Background: Scrophulariae Radix (SR) is a commonly used medicinal plant. Alzheimer's disease (AD) is a neurodegenerative disease for which there is no effective treatment. This study aims to initially clarify the potential mechanism of SR in the treatment of AD based on network pharmacology and molecular docking techniques. Methods: The principal components and corresponding protein targets of SR were conducted by HPLC analysis and searched on TCMSP. AD targets were searched on DrugBank, Chemogenomics, TTD, OMIM and GeneCards databases. The compound-target network was constructed by Cytoscape3.8.2. The intersection of compound target and disease target was obtained and the coincidence target was imported into STRING database to construct a PPI network. We further performed GO and KEGG enrichment analysis on the targets. Meanwhile, molecular docking study and cell experiments were approved for the core target and the active compound. Results: Through multidatabase retrieval and integration, it was found that 17 components of SR could exert anti-AD effects against 40 targets. KEGG enrichment analysis indicated that Alzheimer's disease (hsa05010) was one of the most significant AD enrichment signalling pathways. Combined with the gene expression profile information in the AlzData database, 15 targets were found to be associated with tau or beta-amyloid protein (Aβ). GO analysis indicated that the primary molecular functions of SR in the treatment of AD were neurotransmitter receptor activity (GO:0007268), postsynaptic neurotransmitter receptor activity (GO:0070997), and acetylcholine receptor activity (GO:0050435). Moreover, we explored the anti-AD effects of SR extract and ursolic acid (UA) using SH-SY5Y cells. Treatment of SH-SY5Y cells with 20 μM UA significantly reduced the oxidative damage to these neuronal cells. Conclusion: This study reveals the active ingredients and potential molecular mechanism of SR in the treatment of AD, and provides a theoretical basis for further basic research and clinical application.

Background: Exercise is recommended as the first -line management for knee osteoarthritis (KOA); however, it is difficult to determine which specific exercises are more effective. This study aimed to explore the potential mechanism and effectiveness of a leg -swinging exercise practiced in China, called 'KOA pendulum therapy' (KOAPT). Intraarticular hydrostatic and dynamic pressure (IHDP) are suggested to partially explain the signs and symptoms of KOA. As such this paper set out to explore this mechanism in vivo in minipigs and in human volunteers alongside a feasibility clinical trial. The objective of this study is 1) to analyze the effect of KOAPT on local mechanical and circulation environment of the knee in experimental animals and healthy volunteers; and 2) to test if it is feasible to run a large sample, randomized/single blind clinical trial. Methods: IHDP of the knee was measured in ten minipigs and ten volunteers (five healthy and five KOA patients). The effect of leg swinging on synovial blood flow and synovial fluid content depletion in minipigs were also measured. Fifty KOA patients were randomly divided into two groups for a feasibility clinical trial. One group performed KOAPT (targeting 1000 swings/leg/day), and the other performed walking exercise (targeting 4000 steps/day) for 12 weeks with 12 weeks of follow-up. Results: The results showed dynamic intra-articular pressure changes in the knee joint, increases in local blood flow, and depletion of synovial fluid contents during pendulum leg swinging in minipigs. The intra-articular pressure in healthy human knee joints was -11.32 +/- 0.21 (cmH(2)O), whereas in KOA patients, it was -3.52 +/- 0.34 (cmH(2)O). Measures were completed by 100% of participants in all groups with 95-98% adherence to training in both groups in the feasibility clinical trial. There were significant decreases in the Oxford knee score in both KOAPT and walking groups after intervention (p < 0.01), but no significant differences between the two groups. Conclusion: We conclude that KOAPT exhibited potential as an intervention to improve symptoms of KOA possibly through a mechanism of normalising mechanical pressure in the knee; however, optimisation of the method, longer -term intervention and a large sample randomized -single blind clinical trial with a minimal 524 cases are needed to demonstrate whether there is any superior benefit over other exercises. The translational potential of this article: The research aimed to investigate the effect of an ancient leg -swinging exercise on knee osteoarthritis. A minipig animal model was used to establish the potential mechanism underlying the exercise of knee osteoarthritis pendulum therapy, followed by a randomised, single-blind feasibility clinical trial in comparison with a commonly -practised walking exercise regimen. Based on the results of the feasibility trial, a large sample clinical trial is proposed for future research, in order to develop an effective exercise therapy for KOA.

Knee osteoarthritis (KOA) is one of the most common degenerative joint diseases in the elderly worldwide. The primary lesion in patients with KOA is the degeneration of articular cartilage. This study aimed to observe the biological effects of cyclic negative pressure on C28/I2 chondrocytes and to elucidate the underlying molecular mechanisms. We designed a bi-directional intelligent micro-pressure control device for cyclic negative pressure intervention on C28/I2 chondrocytes. Chondrocyte vitality and proliferation were assessed using Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. The extracellular matrix was analyzed using real-time fluorescence quantitative polymerase chain reaction (PCR) and western blot, while the molecular mechanism of the chondrocyte response to cyclic negative pressure was explored through mRNA sequencing. Experimental data demonstrated that cyclic negative pressure promoted chondrocyte proliferation and upregulated the expression of chondrocyte-specific protein, namely the collagen type II alpha 1 chain (COL2A1) protein, and the transcription factor SRY-box transcription factor 9 (SOX9). Additionally, RNA sequencing analysis revealed that the gene levels of insulin-like growth factor 2 (IGF-2) and early growth response 1 (EGR-1) were significantly elevated in the cyclic negative pressure group. This study demonstrates that cyclic negative pressure stimulates the proliferation of C28/I2 chondrocytes by promoting the expression of EGR-1 and IGF-2. This new discovery may provide novel insights into cartilage health and KOA prevention.

Limited research has focused on the correlation between an external compression and the regeneration of ruptured Achilles tendons. The aim of this study was to evaluate the influence of a constricted paratenon with external compression on the regeneration process of separated rabbit common calcanean tendon stumps. A transection, establishing a 4 mm gap, was created in the right common calcanean tendon of 24 young adult male New Zealand white rabbits. The animals were assigned to two groups: In the control group, only received cast immobilization. In the constricted paratenon (CP) group, the rabbits had a local 3-dimensional printed clasp applied to mimic external compression and same cast immobilization as the control group. Morphologic, histologic and immunohistochemistry examinations were performed at 2 and 4 weeks postoperative. Separated tendon stumps were connected by novel granulated tendon fibrils in the control group. However, the regenerated tendon fibrils appeared insufficient in the CP group, the tendon length and the adhesion grade of the CP group was significantly larger than that of the control group at 4 weeks (P < 0.05, P = 0.030). Disorganized collagen and round-shaped fibroblasts were demonstrated in the CP group. A prolonged expression of proliferating cell nuclear antigen (PCNA) and lower intensity in clusters of differentiation 146 (CD146) were also shown in the CP group. A prolonged existence of the vascular endothelial growth factor (VEGF) and lesser intensity of the transforming growth factor-beta 1 (TGF-β1) were confirmed within this group. Furthermore, the CP group’s expression had less collagen I than that of the control group at 4 weeks. Sufficient regeneration can be obtained, even though there is an obvious gap between severed rabbit common calcanean tendon stumps. However, constricted paratenons with external compression can negatively influence the intrinsic regeneration process of the tendon fibrils and promotes the disorganization of regenerated collagen.

IntroductionAlthough many studies have demonstrated the existing neurological symptoms in COVID-19 patients, the mechanisms are not clear until now. This study aimed to figure out the critical molecular and immune infiltration situations in the brain of elderly COVID-19 patients.MethodsGSE188847 was used for the differential analysis, WGCNA, and immune infiltration analysis. We also performed GO, KEGG, GSEA, and GSVA for the enrich analysis.Results266 DEGs, obtained from the brain samples of COVID-19 and non-COVID-19 patients whose ages were over 70 years old, were identified. GO and KEGG analysis revealed the enrichment in synapse and neuroactive ligand-receptor interaction in COVID-19 patients. Further analysis found that asthma and immune system signal pathways were significant changes based on GSEA and GSVA. Immune infiltration analysis demonstrated the imbalance of CD8+ T cells, neutrophils, and HLA. The MEpurple module genes were the most significantly different relative to COVID-19. Finally, RPS29, S100A10, and TIMP1 were the critical genes attributed to the progress of brain damage.ConclusionRPS29, S100A10, and TIMP1 were the critical genes in the brain pathology of COVID-19 in elderly patients. Our research has revealed a new mechanism and a potential therapeutic target.

In China, swinging the leg backwards and forwards is a commonly used therapy for people with osteoarthritis of the knee. One rationale is that movement without weightbearing may reduce pain of the knee by strengthening the muscles and changing the dynamic pressure of at the at the knee. There have been no studies evaluating its effectiveness. Before undertaking a large trial, a pilot study is needed to establish feasibility and an estimate of the sample size needed. This will be a parallel-group, assessor-masked, randomised, controlled study comparing the effect of pendulum leg swinging against an equivalent time of walking exercise. Patients will be recruited from the outpatient and inpatient orthopaedic surgery services in a large, class III general hospital in Wuhan, China. To be selected they must have clinically diagnosed osteoarthritis of the knee. Patients will be excluded if they have additional knee disease, have had hip or knee arthroplasty or a tibial osteotomy, are taking steroids or have done so in the preceding three months, have another illness affecting mobility or participation in the study, are pregnant, or have a body mass index (BMI) over 35. They will be allocated randomly using sealed, prefilled envelopes on a 1:1 basis. Data will be collected by masked observers at baseline and 12 weeks with additional 12 weeks follow-up. Measures include the Oxford Knee Score, the six-minute walking distance, pain measured on a numerical rating scale, the 30 second sit-to-stand test, quadriceps muscle strength, and accelerometer data. Feasibility data will record data-completion rates, recruitment and retention rates, adherence with treatment, and patient experience including adverse events. The two interventions will involve a gradual increase of exercise between baseline and 6 weeks with a further six weeks at the level set for each patient. Data analysis will be descriptive, with comparative analysis on outcome measures to give an estimate of sample size needed in a full trial. This feasibility trial started in October 2021 and completed in October 2022. A total of 174 participants were recruited and 50 patients were accepted for this trial. There were 24 cases in control (walking) group and 26 in KOAPT group. All patients completed 12 weeks intervention and 12 weeks follow-up. Swinging the leg like a pendulum combines exercise and movement of the knee without bearing weight. Exercise is known to give some benefit but it is not known whether joint movement without weight-baring has any beneficial effect. A large trial would be needed. This trial will establish how feasible it might be to undertake a large trial. Registry: Chinese Clinical Trial Registry Number: ChiCTR2100051275 Date: 17th September 2021 URL: https://www.chictr.org.cn/historyversionpuben.aspx?regno=ChiCTR2100051275

医学免疫学是基础医学的一个重要分支学科,该学科具有理论概念抽象、逻辑性强与学习难度较高等特点."混合式"教学突出"以学生为中心"的核心理念,充分融合现代信息技术,在提高教学质量的同时着力培养学生的自主学习能力和综合素质.本研究依托医学免疫学在线资源和超星平台,将线上学生自主学习和线下课堂教学有机结合,构建"以学生为主体"的混合式教学模式.结果表明基于在线课程的混合式教学模式可有效提高教学质量,在向学生传授专业知识的同时,帮助学生培养自主学习习惯,提高学生分析和解决问题的能力.但线上资源的丰富度及教学安排等方面尚需进一步优化和改进.

MicroRNAs (miRNAs) are important molecules that mediate virus-host interactions, mainly by regulating gene expression via gene silencing. Here, we demonstrated that HIV-1 infection upregulated miR-210-5p in HIV-1-inoculated cell lines and in the serum of HIV-1-infected individuals. Luciferase reporter assays and western blotting confirmed that a target protein of miR-210-5p, TGIF2, is regulated by HIV-1 infection. Furthermore, HIV-1 Vpr protein induced miR-210-5p expression. The use of a miR-210-5p inhibitor and TGIF2 overexpression showed that Vpr upregulated miR-210-5p and thereby downregulated TGIF2, which might be one of the mechanisms used by Vpr to induce G2 arrest. Moreover, we identified a transcription factor, NF-κB p50, which upregulated miR-210-5p in response to Vpr protein. In conclusion, we identified a mechanism whereby miR-210-5p, which is induced upon HIV-1 infection, targets TGIF2. This pathway was initiated by Vpr protein activating NF-κB p50, which promoted G2 arrest. These alterations orchestrated by miRNA provide new evidence on how HIV-1 interacts with its host during infection and increase our understanding of the mechanism by which Vpr regulates the cell cycle.

目的 探讨熊果酸(UA)对脂多糖(LPS)诱导的人髓系白血病单核细胞(THP-1)来源巨噬细胞(Mφ)白细胞介素-1β(IL-1β),白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的表达调节和可能机制.方法 对照组用佛波酯(PMA)处理THP-1细胞使其分化成巨噬细胞,模型组用脂多糖刺激THP-1源巨噬细胞建立炎症细胞模型,低、中、高浓度实验组在模型组的基础上分别加入5,10和20μmol·mL-1熊果酸处理12 h,然后加入脂多糖处理6 h.以噻唑蓝比色法检测细胞活性,以流式细胞术检测细胞凋亡和活性氧(ROS)产生,以实时定量聚合酶链反应检测IL-1β、IL-6和TNF-αmRNA水平,以蛋白质印迹法检测含NLR家族Pyrin域蛋白3(NLRP3),胱天蛋白酶-1(caspase-1),IL-1β蛋白的表达.结果 对照组和低、中、高浓度实验组的细胞凋亡率分别为(2.20±0.52)％,(2.40±0.26)％,(5.23±0.52)％和(11.27±1.03)％.对照组、模型组和低、中、高浓度实验组的IL-1β基因相对表达量分别为1.02±0.14,16.46±2.99,14.22±0.50,7.41±0.79和2.20±0.57;IL-6基因相对表达量分别为1.08±0.28,17.61±5.55,4.42±0.41,2.14±0.23和1.56±0.37;TNF-α基因相对表达量分别为1.01±0.10,7.62±0.33,6.40±0.84,3.79±0.88和4.03±0.35;细胞ROS产生情况分别为(100.00±1.16)％,(131.70±4.41)％,(124.70±2.60)％,(107.30±1.45)％和(107.30±3.71)％;NLRP3蛋白表达的相对水平分别为1.18±0.01,1.31±0.02,1.20±0.02,0.94±0.01和0.97±0.01;caspase-1蛋白表达的相对水平分别为1.20±0.01,1.31±0.03,1.17±0.02,0.97±0.01和0.81±0.01;IL-1β蛋白表达的相对水平分别为0.89±0.01,1.10±0.01,1.22±0.02,0.95±0.02和0.89±0.01;上述指标,模型组与对照组比较,中、高浓度实验组与模型组比较,差异均有统计学意义(均P<0.05).结论 熊果酸可能通过抑制ROS产生和NLRP3炎症小体的激活下调THP-1源巨噬细胞中炎性因子IL-1β、IL-6和TNF-α的表达以发挥免疫调节的作用.

Novel coronavirus (2019-nCoV) is the pathogen of COVID-19. Some severe cases may suffer from respiratory failure or even death, which poses a great challenge to global public health. 2019-nCoV proteins not only participate in virus proliferation, but also play an important role in antagonizing host innate immune response, especially interferon response. In this paper, 2019-nCoV proteins involved in regulating host interferon response and the complex interaction between 2019-nCoV and interferons were summarized, aiming to provide a theoretical reference for the prevention and control of COVID-19.

In response to the ministry of education proposed measure suspended class, ongoing learning under the COVID- 19 epidemic Taking the course of Medical Immunology as an example, this article discusses the implementation of full online teaching mode facing the particularity during coronavirus pneumonia epidemic, cultivation of scientific and humanistic spirit and the inspiration of students' curiosity by introducing hot issues in epidemic life This paper provides case and reference for the distance teaching of medical immunology in local colleges and universities

目的 探寻金叶败毒颗粒治疗新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)的药理作用机制.方法 通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)、中药分子机制的生物信息学分析工具(Bioin?formatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine,BATMAN-TCM)检索筛选金叶败毒颗粒中金银花、蒲公英、鱼腥草、大青叶的化学成分和作用靶点.查询OMIM(Online Mendelian Inheritance in Man)、GeneCards数据库获得疾病相关靶点基因,进而运用Cytoscape软件构建药物活性分子-靶点基因作用网络,通过R语言包clusterProfiler进行基因本体(gene ontology,GO)功能注释和基于京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,预测金叶败毒颗粒对COVID-19的作用机制.结果 共筛选获得药物活性分子31个.靶点基因110个,主要包含PTGS2、AR、ESR1、PPARG、PRSS1、NOS2、NR3C2等核心靶点.富集分析得到GO条目2138项(P<0.05),KEGG信号通路134条(P<0.05),主要富集的通路有AGE-RAGE信号通路、动脉粥样硬化、TNF-α信号通路、甲型流感等.结论 金叶败毒颗粒的活性化合物能作用于TNF信号等核心炎症通路,从而对COVID-19起到抗氧化损伤、抗炎作用.

The world is in the grip of the COVID-19 caused by SARS-Cov-2 pandemic Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed Malnutrition and various non-communicable underlying diseases, such as obesity, diabetes mellitus, cardiovascular diseases, leading to immunodeficiency in patients are important risk factors for severe COVID-19 Special nutrient supplement have pharmacological effect, stimulate the immune cells in a particular way, strengthen the function of immune response, maintain appropriate immune response, adjustment of cytokine production and release, reduce harmful or excessive inflammation, have positive sense to the prognosis of patients with COVID-19 This article reviewed the role of immune nutrients such as vitamins, mineral elements, polyunsaturated fatty acids, dietary fiber in reducing the risk of respiratory tract infections, as well as the current application of immunonutrition in COVID-19, in order to provide reliable reference for the adjuvant role of immunonutrition in the comprehensive treatment of COVID-19

In recent years, acute infectious diseases, such as, COVID-19, SARS, avian influenza, are frequently in epidemic, and continually cause patients’ temperature rising even hyperpyrexia and seriously threaten the life of patients. The Chaishi-Tuire Granules (CTG)is used to treathyperpyrexia and infectious diseases. The purpose of this study is to investigate the potential pharmacological mechanisms of CTG action on hyperthermia. The drug target prediction tool is used in the TCM comprehensive pharmacology research platform(TCMIP, www.tcmip.cn), the target of active compound in CTG compound of Chinese herbal medicine was predicted. Then, the interaction network between CTG hypothesis targets and known heat-related genes was constructed, and the candidate targets of CTG therapy for heat-related genes were determined by the topology characteristics of the network. The gene ontology (GO) analysis and the enrichment analysis of Reactome pathway were carried out to study the specific functions and participating pathways of CTG acting on high-heat candidate targets, and further verification was conducted through animal experiments. CTG was composed of nine herbs, and 1721 related chemical components were retrieved in total. By constructing the known hyperthermally related gene network of CTG presumed targets, and calculating the topology characteristics of the network, we determined 72 candidate CTG targets related to the treatment of hyperpyretic, involving 93 active components in CTG. Functionally, these candidate CTG targets are significantly correlated with apoptosis, cytokine mediated signaling, DNA damage-induced protein phosphorylation, inflammation, and immune-related pathways. Furthermore, the antipyretic effects of CTG on rat hyperthermia and its regulatory effects on serum interleukin-1, interleukin-6, tumor necrosis factor, and hypothalamus cAMP were confirmed in vivo by lPS-induced rat hyperthermia model. CTG can play an antipyretic role by regulating its candidate targets, and its intrinsic mechanism is mainly through regulating inflammatory cytokines in hypothalamus and peripheral blood.

目的:探究降酸消脂胶囊对高尿酸血症(Hypemricemia,HUA)大鼠血尿酸(Uric acid,UA)及黄嘌呤氧化酶(Xanthine oxidase,XOD)的影响.方法:腹腔注射次黄嘌呤及皮下注射氧嗪酸钾制备HUA大鼠模型,随机分成模型组、别嘌醇组、降酸消脂胶囊低、中、高剂量组,每组10只,并以未造模10只大鼠为正常组.正常组及模型组分别予等量0.9％生理盐水灌胃,别嘌醇组按40 mg/(kg·d)剂量予别嘌醇灌胃,降酸消脂胶囊高、中、低剂量组分别按24 g/(kg·d),12g/(kg·d),6g/(kg·d)剂量灌胃,连续4周后采血检测各组大鼠血UA、血XOD、血清甘油三酯(Triglyceride,TG)、总胆固醇(Total cholesterol,TC)、尿素氮(Blood urea nitrogen,BUN)及血肌酐(Serum creatinine,SCr).结果:与正常组比较,模型组大鼠血UA、XOD、TG、TC及BUN、SCr明显升高(P＜ 0.05,P＜0.01).与模型组比较,降酸消脂胶囊各剂量组与别嘌醇组都能显著抑制血XOD活性,降低血UA含量(P＜ 0.05,P＜0.01),降酸消脂胶囊各剂量组及别嘌醇组血清TG、TC、BUN、SCr水平均有不同程度的下降,但仅高剂量组及别嘌醇组差异均有统计学意义(P＜ 0.05,P＜ 0.01).结论:降酸消脂胶囊能显著降低HUA大鼠血UA含量,抑制XOD活性,缓解高血脂状态,改善肾功能,对大鼠HUA有一定的防治作用.

目的 骨关节炎(osteoarthritis,OA)是最常见的退行性慢性关节疾病,然而其具体的基因机制至今尚不完全清楚,通过基因芯片检测OA细胞模型的基因表达谱变化,为深入研究OA发病机制提供更多生物学依据.方法 胰酶结合胶原酶分离获得小鼠原代软骨细胞,以50 ng/mL的肿瘤坏死因子 α(TNF-α)孵育原代软骨细胞24 h制备OA细胞模型.收获细胞提取总RNA用于基因芯片检测,以表达差异倍数(fold change,FC)>2且P<0.01为条件筛选差异表达基因(differentially expressed genes,DEGs),利用生物信息学软件对差异表达结果 进行基因功能分类体系(gene ontology,GO)、KEGG通路注释分析.结果原代软骨细胞经TNF-α 处理后,共筛选获得8096个表达上调DEG和6413个表达下调DEG,其中有诸如基质金属蛋白酶、炎性因子、基因凋亡及成骨相关基因等已知的OA相关的差异表达基因.此外,还有Olfml1等olfactomedin超家族成员、Nf1等未见报道的与OA相关的基因,尤其发现大量细胞色素超家族成员基因的异常表达,提示线粒体相关功能基因及信号途径可能与OA进程有重要关联.结论 项目从转录组水平整体分析了TNF-α 诱导的OA软骨细胞模型基因表达谱变化,为进一步深入探究OA发病机制提供了新思路.

Purpose: To investigate the efficacy of capecitabine and ludartin in the treatment of colon cancer in mice. Methods: Mice model of colon cancer was used in this study. Quantitative real-time polymerase chain reaction (Qrt-PCR) was used to quantify the expression of vascular endothelial growth factor (VEGF) mRNA. Micro-vessel density was assessed using immunohistochemical analysis. Results: When administered separately, capecitabine and ludartin treatments significantly suppressed tumor growth in the mice model of colon cancer for 4 weeks, compared to control group. Co-administration of capecitabine and ludartin significantly inhibited tumor growth for 6 weeks (p < 0.05). Symptoms of colon cancer such as weight loss, skin discoloration and leukopenia were observed in untreated control group. However, these symptoms were completely absent in the group treated with combination of capecitabine and ludartin. The combined treatment also prevented colon cancer-induced increase in white blood cell (WBC) count, and increased median survival time of colon cancer mice from 38 to 55 days. Expression of VEGF in combination (capecitabine + ludartin) treatment group was significantly lower than in the control, i.e., untreated group (p. 0.05). The combination treatment group also had significantly lower micro-vessel density in the tumor tissues, compared to the untreated control mice (p < 0.05). Conclusion: These results show that a combination treatment of capecitabine and ludartin effectively inhibits colon tumor growth and angiogenesis in mice via a mechanism involving suppression of VEGF expression. Thus, capecitabine and ludartin combination is a potentially suitable treatment for colon cancer.

目的:探讨鸦胆子油(Brucea javanica oil,BJO)和卡培他滨(Capecitabine,Cap)合用对体外培养的人结直肠癌LOVO和HT29细胞周期和增殖及对Wnt/β-catenin信号通路的影响.方法:以CCK-8比色法,检测不同浓度的鸦胆子油(0.0625、0.125、0.25、0.50和1.00mg/ml)、卡培他滨(0.025、0.050、0.100、0.200、0.400μM)作用不同时间(2h、12h、24h和48h)以及单独、联合应用对LOVO和HT29细胞增殖能力影响;PI染色分析鸦胆子油、卡培他滨以及联合应用对细胞周期的影响;免疫印迹法检测结直肠癌细胞系(SW620、LOVO、LS174T、HT29和SW116)和人正常结直肠粘膜细胞系,以及鸦胆子油、卡培他滨单用及合用对细胞p-catenin和Wnt3a蛋白的表达影响;实时荧光定量PCR法检测结直肠癌细胞系(SW620、LOVO、LS174T、HT29和SW116)和人正常结直肠粘膜细胞系,鸦胆子油、卡培他滨单用及合用对细胞Wnt3a、β-catenin及其下游CyclinD1和c-Myc mRNA含量的影响.结果:结直肠癌细胞系(SW620、LOVO、LS174T、HT29和SW116)中β-catenin蛋白和mRNA含量均明显高于正常结直肠上皮细胞系;0.25、0.50和1.00 mg/ml鸦胆子油作用12h(分别为:93.1％,90.8％和90.5％),24h(分别为:76.7％,71.1％和72.7％)可明显抑制LOVO细胞生长,且呈现时间和剂量依赖性的变化,同时抑制HT29细胞,卡培他滨与鸦胆子油作用相同;0.125、0.25、0.50和1.00mg/ml的鸦胆子油联合0.4μM卡培他滨比单独卡培他滨作用结直肠癌细胞系LOVO和HT29的细胞增殖率明显较低,且具有剂量依赖性,分别为:对LOVO分别为70.9％、67.0％、61.3％和55.7％;对HT29分别为70.1％、58.1％、48.3％和40.4％;1.00 mg/ml鸦胆子油和0.4 μM卡培他滨合用于LOVO和HT29细胞48 h的增殖抑制率为55.7％和40.4％,明显低于单独使用0.4μM卡培他滨(72.5％和55.1％);DAPI染色证实,合用1.00mg/ml的鸦胆子油联合0.4μM卡培他滨比单独鸦胆子油和卡培他滨作用结直肠癌细胞系LO-VO和HT29增殖抑制作用更强;联合使用明显增加两种细胞G1/G0期细胞数量,同时增加G2/M细胞数量;再者,联合使用明显抑制细胞Wnt3a、β-catenin蛋白和mRNA及其下游CyclinD1和c-Myc mRNA含量表达.结论:鸦胆子油和卡培他滨合用可抑制结直肠癌细胞增殖,促进凋亡,该作用可能是通过抑制Wnt/β-catenin信号通路和细胞周期阻滞实现的.

Japanese encephalitis virus (JEV), known to affect children, is a major cause of severe encephalopathy. Its prevalence has been percolated over wider regions of Southern Asia. JEV is associated with neurodegeneration, severe inflammation, increased oxidative stress and elevated levels of stress linked proteins. Four groups of 15 mice each (4-5 weeks old BALB/c mice of either sex) was used for the study. Mice were intravenously infected with lethal dose of 3 x 10(5) pfu of JEV, followed by mortality after 8 days. On the next day and onwards, the animals were administered intraperitonially with (-)-tetrahydropalmatine (LTHP) solution (0.1 mg/mL in PBS) for the next 7 days. Animals exhibited protection against JEV infection, after being administered with LTHP. Reduction in levels of, viral population, caspase-2 expression, reactive oxygen and nitrogen species, microglial cells and proinflammatory mediators, stress linked protein molecules and neuronal apoptosis was exhibited in JEV infected animals treated with LTHP. The effects produced by the administration of LTHP indicated its possible use to treat JEV in mouse model. Potential to reduce viral count in brain and subsequent neuronal apoptosis, reduction in mediators of inflammation and oxidative stress, strictly advocate the use of LTHP for treatment of JEV. Thus, the present investigation indorses LTHP as a potentially strong drug candidate for the treatment of JEV infection due to its neuroprotective, anti-inflammatory, antiviral and anti-oxidative effect.

This study evaluates the protective effect of corilagin against Parkinsonismin Japanese encephalitis virus (JEV) induced Parkinson's disease. The JaGAr-01 strain of virus was used to induce JE. The virus was injected into the rats (13 days age) at the midpoint between the two ears. Adult rats, 12 week after the inoculation of virus, were used for the further study. Corilagin (20 mg/kg) and levodopa with dopa decarboxylase inhibitor (LEV, 10 mg/kg) were administered intraperitoneally for the duration of one week. Bradykinesia and the levels of dopamine in the brain were estimated at the end of protocol. There was a significant decrease inthe motor function in the corilagin, LEV and LEV + corilagin treated groupscompared to the negative control group. However treatment with corilagin, LEV and LEV + corilagin significantly increases the level of dopamine in the brain compared to the negative control group. This study concludes that corilagin ameliorates the Parkinsonismin JEV induced Parkinsonism. Moreover it shows a synergistic effect when treated with LEV. Data presented in the investigation supports that corilagin can be used clinically.