Inhibition of subicular seizure-labeled c-fos+ neurons alleviates cognitive deficit in epilepsy / 中国药理学与毒理学杂志

OBJECTIVE Cognitive deficit is a com-mon comorbidity in temporal lobe epilepsy(TLE)and that is not well controlled by current therapeutics.Currently,how epileptic seizure affects cognitive performance remains largely unclear.The subiculum is the major out-put of the hippocampus,which projects to entorhinal cor-tex and other more distinct brain regions.Physiologically,the subiculum codes spatial working memory and naviga-tion information including place,speed,and trajectory.Importantly,prior studies have noted the importance of the subiculum in the beginning,spreading,and generaliz-ing process of hippocampal seizure.How seizure-activated neurons in subiculum participate in cognitive impairment remains largely elusive.METHODS In this study,we sought to label the subicular seizure-activated c-fos+ neu-rons with a special promoter with enhanced synaptic activity-responsive element E-SARE in the subiculum,combined with chemogenetics and designer receptors exclusively activated by designer drugs(DREADDs),Ca2+ fiber photometry approaches,and behavioral tasks,to reveal the role of these neurons in cognitive impairment in epilepsy.RESULTS We found that chemogenetic inhibi-tion of subicular seizure-tagged c-fos+ neurons(mainly CaMK Ⅱ α+ glutamatergic neurons)alleviates seizure generalization and improves cognitive performance in the hippocampal CA3 kindling TLE model.While inhibition of seizure-labeled c-fos+ GABAergic interneuron shows no effect on seizure and cognition.As a comparison,che-mogenetic inhibition of the whole subicular CaMK Ⅱ α+ neuron impairs cognitive function in na?ve mice in basal condition.Notably,inhibition of subicular seizure-tagged c-fos+ neurons enhances the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks.CONCLUSION Our results dem-onstrate that subicular seizure-activated c-fos+ neurons contribute to cognitive impairment in TLE,suggesting sei-zure-tagged c-fos+ neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.

Clinical features of anti-signal recognition particle antibody-positive patients with dermatomyositis or clinically amyopathic dermatomyositis / 中华皮肤科杂志

Objective@#To investigate the clinical features of anti-signal recognition particle (SRP) antibody-positive patients with dermatomyositis/clinically amyopathic dermatomyositis (DM/CADM) .@*Methods@#Clinical data were collected from 90 patients with DM/CADM, who were hospitalized at the Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from June 2015 to July 2017. Immunoblotting assay was performed to determine the serum level of anti-SRP antibody in these patients. Statistical analysis was carried out using t test and Chi-square test.@*Results@#Of the 90 patients with DM/CADM, 11 (12.2%) were positive for serum anti-SRP antibody, including 6 with DM and 5 with CADM. Among 82 adult patients with DM/CADM, the prevalence of malignant tumors was significantly higher in the patients with anti-SRP antibody than in those without (7/9 vs. 31.5%[23/73], χ2 = 7.394, P = 0.006) . The 11 patients with anti-SRP antibody had typical DM skin lesions, and their cutaneous dermatomyositis disease area and severity index (CDASI) was 18.1 ± 2.9. The prevalence of "angel wings sign" (aliform erythema on the trunk) was significantly higher in the patients with anti-SRP antibody than in those without (7/11 vs. 29.9%[20/67], Fisher′s exact test, P = 0.028) . The positive rate of antinuclear antibody was significantly higher in the patients with anti-SRP antibody than in those without (4/8 vs. 16.7%[13/78], χ2 = 6.053, P = 0.014) . Magnetic resonance imaging of muscles of both thighs of the 10 patients with anti-SRP antibody (6 with DM and 4 with CADM) showed the presence of abnormal signals in the thigh muscle group in 8, swelling of the muscle group in 2, subcutaneous edema in 2, myofascial swelling in 1, and no abnormities in 2. No interstitial lung disease or myocardial involvement was observed in the patients with anti-SRP antibody.@*Conclusions@#The anti-SRP antibody-positive patients with DM/CADM showed a high prevalence of "angel wings sign" , and a high risk of malignant tumors. Early detection of the anti-SRP antibody in patients with DM/CADM is helpful to predict the occurrence of malignant tumors.

Polysorbate-80 modified neurotoxin nanoparticle with its transport and cytotoxicity against blood-brain barrier / 药学学报

This study was aimed at the transport across blood-brain barrier (BBB) of polysorbate-80 modified neurotoxin loaded polybutylcyanoacrylate nanoparticle (P-80-NT-NP) and its cytotoxicity. An in vitro model of BBB using rat brain microvascular endothelial cells (rBMECs) was established. The cytotoxicity of P-80-NT-NP was measured by the MTT assays, where neurotoxin (NT), nanoparticle (NP), neurotoxin nanoparticle (NT-NP) as control, and the permeability of P-80-NT-NP was determined by using of Millicell insert coculture with rBMECs and fluorescence spectrophotometry. MTT results showed that NT, NP, NT-NP and P-80-NT-NP were avirulent to rBMECs when the concentration of NT was lower than 200 ng x mL(-1). But the cytotoxicity of NP, NT-NP and P-80-NT-NP would be augmented accordingly as concentration increased (P 0.05). When the concentration of NT was 150 ng x mL(-1), the permeability on rBMECs of P-80-NT-NP and NT-NP were both significantly higher than that of NT (P < 0.01), and the permeability of P-80-NT-NP was greater than that of NT-NP (P < 0.05). In conclusion, polysorbate-80 modified neurotoxin nanoparticles can transport across the BBB, while concentration of NT is greater than 200 ng x mL(-1), P-80-NT-NP has a little cytotoxicity against rBMECs.

Analysis on the metabolites of mesaconitine in the rat urine by liquid chromatography and electrospray ionization mass spectrometry / 药学学报

The mesaconitine and its major metabolites in the rat urine were identified by liquid chromatography and electrospray ionization tandem mass spectrometry. The rat urine was collected for consecutive 24 hours from the rat following intragastric infusion of mesaconitine, subsequently which were enriched and purified using solid phase extraction. The metabolites of mesaconitine in the rat urine were analyzed by the liquid chromatography and electrospray ionization tandem mass spectrometry. It is shown that the parent drug mesaconitine and its metabolites were found in the rat urine, such as hypo-mesaconitine glucuronic acid conjugate, 10-hydroxy-mesaconitine, 1-O-demethyl mesaconitine, deoxy-mesaconitine and hypo-mesaconitine. Among the five of metabolites, the hypo-mesaconitine glucuronic acid conjugate (m/z 766) was first discovered as the aconitine in rats phase II metabolites, which revealed a new way of mesaconitine metabolism in rats.

Pharmacodynamics Research of Qilian Compound Oral Solution Treating Digestion Ulcer / 浙江中医药大学学报

[Objective]Through the experimental study,appraise the curative effect of Qilian Compound Oral Solution on Digestion Ulcer.[Method]According to pharmacodynamics experimental technique of anti-ulcer,carry on the ulcer to intervene experiment separately corresponding to stirring,the medicine,the surgery of ulcers model.[Result]The effect of suppression ulcer index is remarkable to kinds of ulcer,also has certain suppression rate to the ulcer,the effect similar to Masculine group.[Conclusion]The Qilian Compound Oral Solution may remarkably resist the mouse gastric ulcer caused by stirring,Indomethacin and the pylorus tied up,having the function of suppressing the ulcer.

Experimental Research of Jianlifang Granules on Anti-fatigue / 浙江中医药大学学报

[Objective]To observe the efficacy of Jianlifang granules on anti-kinetic and anti-mental fatigue by experimental research.[Methods]SPF ICR mice were randomly divided into 5 groups:negative control group,Sanlejiang group,low-dose Jianlifang granules group,middle-dose Jianlifang granules group and high-dose Jianlifang granules group.The experiments of swimming,hypoxia tolerance test,pole-jump test,sedation,analgesia and improving the ability of learning and memory were used to test the ability of anti-fatigue in mice.[Results]The time of swimming,hypoxia tolerance,pole-jump and locomotor activity was remarkably prolonged in different doses of Jianlifang granules groups and Sanlejiang group compared with the negative control;the reaction time of licking foot was delayed and the pain threshold was increased;the correct rate of water maze test was significantly improved and the time of reaching destination was shortened(P

Experimental Research on Jinqianduizuo Mixture Preventing and Treating Cholelithiasis / 浙江中医药大学学报

ObjectiveTo observe the preventative and therapeutical effect on bile pigment calculus of Jinqianduizuo Mixture which is a traditional Chinese medicine empirical formula and provide foundation for the therapy of cholelithiasis. MethodUsing the model of bile pigment calculus in guinea pigs. Observing the gall bladder’s shape,the rate of forming gallstone and the total bile. Then making biochemical determination of the bile and the blood serum. Result There are significant differences between model control group and three treated groups of Jinqianduizuo Mixture in the rate of forming gallstone,the bilious quantity,the contents of total bilirubin and total bile acids. While in the contents of direct bilirubin,total cholesterol,triglycerides and high-density lipoproteins,they have no significant difference. ConclusionThe results indicate that Jinqianduizuo Mixture can conspicuously cut down the gallstone’s incidence of guinea pigs and can obviously promote the bilious externalization in guinea pigs. It also can promote bile secretion distinctly,but have no evident effect on the ingredients of blood-lipid.

Experimental study on effect of JianLiKeLi on immune function of rat with exercise-induced fatigue / 中华中医药杂志

Objective: To observe the effect of JianLiKeLi(JLKL) on immune function of rat with exercise-induced fatigue and discuss the mechanism of its anti-fatigue.Methods: SPF healthy SD rats were randomly divided into five groups:the control group,the SLJ group,the low dose of JLKL group,middle dose of JLKL group and high dose of JLKL group.The chronic fatigue model was established by exhaustive swimming.Eyeball was removed to collect blood,and the ability of T lymphocyte proliferation,NK cells,IL-1 and IL-6 were tested.Results: Compared with the control group,T cells proliferation in the high and middle dose of JKLL groups increased,the activities of NK cells,IL-1 and IL-6 in the three doses of JLKL groups and the SLJ group were all higher(P