3-hydroxybenzaldehyde (3-HBA) is a precursor compound for phenolic compounds like Protocatechuic aldehyde (PCA). From recent reports, PCA has shown vasculoprotective potency, but the effects of 3-HBA remain unclear. The aim of this study is to investigate the vasculoprotective effects of 3-HBA in endothelial cells, vascular smooth muscle cells and various animal models. We tested effects of 3-HBA in both vitro and vivo. 3-HBA showed that it prevents PDGF-induced vascular smooth muscle cells (VSMCs) migration and proliferation from MTS, BrdU assays and inhibition of AKT phosphorylation. It arrested S and G0/G1 phase of VSMC cell cycle in PI staining and it also showed inhibited expression levels of Rb1 and CD1. In human umbilical vein endothelial cells (HUVECs), 3-HBA inhibited inflammatory markers and signaling molecules (VCAM-1, ICAM-1, p-NF-κB and p-p38). For ex vivo, 3-HBA has shown dramatic effects in suppressing the sprouting from aortic ring of Spargue Dawley (SD) rats. In vivo data supported the vasculoprotective effects of 3-HBA as it inhibited angiogenesis from Matrigel Plug assay in C57BL6 mouse, prevented ADP-induced thrombus generation, increased blood circulation after formation of thrombus, and attenuated neointima formation induced by common carotid artery balloon injury of SD rats. 3-HBA, a novel therapeutic agent, has shown vasculoprotective potency in both in vitro and in vivo.
PurposeIt is often difficult to discriminate focal lymphocytic thyroiditis (FLT) or adenomatous hyperplasia (AH) from thyroid cancer if they both have suspicious ultrasound (US) findings. We aimed to make a predictive model of FLT from papillary thyroid cancer (PTC) in suspicious nodules with benign cytologic results.Materials and MethodsWe evaluated 214 patients who had undergone fine-needle aspiration biopsy (FNAB) and had shown thyroid nodules with suspicious US features. PTC was confirmed by surgical pathology. FLT and AH were confirmed through more than two separate FNABs. Clinical and biochemical findings, as well as US features, were evaluated.ResultsOf 214 patients, 100 patients were diagnosed with PTC, 55 patients with FLT, and 59 patients with AH. The proportion of elevated thyrotropin (TSH) levels (p=0.014) and thyroglobulin antibody (Tg-Ab) or thyroid peroxidase antibody (TPO-Ab) positivity (p<0.001) in the FLT group was significantly higher than that in the PTC group. Regarding US features, absence of calcification (p=0.006) and "diffuse thyroid disease" (DTD) pattern on US (p<0.001) were frequently seen in the FLT group. On multivariate analysis, Tg-Ab positivity, presence of a DTD pattern on US, and absence of calcification in nodules were associated with FLT with the best specificity of 99% and positive predictive value of 96%. In contrast, a taller than wide shape of nodules was the only variable significant for differentiating AH from PTC.ConclusionSuspicious thyroid nodules with cytologic benign results could be followed up with US rather than repeat FNAB, if patients exhibit Tg-Ab positivity, no calcifications in nodules, and a DTD pattern on US.
Objective This study aimed to investigate the long-term effects of aripiprazole treatment during adolescence on behavior, cognitive function, and dopamine D2 receptor (D2R) expression in adult rats. Methods Adolescent male Sprague-Dawley rats were injected intraperitoneally with aripiprazole, risperidone, or vehicle control for 3 weeks (postnatal day 36–56). After a 2-week washout period, locomotion, anxiety, and spatial working memory were evaluated in adulthood (postnatal day 71–84), using an open field test, elevated plus maze, and Y-maze, respectively. In addition, we assessed D2R levels in the dorsolateral and medial prefrontal cortex (PFC), dorsal and ventral striatum, and hippocampus using western blot analysis. Results Spontaneous alternation performance (SAP) in the Y-maze, a measure of spatial working memory, differed significantly among the 3 groups ( F = 3.89, p = 0.033). A post-hoc test confirmed that SAP in the aripiprazole group was significantly higher than that in the risperidone group ( post-hoc test p = 0.013). D2R levels in the medial PFC ( F = 8.72, p = 0.001) and hippocampus ( F = 13.54, p < 0.001) were different among the 3 groups. D2R levels in the medial PFC and hippocampus were significantly lower in the aripiprazole-treated rats than that in the risperidone-treated rats ( post-hoc test p = 0.025 and p < 0.001, respectively) and controls ( post-hoc test p < 0.001, all). Conclusion This study showed that aripiprazole treatment in adolescence could influence cognitive function and dopaminergic neurotransmission into early adulthood.
Moesin-like gene 1 antisense was increased in the postmortem cortex of patients with autism spectrum disorders. Overexpression of moesin-like gene 1 antisense induces downregulation of moesin expression in cortical neurons, resulting in decreased neurite numbers and length. However, moesin knockout (KO) mice have not been reported about behavioral abnormalities or delayed brain development, indicating autism spectrum disorders. Here, we generated moesin KO mice by using the CRISPR/CAS9 system and observed their behaviors. Moesin KO mice exhibited abnormal developmental behaviors at 7 days, cognitive decline in the passive avoidance and Y maze tests, and anxiety symptoms in the open field test compared to wild-type mice at 3 months. Moreover, the primary cortical neurons of moesin KO mice showed a low cell survival rate and low expression of proteins involved in neuronal development and growth, such as MAP2, DCX, SOX2, SNAP25, and PSD95. Western blot analysis also revealed the downregulation of various synaptic proteins, such as syntaxin 1A and CDK5, in the brain of moesin KO adult mice. Moreover, the phosphorylation levels of synapsin I, MUNC18, ERK, and CREB were downregulated in the brains of moesin-KO mice. Furthermore, risperidone reversed the impaired memory function and synapsin I and ERK phosphorylation in the cortical tissue of moesin-KO mice. Thus, these results suggest that moesin affects neurodevelopmental and cognitive processes, plays an important role in the synaptic plasticity showing normal synapse structure and function, and that risperidone can reverse these synaptopathy and neurodevelopmental disorders.
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