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1.
Molecules ; 25(3)2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32019194

RESUMO

Drug resistance presents serious difficulties for cancer treatment. A combination of paclitaxel (PTX) and lapatinib (LAPA) shows potentials in multiple drug resistant cancers in the clinic, but it is almost impossible to deliver these two drugs to the tumor at the same time with the best proportion by simple co-administration of the respective current formualtions for their different pharmacokinetic profiles. Here composite nanocrystals of PTX and LAPA (cNC) were designed with a ratio of 2:1 (w/w), which was their intracellular ratio at the best synergistic efficacy on a drug-resistant cancer cell line (MCF-7/ADR). Such cNC were prepared using a bottom-up method to achieve a nearly spherical appearance and a narrow size distribution of 95.1 ± 2.1 nm. For nanocrystal stabilization, Polyethylene glycol (PEG) coating was introduced into the cNC via polydopamine (PDA) coating in order to get a PEGylated composite nanocrystal (cNC@PDA-PEG) with nanoscale size (170.5 ± 1.4 nm), considerable drug loading (PTX: 21.33 ± 1.48%, LAPA: 10.95 ± 1.24%) and good stability for at least 4 days in plasma-containing buffers. Differential scanning calorimeter (DSC) and XRD data both indicated the different crystalline states of the cNC as well as the cNC@PDA-PEG in comparison with bulk drugs. In vitro release data showed that PTX and LAPA were gradually and completely released from cNC@PDA-PEG in 3 days, while drug release from bulk drugs or cNC was only 30%. cNC@PDA-PEG also showed negligible hemolysis in vitro. Cellular uptake experiments in the MCF-7/ADR cell line showed that the nanocrystals entered the cells in a complete form through endocytosis and then released the drug in the cell. cNC@PDA-PEG inhibits the growth of this drug-resistant cell more effectively than the unmodified version (cNC). In summary, PEGylated PTX and LAPA composite nanocrystals showed the potential for treament of drug-resistant tumors by simultaneously delivering two drugs to tumor cells with the best proportion.

2.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(2): 240-245, 2020 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-32030958

RESUMO

Objective: To investigate the regulatory effect of long chain non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) adsorbing microRNA-124 (miR-124) on osteogenic differentiation of mesenchymal stem cells (MSCs). Methods: C3H10T1/2 cells derived from mouse embryos were cultured in vitro, then randomly divided into control group (group A), lncRNA MALAT1 no-load plasmid group (group B), lncRNA MALAT1 overexpression plasmid group (group C), lncRNA MALAT1 small interfering RNA (siRNA) group (group D), and lncRNA MALAT1 siRNA negative control group (group E). The cells were transfected into plasmids and siRNA, then induced to differentiate into osteoblasts. Alkaline phosphatase (ALP) and alizarin red staining were used to detect the osteogenic differentiation of cells in each group, real-time fluorescence quantitative (qRT-PCR) analysis was used to detect the expressions of lncRNA MALAT, miR-124, and osteogenesis-related genes such as Runt-related transcription factor 2 (Runx2), osteopontin (OPN), and osteocalcin (OCN) in each group. Double luciferase reporter gene was used to detect the targeting regulation of lncRNA MALAT1 to miR-124. Results: The relative contents of ALP positive cells, mineralized nodule, and the relative mRNA expressions of lncRNA MALAT1, Runx2, OPN, and OCN in group C were significantly higher than those in other groups ( P<0.05), while in group D significantly lower than in other groups ( P<0.05); the relative expression of miR-124 in group C was significantly lower than that in other groups( P<0.05), while in group D significantly higher than in other groups ( P<0.05). There was no significant difference in these indexes between groups A, B, and E ( P>0.05). The results of double luciferase reporter gene assay showed that lncRNA MALAT1 targeting down-regulated the expression of miR-124. Conclusion: LncRNA MALAT1 can targeting down-regulate the expression of miR-124 and promote the osteogenic differentiation of MSCs.


Assuntos
Células-Tronco Mesenquimais , Adsorção , Animais , Diferenciação Celular , Camundongos , MicroRNAs , Osteogênese , RNA Longo não Codificante
3.
Bioresour Technol ; 303: 122906, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32028218

RESUMO

Lignite could be used to promote methane production during high-solid anaerobic co-digestion (HS-AcoD) of pig manure, however, the effects of lignite amendment on the fate of ARGs during HS-AcoD are unknown. Here, we explored the influence of lignite (0%, 8%, 16%, 32%, and 64%) on the fate of ARGs during HS-AcoD of pig manure. The results showed that 16% lignite reduced the absolute abundance of ARGs by 28.71% compared with the 0% lignite treatment. Variation partitioning analysis suggested the combined effect of microbial community, mobile genetic elements (MGEs) and environmental factors was the major driver shaping the pattern of ARGs. The potential hosts of ARGs were Bifidobacterium, Lactobacillus, Tissierella and Streptococcus. Structural equation models analysis suggested lignite indirectly impacted the pattern of ARGs by significantly reducing the abundance of microbial community and MGEs. These findings give an insight into the mechanistic understanding of the lignite influence on the reduction of ARGs during HS-AcoD.


Assuntos
Antibacterianos , Esterco , Anaerobiose , Animais , Carvão Mineral , Resistência Microbiana a Medicamentos , Genes Bacterianos , Suínos
4.
Exp Parasitol ; 211: 107843, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32044321

RESUMO

The intracellular protozoan Toxoplasma gondii infects approximately one-third of the world's population as well as various animals, causing toxoplasmosis. However, there remains a need to define the functions of newly identified genes of T. gondii. In the present study, a novel molecule, immune mapped protein 1 of T. gondii (TgIMP1), was devitalized by CRISPR/Cas9 system to investigate the phenotypic changes of the parasite. We found that the virulence of ΔTgIMP1 knockout strain was reduced in comparison with wild-type GT1 tachyzoites, showing a statistically decreased plaque in HFF cells and a significantly prolonged survival period of mice (P < 0.05). Moreover, the data of phenotype analyses in vitro showed a different level of the intracellular proliferation and the subsequent egress between ΔTgIMP1 and wild-type GT1 strain (P < 0.05); while no statistically significant difference was detected during the process of attachment or invasion. These results suggested that TgIMP1 is closely associated with the intracellular proliferation of this parasite.

5.
Life Sci ; 248: 117459, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32092332

RESUMO

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus that affects approximately half of patients with diabetes. Current treatment regimens cannot treat DPN effectively. Schwann cells (SCs) are very sensitive to glucose concentration and insulin, and closely associated with the occurrence and development of type 1 diabetic mellitus (T1DM) and DPN. Apoptosis of SCs is induced by hyperglycemia and is involved in the pathogenesis of DPN. This review considers the pathological processes of SCs apoptosis under high glucose, which include the following: oxidative stress, inflammatory reactions, endoplasmic reticulum stress, autophagy, nitrification and signaling pathways (PI3K/AKT, ERK, PERK/Nrf2, and Wnt/ß-catenin). The clarification of mechanisms underlying SCs apoptosis induced by high glucose will help us to understand and identify more effective strategies for the treatment of T1DM DPN.


Assuntos
Apoptose/efeitos dos fármacos , Neuropatias Diabéticas/genética , Glucose/farmacologia , Hiperglicemia/genética , Células de Schwann/efeitos dos fármacos , Animais , Apoptose/genética , Autofagia/efeitos dos fármacos , Autofagia/genética , Neuropatias Diabéticas/complicações , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica , Glucose/metabolismo , Humanos , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Insulina/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células de Schwann/metabolismo , Células de Schwann/patologia , Transdução de Sinais , beta Catenina/genética , beta Catenina/metabolismo
6.
Aging (Albany NY) ; 12(1): 866-883, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915310

RESUMO

Epithelial-to-mesenchymal transition (EMT) is important in tumor invasiveness and metastasis. We aimed to determine prognostic value of six key EMT markers (CDH1, CDH2, SNAI1, SNAI2, VIM, TWIST1) in clear cell renal cell carcinoma (ccRCC). A total of 533 ccRCC patients with RNASeq data from The Cancer Genome Atlas (TCGA) cohort were included for analysis. Gene expression of these EMT markers was compared between tumor and normal tissues based on Oncomine database and TCGA cohort. Their correlations with progression-free survival (PFS) and overall survival (OS) were also examined in both TCGA cohort and FUSCC (Fudan University Shanghai Cancer Center) cohort. Cox proportional hazards regression model and Kaplan-Meier plot were used to assess the relative factors. Functional enrichment analyses were utilized to describe biologic function annotations and significantly involved hallmarks pathways of each gene. We found that Epithelial marker, CDH1 expression was lower, while mesenchymal markers (CDH2, SNAI1, VIM, TWIST1) expression was higher in ccRCC primary tumors. In the TCGA cohort, we found that patients with higher expression of VIM, TWIST1 or lower expression of CDH1 had worse prognosis. Further, in the FUSCC cohort, we confirmed the predictive ability of mesenchymal markers and epithelial marker expression in PFS and OS of ccRCC patients. After generating Cox regression models, EMT markers (CDH1, SNAI1, VIM, and TWIST1) were independent prognostic factors of both PFS and OS in ccRCC patients. Our preliminary EMT prediction model can facilitate further screening of EMT biomarkers and cast a better understanding of EMT gene function in ccRCC.

7.
Gastrointest Endosc ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31911077

RESUMO

BACKGROUND AND AIMS: Prediction models for esophageal squamous cell carcinoma are not common, and no model targeting a clinical population has previously been developed and validated. We aimed to develop a prediction model for estimating the risk of high-grade esophageal lesions for application in clinical settings and to validate the performance of this model in an external population. METHODS: The model was developed based on the results of endoscopic evaluation of 5624 outpatients in one hospital in a high-risk region in northern China and was validated using 5765 outpatients who had undergone endoscopy in another hospital in a non-high-risk region in southern China. Predictors were selected with unconditional logistic regression analysis. The Akaike information criterion was used to determine the final structure of the model. Discrimination was estimated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed using a calibration plot with an intercept and slope. RESULTS: The final prediction model contained 5 variables, including age, smoking, body mass index, dysphagia, and retrosternal pain. This model generated an AUC of 0.871 (95% confidence interval, 0.842-0.946) in the development set, with an AUC of 0.862 after bootstrapping. The 5-variable model was superior to a single age model. In the validation population, the AUC was 0.843 (95% confidence interval, 0.793-0.894). This model successfully stratified the clinical population into 3 risk groups and showed high ability for identifying concentrated groups of cases. CONCLUSIONS: Our model for esophageal high-grade lesions has a high predictive value. It has the potential for application in clinical opportunistic screening to aid decision making for both health care professionals and individuals.

8.
Chemosphere ; 246: 125731, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31918083

RESUMO

Volatile organic compounds (VOCs) are ubiquitous in the atmosphere and the majority of them have been proved to be detrimental to human health. The hazardous VOCs were studied very insufficiently in China, despite the enormous emissions of VOCs. In this study, the concentrations and sources of 17 hazardous VOCs reported in literature were reviewed, based on which the health effects were assessed. In-depth survey indicated that benzene and toluene had the highest concentrations in eastern China (confined to the study regions reviewed, same for the other geographic generalization), which however showed significant declines. The southern China featured high levels of trichloroethylene. Dichloromethane and chloroform were observed to be concentrated in northern China. The distributions of 1,2-dichloropropane and tetrachloroethylene were homogeneous across the country. Basically consistent with the spatial patterns of ozone, the summertime formaldehyde exhibited higher levels in eastern and northern China, and increased continuously. While transportation served as the largest source of benzene and toluene, industrial emissions and secondary formation were the predominant contributors of halogenated hydrocarbons and aldehydes (formaldehyde and acetaldehyde), respectively. The chronic non-cancer effects of inhalation exposure to the hazardous VOCs were insignificant, however the probabilities of developing cancers by inhaling the hazardous VOCs in ambient air of China were quite high. Formaldehyde was identified as the primary carcinogenic VOC in the atmosphere of most regions. The striking results, especially the high inhalation cancer risks, alerted us that the emission controls of hazardous VOCs were urgent in China, which must be grounded upon full understanding of their occurrence, presence and health effects.

9.
Clin Chim Acta ; 503: 169-174, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31991129

RESUMO

BACKGROUND: Reduced serum omentin-1 concentrations might be related to an increased risk for poor functional outcome after acute ischemic stroke. We intended to explore whether serum omentin-1 could be a promising prognostic biomarker for acute intracerebral hemorrhage. METHODS: A total of 104 consecutive patients with hemorrhagic stroke underwent 90-day follow-up. The modified Rankin scale score >2 was evaluated as worse prognosis. A multivariable logistic model was conFig.d for assessing the relationship between serum omentin-1 concentrations and functional outcome. RESULTS: Serum omentin-1 concentrations, with the median value of 147.9 ng/ml (interquartile range, 114.7-199.8 ng/ml), were substantially declined with rising modified Rankin scale scores (P < 0.001). Serum omentin-1 concentrations <147.9 ng/ml was independently related to higher risk of 90-day worse prognosis (odds ratio, 3.789; 95% confidence interval, 1.819-8.608; P = 0.018). Under receiver operating characteristic curve, an optimal value of serum omentin-1 concentrations was selected as 179.7 ng/ml, which yielded 0.88 sensitivity value and 0.70 specificity value for discriminating patients at risk of 90-day worse prognosis (area under curve, 0.82; 95% confidence interval, 0.73-0.89). CONCLUSIONS: Lower serum omentin-1 concentrations are closely associated with poor functional outcome after hemorrhagic stroke, substantializing serum omentin-1 as a potential prognostic biomarker for acute intracerebral hemorrhage.

10.
Mikrochim Acta ; 187(2): 141, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965324

RESUMO

A method is described for the determination of microRNAs via two-stage signal enhancement. This is attained by combining hairpin (HP) assisted cascade isothermal amplification with light-up DNA-Ag nanoclusters. A rationally designed dual-functional HP is used, and microRNA-21 is chosen as a model analyte. At the first stage, upon the hybridization of the microRNA-21 with HP, microRNA recycling via polymerase-displacement reaction and a circulative nicking-replication process are achieved. This generates numerous G-abundant overhang DNA sequences. In the second stage, the above-released G-abundant overhang DNA sequences hybridize with the dark green Ag NCs, and this results in the appearance of bright red fluorescence. Thanks to the two signal enhancement processes, a linear dependence between the fluorescence intensity at 616 nm and the concentration of microRNA-21 is obtained in the range from 1 pM to 20 pM with a detection limit of 0.7 pM. The strategy clearly discriminates between perfectly-matched and mismatched targets. The method was applied to the determination of microRNA-21 in a spiked serum sample. Graphical abstractSchematic representation of microRNA detection by integrating hairpin assisted cascade isothermal amplification with light-up DNA Ag nanoclusters. With microRNA, G-abundant overhang DNA sequences from amplification reaction hybridize with dark green Ag nanoclusters to produce a concentration-dependent bright red fluorescence.

11.
Zhongguo Zhen Jiu ; 40(1): 17-20, 2020 Jan 12.
Artigo em Chinês | MEDLINE | ID: mdl-31930893

RESUMO

OBJECTIVE: To compare the therapeutic effect of thunder-fire moxibustion combined with vibration training and simple vibration training on low back pain of primary osteoporosis by Young's modulus of ultrasonic wave, and seek an objective evaluating method. METHODS: A total of 60 patients were randomized into an observation group and a control group, 30 cases in each one. The patients in the two groups were treated with vibration training using whole body vibration treatment bed. In the observation group, thunder-fire moxibustion was applied at Yaoyangguan (GV 3), Mingmen (GV 4), Ganshu (BL 18), Shenshu (BL 23) and Dachangshu (BL 25). The treatment was given once every other day, 3 times a week for 4 weeks. The visual analogue score (VAS), real-time shear wave elastography (RTSWE) and medical outcomes study 36-item short-form hearth survey (SF-36) were used to evaluate pain intensity, multifidus muscle tone (Young's modulus) and quality of life before treatment, after 4-week treatment and 1 month after treatment. RESULTS: Compared before treatment, the VAS scores, Young's modulus of multifidus muscle and 5 dimensions of SF-36 (physical condition, body pain, general health, social function and mental health) after 4-week treatment and 1 month after treatment were significantly improved in the two groups (all P<0.05), the physiological role in the observation group after 4-week treatment and 1 month after treatment were improved (both P<0.05). In the observation group, the VAS scores, Young's modulus of multifidus muscle and 3 dimensions of SF-36 (physiological role, body pain and general health) after 4-week treatment and 1 month after treatment were superior to the control group (all P<0.05). CONCLUSION: The therapeutic effect of thunder-fire moxibustion combined with vibration training is superior to simple vibration training in relieving low back pain intensity and multifidus muscle tone, and improving quality of life for primary osteoporosis. RTSWE technique can be an objective examination method to evaluate pain.


Assuntos
Dor Lombar , Moxibustão , Osteoporose , Pontos de Acupuntura , Humanos , Dor Lombar/etiologia , Dor Lombar/terapia , Osteoporose/complicações , Qualidade de Vida , Resultado do Tratamento , Vibração
12.
Asian J Androl ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31929196

RESUMO

Surgical repair of complex posterior urethral disruptions remains one of the most challenging problems in urology. The efficacy of using a tissue expander capsule as an induced vascular bed to prefabricate axial vascularized buccal mucosa-lined flaps for tubularized posterior urethral reconstruction in a rabbit model was tested. The experiments were performed in three stages. First, silicone tissue expanders were inserted into the groin to induce vascularized capsule pouch formation. Next, buccal mucosa grafts were transplanted into the newly formed capsular tissue supplied by axial vessels for buccal mucosa-lined flap prefabrication. Then, circumferential posterior urethral defects were created and repaired with the buccal mucosa graft (Group 1), the capsule flap (Group 2), and the prefabricated capsule buccal mucosa composite flap (Group 3). After surgery, notable contracture of the tubularized buccal mucosa graft was observed in the neourethra, and none of the rabbits in Group 1 maintained a wide urethral caliber. In Group 2, the retrieved neourethra showed little evidence of epithelial lining during the study period, and the lumen caliber was narrowed at the 3-month evaluation. In Group 3, the buccal mucosa formed the lining in the neourethra and maintained a wide urethral caliber for 3 months. The capsule may serve as an induced vascular bed for buccal mucosa-lined flap prefabrication. The prefabricated buccal mucosa-lined flap may serve as a neourethra flap for posterior urethral replacement.

13.
Cancer Res ; 80(2): 319-333, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31690668

RESUMO

The tumorigenic role and underlying mechanisms of lipid accumulation, commonly observed in many cancers, remain insufficiently understood. In this study, we identified an AMP-activated protein kinase (AMPK)-GATA-binding protein 3 (GATA3)-enoyl-CoA hydratase short-chain 1 (ECHS1) pathway that induces lipid accumulation and promotes cell proliferation in clear cell renal cell carcinoma (ccRCC). Decreased expression of ECHS1, which is responsible for inactivation of fatty acid (FA) oxidation and activation of de novo FA synthesis, positively associated with ccRCC progression and predicted poor patient survival. Mechanistically, ECHS1 downregulation induced FA and branched-chain amino acid (BCAA) accumulation, which inhibited AMPK-promoted expression of GATA3, a transcriptional activator of ECHS1. BCAA accumulation induced activation of mTORC1 and de novo FA synthesis, and promoted cell proliferation. Furthermore, GATA3 expression phenocopied ECHS1 in predicting ccRCC progression and patient survival. The AMPK-GATA3-ECHS1 pathway may offer new therapeutic approaches and prognostic assessment for ccRCC in the clinic. SIGNIFICANCE: These findings uncover molecular mechanisms underlying lipid accumulation in ccRCC, suggesting the AMPK-GATA3-ECHS1 pathway as a potential therapeutic target and prognostic biomarker.

14.
Org Lett ; 22(1): 164-167, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31868372

RESUMO

A straight synthetic approach to fused polycyclic tropane scaffold formation through an asymmetric dearomatization cycloaddition process of 2-nitrobenzofurans with cyclic azomethine ylides was successfully developed. In the presence of a chiral copper complex, derived from Cu(OAc)2 and a diphosphine ligand, a series of fused polycyclic tropane derivatives were obtained in high yields (75-91%) with excellent enantioselectivities (90-98%). The utility of this method was showcased by the facile transformation of product.

15.
Front Oncol ; 9: 879, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824835

RESUMO

Objective: To investigate the association between tumor PD-L1 expression and patient survival to determine whether PD-L1 represents an independent prognostic feature for patients with non-metastatic clear cell renal cell carcinoma (RCC). Patients and Methods: The tissue bank of the Fudan University Shanghai Cancer Center was queried to identity tissue samples of patients treated with radical nephrectomy, for non-metastatic sporadic clear cell RCC (ccRCC) between 2008 and 2015. Real-time polymerase chain reaction and immunohistochemistry staining was performed to detect the expression level of PD-L1 in paired cancer tissue and paracancerous tissue. Results: Three-hundred-and-thirty patients were enrolled in this study, with a mean age of 55.0 years at surgery and a mean tumor size of 5.2 cm. Two-hundred-and-forty-two (73.3%) and 88 (26.7%) patients showed a high and low expression of PD-L1 mRNA, respectively, while 254 patients had positive PD-L1 immunohistochemistry staining. Two-hundred-and-ninety-two patients had consistent results for mRNA and the PD-L1 protein based on these different detection methods. Patients with high PD-L1 expression were more likely to exhibit adverse pathologic features including an advanced T stage (P = 0.002) and lymph node metastasis (P = 0.044). The Kaplan-Meier curves of PFS and OS stratified by PD-L1 expression had a statistically significant difference. PD-L1 expression maintained a significant predictive role for PFS and OS in the multivariate cox model. Conclusions: Our data suggests that PD-L1 correlates with prognosis in RCC and targeting the PD-1/PD-L1 pathway should be considered in the treatment of RCC patients.

16.
Yi Chuan ; 41(12): 1148-1155, 2019 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-31857286

RESUMO

The cultivation of innovative abilities has become an important guide for higher education in China. Strengthening the integrated knowledge to design experiments is an effective way to improve undergraduate students' innovative abilities. Herein we designed a comprehensive experiment for molecular genetics by utilizing a rice Ds insertion mutant identified previously in our research project. In the comprehensive experiment, we adopt the method of scientific research as the main line of teaching and take the interesting phenotype of the rice mutant as the breakthrough point to reform and innovate genetics laboratory teaching. On the basis of this, we combined the progressive teaching method and guided the students to learn the TAIL-PCR skill and conduct an innovative experiment through expanding their knowledge. The comprehensive experiment will deepen students' understandings of the relationship between genotypes and phenotypes, help them master the effective way of thinking and technologies for scientific research to further improve their ability of the integrated application capability of theory and practices.


Assuntos
Genética , Mutagênese Insercional , China , Genética/educação , Humanos
17.
J Cell Biochem ; 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31886567

RESUMO

Increasing evidence has shown that Rad50, a protein involved in the DNA damage repair process, significantly correlated with tumor prognosis. This study focused on Rad50 expression in tumor samples and its prognostic value for patients with prostate cancer (PCa). In this study, significantly elevated Rad50 expression in PCa tissues compared to normal tissues (P < .01). Five independent Oncomine databases validated significant differential expression of Rad50 (P < .001). Hence, 80 patients with PCa from Fudan University Shanghai Cancer Center (FUSCC) and 351 patients with PCa with available protein expression data from The Cancer Genome Atlas (TCGA) were included to investigate the survival benefit. Univariate and multivariate Cox regression analyses were performed to investigate the significance of clinicopathological factors on disease-free survival (DFS) and overall survival (OS). Kaplan-Meier analysis indicated that elevated Rad50 protein expression levels significantly correlated with unfavorable DFS (P = .005) in the FUSCC cohort and poorer OS (P = .04) in TCGA cohort. Furthermore, coregulation analysis of proteins indicated that 76 coregulated proteins were associated with Rad50, while 11 most highly involved hub proteins, including Rad50, MRE11A, DUT, POLR3A, MCM3AP, RECQL, PNPT1, RANBP3, DDX1, SNRPB, and UGN, were significantly coregulated in the protein-protein interaction network. Functional enrichment analysis consecutively indicated significant functions and signaling pathways including DNA replication, spliceosome, DNA geometric change, homologous recombination, and G2M checkpoint. This study first reveals that elevated Rad50 expression is significantly associated with aggressive progression and poor survival for patients with PCa. Together, these data suggest that Rad50 may act as an oncoprotein, guide the molecular diagnosis, and may shed light on novel individual therapeutic strategies for progressive PCa patients.

18.
Huan Jing Ke Xue ; 40(9): 3886-3897, 2019 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854850

RESUMO

Based on the latest monthly data of moderate resolution imaging spectroradiometer (MODIS)/Terra C6.1 aerosol optical depth (AOD), the temporal-spatial distribution and variability trend in AOD over China during 2001-2017 are analyzed to explore the distribution and variation characteristics of AOD in China. Regarding the spatial characteristics, the first prominent high-value center of the annual mean AOD was located in the industrially and economically developed areas of the North China Plain, Central China, the Yangtze River Delta region, the Pearl River Delta region, and the Sichuan Basin. The second prominent high-value center of the annual mean AOD was located in the dust aerosol-dominated areas of Taklimakan Desert. Two low-value centers of the annual mean AOD were located in the eastern part of Inner Mongolia to the north of Northeast China and the Tibet Plateau. Regarding the temporal characteristics, the AOD value peaked in eight areas in spring and summer. The annual mean AOD values in the Taklimakan Desert, Sichuan Basin, and Pearl River Delta peaked from March to May, and those in the North China Plain, Central China, and Yangtze River Delta peaked from May to July. The trend characteristics showed that during 2001-2006, the AOD in Northwest China and Inner Mongolia showed a downtrend, and that in the east-central China and the eastern part of southwest China showed a growth trend. During 2007-2012, the trend of AOD in the Tibetan Plateau and the Taklimakan Desert changed from decreasing to increasing. The growth trend of AOD in the North China Plain and the Sichuan Basin was weakened, and the AOD in the Yangtze River Delta showed a weak downward trend. During 2013-2017, the AOD in most areas of China showed a significant downward trend.

19.
J Transl Med ; 17(1): 363, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703694

RESUMO

BACKGROUND: Growing evidence has demonstrated immune reactivity as a confirmed important carcinogenesis and therapy efficacy for clear cell renal cell carcinoma (ccRCC). Aquaporin 9 (AQP9) is involved in many immune-related signals; however, its role in ccRCC remains to be elucidated. This study investigated AQP9 expression in tumor tissues and defined the prognostic value in ccRCC patients. METHODS: A total of 913 ccRCC patients with available RNA-sequence data from the Cancer Genome Atlas (TCGA) database and Fudan University Shanghai Cancer Center (FUSCC) were consecutively recruited in analyses. Differential transcriptional and proteome expression profiles were obtained and validated using multiple datasets. A partial likelihood test from Cox regression analysis was developed to address the influence of independent factors on progression-free survival (PFS) and overall survival (OS). The Kaplan-Meier method and log-rank test were performed to assess survival. Receiver operating characteristic (ROC) curves were used to describe binary classifier value of AQP9 using area under the curve (AUC) score. Functional enrichment analyses and immune infiltration analysis were used to describe significantly involved hallmark pathways of hub genes. RESULTS: Significantly elevated transcriptional and proteomic AQP9 expressions were found in ccRCC samples. Increased AQP9 mRNA expression was significantly associated with advanced clinicopathological parameters and correlated with shorter PFS and OS in TCGA and FUSCC cohorts (p < 0.001). ROC curves suggested the significant diagnostic and prognostic ability of AQP9 (PFS, AUC = 0.823; OS, AUC = 0.828). Functional annotations indicated that AQP9 is involved in the most significant hallmarks including complement, coagulation, IL6/JAK-STAT3, inflammatory response and TNF-alpha signaling pathways. CONCLUSION: Our study revealed that elevated AQP9 expression was significantly correlated with aggressive progression, poor survival and immune infiltrations in ccRCC patients, and we validated its prognostic value in a real-world cohort. These data suggest that AQP9 may act as an oncogene and a promising prognostic marker in ccRCC.

20.
J Cancer ; 10(24): 6170-6174, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31762827

RESUMO

Telomere length measured in lymphocytes has been evaluated as a potential biomarker for prostate cancer (PCa) risk. Identifying genetic variants that affect telomere length and testing their association with disease could clarify any causal role. We therefore investigated associations between genetic variants in three telomere length-related genes and PCa risk in a case-control study. The influence of these variants on the leukocyte telomere lengths was then appraised by real-time PCR. RTEL1 rs2297441 [odds ratio (OR): 1.23; 95% confidence interval (CI): 1.03-1.46, P = 0.021] and rs3208008 (OR: 1.23; 95% CI: 1.03-1.46) were associated with PCa risk. These two risk single nucleotide polymorphisms (SNPs) (OR: 0.59; 95% CI: 0.39-0.89, P = 0.012 and OR: 0.58; 95% CI: 0.38-0.87, P = 0.009, respectively) and another SNP PARP1 rs1136410 (OR: 1.53; 95% CI: 1.01-2.31, P = 0.043) were also associated with leukocyte telomere length. These findings support that genetic determinants of telomere length may influence PCa risk.

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