotoxic class of compounds. However, metallation of these compounds may modulate their activation, and thus their cytotoxicity. We previously demonstrated that cytotoxicity of two different metalloenediynes, including (Z)-N,N'-bis[1-pyridyl-2-yl-meth-(E)-ylidene]octa-4-ene-2,6-diyne-1,8-diamine] (PyED), is potentiated when the compounds are administered to HeLa cells during hyperthermia treatment at concentrations that are minimally or not cytotoxic at 37°C. In this study, we further characterized the concentration, time and temperature dependence of cytotoxicity of PyED on human U-1 melanoma cells. We also investigated the potential mechanisms by which PyED cytotoxicity is enhanced during hyperthermia treatment. Cell killing with PyED was dependent on concentration, temperature during treatment and time of exposure. Potentiation of cytotoxicity was observed when cells were treated with PyED at temperatures ≥39.5°C, and enhancement of cell killing increased with temperature and with increasing time at a given temperature. All cells treated with PyED were shown to have DNA damage, but substantially more damage was observed in cells treated with PyED during heating. DNA repair was also inhibited in cells treated with the drug during hyperthermia. Thus, potentiation of PyED cytotoxicity by hyperthermia may be due to enhancement of drug-induced DNA lesions, and/or the inhibition of repair of sublethal DNA damage. While the selective thermal activation of PyED supports the potential clinical utility of metalloenediynes as cancer thermochemotherapeutic agents, therapeutic gain could be optimized by identifying compounds that produce minimal toxicity at 37°C but which become activated and show enhancement of cytotoxicity within a tumor subjected to localized hyperthermic or thermal ablative treatment, or which might act as bifunctional agents. We thus also describe the development and initial characterization of a novel cofactor complex of PyED, platinated PyED (Pt-PyED). Pt-PyED binds to DNA-like cisplatin, and much like PyED, cytotoxicity is greatly enhanced after treatment with the drug at elevated temperatures. However, in contrast to PyED, Pt-PyED is only minimally cytotoxic at 37°C, at concentrations at which cytotoxicity is enhanced by hyperthermia. Further development of cisplatin-based enediynes may result in compounds which, when activated, will possess multiple DNA binding modalities similar to cisplatin, but produce less side effects in tissues at normothermic temperatures.

Effect of dietary supplementation of organic zinc on laying performance, egg quality and some biochemical parameters of laying hens.

This study was conducted to evaluate the effects of zinc methionine (Zn-Met) supplementation on the performance, egg quality, antioxidant status and some biochemical parameters of blood serum in laying hens from 22 to 34 weeks of age. A total of 120 Hisex Brown laying hens of 22-week-old were randomly allocated into five treatments with six cage replicates for each (four hens/replicate). Dietary treatments consisted of the basal diet with no Zn-Met supplementation (control group) and basal diet supplemented with 25, 50, 75 or 100 mg Zn-Met/kg diet. No significant differences were observed on body weight, body weight gain or feed conversion ratio due to dietary Zn-Met supplementation. However, highly significant impact was observed on daily feed intake. Egg number, egg weight and egg mass were increased in the group fed diet supplemented with the highest level of Zn-Met (100 mg/kg of diet) as compared to other groups. All egg quality traits were statistically (p > .05 or .01) affected as a response to dietary Zn-Met supplementation except egg shape index, shell percentage and yolk index. In comparison with the control group, dietary supplementation of 25, 50, 75 or 100 mg Zn-Met/kg decreased serum triglyceride and LDL-cholesterol levels. Serum cholesterol level was increased with all dietary levels of Zn-Met in comparison with the control group. Dietary Zn-Met supplementation increased the serum content of zinc, where the highest values were recorded with 50 and 100 mg Zn-Met/kg diet. Dietary Zn-Met levels did not affect the antioxidant indices in blood serum except for the activity of copper-zinc superoxide dismutase (Cu-Zn-SOD). The activity of Cu-Zn-SOD was increased with Zn-Met supplementations with no differences among supplemental zinc levels. It is concluded that dietary Zn-Met supplementation reduced serum triglyceride, LDL-cholesterol and increased Zn status and resulted in promoting antioxidant ability of laying hens, and the addition of 100 mg Zn-Met/kg to layer diet was appropriate for improving the above parameters in addition to egg production indices and Haugh unit score.

Effects of dietary Mn-methionine supplementation on the egg quality of laying hens.

This study was conducted to investigate the effects of dietary manganese-methionine (Mn-Met) supplementation on the egg quality of laying hens. A total of 480 Jinghong-1 strain layers aged 53 wk were divided into 5 groups with 6 replicates of 16 layers. Birds in the control group were fed a diet supplemented with 60 mg Mn/kg in the form of MnSO4; the birds in other 4 experimental groups were fed a diet supplemented with 20, 40, 60, and 80 mg Mn/kg as Mn-Met, respectively. Dietary Mn-Met treatments significantly affected (P < 0.05) the albumen height, yolk color, and Haugh unit compared to those of the control diet. The Mn contents in the eggshell increased (P < 0.01) significantly by increasing the Mn-Met supplementation, whereas Mn content in eggshell was triple that in the yolk or albumen. Compared with the 60 mg/kg Mn-Met group, the transverse surface in the control group had (P < 0.01) a greater width of mammillary cones, and there were obvious cracks on the outer surface in the control. There was no difference (P > 0.05) in the eggshell gland (ESG) in the expression of calbindin-D28k (CaBP-D28k) mRNA in response to any diet treatment. In conclusion, dietary Mn-Met supplementation increased internal egg quality and the ultrastructure of the eggshell. Compared to the control, 60 mg/kg Mn-Met treatment resulted in improving egg quality, and 20 mg/kg Mn-Met treatment had similar effects the control treatment had on the egg quality. This indicates that the inorganic Mn can be replaced by the lower concentration of Mn-Met.

Oolong tea extract as a substitute for uranyl acetate in staining of ultrathin sections based on examples of animal tissues for transmission electron microscopy.

Oolong tea extract (OTE) was assessed for its potential as an electron stain to substitute for uranyl acetate (UA) in transmission electron microscopy (TEM). A comparative analysis of the ultrastructures of biological specimens (i.e. compound eye and sciatic nerve tissue) stained by different methods (UA and 0.1% OTE) has been performed. Results revealed that there was no significant difference between the OTE double staining method and the traditional double staining method, except the contrast in the OTE method was slightly lower than the UA method. Nevertheless, the OTE method yielded better or equal details in collagen fibres, neurofilaments and basal lamina in the mammalian sciatic nerve samples, as well as in the microvilli between the cornea and crystalline cone of the insect compound eye. On the whole, it was suggested that OTE could potentially be used as a nonradioactive and hazard-free alternative to UA in TEM staining.

Antimicrobial activity of biogenically produced spherical Se-nanomaterials embedded in organic material against Pseudomonas aeruginosa and Staphylococcus aureus strains on hydroxyapatite-coated surfaces.

In an effort to prevent the formation of pathogenic biofilms on hydroxyapatite (HA)-based clinical devices and surfaces, we present a study evaluating the antimicrobial efficacy of Spherical biogenic Se-Nanostructures Embedded in Organic material (Bio Se-NEMO-S) produced by Bacillus mycoides SelTE01 in comparison with two different chemical selenium nanoparticle (SeNP) classes. These nanomaterials have been studied as potential antimicrobials for eradication of established HA-grown biofilms, for preventing biofilm formation on HA-coated surfaces and for inhibition of planktonic cell growth of Pseudomonas aeruginosa NCTC 12934 and Staphylococcus aureus ATCC 25923. Bio Se-NEMO resulted more efficacious than those chemically produced in all tested scenarios. Bio Se-NEMO produced by B. mycoides SelTE01 after 6 or 24 h of Na2 SeO3 exposure show the same effective antibiofilm activity towards both P. aeruginosa and S. aureus strains at 0.078 mg ml-1 (Bio Se-NEMO6 ) and 0.3125 mg ml-1 (Bio Se-NEMO24 ). Meanwhile, chemically synthesized SeNPs at the highest tested concentration (2.5 mg ml-1 ) have moderate antimicrobial activity. The confocal laser scanning micrographs demonstrate that the majority of the P. aeruginosa and S. aureus cells exposed to biogenic SeNPs within the biofilm are killed or eradicated. Bio Se-NEMO therefore displayed good antimicrobial activity towards HA-grown biofilms and planktonic cells, becoming possible candidates as new antimicrobials.