Screening for Anti-tumor Activity of Fractions from Buddleja officinalis Maxim

[Objectives]The anti-tumor activity of fractions from Buddleja officinalis Maxim.by petroleum ether,ethyl acetate,n-butanol and water solvent was studied.[Methods]The ethanol extract from B.officinalis Maxim.was extracted and then concentrated with petroleum ether,ethyl acetate,n-butanol and water,respectively,and the extracts were obtained.The inhibitory effects of the four different fractions on the growth of three tumor cell lines in vitro were detected by CCK-8 method,and the median inhibitory concentration(IC 50 value)was calculated.[Results]The four fractions inhibited the growth of the three tumor cell lines in vitro,among which the n-butanol fraction had the best anti-tumor activity.The IC 50 values of the n-butanol fraction on human gastric cancer(SGC-7901),human breast cancer(MCF-7)and human liver cancer(BEL-7404)cell lines were 0.08,1.58 and 0.12 mg/mL,respectively.[Conclusions]Petroleum ether,ethyl acetate,n-butanol and water fractions from the ethanol extract of B.officinalis Maxim.had certain anti-tumor effects,and the n-butanol fraction had the best anti-tumor activity.

Preparation of kakkatin derivatives and their anti-tumor activity

BACKGROUND Modern pharmacological studies have confirmed that plant-derived compounds from Puerariae flos(PF)has significant biological activities against liver damage,tumors and inflammation.Kakkatin is an isoflavone polyphenolic compound isolated from PF flower.However,the effect of kakkatin and its derivatives on anti-tumor has not been well explored.AIM To design and synthesize a kakkatin derivative[6-(hept-6-yn-1-yloxy)-3-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one(HK)]to explore its anti-tumor biological activity.METHODS Hept-6-yn-1-yl ethanesulfonate was introduced to replace hydrogen at the hydroxyl position of kakkatin phenol,and the derivative of kakkatin was prepared;the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to detect cell viability,a clone formation assay was adopted to detect cell proliferation,apoptosis,necrosis,and cell cycles were analyzed by Annexin V/propidium iodide staining and flow cytometry.Cell migration and invasion ability were evaluated by cell scratch assay and transwell assay.The potential mechanism of HK on hepatocellular carcinoma(HCC)SMMC-7721 cells was explored through network pharmacology and molecular docking,and finally real-time PCR assays was used to verify the potential targets and evaluate the biological activity of HK.RESULTS Compared with kakkatin,the modified HK did not significantly increase the inhibitory activity of gastric cancer MGC803 cells,but the inhibitory activity of HCC SMMC-7721 cells was increased by about 30 times,with an IC50 value of 2.5μM,and the tumor inhibition effect was better than cisplatin,which could significantly inhibit the cloning,invasion and metastasis of HCC SMMC-7721 cells,and induce apoptosis and G2/M cycle arrest.Its mechanism of action is mainly related to the upregulation of PDE3B and NFKB1 target proteins in the cAMP pathway.CONCLUSION HK have a significant inhibitory effect on HCC SMMC-7721 cells,and the targets of their action may be PDE3B and NFKB1 proteins in the cAMP pathway,making it a good lead drug for the treatment of HCC.

Galectin 2 regulates JAK/STAT3 signaling activity to modulate oral squamous cell carcinoma proliferation and migration in vitro

Background:Galectin 2(LGALS2)is a protein previously reported to serve as a mediator of disease progression in a range of cancers.The function of LGALS2 in oral squamous cell carcinoma(OSCC),however,has yet to be explored,prompting the present study to address this literature gap.Methods:Overall,144 paired malignant tumor tissues and paracancerous OSCC patient samples were harvested and the LGALS2 expression levels were examined through qPCR and western immunoblotting.The LGALS2 coding sequence was introduced into the pcDNA3.0 vector,to enable the overexpression of this gene,while an LGALS2-specific shRNA and corresponding controls were also obtained.The functionality of LGALS2 as a regulator of the ability of OSCC cells to grow and undergo apoptotic death in vitro was assessed through EdU uptake and CCK-8 assays,and flow cytometer,whereas a Transwell system was used to assess migratory activity and invasivity.An agonist of the Janus Kinase 2(JAK2)/Signal Transducer and Activator of Transcription 3(STAT3)pathway was also used to assess the role of this pathway in the context of LGALS2 signaling.Results:Here,we found that lower LGALS2 protein and mRNA expression were evident in OSCC tumor tissue samples,and these expression levels were associated with clinicopathological characteristics and patient survival outcomes.Silencing LGALS2 enhanced proliferation in OSCC cells while rendering these cells better able to resist apoptosis.The opposite was instead observed after LGALS2 was overexpressed.Mechanistically,the ability of LGALS2 to suppress the progression of OSCC was related to its ability to activate the JAK/STAT3 signaling axis.Conclusion:Those results suggest a role for LGALS2 as a suppressor of OSCC progression through its ability to modulate JAK/STAT3 signaling,supporting the potential utility of LGALS2 as a target for efforts aimed at treating OSCC patients.

Vaccinia-related kinase 2 variants differentially affect breast cancer growth by regulating kinase activity

Genetic information is transcribed from genomic DNA to mRNA,which is then translated into threedimensional proteins.mRNAs can undergo various post-transcriptional modifications,including RNA editing that alters mRNA sequences,ultimately affecting protein function.In this study,RNA editing was identified at the 499th base(c.499)of human vaccinia-related kinase 2(VRK2).This RNA editing changes the amino acid in the catalytic domain of VRK2 from isoleucine(with adenine base)to valine(with guanine base).Isoleucine-containing VRK2 has higher kinase activity than the valine-containing VRK2,which leads to an increase in tumor cell proliferation.Earlier we reported that VRK2 directly interacts with dystrobrevin-binding protein(dysbindin)and results in reducing its stability.Herein,we demonstrate that isoleucine-containing VRK2 decreases the level of dysbindin than valinecontaining VRK2.Dysbindin interacts with cyclin D and thereby regulates its expression and function.The reduction in the level of dysbindin by isoleucine-containing VRK2 further enhances the cyclin D expression,resulting in increased tumor growth and reduction in survival rates.It has also been observed that in patient samples,VRK2 level was elevated in breast cancer tissue compared to normal breast tissue.Additionally,the isoleucine form of VRK2 exhibited a greater increase in breast cancer tissue.Therefore,it is concluded that VRK2,especially dependent on the 167th variant amino acid,can be one of the indexes of tumor progression and proliferation.

Discovery and structure-activity relationship studies of novel tetrahydro-β-carboline derivatives as apoptosis initiators for treating bacterial infections

Developing and excavating new agrochemicals with highly active and safe is an important tactic for protecting crop health and food safety.In this paper,to discover the new bactericide candidates,we designed,prepared a new type of1,2,3,4-tetrahydro-β-carboline(THC)derivatives and evaluated the in vitro and in vivo bioactivities against the Xanthomonas oryzae pv.oryzae(Xoo),Xanthomonas axonopodis pv.citri(Xac),and Pseudomonas syringae pv.actinidiae(Psa).The in vitro bioassay results exhibited that most title molecules possessed good activity toward the three plant pathogenic bacteria,the compound A17 showed the most active against Xoo and Xac with EC50 values of 7.27 and 4.89 mg mL^(-1)respectively,and compound A8 exhibited the best inhibitory activity against Psa with EC50value of 4.87 mg mL^(-1).Pot experiments showed that compound A17 exhibited excellent in vivo antibacterial activities to manage rice bacterial leaf blight and citrus bacterial canker,with protective efficiencies of 52.67 and 79.79%at 200 mgmL^(-1),respectively.Meanwhile,compound A8 showed good control efficiency(84.31%)against kiwifruit bacterial canker at 200 mg mL^(-1).Antibacterial mechanism suggested that these compounds could interfere with the balance of the redox system,damage the cell membrane,and induce the apoptosis of Xoo cells.Taken together,our study revealed that tetrahydro-β-carboline derivatives could be a promising candidate model for novel broadspectrum bactericides.

Study on Antitumor Activity of Piperidine Derivatives

[Objectives]This study was conducted to investigate the effects of piperidine derivatives on the proliferation and apoptosis of tumor cells(Hele).[Methods]The target end product(piperidine derivative)was synthesized through a series of organic reactions.The MTT assay was adopted to detect the effect of piperidine derivative on the proliferation activity of Hele cells.The ROS fluorescence probe method was used to detect the changes of reactive oxygen species.The JC-1 method was applied to detect the changes of MMP in Hele cells.Flow cytometry was adopted to detect the apoptosis of Hele cells.[Results]The cell survival rates were 70.84%,65.46%and 54.48%when the drug concentration was 100,110 and 120μmol/L,respectively.When the drug concentration increased to 120μmol/L,the cell survival rate decreased by nearly half.The fluorescence intensity of active oxygen in the control group was 1,and when the drug concentrations were 100,110 and 120μmol/L,the fluorescence intensity of active oxygen was,respectively,1.315,1.478 and 1.677,which were higher than that in the control group.The red/green fluorescence intensity of the MMP control group was 1.819,and that of drug groups was,respectively,1.643,1.164 and 0.665,which were lower than that of the control group.The apoptosis rates were 10.79%,22.91%and 38.54%at the drug concentrations of 100,110 and 120μmol/L,respectively,showing a concentration dependent effect.The results showed that the piperidine derivative could inhibit the proliferation of Hele cells and induce apoptosis,which was positively correlated with the concentration.[Conclusions]This study provides theoretical basis and reference for the anti-tumor research of piperidine.

Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway

BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIM To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory environment.METHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BMSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs.Mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.

Mast cell activation syndrome:An up-to-date review of literature

Mast cells are a subtype of white blood cells and are involved in the immune system.These cells contain many chemical substances called mediators,which are involved in the allergic response.The fact that mast cells play a role in many events that require urgent intervention,especially anaphylaxis,has led to a more detailed study of these cells.The diseases also caused by dysfunctions of mast cells have been examined in many circumstances.For instance,mast cell activation syndrome is known as an augmented number of cells due to decreased cell death,resulting in clinical symptoms affecting many systems.The main common symptoms include flushing,hypotension,urticaria,angioedema,headache,vomiting and diarrhea.Although the underlying mechanism is not yet clearly known,we aim to review the literature in a broad perspective and bring together the existing knowledge in the light of the literature due to the diversity of its involvement in the body and the fact that it is a little known syndrome.

Long noncoding RNA steroid receptor RNA activator 1 inhibits proliferation and glycolysis of esophageal squamous cell carcinoma

BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.

Activity Screening Study on the Anti-tumor Effects of Extracts from Mahoniae caulis

[Objectives]To explore the anti-tumor activity of the extracts of petroleum ether,ethyl acetate,n-butanol and aqueous solution from Mahoniae caulis.[Methods]The extracts were extracted with petroleum ether,ethyl acetate,n-butanol and aqueous solution respectively,and then concentrated.The inhibitory effects of these extracts on the growth of three tumor cell lines in vitro were detected by CCK-8 method,and the IC 50 value was calculated.[Results]The four extracts inhibited the growth of the three tumor cell lines in vitro,among which the n-butanol extract had the best anti-tumor activity.The IC 50 values of the n-butanol extract on human gastric cancer(SGC-7901),human breast cancer(MCF-7)and human liver cancer(BEL-7404)cell lines were 0.23,0.25 and 0.58 mg/mL,respectively.[Conclusions]The ethanol extract of Mahoniae caulis under petroleum ether,ethyl acetate,n-butanol and aqueous solution had certain anti-tumor effect,and n-butanol extract had the best anti-tumor activity.

Anti-tumor Activity of Isovanillin and Its Molecular Mechanism

Taking isovanillin and the important products synthesized from raw materials of isovanillin as objects,this paper reviews its pharmacological effects and molecular mechanisms,including inhibiting tumor angiogenesis,blocking cancer cell self-repair,inducing cancer cell DNA fragmentation,cytotoxicity,inhibiting tumor growth,regulating brain nerves,inhibiting renin and other pharmacological effects,etc.,which provide new ideas for the in-depth research and development of isovanillin.

Surface activity of cancer cells:The fusion of two cell aggregates

A key feature that distinguishes cancer cells from all other cells is their capability to spread throughout the body.Although how cancer cells collectively migrate by following molecular rules which influence the state of cell-cell adhesion contacts has been comprehensively formulated,the impact of physical interactions on cell spreading remains less understood.Cumulative effects of physical interactions exist as the interplay between various physical parameters such as(1)tissue surface tension,(2)viscoelasticity caused by collective cell migration,and(3)solid stress accumulated in the cell aggregate core region.This review aims to point out the role of these physical parameters in cancer cell spreading by considering and comparing the rearrangement of various mono-cultured cancer and epithelial model systems such as the fusion of two cell aggregates.While epithelial cells undergo volumetric cell rearrangement driven by the tissue surface tension,which directs cell movement from the surface to the core region of two-aggregate systems,cancer cells rather perform surface cell rearrangement.Cancer cells migrate toward the surface of the two-aggregate system driven by the solid stress while the surface tension is significantly reduced.The solid stress,accumulated in the core region of the two-aggregate system,is capable of suppressing the movement of epithelial cells that can undergo the jamming state transition;however,this stress enhances the movement of cancer cells.We have focused here on the multi-scale rheological modeling approaches that aimed at reproducing and understanding these biological systems.

Research on the biological activity and anti-tumor effect against lymphoma cells of DC-CIK cells

Objective： To investigate the proliferation capabilities, immunophenotype changes, level of secreted cytokines and activities against lymphoma cells under the condition that cytokine-induced killer （CIK） cells co-cultured with dendritic cells （DC） in vitro. Methods： DC and CIK cells were induced from peripheral blood mononuclear cells of healthy volunteers. They were co-cultured meanwhile CIK cells were cultured alone as controls. Increased number of cells were counted by tapan-blue staining, killing activities were detected by MTT assay, immunophenotype changes were analyzed by flow cytometry, the IL-12 and INF-y levels of the cultured supernatants were detected by ELISA kits. Results： The proliferation capabilities of DC-CIK cells were significantly higher than that of CIK cells （P 〈 0.05）. Under the same condition, the ratio of double positive cells such as CD3^＋ CD8^＋, CD3^＋ CD56^＋ in CIK cells was significantly enhanced by co-cultured with DC cells （P 〈 0.05）. The level of IL-12 and INF-y secreted in supernatants was increased noticeably by co-cultured DC-CIK cells on day 3 compared to CIK cells which were cultured alone （P 〈 0.01 and P 〈 0.05）. Within the effector-target ratio range between 5：1 to 40：1, the activities against lymphoma cells of DC-CIK cells were much higher than that of CIK cells （P 〈 0.05）, and this effect was showed a positive correlation with the effector-target ratio. Conclusion： The proliferation capabilities, the level of secreted cytokines and the activities against lymphoma cells of DC-CIK cells were significantly higher than those of CIK cells. The research might provides theoretical and experimental basis for clinical immunotherapy of DC-CIK cells.

Effect of anti-asthma Chinese medicine Chuankezhi on the anti-tumor activity of cytokine-induced killer cells

Chuankezhi(CKZ),a new Chinese medicine,plays an important role in immunoregulation.Cytokineinduced killer(CIK)cells have been commonly used for immunotherapy in recent years.In this study,we aimed to investigate the immunoregulatory effect of CKZ on CIK cells.Peripheral blood monocytes were isolated from healthy donors,and CIK cells were generated by culturing monocytes with interferon-gamma(IFN-γ)and interleukin 2.Different concentrations of CKZ were added on day 2.After incubation for 14days in culture,the antitumor effects of CIK cells were measured by cytotoxicity assay.Flow cytometry was used to explore the effect of CKZ on CIK cell immunophenotype,intracellular cytokine production,and apoptosis.The effect of CKZ on the antitumor activity of CIK cells in nude mice was also investigated.CKZ increased the percentage of CD3+CD56+CIK cells but did not significantly change the percentage of CD4+,CD8+,or CD4+CD25+CIK cells.CKZ-conditioned CIK cells showed a greater ability to kill tumor cells,as well as a higher frequency of IFN-γand TNF-αproduction,compared with the CIK cells in the control group.CKZ also suppressed the apoptosis of CIK cells in vitro.Furthermore,CKZ combined with CIK cells had a stronger suppressive effect on tumor growth in vivo than the CIK,CKZ,or normal saline control groups.Our results indicate that CKZ enhances the antitumor activity of CIK cells and is a potential medicine for tumor immunotherapy.

Study of Multi-directional Derivation of Cord Blood Mononuclear Cells and Observation of Killing Activity to MGC-803 Gastric Cancer Cell Strain In Vitro

Objective： To study multi-directional derivation of cord blood mononuclear cells to CD3AK, LAK and CIK cells as well as changes of killing activity to gastric cancer cell strain in vitro. Methods： CD3mAb and IL-2 were used to induce CD3AK cells, and IL-2 was used to induce LAK cells; IFN-γ was used in the beginning, then IL-1, CD3mAb and IL-2 were used to induce CIK cells after 24 h for observing amplification and analyzing their relationship. The phenotypes of the cultured CIK cells were analyzed by flow cytometry. Subsequently, by using MGC-803 gastric cancer cell strain as target cells, the killing activity of CD3AK, LAK and CIK cells was evaluated by using MTT method. Results： The amplification activity of CD3AK and CIK cells was all far higher than LAK cells （P〈0.05）. The amplification activity had no obvious difference between CIK cells and CD3AK cells at prophase, but that was far higher in CIK cells than CD3AK cells at about 20^th day （P〈0.05）. The flow cytometry revealed that the amount of CD3^＋ CD56^＋ cells, major effector cells after CIK cells being cultured was significantly increased （P〈0.05）, moreover, the amount of CD8^＋ cells was significantly increased as well （P〈0.05）. The killing activities of CD3AK and CIK cells to the MGC-803 gastric cancer cell strain were all significantly higher than LAK cells, while the killing activity of CIK cells was stronger than CD3AK cells （P〈0.05）. Conclusion： CIK cells have stronger amplification activity and killing activity, and can be taken as more effective killing cells applied to the tumor adoptive immunotherapy.

Mechanism of annexin A1/N-formylpeptide receptor regulation of macrophage function to inhibit hepatic stellate cell activation through Wnt/β-catenin pathway

BACKGROUND Hepatic fibrosis is a common pathological process of chronic liver diseases with various causes,which can progress to cirrhosis.AIM To evaluate the effect and mechanism of action annexin(Anx)A1 in liver fibrosis and how this could be targeted therapeutically.METHODS CCl4(20%)and active N-terminal peptide of AnxA1(Ac2-26)and N-formylpeptide receptor antagonist N-Boc-Phe-Leu-Phe-Leu-Phe(Boc2)were injected intraperitoneally to induce liver fibrosis in eight wild-type mice/Anxa1 knockout mice,and to detect expression of inflammatory factors,collagen deposition,and the role of the Wnt/β-catenin pathway in hepatic fibrosis.RESULTS Compared with the control group,AnxA1,transforming growth factor(TGF)-β1,interleukin(IL)-1βand IL-6 expression in the liver of mice with hepatic fibrosis induced by CCl4 was significantly increased,which promoted collagen deposition and expression ofα-smooth muscle actin(α-SMA),collagen type I and connective tissue growth factor(CTGF),and increased progressively with time.CCl4 induced an increase in TGF-β1,IL-1βand IL-6 in liver tissue of AnxA1 knockout mice,and the degree of liver inflammation and fibrosis and expression ofα-SMA,collagen I and CTGF were significantly increased compared with in wild-type mice.After treatment with Ac2-26,expression of liver inflammatory factors,degree of collagen deposition and expression of a-SMA,collagen I and CTGF were decreased compared with before treatment.Boc2 inhibited the anti-inflammatory and antifibrotic effects of Ac2-26.AnxA1 downregulated expression of the Wnt/β-catenin pathway in CCl4-induced hepatic fibrosis.In vitro,lipopolysaccharide(LPS)induced hepatocyte and hepatic stellate cell(HSC)expression of AnxA1.Ac2-26 inhibited LPS-induced RAW264.7 cell activation and HSC proliferation,decreased expression ofα-SMA,collagen I and CTGF in HSCs,and inhibited expression of the Wnt/β-catenin pathway after HSC activation.These therapeutic effects were inhibited by Boc2.CONCLUSION AnxA1 inhibited liver fibrosis in mice,and its mechanism may be related to inhibition of HSC Wnt/β-catenin pathway activation by targeting formylpeptide receptors to regulate macrophage function.

3D-QSAR Studies on the Anti-tumor Activity of N-Aryl-salicylamide Derivatives

In the present work,comparative molecular field analysis(CoMFA)techniques were used to perform three-dimensional quantitative structure-activity relationship(3D-QSAR)studies on the anti-tumor activity(pHi,i=1,2,3,4)of N-aryl-salicylamide derivatives against four cancer cell lines,including A549,MCF-7,SGC-7901,and Bel-7402.12 compounds were randomly selected as the training set to establish the prediction models,which were verified by the test set of 5 compounds containing template molecule.The contributions of steric and electrostatic fields to pH1,pH2,pH3,and pH4 were 23.8% and 76.2%,20.1% and 79.9%,18.7% and 81.3%,and 14.3%and 85.7%,respectively.The cross-validation(Rcv 2)and non-cross-validation coefficients(R2)were 0.826 and 0.963 for pH1,0.867 and 0.974 for pH2,0.941 and 0.989 for pH3,and 0.797 and 0.961 for pH4,respectively.The CoMFA models were then used to predict the activities of the compounds,and it was found that the models had strong stability and good predictability.Based on the CoMFA contour maps,some key structural factors responsible for the anticancer activity of the series of compounds were revealed.The results provide some useful theoretical references for understanding the mechanism of action,designing new N-aryl-salicylamide derivatives with high anti-tumor activity,and predicting their activities.

Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10,MC38 and Hep1-6 Tumor Models

Objective To investigate the anti-tumor effects of Pien Tze Huang(PZH)in mouse models of B16–F10 melanoma,MC38 colorectal cancer,Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model.Methods Various tumor models,including B16–F10,MC38 and Hep1-6 tumor hypodermic inoculation models,B16–F10 and Hep1-6 pulmonary metastasis models,Hep1-6 orthotopic implantation model,and chemically induced hepatocellular carcinoma model,were utilized to evaluate the anti-tumor function of PZH.Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice.For cell proliferation and death of tumor cells in vitro,as well as T cell activation markers,cytokine production and immune checkpoints analysis,single-cell suspensions were prepared from mouse spleen,lymph nodes,and tumors after PZH treatment.Results PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth(P<0.01).Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16–F10 melanoma models,and decreased pulmonary metastasis of B16–F10 melanoma and Hep1-6 hepatoma(P<0.01).However,in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells(P>0.05).Nevertheless,PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma,tumor necrosis factor alpha,and interleukin 2 in CD4^(+)T cells in vitro(P<0.01 or P<0.05).Importantly,PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8^(+)T cells(P<0.01 or P<0.05).Conclusion This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity,indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

Free radical scavenging property and antiproliferative activity of Rhodiola imbricata Edgew extracts in HT-29 human colon cancer cells

Objective:To investigate the in vitro antioxidant and antiproliferative activity of rhizome extracts of Rhodiola imbricata(R.imbricata) in HT-29 human colon cancer cell line.Methods:The successively extracted rhizome of R.imbricata using various solvents was analyzed for their total phenolics,tannins and flavonoid contents.In vitro antioxidant activity was evaluated by employing different assays,including DPPH,ABTS radical scavenging assays,FRAP, phosphomolybdenum reduction assay,superoxide anion,hydroxyl radical scavenging activities and metal chelating ability.Results:Acetone and methanol extracts recorded higher phenolic content and showed comparable antioxidant activity with standard reference.Additionally,they also inhibited the proliferation of HT-29 cells upon treatment at higher concentration(200μg/mL) (acetone and methanol,84%and 84%.respectively).On examination acetone extract exhibited antiproliferative activity in a concentration dependent manner whereas,methanol extract showed both dose dependent and lime dependent inhibitory activity.Conclusions:The results obtained justify the traditional usage of R.imbricata from their promising antioxidant activity.

T cell immune response is correlated with fibrosis and inflammatory activity in hepatitis B cirrhotics

AIM： TO explore the relationship among interferon-γ （IFN-γ） activity, fibrogenesis, T cell immune responses and hepatic inflammatory activity. METHODS： Peripheral blood samples from a total of 43 hepatitis B cirrhotic patients （LC） and 19 healthy controls （NC） were collected to measure their serum levels of IFN-γ, interleukin-2 （IL-2）, soluble interleukin-2 receptor （sIL-2R）, interleukin-10 （IL-10） and three serological markers of fibrosis including hyaluronic acid （HA）, procollagen type III peptide （PIIIP）, and type iV collagen were measured using a double antibody sandwich ELISA. Also, serum total bilirubin （TB） and alanine aminotransferase （ALT） were measured by routine measures. RESULTS： The concentrations of serological markers of fibrosis in patients with active cirrhosis （ALC） were significantly higher than those in stationary liver cirrhosis （SLC） or NC groups. The levels of serological markers in HBeAg-positive patients were significantly higher than those in HBeAg-negative patients. In SLC and ALC patients, a negative linear correlation was found between IFN-γ levels and the serological markers of fibrosis. IFN-γ and IL-2 levels in the ALC group were significantly higher than those in the SLC and NC groups, but the statistical difference was not significant between the latter two. In contrast, IL-10 levels in the SLC group were significantly higher than that in the NC group, but no significant difference was found between SLC and ALC groups. The sIL-2R level was elevated gradually in all these groups, and the differences were significant. Positive linear correlations were seen between IFN-γ activity and ALT levels （r = 0.339, P 〈 0.05）, and IL-2 activity and TB levels （r = 0.517, P 〈 0.05）. sIL-2R expression was positively correlated with both ALT and TB levels （r = 0.324, 0.455, P 〈 0.05）, whereas there was no statistically significant correlation between IL-10 expression and serum ALT and TB levels （r = -0.102, -0.093, P 〉 0.05）. Finally, there was a positive correlation between IFN-γ and IL-2 levels. CONCLUSION： T cell immune responses are correlated with fibrosis and hepatic inflammatory activity and may play an important role in liver cirrhosis.