AIM　To determine whether ONO-1078 {pranlukast, 4-oxo-8-［p-(4-phenylbutyloxy) benzoyl-amino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate}, a potent leukotriene antagonist, has protective effect on focal cerebral ischemia in mice. METHODS　Focal cerebral ischemia was induced by permanent middle cerebral artery (MCA) occlusion in mice. ONO-1078 (0.01, 0.05, 0.10 mg*kg-1), dexamethasone (0.5 mg*kg-1), nimodipine (0.2 mg*kg-1) or saline (control) were injected ip once daily for 3 days, and 30 min before MCA occlusion. Twenty-four hours after cerebral ischemia, the neurological scores were evaluated, infarct volumes and areas of the right and left cerebral hemispheres were measured by computer imaging analysis. RESULTS　ONO-1078, dexamethasone and nimodipine reduced the neurological scores. ONO-1078 and dexamethasone reduced the ratio of right/left hemisphere area, indicating inhibition of brain edema, while nimodipine showed no effect. ONO-1078 dose-dependently reduced infarct size, and dexamethasone and nimodipine showed the same effect. CONCLUSION　ONO-1078 showed protective effect on focal cerebral ischemia. This may represent a novel approach to the treatment of acute cerebral ischemia.

Objectives To explore the correlation of level of serum 25-hydroxyvitamin D with pulmonary function in adult with asthma. Methods Patients were divided into Asthmatic group(n=62)and Control group (n=28). The Asthmatic group was further divided into Mild Group (n=6), Moderate Group (n=13) and Severe Group (n=43). Serum levels of 25-hy?droxyvitamin D [25(OH)D], denoted as 25(OH) Vit D was detected by ELISA. Pulmonary function indicators,including FVC (forced vital capacity) , FEV1 (forced expiratory volume in 1 second) , FEV1%predicted , and FEV1/FVC%were deter?mined by a pulmonary function testing device. General profiles such as medical history, age and height as well as serum VitD levels were compared between subgroups of the asthmatic groups and between two genders. Serum levels of 25 (OH) VitD were compared between asthmatic group and control group while its correlation with FEV1%predicted were calculated in all three sub asthmatic groups. Results There was no significant difference in medical history, age, height and the 25(OH) VitD levels between male and female participants. Serum 25(OH) Vit D level was significantly lower in the asthmatic patient group [(29.69±20.45) nmol/L] compared to that in control group [(75.16±4.06) nmol/L] (P<0.05). It was significantly lower in severe sub group than those in the mild and moderate sub groups. The differences were both statistically significant ( P<0.05). There were positive correlations between serum 25(OH) Vit D levels and FEV1%predicted ( P<0.05) in all sub asth?matic groups. Conclusion Vitamin D deficiency is highly prevalent in asthmatic patients, and there is a strong correlation between 25(OH) Vit D asthma severity as well as between lung function.

SIRT3, SIRT4 and SIRT5 are located in mitochondria and also known as mitochondrial sirtuins. They play important roles in regulating many cellular functions including cell survival, cell cycle or apoptosis, DNA repair and metabolism. Mitochondrial sirtuins are involved in the protection of mitochondrial integrity and energy metabolism under stress regulating the expression of neurotransmitter receptors, neurotrophins, extracellular matrix proteins and various transcription factors, thus involved in epileptogenesis triggered by both genetic or acquired factors. Here we review research progress on the actions of mitochondrial sirtuin in epilepsy; and discuss the challenges and perspectives of mitochondrial sirtuin as a potential therapeutic target for epilepsy.
Apoptosis ; Epilepsy/genetics* ; Humans ; Mitochondria/genetics* ; Sirtuin 3 ; Sirtuins

OBJECTIVE To explore the safe and effective dose of sirolimus (Rapamycin,Sir) and its effect on seizure comorbidities. METHODS Immature C57BL/6 mice at postnatal 10 d of age were administered with kainic acid(KA) 12.0 mg · kg-1 intraperitoneally by a single injection to induce acute seizure. Sir 0.3, 1.0 and 3.0 mg · kg-1 was injected 24 h after seizure every other day until 3 d, 1 week, 3 weeks, 5 weeks and 6 weeks. Western blotting analysis was used to detect the expression and phos?phorylation level of S6 protein and to determine the minimum effective dose of Sir. Effect of the mini?mum effective dose of Sir on cognitive function and body growth was observed by several evaluations. Immunofluorescent intensity of Doublecortin (DCX) immunofluorescent staining was conducted to evaluate the development of neurons in the hippocampus. Morris water maze was used to assess the cognitive function. Tail suspension test, O maze and new object recognition test were used to study the anxiety-like behaviors of mice. RESULTS The result of Western blotting showed that Sir 0.3 mg · kg-1 had no significant effect on the phosphorylation of S6 protein in normal mice or KA mice, whereas 1.0 and 3.0 mg · kg- 1 could significantly inhibit the phosphorylation of S6 protein in KA mice (P<0.05). Sir 1.0 mg·kg-1 had no obvious effect on DCX-positive cells or body wass. Morris water maze showed that KA-induced seizure resulted in prolonged escape latency and swimming length (P<0.05), and a decreased crossing number of target quadrant (P<0.05). Sir 1.0 mg·kg-1 significantly reversed the deficit of cognitive function of KA-induced seizure mice (P<0.05), whereas no significant difference was found between Sir group and normal control group. Compared with normal control group, model group showed increased freezing time in tail suspension test (P<0.05), decreased migration length and reten?tion time in open arms in O maze (P<0.05), decreased retention time and touch frequency with new objects, migration length and average speed in new object recognition test (P<0.05). Sir 1.0 mg · kg-1 significantly reversed the above anxiety and depression status, whereas no significant difference was found between sirolimus group and normal control group. CONCLUSION Sir 1.0 mg · kg-1 inhibits the abnormal activation of mTOR pathway and the formation of epilepsy comorbidity in immature mice. Along with its mild side effect in development, Sir 1.0 mg · kg-1 will be an ideal dose to be used in the treatment of seizure in immature mice.

Objective To observe the clinical efficacy of Zhuang’s Moxibustion plus acupuncture in treating spastic paralysis due to craniocerebral injury.Method Ninety-two patients with spastic paralysis due to craniocerebral injury were randomized into a treatment group of 60 cases and a control group of 32 cases. The control group was intervened by conventional internal medicine and rehabilitation, while the treatment group was intervened by Zhuang’s moxibustion plus acupuncture in addition to the intervention given to the control group. The modified Ashworth Scale (MAS) was adopted to evaluate the clinical efficacy.Result The total effective rate was 75.0% in the treatment group versus 65.6% in the control group, and the between-group difference was statistically significant (P<0.01).Conclusion Zhuang’s moxibustion plus acupuncture is an effective approach in treating spastic paralysis due to craniocerebral injury.

OBJECTIVETo investigate the effect of rapamycin, an mTOR inhibitor, on learning and memory ability of mice with pilocarpine (PILO)-induced seizure.

METHODSOne hundred and sixty male adult ICR mice were randomly grouped as vehicle control (n=20), rapamycin control (n=20), PILO model (n=40), rapamycin pre-treatment (n=40) and rapamycin post-treatment (n=40). PILO model and rapamycin treatment groups were injected with PILO to induce temporal lobe seizure. Rapamycin was administrated for 3 days before or after seizure. Morris water maze, Y maze and open field were used for the assessment of learning and memory, and FJB and Timm staining were conducted to detect the neuronal cell death and mossy fiber sprouting, respectively.

RESULTSNo significant cell death was observed in the mice with PILO-induced seizure. The learning and memory were impaired in mice 7 to 10 days after PILO-induced seizure, which was evident by prolongation of avoiding latency (P<0.05), decrease in number of correct reaction (P<0.01) and number of crossing (P<0.05). Treatment with rapamycin both pre-and post- PILO injection reversed seizure-induced cognitive impairment. In addition, rapamycin inhibited the mossy fiber sprouting after seizure (P<0.001).

CONCLUSIONRapamycin improves learning and memory ability in ICR mice after PILO-induced seizure, and its mechanism needs to be further studied.

Animals ; Cell Death ; drug effects ; Disease Models, Animal ; Epilepsy ; chemically induced ; drug therapy ; Learning ; drug effects ; Memory ; drug effects ; Mice ; Mice, Inbred ICR ; Neurons ; drug effects ; pathology ; Pilocarpine ; toxicity ; Sirolimus ; pharmacology

OBJECTIVETo determine the effects of ginsenosides Rb1(GSRb1) on learning and memory and expression of somatostatin (SS) in the hippocampus and the frontal cortex in rat model of sleep deprivation (SD).

METHODSRats were randomized into groups of SD 2 d, SD 4 d, SD 6 d, and SD 0 d, while each group was sub-divided into GSRb1 group and normal saline (NS) sub-groups. Rats were intraperitoneal administered with 30 mg/(kg*d) of GSRb1 or NS for 7 d, then the learning and memory abilities were examined by measuring average swimming speed and mean escape latency using Morris maze.Expression of somatostatin was detected with immunohistochemical method and image analysis in the hippocampus and the frontal cortex.

RESULTSCompared with SD 0 d rats, SD rats exhibited significant decrease in the average swimming speed and increase in the escape latency (P <0.01). The expression of somatostatin in the hippocampus was decreased significantly in SD 2 d, SD 4 d and SD 6 d rats (P<0.05). However, decrease was only observed in SD 4 d and SD 6 d rats in the frontal cortex (P <0.05). Parallel comparison between NS control and GSRb1 treated rats demonstrated that rats treated with GSRb1 in each subgroup exhibited faster swimming speed and shorter escape latency (P <0.05). Meanwhile, the expression of somatostatin was increased in SD 2 d, SD 4 d and SD 6 d rats in the hippocampus and in SD 4 d and SD 6 d rats in the frontal cortex (P <0.05), respectively.

CONCLUSIONGSRb1 enhances the expression of somatostatin in sleep deprivation rats and subsequently may improve learning and memory abilities of rats.

Animals ; Brain ; metabolism ; Disease Models, Animal ; Ginsenosides ; pharmacology ; Learning ; drug effects ; Male ; Memory ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sleep Deprivation ; metabolism ; Somatostatin ; metabolism

Therapeutic monoclonal antibodies have become one of the central components of the healthcare system and continuous efforts are made to bring innovative antibody therapeutics to patients in need. It is equally critical to acquire sufficient knowledge of their molecular structure and biological functions to ensure the efficacy and safety by incorporating new detection approaches since new challenges like individual differences and resistance are presented. Conventional techniques for determining antibody disposition including plasma drug concentration measurements using LC-MS or ELISA, and tissue dis-tribution using immunohistochemistry and immunofluorescence are now complemented with molecular imaging modalities like positron emission tomography and near-infrared fluorescence imaging to obtain more dynamic information, while methods for characterization of antibody's interaction with the target antigen as well as visualization of its cellular and intercellular behavior are still under development. Recent progress in detecting therapeutic antibodies, in particular, the development of methods suitable for illustrating the molecular dynamics, is described here.

The traditional Chinese medicine Aralia elata (Miq.) Seem., also known as Aralia mandshurica, has the effect of "tonifying Qi and calming the mind, strengthening the essence and tonifying the kidneys, and dispelling wind and invigorating blood circulation". It is used in the treatment of neurasthenia, Yang deficiency and Qi deficiency, kidney Qi deficiency, spleen Yang deficiency, water-dampness stagnation, thirst, and bruises. Aralia elata saponins are the main components for the pharmacological effects. From the perspective of modern pharmacological science, Aralia elata has a wide range of effects, including anti-myocardial ischaemia and alleviation of secondary myocardium ischemic reperfusion injury by regulating ionic homeostasis, anti-tumor activity by inhibiting proliferation, promoting apoptosis and enhancing immunity, hypoglycemia and lipid lowering effects by regulating glucose and lipid metabolism, and hepato-protective, neuroprotective, anti-inflammatory/analgesic effects. The studies on pharmacological mechanisms of Aralia elata will be conducive to its development and application in the future. This article reviews the research progress of Aralia elata domestically and internationally in the last two decades and proposes new directions for further research.
Aralia ; Yang Deficiency ; Apoptosis ; Saponins/pharmacology* ; Myocardial Ischemia

OBJECTIVE Parkinson's disease(PD)is a progressive neurodegenerative disease clinically char-acterized by dyskinesia,tremor,rigidity,abnormal gait,whereas 90%of patients with PD suffer from defects of the sense of smell before the appearance of the motor dysfunctions.However,the mechanism of olfactory disor-der is still not clear.METHODS We utilized olfaction based delayed paired association task in head-fixed mice.We focused on functional role of neural circuit using opto-genetic techniques.In addition,we viewed the synaptic transmission by slice physiological recording and count-ed the cell number of targeted circuits.RESULTS AND CONCLUSION In our experiments,olfactory working memory impairments were found in the PD mice,and the working memory impairment appeared before motor dys-functions.Furthermore,we also investigated the functional role of neural circuit for olfactory working memory in PD mice.Meanwhile,the excitatory post synaptic currents were decreased as a result of presynaptic release proba-bility suppression in PD mice.However cell loss wasn't found in working memory related circuit recently.These will provide a new idea of clinic diagnosis for PD.