RESUMO
PURPOSE: Paeonol is a natural chemical medicine derived from the bark of peony root, which has been found to inhibit tumor activity in various tumor cell lines, and can play a synergistic anti-tumor effect with chemotherapy or radiotherapy. METHODS: We used paeonol to act on human bladder cancer T24 and 5637 cells, and established xenograft tumor in nude mice by subcutaneous injection of T24 cells. RESULTS: CCK-8 assay and plate cloning experiments showed that paeonol could inhibit the proliferation of T24 and 5637 cells in vitro. The results of flow cytometry and the detection of BAX, Bcl-2 and Caspase-3 proteins suggested that paeonol can induce apoptosis of T24 and 5637 cells in vitro. Tumor formation, TUNEL detection and immunohistochemical results of Ki67, BAX, Bcl-2 and Caspase-3 in nude mice showed that paeonol could inhibit T24 cell proliferation and induce apoptosis in vivo, thus inhibiting tumor growth. Further research revealed that paeonol could reduce phosphorylation expression of PI3K and AKT in T24 and 5637 cells. CONCLUSION: We confirmed that paeonol could inhibit proliferation and induce apoptosis of human bladder cancer T24 and 5637 cells in vitro and in vivo, inhibit the growth of T24 tumor-forming nude mice, and possibly play a role by inhibiting the PI3K/AKT signaling pathway, so as to provide a potential therapeutic drug for bladder cancer.
Assuntos
Acetofenonas/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias da Bexiga Urinária/patologia , Animais , Caspase 3/análise , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Marcação In Situ das Extremidades Cortadas , Técnicas In Vitro , Antígeno Ki-67/análise , Camundongos , Camundongos Nus , Transplante de Neoplasias , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/análise , Neoplasias da Bexiga Urinária/química , Neoplasias da Bexiga Urinária/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/análiseRESUMO
OBJECTIVE: Recently, numerous studies have yielded inconsistent results regarding the effect of metformin on esophageal cancer risk in type 2 diabetes mellitus patients. The purpose of this study is to systematically assess this effect using meta-analysis. METHODS: We searched clinical studies on metformin and esophageal cancer risk in PubMed, Embase, and the Cochrane Library. After literature screening, a series of meta-analyses were conducted using RevMan 5.3 software. The pooled hazard ratio (HR) and the corresponding 95% confidence interval (CI) were used as the effect size. RESULTS: Five eligible studies (four cohort studies and one case-control study) were included for our meta-analysis using a random-effect model. The analysis showed that metformin could not reduce esophageal cancer risk in type 2 diabetes mellitus patients (HR 0.88, 95% CI 0.60-1.28, P > 0.05). Subgroup analyses by geographic location showed that metformin significantly reduced esophageal cancer risk in Asian patients with type 2 diabetes mellitus (HR 0.59, 95% CI 0.39-0.91, P = 0.02), without heterogeneity between studies (P = 0.80 and I2 = 0%). CONCLUSIONS: Overall, our systematic review and meta-analysis demonstrate that metformin does not reduce esophageal cancer risk in type 2 diabetes mellitus patients. However, a significant reduction in esophageal cancer risk in Asian populations remains to be clarified.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Neoplasias Esofágicas/prevenção & controle , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Povo Asiático , Estudos de Casos e Controles , Intervalos de Confiança , Diabetes Mellitus Tipo 2/etnologia , Neoplasias Esofágicas/etnologia , Humanos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Viés de Publicação , Estudos Retrospectivos , RiscoRESUMO
Coilia ectenes is a commercially important fishery species in China. C. ectenes taihuensis is an endemic and dominant species found in Taihu Lake of China. When compared with C. ectenes, C. ectenes taihuensis lacks anadromous behavior, and can independently grow and reproduce in Taihu Lake. In this study, the mitochondrial DNA control region (D-loop) sequences were employed to investigate the genetic diversity and population structure of C. ectenes taihuensis. Sixty-eight individuals collected from 4 localities in Taihu Lake were examined. Results indicated that in the 887-bp D-loop region, seventy-seven (8.68%) sites were variant, contributing to 53 distinct haplotypes. Although the population haplotype diversity (Hd = 0.971 to 1.000) was generally high, the nucleotide diversity (π = 0.616 to 0.731%) was relatively low among the 4 populations. Additionally, the genetic distances ranged from 0.62 to 0.74% within the populations and from 0.67 to 0.74% between the populations. The neighbor-joining tree indicated that a distinct distribution of phylogenetic structure existed among haplotypes. Analysis of molecular variance and FST statistics suggested that a divergence existed among populations in 4 localities, indicating that gene communication might have occurred among those populations. Furthermore, neutral tests and analysis of mismatch distribution reflected that C. ectenes taihuensis might have undergone a population expansion during the evolution process. Our study showed the population genetic diversity and structure of C. ectenes taihuensis. Results from this study might be helpful in the development and protection of fishery resource within the localities in Taihu Lake in future.
Assuntos
DNA Mitocondrial/genética , Peixes/genética , Polimorfismo Genético , Animais , China , Evolução Molecular , Genética Populacional , Haplótipos , Lagos , FilogeniaRESUMO
Flowering-related traits in maize are affected by complex factors and are important for the improvement of cropping systems in the maize zone. Quantitative trait loci (QTLs) detected using different materials and methods usually vary. In the present study, 266 maize (Zea mays) F2:3 families and 301 recombinant inbred lines (RIL) derived from a cross between 08-641 (founding parent from southeast China) and Ye478 (founding parent from China) were evaluated for four flowering-related traits, including days to tasseling (DTT), days to pollen shedding (DPS), days to silking (DTS), and anthesis-silking interval. Sixty-six QTLs controlling the target traits were detected in the F2:3 and RIL populations via single environment analysis and joint analysis across all environments (JAAE). The QTLs explained 0.8-13.47% of the phenotypic variation, with 12 QTLs explaining more than 10%. The results of meta-QTL (MQTL) analysis indicated that 41 QTLs could be integrated into 14 MQTLs. One MQTL included 2.9 QTLs, ranging from two to ten QTLs for one to three traits. QTLs, including MQTL1-1 and MQTL9-1, were detected across the F2:3 and RIL populations via SAE and JAAE. Among the MQTLs, nine QTLs were integrated into MQTL9-1 and affected DTT, DPS, and DTS, with the favored allele being derived from 08-641. MQTL3-2 showed high phenotypic variation and was suitable for fine mapping to determine the genetic mechanisms of flowering. MQTL3-2 could be applied to improve inbred lines using marker-assisted selection.
Assuntos
Cromossomos de Plantas/genética , Flores/genética , Endogamia , Locos de Características Quantitativas , Zea mays/genética , Flores/crescimento & desenvolvimento , Ligação Genética , Característica Quantitativa Herdável , Zea mays/crescimento & desenvolvimentoRESUMO
Considerable attention is currently being directed toward methods for producing recombinant human proteins in the mammary glands of genetically modified transgenic livestock. However, the expression of inserted genes in transgenic animals is variable and often very low because of the randomness of the site of transgene integration. One possible strategy to avoid the expression problem associated with random integration is to use site-specific integration by targeting integration to a high expression locus and, thereby, to improve expression of the transferred gene. In the present study, we focused on glial cell line-derived neurotrophic factor (GDNF), a novel type of neurotrophic factor first cloned in 1993. Research has shown that GDNF may have potential applications in the treatment of Parkinson's disease and other diseases of the central nervous system since it acts as a protective factor for central dopaminergic neurons. Here, we constructed a gene targeting vector to knock-in the human GDNF gene at the bovine beta-casein gene locus as a first step to producing transgenic animals with a high level of expression of human GDNF protein in their mammary glands. Bovine fetal fibroblast cells were transfected with linearized pNRTCNbG by electroporation. Three cell clones were identified with successful targeting to the beta-casein locus; and were confirmed using both polymerase chain reaction analysis and sequencing. Gene-targeted cells were used as nuclear donors; a total of 161 embryos were reconstructed, 23 of which developed to the blastocyst stage. These blastocysts were transferred to 8 recipient cows, but no offspring were obtained.
Assuntos
Caseínas/genética , Bovinos/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Animais , Animais Geneticamente Modificados , Blastocisto , Bovinos/metabolismo , Feminino , Marcação de Genes , Genes Reporter , Vetores Genéticos , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Humanos , TransfecçãoRESUMO
The goal of this study was to investigate the expression profiles of nuclear factor-kappa B (NF-κB) and epidermal growth factor receptor (EGFR) in esophageal cancer and to determine their association with tumor prognosis. This study included 40 esophageal cancer patients [22 men and 18 women; average age = 62.7 ± 3.9 years; tumor-node-metastasis (TNM) staging: 12 patients with stage I, 13 patients with stage II, and 15 patients with stage III disease]. Tumor tissues and tumor-adjacent tissue specimens were collected during radical resections at our hospital. Immunohistochemical staining was used to examine these tissues for NF-κB and EGFR expression. Follow-up of all patients included gathering information such as the 3-year survival rate. We found that NF-κB and EGFR expression was significantly higher in tumor tissues compared to tumor-adjacent normal tissues. Expression was not related to gender or age, but was positively associated with the degree of tumor infiltration. NF-κB and EGFR expression levels gradually increased with higher TNM stage, but this difference was not significant. Follow-up results showed that patients with higher NF-κB and EGFR levels had a lower survival rate and unfavorable prognosis. In conclusion, we found that NF-κB and EGFR expression was significantly elevated during the occurrence and development of esophageal carcinoma, and expression of these factors appears to be correlated with cancer progression. Higher expression of both genes is associated with an unfavorable prognosis.
Assuntos
Receptores ErbB/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidade , Expressão Gênica , NF-kappa B/genética , NF-kappa B/metabolismo , Idoso , Receptores ErbB/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Coronary angiography can be a high-risk condition for the incidence of contrast-induced nephropathy (CIN) in elderly patients. Reduced glutathione, under a variety of mechanisms, may prevent CIN in this procedure. We prospectively examined whether hydration with reduced glutathione is superior to hydration alone for prevention of CIN in an elderly Han Chinese population. A total of 505 patients (271 males and 234 females) aged 75 years or older who underwent non-emergency coronary angiography or an intervention were randomly divided into two groups. The treatment group received hydration with reduced glutathione (n=262) and the control group received hydration alone (n=243). Serum creatinine and blood urea nitrogen levels were measured prior to coronary angiography and 48 h after this procedure. The primary endpoint was occurrence of CIN, which was defined as 25% or 44.2 µmol/L above baseline serum creatinine levels 48 h after the procedure. The overall incidence of CIN was 6.49% in the treatment group and 7.41% in the control group, with no significant difference between the groups (P=0.68). In subgroup analysis by percutaneous coronary intervention, no significant differences were found between the two groups. In summary, reduced glutathione added to optimal hydration does not further decrease the risk of CIN in elderly patients undergoing coronary angiography or an intervention.
Assuntos
Meios de Contraste/efeitos adversos , Angiografia Coronária/métodos , Glutationa/administração & dosagem , Nefropatias/prevenção & controle , Idoso , Angiografia Coronária/efeitos adversos , Feminino , Humanos , Nefropatias/induzido quimicamente , Masculino , Estudos ProspectivosRESUMO
Genome-wide association studies in several ethnic groups have reported that polymorphisms of the telomerase reverse transcriptase (TERT) and cleft lip and palate transmembrane 1-like (CLPTM1L) genes, located on 5p15.33, are associated with susceptibility to lung cancer. However, whether genetic variants of TERT-CLPTM1L are associated with an increased risk of lung cancer in the Chinese Han population is unknown. This study examined associations between five single nucleotide polymorphisms (SNPs) of TERT-CLPTM1L (rs402710, rs401681, rs465498, rs4975616, and rs2736100) and lung cancer in a Chinese Han population in the Hubei Province. The five SNPs were detected using the Sequenom MassArray(®) iPLEX System in 304 lung cancer patients and 319 controls. Of the five SNPs, rs4975616 did not conform to Hardy-Weinberg equilibrium in the controls. Only rs2736100 was significantly (P = 0.034) associated with an increased risk of lung cancer. In the linkage disequilibrium analyses, a block of strong linkage disequilibrium was observed between rs401681 and rs465498 (D' = 0.986; r(2) = 0.546). No linkage disequilibrium between rs2736100 and the other three SNPs was found. In the haplotype analyses, the frequencies of the TTCT haplotype in rs402710, rs401681, rs465498, and rs2736100 differed significantly between case and control subjects (odds ratio = 0.56; 95% confidence interval, 0.36-0.88; P = 0.012). The results of this study suggested that rs2736100 on TERT-CLPTM1L indicates a poor prognosis for lung cancer in the Chinese Han population.
Assuntos
Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Telomerase/genética , Adulto , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Estudos de Associação Genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-IdadeRESUMO
Starch is the major storage product in the endosperm of cereals. Its synthesis is closely related to sucrose metabolism. In our previous study, we found that the expression of most of the genes involved in starch synthesis might be regulated by sugars and hormones in the maize endosperm. However, little is known regarding the transcriptional regulation of genes involved in sucrose metabolism. Thus, in this study, maize endosperms were treated with different sugars and hormones and the expression of genes involved in sucrose metabolism (including synthesis, degradation, and transport) were evaluated using real-time quantitative reverse transcription-polymerase chain reaction. We found that genes affected by different sugars and hormones were primarily regulated by abscisic acid. Sucrose and abscisic acid showed an additive effect on the expression of some genes. Differences in the transcriptional regulation of genes involved in sucrose metabolism and starch biosynthesis were observed.
Assuntos
Metabolismo dos Carboidratos , Endosperma/metabolismo , Regulação da Expressão Gênica de Plantas , Zea mays/metabolismo , Ácido Abscísico/metabolismo , Endosperma/genética , Frutose/metabolismo , Giberelinas/metabolismo , Glucose/metabolismo , Ácidos Indolacéticos/metabolismo , RNA de Plantas/genética , Amido/biossíntese , Sacarose/metabolismo , Zea mays/genéticaRESUMO
This study aimed to screen single nucleotide polymorphisms (SNPs) in the chicken gap junction protein alpha 1 (GJA1) gene, and to investigate their association with five growth traits measured in 269 chickens encompassing Chinese indigenous Beijing-You (BJY) and commercial Cobb broiler (CB) populations. Four variants were detected in the chicken GJA1 gene, in which one synonymous mutation was located in an exon (C61223231T or c.-1110 C>T), two in an intron (A61229799C or c.5460 A>C, T61229928A or c.5589 T>A) and one in the promoter (A61230599C or c. 6260 A>C) regions. Genotyping was performed by high-resolution melting analysis (SNP in an exon) and DNA sequencing (SNP in the introns and promoter). Association analysis revealed that each SNP had a significant effect on growth traits in chicken. A higher level of genetic diversity was observed in the indigenous BJY breed than in the commercial CB breed. Strong linkage disequilibrium was observed between the C61223231T and A61229799C polymorphisms, and four previously undiscovered haplotypes (CA, TC, CC, TA) were constructed from those two mutations. Association analysis between haplotype combinations (diplotypes) and growth traits was highly significant where diplotype CC + CC was dominant for all traits. We speculated that GJA1 either is a major gene, or is associated with a major gene, affecting chicken growth traits. Therefore, further studies are needed in large populations to evaluate polymorphisms located in different regions of this gene, as well as its functional study, to better understand its role in muscle development in chicken.