Effects of nano zinc oxide and nano chitosan on the taste masking paracetamol granules.

OBJECTIVE: The purpose of this study is to investigate the taste masking of Paracetamol granules in the range of 250-850 µm, coated by two nanocomposites prepared from Eudragit® E100, nanozinc oxide, and nanochitosan, respectively, from 1 to 5% by the weight of the granules. METHODS: In this study, Paracetamol granules were coated in several formulas with two different types of nanocomposites (polymeric and mineral) on two sizes of granules to reduce bitter taste and with the FBC method and pH-sensitive polymers (Eudragit® E100). RESULTS: The effect of nanoparticles (Nano zinc oxide and Nanochitosan) on taste-masking Paracetamol was studied with dissolution-coated granules in vitro by simulating in the oral (pH 6.8) range. Based on the results of the studies, the rate of drug release was confirmed by the taste test, and the formulated granule with 5% nano-chitosan (F14) had the best bitter taste mask function of all samples. These results were also confirmed by scanning electron microscopy (SEM) analysis, which showed a smoother and more stable surface than the samples obtained from other formulations. CONCLUSION: In the comparison of the release of two types of nanocomposites in the dissolution test, it was shown that the type B granules of Paracetamol's 5% nano-chitosan-coated granule (F14) were released 99% less than Paracetamol's 5% nano-ZnO-coated granule (F11). and Paracetamol's 1% nano-chitosan-coated granule (F12) was released 91% less than Paracetamol's 1% nano-ZnO-coated granule (F9). The results showed that nano-chitosan-coated granules have better coverage of bitter taste instead of nano-ZnO.

Bone characteristics, pre-caecal phytate degradation, mineral digestibility and tissue expression were marginally affected by zinc level and source in phytase-supplemented diets in 21-day-old broiler chickens.

1. This study determined the effect of dietary Zn concentration and source in phytase-supplemented diets on bone mineralisation, gastrointestinal phytate breakdown, mRNA-level gene expression (in jejunum, liver and Pectoralis major muscle) and growth performance in broiler chickens.2. Male Cobb 500 broilers were housed in floor pens (d 0-d 21) to test seven treatments with six replicate pens (12 birds per pen). Diets were arranged in a 2 × 3 + 1-factorial arrangement. The experimental factors were Zn source (Zn-oxide (ZnO) or Zn-glycinate (ZnGly) and Zn supplementation level (10, 30 or 50 mg/kg of diet). A maize-soybean meal-based diet without supplementation and formulated to contain 28 mg Zn/kg (analysed to be 35 mg Zn/kg), served as a control.3. Zinc source and level did not influence (p > 0.05) bone ash concentration and quantity or mineral concentrations in bone ash. Tibia thickness was greater in the treatment ZnO10 than in the treatments ZnO30 and ZnGly50 (Zn level × Zn source: p = 0.036), but width and breaking strength were not affected.4. Pre-caecal P digestibility and concentrations of phytate breakdown products in the ileum, except for InsP5, were not affected by Zn source or level. Only the expression of EIF4EBP1 (eukaryotic translation initiation factor 4E-binding protein 1) and FBXO32 (F-box only protein 32) in Pectoralis major muscle was affected by source, where expression was increased in ZnO compared to ZnGly diets (p < 0.05).5. In conclusion, Zn level and source did not affect gastrointestinal phytate degradation and bone mineralisation in phytase-supplemented diets. The intrinsic Zn concentration appeared to be sufficient for maximum bone Zn deposition under the conditions of the present study but requires validation in longer-term trials.

Naringenin-Zinc Oxide Nanocomposites Amalgamated Polymeric Gel Augmented Drug Delivery and Attenuated Experimental Cutaneous Candidiasis in Balb/c Mice: In Vitro and In Vivo Studies.

Naringenin (NRG) inhibits the fungal 17ß-hydroxysteroid dehydrogenase accountable for ergosterol synthesis in Candida albicans (C. albicans), a causative agent for cutaneous candidiasis. In present research, NRG was complexed with ZnO nanomaterial (NRG-Zn2+) to synthesize NRG-Zn2+ nanocomposites. The particle size and ζ-potential of NRG-Zn2+ nanocomposites were respectively estimated to be 180.33 ± 1.22-nm and - 3.92 ± 0.35-mV. In silico data predicted the greater affinity of NRG-Zn2+ nanocomposite for 14α-demethylase and ceramide in comparison to NRG alone. Later, NRG-Zn2+ nanocomposites solution was transformed in to naringenin-zinc oxide nanocomposites loaded chitosan gel (NRG-Zn-CS-Gel) with viscosity and firmness of 854806.7 ± 52386.43 cP and 698.27 ± 10.35 g, respectively. The ex-vivo skin permeation demonstrated 70.49 ± 5.22% skin retention, significantly greater (P < 0.05) than 44.48 ± 3.06% of naringenin loaded chitosan gel (NRG-CS-Gel) and 31.24 ± 3.28% of naringenin solution (NRG Solution). NRG-Zn-CS-Gel demonstrated 6.71 ± 0.84% permeation of NRG with a flux value of 0.046 ± 0.01-µg/cm2/h. The MIC50 of NRG-Zn-CS-Gel against C. albicans was estimated to be 0.156-µg/mL with FICI (fractional inhibitory concentration index) of 0.018 that consequently exhibited synergistic efficacy. Further, NRG-Zn-CS-Gel demonstrated superior antifungal efficacy in C. albicans induced cutaneous candidiasis infection in Balb/c mice. The fungal burden in NRG-Zn-CS-Gel treated group was 109 ± 25 CFU/mL, significantly lower (P < 0.05) than positive control (2260 ± 446 CFU/mL), naringenin loaded chitosan gel (NRG-CS-Gel; 928 ± 127 CFU/mL) and chitosan gel (CS-Gel; 2116 ± 186 CFU/mL) treated mice. Further, histopathology examination and cytokine profiling of TNF-α, IL-1ß and IL-10 revealed the healing of skin and inflammation associated with cutaneous candidiasis infection. In conclusion, NRG-Zn-CS-Gel may be a potential candidate for translating in to a clinical viable topical nanotherapeutic.

Effectiveness and safety of a cream product containing zinc oxide for alleviating mosquito bite symptoms.

BACKGROUND: People frequently experience discomfort with immediate wheal, delayed papules, and pruritus from mosquito bites. A topical cream product containing zinc oxide is commercially available for the management of insect bites, but there has been no published evidence for its effectiveness and safety. AIMS: To evaluate the effectiveness and safety of this product in symptoms caused by mosquito bites. METHODS: An open-label, controlled study was performed on 41 healthy participants. All subjects received Aedes aegypti mosquito bites on the forearm. Then test product was randomly applied to the bitten areas of the left or right arm. The other arm was left untreated (control). The onset of pruritus relief was noted. The severity of pruritus was assessed using a visual analogue scale (VAS), ranging from 0 mm (no pruritus) to 100 mm (severe pruritus), and a 4-point pruritus score (0 = none; 1 = mild, not affecting normal activities; 2 = moderate, affecting normal activities to some extent; 3 = severe, significantly affecting activities) at four time points: 15 minutes after the mosquito bite (baseline), as well as 1 hour, 24 hours, and 48 hours after initiating treatment. The size of the bite reaction lesion was also measured at all time points. Any local cutaneous adverse reactions observed during the study were documented. RESULTS: The onset of pruritus relief in the treated group (25 ± 21.7 minutes) was significantly faster compared to the untreated group (118.7 ± 304.8 minutes). The reduction in VAS score at 1 hour was significantly greater in the product group (30.5 ± 16.22) compared to the control group (14.9 ± 9.9). Moreover, there was a significant difference in the reduction of pruritus score at 1 hour, with the product group (1.1 ± 0.5) showing a higher reduction compared to the control group (0.3 ± 0.4). However, there was no significant difference in the reduction of bite lesion size between the two groups. Throughout the study, no adverse events were reported. CONCLUSION: Our preliminary findings indicate that the product effectively reduces pruritus caused by mosquito bites but does not have a significant impact on the size of the bite lesions. The product was found to be safe and may be an option for managing mosquito bites pruritus.

Anticancer properties of novel zinc oxide quantum dot nanoparticles against breast cancer stem-like cells.

Cancer stem cells (CSCs) play an essential role in cancer development, metastasis, relapse, and resistance to treatment. In this article, the effects of three synthesized ZnO nanofluids on proliferation, apoptosis, and stemness markers of breast cancer stem-like cells are reported. The antiproliferative and apoptotic properties of ZnO nanoparticles were evaluated on breast cancer stem-like cell-enriched mammospheres by MTS assay and flowcytometry, respectively. The expression of stemness markers, including WNT1, NOTCH1, ß-catenin, CXCR4, SOX2, and ALDH3A1 was assessed by real-time PCR. Western blotting was used to analyze the phosphorylation of Janus kinase 2 (JAK2) and Signal Transducer and Activator of Transcription 3 (STAT3). Markers of stemness were significantly decreased by ZnO nanofluids, especially sample (c) with code ZnO-148 with a different order of addition of polyethylene glycol solution at the end of formulation, which considerably decreased all the markers compared to the controls. All the studied ZnO nanofluids considerably reduced viability and induced apoptosis of spheroidal and parental cells, with ZnO-148 presenting the most effective activity. Using CD95L as a death ligand and ZB4 as an extrinsic apoptotic pathway blocker, it was revealed that none of the nanoparticles induced apoptosis through the extrinsic pathway. Results also showed a marked inhibition of the JAK/STAT pathway by ZnO nanoparticles; confirmed by downregulation of Mcl-1 and Bcl-XL expression. The present data demonstrated that ZnO nanofluids could combat breast CSCs via decreasing stemness markers, stimulating apoptosis, and suppressing JAK/STAT activity.

ZnO, TiO2 and Ag nanoparticles impact against some species of pathogenic bacteria and yeast.

The economic approaches for manufacturing the nanoparticles with physical and chemical effects and limited resistance to antibiotics have been progressed recently due to the rise of microbial resistance to antibiotics. This research aimed to study the antimicrobial efficacy of silver nanoparticles Ag, ZnO, and Tio2 nanoparticles against Salmonella typhimurium and Brucella abortus and Candida albicans. Two isolates of Salmonella and two isolates of Brucella abortus were isolated from food spastically meat and blood specimens, respectively. Candida albicans were isolated from the patient's mouth with oral candidiasis (oral thrush) and confirmed diagnosis by API 20C test. The antimicrobial susceptibility of Salmonella typhimurium and B. abortus isolates were performed against nine different antibiotics. Silver nanoparticles consisting of AgNPs size (90) nm, ZnO NPs size (20, 50) nm as well as TiO2 NPs size (10, 50) nm, were used. UV-Visible spectrophotometer was used to characterize silver nanoparticles. The highest resistance of Candida albicans was seen for fluconazole, Clotrimazole and Itraconazole. The results of the Minimum Inhibitory Concentration (MIC) of nanoparticles against Salmonella typhimurium showed the average MIC of Tio2-10nm and Tio2-50nm were 5000 and 2500 µg\ml for S1 and S2 isolates, respectively. The isolated Brucella abortus (B1 and B2) showed sensitivity to NPs with different MIC. The average MIC for Ag-90nm was 5000 and 2500 µg/ml for B1 and B2 isolates, respectively. The findings suggest NP solution has fungicidal and bactericidal impacts on the tested microorganisms so they can be suitable for multiple applications of the biomedical field such as developing new antimicrobial agents.

Health effects after inhalation of micro- and nano-sized zinc oxide particles in human volunteers.

Inhalation of ZnO particles can cause inflammation of the airways and metal fume fever. It is unclear if different sizes of the particles alter these effects. However, various studies report higher biological activity of other nano-sized particles compared to microparticles. No effects at all were observed after inhalation of micro- and nano-sized zinc oxide (ZnO) particle concentrations of 0.5 mg/m3. Studies with different particle sizes of ZnO at higher exposures are not available. Accordingly, we hypothesized that inhalation of nano-sized ZnO particles induces stronger health effects than the inhalation of the same airborne mass concentration of micro-sized ZnO particles. 16 healthy volunteers (eight men, eight women) were exposed to filtered air and ZnO particles (2.0 mg/m3) for 2 h (one session with nano- and one with micro-sized ZnO) including 1 h of cycling at moderate workload. Effect parameters were symptoms, body temperature, inflammatory markers in blood and in induced sputum. Induced sputum was obtained at baseline examination, 22 h after exposure and at the end of the final test. The effects were assessed before, immediately after, about 22 h after, as well as two and three days after each exposure. Neutrophils, monocytes and acute-phase proteins in blood increased 22 h after micro- and nano-sized ZnO exposure. Effects were generally stronger with micro-sized ZnO particles. Parameters in induced sputum showed partial increases on the next day, but the effect strengths were not clearly attributable to particle sizes. The hypothesis that nano-sized ZnO particles induce stronger health effects than micro-sized ZnO particles was not supported by our data. The stronger systemic inflammatory responses after inhalation of micro-sized ZnO particles can be explained by the higher deposition efficiency of micro-sized ZnO particles in the respiratory tract and a substance-specific mode of action, most likely caused by the formation of zinc ions.

Zinc oxide nanoparticles alleviates the adverse effects of cadmium stress on Oryza sativa via modulation of the photosynthesis and antioxidant defense system.

Cadmium (Cd) is a trace element causing severe toxicity symptoms in plants, besides posing hazardous fitness issue due to its buildup in the human body through food chain. Nanoparticles (NPs) are recently employed as a novel strategy to directly ameliorate the Cd stress and acted as nano-fertilizers. The intend of the current study was to explore the effects of zinc oxide nanoparticles (ZnO-NPs; 50 mg/L) on plant growth, photosynthetic activity, elemental status and antioxidant activity in Oryza sativa (rice) under Cd (0.8 mM) stress. To this end, the rice plants are treated by Cd stress at 15 days after sowing (DAS), and the treatment was given directly into the soil. Supply of ZnO-NPs as foliar spray was given for five consecutive days from 30 to 35 DAS, and sampling was done at 45 DAS. However, rice plants supplemented with ZnO-NPs under the Cd toxicity revealed significantly increased shoot length (SL; 34.0%), root fresh weight (RFW; 30.0%), shoot dry weight (SDW; 23.07%), and root dry weight (RDW; 12.24%). Moreover, the ZnO-NPs supplement has also positive effects on photosynthesis related parameters, SPAD value (40%), chloroplast structure, and qualitatively high fluorescence observed by confocal microscopy even under Cd stress. ZnO-NPs also substantially prevented the increases of hydrogen peroxide (H2O2) and malondialdehyde (MDA) triggered by Cd. Physiological and biochemical analysis showed that ZnO-NPs increased enzymatic activities of superoxide dismutase (SOD; 59%), catalase (CAT; 52%), and proline (17%) that metabolize reactive oxygen species (ROS); these increases coincided with the changes observed in the H2O2 and MDA accumulation after ZnO-NPs application. In conclusion, ZnO-NPs application to foliage has great efficiency to improve biomass, photosynthesis, protein, antioxidant enzymes activity, mineral nutrient contents and reducing Cd levels in rice. This can be attributed mainly from reduced oxidative damage resulted due to the ZnO-NPs application.

Particle Size and Biological Fate of ZnO Do Not Cause Acute Toxicity, but Affect Toxicokinetics and Gene Expression Profiles in the Rat Livers after Oral Administration.

Zinc oxide (ZnO) particles have been used as dietary supplements because zinc is an essential trace element for humans. Along with the rapid development of nanotechnology, the use of ZnO nanoparticles (NPs) is increasing in the food industry, but their oral toxicity potential still remains to be answered. In this study, the effects of particle size and biological fate of ZnO on acute toxicity, toxicokinetics, and gene expression profiles in the livers were investigated after oral administration of ZnO NPs (N-ZnO), bulk-sized ZnO (B-ZnO) or Zn ions in rats. The plasma concentration-time profiles after a single-dose oral administration of ZnOs differed depending on particle/ionic forms and particle size, showing high absorption of Zn ions, followed by N-ZnO and B-ZnO, although in vivo solubility did not differ from particle size. No significant acute toxicity was found after oral administration of ZnOs for 14 days in rats. However, transcriptomic responses in the livers were differently affected, showing that metabolic process and metal biding were up-regulated by Zn ions and N-ZnO, respectively, which were not pronounced in the liver treated with B-ZnO. These findings will be useful to predict the potential oral toxicity of ZnO NPs and further mechanistic and long-term exposure studies are required to assume their safety.

Green Synthesis of Zinc Oxide Nanoparticles: Fortification for Rice Grain Yield and Nutrients Uptake Enhancement.

Applications of metal oxide nanoparticles in the agriculture sector are being extensively included as the materials are considered superior. In the present work, zinc oxide nanoparticle (ZnO NPs), with a developing fertilizer, is applied in the fortification of rice grain yield and nutrient uptake enhancement. To evaluate the role of ZnO NP, two field experiments were conducted during the 2018 and 2019 seasons. ZnO NPs were small, nearly spherical, and their sizes equal to 31.4 nm, as proved via the dynamic light scattering technique. ZnO NPs were applied as a fertilizer in different concentrations, varying between 20 and 60 mg/L as a foliar spray. The mixture of ZnSO4 and ZnO NP40 ameliorated yield component and nutrients (N, K, and Zn) uptake was enhanced compared to traditional ZnSO4 treatment. Nevertheless, the uptake of the phosphorous element (P) was adversely affected by the treatment of ZnO NPs. Thus, treatment via utilizing ZnO NPs as a foliar with a very small amount (40 ppm) with of basal ZnSO4 led to a good improvement in agronomic and physiological features; eventually, higher yield and nutrient-enriched rice grain were obtained.

Ameliorating the Adverse Effects of Tomato mosaic tobamovirus Infecting Tomato Plants in Egypt by Boosting Immunity in Tomato Plants Using Zinc Oxide Nanoparticles.

Tomato mosaic virus (ToMV) is one of the economically damageable Tobamovirus infecting the tomato in Egypt that has caused significant losses. It is therefore of great interest to trigger systemic resistance to ToMV. In this endeavor, we aimed to explore the capacity of ZnO-NPs (zinc oxide nanoparticles) to trigger tomato plant resistance against ToMV. Effects of ZnO-NPs on tomato (Solanum lycopersicum L.) growth indices and antioxidant defense system activity under ToMV stress were investigated. Noticeably that treatment with ZnO-NPs showed remarkably increased growth indices, photosynthetic attributes, and enzymatic and non-enzymatic antioxidants compared to the challenge control. Interestingly, oxidative damage caused by ToMV was reduced by reducing malondialdehyde, H2O2, and O2 levels. Overall, ZnO-NPs offer a safe and economic antiviral agent against ToMV.

Effects of different concentrations of coated nano zinc oxide material on fecal bacterial composition and intestinal barrier in weaned piglets.

BACKGROUND: Coated nano zinc oxide (Cnz) is a new feed or food additive, which is a potential replacement for a pharmacological dose level of ZnO. This study evaluated the positive effects of different concentrations of Cnz on the intestinal bacterial core, enterobacterial composition and mucosal barrier function in a pig model. RESULTS: Microbiota sequencing results showed that Cnz could significantly alter the intestinal microbiota composition and metabolism. Besides increasing the richness indices (ACE and Chao1), 10% Cnz could protect the intestinal mucosal barrier through increasing the expression of occludin and zonula occludens-1 in the small intestine, increase the abundance of Lachnospiraceae UCG-004 and decrease the abundance of Ruminococcus flavefaciens compared to high ZnO diet and 5% Cnz material. CONCLUSIONS: Cnz material at 10% supplementation is more effective than a level of 5% Cnz in increasing intestinal barrier through affecting gut microbiota. © 2020 Society of Chemical Industry.

Active Packaging of Immobilized Zinc Oxide Nanoparticles Controls Campylobacter jejuni in Raw Chicken Meat.

Zinc oxide nanoparticles (ZnO NPs) are regarded as a safe and stable antimicrobial that can inactivate bacteria by several potential working mechanisms. We aimed to incorporate ZnO NPs into packaging material to control Campylobacter in raw chicken meat. ZnO NPs were first incorporated into three-dimensional (3D) paper tubes to identify the lethal concentration against Campylobacter jejuni, which was selected as the working concentration to develop 2D functionalized absorbing pads by an ultrasound-assisted dipping technique. The functionalized pad was placed underneath raw chicken meat to inactivate C. jejuni and the predominant chicken microbiota at 4°C within 8 days of storage. Immobilized ZnO NPs at 0.856 mg/cm2 reduced C. jejuni from ∼4 log CFU/25 g raw chicken meat to an undetectable level after 3 days of storage. Analysis by inductively coupled plasma-optical emission spectroscopy showed that the Zn level increased from 0.02 to 0.17 mg/cm2 in treated raw chicken meat. Scanning electron microscopy validated the absence of nanoparticle migration onto raw chicken meat after treatment. Inactivation of C. jejuni was associated with the increase of lactic acid produced by Lactobacillus in raw chicken meat in a pH-dependent manner. Less than 5% of Zn2+ was released from ZnO NPs at neutral pH, while up to 88% was released when the pH was <3.5 within 2 days. Whole-transcriptome sequencing (RNA-Seq) analysis demonstrated a broad effect of ZnO NPs on genes involved in various cellular developmental processes as annotated by gene ontology. Taken together, the results indicate that functionalized absorbing pads inactivated C. jejuni in raw chicken meat by immobilized ZnO NPs along with the controllable released Zn2+IMPORTANCE Prevalence of Campylobacter in raw poultry remains a major food microbiological safety challenge. Novel mitigation strategies are required to ensure the safety and quality of poultry products. Active food packaging can control pathogens without directly adding antimicrobials into the food matrix and extend the food's shelf life. The functionalized absorbing pad with ZnO NPs developed in this study was able to inactivate C. jejuni in raw chicken meat and keep the meat free from C. jejuni contamination during shelf life without any observed migration of nanoparticles. The controllable conversion of immobilized ZnO NPs to free Zn2+ makes this approach safe and eco-friendly and paves the way for developing a novel intervention strategy for other high-risk foods. Our study applied nanotechnology to exploit an effective approach for Campylobacter control in raw chicken meat products.

Silk Fibroin-Modified Disulfiram/Zinc Oxide Nanocomposites for pH Triggered Release of Zn2+ and Synergistic Antitumor Efficacy.

Disulfiram (DSF) is an FDA-approved anti-alcoholic drug that has recently proven to be effective in cancer treatment. However, the short half-life in the bloodstream and the metal ion-dependent antitumor activity significantly limited the further application of DSF in the clinical field. To this end, we constructed a silk fibroin modified disulfiram/zinc oxide nanocomposites (SF/DSF@ZnO) to solubilize and stabilize DSF, and, more importantly, achieve pH triggered Zn2+ release and subsequent synergistic antitumor activity. The prepared SF/DSF@ZnO nanocomposites were spherical and had a high drug loading. Triggered by the lysosomal pH, SF/DSF@ZnO could induce the rapid release of Zn2+ under the acidic conditions and caused nanoparticulate disassembly along with DSF release. In vitro experiments showed that cytotoxicity of DSF could be enhanced by the presence of Zn2+, and further amplified when encapsulated into SF/DSF@ZnO nanocomposites. It was confirmed that the significantly amplified cytotoxicity of SF/DSF@ZnO was resulted from pH-triggered Zn2+ release, inhibited cell migration, and increased ROS production. In vivo study showed that SF/DSF@ZnO nanocomposites significantly increased the tumor accumulation and prolonged the retention time. In vivo antitumor experiments in the xenograft model showed that SF/DSF@ZnO exerted the highest tumor-inhibition rate among all the drug treatments. Therefore, this exquisite study established silk fibroin-modified disulfiram/zinc oxide nanocomposites, SF/DSF@ZnO, where ZnO not only acted as a delivery carrier but also served as a metal ion reservoir to achieve synergistic antitumor efficacy. The established DSF nanoformulation displayed excellent therapeutic potential in future cancer treatment.

Isolation of swine-derived Lactobacillus plantarum and its synergistic antimicrobial and health-promoting properties with ZnO nanoparticles.

AIMS: The purpose of this study was to isolate Lactobacillus from gastrointestinal tract of healthy postweaning piglets and investigate its synergistic antimicrobial and probiotic effects with ZnO nanoparticles (nZnO). METHODS AND RESULTS: Of the 128 isolates, Lactobacillus plantarum BLPL03 was selected based on its excellent acid and bile salt tolerance properties. Lactobacillus plantarum BLPL03 was sensitive to ß-lactams, macrolides, amphenicols and cephalosporins, whereas it displayed the steady resistance to aminoglycosides, tetracyclines, quinolones and peptide antibiotics. In vitro analysis of antibacterial activities showed that L. plantarum BLPL03 inhibited the four common food-borne pathogenic bacteria including Escherichia coli O157:H7 CMCC 44828, Salmonella Typhimurium ATCC 13311, Staphylococcus aureus CMCC 26003 and Listeria monocytogenes CMCC 54007 in synergy with nZnO. Furthermore, the quantitative polymerase chain reaction test demonstrated that the combined administration of L. plantarum BLPL03 fermentation liquor (LFL) and nZnO synergistically elevated the faecal number of Bifidobacterium by 73·19-fold, and reduced the two potential enteropathogenic bacteria Enterobacteriaceae and Clostridium perfringens in mice challenged with Salm. Typhimurium. Finally, dietary supplementation with low dose of nZnO (20 mg kg-1 ) when combined with LFL administration enhanced final body weight, fur appearance and average daily gain, and decreased feed conversion ratio and diarrhoea incidence in weaned piglets. The faecal Bifidobacterium and Lactobacillus of piglets were dramatically enhanced by 81·96- and 3·15-fold, respectively, after administration of a mixture of nZnO and LFL. Meanwhile, combination of nZnO with LFL resulted in low levels of Bacteroides, Enterococcus, and Enterobacteriaceae. CONCLUSIONS: A combination of nZnO and LFL exhibits potential health-benefit properties for the control of gut microbial composition by their synergistic antimicrobial and probiotic effects. SIGNIFICANCE AND IMPACT OF THE STUDY: This study may provide a potential nutritional strategy to improve performance and gut health of animals with gut microbiota disorders caused by pathogen infections and weanling, and so on.

Whole Blood Assay as a Tool to Describe the Effects of Zinc Oxide Exposure on Innate Immunity.

Inhalation of high concentrations of zinc oxide (ZnO) particles may cause metal fume fever. A useful tool to characterize the reactivity of innate immune cells of an individual, e.g., after in vivo exposure, is the whole blood assay (WBA). The measurable outcome of WBA is the release of cytokines, especially pro-inflammatory and pyrogenic cytokines induced by stimulation in vitro. The aim of the study was to evaluate whether inhalation of nano-sized zinc oxide particles modifies the results of WBA from healthy blood donors. Sixteen healthy subjects were exposed to filtered air and ZnO particles (0.5, 1.0, and 2.0 mg/m3) for 4 h on four different days. Blood was collected before and 24 h after exposure, and ex vivo stimulation of the whole blood was performed using different endotoxin concentrations. The release of interleukin (IL)-1ß and IL-8 after 22-h incubation was quantified with specific immunoassays. The dose-response relationship of ex vivo stimulation with different endotoxin concentrations was not affected by previous ZnO exposure. However, based on the previously established calculation models, changes due to ZnO exposure could be described. The range of cytokine release in WBA was calculated for the whole group of blood donors, for the subgroups of low and high responders (each n = 8), and on the individual level. Most changes were observed after 0.5 mg/m3 ZnO exposure. Higher ZnO exposure did not yield higher effects. We conclude that the effects of inhalation of nano-sized ZnO particles in blood of healthy donors using the WBA could be determined. However, it should be noted that cytokine release as outcome of WBA is not a marker of disease.

Oral Co-Exposures to zinc oxide nanoparticles and CdCl2 induced maternal-fetal pollutant transfer and embryotoxicity by damaging placental barriers.

Synergistic toxicity from multiple environmental pollutants poses greater threat to humans, especially to susceptible pregnant population. Here we evaluated combined toxicity from environment pollutants zinc oxide nanoparticles (ZnO NPs) and cadmium chloride (CdCl2) using two pregnant mice models established by oral administration during peri-implantation or organogenesis period. We found that exposures to combined pollutants only at organogenesis stage induced higher fetal deformity rate compared to co-exposures at peri-implantation stage. We further discovered that surface charge of ZnO NPs were modified after Cd2+ adsorption and the resulting nanoadducts caused more severe damages in placental barriers by causing shed endothelial cells and decreased expressions of tight junction proteins ZO1, occludin, claudin-4 and claudin-8. These cellular and molecular events enhanced maternal-fetal transfer of both pollutants and aggravated embryotoxicity. Our findings help elucidate synergistic embryotoxicity by nanoparticle/pollutant adducts and establish proper safety criteria for pregnant population in an era that nanotechnology-based products are widely used.

Anticancer properties of green-synthesised zinc oxide nanoparticles using Hyssopus officinalis extract on prostate carcinoma cells and its effects on testicular damage and spermatogenesis in Balb/C mice.

The unclear bio-safety issue and potential risk of nanoparticles (NPs) on various organelles can be considered as a major challenge. In the present study, we have assessed the green synthesis of ZnO nanoparticles using Hyssop (Hyssopus officinalis) extract and their effects on PC3 cell line and BALB/c mice model. The cytotoxicity of the ZnO-NPs was assessed on PC3 cell line by MTT test after characterisation. Apoptotic effect of ZnO-NPs was determined by in vitro AO/PI staining. The histopathological assessments and determination of LH and FSH levels carried out as in vivo analysis in BALB/c adult male mice. The expression of major genes involved in spermatogenesis and sperm maturation (Adam3, Prm1, Spata19, Tnp2, Gpx5) were also analysed. The obtained result demonstrated that the IC50 for PC3 cell line treated with green-synthesised ZnO-NPs during 24 and 48 hr was reported 8.07 and 5 µg/ml respectively. Meanwhile, the induced apoptosis was recorded 26.6% ± 0.05, 44% ± 0.12 and 80% ± 0.07 of PC3 cells. The results of gene expression analysis revealed that the increase in the concentration of ZnO-NPs significantly (p < .05) down-regulated the Adam3, Prm1, Spata-19, Tnp2 and Gpx5 genes. The overall results of this research elucidated that ZnO-NPs impaired spermatogenesis, sperm maturation process and sperm motility.

A minimally invasive clinical model to test sunscreen toxicity based on oxidative stress levels using microbiopsy and confocal microscopy - a proof of concept study.

OBJECTIVE: This proof-of-concept study demonstrated that using minimally invasive skin microsampling could enable significantly higher throughput of cosmetic testing in volunteers than conventional biopsy. Nanoparticle sunscreen was used as a model to test toxicity based on oxidative stress using microbiopsy and confocal imaging. METHODS: Six volunteers were recruited for this study (3 males and 3 females). Zinc oxide nanoparticle containing topical formulation was prepared at 10% w/v. Each volunteer had 3 areas of 4 cm2 each mapped on each inner forearm for a total of 6 treatment areas (intact/ tape-stripped and with/without treatment). The topical zinc-nanoparticle formulation was applied directly to volunteer skin (2mg/cm2 ) for 2 hrs. Microbiopsied tissue from each treatment group was stained for reactive oxygen and nitrogen species in addition to mitochondrial superoxide. The stained samples were then imaged using confocal microscopy prior to image analysis. RESULTS: Skin exposed to zinc oxide nanoparticles did not show any significant increases in oxidative stress. Zinc oxide nanoparticle tape-stripped skin resulted in signal significantly lower (P < 0.001) oxidative stress levels than t-butylated hydroxytoluene treated tape-stripped skin for oxidative stress markers. Topically applied zinc oxide nanoparticles had no detectable effect on the oxidative status in volunteer skin. No adverse reactions or effects were observed after all treatments including microbiopsy. CONCLUSION: The data support the hypothesis that microbiopsy is a viable approach to study cosmeceutical- skin interactions in volunteers with capacity for molecular assays and high throughput with very low risk to the volunteer.

OBJECTIFS: Cette étude de validation de concept a démontré que le microprélèvement cutané minimalement invasif pouvait augmenter considérablement la cadence des essais de produits cosmétiques sur des volontaires par rapport à une biopsie conventionnelle. Un écran solaire contenant des nanoparticules a été utilisé comme modèle pour tester la toxicité liée au stress oxydatif à l'aide de la microbiopsie et de l'imagerie confocale. MÉTHODES: Six volontaires ont été recrutés pour cette étude (3 hommes et 3 femmes). Une formulation topique contenant des nanoparticules d'oxyde de zinc a été préparée à 10 % p/v. Chaque volontaire disposait de 3 zones de 4 cm2 situées sur chaque pliure de coude pour un total de 6 zones de traitement (intactes / strippée et avec / sans traitement). La formulation topique contenant des nanoparticules d'oxyde de zinc a été appliquée directement sur la peau des volontaires (2 mg/cm2 ) pendant 2 heures. Les tissus microbiopsiés de chaque groupe de traitement ont été colorés pour détecter des espèces réactives de l'oxygène et de l'azote en plus de la superoxyde mitochondriale. Les échantillons colorés ont ensuite été examinés par microscopie confocale avant l'analyse des images. RÉSULTATS: La peau exposée aux nanoparticules d'oxyde de zinc n'a pas montré de hausse significative de stress oxydatif. La peau strippée traitée aux nanoparticules d'oxyde de zinc a entraîné des niveaux de stress oxydatif nettement inférieurs (p<0,001) comparés à ceux de la peau strippée traitée à l'hydroxytoluène t-butylé en ce que concerne les marqueurs de stress oxydatif. Les nanoparticules d'oxyde de zinc appliquées par voie topique n'ont eu aucun effet détectable sur l'état oxydatif de la peau des volontaires. Aucune réaction ou effet indésirable n'a été observé(e) après tous les traitements, y compris la microbiopsie. CONCLUSION: Les données obtenues étayent l'hypothèse selon laquelle la microbiopsie est une approche viable pour étudier les interactions des produits cosmétiques sur la peau des volontaires, avec la possibilité de réaliser des dosages moléculaires et à haut débit, avec un risque très faible pour les volontaires.

Effects of reducing dietary crude protein concentration and supplementation with laminarin or zinc oxide on the faecal scores and colonic microbiota in newly weaned pigs.

A 2 × 3 factorial design experiment was conducted to examine the effects of reducing dietary crude protein (CP) concentration and/or supplementation with zinc oxide (ZnO) or laminarin on faecal scores (FS) and the large intestinal microbiota post-weaning (PW). One hundred and forty-four pigs were assigned to (T1) 21% standard CP diet (SCP); (T2) SCP + ZnO (SCP ZnO); (T3) SCP + laminarin (SCP LAM); (T4) 18% low CP diet (LCP); (T5) LCP + ZnO (LCP ZnO); and (T6) LCP + laminarin (LCP LAM; n = 8 replicates/treatment). The LCP diet had no effect on FS (p > .05), it increased two measures of alpha diversity, reduced Bacteroidetes and increased Enterobacteriaceae and Helicobacteraceae in the colon relative to the SCP diet (p < .05). ZnO supplementation reduced FS and increased Ruminococcaceae compared with unsupplemented pigs (p < .05). ZnO supplementation increased the genera Frisingicoccus (p < .001), Lachnoclostridium (p < .05) and Peptoclostridium (p < .05) in the colon and reduced total caecal volatile fatty acids (VFA) concentrations compared with the unsupplemented and laminarin-supplemented pigs. Laminarin supplementation reduced FS compared with unsupplemented pigs but had no major effect on the microbiota compared with the unsupplemented pigs. There were CP concentration × additive interactions on both Firmicutes and Proteobacteria. Firmicutes were increased in the LCP ZnO group compared with the LCP group, but there was no difference between the SCP groups. Proteobacteria were reduced in the LCP ZnO group compared with the LCP and LCP LAM groups (p < .05), but there was no difference between the SCP groups. In conclusion, reducing CP did not improve FS; it increased the relative abundance of Enterobacteriaceae; however, it also increased bacterial diversity. Supplementation with ZnO and laminarin improved FS, although all groups had scores within the healthy range. ZnO altered the large intestinal microbiota and VFA concentrations; however, laminarin did not enhance these parameters, suggesting these compounds have differing modes of action.