RESUMO
Reduced myelin stability observed in the early stages of Alzheimer's disease leads to spatial learning and memory impairment. Exercise has been shown to protect nerves, reduce the risk of Alzheimer's disease, and strengthen synaptic connectivity. However, the underlying mechanisms of how exercise can promote myelin repair and coordinate inflammation and proliferation are still uncertain. In this study, we conducted histological and biochemical assays of cortical lysates after behavioral testing to detect pathological changes, myelin sheath thickness, and mRNA and protein levels. It is notable that D-galactose model mice exhibited elevated miRNA-34a levels, overactive astrocytes, decreased myelin staining scores, increased apoptosis, and decreased synaptic plasticity in the brain. Significantly, after eight weeks of exercise, we observed improvements in LFB scores, NeuN( +) neuron counts, and myelin basic protein (MBP) expression. Additionally, exercise promoted the expression of oligodendrocyte markers Olig2 and PDFGR-α associated with brain proliferation, and improved spatial cognitive function. Furthermore, it decreased the inflammation caused by astrocyte secretions (TNF-α, Cox-2, CXCL2). Interestingly, we also observed downregulation of miR-34a and activation of the TAN1/PI3K/CREB signaling pathway. Our data shed light on a previously unsuspected mechanism by which exercise reduces miR-34a levels and protects neuronal function and survival by preventing excessive demyelination and inflammatory infiltration in the CNS.
Assuntos
Doença de Alzheimer , MicroRNAs , Animais , Camundongos , Doença de Alzheimer/metabolismo , Astrócitos/metabolismo , Inflamação/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Bainha de Mielina/metabolismo , Doenças Neuroinflamatórias , Oligodendroglia/metabolismoRESUMO
The crisp grass carp (CGC; Ctenopharyngodon idellus C. et V.), known for its unique texture and flavour, is a culinary delicacy whose quality is significantly influenced by thermal processing. This study employed 4D label-free proteomics and data mining techniques to investigate the proteomic changes in CGC muscle tissue induced by various heating temperatures. CGC samples were subjected to a series of heat treatments at increasing temperatures from 20 °C to 90 °C. Proteins were extracted, digested, and analysed using high-resolution mass spectrometry. The proteomic data were then subjected to extensive bioinformatics analysis, including GO and KEGG pathway enrichment. We identified a total of 1085 proteins, 516 of which were shared across all the temperature treatments, indicating a core proteome responsible for CGC textural properties. Differential expression analysis revealed temperature-dependent changes, with significant alterations observed at 90 °C, suggesting denaturation or aggregation of proteins at higher temperatures. Functional enrichment analysis indicated that proteins involved in amino acid metabolism, glutathione metabolism, and nucleotide metabolism were particularly affected by heat. Textural analysis correlated these proteomic changes with alterations in CGC quality attributes, pinpointing 70 °C as the optimum temperature for maintaining the desired texture. A strong positive correlation between specific upregulated proteins was identified, such as the tubulin alpha chain and collagen alpha-1(IV) chain, and the improved textural properties of CGC during thermal processing, suggesting their potential as the potential biomarkers. This study offers a comprehensive proteomic view of the thermal stability and functionality of CGC proteins, delivering invaluable insights for both the culinary processing and scientific management of CGC. Our findings not only deepen the understanding of the molecular mechanisms underpinning the textural alterations in CGC during thermal processing but also furnish practical insights for the aquaculture industry. These insights could be leveraged to optimize cooking techniques, thereby enhancing the quality and consumer appeal of CGC products.
RESUMO
The Petasis reaction using (1S,2R)-1-amino-2-indanol as the substrate and an activator to construct α- and ß-butadienyl amines in optically pure forms was realized, which are otherwise difficult to prepare. The reactions feature a metal-free nature, broad substrate scope, complete regioselectivities (γ-selectivity of pinacol homoallenyl- and isoprenylboronates), and high to excellent chirality induction (up to >20 : 1 dr). The favored nucleophilic addition across the Si-face of the imine intermediate was explained using DFT calculations of the six-membered chair-like transition state.
RESUMO
OBJECTIVES: To investigate the clinical effect of the arytenoid cartilage reposition using snake mouth reduction forceps under general anesthesia. METHODS: Data of twenty-six cases accepted arytenoid cartilage reposition under intravenous general anesthesia were analyzed, nineteen cases accepted laryngeal CT scan and cricoarytenoid joint reconstruction, all patients underwent endolaryngeal muscle electromyography examination. According to the position of cartilage dislocation prompted by laryngoscope and CT, the arytenoid cartilage was repositoned under the visual laryngoscope using special snake mouth reduction forceps. If bilateral arytenoid cartilage were still asymmetrically at the end of the surgery, patients needed repeated reposition 1 to 2 times 1 week after operation. The efficacy was evaluated 4 weeks later. RESULTS: All patients had a hoarse and breathing voice preoperative. Under laryngoscope, there were different degrees of vocal cord movement disorders accompanied by incomplete glottis closure, 22 cases happened in left side and 4 in right side. The arytenoid cartilage was dislocated anteromedially in 25 cases and posterolaterally in 1 case. CT showed that 15 cases of arytenoid cartilage were tilted anteromedially; the interval of the cricoarytenoid joint was widened. In axial CT images, there were no direct signs of the arytenoid cartilage dislocation in the 4 cases, but the abnormal position was seen in the reconstruction images. The laryngeal electromyography indicated that 7 cases were abnormal, duration of motor unit potential were visible and the raising potential were mixed. There were 4 patients with normal voice in the first day after surgery, and 19 cases underwent twice and 3 cases underwent three times surgery. Vioce became normal in 4 weeks. Swallowing pain and bucking were all disappeared. Vocal cords movement were recovered to normal level in 25 cases. In 1 case with neck strangulation, the vocal cord movement was slightly worse than health side, but significantly better than that before operation. CONCLUSIONS: The arytenoid cartilage reposition using snake mouth reduction forceps under general anesthesia was an effective method for the treatment of the cricoary-tenoid joint dislocation.
Assuntos
Anestesia Geral/instrumentação , Cartilagem Aritenoide/lesões , Laringoscópios , Rouquidão , Humanos , Boca , Instrumentos CirúrgicosRESUMO
Insulin resistance is the pathophysiological basis of many diseases. Overcoming early insulin resistance highly significant in prevention diabetes, non-alcoholic fatty liver, and atherosclerosis. The present study aimed at evaluating the therapeutic effects of baicalin on insulin resistance and skeletal muscle ectopic fat storage in high fat diet-induced mice, and exploring the potential molecular mechanisms. Insulin resistance in mice was induced with a high fat diet for 16 weeks. Animals were then treated with three different doses of baicalin (100, 200, and 400 mg·kg(-1)·d(-1)) for 14 weeks. Fasting blood glucose, fasting serum insulin, glucose tolerance test (GTT), insulin tolerance test (ITT), and skeletal muscle lipid deposition were measured. Additionally, the AMP-activated protein kinase/acetyl-CoA carboxylase and protein kinase B/Glycogen synthase kinase 3 beta pathways in skeletal muscle were further evaluated. Baicalin significantly reduced the levels of fasting blood glucose and fasting serum insulin and attenuated high fat diet induced glucose tolerance and insulin tolerance. Moreover, insulin resistance was significantly reversed. Pathological analysis revealed baicalin dose-dependently decreased the degree of the ectopic fat storage in skeletal muscle. The properties of baicalin were mediated, at least in part, by inhibition of the AMPK/ACC pathway, a key regulator of de novo lipogenesis and activation of the Akt/GSK-3ß pathway, a key regulator of Glycogen synthesis. These data suggest that baicalin, at dose up to 400 mg·kg(-1)·d(-1), is safe and able to attenuate insulin resistance and skeletal muscle ectopic fat storage, through modulating the skeletal muscle AMPK/ACC pathway and Akt/GSK-3ß pathway.