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Parkinson's disease (PD) is the second most common chronic progressive neurodegenerative disorder in the elderly after Alzheimer' 8 disease. Over the decadcs, levodopa has been considered the main therapy against PD. However, long term use of levodopa is often accompanicd by adverse reactions, including nausea, insomnia, dyskinesia, and "wetring-off" and " on-o/T" phenomena, ranging in severity from mild and non-disabling to incapacitating. On March 21 2017, US Food and Drug Administration ( FDA ) approved safinamide us an adjunctive treatment to levodopa in patients vilh PD experiencing " off" episodes. As a new drug for the treatment of PD, safinamide has the advantage of high selectivity and safely. This paper reviews the mechanisms and some clinical trials of safinamide.
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Objective To study the impact of aspirin resistance(AR)on the recurrence of artery athero-sclerotic cerebral infarction,and analyze the risk factors of AR. Methods According to TOSAT classification, newly diagnosed cerebral infarction patients with artery atherosclerotic cerebral infarction were selected into groups,and aspirin enteric-coated tables(ASP)was used to prevent platelet aggregation.One week later,the inhi-bition rate of platelet was detected by thrombelastogram(TEG),and the patients were divided into aspirin sensi-tive(AS)group and AR group,and were followed-up for at least 6 months.According to whether they were recur-rent cerebral infarction,the patients were divided into recurrent group and non-recurrent group. Then,statistical analysis was conducted.Results The incidence rate of AR in recurrent group was significantly higher than that in non-recurrence group(P < 0.05);the recurrence rate of cerebral infarction in AR group was significantly higher than that in AS group(P<0.05).When compare the clinical indexes between the recurrence group and non-recur-rence group,age,diabetes,TC,Hcy,Apo-a in the two groups were different(P<0.05).In recurrent group,the distribution of diabetes,LDL-C and Hs-CRP were different between AR and AS group(P<0.05).Age,gender, hypertension,diabetes,Hs-CRP and TC were risk factors for AR.Conclusions AR plays an important role in the relapse of artery atherosclerotic cerebral infarction and it is more likely to occur especially accompanied by adverse factors such as underlying diseases. TEG can be used to detect AR rapidly and conveniently,which has practical significance in preventing recurrent cerebral infarction.
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The cerebral cortex contains a large variety of neuronal cells, which connect with each other via synapses to form different neural networks and fundamental elements for brain functions such as sense, movement, learning, language and decision making. Information processing in the cerebral cortex requires the activation of individual neurons and their recurrent networks,that is,the generation of action potential (AP) (excitability of single neurons) and network activity (excitability of neural networks).Initiation of AP occurs at the axon and is determined by axonal ion channels as well as intrinsic biophysical properties.The excitability of recurrent networks is not only determined by the excitability of different types of neurons, but also regulated by the unique properties of neurotransmitter release in distinct synapses including excitatory and inhibitory ones.Traditionally,it is believed that the all-or-none AP is the only mode of information transmission-digital mode.Recent studies have shown that the subthreshold membrane potential fluctuations regulate AP-induced the synaptic transmission-analog mode. At the network level, the network activity is relatively stable, resulting from a dynamic balance of excitation and inhibition. The microcircuits of recurrent inhibition mediated by distinct inhibitory interneuron types and the modes of synaptic transmission,such as the analog mode of signal communication and asyn-chronous neurotransmitter release,play critical roles in maintaining the excitation and inhibition balance. Together,we present here some new insights into the mechanisms underlying the excitability of distinct types of cortical neurons and their interconnected networks.
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Objective To investigate the effects of stress intensity and the expected duration of stress on the inhibition ability of individual responses to stress. Methods A total of 60 cases of hospitalized patients in respiratory department were selected in the study,including 31 male cases and 29 female cases. Incorporated patients were divided into the high-stress group and the low-stress group ( 30 cases in each group) according to whether the patient accepted a invasive examination or not. Then,within each group,pa-tients were further randomly sub-divided into the acute expectation group and the chronic expectation group ( 15 cases in each group) in the form of a lottery. Detection risk disclosure was conducted at 2 hours and at 24 hours before the examination. Visual analogue scale ( VAS) and stop-signal task were used to detect the level of psychological fear and the inhibition ability of individual responses to stress of each group following informing of the detection risk,and the comparative analysis was conducted afterwards. Results ( 1) The score of psychological fear in the high-stress group was significantly increased when compared to the low-stress group ((3.90±2.71) vs (0.80±1.24)),showing statistical difference (F(1,58)=30.16, P0.05);meanwhile,no statisti-cal difference of the interaction between stress intensity and the expected duration of stress on the level of psychological fear (F(1,58)=0.031, P>0.05). (2) As for stop-signal task,the signal execution error rate of the high-stress group was significantly increased than that in the low-stress group ((9.40±5.80)%vs (8.30± 12.60)%),and the statistical difference was significant (P0.05) . Conclusion There is no interaction be-tween the effect of the stress intensity and the expected duration of stress on the inhibition ability of individu-al responses to stress. The stress intensity is more important than the expected duration of stress to exert more important influence in the inhibition ability of individual responses to stress.
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Aim Toevaluatethesynergisticeffectof anti-tumor by the pterostilbene and acetylshikonin act-ing on B16F10 cells and investigate the interrelated mechanisms.Methods Theresearchscreenedandan-alyzed the target-related of pterostilbene and ace-tylshikonin by system-pharmacological methods. The proliferative inhibition rate of B16F10 cells were meas-ured by MTT.The apoptosis in B16F10 cells were proved by both cellular morphological and biochemical methods.The expression of apoptotic genes were as-sessed via RT-PCR.The apoptotic rate and cell cycle were measured by flow cytometry.Melanoma models were established in C57BL/6 mice,and the inhibitory rateoftumorgrowthwasmeasured.Results The14 targets of pterostilbene were closely related to cell cy-cle,acetylshikonin′s 12 targets displayed a relationship with apoptosis,and correlated with p53 signaling path-way.Pterostilbene along with acetylshikonin signifi-cantly inhibited cell proliferation of B16F10 cells in a dose-dependent way and resulted a remarkable syner-gistic effect.The apoptotic rate reached highest with a blocked-cell cycle at G1 phase in the co-treatment group.The RT-PCR results showed that the expres-sions of p53,Bax and p21 were up-regulated and the expressions of Bcl-2,CDK2 and Cyclin E were down-regulated with time.The changes of p53,Bax and Bcl-2 were obvious in combined treated group.All treat-ments in vivo showed different tumor inhibition rates while co-treatment group showed highest.Conclusion Pterostilbenecooperatedwithacetylshikonininhibits the proliferation in B16F10 cells,and activates the p53 signaling pathway to induce the B16F10 cells apoptosis and a cell cycle arrest.
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Aim To study the effect of Radix Tetrastig-ma Hemsleyani Flavone ( RTHF ) on the proliferation and invasion in lung carcinoma A549 cells as well as the possible mechanisms underlying these processes. Methods A549 cells were treated with different con-centrations of RTHF for different time. MTT assay and colone formation assay were used to detect the ability of cell proliferation. Wound healing methods and tran-swell chamber assay were adopted to determine cell mi-gration and invasion. Western blotting assay was used to detect the expression of metastasis-related proteins MMP-2 , MMP-9 , and TIMP-2 . Results RTHF obvi-ously suppressed the proliferation of A549 cells in a dose-and time-dependent manner. Microscope found an apparent decrease of cells in the denude zone of cell migration and transwell testing results show that the treatment of invasion was significantly lower than the proportion in the control group ( P <0. 01 ) . The pro-tein expressions of MMP-2 and MMP-9 were down-reg-ulated and that of TIMP-2 was up-regulated in a dose-dependent manner. Conclusion RTHF inhibits the growth and invasion of lung carcinoma A549 cells, which might be achieved by down-regulating the ex-pressions of MMP-2 and MMP-9 protein.