ABSTRACT
BACKGROUND: The objective of this study was to evaluate the comparative efficacy of current interventions for the prevention of retinopathy of prematurity (ROP) in premature infants. METHODS: A network meta-analysis (NMA) was performed. We searched PubMed, Web of Science, Scopus, Embase, and the Cochrane Library for relevant studies from their inception to May 5, 2022. Publications were eligible for our study if they were randomized controlled trials (RCTs) involving preterm infants at <37 weeks of gestational age and reported the incidence of any-stage ROP treated with the interventions of interest. The overall effect was pooled using the random effects model. RESULTS: We identified 106 RCTs (involving 23894 participants). This NMA showed that vitamin A supplementation markedly reduced the incidence of ROP, in comparison with placebo (odds ratio [OR] = 0.59, 95% credible interval [95% CrI] 0.33, 0.85), fish oil-based lipid emulsion (OR = 0.57, 95% CrI 0.24, 0.90), early erythropoietin (OR = 0.51, 95% CrI 0.34, 0.98), probiotics (OR = 0.48, 95% CrI 0.32, 0.97), and human milk (OR = 0.50, 95% CrI 0.21, 0.78). Vitamin A supplementation has the highest probability of being the best option for reducing the ROP risk compared with the other 20 interventions based on its surface under the cumulative ranking curve (SUCRA) value (SUCRA = 92.50%, 95% CrI 0.71, 1.00). CONCLUSIONS: Our findings suggest that among 21 interventions, vitamin A supplementation might be the best method of preventing ROP. This NMA offers an important resource for further efforts to develop preventive strategies for ROP.
Subject(s)
Retinopathy of Prematurity , Infant, Newborn , Humans , Network Meta-Analysis , Vitamin A , Randomized Controlled Trials as Topic , Infant, PrematureABSTRACT
BACKGROUND: There are conflicts in guideline recommendations about the value and range of vancomycin trough concentration during therapeutic drug monitoring (TDM). This multicentre, retrospective study was conducted to explore the usefulness of trough concentration in specific patients who were critically ill and without any form of dialysis. METHODS: Patient information from five centres was retrospectively collected and the 24-hour area under the curve (AUC) was estimated by a Bayesian method. Patients were categorised into four groups according to trough concentration: < 10, 10-15, 15-20 and > 20 mg/L, and the corresponding AUC was analysed. A multivariable logistic regression model was used to investigate the relationship between trough concentration and AUC. RESULTS: Overall, 645 trough concentrations available from 416 patients were included in this study. The results indicated that the AUC was always < 400 mg/Lâh or > 600 mg/Lâh in the < 10 or > 20 mg/L groups, whereas the ratios of vancomycin AUC target attainment (400-600 mg/Lâh) were 48.8% and 92.3% in the 10-15 mg/L and 15-20 mg/L groups, respectively. Augmented renal clearance, low daily dose and non-q12h administration were found to be independent risk factors associated with AUC target non-attainment for patients with trough concentrations of 10-15 mg/L. CONCLUSION: Vancomycin trough concentration is a good marker of AUC for critically ill adults without any form of dialysis. However, AUC-guided TDM may be needed for patients with trough concentrations of 10-15 mg/L, especially for those with risk factors.
Subject(s)
Anti-Bacterial Agents , Vancomycin , Adult , Humans , Vancomycin/therapeutic use , Retrospective Studies , Anti-Bacterial Agents/therapeutic use , Drug Monitoring/methods , Critical Illness , Bayes Theorem , Renal Dialysis , Microbial Sensitivity Tests , Area Under CurveABSTRACT
BACKGROUND AND AIMS: The association between serum uric acid (SUA) and tea consumption has been studied in previous work, and there were arguments among various population group employed as well as different statistical approaches. The aim of this work is to investigate the tea effect on SUA levels among older adults by comparing three large-scale populations with both cross-sectional and longitudinal analyses. METHOD: We examined the relationship between intake and SUA levels among older adults using linear regression. All the studies include the parameters SUA levels, tea intake, age, sex, education level, smoking status, alcohol drinking status, body mass index (BMI), and health history (diabetes, hypertension, and fasting plasma glucose). The cross-sectional analyses were conducted with 4579 older adults in the Weitang Geriatric Diseases Study (WGDS, ≥60 years), 2440 in the China Health and Nutrition Survey (CHNS, ≥60 years) and 1236 in the Chinese Longitudinal Healthy Longevity Survey (CLHLS, ≥62 years); and the longitudinal analyses were performed with 3870 (84.5%) in the WGDS and 420 (34.0%) in the CLHLS. Multivariable linear regression analyses were performed in both cross-sectional and longitudinal studies. RESULTS: Cross-sectional studies showed that tea consumers tended to have higher SUA levels than non-tea consumers in all the three datasets (P < 0.05). However, longitudinal associations of SUA levels with tea consumption had no statistical significance (P>0.05). The results of sex-stratified analyses were consistent with those of the whole datasets. CONCLUSIONS: This work implied that any possible association between tea consumption and SUA levels could be very weak.
Subject(s)
Hypertension , Uric Acid , Aged , China/epidemiology , Cross-Sectional Studies , Humans , TeaABSTRACT
Although the crosstalk between iron (Fe) and copper (Cu) homeostasis signalling networks exists in plants, the underlined molecular mechanism remains unclear. FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) and four bHLH Ib members (bHLH38, bHLH39, bHLH100 and bHLH101) are the key regulators of Fe homeostasis. Here, we reveal that FIT and bHLH Ib control the up-regulation of Cu-uptake genes (COPT2, FRO4 and FRO5) by Fe deficiency, and Cu is required for improving plant growth under Fe-deficiency conditions. The induction of Cu-uptake gene expression and the elevation of Cu concentration are inhibited in the fit-2 or bhlh4x (the quadruple mutant of four bHLH Ib genes) under Fe-deficiency conditions. The dual overexpression of both bHLH38 (or bHLH39) and FIT activates the expression of COPT2, FRO4 and FRO5 and increases Cu accumulation. Furthermore, bHLH Ib proteins directly bind to the promoters of COPT2, FRO4 and FRO5. Either Cu supplement or overexpression of COPT2 or FRO4 improves the growth of fit-2 under Fe-deficiency conditions. Moreover, the induction of COPT2, FRO4 and FRO5 by Fe deficiency is independent of SPL7, a central regulator of Cu-deficiency responses. This work through the link between bHLH Ib/FIT and COPT2/FRO4/FRO5 under Fe-deficiency conditions establishes a new relationship between Cu and Fe homeostasis.
Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Basic Helix-Loop-Helix Transcription Factors/metabolism , Copper/metabolism , Iron/metabolism , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Basic Helix-Loop-Helix Transcription Factors/genetics , DNA-Binding Proteins/metabolism , Gene Expression Regulation, Plant , Genes, Plant , Homeostasis/genetics , Iron Deficiencies , Models, Biological , Mutation/genetics , Plants, Genetically Modified , Promoter Regions, Genetic , Transcription Factors/metabolism , Up-Regulation/geneticsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Green tea is the most ancient and popular beverage worldwide and its main constituent epigallocatechin-3-gallate (EGCG) has a potential role in the management of cancer through the modulation of cell signaling pathways. However, EGCG is frangible to oxidation and exhibits low lipid solubility and bioavailability, and we synthesized a derivative of EGCG in an attempt to overcome these limitations. AIM OF THE STUDY: The anthracycline antibiotic daunorubicin (DNR) is a potent anticancer agent. However, its severe cardiotoxic limits its clinical efficacy. Human carbonyl reductase 1 (CBR1) is one of the most effective human reductases for producing hydroxyl metabolites and thus may be involved in increasing the cardiotoxicity and decreasing the antineoplastic effect of anthracycline antibiotics. Accordingly, in this study, we investigated the co-therapeutic effect of Y6, a novel and potent adjuvant obtained by optimization of the structure of EGCG. MATERIAL AND METHODS: The cellular concentrations of DNR and its metabolite DNRol were measured by HPLC to determine the effects of EGCG and Y6 on the inhibition of DNRol formation. The cytotoxic effects of EGCG and Y6 were tested by MTT assay in order to identify non-toxic concentrations of them. To understand their antitumor and cardioprotective mechanisms, hypoxia-inducible factor-1α (HIF-1α) and CBR1 protein expression was measured via Western blotting and immunohistochemical staining while gene expression was analyzed using RT-PCR. Moreover, PI3K/AKT and MEK/ERK signaling pathways were analyzed via Western blotting. HepG2 xenograft model was used to detect the effects of EGCG and Y6 on the antitumor activity and cardiotoxicity of DNR in vivo. Finally, to obtain further insight into the interactions of Y6 and EGCG with HIF-1α and CBR1, we performed a molecular modeling. RESULTS: Y6(10 µg/ml or 55 mg/kg) decreased the expression of HIF-1α and CBR1 at both the mRNA and protein levels during combined drug therapy in vitro as well as in vivo, thereby inhibiting formation of the metabolite DNRol from DNR, with the mechanisms being related to PI3K/AKT and MEK/ERK signaling inhibition. In a human carcinoma xenograft model established with subcutaneous HepG2 cells, Y6(55 mg/kg) enhanced the antitumor effect and reduced the cardiotoxicity of DNR more effectively than EGCG(40 mg/kg). CONCLUSIONS: Y6 has the ability to inhibit CBR1 expression through the coordinate inhibition of PI3K/AKT and MEK/ERK signaling, then synergistically enhances the antitumor effect and reduces the cardiotoxicity of DNR.
Subject(s)
Alcohol Oxidoreductases/antagonists & inhibitors , Antibiotics, Antineoplastic/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Arrhythmias, Cardiac/prevention & control , Carcinoma, Hepatocellular/drug therapy , Catechin/analogs & derivatives , Daunorubicin/pharmacology , Enzyme Inhibitors/pharmacology , Liver Neoplasms/drug therapy , Alcohol Oxidoreductases/genetics , Alcohol Oxidoreductases/metabolism , Animals , Antibiotics, Antineoplastic/toxicity , Antineoplastic Combined Chemotherapy Protocols/toxicity , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/physiopathology , Carcinoma, Hepatocellular/enzymology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Cardiotoxicity , Catechin/pharmacology , Cell Proliferation/drug effects , Daunorubicin/toxicity , Drug Synergism , Female , Gene Expression Regulation, Neoplastic , Heart Rate/drug effects , Hep G2 Cells , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Liver Neoplasms/enzymology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Male , Mice, Inbred BALB C , Mice, Nude , Signal Transduction , Tumor Burden/drug effects , Xenograft Model Antitumor AssaysABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Hypervascularity has been considered as one of the major features of many solid tumors. Green tea is one of the commonly drink resources in China, and its active component, Epigallocatechin gallate (EGCG), exhibits antiangiogenic activities in various experimental tumor models. However, EGCG has many shortages, e.g., relatively unstable, low lipid solubility, poor bioavailability, and short duration of action. AIM OF THE STUDY: To overcome the shortages of EGCG for antiangiogenic antitumor usage, our study developed a novel EGCG derivate, Y6(5,3',4',3â³,4â³,5â³-6-0-ethyl-EGCG). The underlying mechanism was also elucidated. MATERIAL AND METHODS: we evaluated the effects of EGCG, Y6 on HCC and angiogenesis in vivo and in vitro. Moreover, to understand their antitumor mechanisms, key factors within angiogenesis-related signaling pathways (MAPK/ERK1/2, PI3K/AKT, HIF-1 VEGF) were analyzed by using western blot, immunohistochemistry (IHC), quantitative real-time quantitative PCR (RT-PCR). HepG2 xenograft model and the chorioallantoic membrane (CAM) were used to investigate the effects of Y6 and EGCG on tumors and anti-angiogenesis in vivo. Micro-vessel density (MVD) was analyzed by IHC of CD34 staining. IHC, qRT-PCR and Western blot were used to detect the expression of HIF-1α and VEGF protein in tumor tissues. The protein levels of MAPK/ERK1/2, PI3K/AKT, HIF-1α, and VEGF in tumor tissues were detected by western blot. RESULTS: Our results demonstrated that both EGCG and Y6 displayed antiangiogenetic and antitumor effects against HCC cells in vitro and in vivo. We found that rather than equal amount of EGCG, Y6 displayed better abilities in inhibiting the growth of HCC tumor cells, as well as inhibiting the growth of neovascularization in the chick embryos and HepG2 xenograft tumors bearing-mice, based on the data obtained from MTT assay, immunohistochemistry (IHC), chick chorioallantoic membrane (CAM) assays. In the comparison of equivalent dose of EGCG, qRT-PCR data showed that Y6 induced more significant decrease of the mRNA levels of HIF-1α and VEGF in supernatant-treated SMMC-7721â¯cells under hypoxic condition, as well as in the in xenograft tumor tissues; whereas Y6 also significantly reduced the protein levels of MAPK/ERK1/2, PI3K/AKT, HIF-1α, and VEGF to a greater extent than EGCG, determined by western blotting assay. CONCLUSIONS: our work suggests that the new EGCG derivate Y6 could significantly inhibit tumor growth and angiogenesis which is possibly involved with the signaling intervention of MAPK/ERK1/2 and PI3K/AKT/HIF-1α/VEGF pathways, and is supposed to be a potential therapeutic reagent for anti-angiogenesis treatment of solid tumors.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Carcinoma, Hepatocellular/drug therapy , Catechin/analogs & derivatives , Liver Neoplasms/drug therapy , MAP Kinase Signaling System/drug effects , Animals , Carcinoma, Hepatocellular/blood supply , Carcinoma, Hepatocellular/metabolism , Catechin/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Chick Embryo , Chorioallantoic Membrane/pathology , Hep G2 Cells , Human Umbilical Vein Endothelial Cells , Humans , Liver Neoplasms/blood supply , Liver Neoplasms/metabolism , Mice , Mitogen-Activated Protein Kinase Kinases/metabolism , Neovascularization, Pathologic/drug therapy , Phosphatidylinositol 3-Kinases/metabolism , Vascular Endothelial Growth Factor A/metabolism , Xenograft Model Antitumor AssaysABSTRACT
Chrysanthemum (Dendranthema grandiflora) flowers are consumed as a popular, traditional herbal tea worldwide. During tea infusion with hot water pesticide residues in chrysanthemum flowers can be transferred into tea solution, posing potential health risks to consumers. Using greenhouse chrysanthemum this study systematically investigated the transfer of metalaxyl-M, fludioxonil, cyantraniliprole, thiamethoxam, and clothianidin (a major metabolite of thiamethoxam) from dry chrysanthemum flowers to tea solution at a range of infusion repetitions, duration and water temperature. The tested pesticides were released into tea solution at varying degrees, and the maximum transfer percentage was 59.9%, 9.8%, 29.4%, 88.2% and 68.4% for metalaxyl-M, fludioxonil, cyantraniliprole, thiamethoxam, and clothianidin, respectively. The transfer of pesticides into tea solution generally increased with increasing pesticide water solubility, water temperature, infusion duration, and pesticide concentrations in dry chrysanthemum flowers, but decreased with increasing octanol-water partition coefficient and the number of infusion repetitions. Risk quotient for pesticide intake via consuming tea solution of chrysanthemum flowers (one and two times of recommended pesticide dosages) ranged from <0.00003 to 0.0924, indicating a low health risk. This study provides useful information for risk assessment of pesticide residues in greenhouse chrysanthemum flowers and may help establish realistic maximum residue limit of pesticides in chrysanthemum flowers and tea solution.
Subject(s)
Chrysanthemum/chemistry , Flowers/chemistry , Food Contamination/analysis , Pesticide Residues/analysis , Teas, Herbal/analysis , Risk Assessment , SolubilityABSTRACT
Based on the high sensitivity and stable fluorescence of CdTe quantum dots (QDs) in conjunction with a specific DNA aptamer, the authors describe an aptamer-based fluorescence assay for the determination of Salmonella Typhimurium. The fluorescence detection and quantification of S. Typhimurium is based on a magnetic separation system, a combination of aptamer-coated Fe3O4 magnetic particles (Apt-MNPs) and QD-labeled ssDNA2 (complementary strand of the aptamer). Apt-MNPs are employed for the specific capture of S. Typhimurium. CdTe QD-labeled ssDNA2 was used as a signaling probe. Simply, the as-prepared CdTe QD-labeled ssDNA2 was first incubated with the Apt-MNPs to form the aptamer-ssDNA2 duplex. After the addition of S. Typhimurium, they could specifically bind the DNA aptamer, leading to cleavage of the aptamer-ssDNA2 duplex, accompanied by the release of CdTe QD-labeled DNA. Thus, an increased fluorescence signal can be achieved after magnetic removal of the Apt-MNPs. The fluorescence of CdTe QDs (λexc/em = 327/612 nm) increases linearly in the concentration range of 10 to 1010 cfuâ¢mL-1, and the limit of detection is determined to be 1 cfuâ¢mL-1. The detection process can be performed within 2 h and is successfully applied to the analysis of spiked food samples with good recoveries from 90% to 105%.
Subject(s)
Aptamers, Nucleotide/chemistry , Biosensing Techniques , Salmonella Infections/diagnosis , Salmonella typhimurium/isolation & purification , Cadmium Compounds/chemistry , Ferrosoferric Oxide/chemistry , Fluorescence , Humans , Quantum Dots/chemistry , Salmonella Infections/microbiology , Salmonella typhimurium/pathogenicity , Tellurium/chemistryABSTRACT
The underground cane of Schizocapsa plantaginea (Hance) has long been used by Chinese ethnic minority as a constituent of anti-cancer formulae. Saponins are abundant secondary metabolic products located in the underground cane of this plant. The potential therapeutic effects of total saponins isolated from Schizocapsa plantaginea (Hance) (SSPH) on human hepatocellular carcinoma (HCC) were tested in vitro in human liver cancer cell lines, SMMC-7721 and Bel-7404. Apoptosis and cell cycle arrest were determined using flow cytometry, caspase activation was determined by ELISA, and PARP, cleaved PARP, mitogen-activated protein kinase (MAPK) expression and phosphorylation were measured using Western blotting analysis. In vivo anti-HCC effects of SSPH were verified in nude mouse xenograft model. SSPH exerted markedly inhibitory effect on HCC cell proliferation in time- and concentration-dependent manner. Moreover, SSPH significantly induced apoptosis through caspase-dependent signaling and arrested cell cycle at G2/M phase. These anti-proliferation effects of SSPH were associated with up-regulated phosphorylation of extracellular signal-regulated kinase-1/2 (Erk1/2) and c-jun-NH2-kinase-1/2 (JNK1/2) and reduced phosphorylation of p38MAPK. Furthermore, inhibitors of ERK, UO126, and JNK, SP600125 inhibited the anti-proliferation effects by SSPH, suggesting that Erk and JNK were the effector molecules in SSPH induced anti-proliferative action. During in vivo experiments, SSPH was found to inhibit xenograft tumor growth in nude mice, with a similar mechanism in vitro. Our study confirmed that SSPH exerted antagonistic effects on human liver cancer cells both in vitro and in vivo. Molecular mechanisms underlying SSPH action might be closely associated with MAPK signaling pathways. These results indicated that SSPH has potential therapeutic effects on HCC.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Dioscoreaceae/chemistry , MAP Kinase Signaling System/drug effects , Saponins/pharmacology , Animals , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/toxicity , Caspases/genetics , Caspases/metabolism , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Heterografts/drug effects , Heterografts/growth & development , Humans , Inhibitory Concentration 50 , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Mice , Mice, Nude , Phosphorylation/drug effects , Plant Tubers/chemistry , Poly (ADP-Ribose) Polymerase-1/metabolism , Saponins/isolation & purification , Saponins/toxicityABSTRACT
6-Gingerol is the major active constituent of ginger. In the current study, we aimed to investigate the mechanisms underlying the effects of 6-Gingerol on hair growth. Mice were randomly divided into five groups; after hair depilation (day 0), mice were treated with saline, or different concentrations of 6-Gingerol for 11 days. The histomorphological characteristics of the growing hair follicles were examined after hematoxylin and eosin staining. The results indicated that 6-Gingerol significantly suppressed hair growth compared with that in the control group. And choose the concentration of 6-Gingerol at 1 mg/mL to treated with mice. Moreover, 6-Gingerol (1 mg/mL) significantly reduced hair re-growth ratio, hair follicle number, and hair follicle length, which were associated with increased expression of MMP2 and MMP9. Furthermore, the growth factors, such as EGF, KGF, VEGF, IGF-1 and TGF-ß participate in the hair follicle cycle regulation and regulate hair growth. We then measured the concentrations of them using ELISA assays, and the results showed that 6-Gingerol decreased EGF, KGF, VEGF, and IGF-1 concentrations, and increased TGF-ß concentration. Thus, this study showed that 6-Gingerol might act as a hair growth suppressive drug via induction of MMP2 and MMP9 expression, which could interfere with the hair cycle.
Subject(s)
Catechols/pharmacology , Fatty Alcohols/pharmacology , Hair Follicle/drug effects , Matrix Metalloproteinase 2/biosynthesis , Matrix Metalloproteinase 9/biosynthesis , Plant Extracts/pharmacology , Animals , Enzyme Induction , Female , Fibroblast Growth Factor 7/biosynthesis , Hair Follicle/pathology , Insulin-Like Growth Factor I/biosynthesis , Male , Mice , Mice, Inbred C57BL , Random Allocation , Transforming Growth Factor beta/biosynthesis , Vascular Endothelial Growth Factor A/biosynthesisABSTRACT
ABSTRACT 6-Gingerol is the major active constituent of ginger. In the current study, we aimed to investigate the mechanisms underlying the effects of 6-Gingerol on hair growth. Mice were randomly divided into five groups; after hair depilation (day 0), mice were treated with saline, or different concentrations of 6-Gingerol for 11 days. The histomorphological characteristics of the growing hair follicles were examined after hematoxylin and eosin staining. The results indicated that 6-Gingerol significantly suppressed hair growth compared with that in the control group. And choose the concentration of 6-Gingerol at 1 mg/mL to treated with mice. Moreover, 6-Gingerol (1 mg/mL) significantly reduced hair re-growth ratio, hair follicle number, and hair follicle length, which were associated with increased expression of MMP2 and MMP9. Furthermore, the growth factors, such as EGF, KGF, VEGF, IGF-1 and TGF-β participate in the hair follicle cycle regulation and regulate hair growth. We then measured the concentrations of them using ELISA assays, and the results showed that 6-Gingerol decreased EGF, KGF, VEGF, and IGF-1 concentrations, and increased TGF-β concentration. Thus, this study showed that 6-Gingerol might act as a hair growth suppressive drug via induction of MMP2 and MMP9 expression, which could interfere with the hair cycle.
Subject(s)
Animals , Male , Female , Rabbits , Plant Extracts/pharmacology , Catechols/pharmacology , Hair Follicle/drug effects , Matrix Metalloproteinase 2/biosynthesis , Matrix Metalloproteinase 9/biosynthesis , Fatty Alcohols/pharmacology , Insulin-Like Growth Factor I/biosynthesis , Random Allocation , Enzyme Induction , Transforming Growth Factor beta/biosynthesis , Hair Follicle/pathology , Vascular Endothelial Growth Factor A/biosynthesis , Fibroblast Growth Factor 7/biosynthesis , Mice, Inbred C57BLABSTRACT
Objective Taccaoside, a steroidal saponin, has been shown to be cytotoxic, although the mechanism of cytotoxicity remains unclear. This study examined the effect of taccaoside on the human hepatocellular carcinoma (HCC) cell lines SMMC-7721 and Bel-7404. Methods The antiproliferative effect of taccaoside were measured using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Cells were stained with Hoechst 33258 to observe morphology. Cell cycle and apoptosis were analysed by flow cytometry. Caspase activation was detected using specific assays, and PARP, Bax and Bcl-2 expression were analysed using western blotting. Results Taccaoside showed antiproliferative effect on HCC cell lines growth in a concentration- and time-dependent manner. Taccaoside arrested cell cycle in the G2/M phase and induced caspase-dependent apoptosis. Western blotting indicated that taccaoside upregulated Bax expression and downregulated Bcl-2 expression. PARP cleavage was observed following taccaoside treatment. Conclusions This study showed that taccaoside may inhibit HCC cell proliferation by inducing apoptosis.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Dioscoreaceae/chemistry , Gene Expression Regulation, Neoplastic , Hepatocytes/drug effects , Saponins/pharmacology , Steroids/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Apoptosis/genetics , Caspase 3/genetics , Caspase 3/metabolism , Caspase 8/genetics , Caspase 8/metabolism , Cell Line, Tumor , Dose-Response Relationship, Drug , G2 Phase Cell Cycle Checkpoints/drug effects , Hepatocytes/metabolism , Hepatocytes/pathology , Humans , Plant Extracts/chemistry , Poly(ADP-ribose) Polymerases/genetics , Poly(ADP-ribose) Polymerases/metabolism , Proteolysis/drug effects , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Saponins/isolation & purification , Signal Transduction , Steroids/isolation & purification , bcl-2-Associated X Protein/agonists , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolismABSTRACT
Green tea catechins have been reported to have antitumor activity. The objective of this study was to examine the effect of catechins on the antitumor efficacy of doxorubicin (DOX) in a murine model for chemoresistant hepatocellular carcinoma (HCC). Epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) are the most abundant polyphenolic compounds in green tea. Here, we show that ECG or EGCG at higher doses had a slight inhibitory effect on cell proliferation in the resistant human HCC cell line BEL-7404/DOX in vitro and in vivo, whereas the administration of DOX with these compounds at lower doses significantly inhibited HCC cell proliferation in vitro and hepatoma growth in a xenograft mouse model, compared with treatment with either agent alone at the same dose. Furthermore, the administration of DOX in combination with ECG or EGCG markedly enhanced intracellular DOX accumulation, which implies that the catechins inhibited P-glycoprotein (P-gp) efflux pump activity. Consistent with these results, the intracellular retention of rhodamine 123, a P-gp substrate, was increased and the level of P-gp was decreased in cells concurrently treated with DOX and ECG or EGCG. EGCG increased topo II expression, but did not alter GST protein levels in tumor xenografts. The expression of MDR1 and HIF-1alpha mRNA was obviously reduced, whereas MRP1 and LRP expression was not changed significantly. These data suggest that tea catechins at non-toxic doses can augment DOX-induced cell killing and sensitize chemoresistant HCC cells to DOX. The chemosensitizing effect of catechins may occur directly or indirectly by reversal of multidrug resistance, involving the suppression of MDR1 expression, or by enhancement of intracellular DOX accumulation, involving inhibition of P-gp function.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Catechin/administration & dosage , Catechin/pharmacology , Doxorubicin/administration & dosage , Liver Neoplasms, Experimental/drug therapy , Animals , Carcinoma, Hepatocellular/pathology , Drug Resistance, Neoplasm/drug effects , Drug Synergism , Female , Humans , Liver Neoplasms, Experimental/pathology , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Models, Biological , Tea/chemistry , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
OBJECTIVE: To explore the effects of the method of soothing the liver and regulating qi on expression of gastrin and somatostatin in hypothalamus and gastric antrum of functional dyspepsia model rats. METHOD: The 32 rats were randomly divided into normal group, model group, Chaihu Shugansan group and domperidone group (n = 8). The functional dyspepsia model was established by constantly squeezing their tails and mean while saline, Chaihu Shugansan decoction and domperidone suspension were administered respectively to 4 groups by gavage. The expression of gastrin and somatostatin in hypothalamus and gastric antrum of rats by immunohistochemical were detected 3 weeks later. RESULT: The expression of GAS in the hypothalamus and gastric antrum of model group were less than those of normal group (P < 0.05, P < 0.01), while the expression of SS in the hypothalamus and gastric antrum in Model group were significantly increased than those of normal group (P < 0.01). The expression of GAS and SS in gastric antrum of Chaihu Shugansan group and domperidone group were increased and decreased respectively, and the differences were significant (P < 0.05, P < 0.01). There were no obvious difference about expression of GAS, SS in the hypothalamus between domperidone group and model group. GAS expression in hypothalamus of Chaihu Shugansan group were increased than those of normal group but there was no obvious difference in SS expression in hypothalamus between Chaihu Shugansan group and model group. CONCLUSION: The method of soothing the liver and regulating qi can increase GAS expression in central and peripheral and decrease SS expression in peripheral gastric antrum, which may be one of its therapeutic mechanisms on functional dyspepsia.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Dyspepsia/drug therapy , Gastrins/genetics , Hypothalamus/metabolism , Liver/physiopathology , Pyloric Antrum/metabolism , Somatostatin/genetics , Animals , Disease Models, Animal , Dyspepsia/genetics , Dyspepsia/metabolism , Female , Gastrins/metabolism , Gene Expression Regulation/drug effects , Humans , Hypothalamus/drug effects , Liver/drug effects , Pyloric Antrum/drug effects , Qi , Random Allocation , Rats , Rats, Wistar , Somatostatin/metabolismABSTRACT
OBJECTIVE: This study was designed to evaluate the effect of zhongjiefeng extracts on telomerase activity and apoptosis of implanted human nasopharyngeal carcinoma cell lines in nude mice. METHOD: Nude mice with implanted human nasopharyngeal carcinoma cell lines CNE1 and CNE2 were randomly divided into three groups, which were the group of zhong-jiefeng, normal control group, and CTX therapy group. The weight of nude mice and the volume of tumor were regularly measured. After a course of treatment (30 d), tumor tissues were obtained with autopsy, and then they were weighed to calculate the inhibitive rate of the growth of tumor. The changes of ultra micro-structure of NPC cells were observed by transmission electron microscope. Expressions of Bcl-2 and Bax of xenografts were investigated by immunohistochemistry. The apoptosis of CNE1 and CNE2 cells was observed using TUNEL and FACS with PI-staining. The telomerase activity was observed by TRAP-ELISA method. RESULT: The zhongjiefeng extracts significantly inhibit the growth of tumor compared to normal control group. The inhibitory rate were 40.8% (P < 0.01) and 46.8% (P < 0.01), respectively. The expression of Bcl-2 was lower (P < 0.01) and the expression of Bax was higher (P < 0.01) in the zhongjiefeng group than that in normal control group. Electron microscopy indicated the typical apoptosis of tumor cells, such as marginal nuclei, chromatin condensation and nuclei fragmentation, and apoptotic bodies. As result of the flow cytometry showed, the exhibition rate of apoptosis of cell in the group treated with zhongjiefeng was higher than that of normal control group (P < 0.01) in G0/G1 phase. Zhongjiefeng arrested cells in G0/G1 phase of the cell cycle. The telomerase activity of zhongjiefeng and CTX group was lower than that of the normal group (P < 0.01). CONCLUSION: Zhongjie feng suppressed the growth of tumor in vivo. The anticancer effects of zhongjiefeng were associated with the induction of apoptosis and partly with the suppression of telomerase activity.
Subject(s)
Apoptosis/drug effects , Drugs, Chinese Herbal/pharmacology , Nasopharyngeal Neoplasms/drug therapy , Telomerase/metabolism , Animals , Cell Line, Tumor , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/pathology , Neoplasm Transplantation , Xenograft Model Antitumor AssaysABSTRACT
OBJECTIVE: To evaluate the effect of Sarcandra glabra extracts on anti-tumor and apoptosis of implanted human nasopharyngeal carcinoma cell lines in nude mice. METHODS: Models of CNE1 and CNE2 xenograft in nude mice were established to investigate the anti-tumor effect of Sarcandra glabra. The apoptosis of CNE1 and CNE2 cells were observed with TUNEL and FACS with PI-staining. The ultra micro-structured changes of CNE1 and CNE2 cells were observed by transmission electron microscope. The expression of Bcl-2 and Bax of xenografts were investigated by immunohistochemistry. RESULTS: The Sarcandra glabra extracts significantly inhibited the growth of tumor when compared with normal control group. The expression of Bcl-2 was lower (P<0.01) and the expression of Bax of the Sarcandra glabra group was higher(P<0.01) than that of normal control group. The rate of cell apoptosis exhibiting was higher than that of normal control group(P<0.01). Electron microscopy indicated the apoptosis of tumor cells with marginal nuclei, chromatin condensation and nuclei fragmentation, and apoptotic bodies were observed. CONCLUSION: Sarcandra glabra suppresses the growth of tumor in vivo. The mechanism is associated with down-regulating the expression of Bcl-2 and up-regulating the expression of Bax to promote apoptosis.