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Plaque angiogenesis and plaque hemorrhage are major players in the destabilization and rupture of atherosclerotic lesions. As these are dynamic processes, imaging of plaque angiogenesis, especially the integrity or leakiness of angiogenic vessels, can be an extremely useful tool in the studies on atherosclerosis pathophysiology. Visualizing plaque microvessels in 3D would enable us to study the architecture and permeability of adventitial and intimal plaque microvessels in advanced atherosclerotic lesions. We hypothesized that a comparison of the vascular permeability between healthy continuous and fenestrated as well as diseased leaky microvessels, would allow us to evaluate plaque microvessel leakiness. We developed and validated a two photon intravital microscopy (2P-IVM) method to assess the leakiness of plaque microvessels in murine atherosclerosis-prone ApoE3*Leiden vein grafts based on the quantification of fluorescent-dextrans extravasation in real-time. We describe a novel 2P-IVM set up to study vessels in the neck region of living mice. We show that microvessels in vein graft lesions are in their pathological state more permeable in comparison with healthy continuous and fenestrated microvessels. This 2P-IVM method is a promising approach to assess plaque angiogenesis and leakiness. Moreover, this method is an important advancement to validate therapeutic angiogenic interventions in preclinical atherosclerosis models.The potential beneficial effects of the antioxidant properties of vitamin C have been investigated in a number of pathological conditions. In this review, we assess both clinical and preclinical studies evaluating the role of vitamin C in cardiac and vascular disorders, including coronary heart disease, heart failure, hypertension, and cerebrovascular diseases. Pitfalls and controversies in investigations on vitamin C and cardiovascular disorders are also discussed.Background-Elevated circulating fatty-acid-binding protein 4 (FABP4) levels may be linked with cardiovascular events. This study aimed to investigate the mechanistic role of FABP4 in atherosclerosis. Methods-We recruited 22 patients with angiographically proven coronary artery disease (CAD) and 40 control subjects. Mononuclear cells (MNCs) and human coronary endothelial cells (HCAECs) were used for in vitro study. Results-Patients with CAD were predominantly male with an enhanced prevalence of hypertension, diabetes, and smoking history. FABP4 concentrations were up-regulated in culture supernatants of MNCs from CAD patients, which were positively correlated with the patients' age, waist-hip ratio, body mass index, serum creatinine, type 2 diabetes, and the presence of hypertension. The adhesiveness of HCAECs to monocytic cells can be activated by FABP4, which was reversed by an FABP4 antibody. FABP4 blockade attenuated the oxidized low-density lipoprotein (oxLDL)-induced expression of ICAM-1, VCAM-1, and P-selectin. FABP4 impaired the tube formation and migration via the ERK/JNK/STAT-1 signaling pathway. FABP4 suppressed phosphorylation of eNOS and expression of SDF-1 protein, both of which can be reversed by treatment with VEGF. Blockade of FABP4 also improved the oxLDL-impaired cell function. Conclusion-We discovered a novel pathogenic role of FABP4 in MNC activation and endothelial dysfunction in atherosclerosis. FABP4 may be a therapeutic target for modulating atherosclerosis.Bovine rotavirus A (RVA), a major causative pathogen of diarrhea in dairy and Japanese beef calves, has led to severe economic losses in numerous countries. A dual genotyping system based on genomic segments encoding VP7 (G genotype) and VP4 (P genotype), comprising the outer layer of the virion, has been used to understand the epidemiological dynamics of RVAs at the national and global levels. This study aimed to investigate occurrence frequency of G and P genotypes for multiple bovine RVAs from calf diarrheic samples collected in Japan from 2017 to 2020. After we produced anti-bovine RVA immunoglobulin yolks (IgYs) from hens immunized with the two RVAs with different genotypes (G6P[5] and G10P[11]) selected on the basis of the current epidemiological survey, we investigated cross-reactivity against bovine RVAs with different G and P combinations owing to establish a useful strategy to protect calves from RVA infections using the two IgYs. Consequently, the two produced anti-bovine IgYs showed strong cross-reactivity against bovine RVAs with the same G and/or P genotypes in neutralization assay, respectively. Therefore, our data suggest the possibility of a passive immunization to protect calves from a bovine RVA infections epidemic in Japan via oral administration of the two IgYs into calves. The findings presented herein will provide important information that IgY is one of the effective tools to prevent infections of various pathogens.The demand of platelet transfusions is steadily growing worldwide, inter-donor variation, donor dependency, or storability/viability being the main contributing factors to the current global, donor-dependent platelet concentrate shortage concern. In vitro platelet production has been proposed as a plausible alternative to cover, at least partially, the increasing demand. However, in practice, such a logical production strategy does not lack complexity, and hence, efforts are focused internationally on developing large scale industrial methods and technologies to provide efficient, viable, and functional platelet production. This would allow obtaining not only sufficient numbers of platelets but also functional ones fit for all clinical purposes and civil scenarios. In this review, we cover the evolution around the in vitro culture and differentiation of megakaryocytes into platelets, the progress made thus far to bring the culture concept from basic research towards good manufacturing practices certified production, and subsequent clinical trial studies. However, little is known about how these in vitro products should be stored or whether any safety measure should be implemented (e.g., pathogen reduction technology), as well as their quality assessment (how to isolate platelets from the rest of the culture cells, debris, microvesicles, or what their molecular and functional profile is). Importantly, we highlight how the scientific community has overcome the old dogmas and how the new perspectives influence the future of platelet-based therapy for transfusion purposes.

Disordered eating behaviors (DEBs), including diagnosable eating disorders, are quite common and can interfere with optimal type 1 diabetes (T1DM) management. We explored DEBs prevalence in youth with T1DM, proposing news diagnostic subscales, to represent the clinical dimensions associated with feeding and eating disorders (ED); Methods additionally to SCOFF questionnaire and Diabetes Eating Problem Survey-Revised (DEPS-R), four subscales combined from the original DEPS-R questionnaire were administered to 40 youths with T1DM (15.0 ± 2.6); Results females showed higher scores than males in DEPS-R original factor 2 ("preoccupations with thinness/weight",

= 0.024) and in DEPS-R proposed "restriction" factor (

= 0.009). SCOFF scores was correlated with original DEPS-R factors 1 ("maladaptive eating habits") and 2 (

< 0.001) and with the newly proposed DEPS-R factors restriction, disinhibition, compensatory behaviors, diabetes management (all

< 0.02). Diabetes management was the only factor relpment target specific questionnaires to be used as screening tools to detect cases of DEBs and exclude non cases. Early recognition of DEBs in adolescents with T1DM is essential for effective prevention and successful treatment.Gel is a two-phase elastic colloidal material, consisting of a dispersed liquid incorporated in the solid phase [...].Plantain (Plantago lanceolata) and chicory (Cichorium intybus) are now widely used in combination with clover species to provide greater annual lamb live weight gains than perennial ryegrass and white clover pasture. Reported selective grazing of the species in herb-clover mixes could potentially detrimentally change the relative abundance of species and decrease lamb production. Lambs were offered three herbage treatments Pasture (perennial ryegrass and white clover) mix, plantain (plantain, red clover and white clover) mix and a chicory (chicory, plantain, red clover and white clover) mix in each of four seasons for two years. The experiment was a randomized complete block design with three replicates with 18-30 lambs per treatment replicate depending on the season. Lambs were rotationally grazed and fed ad libitum. Selection by the lambs of individually tagged plants within the pasture treatments was observed for three days on two occasions per season. Red clover was the most selected species on day 1, but by day 3 there was no difference in the selection of the species (p less then 0.05). Plantain and chicory in the plantain and chicory mixes were selected less on day 1 in autumn relative to the other seasons (p less then 0.05). It was concluded that three days of grazing before moving lambs maintained the relative abundance of species in the herb-clover mixes.Patients with extensive-stage small cell lung cancer (ED-SCLC) have a very short survival time even if they receive standard cytotoxic chemotherapy with etoposide and platinum (EP). Several randomized controlled trials have shown that patients with ED-SCLC who received a combination of EP plus immune checkpoint inhibitors (ICIs) had superior survival compared with those who received EP alone. We conducted a systematic review and network meta-analysis to provide a ranking of ICIs for our primary endpoints in terms of overall survival (OS), progression free survival (PFS), and objective response rate (ORR), as well as our secondary endpoint in terms of adverse events. The fractional polynomial model was used to evaluate the adjusted hazard ratios for the survival indicators (OS and PFS). Treatment rank was estimated using the surface under the cumulative ranking curve (SUCRA), as well as the probability of being best (Prbest) reference. EP plus nivolumab, atezolizumab or durvalumab had significant benefits comp meta-analysis. Further head-to head large-scale phase III randomized controlled studies are needed to verify our conclusions.Scaffolds play an essential role in the success of tissue engineering approaches. Their intrinsic properties are known to influence cellular processes such as adhesion, proliferation and differentiation. Hydrogel-based matrices are attractive scaffolds due to their high-water content resembling the native extracellular matrix. In addition, polymer-based magnetoelectric materials have demonstrated suitable bioactivity, allowing to provide magnetically and mechanically activated biophysical electrical stimuli capable of improving cellular processes. The present work reports on a responsive scaffold based on poly (L-lactic acid) (PLLA) microspheres and magnetic microsphere nanocomposites composed of PLLA and magnetostrictive cobalt ferrites (CoFe2O4), combined with a hydrogel matrix, which mimics the tissue's hydrated environment and acts as a support matrix. For cell proliferation evaluation, two different cell culture conditions (2D and 3D matrices) and two different strategies, static and dynamic culture, were applied in order to evaluate the influence of extracellular matrix-like confinement and the magnetoelectric/magneto-mechanical effect on cellular behavior.

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