Background
A growing number of studies have shown that Yin Yang 1 (YY1) promotes the development of multiple tumours. The purpose of the current study was to determine the mechanism by which YY1 ...mediates neuroendocrine differentiation of prostate cancer (NEPC) cells undergoing cellular plasticity.
Methods
Using the Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases, we bioinformatically analyzed YY1 expression in prostate cancer (PCa). Aberrant YY1 expression was validated in different PCa tissues and cell lines via quantitative reverse transcription polymerase chain reaction, western blotting, and immunohistochemistry. In vivo and in vitro functional assays verified the oncogenicity of YY1 in PCa. Further functional assays showed that ectopic expression of YY1 promoted cellular plasticity in PCa cells via epithelial‐mesenchymal transition induction and neuroendocrine differentiation.
Results
Androgen deprivation therapy induced a decrease in YY1 protein ubiquitination, enhanced its stability, and thus enhanced the transcriptional activity of FZD8. Castration enhanced FZD8 binding to Wnt9A and mediated cellular plasticity by activating the non‐canonical Wnt (FZD8/FYN/STAT3) pathway.
Conclusions
We identified YY1 as a novel dysregulated transcription factor that plays an important role in NEPC progression in this study. We believe that an in‐depth investigation of the mechanism underlying YY1‐mediated disease may lead to improved NEPC therapies.
Objective:
The purpose of this meta-analysis was to study the prognostic effects of androgen receptor splicing variant 7 (AR-V7) on metastatic castration-resistant prostate cancer (mCRPC) under ...different treatment options (chemotherapy, hormone therapy).
Methods:
We conducted a systematic search of PubMed, EMBASE and Cochrane databases for clinical studies up to June 4, 2021, and used prostate-specific antigen (PSA) progression free-survival (PSA-PFS), radiologic PFS (r-PFS), overall survival (OS) and PSA response rate (PSA RR) as the main endpoints. Subgroup analyses were conducted based on the source of the specimens. STATA v.15 software was used for data analysis.
Results:
Twenty-one studies were included in this meta-analysis, with a total of 1578 samples. In the abiraterone (AA)/enzalutamide (E) treatment group, AR-V7 positive patients had worse PSA-PFS (hazard ratio HR = 3.40; 95% confidence interval 95%CI 2.56-4.51; P < 0.05) and worse r-PFS (HR = 2.69; 95%CI 1.70-4.24; P < 0.05) and OS (HR = 3.02; 95%CI 1.73-5.30; P < 0.05). Multivariate Cox regression results showed that AR-V7 positive status was an independent risk factor for OS in the AA/E treatment group. In the taxane treatment group, AR-V7-positive and negative patients had similar PSA-PFS (HR = 0.87; 95%CI 0.46-1.63; P = 0.657), r-PFS (HR = 1.01; 95%CI 0.53-1.96; P = 0.965) and OS (HR = 1.50; 95%CI 0.89-2.52; P = 0.127). For AR-V7-positive patients, the difference in OS between taxane and AA/E treatment was not statistically significant (HR = 1.03; 95%CI 0.52-2.06; P = 0.930). However, multivariate Cox regression results suggested that for AR-V7-positive patients, taxane therapy was a protective factor for OS (HR = 0.35; 95%CI 0.20-0.60; P < 0.05).
Conclusion:
The expression of AR-V7 indicates a poor prognosis and is an independent risk factor for OS in AA/E-treated mCRPC patients. However, AR-V7 positive status does not play the same role in taxane-treated patients. In addition, compared to AA/E, taxane treatment is a protective factor for OS in AR-V7-positive patients. AR-V7 may thus be an effective biomarker for treatment prognosis in patients with mCRPC.
To evaluate the safety and oncological outcomes of laparoscopic colorectal surgery using natural orifice specimen extraction (NOSE) compared with conventional laparoscopic (CL) colorectal surgery in ...patients with colorectal diseases.
We conducted a systematic search of PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs), prospective non-randomized trials and retrospective trials up to September 1, 2018, and used 5-year disease-free survival (DFS), lymph node harvest, surgical site infection (SSI), anastomotic leakage, and intra-abdominal abscess as the main endpoints. Subgroup analyses were conducted according to the different study types RCT and NRCT (non-randomized controlled trial). A sensitivity analysis was carried out to evaluate the reliability of the outcomes. RevMan5.3 software was used for statistical analysis.
Fourteen studies were included (two RCTs, seven retrospective trials and five prospective non-randomized trials) involving a total of 1,435 patients. Compared with CL surgery, the NOSE technique resulted in a shorter hospital stay, shorter time to first flatus, less post-operative pain, and fewer SSIs and total perioperative complications. Anastomotic leakage, blood loss, and intra-abdominal abscess did not differ between the two groups, while operation time was longer in the NOSE group. Oncological outcomes such as proximal margin weighted mean difference WMD = 0.47; 95% confidence interval CI -0.49 to 1.42;
= 0.34, distal margin (WMD= -0.11; 95% CI -0.66 to 0.45;
= 0.70), lymph node harvest (WMD = -0.97; 95% CI -1.97 to 0.03;
= 0.06) and 5-year DFS (hazard ratio = 0.84; 95% CI 0.54-1.31;
= 0.45) were not different between the NOSE and CL surgery groups.
Compared with CL surgery, NOSE may be a safe procedure, and can achieve similar oncological outcomes. Large multicenter RCTs are needed to provide high-level, evidence-based results in NOSE-treated patients and to determine the risk of local recurrence.
is an important tumor suppressor involved in various biological processes and is commonly lost or inactivated in clear-cell renal cell carcinoma (ccRCC). However, the role of the BAP1-deficient tumor ...competing endogenous RNA (ceRNA) network involved in ccRCC remains unclear. Thus, this study aims to investigate the prognostic BAP1-related ceRNA in ccRCC.
Raw data was obtained from the TCGA and the differentially expressed genes were screened to establish a BAP1-related ceRNA network. Subsequently, the role of the ceRNA axis was validated using phenotypic experiments. Dual-luciferase reporter assays and fluorescence
hybridization (FISH) assays were used to confirm the ceRNA network.
Nuclear enriched abundant transcript 1 (NEAT1) expression was significantly increased in kidney cancer cell lines. NEAT1 knockdown significantly inhibited cell proliferation and migration, which could be reversed by miR-10a-5p inhibitor. Dual-luciferase reporter assay confirmed miR-10a-5p as a common target of NEAT1 and Serine protease inhibitor family E member 1 (SERPINE1). FISH assays revealed the co-localization of NEAT1 and miR-10a-5p in the cytoplasm. Additionally, the methylation level of SERPINE1 in ccRCC was significantly lower than that in normal tissues. Furthermore, SERPINE1 expression was positively correlated with multiple immune cell infiltration levels.
In BAP1-deficient ccRCC, NEAT1 competitively binds to miR-10a-5p, indirectly upregulating SERPINE1 expression to promote kidney cancer cell proliferation. Furthermore, NEAT1/miR-10a-5p/SERPINE1 were found to be independent prognostic factors of ccRCC.
Background
Erectile dysfunction (ED) mainly affects men over 40 years of age and is a common clinical condition. In addition to hypertension and diabetes, environment, and lifestyle are also ...significantly associated with erectile dysfunction. The relationship between dietary trace metal intake and ED has not been studied.
Materials and methods
Data on participants were obtained from the National Health and Nutrition Examination Survey for this study, and those with incomplete information on clinical variables were excluded. Dose-response curve analysis was used to investigate the relationship between dietary trace metal intake and ED prevalence. Multivariate logistic regression analysis was used to adjust for confounders to further investigate the relationship between dietary trace metal intake and ED prevalence. 1:1 propensity score matching (PSM) was performed to adjust for differences between clinical variables for data reanalysis to confirm the reliability of the results.
Results
A total of 3,745 individuals were included in the study, including 1096 ED patients and 2,649 participants without ED. Dietary intake of trace metals (Mg, Zn, Cu, and Se) was significantly higher in participants without ED than in ED patients (all
P
< 0.001). Dose-response curve analysis showed a significant negative association between these dietary metal intakes and ED prevalence (all
P
< 0.001). Multivariate logistic regression analysis adjusted for confounders (age, education, BMI, annual household income, hypertension, diabetes, marital status, race, and current health status) revealed that increased dietary metal intake reduced the odds ratio of ED. 1:1 PSM reanalysis further confirmed the validity of the results.
Conclusion
Increasing dietary intake of trace metals (magnesium, zinc, copper, and selenium) within the upper limit is beneficial in reducing the prevalence of ED.
QTL Mapping for Important Agronomic Traits in Synthetic Hexaploid Wheat Derived from Aegiliops tauschii ssp. tauschii YU Ma, CHEN Guo-yue, ZHANG Lian-quan, LIU Ya-xi, LIU Deng-cai, WANG Ji-rui, PU Zhien, ZHANG Li, LAN Xiu-jin, WEI Yu-ming, LIU Chun-ji , ZHENG You-liang (National Key Facility for Crop Gene Resources and Genetic Improvement/Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, P.R.China)
Journal of Integrative Agriculture,
09/2014, Letnik:
13, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Aegiliops tauschii is classified into two subspecies： Ae. tauschii ssp. tauschii and Ae. tauschii ssp. strangulata. Novel genetic variations exist in Ae. tauschii ssp. tauschii that can be utilized ...in wheat improvement. We synthesized a hexaploid wheat genotype（SHW-L1） by crossing an Ae. tauschii ssp. tauschii accession（AS60） with a tetraploid wheat genotype（AS2255）. A population consisting of 171 F8 recombinant inbred lines was developed from SHW-L1 and Chuanmai 32 to identify QTLs associated with agronomic traits. A new genetic map with high density was constructed and used to detect the QTLs for heading date, kernel width, spike length, spikelet number, and thousand kernel weight. A total of 30 putative QTLs were identified for five investigated traits. Thirteen QTLs were located on D genomes of SHW-L1, six of them showed positive effect on agronomic traits. Chromosome region flanked by wPt-6133–wPt-8134 on 2D carried five environment-independent QTLs. Each QTL accounted for more than 10% phenotypic variance. These QTLs were highly consistent across environments and should be used in wheat breeding.
Docetaxel has been proved to provide survival benefit for advanced prostate cancer (PCa) patients. Resistance to docetaxel further reduces the survival of these patients. Herein, we performed a ...comprehensive bioinformatic analysis to identify differentially expressed genes (DEGs) between docetaxel sensitive and resistant PCa (DRPC) cell based on Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied for functional and pathway analysis of DEGs. The STRING database, cytoscape software and plug-in 'cytoHubba' were used to construct protein-protein interaction (PPI) networks and identify hub genes. Survival analysis were performed via GEPIA database. Finally, we conducted immune infiltration analysis by TIMER. A total of 460 DEGs were identified. GO functional analysis showed that these DEGs are mainly enriched in chemotaxis, negative regulation of intracellular signal transduction, and regulation of cell adhesion, positive regulation of inflammatory response, regulation of response to cytokine stimulus. According to the results of KEGG pathway analysis, these DEGs are mainly involved in signaling by Rho GTPases, Miro GTPases and RHOBTB3; interferon Signaling; arginine biosynthesis; PI3K-Akt signaling pathway; cytokine-cytokine receptor interaction; MAPK signaling pathway. Finally, CCNB1 and EZH2 were identified as prognostic hub genes and the expression of these two genes were associated with immune infiltration. The present study may helps to improve the understanding of the molecular mechanisms of DRPC and facilitate the selection of therapeutic and prognostic biomarkers for DRPC.
The advancement of metabolic engineering and synthetic biology has promoted in-depth research on the nonmodel microbial metabolism, and the potential of nonmodel organisms in industrial biotechnology ...is becoming increasingly evident. The nonmodel organism Pseudomonas chlororaphis is a safe plant growth promoting bacterium for the production of phenazine compounds; however, its application is seriously hindered due to the lack of an effective gene expression precise regulation toolkit. In this study, we constructed a library of 108 promoter-5′-UTR (PUTR) and characterized them through fluorescent protein detection. Then, 6 PUTRs with stable low, intermediate, and high intensities were further characterized by report genes lacZ encoding β-galactosidase from Escherichia coli K12 and phzO encoding PCA monooxygenase from P. chlororaphis GP72 and thus developed as a static gene expression regulation system. Furthermore, the stable and high-intensity expressed P MOK_RS0128085 UTR was fused with the LacO operator to construct an IPTG-induced plasmid, and a self-induced plasmid was constructed employing the high-intensity P MOK_RS0116635 UTR regulated by cell density, resulting in a dynamic gene expression regulation system. In summary, this study established two sets of static and dynamic regulatory systems for P. chlororaphis, providing an effective toolkit for fine-tuning gene expression and reprograming the metabolism flux.
Micronutrient malnutrition affects over three billion people worldwide, especially women and children in developing countries. Increasing the bioavailable concentrations of essential elements in the ...edible portions of crops is an effective resolution to address this issue. To determine the genetic factors controlling micronutrient concentration in wheat, the quantitative trait locus （QTL） analysis for iron, zinc, copper, manganese, and selenium concentrations in two recombinant inbred line populations was performed. In all, 39 QTLs for ifve micronutrient concentrations were identiifed in this study. Of these, 22 alleles from synthetic wheat SHW-L1 and seven alleles from the progeny line of the synthetic wheat Chuanmai 42 showed an increase in micronutrient concentrations. Five QTLs on chromosomes 2A, 3D, 4D, and 5B found in both the populations showed signiifcant phenotypic variation for 2-3 micronutrient concentrations. Our results might help understand the genetic control of micronutrient concentration and allow the utilization of genetic resources of synthetic hexaploid wheat for improving micronutrient efifciency of cultivated wheat by using molecular marker-assisted selection.
Lipopolysaccharide (LPS) can activate alveolar epithelial cells (AECs) and induce inflammatory injury. Toll-like receptor-4 (TLR-4) is integrally involved in LPS signaling and has a requisite role in ...the activation of NF-κB. NF-κB is a key intercellular signaling event that mediates cell inflammatory responses. The aim of the study is to investigate in an in vitro model the inflammatory responses of AECs induced by LPS and the probable mechanism underlined the observed inflammatory responses. So cytokines of ICAM-1, TNF-α and IL-8 secreted by LPS-activated AECs were observed. And the initial signal molecule (the expression of TLR-4 mRNA) and the key intracellular steps (the activation of NF-κB) were studied in detail.
The study was performed on A549 cells (Human lung adenocarcinoma cell line). A549 cells were divided into two groups: control, and LPS interference group. Proinflammatory cytokines ICAM-1, TNF-α and IL-8 were detected by ELISA or radioimmunological methods. The expression of TLR-4 mRNA was detec
PDF
