Cordycepin protects against β-amyloid and ibotenic acid-induced hippocampal CA1 pyramidal neuronal hyperactivity

Cordycepin exerts neuroprotective effects against excitotoxic neuronal death. However, its direct electrophysiological evidence in Alzheimer's disease (AD) remains unclear. This study aimed to explore the electrophysiological mechanisms underlying the protective effect of cordycepin against the excitotoxic neuronal insult in AD using whole-cell patch clamp techniques. β-Amyloid (Aβ) and ibotenic acid (IBO)-induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed Aβ + IBO-induced excessive neuronal membrane depolarization. It increased the onset time/latency, extended the duration, and reduced the slope in both slow and rapid depolarization. Additionally, cordycepin reversed the neuronal hyperactivity in Aβ + IBO-induced evoked action potential (AP) firing, including increase in repetitive firing frequency, shortening of evoked AP latency, decrease in the amplitude of fast afterhyperpolarization, and increase in membrane depolarization. Further, the suppressive effect of cordycepin against Aβ + IBO-induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine A₁ receptor-specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the Aβ + IBO-induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of A₁R is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.

Central cholinergic system innervates song control system of songbirds and regulates song behavior / 生理学报

Songbird has become an ideal model for studying motor learning due to its unique learned song behavior. It has been proved that song behavior is directly regulated by song control system in the forebrain of songbirds. There are lines of evidence to show that cholinergic transmitters and their receptors are distributed in song control system, and vocal control nuclei in song control system are innervated by cholinergic nerves from the central cholinergic system in basal forebrain, which can affect activities of vocal control nuclei through cholinergic transmitters, and then affect song behavior. Studies in mammals have confirmed that the central cholinergic system is involved in the regulation of motor behavior and neural process of motor learning. Elucidation of regulation of songbirds' song behavior by central cholinergic system would shed light on the neural mechanism of song motor control and song learning and memory in songbirds, and provide theoretical insights for researches on other animals' sensorimotor processes and human language learning. This review summarized recent progresses, including the research work of our laboratory, in the studies on the selectivity of cholinergic transmitters to their receptors and their effects on neuronal activities in vocal control nuclei of songbirds and provided valuable clues for revealing the regulation mechanism of central cholinergic system on songbirds' song behavior.

Down-regulated serum microRNA-101 is associated with aggressive progression and poor prognosis of cervical cancer / 부인종양

OBJECTIVE: MicroRNAs (miRNAs) play a vital role in pathogenesis and progression of many cancers, including cervical cancer. However, importance of serum level of miR-101 in cervical cancer has rarely been studied. In the present study, clinical significance and prognostic value of serum miR-101 for cervical cancer was investigated. METHODS: Association between miR-101 level in cervical cancer tissues and prognosis of patients was analyzed by using data retrieved from The Cancer Genome Atlas (TCGA) database, which was followed with our clinical study in which miR-101 serum level comparison between cervical cancer patients and healthy controls was conducted by real-time quantitative polymerase chain reaction (PCR). RESULTS: TCGA database demonstrated that miR-101 was down-regulated in cervical cancer tissues compared with normal cervical tissues, and univariate Cox regression analysis indicated that decreased miR-101 expression was a highly significant negative risk factor. Similar trend was found in the serum miR-101. Serum level of miR-101 was associated with International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.003), lymph node metastasis (p=0.001), and serum squamous cell carcinoma antigen (SCC-Ag) level >4 (p=0.007). The overall survival time of cervical cancer patients with a higher level of serum miR-101 was significantly longer than that of patients with a lower level of serum miR-101. Moreover, multivariate Cox regression analysis indicated that the down-regulated serum level of miR-101 was an independent predictor for the unfavorable prognosis of cervical cancer. CONCLUSION: Serum level of miR-101 is closely associated with metastasis and prognosis of cervical cancer; and, hence could be a potential biomarker and prognostic predictor for cervical cancer.

Study on Material Basis and Mechanism of Erzhi Wan prevent Alzheimer's disease by network pharmacology / 中国中药杂志

The present study is to explore the material basis and mechanism of Erzhi Wan the prevented Alzheimer's disease by using network pharmacology. The key target of Alzheimer's disease was docked with the Erzhi Wan compounds, and the drugs-target combined with target-signal pathway network model was established by Cytoscape 3.2.1 software. Thirty compounds have a strong interaction with key target of Alzheimer's disease and three key pathways related with Wnt, MAPK and PI3K-Akt-mTOR. There are 5 ingredients such as quercetin,geraniol,beta-sitosterol,nerol,eriodictyol that could be verified from literature.This result initially revealed the material basis for Erzhi Wan for Alzheimer's disease and the mechanism in terms of three signaling pathways. The network pharmacology method found that the active ingredients of Erzhi Wan for Alzheimer's disease may be quercetin,geraniol,beta-sitosterol,nerol,and eriodictyol, and the mechanism may be related to three signal pathways including Wnt, MAPK, and PI3K-Akt-mTOR.

Effects of Modafinil on Behavioral Learning and Hippocampal Synaptic Transmission in Rats / 대한배뇨장애요실금학회지

PURPOSE: Modafinil is a wake-promoting agent that has been proposed to improve cognitive performance at the preclinical and clinical levels. Since there is insufficient evidence for modafinil to be regarded as a cognitive enhancer, the aim of this study was to investigate the effects of chronic modafinil administration on behavioral learning in healthy adult rats. METHODS: Y-maze training was used to assess learning performance, and the whole-cell patch clamp technique was used to assess synaptic transmission in pyramidal neurons of the hippocampal CA1 region of rats. RESULTS: Intraperitoneal administration of modafinil at 200 mg/kg or 300 mg/kg significantly improved learning performance. Furthermore, perfusion with 1mM modafinil enhanced the frequency and amplitude of spontaneous postsynaptic currents and spontaneous excitatory postsynaptic currents in CA1 pyramidal neurons in hippocampal slices. However, the frequency and amplitude of spontaneous inhibitory postsynaptic currents in CA1 pyramidal neurons were inhibited by treatment with 1mM modafinil. CONCLUSIONS: These results indicate that modafinil improves learning and memory in rats possibly by enhancing glutamatergic excitatory synaptic transmission and inhibiting GABAergic (gamma-aminobutyric acid-ergic) inhibitory synaptic transmission.

Glutamate transporter 1-mediated antidepressant-like effect in a rat model of chronic unpredictable stress / 华中科技大学学报（医学）（英德文版）

In recent years, more attention has been paid to the role of the glutamate transporter 1 (GLT-1, EAAT2) in major depressive disorder (MDD). However, experimental data on brain GLT-1 levels are, to some extent, inconsistent in human postmortem and animal studies. These discrepancies imply that the role of GLT-1 in the pathophysiology of MDD and the action of antidepressants remain obscure. This work was designed to study the impact of chronic unpredictable stress (CUS) for 2 sessions per day for 35 days and four weeks of fluoxetine (FLX) on depressive-like behaviors in rats, as well as the concomitant expression of the GLT-1 protein in the hippocampus. Behavioral changes were assessed by the sucrose preference and open field tests. GLT-1 levels were detected by immunohistchemistry and Western blot analysis. Our study demonstrated that the animals exposed to CUS showed depressive-like behaviors and exhibited a significant decrease in GLT-1 expression in the hippocampus. Chronic FLX treatment reversed the behavioral deficits and the CUS-induced decrease in GLT-1 levels. Taken together, our results support the reduction of GLT-1 in human postmortem studies in MDD and suggest that GLT-1 may be involved in the antidepressant activity of FLX. Our studies further support the notion that GLT-1 is an attractive candidate molecule associated with the fundamental processes of MDD and may be a potential, and novel pharmacological target for the treatment of MDD.

Glutamate transporter 1-mediated antidepressant-like effect in a rat model of chronic unpredictable stress / 华中科技大学学报（医学）（英德文版）

In recent years, more attention has been paid to the role of the glutamate transporter 1 (GLT-1, EAAT2) in major depressive disorder (MDD). However, experimental data on brain GLT-1 levels are, to some extent, inconsistent in human postmortem and animal studies. These discrepancies imply that the role of GLT-1 in the pathophysiology of MDD and the action of antidepressants remain obscure. This work was designed to study the impact of chronic unpredictable stress (CUS) for 2 sessions per day for 35 days and four weeks of fluoxetine (FLX) on depressive-like behaviors in rats, as well as the concomitant expression of the GLT-1 protein in the hippocampus. Behavioral changes were assessed by the sucrose preference and open field tests. GLT-1 levels were detected by immunohistchemistry and Western blot analysis. Our study demonstrated that the animals exposed to CUS showed depressive-like behaviors and exhibited a significant decrease in GLT-1 expression in the hippocampus. Chronic FLX treatment reversed the behavioral deficits and the CUS-induced decrease in GLT-1 levels. Taken together, our results support the reduction of GLT-1 in human postmortem studies in MDD and suggest that GLT-1 may be involved in the antidepressant activity of FLX. Our studies further support the notion that GLT-1 is an attractive candidate molecule associated with the fundamental processes of MDD and may be a potential, and novel pharmacological target for the treatment of MDD.

Prognostic value of cyclin E and its relation to blood vessel invasion in rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of cyclin E in rectal carcinoma and its prognostic significance.</p><p><b>METHODS</b>Cyclin E expression was examined by Western blotting in tumor tissue samples from 130 potentially resected rectal cancer patients with pathological stages I- III. Blood vessel invasion (BVI) was detected by immunohistochemistry. Multivariate analysis using the COX proportional hazards models was applied to evaluate the independent prognostic tumor markers of rectal cancer.</p><p><b>RESULTS</b>The high expression rate of cyclin E in rectal carcinoma tissue was 23.1%(30/130). Except for a positive correlation with BVI and the gross configuration of tumor, the expression of cyclin E showed no significant relation to other clinicopathological factors. The 5-year disease-specific survival rate of cyclin E high expression group was 29.2%, which was significantly lower as compared to that of cyclin low expression group 70.5% (P<0.05). Multivariate analysis revealed that histology and cyclin E expression were independent prognostic indicators for rectal cancer patients at stages I- III. Compared to those with low expression levels, patients with high cyclin E levels had the hazard ratio (95%CI) for death from rectal cancer for 3.544 (1.528-8.215). In stage I- II, multivariate analysis showed that stronger predictive values of cyclin E expression even were detected. Patients with low cyclin E expression and negative BVI had a significantly better prognosis than those with high cyclin E expression and positive BVI.</p><p><b>CONCLUSIONS</b>The expression of cyclin E is independent prognostic factor in rectal carcinoma at stages I- III. Detecting the expression of cyclin E and/or combined with BVI may help to predict clinical outcome and design further individualized intensive adjuvant treatment.</p>