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Abnormal metabolism and uncontrolled angiogenesis are two important characteristics of malignant tumors. Although HBXIP is known to be associated with a poor prognosis for bladder cancer (BC), its effects on glycolysis and angiogenesis in BC have not been investigated. BC prognosis and relative gene expression of HBXIP were analyzed using the GEPIA, UALCAN, and STRING databases. BC cell angiogenesis and glycolysis were assessed by vasculogenic mimicry and glycolysis assay. Human umbilical vein endothelial cell (HUVEC) viability, migration, and angiogenesis were assessed by CCK8, transwell, wound healing, and tube formation assays. The results showed that HBXIP was highly expressed in BC tissues and cells. Knockdown of HBXIP expression decreased the levels of glucose uptake, lactate production, and glycolytic enzyme expression in BC cells, and decreased cell viability and migration of HUVECs. Additionally, silencing HBXIP reduced the total length of tubes and number of intersections, and EPO and VEGF protein expression in BC cells and HUVECs. Furthermore, knockdown of HBXIP expression reversed cell viability, migration, tube formation, and vasculogenic mimicry under high glucose and lactate conditions. Mechanistically, silencing of HBXIP reduced the protein expression levels of pAKT-ser473 and pmTOR, and inhibition of HBXIP, AKT, and mTOR expression decreased glycolytic enzyme protein expression. Our findings suggest that HBXIP reduces glycolysis in BC cells via regulation of AKT/mTOR signaling, thereby blocking BC angiogenesis. Collectively, this study provides a potential strategy to target HBXIP and AKT/mTOR for regulating glycolysis progression concurrently with anti-angiogenesis effects, and thereby develop novel therapeutics for the treatment of BC.Effective listening comprehension not only requires processing local linguistic input, but also necessitates incorporating contextual cues available in the global communicative environment. Local sentence processing can be facilitated by pre-activation of likely upcoming input, or predictive processing. Recent evidence suggests that young adults can flexibly adapt local predictive processes based on cues provided by the global communicative environment, such as the reliability of specific speakers. Whether older comprehenders can also flexibly adapt to global contextual cues is currently unknown. Moreover, it is unclear whether the underlying mechanisms supporting local predictive processing differ from those supporting adaptation to global contextual cues. Critically, it is unclear whether these mechanisms change as a function of typical aging. We examined the flexibility of prediction in young and older adults by presenting sentences from speakers whose utterances were typically more or less predictable (i.isms from adaptation of prediction as a function of global context. These results have important implications for interpreting age-related change in predictive processing, and for drawing more generalized conclusions regarding domain-general versus language-specific accounts of prediction.The present study investigated executive function and sustained attention of non-athlete, young adults (ages 18-23) with a history of concussion beyond ten months post incident. Cognitive functioning was examined in 24 non-athletic, college students with a concussion history (mean age 21 yrs.; mean time and range post-injury 4 years, 10-90 months) and 24 non-athletic controls with no history (NH) of concussion. Computerized versions of two cognitive assessment techniques were utilized to examine executive functioning (Stroop) and sustained attention capacity (D2). Primary dependent variables were response time, error score, and sustained attention score. Relationships between dependent variables and concussion metrics were also analyzed. ANOVA's revealed a significantly higher error rate in concussion history (CH) participants when performing the Stroop task (p 0.05). Nevertheless, there was a significant relationship between D2 error rate and time since concussion (p less then 0.01), showing that D2 error rate was greater for participants with more time since concussion sustainment. Our findings indicate the potential for prolonged cognitive dysfunction linked to decision-making, but not to processing speed, in young adult non-athletes with a CH averaging four years post-injury. These findings may provide evidence of residual cognitive deficits in young adults with a concussion history over time.Deep hypothermic circulatory arrest (DHCA) during heart surgery may induce neuroinflammation leading to neurocognitive dysfunction. Chlorogenic acid (CA) is a common phytochemical, which can attenuate neuroinflammation. Nevertheless, the underlying mechanism involved in the anti-inflammatory effect of CA after DHCA is unknown. The present study therefore characterized the anti-inflammatory functions of CA after DHCA using in vivo and in vitro DHCA models. The activation of microglia, inflammatory cytokine levels, and the NF-κB pathway were measured. The results showed that CA treatment ameliorated neurocognitive function and reduced the inflammatory cytokine levels in the brain and circulation. Furthermore, the microglial and NF-κB activations were suppressed after DHCA. CA exerted the same anti-inflammatory effect in hypothermia OGD microglial cells as the in vivo study. Additional studies indicated that the regulation of ubiquitin ligase activity of TRAF6 and RIP1 by CYLD was related to the mechanism involving inhibition of CA in the NF-κB pathway. Ipatasertib solubility dmso Together, the results showed that CA may attenuate neuroinflammation after DHCA by modulating the signaling of CYLD/NF-κB.
Multiple cellular and molecular changes are involved in the etiology of spinal cord injury (SCI) and the recovery from SCI. link2 Accumulating studies showed aberrant expression of microRNAs (miRNAs) after SCI. Here, we established in vivo and in vitro models to analyze the role of miR-212-3p in SCI.
An in vivo model of SCI was established in Sprague-Dawley rats. SCI-induced histopathological changes of the spinal cord were observed by hematoxylin-eosin staining. Functional recovery of rats with SCI was evaluated using the Basso-Beattie-and-Bresnahan scale. PC12 cells were stimulated by lipopolysaccharide (LPS) to establish SCI model of neuronal apoptosis in vitro. Dual-luciferase reporter assay was performed to validate the potential target of miR-212-3p predicted by TargetScan 7.2. MTT assay and flow cytometry were carried out to measure the viability and apoptosis of PC12 cell, respectively. link3 The expressions of miR-212-3p, PTEN, phosphorylated (p)-AKT, AKT, p-mTOR, mTOR, Cleaved caspase-3 and BCl-2 in spinal cord tissues and PC12 cells were analyzed by qRT-PCR or Western blot.
In the spinal cord of rats with SCI, the expressions of miR-212-3p, p-AKT, p-mTOR and BCl-2 were downregulated, whereas those of PTEN and Cleaved caspase-3 were upregulated. BBB scores were low, and there were histopathological changes, which were all reversed after the injection of agomiR-212-3p. MiR-212-3p directly targeted PTEN. Upregulated miR-212-3p in LPS-injured PC12 cells suppressed apoptosis, downregulated the expressions of PTEN and Cleaved caspase-3, promoted viability and upregulated the expressions of p-AKT, p-mTOR and BCl-2, which were all reversed by overexpressed PTEN.
MiR-212-3p improved functional recovery of SCI rats and inhibited LPS-induced neurocyte apoptosis by targeting PTEN to activate AKT/mTOR pathway.
MiR-212-3p improved functional recovery of SCI rats and inhibited LPS-induced neurocyte apoptosis by targeting PTEN to activate AKT/mTOR pathway.Determining when a partner's spoken or musical turn will end requires well-honed predictive abilities. Evidence suggests that our motor systems are activated during perception of both speech and music, and it has been argued that motor simulation is used to predict turn-ends across domains. Here we used a dual-task interference paradigm to investigate whether motor simulation of our partner's action underlies our ability to make accurate turn-end predictions in speech and in music. Furthermore, we explored how specific this simulation is to the action being predicted. We conducted two experiments, one investigating speech turn-ends, and one investigating music turn-ends. In each, 34 proficient pianists predicted turn-endings while (1) passively listening, (2) producing an effector-specific motor activity (mouth/hand movement), or (3) producing a task- and effector-specific motor activity (mouthing words/fingering a piano melody). In the speech experiment, any movement during speech perception disrupted predictions of spoken turn-ends, whether the movement was task-specific or not. In the music experiment, only task-specific movement (i.e., fingering a piano melody) disrupted predictions of musical turn-ends. These findings support the use of motor simulation to make turn-end predictions in both speech and music but suggest that the specificity of this simulation may differ between domains.Real time analysis of pharmaceuticals in controlled release nano and microsystems remains a challenge. It is hypothesized that fluorine 19 nuclear magnetic resonance (19F qNMR) can be used for real time quantification and in vitro release of maraviroc (MVC). The release of maraviroc was analyzed in simulated body fluids from spray dried sodium alginate microspheres (MS) using the 19F qNMR method. Calibration produced a linearity curve in concentration range (0.42 mg/ml - 15 mg/ml), and the limits of detection and quantification values were 0.97 mg/ml and 2.93 mg/ml, respectively. The method was confirmed to be specific, accurate, precise, and robust (%RSE > 2%). MVC was successfully microencapsulated (18% w/w) as evidenced by the FT-IR spectra and SEM images. The MS had an average diameter of 2.522 ± 0.15 μm, with a zeta potential of - 61.31 ± 2.1 mV. Overall, the 19F qNMR method enabled a direct and real time quantification of MVC for an efficient drug release kinetics. This approach could be potentially used to quantify fluorinated drug potency, purity, and stability, and evaluate in vitro release kinetic from different formulations.Chronic kidney disease (CKD) is an irreversible, progressive disease characterized by persistent kidney damage, and significantly increased risks of cardiovascular event. However, therapeutic strategies to prevent or slow the progression of CKD remain limited. Sacubitril/valsartan (LCZ696), the representative of the first novel angiotensin receptor-neprilysin inhibitor, has been incorporated into clinical practice guidelines for improving outcomes as a milestone in patients with heart failure. Considering the complex and close relationship between CKD and heart failure, LCZ696 may be beneficial in the treatment of CKD. This review summarizes the pharmacological mechanism and clinical application of LCZ696 in patients with CKD, including its effect on cardiovascular risk and renal outcome, together with potential adverse events. Additionally, due to the influence of serum creatinine and estimated glomerular filtration rate on LCZ696 in patients with heart failure, we also discussed the effects of LCZ696 in patients with advanced CKD and end-stage renal disease.
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