C/EBPβ/AEP Signaling Drives Alzheimer's Disease Pathogenesis / 神经科学通报·英文版

Alzheimer's disease (AD) is the most common type of dementia. Almost two-thirds of patients with AD are female. The reason for the higher susceptibility to AD onset in women is unclear. However, hormone changes during the menopausal transition are known to be associated with AD. Most recently, we reported that follicle-stimulating hormone (FSH) promotes AD pathology and enhances cognitive dysfunctions via activating the CCAAT-enhancer-binding protein (C/EBPβ)/asparagine endopeptidase (AEP) pathway. This review summarizes our current understanding of the crucial role of the C/EBPβ/AEP pathway in driving AD pathogenesis by cleaving multiple critical AD players, including APP and Tau, explaining the roles and the mechanisms of FSH in increasing the susceptibility to AD in postmenopausal females. The FSH-C/EBPβ/AEP pathway may serve as a novel therapeutic target for the treatment of AD.

Metabolic disturbances and inflammatory dysfunction predict severity of coronavirus disease 2019 (COVID-19): a retrospective study

BackgroundThe coronavirus disease 2019 (COVID-19) is spreading worldwide with 16,558 deaths till date. Serum albumin, high-density lipoprotein (HDL-C), and C-reactive protein have been known to be associated with the severity and mortality of community-acquired pneumonia. However, the characteristics and role of metabolic and inflammatory indicators in COVID-19 is unclear. MethodsWe included 97 hospitalized patients with laboratory-confirmed COVID-19. Epidemiological, clinical, and laboratory indices; radiological features; and treatment were analysed. The differences in the clinical and laboratory parameters between mild and severe COVID-19 patients and the role of these indicators in severity prediction of COVID-19 were investigated. ResultsAll were Wuhan residents with contact with confirmed COVID-19 cases. The median age was 39 years (IQR: 30-59). The most common presenting symptoms were fever (58.8%), cough (55.7%), and fatigue (33%). Other features were lymphopenia, impaired fasting glucose, hypoproteinaemia, hypoalbuminemia, low high-density lipoproteinemia. Decrease in lymphocyte count, serum total protein, serum albumin, high-density lipoprotein cholesterol (HDL-C), ApoA1, CD3+T%, and CD8+T% were found to be valuable in predicting the transition of COVID-19 from mild to severe illness. Chest computed tomography (CT) images showed that the absorption of bilateral lung lesions synchronized with the recovery of metabolic and inflammatory indicators. ConclusionsHypoproteinaemia, hypoalbuminemia, low high-density lipoproteinemia, and decreased ApoA1, CD3+T%, and CD8+T% could predict severity of COVID-19. Lymphocyte count, total serum protein, and HDL-C may be potentially useful for the evaluation of COVID-19.

The role of organophosphorus compounds in the pathogenesis of Alzheimer′s disease / 中华神经科杂志

Alzheimer′s disease is the most common neurodegenerative disease, which is characterized by the formation of neurofibrillary tangles and amyloid plaques in the brain, and the progressive loss of neurons. Epidemiological studies found that exposure to organophosphorus compounds increases the incidence of Alzheimer′s disease. Organophosphorus compounds accelerate the onset of Alzheimer′s disease pathology by inhibiting enzyme activity, promoting oxidative stress, and affecting axonal transport and nerve growth factor pathway. As a result, they cause cognitive dysfunction. Here we reviewed the current knowledge on the role of organophosphorus compounds in the pathogenesis of Alzheimer′s disease, in order to enhance our understanding of the environmental risk factors that contribute to the pathogenesis of Alzheimer′s disease, and to search for potential therapeutic targets for this disease.

Clinical manifestations and management of thallium poisoning in a single family with 6 cases / 中华神经科杂志

Objective To further investigate clinical manifestations and management for thallium poisoning. Methods Clinical data of 6 patients who were hospitalized in Union Hospital of Tongji Medical College in May 2008 with diagnosis of acute or chronic thallium poisoning,were retrospectively analyzed.Results Six patients (4 male and 2 female) ,aged from 12 to 50,came from one family (two sisters with their husbands and sons). Five of them (3 acute and 2 chronic,for the second time in half a year,thallium poisoning) initiated with peripheral neuritis,represented with severe burning pain,numbness,paresthesia in the lower limbs,accompanied with or without gastrointestinal symptoms. A 12 year-old boy with obviously elevated urinary thallium concentration was asymptomatic. Blood and urinary thallium concentrations of the patients were determined by atomic absorption spectrophotometry and were all significantly elevated.Treatment was initiated using potassium supplementation,diuresis,oral laxatives,Prussian blue and intramuscular injection of dimercaptopropansulfonate sodium.Meanwhile two of them were treated with hemoperfusion. Finally,two of them recovered,another two were transferred to a specialized hospital for continuous treatment,and the rest two deteriorated rapidly with occurrence of unconsciousness and died of multiple organ failure. Conclusions The main clinical manifestations of thallium poisoning are multiple peripheral neuritis,gastrointestinal symptoms and dermatological changes. In order to avoid missed diagnosis and misdiagnosis,a high suspicion should be arose for thallium poisoning when a patient suffering from the above symptoms.Prussian blue was considered traditionally as an effective therapeutic strategy for the condition,and hemoperfusion may be a more effective treatment for acute thallium poisoning.

Effect of somatostain intra-articular injection on metabolism of free radicals in rabbits with knee osteoarthritis / 国际外科学杂志

Objective To discuss the effect of somatostain SS on metabolism of free radicals in animal models of osteoarthritis,so to discuss the treatment mechanism of intra- articular injection of somatostatin on osteoarthritis.MethodsForty experimental Japanese big-ear rabbits were randomly divided into four groups:normal control group,blank model group,normal saline group and SS group,n =10 for each group.After modeling,the rats in SS group and normal saline group received intra- articular injection of somatostain and saline respectively on the right knee.Ten weeks after the modeling,we measured the movement of right knee joint in rabbits,the levels of nitric oxide ( NO ) and hyaluronic acid (HA) in serum from the heart blood,and the activity of SOD and the content of MDA in synovial tissue.Results Compared with the blank model group,the movement of the knee joint was significantly increased in SS group,(96.01 ± 1.06)vs (50.21 ± 1.80) (P ＜ 0.01 ).In the blank model group,the levels of NO and HA (μmoL/mL) in serum were ( 111.60 ± 2.76) and ( 309.11 ± 1.89 ),which was significantly decreased in SS group,which was( 80.14 ± 1.67 ) and ( 133.73 ± 2.75 ) ( P1 =0.0049,P2 =0.0052,P ＜ 0.01 ).Compared with the blank model group,the SOD activity was (15.77 ± 2.76) and the MDA in serum nmol/mg prot was( 1.33 ±1.03),while was significantly increased in SS group,(24.74 ± 1.67) ( P ＜ 0.01 ),and the levels of MDA in serum was significantly decreased in the SS group,(0.89 ±1.46) (P＜0.01).Conclusion Intra-articular injection of somatostatin in knee osteoarthritis can improve the oxidative stress,enhance the activity of the knee joint.

Extracellular signal-regulated kinases 1 and 2 regulating rotenone-induced injury in pheochromocytoma cells / 中华神经科杂志

Objective To investigate the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in rotenone-mediated dopaminergic cell damage. Methods Neuronal rat adrenal pheochromecytoma(PC12) cells treated with rotenone were used as the cell model of Parkinson' s disease (PD). Cell viability of PC12 cells after exposure to rotenone was detected by MTT (methyl thiazolyl tetrazolium) method. Immanohistechemistry was used to detect the phosphorylation of ERK1/2 in cells exposed to rotenone. Western blotting was used to verify the phosphorylation of ERK1/2 and to observe the effect of PD98059, an inhibitor of the upstream mitogen activated protein kinase kinase (MEK) that phosphorylates and activates ERK1/2, on rotenone-induced ERK1/2 phosphorylation and cell viability.Results The viability (represented by A570 of PC12 cells exposed to 5 μmoL/L rotenone) declined with the increase of exposure time from 1 h to 24 h (%, 1 h :75.46±5.47, 2 h : 70.42±1.94, 4 h : 65.23± 0.96, 8 h : 59.04 ± 2.85, 24 h :29.64 ± 1.63, comparison between different time points(F=143.014, P=0.000) ; compared with control groups(100.00±2.89), q value: 17.07, 20.58, 24. 19, 28.50, 48.95 respectively, all P <0.01). After exposure to rotenone, phosphorylated ERK1/2 aggregated in the PC12 cells. Western blotting indicated that rotenone induced a biphasic phosphorylation of ERK1/2, which increased from 30 min after rotenone treatment, reached the peak at 1-2 h, decreased at 4 h, and increased again at 8 h, and disappeared after 16 h; PD98059 significantly inhibited ERK1/2 phosphorylation induced by rotenone, and attenuated cell injury examined at 1, 2 and 8 h. Conclusions Our study suggested that ERK1/2 activation plays a detrimental role in rotenone toxicity, and raised the possibility that abnormal patterns of ERK1/2 activation may contribute to dopaminergic neuronal cell death in PD.

Quantitative autoradiographic study on receptor regulation in the basal ganglia in rat model of levodopa-induced motor complications / 华中科技大学学报（医学）（英德文版）

In order to study neurotransmitter receptor regulation in the basal ganglia involved in the functional changes underlying levodopa-induced motor complications, quantitative autoradiography was used to observe receptor bindings of dopamine D1 and D2, N-methyl-D-aspartate (NMDA), amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) and amino butyric acid (GABA) in the basal ganglia of rats that had unilateral nigrostriatal lesions and had been chronically treated with levodopa until motor complications developed. The rats were randomly assigned to three groups: normal, denervated and treatment-complicated groups. The results showed that response duration to levodopa became progressively shorter and abnormal involuntary movement (AIM) score was progressively increased during the course of levodopa treatment. Chronic treatment augmented D1 receptors more than denervation, and reduced D2 receptors that were also increased by dopamine denervation. Striatal NMDA receptors were substantially up-regulated in the treatment-complicated group. Levodopa treatment did not change receptors of nigral AMPA, pallidal GABA, and subthalamic GABA, which remained the same as that in denervation group. However, chronic treatment reversed the increase of nigral GABA receptors caused by the lesion. It was concluded that a shortening of response duration and AIM mimicked levodopa-induced motor complications of Parkinson's patients. These data suggested that up-regulation of dopamine D1 and NMDA receptors in the striatum leads to an imbalance of stimulation through the striatal output pathways, which is associated with levodopa-induced motor complications.