Current status of treatment and drug discovery for epilepsy / 药学学报

Epilepsy is one of the most common neurological conditions, which is characterized by recurrent unprovoked seizures. Drug treatment is still the main method for the disease. Although remarkable progress has been made in the development of antiepileptic drugs in recent years, there is still a poor curative effect on patients with refractory epilepsy. This review will focus on the current status and pathogenesis of epilepsy, as well as the antiepileptic drugs (targeting sodium channels, calcium channels, potassium channels, and the balance of γ-aminobuyric acid /glutamate system, respectively) that have been developed based on classical epileptogenic mechanisms. Further the antiepileptic drugs acting on new targets (epigenetic interferers, synaptic vesicle glycoprotein 2A modulators, mammalian target of rapamycin signal pathway blockers, carbonic anhydrase inhibitors, cannabidiol and adenosine inhibitors) have also been discussed.

Enhancement of T Follicular Helper Cell-Mediated Humoral Immunity Reponses During Development of Experimental Autoimmune Myasthenia Gravis / 神经科学通报·英文版

Myasthenia gravis (MG) is a prototypical antibody-mediated neurological autoimmune disease with the involvement of humoral immune responses in its pathogenesis. T follicular helper (Tfh) cells have been implicated in many autoimmune diseases. However, whether and how Tfh cells are involved in MG remain unclear. Here, we established and studied a widely-used and approved animal model of human MG, the rat model with acetylcholine receptor alpha (AChRα) subunit (R-AChR)-induced experimental autoimmune myasthenia gravis (EAMG). This model presented mild body-weight loss 10 days after the first immunization (representing the early stage of disease) and more obvious clinical manifestations and body-weight loss 7 days after the second immunization (representing the late stage of disease). AChR-specific pre-Tfh cells and mature Tfh cells were detected in these two stages, respectively. In co-cultures of Tfh cells and B cells, the number of IgG2b-secreting B cells and the level of anti-AChR antibodies in the supernatant were higher in the cultures containing EAMG-derived Tfh cells. In immunohistochemistry and immunofluorescence assays, a substantial number of CD4/Bcl-6 T cells and a greater number of larger germinal centers were observed in lymph node tissues resected from EAMG rats. Based on these results, we hypothesize that an AChR-specific Tfh cell-mediated humoral immune response contributes to the development of EAMG.

Levels of Th1/Th2 in spleen lymphocyte of colitic mice without or with Trichinella spiralis infection / 中国免疫学杂志

Objective:To study the levels of Th1 and Th2 in spleen lymphocyte of TNBS and OXZ colitis without or with Trichinella spiralis(T.spiralis)infection.Methods:Female BALB/c mice were randomly divided into 3 groups:50％ Ethanol,TNBS or OXZ,T.spiralis+TNBS or OXZ(at least 6 in each group when mice were killed).The ratio of Th1/Th2 lymphocyte in spleen was detected by FCM with three color intracellular cytokine staining.Results:In spleen lymphocyte of TNBS colitic mice with prior nematode infection,the ratio of Th1/Th2 were not significantly different compared with that seen in colitic mice without prior nematode infection on day 3 post-induction of colitis(P＞0.05),the ratio of Th1/Th2 was significantly lower than which on day 7 post-induction of colitis (P＜0.05).In spleen lymphocyte of OXZ colitic mice with prior nematode infection on days 3 and 7 post-induction of colitis,the ratio of Th1/Th2 was significantly higher than that seen in colitic mice without prior nematode infection(P＜0.05).Conclusion:Infection of mice with T.spiralis distracts the mucosal immune system response from a Th1 response toward a protective Th2 response and up-regulate Tr1-cytokines with an attendant reduction in the severity of colonic damage and balance of Th1/Th2.Prior T.spiralis infection doesn't reduce the severity of OXZ-induced colitis,but without aggravating colitis.

A review of 3D printing via fused deposition modeling in pharmaceutics / 药学学报

Three dimensional printing (3D printing) has been known as additive manufacturing technique based on digitally-controlled deposition of materials. Fused deposition modeling (FDM) is one of techniques commonly used in 3D printing, in which materials are soften or melt by heat to create objects during printing. This paper is prepared to review the research and application of 3D printing via FDM in the pharmaceutical sciences, including its advantages and limitations.

Association between transforming growth factor-β1 gene polymorphism and risk of chronic hepaitis B virus infection progressing to hepatocellular carcinoma / 国际检验医学杂志

Objective To investigate the relationship between the polymorphism of transforming growth factor-β1 (TGF-β1 ) gene and risk of chronic hepatitis B virus(HBV)infection progressing to hepatocellular carcinoma(HCC).Methods 120 patients with chronic HBV infection(case group)and 100 age-and sex-matched healthy individuals(healthy control group)were randomly enrolled to this study.The polymerase chain reaction-restriction fragment length polymorphism technique was adopted to detect the single nucleotide polymorphism of TGF-β1 gene(T29C),and made the comparative analysis combined with TGF-β1 mRNA level. Results The risk of HCC occurrence in the patients carrying genotype CC was decreased than that in the patients carrying geno-type TT (OR=0.317,95%CI =0.110-0.913,P =0.033;OR=284,95%CI =0.093 -0.866,P =0.027),the risk of HCC in pa-tients carrying allele C was significantly decreased compared with that in the patients carrying allele T(OR =0.570,95%CI =0.341 -0.953,P =0.032;OR=0.548,95%CI =0.320-0.936,P =0.028).In the HCC group,the patients carrying genotype CC had the lower lever of TGF-β1 mRNA.Conclusion TGF-β1 gene polymorphism(T29C)may be related to the risk of chronic HBV infection progressing to HCC.

Generation and comparison of two genetically engineered mouse models of ErbB2/Neu positive-PTEN deficient breast cancer / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To generate two genetically engineered mouse models of ErbB2/Neu positive-PTEN deficient breast cancer and to compare their biological properties.</p><p><b>METHODS</b>The genetically engineered mice previously developed with mouse mammary tumor virus (MMTV) promoter driven expression of activated ErbB2/Neu and recombinant Cre (FVB/N-MMTV-NIC) were interbred with Flox-PTEN mice; and FVB/N-ErbB2KI mice, harboring endogenous promoter driven activated ErbB2/Neu expression, FVB/N-MMTV-Cre mice and the flox-PTEN mice were interbred. Neu, Cre and PTEN genes were amplified by PCR for genotyping of the offsprings. ErbB2/Neu and PTEN expression in mammary tumors were detected by immunohistochemistry. Tumor formation time, tumor number, histopathology and lung metastasis were compared between two models, Ki-67 expression was detected by immunohistochemistry, and TUNEL staining of tumor tissues was performed.</p><p><b>RESULTS</b>Two genetically engineered mouse models of ErbB2/Neu positive-PTEN homozygous deficient breast cancer were generated. The models were confirmed by genotyping and immunohistochemistry. One model with exogenous MMTV promoter driven expression of activated ErbB2/Neu and Cre coupling PTEN disruption was designated as NIC/PTEN(-/-) mice, and the other with MMTV-Cre induced endogenous promoter driven expression of activated ErbB2/Neu with PTEN disruption was designated as ErbB2KI/PTEN(-/-) mice. The tumor formation time in NIC/PTEN(-/-) mice was significantly shorter than that of ErbB2KI/PTEN(-/-) mice (30 vs 368 d, P<0.01); the number of tumor and incidence of lung metastasis was also significantly higher in NIC/PTEN(-/-) mice (10 vs 1-2 and 75.0% vs 37.5%, respectively, Ps<0.01). The Two models displayed distinct histopathological morphology. NIC/PTEN(-/-) tumor showed more Ki-67 positive cells than ErbB2KI/PTEN(-/-) tumor did (86.9%±2.8% vs 37.4%±7.2%, P<0.01), while the amount of cell apoptosis in tumors was not significantly different between two models.</p><p><b>CONCLUSION</b>Two genetically engineered mouse models of ErbB2/Neu positive-PTEN homozygous deficient breast cancer with different phenotypes have been successfully generated, which may provide useful resource for further investigation of the initiation and progression of HER2/ErbB2 breast cancer, as well as for the development of novel prevention and treatment regimens of this malignance.</p>

Synergistic effect and mechanism of cineole and terpineol on in-vitro transdermal delivery of Huperzine A from microemulsions

The aim of the present study was to investigate the influence and the mechanisms of cineole and terpineol on the in-vitro transdermal delivery of huperzine A from microemulsions, and their potential synergistic effect on the permeation enhancement. The transdermal delivery of huperzine A from microemulsions with different concentrations of cineole and terpineol through the rat abdominal skin was determined by Franz-type diffusion cells. The partition coefficient of huperzine A between the full thickness skin and microemulsion was determined. Attenuated total reflection-Fourier transform infrared spectroscopy [ATR-FTIR] was carried out to analyze the effects of cineole and terpineol on the biophysical properties of the stratum corneum [SC] and the mechanisms of permeation enhancement. These results indicated that cineole and terpineol could synergistically increase the transdermal delivery of huperzine A from microemulsions through increasing the partition and diffusion coefficients of huperzine A. ATR-FTIR studies further validated the synergistic effect and revealed that the enhancing mechanisms were due to increasing the disorderliness and fluidity of SC lipid alkyl chains, disrupting the structure of keratin in SC, and extracting SC lipids. In conclusion, cineole and terpineol, acting synergistically to enhance the transdermal delivery of huperzine A from microemulsions, might provide an alternative permeation enhancer combination for the transdermal delivery of huperzine A

Latest update on immunotherapy of Epstein-Barr virus-associated post-transplantation lymphoproliferative disease / 中国当代儿科杂志

Epstein-Barr virus (EBV)-associated post-transplantation lymphoproliferative disease (EBV-PTLD) is a potentially life-threatening complication after hematopoietic stem cell transplantation or solid organ transplantation. In the last decade, the survival of patients with EBV-PTLD has been significantly improved by immunotherapeutic interventions among high-risk patients. The immunotherapeutic interventions for EBV-PTLD include reduction in immunosuppression, CD20 monoclonal antibodies (rituximab) as monotherapy or in combination with chemotherapy, and adoptive immunotherapy with EBV-specific T cells. This paper reviews the latest update on the high-risk factors, clinical manifestations and immunotherapy of EBV-PTLD.

Four hundred and eighty five cases of HIV/AIDS patients based on expert interpretation of characteristics of syndromes / 中国中药杂志

This study aims to explore HIV traditional Chinese medicine (TCM) syndrome distribution and TCM syndrome evolution. The 485 cases of HIV/AIDS patients from 10 major regions of the AIDS epidemic in HIV. In this study, the interpretation of experts to explore the TCM syndromes in different routes of infection, different stage of disease, with syndrome distribution under different interventions. The results showed that Yang deficiency of spleen and kidney and liver Qi stagnation is the most common type in the patients who with sexually transmitted infections. TCM syndrome type most commonly seen in patients infected by the blood collection is yang deficiency of spleen and kidney and spleen deficiency wet-sheng. Including Yang deficiency of spleen and kidney with the highest frequency in patients with AIDS, people who with sexually transmitted infections and patients that treated with simple HAART were prone to liver-stagnation and spleen-deficiency syndrome. In short, such as Yang deficiency of spleen and kidney, liver Qi stagnation, deficiency of both Qi and Yin, deficiency-weakness of spleen-Qi, syndrome of damt-heat ftagnation were the main AIDS syndrome types.

Research of Chinese herbal compound on promoting HIV immune reconstitution / 中国中药杂志

This article reviews the research reports of Chinese herbal compound on AIDS immune reconstitution for nearly 20 years, found that Chinese herbal compound has exact clinical efficacy for AIDS immune reconstitution. Therefore, we should give full play to the unique advantages of Chinese herbal compound in improving immunity, thus improving symptoms and improve quality of life, to achieve optimal clinical treatment of AIDS.

Research progress of Chinese medicine treatment of HAART-related hyperlipidemia / 中国中药杂志

Highly active antiretroviral therapy (HAART) for the treatment of HIV infection had a revolutionary impact, with the universal application of the anti-retroviral drugs, HAART-related adverse reactions have attracted more and more attention. HAART-related hyperlipidemia is one of the common adverse reactions with more and more scholars study the pathogenesis and therapy of hyperlipidemia in recent years. This article elaborated the latest research of Chinese medicine treatment of HAART-related hyperlipidemia.

Research development of HIV drug resistance / 中国中药杂志

Highly active antiretroviral combination therapy significantly reduced the mortality, but in the high-speed copying, high genetic variation and drug selection pressure under the effect of the increasingly serious problem of drug resistance greatly weakened the role of HAART inhibit viral replication and reduce antiviral treatment. This paper reports the latest trends in HIV drug-resistance in order to develop anti-HIV drugs in clinical programs, research and development of new guidance anti-HIV-1 strategy to bring guidance.

Achene morphology cluster analysis of Taraxacum F. H. Wigg. from northeast China and molecule systematics evidence determined by SRAP / 药学学报

The achenes morphological and micro-morphological characteristics of six species of genus Taraxacum from northeastern China as well as SRAP cluster analysis were observed for their classification evidences. The achenes were observed by microscope and EPMA. Cluster analysis was given on the basis of the size, shape, cone proportion, color and surface sculpture of achenes. The Taraxacum inter-species achene shape characteristic difference is obvious, particularly spinulose distribution and size, achene color and achene size; with the Taraxacum plant achene shape the cluster method T. antungense Kitag. and the T. urbanum Kitag. should combine for the identical kind; the achene morphology cluster analysis and the SRAP tagged molecule systematics's cluster result retrieves in the table with "the Chinese flora". The class group to divide the result is consistent. Taraxacum plant achene shape characteristic stable conservative, may carry on the inter-species division and the sibship analysis according to the achene shape characteristic combination difference; the achene morphology cluster analysis as well as the SRAP tagged molecule systematics confirmation support dandelion classification result of "the Chinese flora".

Induction of apoptosis by proteasome inhibitor MG-132 in human erythroleukemia cell line K562 / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate whether proteasome inhibitor MG-132 induces apoptosis of human erythroleukemia cell line K562 and possible mechanisms.</p><p><b>METHODS</b>K562 cells were incubated with RPMI 1640 and exposed to 0, 1, 5, 10, 15 micromol/L of MG-132 for 24 hrs, respectively. The apoptosis of cells were detected by fluorescence microscope, DNA fragments and flow cytometry. The NF-kappaB mRNA expression was quantified by reverse transcription-polymerase chain reaction (RT-PCR). Expression of NF-kappaB and caspase-3 was semiquantitatively analyzed with SABC techniques. Caspase-3 activities were measured with a colorimetric method.</p><p><b>RESULTS</b>The growth of K562 cells was inhibited and the apoptosis of the cells increased after MG-132 treatment in a dose-dependent manner. After 24 hrs of 15 micromol/L MG-132 treatment, the percentage of apoptotic cells (26.5+/-0.6%) increased significantly when compared with the untreated controls (1.2+/-0.1%) (P<0.01). MG-132 treatment decreased the mRNA and protein expression of NF-kappaB, and increased the protein expression of caspase-3.</p><p><b>CONCLUSIONS</b>MG-132 can induce apoptosis of human erythroleukemia cell line K562 through the down-regulation of NF-kappaB expression and up-regulation of caspase-3 expression.</p>

Study on determination of entrapment efficiency of sinomenine liposomes / 中国中药杂志

<p><b>OBJECTIVE</b>To establish an HPLC method for the determination of entrapment efficiency of sinomenine liposomes.</p><p><b>METHOD</b>The liposomes and dissociated drugs were separated by sephadex filtration, mini-column centrifugation and dialysis. The methodology study and the optimization of determining condition were carried out at the same time.</p><p><b>RESULT</b>Sephadex filtration could effectively separate the sinomenine liposomes from dissociated sinomenine. The column recovery was 98.8%, the average entrapment efficiency of three tests was64.9%, RSD 2.67%.</p><p><b>CONCLUSION</b>The method was simple, exact, and had a good reappearance. It can be used to examine the entrapment efficiency of sinomenine liposomes.</p>

Chemical investingation of Chinese mangrove Sonneratia apetala II / 中国中药杂志

<p><b>OBJECTIVE</b>Isolation and structural elucidation of the constituents of China mangrove Sonneratia apetala.</p><p><b>METHOD</b>chromatography methods were used for isolation of compounds, spectroscopic methods were used for structural identifyication.</p><p><b>RESULT</b>seven known compounds named (+/-) symgaresinol, betulinic acid, lupeol, lupeone, stigmast-5-ene-3beta, 7alpha-diol, beta-alpha myrin hexadecaneate, physcoion were isolated.</p><p><b>CONCLUSION</b>these known compouns were unreported previously from this plant.</p>