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1.
BMC Vet Res ; 15(1): 446, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818287

RESUMO

BACKGROUND: Leishmaniosis, a disease caused by pathogenic Leishmania parasites, remains an unresolved health problem in the New World and the Old World. It is well known that lizards can be infected by a subgenus of Leishmania parasites, i.e. Sauroleishmania, which is non-pathogenic to humans. However, evidence suggests that lizards may also harbor pathogenic Leishmania species including the undetermined Leishmania sp., discovered in our previous work. Leishmania DNA in lizard blood can be detected by using molecular methods, such as the polymerase chain reaction (PCR). RESULTS: Three hundred and sixteen lizards, representing 13 species of four genera, were captured for blood samples collection in Northwest China. Two reliable molecular markers (cytochrome b and heat shock protein 70 genes) were used for detection in the lizard blood samples, to confirm a widespread presence of pathogenic Leishmania parasites and the distribution pattern of Leishmania spp. in lizards from Northwest China. The PCR data indicated positive detection rate for Leishmania in all the tested lizards with an overall prevalence of 57.91% (183/316). Apart from lizard parasites like Leishmania tarentolae and Leishmania sp., several pathogenic Leishmania including L. turanica, L. tropica and L. donovani complex were identified by using phylogenetic analysis. Co-existence of different haplotypes was observed in most Leishmania DNA-positive lizards with an overall rate of 77.6% (142/183). Even mixed infections with different Leishmania species appeared to occur in the lizards with an overall rate of 37.7% (69/183). CONCLUSIONS: Lizards can harbor pathogenic Leishmania spp. Co-existence of different haplotypes or even species of Leishmania indicates mixed infections in natural lizard host. Lizards may contribute to the spread of Leishmania parasites. The pathogenic Leishmania species detected in lizards from Northwest China may be of great eco-epidemiological importance.

2.
Trials ; 20(1): 719, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831051

RESUMO

BACKGROUND: Hair loss is one of the most common side effects of chemotherapy, and can cause persistent negative emotions, further affecting therapeutic effects and reducing the quality of life. However, there are no clinically safe and effective methods to solve the problem at present. Our previous clinical and animal studies showed that a medicinal and edible decoction, YH0618, could significantly promote hair growth in cancer patients after chemotherapy, without interfering with the anti-tumor effects of chemotherapy. Besides, the theory of Chinese Medicine believes that the "Essence of the kidney is reflected on the hair". Therefore, this study will further explore the efficacy of YH0618 granule on chemotherapy-induced hair loss in patients with breast cancer by a randomized, double-blind, multi-center clinical trial and elucidate the potential mechanism from the aspect of kidney deficiency or renal dysfunction. METHODS/DESIGN: Eligible breast cancer patients who will start chemotherapy will be randomly divided into group A (YH0618 granule) and group B (placebo). The chemotherapeutic agents contain taxanes or/and anthracyclines, and the chemotherapy regimen will be for at least six cycles with a cycle every 3 weeks. Subjects assigned to group A will receive YH0618 granules twice a day (6 g each time), 6 days a week, mixed with 300 ml warm water from the first to the fourth chemotherapy cycle. Subjects in group B will receive the placebo granule in the same manner. The primary outcome is the time point of occurrence of hair loss reaching grade II as assessed by the WHO Toxicity Grading Scale, and objective indices of hair quality and hair-follicle growth recorded by a hair and scalp detector before the fifth chemotherapy cycle. Secondary outcomes include changes of facial color and thumbnail color, grading of thumbnails ridging, assessment of quality life, level of fatigue, routine blood test results, hepatic and renal function, and certain medical indicators which can reflect kidney deficiency in Chinese Medicine. DISCUSSION: This research is of great significance for the treatment of cancer and improving the quality of life of cancer patients. The study may provide the most direct evidence for meeting clinical needs and lay a solid scientific foundation for later product development. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR1800020107. Registered on 14 December 2018.

3.
Mar Drugs ; 18(1)2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31861572

RESUMO

Heparin from mollusks with unique sulfated glycosaminoglycan exhibits strong anti-thrombotic activities. This study reports on a purified heparinoid from Coelomactra antiquata, which shows potent anticoagulant and fibrinolytic abilities. Its structure was characterized by infrared spectroscopy, high-performance liquid chromatography, and one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy. Its fibrinolytic activity was determined in vitro and in vivo. Its anticoagulant activity was determined by activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicated that clam heparinoid was a homogeneous glycosaminoglycan with a molecular weight of 30.99 kDa, mainly composed of →4)-α-IdoA2S-(1→4)-α-GlcNS3S6S (or GlcNS6S)-(1→4)-ß-GlcA-(1→4)-α-GlcNS6S (or GlcNAC)-(1→. Furthermore, this heparinoid showed a highly anticoagulant titer and fibrinolytic value of 149.63 IU/mg and 1.96 IU/mg, respectively. In summary, clam heparinoid shows great potential for application in the clinic and antithrombotic drugs industry.

4.
Gland Surg ; 8(5): 557-568, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31741887

RESUMO

Background: Papillary thyroid cancer (PTC) has a strong propensity to metastasize to the cervical lymph nodes. Little was known currently about whether tumor's location would influence the risk of lymph node metastasis in PTC. Methods: The study enrolled PTC patients who underwent primary surgical therapy in our center for small unifocal tumor. The tumor's location was evaluated by ultrasound in three axes, three planes and 3D space. Logistic univariate and multivariate analysis were applied to explore the association between tumors' location and the risk of lymph node metastasis in PTC. Different localization methods of thyroid tumors were evaluated using ROC curve. Results: Totally 1,266 PTC patients were enrolled in this study. Univariate and multivariate analyses showed that gender, age, tumor size and tumor's location (in longitudinal axis, longitudinal sagittal plane, longitudinal coronal plane, sagittal coronal plane and 3D space) was associated with central lymph node dissection (CLND); gender, tumor size and tumor's location (in longitudinal axis, coronal axis, longitudinal sagittal plane, longitudinal coronal plane, sagittal coronal plane and 3D space) was related with lateral lymph node dissection (LLND) (P<0.05). In the ROC curve analysis, the 3D location showed the highest predictive value of lymph node metastasis (C-statistics: 0.724 for CLNM; 0.763 for LLNM). The middle posterior lateral (OR=2.575, P=0.028), inferior anterior central (OR=2.829, P=0.016), inferior posterior lateral (OR=2.759, P=0.039) and isthmus tumors (OR=4.526, P=0.001) were at a higher risk of CLNM, and the middle anterior central tumors (OR=0.102, P=0.015) were related with lower risk of LLNM. Conclusions: Stereotactic localization showed the highest predictive value of lymph node metastasis. The middle posterior lateral, inferior anterior central, inferior posterior lateral and isthmus tumors were at a higher risk of CLNM when compared to other locations. For such patients, careful preoperative evaluation of nodal status should be done.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31624016

RESUMO

BACKGROUND: This study aimed at establishing the autoimmune hepatitis (AIH) model of C57BL/6 mice, and examining the expression and significance of T follicular helper (Tfh) cells, T follicular regulatory (Tfr) cells, effector B cells and other indicators in this experimental autoimmune hepatitis (EAH) model. METHODS: C57BL/6 mice in experimental group were administered by intraperitoneal injection after fully emulsified on 1st day and 7th day with 0.5 mL of 0.5-2.0 g/L S-100 and an equal volume of Buddha Complete Adjuvant (CFA). The levels of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and interleukin-21 (IL-21) were tested by the corresponding kit. Tfr, Tfh and B cell subsets were quantified by flow cytometry. Histological pathology was completed by pathological section experiments. RESULTS: In comparison with that in the healthy controls (HC), significantly increased numbers of serum ALT and AST, Tfr, IL-21 was observed. The hepatic lobules and hepatocyte cords were severely disorganized. CONCLUSION: The results of liver pathological changes and serum index changes were similar to the chronic and progressive pathogenesis and pathology of AIH patients, providing a detailed pathological basis for the basic research and clinical experiments of AIH.

6.
Int J Cancer ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498891

RESUMO

Metastasis is the leading cause of death for non-small cell lung cancer (NSCLC) patients. However, how lung cancer cells invade blood vessels during metastasis remains unclear. Here, based on bioinformatics analyses, we found that PLEK2 might regulate NSCLC migration and vascular invasion. As little is known about the function of PLEK2 in NSCLC, we aimed to clarify this. We demonstrated that PLEK2 was significantly upregulated in transforming growth factor beta 1 (TGF-ß1)-treated NSCLC cells through ELK1 transcriptional activation, highly expressed in NSCLC tissues, and negatively correlated with NSCLC overall survival. Meanwhile, PLEK2 overexpression significantly promoted NSCLC epithelial-to-mesenchymal transition (EMT) and migration, human lung microvascular endothelial cells endothelial-to-mesenchymal transition (EndoMT), and the destruction of vascular endothelial barriers. Moreover, PLEK2 knockdown inhibited TGF-ß1-induced EMT and EndoMT. Furthermore, PLEK2 was found to directly interact with SHIP2 and target it for ubiquitination and degradation in NSCLC cells. Next, we confirmed that SHIP2 overexpression inhibits NSCLC EMT, migration and invasion and showed that PLEK2 overexpression can activate SHIP2-associated TGF-ß/PI3K/AKT signaling. Our results suggest that PLEK2 could be a novel prognostic marker and potential therapeutic target for NSCLC metastasis and vascular invasion.

7.
Mol Pharmacol ; 96(5): 589-599, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31462456

RESUMO

Licorice is a medicinal herb widely used to treat inflammation-related diseases in China. Isoliquiritigenin (ISL) is an important constituent of licorice and possesses multiple bioactivities. In this study, we examined the selective anti-AML (acute myeloid leukemia) property of ISL via targeting FMS-like tyrosine kinase-3 (FLT3), a certified valid target for treating AML. In vitro, ISL potently inhibited FLT3 kinase, with an IC50 value of 115.1 ± 4.2 nM, and selectively inhibited the proliferation of FLT3-internal tandem duplication (FLT3-ITD) or FLT3-ITD/F691L mutant AML cells. Moreover, it showed very weak activity toward other tested cell lines or kinases. Western blot immunoassay revealed that ISL significantly inhibited the activation of FLT3/Erk1/2/signal transducer and activator of transcription 5 (STAT5) signal in AML cells. Meanwhile, a molecular docking study indicated that ISL could stably form aromatic interactions and hydrogen bonds within the kinase domain of FLT3. In vivo, oral administration of ISL significantly inhibited the MV4-11 flank tumor growth and prolonged survival in the bone marrow transplant model via decreasing the expression of Ki67 and inducing apoptosis. Taken together, the present study identified a novel function of ISL as a selective FLT3 inhibitor. ISL could also be a potential natural bioactive compound for treating AML with FLT3-ITD or FLT3-ITD/F691L mutations. Thus, ISL and licorice might possess potential therapeutic effects for treating AML, providing a new strategy for anti-AML.

8.
Biomed Environ Sci ; 32(7): 520-530, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31331436

RESUMO

OBJECTIVE: To investigate the molecular characteristics and intracellular growth ability of Legionella pneumophila (L. pneumophila) strains from 1989 to 2016 in Sichuan Province, China. METHODS: Seventy-nine isolates of L. pneumophila were collected from environmental and clinical sources, including cooling towers, hot springs, bath water, fountains, and patients, and identified with 16S rRNA gene analysis and serum agglutination assay. The isolates were then typed by Sequence-Based Typing (SBT), and Genotyping of forty-two LP1 strains were analyzed by means of multiple-locus VNTR analysis with 8 loci (MLVA-8). All strains were further analyzed for two virulence genes: Legionella vir homologue (lvh) and repeats in structural toxin (rtxA). The intracellular growth ability of 33 selected isolates was determined by examining their interaction with J774 cells. RESULTS: All isolates were identified to L. pneumophila including 11 serogroups, among which the main serogroup were LP1, accounting for 54.43%. Thirty-three different sequence types (STs) from five main clonal groups and five singletons were identified, along with 8 different MLVA patterns. Both the lvh and rtxA loci were found in all 79 strains. Thirty isolates showed high intracellular growth ability in J774 cells. CONCLUSION: L. pneumophila is a potential threat to public health, and effective control and prevention strategies are urgently needed.


Assuntos
Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Legionella pneumophila/genética , RNA Ribossômico 16S/genética , China , Técnicas de Genotipagem , Humanos , Legionella pneumophila/crescimento & desenvolvimento , Legionella pneumophila/isolamento & purificação , Microbiologia da Água
9.
Onco Targets Ther ; 12: 3595-3607, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190862

RESUMO

Background: miR-106b has been reported to play a vital role in pathogenesis of some types of cancer, whilst the role of miR-106b in renal carcinoma cancer (RCC) remains unknown. Purpose: The objective of this study was to identify the mechanism of miR-106b regulating the progression of renal carcinoma. Method: The expression of miR-106b was analyzed in RCC cell lines, RCC and adjacent normal renal tissues through qRT-PCR assays. Target mRNA of miR-106b was predicted with databases and verified by luciferase reporter assays. And the effects of miR-106b or targeted mRNA on cell proliferation, invasion, the process of epithelial-mesenchymal transitions (EMTs) were assessed in vitrothrough CCK-8, transwell cell invasion assays, qRT-PCR and Western blotting assays respectively. In addition, the effects of miR-106b on the growth of xenografts mice were analyzedin vivo. Results: The results demonstrated that miR-106b was significantly increased both in RCC tissues and cell lines. Luciferase reporter assays revealed that miR-106b inhibited Capicua expression by targeting its 3'-UTR sequence. And miR-106b promoted cell proliferation, invasion, EMT progression in RCC cellin vitro, as well as promoted the tumor growth of 786-O cells derived xenografts mice. Additionally, loss of Capicua promoted the activation of MAPK signaling pathway. Conclusion: The study suggested that miR-106b regulated RCC progression through MAPK signaling pathway partly by targeting Capicua, which might provide valuable evidence for therapeutic target development of RCC.

10.
Cell Death Dis ; 10(7): 498, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31235687

RESUMO

After publication of this article, it came to the attention of the authors that their names had been reordered. Professor. Jia Cao and Prof. Jin-yi Liu are the co-corresponding authors, and Prof. Jin-yi Liu should be the last author.

11.
Cell Death Dis ; 10(6): 424, 2019 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142739

RESUMO

Although TC2N has proven to be an oncogene in lung cancer, its biological function and molecular mechanisms in other cancer still remains unclear. Here, we investigate in breast cancer that TC2N expression is sharply overexpressed in breast cancer specimens compared with normal breast specimens, and the low TC2N expression was associated with advanced stage, lymphatic metastasis, larger tumors and shorter survival time. Upregulation of TC2N significantly restrains breast cancer cell proliferation in vitro and tumor growth in vivo. Mechanistically, TC2N blocks AKT signaling in a PI3K dependent and independent way through weakening the interaction between ALK and p55γ or inhibiting the binding of EBP1 and AKT. To sum up, these results unmask an ambivalent role of TC2N in cancer, providing a promising inhibitor for PI3K-AKT signaling.

12.
Pathol Res Pract ; 215(7): 152438, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31126818

RESUMO

BACKGROUND: Plakophilin 2 (PKP2), encodes a plakophilin protein that belongs to the member of desmosomal proteins. It has been reported that high expression of PKP2 is associated with several types of cancer in humans. However, the role of PKP2 in lung cancer remains obscure. METHODS: PKP2 expression was investigated in non-small cell lung cancer (NSCLC) tissues and non-tumor tissues by performing immunohistochemistry on a tissue microarray and using The Cancer Genome Atlas (TCGA) database. Kaplan-Meier survival analysis and multivariate Cox-regression analysis were performed to identify the clinical significance of PKP2. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), colony formation, Transwell and xenograft tumor growth/ metastasis assays were conducted to evaluate the biological function of PKP2 in vitro and in vivo. Gene set enrichment analysis (GSEA), WB and immunoprecipitation (IP) assay were utilized to explore the potential downstream signaling pathway and molecule mechanism of PKP2 in lung adenocarcinoma (LUAD). RESULTS: Analysis of PKP2 expression and clinicopathological parameters reveals a significant correlation of PKP2 expression with gender (n = 1020, P < 0.001) and histological type (n = 1020, P < 0.001). Subsequently, our results demonstrated that high PKP2 expression is not associated with poor survival in different gender of lung cancer patients, and is an unfavorable and independent prognostic biomarker for LUAD patients, but not for LUSC patients. Gene set enrichment analysis (GSEA) revealed that PKP2 expression is positively associated with EGFR signaling in LUAD. Further, in vitro and in vivo assays revealed that PKP2 promotes cell proliferation, migration and invasion through activating EGFR signaling pathway in LUAD cells. CONCLUSION: Our study provides the basis for further investigation of the function and molecular mechanism by which upregulation of PKP2 promotes the development and progression of LUAD. PKP2 may serve as a potential target for anticancer therapies.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Neoplasias Pulmonares/metabolismo , Placofilinas/metabolismo , Transdução de Sinais/fisiologia , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Animais , Linhagem Celular Tumoral , Progressão da Doença , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Fatores Sexuais , Taxa de Sobrevida
13.
J Am Chem Soc ; 141(14): 5617-5622, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30907583

RESUMO

Malonic acid derivatives have been successfully applied in a Ag-catalyzed decarboxylative fluorination reaction, providing an unprecedented route to either gem-difluoroalkanes or α-fluorocarboxylic acids by the judicious selection of base and solvent. This reaction features the use of readily available starting materials, tunable chemoselectivity and good functional group compatibility as well as gram-scale synthetic capability. The advantage of using malonic acid derivatives in this radical decarboxylative functionalization is further highlighted by the facile transformations of the α-fluorocarboxylic acid to valuable fluorine-containing compounds. Preliminary mechanistic studies suggest that an α-carboxylic acid radical is involved in this reaction.

14.
Phytochem Anal ; 30(4): 447-455, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30916852

RESUMO

INTRODUCTION: The Chinese medicine formulation, tumour-shrinking decoction (TSD, FM1523), which consists of 15 natural medicines, is used for uterine fibroids (UFs) therapy and possesses excellent clinical therapeutic effect. OBJECTIVE: To develop a sensitive and validated analytical method for the simultaneous quantification of four crucial bioactive compounds including isorhamnetin-3-O-neohesperidoside, curcumin, peimine and tetrahydropalmatine in the principal formulation of this decoction. METHODS: An ultra-performance liquid chromatography coupled tandem mass spectrometry (UPLC-MS/MS) with an electrospray ionisation (ESI) source in multiple reaction monitoring (MRM) mode was conducted to investigate these bioactive compounds in the TSD. The chromatographic separation was performed on a C18 column when the flow rate was adjusted at 0.2 mL/min with gradient elution of acetonitrile-water with 0.1% formic acid. Accelerated solvent extraction (ASE) method with higher extraction efficiency was employed for TSD sample pre-treatment. RESULTS: The linearity, limit of detection (LOD) and limit of quantification (LOQ) were determined for this analytical method. The mean recoveries of the compounds were determined between 100.23% and 104.02% with satisfactory relative standard deviation (RSD) in the ranges of 2.65% to 3.81%. The precision was evaluated by intra-day and inter-day tests, which revealed RSD within the ranges of 1.21% to 2.14% and 1.24% to 2.32%, respectively. CONCLUSION: The bioactive compounds of TSD samples were successfully quantified via UPLC-MS/MS with MRM mode. This study could help to evaluate the pharmacokinetic study of TSD during clinical applications and present a facile strategy for quantifying bioactive compounds in traditional Chinese Medicine decoction.


Assuntos
Alcaloides de Berberina/química , Cevanas/química , Medicamentos de Ervas Chinesas/química , Leiomioma/tratamento farmacológico , Compostos Fitoquímicos/química , Alcaloides de Berberina/isolamento & purificação , Cevanas/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Humanos , Limite de Detecção , Compostos Fitoquímicos/isolamento & purificação , Espectrometria de Massas em Tandem
15.
Artigo em Inglês | MEDLINE | ID: mdl-30530601

RESUMO

Toxoplasma gondii is one of the most widespread obligatory parasitic protozoa and infects nearly all warm-blooded animals, leading to toxoplasmosis. The therapeutic drugs currently administered, like the combination of pyrimethamine and sulfadiazine, show high rates of toxic side effects, and drug resistance is encountered in some cases. Resveratrol is a natural plant extract with multiple functions, such as antibacterial, anticancer, and antiparasite activities. In this study, we evaluated the inhibitory effects of resveratrol on tachyzoites of the Toxoplasma gondii RH strain extracellularly and intracellularly. We demonstrate that resveratrol possesses direct antitoxoplasma activity by reducing the population of extracellularly grown tachyzoites, probably by disturbing the redox homeostasis of the parasites. Moreover, resveratrol was also able to release the burden of cellular stress, promote apoptosis, and maintain the autophagic status of macrophages, which turned out to be regulated by intracellular parasites, thereby functioning indirectly in eliminating T. gondii In conclusion, resveratrol has both direct and indirect antitoxoplasma effects against RH tachyzoites and may possess the potential to be further evaluated and employed for toxoplasmosis treatment.

16.
Mol Carcinog ; 58(4): 474-487, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30536447

RESUMO

Emerging evidences have revealed tumor-specific gene methylation is considered to be a promising non-invasive biomarker for many different types of cancers. This study was determined whether TMEM196 gene hypermethylation and downregulation are considered to be promising biomarkers for early diagnosis and prognosis in lung cancer. Methylation status was detected with methylation-specific PCR. Kaplan-Meier survival curves and Cox regression analysis were used to determine the significance of prognosis. TMEM196 gene was hypermethylated in 68.1% (64/94) of lung cancer tissues, 52.8% (67/127) of plasma and 55.2% (79/143) of sputum samples, but unmethylated (0/50) in normal tissues. TMEM196 methylation in plasma and sputum samples was significantly correlated with that in the corresponding paired tumor tissues (r = 0.750, r = 0.880, P < 0.001). TMEM196 aberrant methylation in cancer tissues, plasma and sputum DNA was significantly associated with age and pathological type (P < 0.05). TMEM196 high methylation could robustly distinguish lung cancer patients (AUC = 0.905) from normal subjects and patients with TMEM196 high methylation have a significantly poorer survival than those with low level from The Cancer Genome Atlas (Wilcoxon P < 0.001). Multivariate models showed TMEM196 methylation is an independent prognostic marker in lung cancer. Furthermore, the overall survival of patients with low TMEM196 expression was significantly poorer than that of TMEM196-high patients (P < 0.001, log-rank test). Low TMEM196 expression in tumor tissues was found to predict poorer survival (HR = 3.007; 95%CI, 1.918-4.714). Our study provided new insights into the clinical importance and potential use of TMEM196 methylation and expression as novel early diagnostic and prognostic biomarkers for human lung cancers.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Proteínas de Membrana/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Taxa de Sobrevida
17.
Cell Death Differ ; 26(7): 1235-1250, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30254375

RESUMO

The protein containing the C2 domain has been well documented for its essential roles in endocytosis, cellular metabolism and cancer. Tac2-N (TC2N) is a tandem C2 domain-containing protein, but its function, including its role in tumorigenesis, remains unknown. Here, we first identified TC2N as a novel oncogene in lung cancer. TC2N was preferentially upregulated in lung cancer tissues compared with adjacent normal lung tissues. High TC2N expression was significantly associated with poor outcome of lung cancer patients. Knockdown of TC2N markedly induces cell apoptosis and cell cycle arrest with repressing proliferation in vitro, and suppresses tumorigenicity in vivo, whereas overexpression of TC2N has the opposite effects both in vitro and in vivo. Using a combination of TCGA database and bioinformatics, we demonstrate that TC2N is involved in regulation of the p53 signaling pathway. Mechanistically, TC2N attenuates p53 signaling pathway through inhibiting Cdk5-induced phosphorylation of p53 via inducing Cdk5 degradation or disrupting the interaction between Cdk5 and p53. Moreover, the blockade of p53 attenuates the function of TC2N knockdown in the regulation of cell proliferation and apoptosis. In addition, downregulated TC2N is involved in the apoptosis of lung cancer cells induced by doxorubicin, leading to p53 pathway activation. Overall, these findings uncover a role for the p53 inactivator TC2N in regulating the proliferation and apoptosis of lung cancer cells. Our present study provides novel insights into the mechanism of tumorigenesis in lung cancer.

18.
Ying Yong Sheng Tai Xue Bao ; 29(9): 3017-3023, 2018 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30411578

RESUMO

To clarify the effects of soil salinity on the insect-resistance of flower buds in transgenic Bt cotton of Xinmian 33B (salt-sensitive) and Zhong 07 (salt-tolerant), five levels (0, 0.15%, 0.30%, 0.45% and 0.60%) of soil salinity were set to investigate the impacts of soil salinity on Bt protein content, relative expression of Bt gene, activities of nitrogen metabolism-related enzymes and substances in flower buds during flowering stage. The results showed that Bt protein contents of flower buds decreased with increasing soil salinity. The Bt protein contents of flower buds decreased significantly when the soil salinity level was above 0.30% in both cotton cutivars. Greater reduction of Bt protein content occurred under severe than moderate soil salinity stress. However, the relative expression of Cry1Ac gene increased in flower buds of both cultivars when the stress level increased. Greater decreases of Bt protein content of flower buds was observed in Xinmian 33B compared to Zhong 07 under the same salinity level. The cultivars with greater reduction in Bt protein contents of flower buds also had greater reduction in the soluble protein content, glutamate pyruvate transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) activities, and greater increments in free amino acid contents, protease activities and peptidase activities. Therefore, the decrease of Bt protein content was caused by decreased synthesis and increased decomposition of protein in flower buds of Bt cotton under soil salinity stress.


Assuntos
Gossypium/genética , Plantas Geneticamente Modificadas , Salinidade , Solo/química , Animais , Flores , Inseticidas
19.
PLoS One ; 13(11): e0207013, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30403755

RESUMO

Insect-resistance of transgenic Bacillus thuringiensis (Bt) cotton varies among plants organs and with different environmental conditions. The objective of this study was to examine the influence of soil salinity on Bt protein concentration in cotton squares and to elucidate the potential mechanism of Bt efficacy reduction. Two cotton cultivars (NuCOTN 33B and CCRI 07, salt-sensitive and salt-tolerant) were subjected to salinity stress under four natural saline levels in field conditions in 2015 and 2016 and seven regimes of soil salinity ranged from 0.5 to 18.8 dS m-1 in greenhouse conditions in 2017. Results of field studies revealed that Bt protein content was not significantly changed at 7.13 dS m-1 salinity, but exhibited a significant drop at the 10.41 and 14.16 dS m-1 salinity. The greenhouse experiments further showed similar trends that significant declines of the insecticidal protein contents in squares were detected when soil salinity exceeded 9.1 dS m-1. Meanwhile, high salinity resulted in significant reduction in contents of soluble protein and total nitrogen, activities of nitrate reductase (NR), glutamine synthetase (GS) and glutamic-pyruvic transaminase (GPT), but increased amino acid content, activities of protease and peptidase in cotton squares. High salinity also decreased root vigor (RV), root total absorption area (RTA) and root active absorption area (RAA). The extent of decrease of Bt protein content was more pronounced in NuCOTN 33B than CCRI 07, and CCRI07 exhibited stronger enzymes activities involved in square protein synthesis and higher levels of RV, RTA and RAA. Therefore, the results of our present study indicated that insecticidal protein expression in cotton squares were significantly affected by higher salinity (equal to or higher than 9.1 dS m-1), reduced protein synthesis and increased protein degradation in squares and reduced metabolic activities in roots might lead to the decrease of Bt protein content in squares.


Assuntos
Proteínas de Bactérias/metabolismo , Endotoxinas/metabolismo , Gossypium/metabolismo , Proteínas Hemolisinas/metabolismo , Solo/química , Alanina Transaminase/metabolismo , Aminoácidos/metabolismo , Proteínas de Bactérias/análise , Proteínas de Bactérias/genética , Endotoxinas/análise , Endotoxinas/genética , Ensaio de Imunoadsorção Enzimática , Gossypium/crescimento & desenvolvimento , Proteínas Hemolisinas/análise , Proteínas Hemolisinas/genética , Nitrato Redutase/metabolismo , Nitrogênio/análise , Peptídeo Hidrolases/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismo , Salinidade , Tolerância ao Sal
20.
Front Plant Sci ; 9: 1627, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30487803

RESUMO

Virus-induced gene silencing (VIGS) is an important tool for functional genomics studies in plants. With this method, it is possible to target most endogenous genes and downregulate the messenger RNA (mRNA) in a sequence-specific manner. Chinese wheat mosaic virus (CWMV) has a bipartite, single-strand positive RNA genome, and can infect both wheat and Nicotiana benthamiana, and the optimal temperature for systemic infection in plants is 17°C. To assess the potential of the virus as a vector for gene silencing at low temperature, a fragment of the N. benthamiana or wheat phytoene desaturase (PDS) gene was expressed from a modified CWMV RNA2 clone and the resulting photo bleaching in infected plants was used as a reporter for silencing. Downregulation of PDS mRNA was also measured by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR). In experiments using fragments of PDS ranging from 500 to 1500 nucleotides, insert length influenced the stability and the efficiency of VIGS. The CWMV induced silencing system was also used to suppress miR165/166 and miR3134a through expression of miRNA target mimics. The relative expression levels of mature miR165/166 and miR3134a decreased whereas the transcript levels of their target genes increased. Interestingly, we also found the CWMV-induced silencing system was more efficient compare with the vector based on Barley stripe mosaic virus (BSMV) or Foxtail mosaic virus (FoMV) in wheat or the vector based on TRV in N. benthamiana at 17°C. In summary, the CWMV vector is effective in silencing endogenous genes and miRNAs at 17°C, thereby providing a powerful tool for gene function analysis in both N. benthamiana and wheat at low temperature.

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