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Understanding the pathophysiology of thrombotic microangiopathy associated with snake envenoming may lead to emerging therapeutic strategies.The aim of this study is to prepare and characterize an amino-dextran nanoparticle (aDNP) platform and investigate two loading strategies for unmethylated cytosine-phosphate-guanine (CpG) oligonucleotide. aDNP was prepared by desolvation of amino-dextran followed by the chemical crosslinking of amino groups. Size, surface charge, and surface morphology of aDNP was determined by dynamic light scattering and transmission electron microscopy. CpG was either loaded onto aDNP by adsorption (CpG-adsorbed-aDNP) or conjugated to aDNP (CpG-conjugated-aDNP). In vitro cytokine production by bone marrow-derived dendritic cells (BMDCs) was measured by flow cytometry. aDNPs size and zeta potential could be controlled to produce uniform particles in the size range of 50 to 300 nm, surface charge of -16.5 to +14 mV, and were spherical in shape. Formulation control parameters investigated included the anti-solvent, water-to-anti-solvent ratio, level of amine functionality of dextran, and the molar ratio of glutaraldehyde to amine. aDNP could be lyophilized without additional cryoprotectant. Unloaded cationic aDNP (+13 mV) showed acceptable in vitro hemolysis. Unloaded and CpG-loaded aDNPs showed no cytotoxicity on BMDCs. CpG-loaded nanoparticles stimulated cytokine production by BMDCs, the level of cytokine production was higher for CpG-conjugated-aDNP compared to CpG-absorbed-aDNP. aDNP is a promising new drug delivery platform as its offers versatility in loading and tuning of particle properties.Background A wide range of cystic fibrosis (CF)-related conditions are reported in CF carriers, but no study has explored the possibility that such subjects may be affected by cystic fibrosis transmembrane regulator-related disorders (CFTR-RD). No data are available so far on the occurrence of CFTR-RD among CF carriers. Selleck Y-27632 Methods We studied 706 CF carriers-first- and second-degree relatives of CF patients that carried the parental mutation; such subjects were divided in two groups a first group (353 subjects, group A) performed at first only the analysis of the CFTR proband mutation; we retrospectively evaluated the number of cases that had been diagnosed as CFTR-RD based on subsequent symptoms; a second group (353 subjects, group B) performed extensive CFTR molecular analysis in absence of any reported symptoms, followed by a clinical evaluation in cases that carry a second CFTR mutation; we evaluated the number of cases that prospectively were diagnosed as CFTR-RD. Results We found seven (2.0%) out of 353 subjects of group A and 24 (6.8%) out of 353 subjects of group B as affected by CFTR-RD (chi square, p = 0.002). Conclusions A percentage of CF carriers are affected by undiagnosed CFTR-RD. Genetic tasting scanning analysis helps to identify CFTR-RD, some of which may benefit from follow-up and specific therapies improving their outcome.Biliary atresia (BA) is a destructive inflammatory obliterative cholangiopathy of the neonate that affects various parts of the bile duct. If early diagnosis followed by Kasai portoenterostomy is not performed, progressive liver cirrhosis frequently leads to liver transplantation in the early stage of life. Therefore, prompt diagnosis is necessary for the rescue of BA patients. However, the prompt diagnosis of BA remains challenging because specific and reliable biomarkers for BA are currently unavailable. In this study, we discovered potential biomarkers for BA using deep proteome analysis by data-independent acquisition mass spectrometry (DIA-MS). Four patients with BA and three patients with neonatal cholestasis of other etiologies (non-BA) were recruited for stool proteome analysis. Among the 2110 host-derived proteins detected in their stools, 49 proteins were significantly higher in patients with BA and 54 proteins were significantly lower. These varying stool protein levels in infants with BA can provide potential biomarkers for BA. As demonstrated in this study, the deep proteome analysis of stools has great potential not only in detecting new stool biomarkers for BA but also in elucidating the pathophysiology of BA and other pediatric diseases, especially in the field of pediatric gastroenterology.Wheat bran consumption is associated with several health benefits, but its incorporation into food products remains low because of sensory and technofunctional issues. Besides, its full beneficial potential is probably not achieved because of its recalcitrant nature and inaccessible structure. Particle size reduction can affect both technofunctional and nutrition-related properties. Therefore, in this study, wet milling and cryogenic milling, two techniques that showed potential for extreme particle size reduction, were used. The effect of the milling techniques, performed on laboratory and large scale, was evaluated on the structure and physicochemical properties of wheat bran. With a median particle size (d50) of 6 µm, the smallest particle size was achieved with cryogenic milling on a laboratory scale. Cryogenic milling on a large scale and wet milling on laboratory and large scale resulted in a particle size reduction to a d50 of 28-38 µm. In the milled samples, the wheat bran structure was broken down, and almost all cells were opened. Wet milling on laboratory and large scale resulted in bran with a more porous structure, a larger surface area and a higher capacity for binding water compared to cryogenic milling on a large scale. The extensive particle size reduction by cryogenic milling on a laboratory scale resulted in wheat bran with the highest surface area and strong water retention capacity. Endogenous enzyme activity and mechanical breakdown during the different milling procedures resulted in different extents of breakdown of starch, sucrose, β-glucan, arabinoxylan and phytate. Therefore, the diverse impact of the milling techniques on the physicochemical properties of wheat bran could be used to target different technofunctional and health-related properties.Objective and subjective health generally have a positive relationship, although their association may be moderated by factors such as gender and personality. We aimed to analyze the association between personality and objective (metabolic syndrome (MetS)) and subjective-physical health in older men and women. For this purpose, in 138 participants (53.6% women, Mage = 66.85), neuroticism, conscientiousness, extraversion, openness, and agreeableness (NEO Five Factor Inventory), subjective-physical health (Short Form Health Survey, SF-36), and MetS (employing waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and glycated hemoglobin) were assessed. Logistic regression analysis was performed to analyze whether personality was associated with MetS. Moreover, hierarchical regression analyses were conducted to analyze the relationship between personality or MetS, and subjective-physical health. Finally, gender and personality moderation analyses were performed with PROCESS. Results showed that higher neuroticism was associated with an increased likelihood of MetS, whereas higher neuroticism and lower extraversion were associated with lower subjective-physical health.

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