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Oxidative stress, which is one of the main harmful mechanisms of pathologies including ischemic stroke, contributes to both neurons and endothelial cell damages, leading to vascular lesions. Although many antioxidants are tested in preclinical studies, no treatment is currently available for stroke patients. Since cerium oxide nanoparticles (CNPs) exhibit remarkable antioxidant capacities, the objective is to develop an innovative coating to enhance CNPs biocompatibility without disrupting their antioxidant capacities or enhance their toxicity. This study reports the synthesis and characterization of functional polymers and their impact on the enzyme-like catalytic activity of CNPs. To study the toxicity and the antioxidant properties of CNPs for stroke and particularly endothelial damages, in vitro studies are conducted on a cerebral endothelial cell line (bEnd.3). Despite their internalization in bEnd.3 cells, coated CNPs are devoid of cytotoxicity. Microscopy studies report an intracellular localization of CNPs, more precisely in endosomes. 3PO All CNPs reduces glutamate-induced intracellular production of reactive oxygen species (ROS) in endothelial cells but one CNP significantly reduces both the production of mitochondrial superoxide anion and DNA oxidation. In vivo studies report a lack of toxicity in mice. This study therefore describes and identifies biocompatible CNPs with interesting antioxidant properties for ischemic stroke and related pathologies.

This study aimed to quantify the amount of silicone oil (SO) released across a variety of syringe and needle models routinely used for intravitreal injection.

The release of SO was assessed in eight models of syringes, two of which were reported to be 'SO-free', and eleven models of needles with unknown SO content. To evaluate SO release within the context of anti-VEGF therapeutics, syringes were evaluated using aflibercept, bevacizumab, buffer, ziv-aflibercept and formulation buffer. All syringe tests were performed with or without agitation by flicking for syringes. Needles were evaluated without agitation only. Samples were fluorescently labelled to identify SO, and triplicate measurements were collected using imaging flow cytometry.

Seven out of 8 syringe models showed a statistically significant increase in the SO particle count after agitation. The two SO-free syringe models (HSW Norm-Ject, Daikyo Crystal Zenith) released the least SO particles, with or without agitation, whereas the BD Ultra-Fine and Saldanha-Rodrigues syringes released the most. More SO was released when the syringes were prefilled with formulation buffer than with ziv-aflibercept. Syringes filled with aflibercept and bevacizumab had intermediate levels. Agitation increased the release of SO into each of the drug solutions. Silicone oil (SO) was detected in all needles.

Agitation of the syringe by flicking leads to a substantial increase in the number of SO particles. Silicone oil (SO)-free syringes had the best performance, but physicians must also be aware that needles are siliconized and also contribute to the injection of SO into the vitreous.

Agitation of the syringe by flicking leads to a substantial increase in the number of SO particles. Silicone oil (SO)-free syringes had the best performance, but physicians must also be aware that needles are siliconized and also contribute to the injection of SO into the vitreous.

Immunoglobulin A vasculitis (IgAV) is classified as a leukocytoclastic vasculitis characterized by immune deposits in endothelial walls of small vessels causing vascular endothelial injury. The aim of the present study is to evaluate levels of vascular endothelial growth factor-A (VEGF-A) and VEGF receptor-1 (VEGFR-1) levels in adult IgAV patients.

Thirty-seven adult IgAV patients admitted to the Rheumatology Clinic meeting the IgAV American College of Rheumatology (ACR) criteria and 32 control subjects were enrolled in the study. Disease activity was categorized as "remission" or "active" according to Birmingham Vasculitis Activity Score (BVAS). Serum VEGF-A, VEGFR-1 levels and VEGFR-1/VEGF-A ratio were evaluated in patient and control groups.

Serum median VEGF-A, VEGFR-1 and VEGFR-1/VEGF-A ratios were significantly higher in the patient group when compared to controls (235.9 [155-308.4] pg/mL vs. 78.8 [29.7-210.3] pg/mL, 400 [277.2-724.3] pg/mL vs. 31.5 [12.5-214.4] pg/mL and 1.85 [0.57-2.97] vs. 0.46 [0.38-0.63] respectively, all P values <.001). VEGFR-1 had the strongest predictive value with a cut-off value of 0.6 with 75% sensitivity and 73% specificity (P<.001).

This study is the first report indicating elevated serum VEGF-A, VEGFR-1, and more importantly VEGFR-1/VEGF-A ratio can be good representatives of the inflammatory processes together with vascular endothelial injury in adult IgAV patients. VEGFR-1 seems to be a more important indicator of the ongoing inflammation.

This study is the first report indicating elevated serum VEGF-A, VEGFR-1, and more importantly VEGFR-1/VEGF-A ratio can be good representatives of the inflammatory processes together with vascular endothelial injury in adult IgAV patients. VEGFR-1 seems to be a more important indicator of the ongoing inflammation.Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is causally related to fibrotic diseases, including idiopathic pulmonary fibrosis. The identification of Compounds that interfere with the HSP47-collagen interaction is essential for the development of relevant therapeutics. Herein, we prepared human HSP47 as a soluble fusion protein expressed in E. coli and established an assay system for HSP47 inhibitor screening. We screened a natural and synthetic Compound library established at Nagasaki University. Among 1023 Compounds, 13 exhibited inhibitory activity against human HSP47, of which three inhibited its function in a dose-dependent manner. Epigallocatechin-3-O-gallate, one of these three Compounds, is a typical polyphenol Compound derived from tea leaves. Structurally related Compounds were synthesized and examined for their activity, revealing a hydroxyl group at A-ring position 5 as important for its activity. The present findings provide valuable insight for the development of natural product-derived therapeutics for fibrotic diseases, including idiopathic pulmonary fibrosis.Amylin (hIAPP) amyloid formation plays an important role in the pathogenesis of type 2 diabetes (T2D), which makes it a promising therapeutic target for T2D. In this study, we established a screening tool for identifying chemicals affecting hIAPP amyloid formation based on a reported genetic tool, which constantly tracks protein aggregates in Saccharomyces cerevisiae. In order to obtain the hIAPP with better aggregation ability, the gene of hIAPP was tandemly ligated to create 1×, 2×, 4× or 6×-hIAPP expressing strains. By measuring the cell density and fluorescence intensity of green fluorescent protein (GFP) regulated by the aggregation status of hIAPP, it was found that four intramolecular ligated hIAPP (4×hIAPP) could form obvious amyloids with mild toxicity. The validity and reliability of the screening tool were verified by testing six reported hIAPP inhibitors, including curcumin, epigallocatechin gallate and so on. Combined with surface plasmon resonance (SPR) and the screening tool, which could be a screening system for hIAPP inhibitors, we found that crocin specifically binds to hIAPP and acts inhibit amyloid formation of hIAPP. The effect of crocin was further confirmed by Thioflavin T (ThT) fluorescence and transmission electron microscopy (TEM) analysis. Thus, a screening system for hIAPP amyloid inhibitors and a new mechanism of crocin on anti-T2D were obtained as a result of this study.HLA-C*07944 differs from HLA-C*07010101 by one nucleotide substitution in codon 325 in exon 6.

Children receiving intensive chemotherapy for leukemia or undergoing hematopoietic stem cell transplant (HSCT) for solid tumors or leukemia are at risk for musculoskeletal (MSK) impairment from their underlying disease and from treatment. Data are limited on the incidence and nature of these disorders during intensive therapy. This study's objective was to provide a cross-sectional description of MSK impairments in this population.

Children with acute myeloid leukemia (AML), relapsed acute lymphoblastic leukemia (rALL), or undergoing HSCT were systematically assessed for MSK impairments as part of Children's Oncology Group study ACCL0934. Assessments occurred at study entry, at 2months, and at 12months and included evaluation for signs or symptoms of MSK impairment and the type, site, and diagnosis.

Six hundred three patients were included. MSK signs or symptoms were present in 48 (8.0%) children at study entry, 64 (13.5%) children at 2months, and 40 (11.6%) children at 12months. Arthralgia and/or gait abnormalities were the most common impairments; the knee was the most common site. Arthritis and tendonitis were both rare. Vincristine neuropathy, MSK impacts from central nervous system pathology, and bone or joint pain from underlying cancer were the most common diagnoses. Multivariate analysis demonstrated that having rALL (odds ratio [OR] 2.00, 95% CI 1.07-3.76, p=.03) or obesity (OR 2.10, 95% CI 1.12-3.95, p=.02) were risk factors for MSK impairment at study entry.

MSK impairments are common in this intensively treated patient population, especially in those with rALL and those who are obese.

MSK impairments are common in this intensively treated patient population, especially in those with rALL and those who are obese.Pheromone-binding proteins (PBPs) have been extensively investigated in lepidopteran moths, but their evolution and function in hemipteran species remain unclear. Our previous study demonstrated that an odorant-binding protein, OBP4, of the mirid bug Adelphocoris lineolatus functions as a candidate hemipteran PBP but clustered with lepidopteran antennae-binding proteins (ABPs) rather than in the PBP/general odorant-binding protein (GOBP) clade. In this study, we hypothesized that origin and function of PBPs in hemipteran bugs may differ from those of lepidopteran moths. To test this hypothesis, we first constructed a phylogenetic tree using insect OBPs from sister hemipteran and holometabolous lineages, and the results indicated that neither OBP4 nor other types of candidate PBPs of mirid bugs clustered with the lepidopteran PBP/GOBP clade. Then, a fluorescence competitive binding assay was employed to determine binding affinities of recombinant OBP4 protein to host plant volatiles, with functional groups difdes a novel perspective on evolutionary mechanisms of sex pheromone communication across insect orders.Insect herbivores can regulate their food intake by mixing food sources with different nutrient content, but face the resulting challenge of ingesting various plant secondary metabolites. How insects deal with toxins in a complex nutrient environment is unclear. Here we investigated the influence of a classic plant secondary metabolite, allyl glucosinolate (sinigrin), and its hydrolyzed product allyl isothiocyanate (AITC), on the development of Helicoverpa armigera (Hübner) (Lepidoptera Noctuidae) when fed on diets with different protein-to-carbohydrate (p c) ratios. We also examined the effects of these toxins on larval biochemistry, by chemically analyzing the frass produced by insects feeding on the different diets. As expected, AITC had a greater negative effect than sinigrin on H. armigera life-history traits. However, AITC at low concentration appeared to have a positive effect on some traits. Both sinigrin and AITC-induced detoxification activity in the gut, and the reaction was related to diet protein concentration.