PEGylated silver doped zinc oxide nanoparticles as novel photosensitizers for photodynamic therapy against Leishmania

We describe daylight responsive silver (Ag) doped semiconductor nanoparticles of zinc oxide (DSNs) for photodynamic therapy (PDT) against Leishmania. The developed materials were characterized by X-ray diffraction analysis (XRD), Rutherford backscattering (RBS), diffused reflectance spectroscopy (DRS), and band-gap analysis. The Ag doped semiconductor nanoparticles of zinc oxide were PEGylated to enhance their biocompatibility. The DSNs demonstrated effective daylight response in the PDT of Leishmania protozoans, through the generation of reactive oxygen species (ROS) with a quantum yield of 0.13 by nondoped zinc oxide nanoparticles (NDSN) whereas 0.28 by DSNs. None of the nanoparticles have shown any antileishmanial activity in dark, confirming that only ROS produced in the daylight were involved in the killing of leishmanial cells. Furthermore, the synthesized nanoparticles were found biocompatible. Using reactive oxygen species scavengers, cell death was attributable mainly to 77–83% singlet oxygen and 18–27% hydroxyl radical. The nanoparticles caused permeability of the cell membrane, leading to the death of parasites. Further, the uptake of nanoparticles by Leishmania cells was confirmed by inductively coupled plasma atomic emission spectroscopy (ICP-AES). We believe that these DSNs are widely applicable for the PDT of leishmaniasis, cancers, and other infections due to daylight response.     

The beneficial effects of rosuvastatin are independent of zinc supplementation in patients with atherosclerosis

BackgroundStatins have multiple antiatherosclerotic effects, but can reduce blood plasma concentrations of minerals, including zinc. As zinc possesses antiinflammatory and antioxidant effects, low zinc status can promote injuries or inadequate tissue repair in endothelial cells. Metallothionein (MT) expression might modulate responses induced by statins in patients with atherosclerosis. However, research regarding mineral status and the use of statins is scarce. This study evaluated the effects of zinc supplementation on zinc status and expression of the zinc-dependent MT1F and MT2A genes in patients with atherosclerosis treated with rosuvastatin.MethodsA double-blind, randomized clinical trial was performed with 54 participants treated with 10 mg rosuvastatin for 4 months with or without zinc supplementation (30 mg/day). Diet, lipid profile, high-sensitivity reactive protein C (hs-CRP), plasma and erythrocyte zinc concentrations, erythrocyte superoxide dismutase (SOD) activity, and MT1F and MT2A genes expression were analyzed before and after intervention.ResultsRosuvastatin therapy was effective in reducing low- and non-high-density lipoprotein, total cholesterol, triglycerides, and hs-CRP levels, independent of zinc supplementation. Additionally, zinc treatment had no effect on SOD enzyme activity (P = 0.201), plasma (P > 0.671) and erythrocyte (P > 0.123) zinc concentrations, or the pattern of MT1F and MT2A genes expression (P = 0.088 and P = 0.229, respectively).ConclusionsThe effectiveness of rosuvastatin treatment is independent of the effects of zinc supplementation. Moreover, rosuvastatin treatment did not have a significant impact on zinc status or MT1F and MT2A genes expression in patients with atherosclerosis.     

Zinc transporter gene expression and glycemic control in post-menopausal women with Type 2 diabetes mellitus

Type 2 diabetes mellitus (DM) is associated often with underlying zinc deficiency and nutritional supplements such as zinc may be of therapeutic benefit in the disease. In a randomized, double-blind, placebo-controlled, 12-week trial in postmenopausal women (n = 48) with Type 2 DM we investigated the effects of supplementation with zinc (40 mg/d) and flaxseed oil (FSO; 2 g/d) on the gene expression of zinc transporters (ZnT1, ZnT5, ZnT6, ZnT7, ZnT8, Zip1, Zip3, Zip7, and Zip10) and metallothionein (MT-1A, and MT-2A), and markers of glycemic control (glucose, insulin, glycosylated hemoglobin [HbA1c]). The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. No significant effects of zinc or FSO supplementation were observed on glycemic marker concentrations, HOMA-IR or fold change over 12 weeks in zinc transporter and metallothionein gene expression. In multivariate analysis, the change over 12 weeks in serum glucose concentrations (P = 0.001) and HOMA-IR (P = 0.001) predicted the fold change in Zip10. In secondary analysis, marginal statistical significance was observed with the change in both serum glucose concentrations (P = 0.003) and HOMA-IR (P = 0.007) being predictive of the fold change in ZnT6. ZnT8 mRNA expression was variable; HbA1c levels were higher (P = 0.006) in participants who exhibited ZnT8 expression compared to those who did not. The significant predictive relationships between Zip10, ZnT6, serum glucose and HOMA-IR are preliminary, as is the relationship between HbA1c and ZnT8; nevertheless the observations support an association between Type 2 DM and zinc homeostasis that requires further exploration.     

Activation of group II metabotropic glutamate receptors blocks zinc release from hippocampal mossy fibers

Background

The hippocampal CA3 area contains large amounts of vesicular zinc in the mossy fiber terminals which is released during synaptic activity, depending on presynaptic calcium. Another characteristic of these synapses is the presynaptic localization of high concentrations of group II metabotropic glutamate receptors, specifically activated by DCG-IV. Previous work has shown that DCG-IV affects only mossy fiber-evoked responses but not the signals from associational-commissural afferents, blocking mossy fiber synaptic transmission. Since zinc is released from mossy fibers even for single stimuli and it is generally assumed to be co-released with glutamate, the aim of the work was to investigate the effect of DCG-IV on mossy fiber zinc signals.

Results

Studies were performed using the membrane-permeant fluorescent zinc probe TSQ, and indicate that DCG-IV almost completely abolishes mossy fiber zinc changes as it does with synaptic transmission.

Conclusions

Zinc signaling is regulated by the activation of type II metabotropic receptors, as it has been previously shown for glutamate, further supporting the corelease of glutamate and zinc from mossy fibers.     

酪酸梭菌活菌散联合葡萄糖酸锌治疗儿童急性腹泻的疗效观察

目的探讨酪酸梭菌活菌散联合葡萄糖酸锌治疗儿童急性腹泻的疗效。方法选取急性腹泻患儿76例,随机分为观察组和对照组各38例。两组患儿均予以调整饮食、口服或静脉补液和纠正水电解质酸碱失衡紊乱等常规治疗。观察组患儿予以酪酸梭菌活菌散和葡萄糖酸锌联合治疗,对照组患儿予以单纯酪酸梭菌活菌散治疗。观察两组患儿治疗后主要症状和体征改善的时间,并比较其临床疗效及治疗后3个月内腹泻的复发率。结果观察组患儿治疗后的止泻、呕吐、腹痛和粪常规等恢复正常时间均明显短于对照组（P〈0.05）;同时治疗3 d后,观察组患儿临床总有效率为94.74%,明显高于对照组的78.95%（χ2=4.15,P〈0.05）。两组患儿治疗后随访3个月,其中观察组和对照组分别腹泻复发5例（13.16%）和13例（34.21%）,观察组腹泻的复发率明显低于对照组（χ2=4.66,P〈0.05）。结论酪酸梭菌活菌散联合葡萄糖酸锌治疗儿童急性腹泻的疗效较肯定,能明显改善患儿腹泻症状,缩短腹泻病程,并能减少腹泻的复发。     

Influence of +1245 A/G MT1A polymorphism on advanced glycation end-products (AGEs) in elderly: effect of zinc supplementation

Advanced glycation end-products (AGEs) stimulate reactive oxygen species (ROS) generation and represent a risk factor for atherosclerosis, while their formation seems to be prevented by zinc. Metallothioneins (MT), zinc-binding proteins exert an antioxidant function by regulating intracellular zinc availability and protecting cells from ROS damages. +1245 A/G MT1A polymorphism was implicated in type 2 diabetes and in cardiovascular disease development as well as in the modulation of antioxidant response. The purpose of this study was to investigate the influence of +1245 A/G MT1A polymorphism on AGEs and ROS production and to verify the effect of zinc supplementation on plasma AGEs, zinc status parameters and antioxidant enzyme activity in relation to this SNP. One hundred and ten healthy subjects (72 ± 6 years) from the ZincAge study were supplied with zinc aspartate (10 mg/day for 7 weeks) and screened for +1245 MT1A polymorphism. +1245 MT1A G+ (Arginine) genotype showed higher plasma AGEs and ROS production in peripheral blood mononuclear cells (PBMCs) than G− (Lysine) one at the baseline. No significant changes after zinc supplementation were observed for AGEs, ROS and MT levels as well as for enzyme antioxidant activity in relation to the genotype. Among zinc status parameters, major increases were observed for the intracellular labile zinc (iZnL) and the NO-induced release of zinc in PBMCs, in G+ genotype as compared to G− one. In summary, +1245 G+ carriers showed increased plasma AGEs and ROS production in PBMCs at baseline and a higher improvement in iZnL after zinc intervention with respect to G− individuals.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-014-0426-2) contains supplementary material, which is available to authorized users.