对“药号”价值的评估

“药号”是医药生产企业的一项重要的无形资产 ,是企业的重要资源。本文采用对预期收益折现的方法来确定“药号”的价值 ;并采用了乐观、中观、悲观系数对收益时间进行修正 ,以贴合“药号”的实际情况。

药食两用3号方对大鼠热证痛风性关节炎的抗炎抗氧化活性研究

目的:研究药食两用3号方对热证痛风性关节炎的作用。方法:将32只SD大鼠随机分为空白对照组、模型对照组、秋水仙碱组和复方干预组,每组8只。除空白对照组外,其余各组均通过注射尿酸钠造成大鼠痛风性关节炎模型,并置于高温环境下制成热证模型,用秋水仙碱和痛风药食两用3号方分别对秋水仙碱组和复方干预组大鼠灌胃给药。检测踝关节周长增加百分比,末次给药后腹主动脉采血,检测大鼠血清中αN乙酰氨基葡萄糖苷酶、β-半乳糖苷酶、超氧化物歧化酶、尿酸、肿瘤坏死因子-α的水平。结果:与模型对照组比较,复方干预组踝关节周长增加百分比、αN乙酰氨基葡萄糖苷酶、β-半乳糖苷酶、尿酸、肿瘤坏死因子-α均明显降低,超氧化物歧化酶明显升高(P <0.01)。结论:药食两用3号方对热证痛风性关节炎大鼠有降尿酸、抗炎抗氧化的作用。其作用机制可能与降低超氧化物歧化酶活性,抑制肿瘤坏死因子-α、αN乙酰氨基葡萄糖苷酶、β-半乳糖苷酶合成与释放有关。

中洗药1号方联合经肌间沟弧形切口手术治疗高位肛周脓肿的疗效观察

目的观察中洗药1号方联合经肌间沟弧形切口手术治疗高位肛周脓肿的效果。方法选取2021年1月—2021年10月张家口市第五医院接收并对其进行手术治疗的高位肛周脓肿患者200例,根据随机抽样法分为两组。所有患者均给予经肌间沟弧形切口手术治疗,对照组术后给予常规干预,而观察组术后在对照组基础上联合中洗药1号方外用治疗。比较两组疼痛评分、创面情况、门功能指标及血清高敏-C反应蛋白(hs-CRP)、白细胞计数(WBC)、血清激活数A(ACTC)的差异。结果术后3 d、1周、2周时,观察组创面pH值及创面疼痛评分、分泌物评分、肉芽组织生长评分均低于对照组,巨噬细胞数量少于对照组,差异有统计学意义(P<0.05)。术后当天,两组血清hs-CRP、WBC、ACTC比较,差异无统计学意义(P>0.05),术后14 d统计学发现两组hs-CRP、WBC、ACTC均较术后当天下降,且观察组术后14 d上述指标下降后的数值均低于对照组,差异有统计学意义(P<0.05)。观察组创面愈合时间为(18.25±3.12)d,明显短于对照组的(23.14±4.52)d,差异有统计学意义(P<0.05)。术前,两组Wexner评分及肛门功能指标比较,差异无统计学意义(P>0.05),术后6个月统计学发现两组Wexner评分较前升高,肛管静息压、肛管最大收缩压则较前下降,而观察组6个月后Wexner评分低于对照组,肛管静息压、肛管最大收缩压高于对照组,差异有统计学意义(P<0.05)。结论中洗药1号方联合经肌间沟弧形切口手术治疗高位肛周脓肿可减少创面分泌物,促进创面愈合,减轻术后疼痛,可能与降低相关炎症因子有关。

Population pharmacokinetics of paeoniflorin in guanxin Ⅱ prescription

To evaluate the effect of components in Guanxin Ⅱ prescription on the pharmacokinetic profiles of paeoniflorin. Plasma concentration of Paeoniflorin in rats after intravenous injection of Paronia Pall Extract （PPE） and oral administration of PPE and three types of decoctions in Guanxin Ⅱ prescription, respectively, were determined by HPLC analyses. NONMEM （nonlinear mixed-effect modeling） method was used to analyze full set of pharmacokinetic data directly. A two-compartment model with first-order degradation in absorption compartment was employed for the data analysis. The mean of population parameters, CL1, V1, CL2, V2, Ka0, and Kal, were measured to be 0.509 L/h, 0.104 L, 0.113 L/h, 0.123 L, 0.135/h, and 0.0135/h, respectively. Inter-individual variabilities were estimated and dose formulation （DF） was identified as a significant covariate of Ka 1, Ka0, and V1. It is concluded that the pharmacokinetic behaviors of paeoniflorin in rats can alter with different dose formulations.

Breeding and Mechanized Cultivation of the New Bulk Purple Yam Variety Suyu 2

The new bulk purple yam variety Suyu 2,which had high quality,efficiency and was suitable for production in a highly mechanized cultivation,was bred by special and was suitable for whole-course mechanized cultivation.Integrated with agricultural machinery and agricultural trait,four kinds of machines produced by two factories from Jiangsu and Shandong could complete 10 kinds of main production processes,including rotary tillage,ridging,sowing,intertillage,topdressing,drug delivery,weeding,hilling,vine cutting and harvest.The work efficiency of single machine was 4-5 hm^2/d,and the production pattern got the cost saving and effectiveness increasing in the main yam producing area.The benefit reached over RMB 37500 yuan/hm^2 in special vegetable area.It was simple,feasible and easy to popularize the mechanization cultivation technique.

Primary evidence for involvement of IP_(3) in heat-shock signal transduction in Arabidopsis

The role of inositol 1,4,5-trisphosphate （IP3） in transducing heat-shock （HS） signals was examined in Arabidopsis. The whole-plant IP3 level increased within 1 min of HS at 37℃. After 3 min of HS, the IP3 level reached a maximum 2.5 fold increase. Using the transgenic Arabidopsis plants that have AtHsp 18.2 promoter-β-glucuronidase （GUS） fusion gene, it was found that the level of GUS activity was up-regulated by the addition of caged IP3 at both non-HS and HS temperatures and was down-regulated by the phospholipase C （PLC） inhibitors {1-[6-（（ 1713-3-Methoxyestra-1,3,5（10）-trien- 7-yl）amino）hexyl]-2,5-pyrrolidinedione } （U-73122）. The intracellular-free calcium ion concentration （[Ca^2＋]i） increased during HS at 37℃ in suspension-cultured Arabidopsis cells expressing apoaequorin. Treatment with U-73122 prevented the increase of [Ca^2＋]i to some extent. Above results provided primary evidence for the possible involvement of IP3 in HS signal transduction in higher plants.

Signaling pathway/molecular targets and new targeted agents under development in hepatocellular carcinoma

Advances in molecular cell biology over the last de- cade have clarified the mechanisms involved in can- cer growth, invasion, and metastasis, and enabled the development of molecular-targeted agents. To date, sorafenib is the only molecular-targeted agent whose survival benefit has been demonstrated in two global phase 111 randomized controlled trials, and has been approved worldwide. Phase 111 clinical trials of other molecular targeted agents comparing them with sorafenib as first-line treatment agents are ongoing. Those agents target the vascular endothelial growth factor, platelet-derived growth factor receptors, as well as target the epidermal growth factor receptor, insulin- like growth factor receptor and mammalian target of rapamycin, in addition to other molecules targeting other components of the signal transduction pathways. In addition, the combination of sorafenib with standard treatment, such as resection, ablation, transarterial em- bolization, and hepatic arterial infusion chemotherapy are ongoing. This review outlines the main pathways involved in the development and progression of hepato- cellular carcinoma and the new agents that target these pathways. Finally, the current statuses of clinical trials of new agents or combination therapy with sorafenib and standard treatment will also be discussed.

Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signaling plays a very important role in progression, invasion and metastasis of bladder cancer cells. In this study, we investigated whether IGF-1R was involved in the growth stimulating activity and drug resistance of bladder cancer cells. The results showed: The mRNAs of IGF-1, IGF-2 and IGF-1R were strongly expressed in serum-free cultured T24 cell line, whereas normal urothelial cells did not express these factors/receptors or only in trace levels; T24 cell responded far better to growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R by antisense oligodeoxynucleotide (ODN) significantly inhibited the growth of T24 cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin (MMC). These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which are insensitive to chemotherapy.

Therapeutic resistance in cancer: microRNA regulation of EGFR signaling networks

Receptor tyrosine kinases(RTKs)such as the epidermal growth factor receptor(EGFR)regulate cellular homeostatic processes.EGFR activates downstream signaling cascades that promote tumor cell survival,proliferation and migration.Dysregulation of EGFR signaling as a consequence of overexpression,amplification and mutation of the EGFR gene occurs frequently in several types of cancers and many become dependent on EGFR signaling to maintain their malignant phenotypes.Consequently,concerted efforts have been mounted to develop therapeutic agents and strategies to effectively inhibit EGFR.However,limited therapeutic benefits to cancer patients have been derived from EGFR-targeted therapies.A well-documented obstacle to improved patient survival is the presence of EGFR-inhibitor resistant tumor cell variants within heterogeneous tumor cell masses.Here,we summarize the mechanisms by which tumors resist EGFR-targeted therapies and highlight the emerging role of microRNAs(miRs)as downstream effector molecules utilized by EGFR to promote tumor initiation,progression and that play a role in resistance to EGFR inhibitors.We also examine evidence supporting the utility of miRs as predictors of response to targeted therapies and novel therapeutic agents to circumvent EGFR-inhibitor resistance mechanisms.

Investigation of mitigating effect of colon-specific prodrugs of boswellic acid on 2,4,6-trinitrobenzene sulfonic acidinduced colitis in Wistar rats: Design, kinetics and biological evaluation

To develop a colon-targeting bioreversible delivery system for β-boswellic acid (BBA) and explore utility of its prodrugs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.METHODSSynthesis of 4 co-drugs of BBA with essential amino acids was achieved by CDI coupling, followed by their spectral characterization. In vitro kinetics were studied by HPLC in aqueous buffers, homogenates of gastrointestinal tract and fecal matter. In vivo kinetic studies were performed in Wistar rat plasma, urine and feces. The prodrugs were screened in TNBS-induced colitis modeled Wistar rats. Statistical significance was assumed at P < 0.05, P < 0.01, P < 0.001 when compared with disease controls using one-way and two-way ANOVAs.RESULTSProdrugs were stable in 0.05 mol/L HCl buffer (pH 1.2) and stomach homogenates. Negligible hydrolysis was observed in phosphate buffer and intestinal homogenates. Substantial release (55%-72% and 68%-86%) of BBA was achieved in rat fecal matter and homogenates of colon. In vivo studies of BBA with L-tryptophan (BT) authenticated colon-specific release of BBA. But, surprisingly substantial concentration of BBA was seen to reach the systemic circulation due to probable absorption through colonic mucosa. Site-specifically enhanced bioavailability of BBA could be achieved in colon, which resulted in demonstration of significant mitigating effect on TNBS-induced colitis in rats without inducing any adverse effects on stomach, liver and pancreas. Prodrug of BT was found to be 1.7% (P < 0.001) superior than sulfasalazine in reducing the inflammation to colon among all prodrugs tested.CONCLUSIONThe outcome of this study strongly suggests that these prodrugs might have dual applicability to inflammatory bowel disease and chronotherapy of rheumatoid arthritis.

Application of Network Pharmacology to Explore the Mechanism of Yi Xin Tai Formula in Treating Heart Failure

Objective To explore the possible mechanism of Yi Xin Tai Formula(YXTF)in treating heart failure(HF)by network pharmacology method and to verify the related targets by western blotting.Methods Using the traditional Chinese medicine systems pharmacology(TCMSP)database with its analysis platform for HF as a disease model,the active ingredients of YXTF were filtered according to the oral bioavailability(OB)and druglikeness(DL),and the corresponding targets were predicted.The disease targets of HF were retrieved by Human Phenotype Ontology(HPO)database.Then,“YXTF compounds-Targets-HF”network was constructed in the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database,the network visualized through the Cytoscape software,and the key nodes of the network achieved according to Degree(D),Closeness Centrality(CC),and Betweenness Centrality(BC).Kyoto Encyclopedia of Genes and Genomes(KEGG)gene function enrichment analysis was carried out for the key nodes with the help of GATHER database platform.The rabbit model of HF was established by coarctation of the abdominal aorta and perfusion of propylthiouracil(PTU).The pathological changes and protein expression of transforming growth factor beta(TGF-β)protein were observed by western blotting.Results“YXTF compounds-Targets-HF”network consisted of 403 nodes,136 key nodes and 10 related KEGG pathways that included focal adhesions,cell cycles,mitogen-activated protein kinase(MAPK)signaling pathways,Toll-like receptor signaling pathways,Cytokine-cytokine receptor interactions,Gap junctions,adherens junctions,TGF-β signaling pathways,apoptosis and Wnt signaling pathways,respectively.The expression of TGF-β protein in myocardium decreased significantly.Conclusions According to the network pharmacology,the treatment of YXTF for HF might be related to 10 metabolic pathways.The effects of the multicompound-multitarget-multi pathways and the synergistic effect drawn from the compounds that act as the monarch,minister,adjuvant,guide medicines were revealed through this study.

Relationship between p38MAPK activity and apoptosis during the drug resistance of breast carcinoma cell lines

Objective： The aim of this study was to investigate the relationship between p38MAPK activity and apoptosis during the drug resistance of breast carcinoma cell lines. Methods： Using p38MAPK special inhibitor SB203580 to analyze the effect on the cell apoptosis of MCF-7/ADM cell. Cell apoptosis was analysed by PI staining and flow cytometry （FCM） （F test）. 50% inhibition concentration （IC50） of adriamycin on MCF-7/ADM was determined by MTT method （F test） in vitro. MDR-1 mRNA expression was detected by RT-PCR （F test） and Western Blot （F test） respectively. Results： After SB203580 24 h action the MCF-7/ADM＇s apoptosis rate was 26.73±4.90%, higher than the control group and untreated group （F = 143.80, P 〈 0.001）. The sensitity to the ADM was improved significantly （F = 148927.1, P 〈 0.001）, and the reversal effect of treat SB203580 group was 68.45%. The P38MAPK protein （F= 685.419, P 〈 0.001） and MDR-1 mRNAexpression after SB203580 24 h action were lower than the control group and untreated group （F = 9139.24, P 〈 0.001）. Conclusion： P38MAPK signal way plays an important role in drug resistance of breast carcinoma ceil. p38MAPK can protect MCF-7/ADM cells from apoptosis, and blocking the p38MAPK signal way can increase the apoptosis for breast carcinoma drug resistance cell lines.

Cellular processing determinants for the activation of damage signals in response to topoisomerase I-linked DNA breakage

Recent studies have suggested an involvement of processing pathways for the initiation of cellular responses induced by topoisomerase-targeting drugs. Here, we showed that cellular exposure to camptothecin （CPT） induced formation of topoisomerase I cleavable complex （TOPlcc）, degradation of TOP1 and activation of DNA damage responses （DDR）. Transcription and proteasome-dependent proteolysis, but not replication, were involved in CPTo indneed TOPl degradation, while none of above three processing activities affected TOPlcc formation. Replication- and transcription-initiated proeessing （RIP and TIP） of TOPlee were identified as two independent pathways, which contribute distinctly to various CPT-activated DDR. Specifically, in cycling cells, RIP-processed TOPlec triggered the CPT-induced RPA pbosphorylation. At higher CPT dosages, the TIP pathway is required for other DDR activation, including ATM, p53 and Chkl/2 phosphorylation. The TIP pathway was further demonstrated to be S-phase independent by using three nonreplicating cell models. Furthermore, the effect of proteasome inhibitors mimicked that of transcription inhibition on the CPT-induced activation of DDR, suggesting the involvement of proteasome in the TIP pathway. Interestingly, the TIP pathway was important for TOPlcc-activated, but not ionization radiationactivated ATM, p53 and Chk2 phosphorylation. We have also found that pharmacological interferences of TIP and RIP pathways distinctively modulated the CPT-induced cell killing with treatments at low and high dosages, respec- tively. Together, our results support that both RIP and TIP pathways of TOPlcc are required for the activation of CPT-induced DDR and cytotoxicity.

A Network Pharmacology Analysis of Cang Fu Dao Tan Formula for the Treatment of Obese Polycystic Ovary Syndrome

Objective To explore the potential molecular targets of Cang Fu Dao Tan Formula(CFDTF)in the treatment of obese polycystic ovary syndrome(PCOS)using network pharmacology and bioinformatic approaches.Methods The potential blood-entry active compounds and targets of CFDTF were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and obese PCOS related gene targets were retrieved from GeneCard databases.A protein-protein interaction(PPI)network of CFDTF component-targets and obese PCOS diseasetargets was constructed using STRING.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the intersection network were conducted using a Bioconductor database.Results In total,114 active compounds were screened according to oral bioavailability(OB)and drug similarity(DL),and 328 targets related to these constituents were obtained.Further,2559 target genes directly related to obese PCOS were obtained from the GeneCard databases,and 82 genes were obtained from the intersection of the component-target and disease-target PPI network.These genes were mainly involved in response to steroid hormones,nutrient levels and lipopolysaccharide as well as in other biological processes.Their molecular functions were mainly related to nuclear receptor activity,phosphatase binding and cytokine activity,and they were enriched in the cytoplasm,cell membrane and membrane region.Conclusions CFDTF consists of 114 active compounds that are responsible for its pharmacodynamic effects.It mainly regulates the AGE-RAGE signaling pathway in diabetic complications,bladder cancer,and hepatitis B and in other signaling networks.These findings provide certain theoretical and scientific basis for the treatment of obese PCOS with Chinese medicine.

Down-regulation of extracellular signal-regulated kinase 1/2 activity in P-glycoprotein-mediated multidrug resistant hepatocellular carcinoma cells

AIM： To study the expression and phosphorylation of extracellular signal-regulated kinase （ERK） i and ERK2 in multidrug resistant （MDR） hepatocellular carcinoma （HCC） cells.METHODS： MDR HCC cell lines, HepG2/adriamycin （ADM） and SMMC7721/ADM, were developed by exposing parental cells to stepwise increasing concentrations of ADM. MTT assay was used to determine drug sensitivity. Flow cytometry was employed to analyze cell cycle distribution and measure cell P-glycoprotein （P-gp） and multidrug resistant protein 1 （MRP1） expression levels. ERK1 and ERK2 mRNA expression lev-ls were measured by quantitative real-time PCR （QRTPCR）. Expression and phosphorylation of ERK1 and ERK2 were analyzed by Western blot.RESULTS： MTT assay showed that HepG2/ADM andSMMC7721/ADM were resistant not only to ADM, but also to multiple anticancer drugs. The P-gp expression was over 10-fold higher in HepG2/ADM cells than in HepG2 cells （8.92% ±0.22% vs 0.88% ± 0.05%, P 〈 0.001） and over 4-fold higher in SMMC7721/ADM cells than in SMMC7721 cells （7.37% ± 0.26% vs 1.74% ± 0.25%, P 〈 0.001）. However, the MRP1 expression was not significantly higher in HepG2/ADM and SMMC7721/ADM cells than in parental cells. In addition, the percentage of MDR HepG2/ADM and SMMC7721/ADM cells was significantly decreased in the G0/G1 phase and increased in the the S phase or G2/M phase. QRT-PCR analysis demonstrated that the ERK1 and ERK2 mRNA expression increased apparently in HepG2/ADM cells and decreased significantly in SMMC7721/ADM cells. Compared with the expression of parental cells, ERK1 and ERK2 protein expressions were markedly decreased in SMMC7721/ADM cells. However, ERK2 protein expression was markedly increased while ERK1 protein expression had no significant change in HepG2/ADM cells. Phosphorylation of ERK1 and ERK2 was markedly decreased in both HepG2/ADM and SMMC7721/ADM MDR cells.CONCLUSION： ERK1 and ERK2 activities are downregulated in P-gp-mediated MDR HCC cells. ERK1 or ERK2 might be a potential drug target for circumventing MDR HCC cells,

GPCR-CARMA3-NF-kappaB Signaling Axis： A Novel Drug Target for Cancer Therapy

G protein-coupled receptors （GPCRs） play pivotal roles in regulating various cellular functions. It has been well established that GPCR activates NF-κB and aberrant regulation of GPCR-NF-κB signaling axis leads to cancers. However, how GPCRs induce NF-κB activation remains largely elusive. Recently, it has been shown that a novel scaffold protein, CARMA3, is indispensable in GPCR-induced NF-κB activation. In CARMA3-deficient mouse embryonic fibroblast cells, some GPCR ligand-, like lysophosphatidic acid （LPA）, induced NF-κB activation is completely abolished. Mechanistically, upon GPCR activation, CARMA3 is linked to the membrane by β-arrestin 2 and phosphorylated by some PKC isoform. Phosphorylation of CARMA3 unfolds its steric structure and recruits its downstream effectors, which in turn activate the IKK complex and NF-κB. Interestingly, GPCR （LPA）-CARMA3-NF-κB signaling axis also exists in ovarian cancer cells, and knockdown of CARMA3 results in attenuation of ovarian cancer migration and invasion, suggesting a novel target for cancer therapy. In this review, we summarize the biology of CARMA3, discuss the GPCR （LPA）-CARMA3-NF-κB signaling axis in ovarian cancer and speculate its potential role in other types of cancers. With a strongly increasing tendency to identify more LPA-like ligands, such as endothelin-1 and angiotensin II, which also activate NF-κB through CARMA3 and contribute to myriad diseases, GPCR-CARMA3-NF-κB signaling axis is emerging as a novel drug target for various types of cancer and other myriad diseases.

Detection of UXO magnetic anomaly in Jinshan area

Magnetic survey is one of the most successful techniques for locating buried unexploded ordnances( UXO). For the location and identification of buried UXO in Jinshan area,a total-field magnetic survey is applied. The analytic signal of magnetic field is widely used to outline the boundaries of geology bodies,slightly dependent on the magnetization direction. In order to locate the UXO position,the analytic signal is applied to process the magnetic UXO data,which performs better than the conventional magnetic data. Then a typical UXO anomaly is extracted from the original data to invert for its depth by an improved Euler method proposed.The calculated depth is close to the real buried depth.

Mechanism of Pingyang Jiangya Formula in treating hypertension based on network pharmacology and in vivo study

Objective This study aimed to analyze the mechanism of action of the Pingyang Jiangya Formula(平阳降压方,PYJYF)in treating hypertension,based on network pharmacology,and to verify the subsequent predictions through animal experiments.Methods The active components and related target genes of PYJYF were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM),Encyclopedia of Traditional Chinese Medicine(ETCM),and Drug Bank databases and available literature.The hypertension target genes were screened based on Therapeutic Target Database(TTD),GeneCards,Online Mendelian Inheritance in Man(OMIM),UniProt,and relevant literature.The component-disease-target network intersection target genes were inputted into the STRING database,and the key target genes were selected according to the degree algorithm.Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to explore the multitarget mechanism of action and molecular regulatory network of PYJYF in the treatment of hypertension.To verify this prediction,we used PYJYF to intervene in spontaneously hypertensive rats(SHRs)and Wistar–Kyoto rats(WKY)as normal control,and the noninvasive tail artery manometry method was used to measure systolic blood pressure(SBP)in the rat tail before PYJYF intervention.After drug intervention,the SBP of each group rats were measured and compared every week.Enzyme-linked immunosorbent assay(ELISA)was used to test plasma renin,angiotensin II(Ang II),and aldosterone(Ald)levels,and hematoxylin-eosin(HE)staining was used to observe pathological damage to the renal vessels in each group of rats.Western blot and reverse transcription real-time quantitative PCR(RT-PCR)were used to detect the protein and mRNA expression levels of PI3 K,AKT1,BAX,and Bcl-2,respectively.Results A total of 4123 hypertension targets were obtained from related databases.From the TCMSP and chemical databases,78 active components of PYJYF and the corresponding 401 drug targets were retrieved.Data analysis revealed that 208 drug targets directly interacted with the hypertension targets in PYJYF.The 10 targets most closely related to hypertension target proteins in PYJYF were directly retrieved from relevant databases.GO analysis revealed that 10 direct target proteins were involved in all aspects of the antihypertensive effects of PYJYF,as well as molecular biological processes,such as the regulation of blood pressure,renin-angiotensin-aldosterone system(RAAS),angiotensin-mediated ligand reactions,and biological stimulation of cardiomyocyte apoptosis.KEGG pathway enrichment analysis revealed that PYJYF directly affected 20 signaling pathways associated with hypertension.In animal experiments,PYJYF reduced the protein and m RNA levels of PI3 K,Akt,and Bax and upregulated the expression of the protein and m RNA levels of Bcl-2,reduced plasma renin,Ang II,and Ald levels,improved the hyperactivity of RAAS,and significantly reduced SBP in SHRs.Conclusion PYJYF is effective for hypertension therapy that acts through multiple compounds and targets.The possible underlying molecular mechanism includes regulating the PI3 K/Akt signaling pathway to suppress RAAS,increasing the ratio of Bcl-2/Bax proteins,and inhibiting apoptosis,thereby mediating the repair of renal and renal vascular damage caused by hypertension.These findings warrant further research for use in clinical settings.

Toll-like receptors,a double-edged sword in immunity to malaria

Toll-like receptors(TLRs) are a central component of innate immune system and play a major role as the initiator of the innate immune responses to defend against bacteria,viruses,parasite and other pathogens.During malaria infection,TLRs signaling pathways are initialed with the recognition of Plasmodium glycosylphosphatidylinositols(GPI) and hemozoin as pathogen-associated molecular patterns(PAMPs).And then,activation of TLRs signaling induces specific biological responses against malaria parasites invasion.However,TLRs are also involved in malaria pathogenesis and enhancement of immune tolerance and evasion for malaria infection.Moreover,malaria parasites regulate selectively TLRs expression on immune cells.Thus,these evidences indicated that TLRs have contrary roles on malaria infection.Understanding the complicated roles of TLRs on malaria infection will contribute us to design more effective anti-malaria drugs or vaccines.

Explore the direct and/or the synergistic antihypertensive effects of wind-dispelling herbs involving Fangfeng and Baizhi on hypertensive rats with liver-yang hyperactivity based on vasoactive substances

Objective： To explore the direct and/or the enhancing antihypertensive effects of wind-dispelling herbs involvingFangfeng （Saposhnikoviae Radix） and Baizhi （Angelicae dahuricae Radix） using liver-yang hyperactivity renalhypertension rat. Methods： Model rats with hyperactivity of liver-yang hyperactivity were prepared using male SD rats.Once successful, the rats were randomly divided into groups and given medicine by gavage for 4 weeks. Blood wascollected from the abdominal aorta to prepare serum. Serum nitric oxide （NO） concentration was determined bychemical colorimetry. The contents of ET, TXB2 and 6-K-PGF1a were determined by enzyme linked immunosorbentassay （ELISA）. Results： Compared with the control model group, the blood pressure, serum ET and TXB2 of rats in thewind dispelling medicine group was not significantly reduced, while those of rats in captopril group, Tianma GoutengDecoction I group （TGD group） decreased significantly （P 〈0.05 for both）. Interestingly, the blood pressure, serum ETand TXB2 of rats in the combination group （wind dispelling medicine ＆ TGD） decreased significantly compared withboth wind dispelling medicine group and TGD group. Meanwhile, the levels of serum NO and 6- K-PGF1a in thecombination group was much higher than those in the wind dispelling medicine group or TGD group （P 〈0.05 for both）.However, the levels of serum NO and 6- K-PGF1a in the wind dispelling medicine group was not significantly increasedcompared with the model group. Conclusion： There is no direct pressure lowering effects of wind dispelling medicinealone, while wind dispelling medicine could potentiates the antihypertensive effects of Tianma Gouteng Decoction I.Besides, the synergistic effects may be related to decreased ET and TXB2 levels and the increased NO and 6- K-PGF1alevels.