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1.
Toxics ; 11(7)2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37505537

ABSTRACT

Per- and polyfluoroalkyl substances (PFASs) are widespread environmental pollutants. There is increasing evidence that PFASs have various adverse health effects, including renal toxicity, metabolic dysfunction, endocrine disruption, and developmental toxicity. PFASs have been found to accumulate in the placenta, and some PFASs can cross the placental barrier and subsequently accumulate in the fetus via the maternal-fetal circulation. An increasing number of studies have shown that early life exposure to PFASs can affect fetal neurodevelopment. This paper reviews the characteristics of indirect exposure to PFASs in early life, the effects on neurodevelopment in offspring, and the possible mechanisms of toxic effects.

2.
Nat Prod Res ; : 1-8, 2023 Feb 14.
Article in English | MEDLINE | ID: mdl-36787178

ABSTRACT

Chamaecrista rotundifolia (C. rotundifolia) is a perennial herb of leguminosae, which increasingly being grown as a forage in China. In our search for original bioactive metabolites from Cassia plants, the phytochemical reinvestigation of the C. rotundifolia was carried out, which led to the isolation of three new (1-3) and six known (4-9) chromones. Their structures were confirmed by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1-9 were evaluated for their anti-rotavirus activities, and the results revealed that compounds 1-9 exhibited potential anti-rotavirus activities with therapeutic index (TI) valves in the range of 12.0 ∼ 20.2, respectively.

3.
Biomed Res Int ; 2020: 2892734, 2020.
Article in English | MEDLINE | ID: mdl-33102576

ABSTRACT

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are widely spread across the world. Asymptomatic or inconspicuous CT/NG infections are difficult to diagnose and treat. Traditional methods have the disadvantages of low detection rate, inaccurate results, and long detection time. However, Xpert CT/NG makes up for the aforementioned shortcomings and has research value and popularization significance. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched, and studies were screened using Xpert CT/NG for diagnosing CT/NG. QUADAS-2 was used to evaluate the quality of the eligible studies. Then, two groups of researchers independently extracted data from these studies. Meta-analyses of sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve were conducted using Meta-DiSc 1.4. Finally, Deek's funnel plots were made using Stata 12.0 to evaluate publication bias. RESULTS: 14 studies were identified, and 46 fourfold tables were extracted in this meta-analysis. The pooled SEN, SPE, PLR, NLR, DOR, and AUC in diagnosing CT were 0.94 (95% confidence interval (CI): 0.93-0.95), 0.99 (95% CI: 0.99-1.00), 97.17 (95% CI: 56.76-166.32), 0.07 (95% CI: 0.04-0.12), 1857.25 (95% CI: 943.78-3654.86), and 0.9960, respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC in diagnosing NG were 0.95 (95% CI: 0.93-0.96), 1.00 (95% CI: 1.00-1.00), 278.15 (95% CI: 152.41-507.63), 0.08 (95% CI: 0.06-0.12), 4290.70 (95% CI: 2161.78-8516.16), and 0.9980, respectively. CONCLUSIONS: Xpert CT/NG had high diagnostic sensitivity and specificity for CT and NG. However, more evidence is required to confirm that Xpert CT/NG might serve as the primary method for detecting CT and NG and even the gold standard for diagnosis in the future.


Subject(s)
Chlamydia Infections/diagnosis , Gonorrhea/diagnosis , Area Under Curve , Chlamydia Infections/microbiology , Chlamydia trachomatis/pathogenicity , Gonorrhea/microbiology , Humans , Neisseria gonorrhoeae/pathogenicity , Odds Ratio , ROC Curve , Sensitivity and Specificity
4.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1055-1056: 165-171, 2017 Jun 15.
Article in English | MEDLINE | ID: mdl-28478194

ABSTRACT

Biomarkers of serum fatty acids in hyperlipidemia need to be elucidated. 90 SPF KM male mice were randomly divided into 18 groups (n=5/group), control groups, and high fat diet (HFD) groups at 9 time points. On day 7, 10, 15, 18, 21, 24, 28, 31, and 35, the mice were sacrificed; blood was collected into tubes from the eyes, serum samples for clinical biochemistry assays and gas chromatography-mass spectroscopy were attained after centrifugation, and the contents of serum fatty acids were detected with GC-MS. Sections of livers were taken and stored in formalin solution for histological assessments. No species differences existed in all these groups. The contents of C16:1, C18:1, C22:6 were significantly different between HFD groups and the corresponding controls; meanwhile, the proportion of fatty acids, especially the monounsaturated degree, the polyunsaturated degree, changed significantly and regularly (P<0.05). Thus the three unsaturated fatty acids C16:1, C18:1, C22:6 and the monounsaturated/polyunsaturated unsaturated degrees may be as potential biomarkers of hyperlipidemia.


Subject(s)
Fatty Acids/blood , Hyperlipidemias/blood , Animals , Biomarkers/blood , Diet, High-Fat/adverse effects , Fatty Acids/analysis , Gas Chromatography-Mass Spectrometry/methods , Hyperlipidemias/etiology , Hyperlipidemias/pathology , Liver/chemistry , Liver/pathology , Male , Mice
5.
Sci Rep ; 7: 42784, 2017 02 17.
Article in English | MEDLINE | ID: mdl-28211487

ABSTRACT

We studied germination behaviors and persistence mechanism of wild Glehnia littoralis, a typical coastal species at temperate sandy coasts of the North Pacific Ocean, and tested the hypothesis that the coastal plants may have evolved special seeds adapting to the coasts, by which they recruit and persist easily, occupying the coasts as ideal habitats. In the Shandong Peninsula, China, we investigated temperature and moisture conditions of coast sand in relation to germination and evaluated effects of sand burial, seawater immersion and sowing time on germination. When germination began, daily dawn temperatures of sand were about 10 °C and daily noon temperatures were about 25 °C; the temperatures were not different in the sand <8 cm deep. The sand at these depths showed a significant difference in moisture contents. The seeds exhibited large germination rates if sand burial was at depths >= 3 cm and winter freezing was kept longer than 2.5 months. Seeds experiencing seawater immersion were able to germinate well. These evidences suggest that G. littoralis has evolved special seeds adapting to seawater dispersal and specific season rhythm. By the seeds, G. littoralis occupies temperate sandy coasts as ideal habitats to persist.


Subject(s)
Adaptation, Physiological , Apiaceae/physiology , Ecosystem , Apiaceae/growth & development , Germination
6.
Sci Rep ; 6: 33358, 2016 09 16.
Article in English | MEDLINE | ID: mdl-27634378

ABSTRACT

Ursolic acid (UA) is a promising natural compound for cancer prevention and therapy. We previously reported that UA induced apoptosis in CML-derived K562 cells. Here we show that the apoptotic process is accompanied by down-regulation of Bcl-xL and Mcl-1 expression and dephosphorylation of Bad. These events are associated with Stat5 inhibition, which is partially mediated through elevated expression of transcriptional repressor Gfi-1. Gfi-1 knockdown using siRNA abrogates the ability of UA to decrease Stat5b expression and attenuates apoptosis induction by UA. We also demonstrate that UA suppresses the Akt kinase activity by inhibiting Akt1/2 expression, which correlates with Stat5 inhibition. Stat5 activity inhibited by a chemical inhibitor or siRNA, Akt1/2 mRNA expression is suppressed. Moreover, we show that UA exerts growth-inhibition in Imatinib-resistant K562/G01. UA has synergistic effects when used in combination with Imatinib in both K562 and K562/G01. Altogether, the data provide evidence that UA's pro-apoptotic effect in K562 cells is associated with the Gfi-1/Stat5/Akt pathway. The findings indicate that UA could potentially be a useful agent in the treatment of CML.


Subject(s)
Apoptosis/drug effects , DNA-Binding Proteins/metabolism , Proto-Oncogene Proteins c-akt/metabolism , STAT5 Transcription Factor/metabolism , Signal Transduction/drug effects , Transcription Factors/metabolism , Triterpenes/pharmacology , Down-Regulation/drug effects , Drug Synergism , Humans , Imatinib Mesylate/pharmacology , K562 Cells , Models, Biological , Proto-Oncogene Proteins c-bcl-2/metabolism , Ursolic Acid
7.
J Hum Genet ; 61(5): 389-93, 2016 May.
Article in English | MEDLINE | ID: mdl-26740236

ABSTRACT

A large-scale meta-analysis of 14 genome-wide association studies has identified and replicated a series of susceptibility polymorphisms for coronary artery disease (CAD) in European ancestry populations, but evidences for the associations of these loci with CAD in other ethnicities remain lacking. Herein we investigated the associations between ten (rs579459, rs12413409, rs964184, rs4773144, rs2895811, rs3825807, rs216172, rs12936587, rs46522 and rs3798220) of these loci and CAD in Southern Han Chinese (CHS). Genotyping was performed in 1716 CAD patients and 1572 controls using mass spectrography. Both allelic and genotypic associations of rs964184, rs2895811 and rs3798220 with CAD were significant, regardless of adjustment for covariates of gender, age, hypertension, type 2 diabetes, blood lipid profiles and smoking. Significant association of rs12413409 was initially not observed, but after the adjustment for the covariates, both allelic and genotypic associations were identified as significant. Neither allelic nor genotypic association of the other six polymorphisms with CAD was significant regardless of the adjustment. Our results indicated that four loci of the total 10 were associated with CAD in CHS. Therefore, some of the CAD-related loci in European ancestry populations are indeed susceptibility loci for the risk of CAD in Han Chinese.


Subject(s)
Asian People/genetics , Coronary Artery Disease/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Alleles , Case-Control Studies , China , Coronary Artery Disease/diagnosis , Gene Frequency , Genome-Wide Association Study , Genotype , Humans , Odds Ratio , Risk
8.
PLoS One ; 10(9): e0137547, 2015.
Article in English | MEDLINE | ID: mdl-26375920

ABSTRACT

The first genome-wide association study for coronary artery disease (CAD) in the Han Chinese population, we reported recently, had identified rs6903956 in gene ADTRP on chromosome 6p24.1 as a novel susceptibility locus for CAD. The risk allele of rs6903956 was associated with decreased mRNA expression of ADTRP. To further study the correlation of ADTRP expression and CAD, in this study we evaluated the associations of eight common variants in the expression-regulating regions of ADTRP with CAD in the Southern Han Chinese population. Rs169790 in 3'UTR, rs2076189 in 5'UTR, four SNPs (rs2076188, rs7753407, rs11966356 and rs1018383) in promoter, and two SNPs (rs3734273, rs80355771) in the last intron of ADTRP were genotyped in 1716 CAD patients and 1572 controls. The correlations between these loci and total or early-onset CAD were investigated. None of these loci was discovered to associate with total CAD (P > 0.05). However, with early-onset CAD, significant both allelic and genotypic associations of rs7753407, rs11966356 and rs1018383 were identified, after adjustment for risk factors of age, gender, hypertension, diabetes, lipid profiles and smoking (adjusted P < 0.05). A haplotype AGCG (constructed by rs2076188, rs7753407, rs11966356 and rs1018383) was identified to protect subjects from early-onset CAD (OR = 0.332, 95% CI = 0.105-0.879, adjusted P = 0.010). Real-time quantitative reverse transcription polymerase chain reaction assay showed that the risk alleles of the associated loci were significantly associated with decreased expression of ADTRP mRNA. Moreover, the average level of ADTRP mRNA expression in early-onset CAD cases was significantly lower than that in controls. Our results provide new evidence supporting the association of ADTRP with the pathogenesis of early-onset CAD.


Subject(s)
Asian People/ethnology , Coronary Artery Disease/genetics , Ethnicity/genetics , Membrane Proteins/genetics , Polymorphism, Single Nucleotide , Promoter Regions, Genetic/genetics , 3' Untranslated Regions/genetics , 5' Untranslated Regions/genetics , Aged , Asian People/genetics , Cohort Studies , Female , Genetic Predisposition to Disease/genetics , Genotyping Techniques , Humans , Male , Middle Aged
9.
Nanotechnology ; 26(18): 185702, 2015 May 08.
Article in English | MEDLINE | ID: mdl-25872454

ABSTRACT

One-process fabrication of highly active and reproducible surface-enhanced Raman scattering (SERS) substrates via ion beam deposition is reported. The fabricated metal-dielectric-metal (MDM) hierarchical nanostructure possesses rich nanogaps and a tunable resonant cavity. Raman scattering signals of analytes are dramatically strengthened due to the strong near-field coupling of localized surface plasmon resonances (LSPRs) and the strong interaction of LSPRs of metal NPs with surface plasmon polaritons (SPPs) on the underlying metal film by crossing over the dielectric spacer. The maximum Raman enhancement for the highest Raman peak at 1650 cm(-1) is 13.5 times greater than that of a single metal nanoparticle (NP) array. Moreover, the SERS activity can be efficiently tailored by varying the size and number of voids between adjacent metal NPs and the thickness of the dielectric spacer. These findings may broaden the scope of SERS applications of MDM hierarchical nanostructures in biomedical and analytical chemistry.

10.
J Cancer ; 5(7): 585-9, 2014.
Article in English | MEDLINE | ID: mdl-25057309

ABSTRACT

PURPOSE: to explore the clinical value of 3.0T magnetic resonance (MR) imaging compared with computer-aided MR diagnosis (MR-CAD) in differential diagnosis of benign and malignant breast tumors. MATERIALS AND METHODS: MRI method and MR-CAD method was used in the diagnosis of a total of 93 breast lesions of 78 patients, based on the morphological and time-intensity-curve (TIC) analysis. The accuracy of the two modalities in differentiating malignant and benign breast tumor was compared. RESULTS: MR-CAD method yielded a statistically better accuracy than MRI method. For 51 mass-like lesions, MRI and MR-CAD had no difference in diagnosing accuracy, but MR-CAD had better accuracy in 42 non-mass-like lesions. CONCLUSION: MR-CAD had a notable advantage over MRI in differential diagnosis of benign and malignant breast tumors, especially non-mass-like tumor.

11.
Nanotechnology ; 24(15): 155203, 2013 Apr 19.
Article in English | MEDLINE | ID: mdl-23519272

ABSTRACT

Metal structures with high optical transparency and conductivity are of great importance for practical applications in optoelectronic devices. Here we investigate the transparency response of a continuous metal film sandwiched by double plasmonic nanoparticle arrays. The upper nanoparticle array shows efficient light trapping of the incident field, acting as a light input coupler, and the lower nanoparticle array shows a light release gate opening at the other side, acting as the light output coupler. The strong near-field light-matter interactions of the nano-scale separated plasmonic nanoparticles, the excitation of surface plasmon waves of the metal film, and their cooperative coupling effects result in broadband scattering cancellation and near-unity transparency (up to 96%) in the optical regime. The transparency response in such a structure can be efficiently modified by varying the gap distance of adjacent nanoparticles, dielectric environments, and the distance between the plasmonic array and the metal film. This motif may provide a new alternative approach to obtain transparent and highly conducting metal structures with potential applications in transparent conductors, plasmonic filters, and highly integrated light input and output components.

12.
Leuk Res ; 36(11): 1417-21, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22938941

ABSTRACT

Pentamidine (PMD) is an anti-protozoa drug with potential anticancer activity. Here we show that PMD at clinically achievable plasma drug concentrations slightly inhibited the growth of human leukemia cell lines. PMD close to its therapeutic doses sensitized TRAIL-resistant K562 cells to the cytokine and potentiated TRAIL-induced apoptosis through activation of caspase-8 and -3. When we investigated the underlying mechanism, we observed that treatment with PMD increased DR5 expression at both mRNA and protein levels and down-regulated anti-apoptotic XIAP and Mcl-1 protein levels. This study provides a rationale for a more in-depth exploration into the combined treatment with PMD and TRAIL as a valuable strategy for leukemia therapy.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Pentamidine/pharmacology , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Blotting, Western , Cell Proliferation/drug effects , Cell Survival/drug effects , Humans , K562 Cells , Reverse Transcriptase Polymerase Chain Reaction
13.
Basic Clin Pharmacol Toxicol ; 108(5): 304-9, 2011 May.
Article in English | MEDLINE | ID: mdl-21159130

ABSTRACT

The dry root of Sophora flavescens Ait. (SF) has long been used in a variety of Chinese herbal formulations to treat patients with cancer. Alkaloids are commonly known to present in SF as main active constituents. Here, we report that among the six characterized SF-derived quinolizidine alkaloids including sophoridine, aloperine, sophocarpine, matrine, oxymatrine and cytisine, aloperine exerted the most potent in vitro cytotoxic activity against the human cancer cell lines and oxymatrine exhibited selective anti-cancer activity against hepatocellular carcinoma HepG2 cells. Analysis of DNA fragmentation and PARP cleavage revealed that aloperine treatment for 48 hr induced apoptosis in HL-60 cells. In addition, autophagic formation of acidic vacuole was also observed in HL-60 cells exposed to aloperine. These results suggest that aloperine may be a novel contributor to the anti-cancer properties of SF.


Subject(s)
Antineoplastic Agents/pharmacology , Phytotherapy , Plant Preparations/pharmacology , Quinolizidines/pharmacology , Sophora/chemistry , Alkaloids/pharmacology , Apoptosis/drug effects , Azocines/pharmacology , Drugs, Chinese Herbal/pharmacology , Electrophoresis, Capillary/methods , HL-60 Cells , Humans , Inhibitory Concentration 50 , K562 Cells , Piperidines/pharmacology , Plant Roots/chemistry , Quinolizines/pharmacology , Matrines
14.
Eur J Pharmacol ; 645(1-3): 9-13, 2010 Oct 25.
Article in English | MEDLINE | ID: mdl-20633548

ABSTRACT

Gossypol is an attractive therapeutic anti-tumor agent as an apoptosis inducer and is being evaluated in preclinical tests. However, the molecular mechanisms underlying apoptosis induction by gossypol in malignant cells have not been completely enunciated. Here we investigate the alterations of Bcl-2/Bcl-xL/Mcl-1 protein levels and Bcl-2 phosphorylation in gossypol-induced apoptosis in human leukemia HL-60 cells. We found that gossypol treatment inhibited cell growth and induced apoptosis in HL-60 cells. Bcl-2/Bcl-xL/Mcl-1 protein levels were slightly reduced and phosphorylation of Bcl-2 at threonine 56 (phospho T56) was not altered. However, phosphorylation of Bcl-2 at serine 70 (phospho S70) was strikingly down-regulated in gossypol-exposed cells. This reduction was found to be not only in both dose- and time-dependent fashion but also obviated by phorbol l2,13-dibutyrate (PDBu), an activator of protein kinase C (PKC). In addition, pre-treatment of PDBu partially prevented gossypol-induced apoptosis in HL-60 cells. Collectively, gossypol treatment can reduce phosphorylation of Bcl-2 at serine 70 in leukemia HL-60 cells and gossypol may be a promising therapeutical candidate for leukemia patients especially expressing phosphorylated Bcl-2 at Ser70.


Subject(s)
Antineoplastic Agents/pharmacology , Gossypol/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , Apoptosis/drug effects , Blotting, Western , DNA Fragmentation/drug effects , Dose-Response Relationship, Drug , Down-Regulation , Enzyme Activators/pharmacology , Genes, bcl-2 , HL-60 Cells , Humans , Phorbol 12,13-Dibutyrate/pharmacology , Phosphorylation , Poly(ADP-ribose) Polymerases/metabolism , Protein Kinase C/metabolism
15.
Fa Yi Xue Za Zhi ; 26(5): 321-4, 2010 Oct.
Article in Chinese | MEDLINE | ID: mdl-21287731

ABSTRACT

OBJECTIVE: To explore the changes of c-fos in apoptosis of cerebellar granular neuron of neonatal SD rats induced by heroin and the mechanisms of neuronal injury caused by heroin. METHODS: Primary cerebellar granular neuron were cultured in vitro, the model of apoptosis induced by heroin was established. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were adopted to investigate the changes of c-fos in cell models. RESULTS: Ten microg/mL of heroin was the optimal dose to induce the apoptosis of cerebellar granular neuron at 48 h. Both Western blotting and RT-PCR showed down regulation of c-fos expression. CONCLUSION: Heroin could induce apoptosis of cerebellar granular neuron and down regulation of c-fos, which may be one of the apoptosis mechanisms.


Subject(s)
Apoptosis/drug effects , Cerebellum/metabolism , Heroin/pharmacology , Neurons/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Animals , Animals, Newborn , Blotting, Western , Cells, Cultured , Cerebellum/cytology , Cerebellum/drug effects , Dose-Response Relationship, Drug , Down-Regulation , Gene Expression Regulation/drug effects , Male , Neurons/drug effects , Proto-Oncogene Proteins c-fos/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction
16.
Leuk Lymphoma ; 51(2): 297-303, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20038232

ABSTRACT

Arsenic trioxide (ATO) is an effective therapeutic agent for acute promyelocytic leukemia (APL) and other hematopoietic malignancies. We found that ATO down-regulated the global DNA methylation level in HL-60 cells with high-performance capillary electrophoresis (HPCE) assay. Using combination index method of Chou and Talalay, interactions between ATO and epigenetic therapeutic agents were analyzed in three human leukemia cell lines (HL-60, U937, and K562). A synergistic interaction was observed in HL-60 cells between ATO and 5-Aza-2'-Deoxycytidine (DAC), while an antagonistic interaction was found in U937 cells between ATO and valproic acid (VPA). The combination of ATO with trichostatin A (TSA) caused an antagonistic interaction in U937 and K562 cells. These results not only highlight possible diversity of the anti-leukemia mechanisms of ATO, but also provide initial guide for further investigation of leukemia therapies based on the combination of ATO with epigenetic agents.


Subject(s)
Arsenicals/pharmacology , Azacitidine/analogs & derivatives , Cell Proliferation/drug effects , Hydroxamic Acids/pharmacology , Oxides/pharmacology , Valproic Acid/pharmacology , Antineoplastic Agents/pharmacology , Arsenic Trioxide , Azacitidine/pharmacology , Cell Survival/drug effects , DNA Methylation/drug effects , DNA Modification Methylases/antagonists & inhibitors , DNA, Neoplasm/genetics , DNA, Neoplasm/metabolism , Decitabine , Drug Antagonism , Drug Synergism , Electrophoresis, Capillary/methods , Growth Inhibitors/pharmacology , HL-60 Cells , Histone Deacetylase Inhibitors/pharmacology , Humans , K562 Cells , Leukemia/genetics , Leukemia/pathology , U937 Cells
17.
Cancer Lett ; 274(1): 16-24, 2009 Feb 08.
Article in English | MEDLINE | ID: mdl-18829157

ABSTRACT

Lycorine is an alkaloid isolated from the bulb of the Amaryllidaceae Lycoris. Here, we report that treatment with lycorine resulted in survival inhibition and apoptosis induction in human leukemia cell lines. Lycorine induced apoptosis in human leukemia cells via intrinsic mitochondria pathway and caused a rapid-turnover of protein level of Mcl-1 which occurred before caspases activation. Furthermore, pronounced apoptosis accompanied by the down-regulation of Mcl-1 was also observed in blasts from patients with acute myeloid leukemia. Our findings suggest that lycorine may be a good candidate therapeutic agent against leukemia in worth of further evaluation.


Subject(s)
Amaryllidaceae Alkaloids/pharmacology , Apoptosis/drug effects , Leukemia/metabolism , Phenanthridines/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , Blotting, Western , Caspases/metabolism , Cytochromes c/metabolism , Down-Regulation/drug effects , Humans , Leukemia/pathology , Mitochondria/drug effects , Mitochondria/metabolism , Myeloid Cell Leukemia Sequence 1 Protein , Proto-Oncogene Proteins c-bcl-2/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transcription, Genetic , Tumor Cells, Cultured
18.
Zhonghua Zhong Liu Za Zhi ; 30(4): 255-8, 2008 Apr.
Article in Chinese | MEDLINE | ID: mdl-18788626

ABSTRACT

OBJECTIVE: To investigate the effects of matrine on the anti-tumor efficiency of TIM2 gene-modified murine hepatocarcinoma H22 cells. METHODS: A combined eukaryotic expression vector pIRES2-EGFP-TIM2 was constructed and transfected into H22 cells by lipofectamin. The monoclone of positive H22-TIM2 cells and negative control H22-EGFP cells transfected with pIRES2-EGFP vector were selected by G418 pressure and limited dilution method in turn and were inoculated to establish the tumor-bearing mouse model. Next, matrine was administered to the tumor-bearing mice and the inhibitory effect of matrine was determined. RESULTS: The co-expression of EGFP protein and TIM2 gene was detected in H22 cells selected after TIM2 gene transfecion. After subcutaneous injection of H22-TIM2 cells, the rate of tumor formation (41%) was lower than that of H22 cells and H22-EGFP cells injection (92%) in mice. The tumor growth was significantly inhibited in mice vaccinated with H22-TIM2 cells. After the experiment was completed, the volume of tumors in mice of H22-TIM2 group was 31.34 +/- 9.21 mm3, smaller than those in H22-EGFP group (98.25 +/- 25.23)mm3 and H22 cells group (114.08 +/- 36.45)mm3 (P < 0.01). Matrine dramatically enhanced the anti-tumor efficiency of TIM2 gene-modified H22 cells, with the highest tumor inhibitory rate (IR) 90.6% among the H22-TIM2 group, matrine treatment group and H22-EGFP cells combined with matrine treatment group (69.2%, 67.5% and 70.8%, respectively) in the experimental mice. CONCLUSION: The tumorigenesity of H22 cells has been markedly impaired after modification by TIM2 gene. Matrine can enhance its inhibitory effect on tumors of H22-TIM2 cells in vivo. These data indicate importance to further study on the biological role of TIM2 gene in tumor immunity and explore the molecular mechanism of matrine in suppressing of tumor growth.


Subject(s)
Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Liver Neoplasms, Experimental/pathology , Membrane Proteins/genetics , Quinolizines/pharmacology , Tumor Burden/drug effects , Animals , Cell Line, Tumor , Genetic Vectors , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Liver Neoplasms, Experimental/metabolism , Membrane Proteins/metabolism , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Transfection , Matrines
19.
Zhongguo Zhong Yao Za Zhi ; 33(10): 1175-9, 2008 May.
Article in Chinese | MEDLINE | ID: mdl-18720871

ABSTRACT

OBJECTIVE: To investigate the effects of matrine on the anti-tumor efficiency of H22 murine hepatocarcinoma cell-based vaccine modified by TIM2 gene in vivo. METHOD: The combinant eukaryotic expression vector pIRES2-EGFP-TIM2 was constructed and transfected into H22 cells by lipofectamin. The monoclone of the positive H22-TIM2 cells and negative control H22-EGFP cells were selected by G418 pressure and limited dilution method in turn. The H22 whole-cell-based vaccine were inoculated to establish the tumor-bearing mouse model, and its oncogenicity and immunogenicity were observed in vivo. Then the matrine was administered to the tumor-bearing mice inoculated by H22-TIM2 cells, H22-EGFP cells and H22 cells, and the inhibitory effect of matrine on tumor was studied. RESULT: The co-expression of EGFP protein and TIM2 mRNA were detected in H22-TIM2 cells. The rate of tumor formation in mice injected of H22-TIM2 cells was 41%, lower than that of H22 cells and H22-EGFP cells injection (92%) in mice. The growth of tumor were significantly inhibited vaccinated with H22-TIM2 cells in mice. The inhibitory rate of tumor (IR) was 69.2% in mice of H22-TIM2 group, higher than that of mice treated with matrine and H22 cells injection, the later was 67.5%. Matrine could dramatically strengthen the anti-tumor efficiency of H22 cells modified by TIM2 gene, with the highest tumor inhibitory rate (IR) (90.6%) in all the experimental mice. The spleen index, populations of CD4-positive lymphocytes and the ratio of CD4-positive to CD8-positive lymphocytes of spleen in mice vaccinated of H22-TIM2 cells were obviously higher than those in the other groups. CONCLUSION: The oncogenicity of H22 cells is markedly impaired after modified by TIM2 gene. Matrine can strengthen the inhibitory effect of H22-TIM2 cells on tumor in mice. These data give us important clues to further study the biological role of TIM2 gene in tumor immunity and explore the molecular mechanism of matrine in suppressing tumor.


Subject(s)
Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Carcinoma, Hepatocellular/drug therapy , Gene Expression/drug effects , Membrane Proteins/genetics , Quinolizines/pharmacology , Alkaloids/administration & dosage , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Female , Humans , Male , Membrane Proteins/metabolism , Mice , Mice, Inbred BALB C , Neoplasms, Experimental , Quinolizines/administration & dosage , Spleen/drug effects , Spleen/immunology , Matrines
20.
Planta Med ; 73(11): 1192-4, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17764066

ABSTRACT

Ursolic acid (UA) is a pentacyclic triterpene acid naturally occurring in a number of foods and medicinal plants. It is one of the most promising chemopreventive agents and has been reported to induce apoptosis in many cancer cells. Here, we report that treatment with UA induces apoptosis in human leukemia K562 cells and down-regulates protein levels of bcl-xL. Treatment also increases phospho-JNK in a dose- and time-dependent manner but does not alter phospho-Erk1/2 and phospho-P38. These results suggest that JNK may participate in UA-induced apoptosis in K562 cells.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Phytotherapy , Plants, Medicinal , Triterpenes/pharmacology , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/therapeutic use , Humans , K562 Cells/drug effects , Mitogen-Activated Protein Kinases/metabolism , Triterpenes/administration & dosage , Triterpenes/therapeutic use , Ursolic Acid
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