• Dall Clay posted an update 4 hours, 32 minutes ago

    Overall, RUNX1-IT1 is a crucial oncogenic lncRNA that activates C-FOS expression by regulating and recruiting RUNX1 and is a potential prognostic biomarker and therapeutic target for PC.The fovea undergoes significant developmental changes from birth into adolescence. However, there is limited data examining cone photoreceptor density, foveal pit shape, and foveal avascular zone (FAZ) size in children. Irbinitinib The purpose of this study was to determine whether overall foveal structure differs as a function of age and refractive status in children. Forty-eight healthy children (ages 5.8 to 15.8 years) underwent optical coherence tomography imaging to quantify foveal point thickness and foveal pit diameter, depth, and slope. Adaptive optics scanning laser ophthalmoscope (AOSLO) images of foveal capillaries and cone photoreceptors were acquired in a subset of children to quantify FAZ metrics and cone densities at 0.2, 0.3, and 0.5 mm eccentricities. Results show that foveal pit and FAZ metrics were not related to age, axial length, or refractive status. However, linear cone density was lower in myopic versus non-myopic children at eccentricities of 0.2 mm (mean ± SD = 50,022 ± 5,878 cones/mm2 vs 58,989ic children have lower linear cone densities close to the foveal center compared to non-myopic children.Acute chest syndrome (ACS) is a significant cause of morbidity and mortality in sickle cell disease (SCD), but preventive, diagnostic, and therapeutic options are limited. Further, ACS and acute vasoccclusive pain crises (VOC) have overlapping features, which causes diagnostic dilemmas. We explored changes in gene expression profiles among patients with SCD hospitalized for VOC and ACS episodes to better understand ACS disease pathogenesis. Whole blood RNA-Seq was performed for 20 samples from children with SCD at baseline and during a hospitalization for either an ACS (n = 10) or a VOC episode (n = 10). Respiratory viruses were identified from nasopharyngeal swabs. Functional gene analyses were performed using modular repertoires, IPA, Gene Ontology, and NetworkAnalyst 3.0. The VOC group had a numerically higher percentage of female, older, and hemoglobin SS participants compared to the ACS group. Viruses were detected in 50% of ACS cases and 20% of VOC cases. We identified 3004 transcripts that were differentially expressed during ACS episodes, and 1802 transcripts during VOC episodes. Top canonical pathways during ACS episodes were related to interferon signaling, neuro-inflammation, pattern recognition receptors, and macrophages. Top canonical pathways in patients with VOC included IL-10 signaling, iNOS signaling, IL-6 signaling, and B cell signaling. Several genes related to antimicrobial function were down-regulated during ACS compared to VOC. Gene enrichment nodal interactions demonstrated significantly altered pathways during ACS and VOC. A complex network of changes in innate and adaptive immune gene expression were identified during both ACS and VOC episodes. These results provide unique insights into changes during acute events in children with SCD.Poor access to human left ventricular myocardium is a significant limitation in the study of heart failure (HF). Here, we utilise a carefully procured large human heart biobank of cryopreserved left ventricular myocardium to obtain direct molecular insights into ischaemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), the most common causes of HF worldwide. We perform unbiased, deep proteomic and metabolomic analyses of 51 left ventricular (LV) samples from 44 cryopreserved human ICM and DCM hearts, compared to age-, gender-, and BMI-matched, histopathologically normal, donor controls. We report a dramatic reduction in serum amyloid A1 protein in ICM hearts, perturbed thyroid hormone signalling pathways and significant reductions in oxidoreductase co-factor riboflavin-5-monophosphate and glycolytic intermediate fructose-6-phosphate in both; unveil gender-specific changes in HF, including nitric oxide-related arginine metabolism, mitochondrial substrates, and X chromosome-linked protein and metabolite changes; and provide an interactive online application as a publicly-available resource.Plasmodium vivax is the most widely distributed human malaria parasite. Previous studies have shown that circulating microparticles during P. vivax acute attacks are indirectly associated with severity. Extracellular vesicles (EVs) are therefore major components of circulating plasma holding insights into pathological processes. Here, we demonstrate that plasma-derived EVs from Plasmodium vivax patients (PvEVs) are preferentially uptaken by human spleen fibroblasts (hSFs) as compared to the uptake of EVs from healthy individuals. Moreover, this uptake induces specific upregulation of ICAM-1 associated with the translocation of NF-kB to the nucleus. After this uptake, P. vivax-infected reticulocytes obtained from patients show specific adhesion properties to hSFs, reversed by inhibiting NF-kB translocation to the nucleus. Together, these data provide physiological EV-based insights into the mechanisms of human malaria pathology and support the existence of P. vivax-adherent parasite subpopulations in the microvasculature of the human spleen.Cardiac constructs fabricated using human induced pluripotent stem cells-derived cardiomyocytes (iPSCs-CMs) are useful for evaluating the cardiotoxicity of and cardiac response to new drugs. Previously, we fabricated scaffold-free three-dimensional (3D) tubular cardiac constructs using a bio-3D printer, which can load cardiac spheroids onto a needle array. In this study, we developed a method to measure the contractile force and to evaluate the drug response in cardiac constructs. Specifically, we measured the movement of the needle tip upon contraction of the cardiac constructs on the needle array. The contractile force and beating rate of the cardiac constructs were evaluated by analysing changes in the movement of the needle tip. To evaluate the drug response, contractile properties were measured following treatment with isoproterenol, propranolol, or blebbistatin, in which the movement of the needle tip was increased following isoproterenol treatment, but was decreased following propranolol or blebbistain, treatments.