Gallic Acid Ameliorates Cognitive Impairment Caused by Sleep Deprivation through Antioxidant Effect

Sleep deprivation (SD) has a profound impact on the central nervous system, resulting in an array of mood disorders, including depression and anxiety. Despite this, the dynamic alterations in neuronal activity during sleep deprivation have not been extensively investigated. While some researchers propose that sleep deprivation diminishes neuronal activity, thereby leading to depression. Others argue that short-term sleep deprivation enhances neuronal activity and dendritic spine density, potentially yielding antidepressant effects. In this study, a two-photon microscope was utilized to examine the calcium transients of anterior cingulate cortex (ACC) neurons in awake SD mice in vivo at 24-hour intervals. It was observed that SD reduced the frequency and amplitude of Ca2+ transients while increasing the proportions of inactive neurons. Following the cessation of sleep deprivation, neuronal calcium transients demonstrated a gradual recovery. Moreover, whole-cell patch-clamp recordings revealed a significant decrease in the frequency of spontaneous excitatory post-synaptic current (sEPSC) after SD. The investigation also assessed several oxidative stress parameters, finding that sleep deprivation substantially elevated the level of malondialdehyde (MDA), while simultaneously decreasing the expression of Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) and activities of Superoxide dismutase (SOD) in the ACC. Importantly, the administration of gallic acid (GA) notably mitigated the decline of calcium transients in ACC neurons. GA was also shown to alleviate oxidative stress in the brain and improve cognitive impairment caused by sleep deprivation. These findings indicate that the calcium transients of ACC neurons experience a continuous decline during sleep deprivation, a process that is reversible. GA may serve as a potential candidate agent for the prevention and treatment of cognitive impairment induced by sleep deprivation.

The novel ER stress inducer Sec C triggers apoptosis by sulfating ER cysteine residues and degrading YAP via ER stress in pancreatic cancer cells

Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect (80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-l-cysteine (NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum (ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation (ERAD) ubiquitinates and downregulates YAP to enhance ER stress via destruction complex (YAP-Axin-GSK-βTrCP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.

COVID-19-Associated Acute Disseminated Encephalomyelitis: A Case Report

We present the first described case of acute disseminated encephalomyelitis (ADEM) in a COVID-19 patient. The clinical features with head CT and brain MRI changes were described. Our described case is an atypical presentation of the novel coronavirus in a young patient and is illustrative of the possible approaches to explore the treatable differential etiologies.

Netrin-1 plays a role in the effect of moderate exercise on myocardial fibrosis in rats.

INTRODUCTION: This study aimed to investigate the effect of aerobic exercise on the expression of neitrin-1,DCC receptor and myocardial fibrosis in rats with acute myocardial infarction. METHODS: Twenty-four rats were randomly divided into three groups: the sham group (n = 8), the acute myocardial infarction (AMI) model group (n = 8), and the aerobic exercise treatment after acute myocardial infarction group (ET) (n = 8). After 10 weeks, the serum levels of netrin-1, tumor necrosis factor alpha α (TNF-α), and interleukin 6 (IL-6) were measured. The expression of matrix metalloproteinase 2 and 9 (MMP2, 9), and their inhibitor, tissue inhibitor of metalloproteinase 2 (TIMP2), myocardial netrin-1, and the deleted in colorectal cancer (DCC) receptor were evaluated. Histopathological results were also evaluated. The collagen volume fraction of the myocardial tissues was also calculated. RESULTS: Compared with the sham group, in the AMI and ET groups, left ventricular end diastolic pressure (LVEDP) were increased, while left ventricular systolic pressure (LVSP), and left ventricular pressure maximal rate of rise and fall (± dp/dtmax) were significantly decreased (P<0.05,). Compared with the AMI group, in the ET group, LVSP, and ±dp/dtmax were significantly increased while LVEDP was decreased (P<0.05). Compared with the sham group, the AMI group and ET groups showed increased levels of serum TNF-α, IL-6 and significantly reduced levels of netrin-1. Levels of TNF-α and IL-6 were significantly reduced in the ET group compared with the AMI group, whereas the level of netrin-1 was increased. The expression of myocardial MMP2 and MMP9 was significantly increased in the AMI group compared with the sham group, whereas that of myocardial netrin-1, TIMP2 and the DCC receptor, was significantly reduced. Compared with the AMI group, the ET group showed reduced expression of myocardial MMP2 and MMP9 proteins, whereas expression of myocardial netrin-1, TIMP2 and the DCC receptor, was significantly increased. The collagen volume fraction of the myocardial tissues was significantly increased in the AMI group and the ET group compared with the sham group, with a greater increase in the AMI group. CONCLUSIONS: Aerobic exercise increased levels of serum netrin-1, myocardial netrin-1, and the DCC receptor and reduced the expression of myocardial MMP2 and MMP9 proteins, to improve the degree of fibrosis following myocardial infarction in rats.

Effect of aerobics exercise on myocardial fibrosis after acute myocardial infarction in rat / 中国医师杂志

Objective To observe the effect of aerobics exercise on myocardial fibrosis after acute myocardial infarction (AMI) in rat.Methods Twenty-four AMI Sprague Dawley (SD) rats were randomly assigned to sham-operated group (Sham),AMI group and aerobics exercise treatment group (ET).Except Sham,other groups of rats were underwent anterior wall myocardial infarction.After ten weeks,the myocardial mRNA level of connective tissue growth factor (CTGF),collagen Ⅰ (COL1 a1),collagen Ⅲ (COL3a1) detected by real time-quantitative polymerase chain reaction (PCR) analysis and myocardial collagen volume fraction (CVF) was determined on Masson stained sections.Results Campared to Sham-operated group,AMI group the level of CTGF,COL1a1,COL3a1,and CVF were increased (P ＜0.05,P ＜ 0.01).Campared to AMI and ET groups,the levels of CTGF,COL1a1,COL3a1,and CVF were decreased (P ＜ 0.05,P ＜ 0.01).Conclusions Aerobics exercise can reduced the myocardial fibrosis after AMI in rat.

NMR-based metabolomic investigation of regional brain tissue dysfunctions of MCAO rats induced by ischemia / 中国药科大学学报

@#In this paper, an NMR-based metabolomic study was applied to unravel the pathological mechanisms of focal cerebral ischemia at the metabolic level by investigating the metabolic profile changes of regional brain tissues of male rats upon MCAO operation. In our study, to induce ischemic defects, the operation of middle cerebral artery occlusion was applied to rats in the model group. Meanwhile, the sham-operation was subjected to the rats in sham group by following the same surgical procedure as that applied to the model group rats without occlusion. Three hours after the operation, the metabolites from regional brain tissues including cortex, hippocampus and striatum from the ischemic left hemisphere and the non-ischemic right hemisphere of experimental rats were extracted and subjected to NMR. Multivariate data analysis of PCA and OPLS-DA methods were then applied to analyze the NMR data and thus unravel the possible correlations between the metabolic profile changes and the variations in biological pathways of MCAO rats. The obtained metabolomic data demonstrated that the neural cell damages and the systematic metabolic disorders including energy deficiency(the decrease in AMP level and the increase in uridine concentration), up-regulation of anaerobic glycolysis(a significant up-regulation of the lactate level), oxidative stress(the up-regulation of either malonate level or succinate concentration), dysfunction of choline metabolism(the significant up-regulation of choline level and the decrease in both GPC level and phosphorylcholine concentration), neurotransmitter imbalances(the down-regulation of glutamate level and the up-regulation of GABA, glycine and alanine concentration), and neuronal cell damage(a decrease in the NAA level), were induced in the regional brain tissues of ischemic left hemispheres of MCAO rats. Moreover, the patterns of the metabolic variations in the non-ischemic hemispheres of MCAO rats were similar to those in the left ones, although the metabolic disorders in the non-ischemic right hemisphere were much less severe. Our results suggest that close attention should be paid to the non-ischemic cerebral regions in the treatment of patients with focal ischemic stroke.