NP Treatment Research Articles

Effects of biogenerated ferric hydroxides nanoparticles on truffle mycorrhized plants.

Truffles are highly valuable ectomycorrhizal fungi that grow naturally in alkaline, calcareous soils. Iron deficiency chlorosis is a common problem in truffle (Tuber spp.) cultivation due to the high quantity of lime added to increase the pH of acidic soils. In this work, the effects of ferric hydroxide nanoparticles embedded in an exopolysaccharide (Fe-EPS NPs), extracted from cultures of Klebsiella oxytoca DSM 29614, were investigated on Quercus robur seedlings under greenhouse conditions. The plants were inoculated with Tuber borchii (the bianchetto truffle) and were cultivated with and without iron nanoparticle additions and compared with non-inoculated control plants. The seedlings were grown in limed soil in order to induce iron deficiency. Low doses of Fe-EPS NPs had a beneficial effect on the growth of the plants inoculated with T. borchii, increasing their height and reducing their leaf chlorosis 5months after the first Fe-EPS NP treatment. Moreover, Fe-EPS NP treatments significantly increased the level of T. borchii mycorrhizal colonization and the ectomycorrhizal mantle thickness. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) applied to cross sections of mycorrhizas showed that Fe accumulated in the fungal mantle and apparently was slowly released serving as a resilient reservoir of iron for the plant. The results suggest that the application of Fe-EPS NPs is a promising technique in the production of Tuber mycorrhized plants in the nursery and could have future applications in the field.

Effects of the Morphology, Surface Modification and Application Methods of ZnO-NPs on the Growth and Biomass of Tomato Plants

Benefits of nanotechnology in agriculture include reduced fertilizer loss, improved seed germination rate and increased crops quality and yield. The objective of this research was to evaluate the effects of zinc oxide nanoparticles (ZnO-NPs), at 1500 ppm, on tomato (Solanum lycopersicum L.) growth. ZnO-NPs were synthetized to produce either spherical or hexagonal morphologies. In this research, we also studied two application methods (foliar and drench) and nanoparticles’ (NPs) surface modification with maltodextrin. The results obtained indicate that ZnO-NP-treated tomato plants significantly increased plant height, stem diameter and plant organs (leaves, stem and root) dry weight compared to plants without NP treatment.

Impact of long-term chemical fertilizer and organic amendment to Fusarium root rot of soybean

Soil suppressiveness to Fusarium root rot of soybean had been observed in a black soil field after a long-term fertilization with nitrogen (N) and phosphorus (P) fertilizer combined with pig manure as organic amendment (NPM), rather than that with only nitrogen and phosphorus fertilizer (NP) or no fertilizer (NF). To determine the microbial role on this suppressiveness, fungal and bacterial community characteristics in NPM, NP and NF treatments were investigated by qPCR and DGGE. Compared with the similar bacterial community characteristics among 3 treatments, fungal community, especially Fusarium population size and community composition in NPM treatment were different with those of NP and NF groups. Based on the isolation and pathogenicity test, pathogenic F. oxysporum, F. graminearum, F. verticillioide and F. lateritium absolutely dominated Fusarium community in NF and NP groups. Nonpathogenic F. avenaceum, F. equiseti, F. culmorum, F. redolens, F. solani and F. tricinctum dominated Fusarium community in NPM group. Isolation rate of pathogenic Fusarium in NPM reduced from 100% to 38% in NF. These results suggested that the dominance of soil non-pathogenic Fusarium population induced by organic amendment might play an important role on suppressing Fusarium root rot in the tested field.

Abstract PD1-07: Exploratory analytical harmonization of PD-L1 immunohistochemistry assays in advanced triple-negative breast cancer: A retrospective substudy of IMpassion130

Abstract Background: In the Phase 3 IMpassion130 (NCT02425891) trial in metastatic triple-negative breast cancer (mTNBC), first-line atezolizumab + nab-paclitaxel (A+nP) significantly improved PFS vs placebo + nab-paclitaxel (P+nP) in the intent-to-treat (ITT) and PD-L1+ (PD-L1-stained immune cells [IC] ≥ 1% of the tumor area by VENTANA PD-L1 SP142 assay) populations. SP142 is currently the only validated assay for selecting patients who may derive benefit with A+nP. In post-hoc analyses of IMpassion130 (Rugo, ESMO 2019, submitted), PD-L1 status was also evaluated by Dako 22C3 and VENTANA SP263 assays. The SP142+ population (IC ≥ 1%; 46% prevalence) was captured within the 22C3 (CPS ≥ 1, 81% prevalence) and SP263 (IC ≥ 1%, 75% prevalence) subgroups, which identified more patients (pts) with PD-L1+ tumors. A+nP clinical activity was highest in pts identified as PD-L1+ by both SP142 and 22C3/SP263. HRs for clinical activity were lower in pts identified as PD-L1+ by 22C3/SP163, but PD-L1- by SP142. There was no suggestion of clinical benefit in pts identified as PD-L1- by both SP142 and 22C3/SP263. In the current retrospective exploratory analysis, we attempted to harmonize the PD-L1 assays by identifying cutoffs for 22C3 or SP263 that replicate the SP142 IC ≥ 1% population. Methods: Samples from IMpassion130 were assessed by a central laboratory for PD-L1 expression using VENTANA SP142 or SP263 IHC assays or Dako 22C3 IHC assay. Optimal cutoffs for 22C3 and SP263 were identified as those that maximize the analytical concordance (defined as overall percentage agreement; OPA) with the clinically validated SP142 IC 1% cutoff as the reference standard. Association with clinical activity was analyzed in the biomarker-evaluable population (BEP) in tumor samples from pts evaluated by the three PD-L1 assays. Results: In the BEP (n = 614; 68% of ITT), the intraclass correlation index (Spearman r) between SP142 IC and 22C3 CPS or SP263 IC was 0.57 and 0.69, respectively. The model-derived cutoffs with highest OPA (75%) for SP142 IC ≥ 1% were CPS 10 for 22C3 and IC 4% for SP263. Compared with our previous analyses at standard cutoffs (22C3 CPS 1; SP263 IC 1%), model-derived cutoffs resulted in negative percentage agreement increases from 45% to 74% (22C3) and from 34% to 77% (SP263), accompanied by positive percentage agreement reductions from 98% to 74% (22C3) and to 73% (SP263). These data suggest that the SP142 assay may identify a different population from the 22C3 or SP263 assays. For 22C3 at CPS 10, 36% of pts were SP142+/22C3+, but 10% were SP142+/22C3-, and 17% SP142-/22C3+. For SP263 at IC 4%, 34% of pts were SP142+/SP263+, but 12% were SP142+/SP263-, and 12% SP142-/SP263+. See table for prevalences, medians and HR point estimates for PFS and OS with the model-derived cutoffs. Conclusions: The suboptimal OPAs achieved with the model-derived cutoffs indicate that the assays could not be harmonized. Differences in SP142+ vs 22C3+ or SP263+ populations at model-derived cutoffs suggest that SP142, 22C3 and SP263 may not identify the same tumor biology. Additional data are required to understand these differences. Findings from these hypothesis-generating, post-hoc exploratory analyses based on mathematical modeling should be interpreted with caution. Currently, the VENTANA PD-L1 SP142 IHC assay (IC ≥ 1%) is the only clinically validated companion assay to select pts with mTNBC for A+nP treatment. Populationn (%)Median PFS, moPFS HRMedian OS, moOS HRA+nPP+nP(95% CI)A+nPP+nP(95% CI)BEP614 (100)7.45.40.7221.119.20.84(0.61, 0.86)(0.68, 1.03)SP142IC ≥ 1%285 (46)8.34.10.627.317.90.74(0.47, 0.78)(0.54, 1.01)IC < 1%329 (54)5.75.60.8620.820.70.95(0.68, 1.09)(0.72, 1.27)22C3CPS ≥ 10325 (53)7.55.50.712218.70.77(0.56, 0.91)(0.57, 1.03)CPS < 10289 (47)5.85.40.7320.219.40.94(0.57, 0.93)(0.69, 1.26)SP263IC ≥ 4%286 (47)8.75.50.6428.919.60.71(0.49, 0.83)(0.51, 0.98) Citation Format: Hope Rugo, Sherene Loi, Sylvia Adams, Peter Schmid, Andreas Schneeweiss, Carlos H Barrios, Hiroji Iwata, Véronique Diéras, Eric P Winer, Mark M Kockx, Dieter Peeters, Stephen Y Chui, Jennifer C Lin, Anh Nguyen Duc, Guiseppe Viale, Luciana Molinero, Leisha A Emens. Exploratory analytical harmonization of PD-L1 immunohistochemistry assays in advanced triple-negative breast cancer: A retrospective substudy of IMpassion130 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD1-07.

Specific oceanographic characteristics and phytoplankton responses influencing the primary production around the Ulleung Basin area in spring

The East Sea (Sea of Japan) is a marginal, semi-closed sea in the northwestern Pacific. The Ulleung Basin area, which is located near the subpolar front of the East Sea, is known to have high primary production and good fisheries in spring season. After episodic wind-driven events during the spring of 2017, horizontal and vertical profiles of physical chemical biological factors were investigated at 29 stations located in the Ulleung Basin area. In addition, growth responses of phytoplankton communities to nutrient additions were evaluated by bioassay experiments to understand the fluctuation of phytoplankton biomass. Because of strong northwestern wind, phytoplankton biomass was scattered and upwelling phenomenon might be suppressed in this season. The phytoplankton abundances in the coastal stations were significantly higher than offshore and island stations. In contrast, the nutrient and chlorophyll a (Chl a) concentrations and the phytoplankton biomass were quite low in all locations. Bacillariophyceae was dominated group (75.1% for coastal, 40.0% for offshore and 43.6% for island stations). In the algal bioassays, the phytoplankton production was stimulated by N availability. The in vivo Chl a values in the +N and +NP treatments were significantly higher than the values in the control and the +P treatments. Based on the field survey, the higher nutrients in coastal waters affected the growth of diatom assemblages, however, little prosperity of phytoplankton was observed in the offshore waters despite the injection of sufficient nutrients in bioassay experiments. The growth of phytoplankton depended on the initial cell density. All of results indicated that a dominant northwestern wind led to a limited nutrients condition at euphotic layers, and the low level of biomass supply from the coasts resulted in low primary production. Both supplying nutrients and introducing phytoplankton through the currents are critical to maintain the high productivity in the Ulleung Basin area of the East Sea.

Cerium Oxide Nanoparticles Rescue α-Synuclein-Induced Toxicity in a Yeast Model of Parkinson's Disease.

Over the last decades, cerium oxide nanoparticles (CeO2 NPs) have gained great interest due to their potential applications, mainly in the fields of agriculture and biomedicine. Promising effects of CeO2 NPs are recently shown in some neurodegenerative diseases, but the mechanism of action of these NPs in Parkinson’s disease (PD) remains to be investigated. This issue is addressed in the present study by using a yeast model based on the heterologous expression of the human α-synuclein (α-syn), the major component of Lewy bodies, which represent a neuropathological hallmark of PD. We observed that CeO2 NPs strongly reduce α-syn-induced toxicity in a dose-dependent manner. This effect is associated with the inhibition of cytoplasmic α-syn foci accumulation, resulting in plasma membrane localization of α-syn after NP treatment. Moreover, CeO2 NPs counteract the α-syn-induced mitochondrial dysfunction and decrease reactive oxygen species (ROS) production in yeast cells. In vitro binding assay using cell lysates showed that α-syn is adsorbed on the surface of CeO2 NPs, suggesting that these NPs may act as a strong inhibitor of α-syn toxicity not only acting as a radical scavenger, but through a direct interaction with α-syn in vivo.

Titanium dioxide nanoparticles (TiO2 NPs) promote growth and ameliorate salinity stress effects on essential oil profile and biochemical attributes of Dracocephalum moldavica

Considering titanium dioxide nanoparticles (TiO2 NPs) role in plant growth and especially in plant tolerance against abiotic stress, a greenhouse experiment was carried out to evaluate TiO2 NPs effects (0, 50, 100 and 200 mg L−1) on agronomic traits of Moldavian balm (Dracocephalum moldavica L.) plants grown under different salinity levels (0, 50 and 100 mM NaCl). Results demonstrated that all agronomic traits were negatively affected under all salinity levels but application of 100 mg L−1 TiO2 NPs mitigated these negative effects. TiO2 NPs application on Moldavian balm grown under salt stress conditions improved all agronomic traits and increased antioxidant enzyme activity compared with plants grown under salinity without TiO2 NP treatment. The application of TiO2 NPs significantly lowered H2O2 concentration. In addition, highest essential oil content (1.19%) was obtained in 100 mg L−1 TiO2 NP-treated plants under control conditions. Comprehensive GC/MS analysis of essential oils showed that geranial, z-citral, geranyl acetate and geraniol were the dominant essential oil components. The highest amounts for geranial, geraniol and z-citral were obtained in 100 mg L−1 TiO2 NP-treated plants under control conditions. In conclusion, application of 100 mg L−1 TiO2 NPs could significantly ameliorate the salinity effects in Moldavian balm.

A mesoporous silica nanoparticle technology applied in dilute nutrient solution accelerated establishment of zoysiagrass

AbstractUse of nanoparticles in agriculture is anticipated to have beneficial outcomes, including the potential for improving nutrient delivery. Mesoporous silica nanoparticles (MSNPs) are hydrophilic porous materials with high surface area and charge and have been shown to be taken up and mobilized by plants. Untreated MSNPs have interacted with plant nutrition in controlled studies, but little research has been conducted in the field. In this study, we tested the impact of a commercially available MSNP technology on establishment of two turfgrasses from sprigs in North Central Florida. Treatments included combinations of MSNPs (–NP, with no nanoparticles; +NP, with nanoparticles), which were foliarly applied in dilute nutrient solution, and two rates of background fertility (high and low fertility), which were applied by granular fertilizer. All treatments were applied weekly. The MSNPs were effective in enhancing the rate of establishment in zoysiagrass (Zoysia japonica Steud.) in combination with both high and low fertility. For the low fertility +NP treatment, this substantially improved nutrient‐use efficiency, as establishment was reduced by just 7.6% compared to the high fertility –NP treatment with 75% less fertilizer. No impact was observed on bermudagrass (Cynodon dactylon (L.) Pers. × C. Transvaalensis Burtt‐Davy). Tissue nutrient concentrations indicated the nutrients most likely limiting growth were K, Mg, Ca, Zn, and Mn. The results suggest MSNPs provided more effective delivery of one or more limiting nutrients to zoysiagrass than nutrients from other sources, enhancing the rate of growth. The MSNPs offer the potential to establish turfgrasses with lower fertilizer inputs.

Mineral fertilizers with recycled manure boost crop yield and P balance in a long-term field trial

Crop uptake and neglecting to apply phosphate (P) fertilizer are important reasons for P deficit in the agro-ecosystem. Recycled manure from within the system was adopted to evaluate the effects of mineral fertilizer combined with or without manure on crop yield, P budget, and P use efficiency in a continuous 20-year field trial. The experiment contained eight treatments: no fertilizer, manure (M), N fertilizer (N), N fertilizer with manure (N + M), N and P fertilizers (NP), NP fertilizers with manure (NP + M), N, P, and K fertilizers (NPK), and NPK fertilizers with manure (NPK + M). The yield and P uptake of soybean and maize increased with the sequential supplement of N, P, and K fertilizers. Application of recycled manure not only increased the yield and P uptake of crops but also reduced the inter-annual fluctuations in soybean yield. Although application of mineral P fertilizer was the main method to preserve P budget surplus and increase soil available P, recycled manure could be a positive supplement. The proportion of residual fertilizer P converted to soil available P under NP, NP + M, NPK, and NPK + M treatments was 9%, 7%, 3%, and 8%, respectively over a 20-year period. Moreover, P use efficiency in NP and NPK treatments gradually increased first and then stabilized at around 20%, but the value was obviously lower than that from manure. The results clearly demonstrated that integrated application of mineral NPK fertilizers and recycled manure was a useful method to improve crop yield and soil P fertility.

Nutrient management options for enhancing productivity and profitability of conservation agriculture under on-farm conditions in central highlands of Kenya

Decline in soil fertility is one of the major constraints to sustainable crop production and profitability. To meet the increasing demand for the growing population the issue of low soil fertility needs to be addressed. An on-farm experiment was established to evaluate the effect of interaction between NPK fertilizers and minimum tillage on soil fertility, maize crop yield and on farm profit margins. The field trials were set up in a split-plot design organized in a randomized complete block design in 28 farmers' fields. Application of all the three macronutrients i.e. NPK had the highest and significant (P < 0.0001) yields relative to treatments, where any of the three nutrients was omitted. Maize grain yield increased by over 150% with NPK, NP and NK application in all the three cropping seasons over the control. Grain losses with the omission of a single nutrient were highest with N (2.06, 2.40 & 2.42 t ha-1) followed by P (0.8, 0.59 & 0.43 t ha-1) in the short rain 2014 (SR2014), long rains 2015 (LR2015) and SR2015 seasons, respectively. Conservation agriculture recorded a significant (P < 0.0007) increase in P over the three seasons. There was significantly higher K in the soil within the NP and PK treatments and in the conservation agriculture compared to the conventional agriculture systems. Compared with conventional tillage, the benefit to cost ratio was higher by 3 and 5% under minimum tillage during the LR2015 and SR2015 seasons, respectively. Total variable cost was 4 and 2% higher under conventional tillage compared to minimum tillage during the LR2015 and SR2015 seasons, respectively. Treatments with N and conservation agriculture were the most profitable. A combined use of conservation agriculture and all the three macro-nutrients (NPK) is the best bet for increasing, maize crop yield and associated return on investment.

Surface sulfonation and nitrification enhance the biological activity and osteogenesis of polyetheretherketone by forming an irregular nano-porous monolayer.

Polyether-ether-ketone (PEEK) is becoming a popular component of clinical spinal and orthopedic applications, but its practical use suffers from several limitations. In this study, irregular nano-porous monolayer with differently functional groups was formed on the surface of PEEK through sulfonation and nitrification. The surface characteristics were detected by field-emission scanning electron microscopy, atomic force microscopy, energy-dispersive X-ray spectrometry, water contact angle measurements and Fourier transform infrared spectroscopy. In vitro cellular behaviors were evaluated by cell adhesion, morphological changes, proliferation, alkalinity, phosphatase activity, real-time RT-PCR and western blot analyses. In vivo osseointegration was examined through micro-CT and histological assessments. Our results reveal that the irregular nano-porous of PEEK affect the biological properties. High-temperature hydrothermal NP treatment induced early osteogenic differentiation and early osteogenesis. Modification by sulfonation and nitrification can broaden the use of PEEK in orthopedic and dental applications. This study provides a theoretical basis for the wider clinical application of PEEK. a To obtain a uniform porous structure, PEEK samples were treated by concentrated sulfuric acid and fuming nitric acid (82-80%) with magnetic stirring sequentially. b Effects of nanopores on biological behavior of bMSCS.

Biogenic synthesis of silver nanoparticles using Gliocladium deliquescens and their application as household sponge disinfectant.

The topic of this investigation was to evaluate the microbial contamination of household sponges, biosynthesize of silver nanoparticles (Ag NPs) by Gliocladium deliquescens cell-free supernatant, and estimate the efficiency of Ag NPs as an acceptable disinfectant. The 23 factorial design was applied for the optimization of Ag NPs synthesis. Silver nitrate (AgNO3) concentration was the main positive impact on Ag NP biosynthesis. Various gamma irradiation doses were used in Ag NP production where the highest yield production was at 25.0 kGy. Ag NPs were characterized by UV-Vis. spectroscopy, The Fourier-transform infrared spectroscopy analysis (FTIR), dynamic light scattering (DLS), X-ray diffraction (XRD), and transmission electron microscope (TEM). Ag NPs were monodispersed spherical-shaped with 9.68 nm mean size. Two hundred sponge samples that were collected from different Egyptian household furniture and kitchens were highly contaminated by various contaminants including Salmonella spp., Staphylococcus spp., coliform bacteria, Gram-negative bacteria, yeasts, and molds. Ag NPs showed functional antimicrobial activity against all the microbial contaminants; Salmonella spp. was completely inhibited by Ag NP (50.0 μg/mL) treatment. The Ag NPs have the maximum inhibition zone against Salmonella spp. (14 mm) compared with the Staphylococcus spp. (12.3 mm). The minimum inhibitory concentration (MIC) of Ag NPs against Salmonella spp. and Staphylococcus spp. were 6.25 μg/ mL and 12.5 μg/ mL, respectively. The antibiofilm activity of Ag NPs was the highest at the concentration of 50.0 μg/mL recording 63.3 % for Salmonella spp. and 54.5 % for Staphylococcus spp. Ag NPs may find potent disinfectant applications for household purposes.

Effects of long-term fertilization treatments on the weed seed bank in a wheat-soybean rotation system

Controlling weed populations by manipulating their seed banks is an important weed management option. To assist such efforts, we investigated relationships between fertilization treatments and depth-related characteristics of the weed seed bank (density, species composition and diversity) under a wheat-soybean rotation after long-term (16 years) fertilization. Numbers of weed species present and the Shannon-Wiener index were significantly lower under NPK, NP, NK, and PK fertilization treatments than under the fertilization-free control treatment (CK), and the vertical distribution of dominant species differed under the treatments. Generally, the species richness and Shannon-Wiener index decreased and the Pielou index increased with increases in soil depth, but the relationship of the Simpson index with depth was complex and unclear. The results show that effects of considered fertilization treatments on weeds warrant careful attention, and that PK fertilization would be optimal for suppressing weeds in the wheat-soybean rotation system studied.

Nitrogen and Phosphorus Additions Alter the Abundance of Phosphorus-Solubilizing Bacteria and Phosphatase Activity in Grassland Soils

Microorganisms mobilize phosphorus (P) in soil by solubilizing bound inorganic P from soil minerals and by mineralizing organic P via phosphatase enzymes. Nitrogen (N) inputs are predicted to increase through human activities and shift plants to be more P limited, increasing the importance of P mobilization processes for plant nutrition. We studied how the relative abundance of P-solubilizing bacteria (PSB), PSB community composition, and phosphatase activity respond to N and P addition (+N, +P, +NP) in grassland soils spanning large biogeographic gradients. The studied soils are located in South Africa, USA, and UK and part of a globally coordinated nutrient addition experiment. We show that the abundance of PSB in the topsoil was reduced by 18 % in the N and by 41 % in the NP treatment compared to the control. In contrast, phosphatase activity was significantly higher in the N treatment than in the control across all soils. Soil C:P ratio, sand content, pH, and water-extractable P together explained 71 % of the variance of the abundance of PSB across all study sites and all treatments. Further, the community of PSB in the N and NP addition treatment differed significantly from the control. Taken together, this study shows that N addition reduced the relative abundance of PSB, altered the PSB community, and increased phosphatase activity, whereas P addition had no impact. Increasing atmospheric N deposition may therefore increase mineralization of organic P and decrease solubilization of bound inorganic P, possibly changing P mobilization processes in grassland soils. Consequently, in ecosystems in which plant P nutrition depends on bound inorganic P, increased N inputs might diminish P supply and thus aggravate P limitation and constrain plant productivity.

Coupled macronutrient cycling in stream biofilms: Effects of stoichiometry, light and temperature

Stream biofilms have the capacity to modify the passage of macronutrients through catchments as they respond to nutrient compositions and ratios from different sources. Knowledge of coupled cycling of N, P and organic C in flowing freshwaters is essential to understanding and predicting aquatic ecosystems responses to environmental change comprising multiple chemical and physical stressors. Colonisation on nutrient diffusing substrates (glucose-C, inorganic NP, combined CNP and control applied in-situ in an oligotrophic, upland stream) led to biofilms differing in community and element compositions. The 72 biofilms were transferred to replicated recirculating water chambers (1 L volume) for 4-days where additional effects of light and temperature treatments were investigated on nutrient exchange with the water column. Chemical (nutrient analyses, 13C, 15N tracing, stoichiometry) and biological (chlorophyll, TRFLP) analyses were performed to understand the biofilm composition changes and interaction with the water column. Biofilms combining C with NP incorporated more N and P relative to controls than did those with NP alone. During the chamber phase C-treated biofilms resulted in lower water column N, P concentrations with CNP relative to NP treatments. The effects of the light and temperature were manifested mainly in impaired net nutrient uptake at temperature deviating from ambient stream temperatures. The effects of organic C on N, P cycling (and vice-versa) in mixed biofilms and their interaction with waters is a developing field. Combining in-stream and chamber tests has shown potential for studying in controlled and replicated systems such complex interactions.

Apatinib-loaded nanoparticles inhibit tumor growth and angiogenesis in a model of melanoma

Anti-angiogenic drugs are an effective therapeutic method for the treatment of melanomas. Apatinib is a small-molecule tyrosine kinase inhibitor, which has potent inhibitory activity on tumor angiogenesis. Due to the low water solubility and stability of Apatinib, we aimed to design and develop poly (lactic-co-glycolic acid) (PLGA) and Poloxamer 407 nanoparticles to encapsulate Apatinib (Apa/p NPs) to improve the efficacy of application in melanoma treatment. The size and morphology of the nanoparticles were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro proliferation assays were used to assess the capacity of Apa/p NPs to suppress the growth of B16 cells. Furthermore, we constructed melanoma models using C57BL/6 mice, and preliminary evaluation of the effect and mechanism of Apa/p NPs on tumor inhibition was performed in vivo. The results showed that the size of Apa/p NPs averaged 136 ± 0.27 nm and the nanoparticles were evenly dispersed. Moreover, Apa/p NPs significantly inhibited the growth of B16 cells and melanoma tumors, compared with the naked drug treatment and control groups. The protein levels of VEGFR-2, phosphorylated (p)-VEGFR-2 and p-ERK1/2 in tumor tissues were inhibited by Apa/p NP treatment, as detected by Western blot. The results of this study suggested that Apa/p NPs could inhibit the growth of melanoma tumors by inhibiting the phosphorylation and expression of VEGFR-2 and downstream ERK1/2, providing a theoretical basis for the clinical application of Apatinib in the treatment of melanoma.

P3100Anti-thrombin nanoparticles limit ischemia-reperfusion injury and no-reflow in myocardial infarction

Abstract Introduction Persistent microvascular thrombosis and thrombin signaling in cardiac ischemia reperfusion injury (IRI) combine to promote infarct expansion and heart failure. We have reported previously that treatment of acute ischemic kidney injury (AKI) in rodents with anti-thrombin perfluorocarbon nanoparticles (PFC NP) limits damage to endothelium, reduces “no reflow”, and hastens recovery of kidney function. In cardiac IRI, we hypothesized that thrombin continues to exert deleterious effects well after reperfusion, but whether this strategy is effective in preserving vascular barrier function and preventing no reflow in cardiac IRI is not known. Accordingly, we postulated that sustained local thrombin inhibition with long acting anti-thrombin nanoparticles might limit vascular damage and barrier disruption that otherwise leads to hemorrhage and no reflow. Methods 14 Sprague Dawley rats undergoing LAD occlusion for 45 min were pretreated with i.v. injection of anti-thrombin PPACK (D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone)-conjugated PFC NP (∼13,000 PPACK per PFC NP), or saline (control) followed by 2 hours of reperfusion. Sham controls (no LAD ligation) were compared. Simultaneous to treatments, a different and unique nontargeted CE PFC NP (CE: Crown Ether core) was injected for subsequent tracking and spectroscopic quantification of the relative distributions and amounts of PFC NP trapped in non-reperfused myocardium. Hearts were perfused with saline in situ, then extracted for ex vivo 19F (fluorine) MRI and spectroscopy at 7T (Bruker). T2* images were acquired for hemorrhage/edema in the area at risk. 19F MRI was acquired for PFC NP trapping (spin echo: TR 2000ms, TE 4.51 ms, FOV 20x20, 64x64 slice 1mm), along with whole heart 19PFC CE spectroscopy. Results Fluorine MRI of an intact heart illustrates the trapping of PFC NP in areas of nonreperfusion (Figure) amidst infarct scar region. Quantification of total heart CE PFC NP signal emanating from trapped NP revealed reduced accumulation (−49%) in the hearts of treated rats (0.47±0.09 vs 0.92±0.19, treated vs control; p&lt;0.05). For sham occlusions, minimal deposition of CE PFC NP was observed irrespective of PPACK PFC NP treatment (n=10 per group). Areas of T2* signal indicative of vascular leakage extended beyond that of the 19F signals (Figure T2*), indicating more severe damage and trapping in central infarct zones than in more peripheral border zones after 2 hours. Discussion Continued inhibition of thrombin in cardiac IRI with locally-acting PPACK PFC NP preserved vascular integrity, and limited hemorrhage and No Reflow (less trapping). Because these PPACK PFC NP do not prolong bleeding times or coagulation parameters beyond ∼30–60 min after injection, yet maintain prolonged local surveillance against activated thrombin, they represent a potentially useful therapeutic strategy for cardiac IRI.

Effect of Increased Influent COD on Relieving the Toxicity of CeO2 NPs on Aerobic Granular Sludge.

Due to the increased use of cerium oxide nanoparticles (CeO2 NPs), their potential environmental risks have caused concern. However, their effects on the aerobic granular sludge (AGS) process and the later recovery of AGS are still unclear. In this study, we comprehensively determined the changes in pollutant removal and the levels of extracellular polymeric substances (EPS) in AGS that were exposed to CeO2 NP treatments (0 (the control, R0), 1 (R1), and 5 (R5) mg/L), following an increase in the influent chemical oxygen demand (COD). An increase in the CeO2 NP concentration enhanced their inhibitory effect on the removal of total nitrogen (TN) and total phosphorus (TP), and promoted the production of polysaccharides (PS) and proteins (PN) in loosely bound EPS (LB-EPS) or tightly bound EPS (TB-EPS), as well as the dissolved organic carbon (DOC) components in EPS, but had no long-term effects on the removal of organic matter. When the addition of CeO2 NPs was stopped and the concentration of influent COD increased, the TN and TP removal efficiencies in R1 and R5 slowly increased and recovered. In R1, they were only 4.55 ± 0.55% and 2.71 ± 0.58% lower than in R0, respectively, while the corresponding values for R5 were 5.06 ± 0.46% and 6.20 ± 0.63%. Despite the LB-EPS and TB-EPS concentrations in the R1 and R5 treatments recovering and being similar to the levels in the control when no CeO2 NPs were added, they were still slightly higher than in the R0, which indicating that the negative effects of CeO2 NPs could not be completely eliminated due to the residual CeO2 NP levels in AGS.

The Toxicity of Nonaged and Aged Coated Silver Nanoparticles to Freshwater Alga Raphidocelis subcapitata.

The transformation of coated silver nanoparticles (AgNPs) and their impacts on aquatic organisms require further study. The present study investigated the role of aging on the transformation of differently coated AgNPs and their sublethal effects on the freshwater alga Raphidocelis subcapitata. The stability of AgNPs was evaluated over 32 d, and the results indicated that transformation of AgNPs occurred during the incubation; however, coating-specific effects were observed. Fresh AgNPs increased reactive oxygen species (ROS) formation, whereas aged AgNPs induced excessive ROS generation compared with their fresh counterparts. Increased ROS levels caused increased lipid peroxidation (LPO) in treatment groups exposed to both fresh and aged NPs, although LPO was comparatively higher in algae exposed to aged AgNPs. The observed increase in catalase (CAT) activity of algal cells was attributed to early stress responses induced by excessive intracellular ROS generation, and CAT levels were higher in the aged NP treatment groups. In conclusion, AgNPs increased ROS levels and LPO in algae and caused the activation of antioxidant enzymes such as CAT. Overall, the results suggest that aging and coating of AgNPs have major impacts on AgNP transformation in media and their effects on algae. Environ Toxicol Chem 2019;38:2371-2382. © 2019 SETAC.

Effect Of Bevacizumab On Growth Of Human Nasal Polyposis In Vitro; An Off-Label Use Of Anti-Angiogenic Agent For Nasal Polyposis Treatment.

IntroductionNasal polyposis (NP) is a frequent problem during adulthood. Treatment of NP is primarily based on drugs, such as oral or topical steroids and in some types, by surgery. Despite of available therapeutic options for NP, recurrence after polypectomy is found. Vascular endothelial growth factor (VEGF) is a known factor involved in NP. Bevacizumab is a monoclonal antibody, which acts against VEGF.AimRegarding the availability of bevacizumab and its use in ophthalmic off-label application, in this study, we hypothesized that it could be a choice of non-invasive treatment. The researchers aimed at evaluating the use of bevacizumab in vitro on the growth of NP.Materials and methodsIn this experimental study, the researchers used eight non-allergic NP tissues from patients admitted for polypectomy clinic of Imam Reza Hospital, Mashhad. Tissues were cultured in DMEM medium based on standard protocols in the presence or absence of bevacizumab (10 to 250 μM) then incubated. The mean of the responses was reported. The level of VEGF and MTT test for NP epithelial cell viability were determined for each group. Data were analyzed using the SPSS software.ResultsThe researchers demonstrated that bevacizumab leads to a decrease in the level of VEGF (the most common cause of angiogenesis in NP) in media culture of NP, dose-dependently (P<0.001). The highest mean was related to the 10-μM group and the least mean was related to the 250-μM group. In MTT test after 5 days, it was shown that the percentage of viable epithelial NP cells (due to apoptosis) was decreased dose-dependently and could lead to resolving NP tissue (P<0.001), significantly.ConclusionThis study showed that bevacizumab could help decrease the growth of NP tissue dose-dependently in organ culture in vitro by inhibiting VEGF. It seems that bevacizumab could be a good candidate for the treatment of non-allergic NP.